Kumpulan Jurnal Penyakit Pulpa Dan Periapikal

Journal of Endodontics
July 2008, Volume 34, Number 7S

Pulp Symposium
S1
AAE and AAPD Symposium Overview: Emerging Science in Pulp Therapy

New Insights Into Dilemmas and Controversies
Gerald N. Glickman and N. Sue Seale
S2
The Caries Process and Its Effect on the Pulp: The Science Is Changing and
So Is Our Understanding
Lars Bjrndal
S6
Diagnosis Dilemmas in Vital Pulp Therapy: Treatment for the Toothache Is

Changing, Especially in Young, Immature Teeth
Joe H. Camp
S13
Regenerative Potential of Dental Pulp

Martin Trope
S18
Vital Pulp Therapy with New Materials for Primary Teeth: New Directions and
Treatment Perspectives
Anna B. Fuks
S25
Vital Pulp Therapy with New Materials: New Directions and Treatment
PerspectivesPermanent Teeth
David E. Witherspoon
S29
Indirect Pulp Therapy and Stepwise Excavation

Lars Bjrndal
S34
Indirect Pulp Capping and Primary Teeth: Is the Primary Tooth Pulpotomy
Out of Date?
James A. Coll
S40
Is Formocresol Obsolete? A Fresh Look at the Evidence Concerning Safety Issues

Alan R. Milnes
S47
New Age Pulp Therapy: Personal Thoughts on a Hot Debate

Paula Jane Waterhouse
S51
Regeneration Potential of the Young Permanent Tooth: What Does the Future
Hold?
Kenneth M. Hargreaves, Todd Geisler, Michael Henry, and Yan Wang
S57
Contemporary Perspectives on Vital Pulp Therapy: Views From the Endodontists

and Pediatric Dentists
N. Sue Seale and Gerald N. Glickman
Pulp Symposium
AAE and AAPD Symposium Overview: Emerging Science

in Pulp TherapyNew Insights Into Dilemmas and
Controversies
vidence-based best practices are yet to be established for the

management of caries-associated pulpal disease in young permanent and primary teeth. Controversies still remain among practitioners, including pediatric dentists and endodontists, as to which treatment modalities are most predictable in the contemporary practice of
pulp therapy. Many clinicians still remain divided as to whether indirect
pulp capping is a viable procedure in primary and young permanent
teeth, or whether formocresol remains the medicament of choice for
pulpotomies in primary teeth. To begin the process of establishing evidence-based best practices in pulpal therapy as well as highlight some of
the future directions in pulp therapy including pulp regeneration with
stem cells and root canal revascularization, the American Academy of
Pediatric Dentistry (AAPD) and the American Association of Endodontists (AAE) jointly sponsored Emerging Science in Pulp Therapy: New
Insights into Dilemmas and Controversies. The symposium was held on
November 23, 2007, in Chicago, Illinois.
The convening of this pulp therapy symposium was heralded as a
major event in that it was a first time conjoint symposium sponsored by
these 2 national specialty organizations. The genesis of the idea for joint
sponsorship was the need to examine the shared procedures performed
by the 2 specialties. With specialty organizations routinely producing
evidence-based practice guidelines that provide the foundation for
treatments performed, it is critical that when 2 specialties perform the
same or similar treatments, their guidelines are parallel in language and
in content. Without these guidelines, confusion and uncertainty will
result in clinical practice when a rational treatment plan is required to
manage a specific pathologic entity such as caries.
Pediatric dentistry and endodontics share in the important treatment decisions associated with pulpal therapy for the cariously involved
young permanent tooth. In addition, endodontists are consultants to
and involved in pulp therapy treatment decisions for the cariously involved primary tooth. With the eventual expectation that the 2 organizations could come together and produce practice guidelines that share
common goals and language for caries-associated pulp therapy for primary and young permanent teeth, the decision was made to bring together a panel of world-renown experts from both specialties to present
the current best evidence as a first step in developing the anticipated
guidelines.
Individuals identified to be on the planning committee from the
AAE were Drs Gerald N. Glickman, Alan Gluskin, and Bradford Johnson.
From the AAPD, Drs Suzi Seale, Elizabeth Barr, and James Coll were
selected. These individuals met and identified the following areas as
appropriate for focus: the nature of the carious lesion of dentin; indirect
pulp therapy, including stepwise excavation for both young permanent
teeth and primary teeth; primary tooth pulpotomy agents with special
emphasis on formocresol and the controversy surrounding its use; and
revascularization of young permanent teeth and pulpal regeneration by
using stem cells. To that end, a cadre of 9 experts was identified and
invited to present evidence for assigned topics. The articles resulting
from their presentations appear in this publication.
JOE Volume 34, Number 7S, July 2008
During the conference Professor Lars Bjrndal discussed the caries process and its effect on the pulp. He applied this information to the
dilemma of the deep carious lesion and indirect pulp capping, with
special emphasis on the coronal seal. Dr Joe Camp focused on diagnostic dilemmas in vital pulp therapy for young immature teeth. Dr Martin
J. Trope spoke on how new trends are changing our understanding of
the regenerative potential of the dental pulp, whereas Dr David Witherspoon spoke on new directions and treatment perspectives involving
pulpal revascularization for permanent teeth. Dr Anna Fuks presented a
compilation of the evidence for different pulpotomy agents in treating
the vital cariously involved primary tooth. Dr Jim Coll provided information about indirect pulp capping for primary teeth as an alternative to
pulpotomy. Drs Alan Milnes and P. J. Waterhouse presented opposing
views about the controversy over formocresol as a pulpotomy agent for
human teeth. Finally, Dr Ken Hargreaves provided evidence for the
future of pulpal regeneration for the young permanent tooth.
Because 2 specialty groups were represented, the planning committee sought to determine, through a brief pretest completed before the
first speaker, the baseline opinions of the audience about the various
topics to be presented. After the last speaker, a more lengthy set of
questions about the same topics were presented to the audience for
their opinions by using an audience response system. Attendees responses were identified by specialty, and the results of the comparisons
of the presymposium and postsymposium opinions within specialty and
across specialties are also presented in this publication.
We believe this symposium represented an important landmark in
bringing together different disciplines with potentially different opinions to reach an evidence-based consensus about common treatment
dilemmas. Because practice guidelines increasingly drive our treatment
decisions, it is important that we are in agreement about their content,
ultimately for the care and benefit of our patients.
Gerald N. Glickman, DDS, MS
Vice-President, American Association of Endodontists
and
Professor and Chairman, Department of Endodontics
Baylor College of Dentistry
Texas A&M University Health Science Center
Dallas, Texas
N. Sue Seale, DDS, MSD

Regents Professor and Chairman, Department of Pediatric Dentistry
Baylor College of Dentistry
Texas A&M University Health Science Center
Dallas, Texas
Conflict of Interest: Gerald N. Glickman, DDS, MS, reports no financial
interests or potential conflicts of interest. N. Sue Seale, DDS, MSD, reports no
financial interests or potential conflicts of interest.
Copyright 2008 American Academy of Pediatric Dentistry and American
Association of Endodontists.
This article is being published concurrently in Pediatric Dentistry, May/June
2008; Volume 30, Issue 3. The articles are identical. Either citation can be used
when citing this article.
doi:10.1016/j.joen.2008.02.036
AAE and AAPD Symposium Overview
S1
Pulp Symposium
The Caries Process and Its Effect on the Pulp: The Science
Is Changing and So Is Our Understanding
Lars Bjrndal, DDS, PhD
Abstract
The understanding of the caries process and its effect
on the pulp is presented in the context that caries does
develop in various rates of progression. Early in the
caries process, the pulp reflects changes within lesion
activity. Thus, the early pulp response is reversible.
Later, the rate of caries progression is reflected by the
quality of the tertiary dentin. Slowly progressing lesions
create tertiary dentin resembling normal tubular dentin.
Rapidly progressing lesions lead to the production of
atubular dentin or complete absence of tertiary dentin,
as well as pulp necrosis and apical pathology. Finally,
the nature of the untreated deep carious lesion is an
ecosystem that might undergo significant changes. The
untreated lesion is temporarily converted from an active
and closed lesion environment into one that is open
and slowly progressing. The analysis of untreated carious lesions has transformed the treatment philosophy
of deep carious lesions. (J Endod 2008;34:S2-S5)
Key Words
Dental caries, dental pulp, dentin, indirect pulp treatment, stepwise excavation, tertiary dentin
From the Department of Cariology and Endodontics,

School of Dentistry, Faculty of Health Sciences, University of
Copenhagen, Denmark.
Address requests for reprints to Dr Bjrndal at lb@odont.
ku.dk.
Conflict of Interest: Lars Bjrndal, DDS, PhD, is a Grant
Recipient from the Danish Agency for Science Technology and
Innovation.
0099-2399/$0 - see front matter
Copyright 2008 American Academy of Pediatric Dentistry and American Association of Endodontists.
This article is being published concurrently in Pediatric
Dentistry, May/June 2008; Volume 30, Issue 3. The articles are
identical. Either citation can be used when citing this article.
doi:10.1016/j.joen.2008.02.037
S2
Bjrndal
Can We Obtain Consensus on Caries Pathology?

Caries can be compared with a train that passes through many stations. Imagine
that each station represents a specific stage of caries progression. The first station
represents the initial surface etching at the outer enamel layer, leading to the dull white
appearance of the active progressing enamel lesion. The last station represents the deepest
layer of the carious tooth, with a necrotic, infected root canal system and the presence of
apical pathosis. Investigators, clinicians, and researchers who enter the caries train have
typically focused on only a few stations. They might also have different understandings
and opinions about how to treat dental caries. Their opinions have developed from a
mixture of clinical empirical tradition and an understanding from research. These
opinions could be named the cariologist opinion, the operative opinion, and the endodontic opinion.
Some Opinions about the Approach to Dental Caries

The classic cariologist opinion is focused on the prevention of caries and further
progression of the established lesion. The initial focus is on the white spot lesion, whose
histologic picture is visualized in the laboratory via transmitted or polarized light.
Treatment philosophies here are typically related to nonoperative and preventive approaches. If caries has progressed into the dentin, with demineralized dentin being
visible on the x-ray or, at most, extending through half the thickness of the dentin,
excavation procedures are planned to avoid pulp exposures.
The operative opinion is typically initiated when caries has progressed into a
clinical breakdown of the enamel surface and with carious dentin exposure. Without
focusing on specific details about caries pathology, the cavity needs to be drilled and
filled. A lesion means an exposure of the pulp, and this might be avoided by leaving
carious dentin behind. The operative opinion also tends to be a two-edged sword,
because sometimes the design of the cavity overrides the fact that the caries lesion might
not be in need of operative intervention. However, for esthetic or other reasons, the
operative intervention is carried out with a minimally invasive approach, even though
the actual lesion is dark, discolored, arrested caries.
Finally, the endodontic opinion deals with the prevention of an infected pulp and
subsequent apical pathosis; the issue of a lesion mainly concerns this region. Therefore,
all carious dentin should be removed, even if the result is a pulp exposure. The existence
of these virtual opinions was reflected in a recent practice-based research network to
determine dentists treatment methods for deep caries lesions in which one would
expect pulpal exposure (1). The survey findings showed that 62% of the responding
dentists would remove all caries (operative opinion), 18% would partially remove
caries (cariologist opinion), and 21% would initiate endodontic treatment (endodontic
opinion). Differences in decision making for treating deep carious lesions in primary
molars have also recently been reported (2).
Actually, this topic is not new, as shown in the following quotations: It is better that
a layer of discolored dentin should be allowed to remain for the protection of the pulp
rather than run the risk of sacrificing the tooth (3). In contrast, Black (4) wrote:
. . . it will often be a question whether or not the pulp will be exposed when all decayed
dentin overlaying it is removed . . . It is better to expose the pulp of a tooth than to leave
it covered only with softened dentin.
It is necessary to remain within the historical perspective to understand how these
different opinions have justified various treatment concepts. The endodontic opinion
advocating an invasive pulp treatment in relation to caries might very well have gained
Pulp Symposium
inspiration from pulp studies carried out on animal models by using
standardized test cavities in sound dentin, in which the pulp reacts very
early to the influx of various external stimuli. These stimuli might include samples of plaque or soft carious dentin (5, 6). In this context, the
study by Brnnstrm and Lind (7) has been a key reference, showing
that the early enamel lesion in human teeth could also lead to odontoblast alterations and signs of pulpal infiltration. This is a key reference
because in this symposium presentation it is hypothesized that these
findings have been used as evidence for the early onset of irreversible
pulpal inflammation caused by caries progression. Taken together, it is
tempting to suggest that the observation of the early influx pulp data
might have led to the clinical interpretation that irreversible pulp inflammation is also reached relatively early in relation to caries. Therefore, radical interventions have been advocated. A recent Cochrane
review of pulp management in extensive caries deals with clinical studies in which deep lesions without clinical symptoms were treated (8).
One could question why a pulp-preserving treatment was not an option.
In contrast, the cariologist opinion, and to some extent the operative opinion, can be traced back decades to Massler (9). Massler,
among others, integrated a sophisticated and advanced biologic understanding of caries into caries treatment. He described acute and chronic
caries on the basis of clinical criteria and histologic descriptions. Consequently, different pulpal reaction patterns were to be expected that
could lead to differing means of treating caries as opposed to only a
radical approach.
With the metaphor of the caries train in mind, it is too much to
force everyone to get on and off at all the stations, but during a symposium such as this, a natural goal would be to reach a consensus of
understanding caries in between these group opinions. Therefore, when
entering a caries discussion aiming to cross invisible lines of dental
subspecialities, it is necessary to be clear and precise with the use of
well-defined terms. Why? Because the interpretation of the very same
clinical situation even today might reflect completely different treatments (1, 2), and misunderstandings might very well occur in communication between clinicians and researchers. Let us update our understanding of caries pathology by considering that the caries train might
use more than one track. This reflects the understanding and importance of caries as a disease that can progress at varying rates.
What is the sequence of the various zones in carious dentin, beginning with early lesions? When and how does the pulp begin to produce extradentinal matrix and tertiary dentin? What is the spreading
pattern of caries? When will microorganisms invade the demineralized
dentin? Can we say something about the prehistory of caries, when
viewing the histologic picture of tertiary dentin? Why do we sometimes
find tertiary dentin produced during caries, whereas at other times it is
difficult to detect? Is knowledge about lesion activity important?
An Update of Caries Pathology: The Non-cavitated

Enamel Lesion ComplexUnderstanding the Early
PulpDentinal Response to Caries
The proximal white spot lesion is triangular when viewed in 2
dimensions and conical when viewed in 3 dimensions. On the basis of
quantitative data related to the degree of porosity in the enamel lesion,
the lesion comprises a multitude of many microlesions following the
direction of the enamel rods. Hence, the topography of the lesion reflects the acidogenic potential of the cariogenic biofilm at the enamel
surface. The central lesion area is the oldest part and shows the deepest
penetration, whereas the peripheral parts represent new beginners
following the direction of the rods (10).
In short, the shape of the enamel lesion represents a transmission
of stimuli from the enamel surface that can be related to time and
provides the possibility for understanding the subjacent pulpal-dentinal

response in relation to time. Thus, the deepest penetration of the entire
caries lesion complex can also be seen as the oldest lesion area along
the dentin-pulp interface following the direction of the dentinal tubules.
Consequently, the peripheral areas represent younger and less progressed areas along the dentin-pulp interface, guided by the cariogenic
biofilm covering the surface of the enamel lesion. The morphology of
reactionary dentinogenesis, defined as tertiary dentin produced by primary odontoblasts, has been described by using this concept (11). I will
return to this subject later.
Examples of Improved Laboratory Methods That Have

Created a Better Understanding
One approach that has improved our understanding from the histologic findings of Brnnstrm and Lind (7) was the use of thin, undemineralized tooth sections in the examination of well-defined carious
lesions. The normal structural relationships between enamel, dentin,
and the pulp were preserved with this new histologic method. Therefore, it was possible to describe morphologic changes in the enamel and
the subjacent pulp-dentinal organ within the same section (12). Also,
the application of immunohistochemistry has improved our understanding of the underlying molecular events (13), as well as reactions
leading to reactionary and reparative dentinogenesis (14).
The Sequence of the Carious Development in

the Tooth
Morphologic changes in odontoblasts have been found in welldefined enamel lesions in freshly extracted third molars (14). Moreover, morphologic and molecular features in the odontoblast cells leading to the production of extradentinal matrix can also be detected (15,
16). During our daily clinical practice we might only recall the early
odontoblast response from the library, but when we experience the pulp
in relation to caries, it is during a very late stage of lesion progression as
we consider whether pulp exposure should be avoided.
How should we interpret the early pulp response? An updated
interpretation and understanding would be that the pulpal response
follows the caries lesion from the very beginning. However, it should not
be considered as a station along the track of irreversible pulp inflammation, hence a point of no return. Some observations even indicate
that the pulp might react to the signals passing through the enamel even
before histologic caries reactions can be observed in the dentin (14).
The first visible histologic change in the dentin subjacent to an
enamel lesion is the formation of hypermineralized dentinal tubules.
This reaction is seen in the dentin before any signs of demineralization.
The reaction might represent activity of the odontoblasts, and it might
very well resemble the age-related intratubular physiologic sclerosis
(17). When the enamel lesion reaches the dentinoenamel junction
(DEJ), dentin demineralization is initiated. Note that the initial dentin
demineralization takes place not in unaffected sound dentin but in dentin with a decreased permeability as a result of the presence of the
hypermineralized dentin.
After the dentin begins the process of demineralization, the advancing front of demineralization also reflects the dynamic nature of the
cariogenic biofilm, expressed as different pH gradient creating either
dissolution or reprecipitation of dentin mineral. Thus, the hypermineralized dentin is probably the result of physiologic activity from the odontoblast, but it also contains reprecipitation of previously dissolved dentin crystals. However, this topic requires additional study (18).
No serious microbial invasion takes place in the dentin as long as
the highly organized enamel layer (even though being demineralized)
separates the biofilm from the dentin. The bacteria are not able to
The Caries Process and Its Effect on the Pulp
S3
Pulp Symposium
Figure 1. Diagrams showing the temporary conversion of the cariogenic ecosystem during untreated lesion progress. A closed lesion environment develops in relation
to an occlusal lesion (a). Eventually the white demineralized and undermined enamel breaks as a result of mechanical stress, changing the environment into an open
ecosystem (b). Consequently, a stage of mixed lesion activity develops. In the occlusal part, classic signs of slow lesion progress are noted in terms of a darker
appearance of the demineralized dentin, whereas at the margins, optimal growth conditions for the plaque are apparent, and active lesion progress continues (c).
Red zones indicate plaque. Reprinted with permission from Blackwell Munksgaard from Bjrndal L. Dentin and pulp reactions to caries and operative treatment:
biological variables affecting treatment outcome. Endodontic Topics 2002;2:10 23. (22)
penetrate through the enamel rod structure (19). The microbial invasion is
related to the gradual structural breakdown of the enamel layer (20).
Another important change in our understanding is the misinterpreted concept of caries spreading along the DEJ subjacent the noncavitated enamel lesion (21). The extent of the demineralized dentin is
restricted to the histologic enamel lesion contact, and no spreading of
demineralized hard tissue is noted undermining sound enamel. The
lateral spread of demineralized dentin and enamel is related to the total
breakdown of the enamel layer and therefore describes a relatively later
stage of tissue destruction than previously believed.
During the stages of dentin exposure a completely different situation is created under heavy bacterial invasion. A moist, soft, disintegrated, demineralized, and necrotic zone is observed. At this active stage
the carious dentin can easily be separated from the enamel. The outflux
of mineral has been extensive, and as the moisture is decreased, eventually the dentin shrinks, and a clinically visible gap develops between
the enamel and dentin (Fig. 1a). Subsequently, the cariogenic biofilm
gains improved growth conditions along the lateral spread of caries or
retrograde caries (23). If the carious tooth is left untreated, further
tissue breakdown occurs. Eventually the caries process will bring about
irreversible changes in the pulp, leading to necrosis and pulpal infection
with apical pathosis. This worst case scenario is often what we find in
many textbooks. It also represents what takes place several times a week
in dental practice. In Denmark caries is still the most frequent reason
for endodontic treatment (24).
Lesion Activity and Pulpal Response

What is the significance of how rapidly caries progresses in relation to a pulpal response? Let us once again benefit from the histologic
findings of the early pulp response to enamel caries (14). In addition to
odontoblast cell reaction per se, the odontoblasts also display a different
response to active versus arrested caries. When the non-cavitated
enamel lesion has histologic contact with the DEJ, the odontoblasts
within active lesions have a significantly lower cytoplasm:nucleus ratio
compared with control sites. In contrast, this situation is not found in the
arrested or slowly progressing enamel lesion. Moreover, only active
enamel lesions show evidence of proliferation of cells from the subodontoblastic cell-rich zone into the cell-free zone. In short, the pulpal
response follows not only the early caries lesion; it also mirrors changes
in lesion activity.
In cavitated lesions, different patterns of tertiary dentin can be
expected relative to the prehistory of each lesion. The presence or
absence of tertiary dentin, as well as its quality, should be seen as a
reflection of the nature of the external stimuli that have previously
passed through the dentin. As an additional example, the rapidly progressing caries lesions would typically follow the sequence of odontoS4
Bjrndal
blast necrosis (25), eventually followed by the presence of atubular

dentin formation, also known as fibrodentin. Let us in this context
return to the morphology of the reactionary dentinogenesis defined as
tertiary dentin produced by primary odontoblasts. A few studies have
described this sequence by comparing central and old lesion areas with
peripheral and lateral parts of younger lesion areas (11, 14). It appears
that the primary odontoblasts are involved in the early onset of new
extradentinal matrix in the younger portions of the lesion, whereas the
older central lesion area shows the gradual development of atubular
fibrodentin (26).
In contrast, slowly progressing lesions characteristically display
tubular dentin formation at the pulpal site. This tertiary dentin shows a
mixture of reactionary dentinogenesis and dentin produced by new
odontoblast-like cells. It appears that this takes place in the same manner as the primary odontoblast cells, with finger-like projections but
into the reactionary dentin (16). Very little attention has been given
previously to the potential capacity of the primary odontoblast to be part
of tertiary dentin formation.
Also within deep carious lesions (Fig. 1), large variation in lesion
activity might appear (27). As the lesion progresses, the enamel breaks
down (Fig. 1b), and at the same time the growth conditions change for
the cariogenic biofilm. The cavitated lesion transforms from a closed
ecosystem into an open ecosystem (Fig. 1c). Different rates of progression can therefore be present within one tooth. After the enamel breakdown, the occlusal part of the tooth has no heavy plaque accumulation,
as the degree of protection of the biofilm has decreased. The subjacent dentin discloses the clinical signs of slowly progressing caries
by its brownish discoloration (Fig. 2a). In contrast, the peripheral
parts are protected, and accumulations of cariogenic biomass are
apparent. On the basis of these observations, pulp vitality is not
necessarily maintained, but it indicates that deep exposed dentin
lesions are not unconditionally related to an irreversible pattern of
pulp pathology, as traditionally taught in textbooks advocating invasive pulp treatments (28). Of course, if nothing is done with the
deep lesion even though it might be temporarily arrested, eventually
the caries activity in the peripheral parts of the lesion leads to the
breakdown of the tooth (Fig. 2b, c).
The pulpal response in lesions with a conversion of lesion activity
can be reflected by the presence of reparative dentinogenesis, defined as
the combination of fibrodentin and new tubular dentin produced by new
odontoblast-like cells (29). The presence of fibrodentin or interface
dentin indicates that all primary odontoblasts have died. After the
change in caries activity, the pulp might respond with reparative dentin
resembling the dentin-bridge formation after a direct pulp capping procedure (16).
Pulp Symposium
Figure 2. The pattern of untreated deep lesions might involve a decrease in lesion activity (a), but it might be temporary because the enamel margins will obtain
protection for the cariogenic process (b). Eventually the entire crown breaks, leaving remnants of roots behind (c). Red zones indicate plaque. Reprinted with
permission from Blackwell Munksgaard from Bjrndal L. Dentin and pulp reactions to caries and operative treatment: biological variables affecting treatment
outcome. Endodontic Topics 2002;2:10 23. (22)
Understanding of Caries Pathology Creates the

Treatment Philosophy Related to Deep Caries
In the past, the following have all been clear justification for the
performance of radical operative intervention: (1) early microbial invasion of carious dentin, (2) early spreading along the DEJ that undermines sound enamel, and (3) the early onset of an irreversible pulp
response. Even though textbooks often illustrate the worst case scenario, this does not mean that we should wait for it to happen! We should be
motivated to understand the lesion activity and use this information in the
treatment of caries. Instead of accepting that there is a steady progression
through the tooth leading toward the same results if left untreated, it might
be more appropriate to understand that caries activity constitutes many
different rates of progression, each of them leading to different pulp reactions. Perhaps with the appropriate clinical intervention we can reduce the
rate of caries progression, perhaps even arresting the subjacent pulpal inflammation. Only well-designed clinical trials will answer this question,
given that we do not yet have noninvasive tools for the measurement of the
severity of the inflamed pulp. Therefore, the clinical discussion of reversible
or irreversible development of pulpitis will continue to be controversial in
relation to the actual state of pulp pathology. However, when diagnosing
deep carious lesions, we must make a choice on the basis of our knowledge
of the caries process and its effect on the pulp and on the basis of existing
diagnostic methods. The noninvasive pulp treatment of deep caries lesions
will be the focus of my second presentation.
References
1. Oen KT, Thompson VP, Vena D, et al. Attitudes and expectations of treating deep
caries: a PEARL network survey. Gen Dent 2007;55:197203.
2. Qudeimat MA, Al-Saiegh FA, AL-Omari Q, Omar R. Restorative decisions for deep
proximal carious lesions in primary molars. Eur Arch Paediatr Dent 2007; 8:37 42.
3. Tomes J. A system of dental surgery. London: John Churchill, 1859:336.
4. Black GV. A work on operative dentistry in two volumes, vol. II. The technical procedures in filling teeth. 2nd ed. Chicago: Medico-Dental Publishing Co, 1908.
5. Bergenholtz G, Lindhe J. Effect of soluble plaque factors on inflammatory reactions in
the dental pulp. Scand J Dent Res 1975;83:153 8.
6. Mjr IA, Tronstad L. Experimentally induced pulpitis. Oral Surg 1972;34:102 8.
7. Brnnstrm M, Lind PO. Pulpal response to early caries. J Dent Res 1965;44:104550.
8. Nadin G, Goel BR, Yeung CA, Glenny AM. Pulp treatment for extensive decay in
primary teeth. Cochrane Database Syst Rev 2003;1:CD003220.
9. Massler M. Pulpal reactions to dental caries. Int Dent J 1967;17:441 60.
10. Bjrndal L, Thylstrup A: A structural analysis of approximal enamel caries lesions and
subjacent dentin reactions. Eur J Oral Sci 1995;103:2531.
11. Lee Y-L, Liu J, Clarkson BH, Lin C-P, Godovikova V, Ritchie HH. Dentin-pulp complex
responses to carious lesions. Caries Res 2006;40:256 64.
12. Bjrndal L, Thylstrup A, Ekstrand KR. A method for light microscopy examination of
cellular and structural interrelations in undemineralized tooth specimens. Acta Odontol Scand 1994;52:18290.
13. Yoshiba N, Yoshiba K, Nakamura H, Iwaka M, Ozawa H. Immunohistochemical localization of HLA-DR-positive cells in unerupted and erupted normal and carious
human teeth. J Dent Res 1996;75:15859.
14. Bjrndal L, Darvann T, Thylstrup A. A quantitative light microscopic study of odontoblast and subodontoblastic reactions to active and arrested enamel caries without
cavitation. Caries Res 1998;32:59 69.
15. Lukinmaa PL, Vaahtokari A, Vainio S, Thesleff I. Expression of type I collagen pro-2
chain mRNA in Adult human permanent teeth as revealed by in situ hybridization. J
Dent Res 1992;71:36 42.
16. Bjrndal L, Darvann T. A light microscopic study of odontoblastic and non-odontoblastic cells involved in tertiary dentinogenesis in well-defined cavitated carious
lesions. Caries Res 1999;33:50 60.
17. Tagami J, Hosoda H, Burrow MF, Nakajima M. Effect of ageing and caries in dentin
permeability. Proc Finn Dent Soc 1992;88(Suppl 1):149 54.
18. Kidd EAM, Bjrndal L, Beighton D, Fejerskov O. Caries removal and the pulpodentinal complex. In: Fejerskov O, Kidd EAM, eds. Dental caries: the disease and its
clinical management. 2nd ed. Oxford: Blackwell Munksgaard, 2008:367 83.
19. Ekstrand KR, Bjrndal L. Structural analyses of plaque and caries in relation to the
morphology of the groove-fossa system on erupting mandibular third molars. Caries
Res 1997;31:336 48.
20. Ricketts D, Ekstrand KR, Kidd EAM, Larsen T. Relating visual and radiographic
ranked scoring systems for occlusal caries detection to histological and microbiological evidence. Oper Dent 2002;27:2317.
21. Silverstone LM, Hicks MJ. The structure and ultrastructure of the carious lesion in
human dentin. Gerodontics 1985;1:18593.
22. Bjrndal L. Dentin and pulp reactions to caries and operative treatment: biological
variables affecting treatment outcome. Endodontic Topics 2002;2:10 23.
23. Bjrndal L, Kidd EAM, The treatment of deep dentine carious lesions. Dent Update
2005;32:40213.
24. Bjrndal L, Laustsen MH, Reit C. Root canal treatment in Denmark is most often
carried out in carious vital molar teeth and retreatments are rare. Int Endod J
2006;39:78590.
25. Magloire H, Bouvier M, Joffre A. Odontoblast response under carious lesions. Proc
Finn Dent Soc 1992;88(Suppl.1):25774.
26. Bjrndal L. Presence or absence of tertiary dentinogenesis in relation to caries
progression. Adv Dent Res 2001;33: 80 3.
27. Edwardsson S. Bacteriology of dentin caries. In: Thylstrup A, Leach SA, Qvist V, eds.
Dentine and dentine reactions in the oral cavity. Oxford: IRL Press, 1987:95102.
28. Tronstad L. Clinical endodontics. 2nd ed. Stuttgard: Thieme, 2003:81.
29. Smith AJ, Tobias RS, Cassidy N, et al. Odontoblast stimulation in ferrets by dentine
matrix components. Arch Oral Biol 1994;39:1322.
The Caries Process and Its Effect on the Pulp
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Pulp Symposium
Diagnosis Dilemmas in Vital Pulp Therapy: Treatment for

the Toothache Is Changing, Especially in Young,
Immature Teeth
Joe H. Camp, DDS, MSD
Abstract
The literature is almost devoid of scientific studies of
diagnosis of pulpal pathology in primary and permanent teeth with open apices. Most reports are empirical
or retrospective studies without adequate prior knowledge of preexisting conditions or histologic findings
leading to the necessity of pulpal procedures. Appropriate diagnostic tests and their effectiveness are documented for both groups. This article reviews the available literature and current techniques of indirect pulp
therapy, pulp capping, and pulpotomy for primary teeth
and permanent teeth with open apex. The apical barrier with mineral trioxide aggregate followed by root
strengthening with bonded composite is reviewed.
(J Endod 2008;34:S6-S12)
Key Words
Diagnosis, pulp, pulp capping, pulpotomy
From private practice of endodontics, Charlotte, North

Carolina, and Department of Endodontics, University of North
Carolina, Chapel Hill, North Carolina.
Address requests for reprints to Dr Camp at E-mail address:
joecamp@carolina.rr.com.
Conflict of Interest: Joe H. Camp, DDS, MSD, is the University Clinical Consultant for Dentsply Tulsa Dental Specialties, a part-time, paid position.
doi:10.1016/j.joen.2008.03.020
S6
Camp
iagnosis in primary and young, permanent, immature teeth varies greatly from that
in fully formed permanent teeth. Most of the diagnostic tests used in conventional
endodontic therapy are of very little or no value in primary teeth and of limited value in
permanent immature teeth. While admittedly poor for diagnosing the degree of inflammation in this group of teeth, diagnostic tests must be performed to obtain as much
information as possible before arriving at treatment options.
Diagnostic literature based on scientific studies is almost nonexistent. Most outcome reports are supported by empirical treatment and anecdotal case reports (1).
Many outcome studies are conducted retrospectively on the basis of clinical signs and
symptoms and make assumptions regarding the pulpal status before treatment without
histologic or bacterial data to support the preoperative diagnosis. Without histologic
examination an accurate determination of the extent of inflammation is impossible (2).
Correlation between clinical symptoms and histopathologic conditions is poor and
complicates diagnosis of pulpal health in exposed pulps of children (3).
Many of our treatments are based on our diagnosis of the root development stage.
Consequently, to properly diagnose and treat primary and young permanent teeth, it is
necessary to have a thorough knowledge of normal root formation and the differences
between developing and fully formed teeth. The decision to render conservative vital
treatment to allow root formation completion or more radical treatment such as root
canal therapy might hinge on our diagnosis of root development.
According to Orban (4), the tooth roots development begins after enamel and
dentin formation has reached the cementoenamel junction (CEJ). Hertwigs epithelial
root sheath is formed by the epithelial dental organ, with one tube for each of the future
roots. As root formation proceeds apically, each root is wide open, diverging apically
and limited by the epithelial diaphragm. Each roots internal surface is lined by odontoblasts. Once root length is established, the sheath disappears, whereas dentin deposition is continued until root formation is completed.
Depending on each roots external anatomy, differentiation into multiple canals
might occur. During this formative stage, communication exists between the canals in
the form of isthmuses. As growth continues, the opposing walls meet and coalesce, and
islands of dentin are formed, which eventually expand to divide the root into separate
canals. Continued dentin deposition narrows the canals, and the apex is eventually
closed with dentin and cementum, creating apical convergence. Isthmuses and fins
extending toward the roots center might persist in fully formed teeth.
In permanent teeth, root formation is not completed until 1 4 years after eruption
into the oral cavity. Because of the shorter roots of primary teeth, root formation is
completed faster than for permanent teeth. Because the faciolingual width of most roots
and canals is greater than the mesiodistal width, apical closure cannot usually be
determined radiographically. The x-ray beam is exposed in the faciolingual plane, but
the radiograph is read mesiodistally. Because of this anatomy, with the exception of the
maxillary central and lateral incisors and some single canal lower premolars, radiographs cannot determine apical closure. Therefore, the clinician must rely on time to
determine root closure in all other teeth to prevent treatment protocols that cannot be
successfully completed without apical convergence (5).
During this formative period, treatments should be oriented toward maintenance
of vitality to allow completion of root formation. Further deposition of dentin will
strengthen the roots thin dentinal walls and help diminish future root fracture.
Pulp Symposium
The root canals of primary teeth differ greatly from those of permanent teeth, and treatment is complicated by apical resorption to
allow for eruption of the succeeding teeth. At the time of root length
completion, the root canals roughly correspond to the external
anatomys form and shape. At this time, resorption of the roots
begins and, combined with additional dentin deposition internally,
might significantly change the number, size, and shape of the canals
within the primary roots. Continued physiologic, apical resorption of
the roots makes the teeth progressively shorter. In addition, resorption
on the roots internal surfaces adjacent to the forming permanent tooth
might open other communications with the periapical tissues. These
factors complicate establishment of working lengths if root canal therapy is necessary.
In the primary anterior teeth (incisors and canines), the permanent tooth buds lie apically and lingually near the primary roots. Resorption is initiated on the primary roots lingual surface. This causes
the apical foramen to move coronally, resulting in a difference in the
apical foramen and the anatomic apex and complicating determination
of root canal length. One study demonstrated that half of the primary
incisors root might be resorbed lingually before it becomes obvious on
a radiograph (6). Primary anterior teeth have one simple root canal and
rarely have lateral or accessory canals.
The primary molar teeth normally have the same number and
position of roots and root canals as the corresponding permanent teeth.
At root length completion, most roots have only 1 canal, but continued
deposition of dentin might divide the root into 2 or more canals (79).
During this time, communication exists between the canals in the form
of isthmuses or fins (Fig. 1). Secondary dentin deposition contributes to
this change in morphology (10, 11). Like the permanent molars, most
variations occur in the mesial roots of mandibular molars and facial
roots of the maxillary molars. Also, these variations are usually in the
facial to lingual plane and cannot be visualized on radiographs (7, 9).
Accessory and lateral canals and apical ramifications of the pulp
are common in primary molars (8). In addition, other communications
between the pulp and the periapical tissues are formed by physiologic
resorption of the internal surfaces of the roots adjacent to the permanent tooth buds.
Diagnosis of Pulpal Status in Primary Teeth

As with any dental procedure, a thorough medical history must be
completed, and any implications related to treatment must be consid-
Figure 1. Silicone models of the pulps of 2 primary mandibular second molars.

Note the communication between the facial and lingual canals in the mesial
roots.
ered. A child with systemic disease might necessitate different treatment

than a healthy one.
The examination should begin with a thorough history and characteristics of any pain, because these are often important in helping to
determine pulpal status and eventual treatment. Whereas pain usually
accompanies pulpal inflammation, extensive problems might arise
without any history of pain. If possible, a distinction between provoked
and spontaneous pain should be ascertained. Provoked pain that ceases
after removal of the causative stimulation is usually reversible and indicative of minor inflammatory changes. Stimuli include thermal, chemical, and mechanical irritants and many times are due to deep caries,
faulty restorations, soreness around a primary tooth nearing exfoliation,
or an erupting permanent tooth.
Spontaneous pain is a constant or throbbing pain that occurs without stimulation or continues long after the causative factor has been
removed. In a well-controlled histologic study of primary teeth with
deep carious lesions, Guthrie et al. (12) demonstrated that a history of
spontaneous toothache is usually associated with extensive degenerative
changes extending into the root canals. Primary teeth with a history of
spontaneous pain should not receive vital pulpal treatments and are
candidates for pulpectomy or extraction.
The clinical examination might produce evidence of pulpal pathosis. Redness, swelling, fluctuance, severe dental decay, defective or
missing restorations, and draining parulis might indicate pulpal involvement. Percussion sensitivity might be valuable to the diagnosis, but it is
complicated by the reliability of the childs response because of the
psychological aspects involved. Tooth mobility might be present normally because of physiologic resorption, and many pulpally involved
teeth have no mobility.
Electric pulp tests are not valid in primary teeth (1). Laser Doppler
flowmetry might be of greater help in determining vitality, but this equipment has not been perfected, and the price is prohibitive (13).
Thermal tests are usually not conducted on primary teeth because
of their unreliability (1, 5).
After the clinical examination, radiographs of good quality are
essential. Like permanent teeth, periapical radiolucencies appear at the
apices in primary anterior teeth. In primary molars, pathologic changes
are most often apparent in the bifurcation or trifurcation areas. Consequently, bite-wing radiographs are often best to observe pathologic
changes in posterior primary teeth. Pathologic bone and root resorptions are signs of advanced pulpal pathosis that has spread into the
periapical tissues and is usually treatable only with extraction.
Mild, chronic pulpal irritation such as seen in caries might stimulate the deposition of tertiary reactionary dentin over the pulp (5).
With acute or rapid onset as the disease reaches the pulp, calcified
masses might form away from the exposure site. Such calcified masses
are always indicative of advanced pulpal degeneration extending into
the root canals (14). Primary teeth with such calcified masses are
candidates for only pulpectomy or extraction (Fig. 2).
Internal resorption in primary teeth is always associated with extensive inflammation (12). Because of the thinness of the primary molar
roots, if internal resorption can be seen radiographically, a perforation
usually exists, and the tooth must be extracted (Fig. 3).
Interpretation of radiographs of primary teeth is always complicated by the presence of the succedaneous tooth and surrounding follicle. Misinterpretation of the follicle can easily lead to an erroneous
diagnosis of periapical pathology. Superimposition of the permanent
tooth might obscure visibility of the furca and roots of the primary tooth,
causing misdiagnosis. Added to this is the normal physiologic resorption process.
Radiographs might also reveal evidence of: previous pulpal treatment; calcification changes in pulp chambers and root canals; oversized
Diagnosis Dilemmas in Vital Pulp Therapy
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Pulp Symposium
Figure 2. Calcified masses within the pulp (arrow), which form away from the
exposure site, and internal resorption (as in this primary mandibular first
molar) are indicative of advanced degeneration.
canals indicative of cessation of root formation and pulpal necrosis; and

after trauma, root fractures, bone fractures, displacement of teeth, imbedded tooth fragments, or foreign bodies in soft tissues.
The size of a pulpal exposure and the amount and color of hemorrhage have been reported as important factors in diagnosing the
extent of inflammation under a carious lesion. Although all carious
exposures are accompanied by pulpal inflammation, the larger the exposure, the more likely it is to be widespread or necrotic.
Excessive (2, 5, 14, 15) or deep purple (15) colored hemorrhage
is evidence of extensive inflammation, and these teeth are candidates for
pulpectomy or extraction. Hemorrhage that cannot be controlled within
12 minutes by light pressure with a damp cotton pellet at an exposure
site indicates more extensive treatment is necessary. The same is true
after removal of tissue when doing a pulpotomy. A pulpectomy or extraction would then be indicated.
In addition to the aforementioned tests and observations when
dealing with traumatic injuries to the primary teeth, other factors must
be considered.
Studies have shown that 1 in 3 children receive traumatic injuries
to the primary dentition (16, 17). Because of the less dense bone and
shorter roots as compared with permanent teeth, most injuries are
displacements rather than fractures. Such injuries might heal normally
without sequelae by formation of an amorphous diffuse calcification
histologically resembling osteodentin, formation of a partial or complete obliteration of the canal (18, 19), or result in pulpal necrosis.
In a study of 545 traumatized primary maxillary incisors, Borum
and Andreasen (20) found that 53% of subjects developed pulpal necrosis, and 25% developed pulp canal obliteration. The factors found to
influence development of pulp necrosis were age of the patient, degree
of displacement and loosening, and concurrent crown fracture. Calcific
obliteration of the canal was influenced by tooth displacement and
amount of root resorption. Crown fracture decreased canal obliteration. They also pointed out that no well-established treatment guidelines
exist concerning healing processes and complications in primary teeth.
It has been suggested that the proximity to the succedaneous tooth
is an important factor when deciding on treatment for the injured primary tooth. The treatment least likely to damage the permanent tooth
should be chosen (1, 20). Conflicting data exist regarding treatment of
primary injuries. Studies have shown no relationship between treating
injured primary teeth compared with extraction regarding disturbance
of the permanent teeth (16, 21). Others have shown a tendency toward
more extensive disturbances in the mineralization when injured primary teeth were retained (22).
S8
Camp
Near universal agreement exists that avulsed primary incisors

should not be replanted because of the possibility of danger to the
permanent tooth bud (1).
Roughly half of traumatized primary teeth presenting for treatment
develop transient or permanent discoloration. These colors vary from
yellow to dark gray and usually become evident 13 weeks after trauma.
Primary teeth with yellow discoloration frequently have radiographic
signs of pulp canal calcification and have a low incidence of pulpal
necrosis (20, 23).
Injured primary teeth with dark gray discoloration are reported to
have necrotic pulps in 50% 82% of the cases. Conversely, necrosis of
the pulp occurred in teeth with no discoloration in approximately 25%
of injured primary incisors (20, 2325). Attempts to correlate discoloration to pathologic, radiographic, and histologic changes in the pulps
of injured primary incisors present mixed findings. Color change of the
tooth alone without other findings is not a reliable indicator of pulpal
health (26). Diagnosis of pulp necrosis in primary incisors is primarily
based on dark gray color change and radiographic evidence of periapical pathology or lack of root formation (1) (Fig. 4). Schroder et al.
(25) reported development of periapical osteitis in 82% of gray discolorations within 1 month. Andreasen and Riis (27) have shown that pulp
necrosis and periapical inflammation of 6 weeks duration did not lead
to developmental disturbances of permanent teeth. Thus, when diagnosis cannot be established, it is justifiable to wait for further developments.
Diagnosis of Pulpal Status in Permanent

Immature Teeth
In teeth with incomplete root formation, correct pulpal and periapical diagnosis is of paramount importance before proceeding with
any endodontic treatment because of the devastating result of loss of
vitality. Every attempt should be made to preserve the vitality of these
immature teeth until maturation has occurred. Loss of pulpal vitality
before completion of dentin deposition leaves a weak root more prone
to fracture as a result of the thin dentinal walls.
In a 4-year study, Cvek (28) noted a significant increase in cervical
root fractures in treated immature teeth compared with those with completed roots. In immature teeth, the frequency of fractures was dependent on the stage of root development, ranging from 77% in teeth with
the least to 28% in teeth with the most developed roots (28). Thus, even
if treatment is successful, prognosis for prolonged retention of the tooth
Figure 3. Internal resorption (arrow), as seen in this primary maxillary second

molar, will always be perforated and a candidate for extraction. Note the perforated root after extraction and the periodontal probe in the resorptive
perforation.
Pulp Symposium
Figure 4. The dark gray discoloration of the crown of this primary maxillary
central incisor is indicative of pulpal necrosis.
is greatly diminished. Loss of vitality before completion of root length

will lead to a poorer crown-to-root ratio, with possible periodontal
breakdown as a result of increased mobility. Therefore, all treatments in
this group of teeth are oriented toward vital procedures. If these more
conservative procedures fail, the tooth can still be treated with apexification, apical barrier techniques, or conventional root canal treatment.
Although numerous scientific studies have been reported on the
treatment of permanent teeth with immature apices, the literature is
almost devoid in the area of diagnosis of pulpal status in this group of
teeth.
The diagnosis begins with a thorough medical history and any
implications related to the anticipated treatment. The dental history and
characteristics of associated pain might be helpful in determining pulpal status. History of any traumatic injury to the facial area should be
explored in depth and recorded for future medical, dental, legal, and
insurance purposes.
The nature, type, length, and distinction between provoked and
spontaneous pain are recorded. Provoked pain caused by thermal,
chemical, or mechanical irritants usually indicates pulpal inflammation
of a lesser degree and is often reversible. Spontaneous pain, on the
other hand, is usually associated with widespread, extensive, degenerative, irreversible pulpal inflammation or necrosis.
The medical and dental histories are followed by a thorough clinical examination. Any areas of redness, swelling, fluctuance, tissue tenderness, dental decay, defective or missing restorations, or fractured or
mobile teeth are noted. Presence of discolored crowns or a parulis
might indicate pulpal necrosis. The alignment of the teeth, including any
infrapositioned or suprapositioned teeth, might provide valuable information.
Electric pulp tests and thermal tests are of limited value because of
the varied responses as roots mature. In addition, invalid data might
be obtained as a result of the often unreliable responses from children because of fear, management problems, and inability to un-
derstand or communicate accurately. Consequently, most diagnoses

are made on observation of clinical symptoms and radiographic
evidence of pathosis.
Numerous studies (29 32) have reported the unreliability of electric pulp tests in permanent teeth with open and developing apices.
Inconsistent results ranging from 11% in 6- to 11-year-olds with completely open apices (29) to 79% in older children (31) have been
reported. It is also possible to obtain a false-positive in teeth with liquefaction necrosis (33). Thus, electric pulp tests are of little value
during the period of root formation, because the data are not reliable.
Electric and thermal tests were shown to be unreliable after
traumatic injury to a tooth, and no response might be elicited even
after circulation has been restored (34, 35). The potential for healing is greater with incomplete root development than in fully formed
teeth.
Laser Doppler flowmetry has been reported to be very reliable for
diagnosing pulpal vitality (13, 36, 37). In a very detailed histologic and
radiographic study of revitalization of dogs teeth after reimplantation,
Yanpiset et al. (36) were able to make a correct diagnosis 84% of the
time. In nonvital pulps, the histologic study proved to be accurate in
95% of cases, whereas in vital ones the data were correct 74% of the
time. This significant difference in readings was observed at as early
as 4 weeks. Although the authors pointed out the validity of determining nonvital teeth, they cautioned against relying solely on this
test and would only initiate pulpal therapy after observing other
signs of pathology.
It has also been shown that blood pigment within a discolored
tooth crown interferes with laser light transmission (38). This limitation
is significant, because discoloration after trauma is frequent. Also, this
equipment has not been perfected for routine dental diagnosis and is
cost-prohibitive for the practicing dentist.
Thermal testing with ice and ethyl chloride are of limited value
diagnostically. Ice and ethyl chloride have consistently been reported to
be inferior to carbon dioxide snow (29 32) and dichlorodifluoromethane (DDM) (31, 39). Researchers have shown carbon dioxide
snow to consistently give positive responses near 100% even with open
apices (29 32).
Figure 5. Dark gray discoloration of the crown of this permanent maxillary

central incisor indicates pulpal necrosis.
S9
Pulp Symposium
Thermal tests with heat in permanent teeth with developing apices
are of limited value because of inconsistent responses (32) and are
rarely performed.
Radiographic examination and interpretation are key elements in the
diagnosis of pulpal pathology in teeth with developing apices. Good quality
periapical radiographs of any involved teeth are used to assess root devel-
opment and discover periapical rarefaction and root resorption. After traumatic injury, radiographs are essential to determine the presence of fractured bone and roots, displaced teeth, and imbedded foreign objects.
In posterior teeth, bite-wing radiographs are also necessary to
detect caries, proximity of lesions to the pulp, previous pulpal treatments, and quality of any restorations.
Figure 6. Apical barrier with MTA and strengthening of the thin root with bonded composite. (A) Preoperative radiograph of permanent maxillary left central incisor.
The pulp is necrotic, and the apex is open. (B) 4-mm plug of MTA placed at the apex. (C) Remainder of canal restored with bonded composite resin.
(D) Two-and-a-halfyear follow-up showing covering of MTA with cementum and healing of a periapical lesion.
S10
Camp
Pulp Symposium
Discoloration of a tooth crown after trauma is a common sequela
and one of the foremost diagnostic indicators (40 42). Yellow discoloration is usually indicative of pulp space calcification, and a gray color
usually signifies pulpal necrosis (40) (Fig. 5).
Transient coronal discoloration has been reported (42) in 4% of
teeth after luxation injuries as a result of vascular damage and hemorrhage immediately after injury. In these cases, it was speculated that
pulpal healing depends on the bacterial status. With bacterial infection,
healing is unlikely. In this group of teeth, determination of bacterial
status could not be ascertained on the basis of coronal discoloration,
loss of pulpal sensibility, or periapical rarefaction (42).
Transient apical breakdown occurs after displacement injuries
and might lead to misdiagnosis (42, 43). The development of transient
periapical radiolucencytogether with coronal discoloration, negative
electric pulp test, and cold response up to 4 monthswas shown to
subsequently regain the original color and normal pulpal responses
(43). Transient apical breakdown apparently is linked to the repair
process in the pulp and periapical tissues and returns to normal when
healing is complete (42). Bone loss, which produces the radiolucency,
eventually heals with new bone.
Universal agreement exists that immature teeth have the greatest
potential to heal after trauma or caries, particularly when the apical
foramen is wide open. This group of teeth also has the greatest chance
of misdiagnosis and mistreatment. To avoid mistakes, treatment must
not be undertaken on the basis of negative responses to pulp testing.
Radiographic and symptomatic assessment is currently the principal
diagnostic criterion. The following factors are key in making the diagnostic determination: symptoms of irreversible pulpitis or apical periodontitis; clinical signs of periradicular infection including swelling,
tenderness to percussion, mobility, or parulis formation; radiographically detectible bone loss; progressive root resorption; and arrested
root development compared with other adjacent teeth (44).
If doubtful, do not start treatment. Keep the patient under close
observation and continue to reassess the diagnostic criteria until a definitive diagnosis can be established.
The treatment of primary and young permanent teeth has changed
dramatically in recent years as new materials have been developed and
researched. The use of calcium hydroxide (for decades the standard for
pulp protection), pulp capping, and pulpotomy procedures in permanent teeth is being replaced with composite resins (45, 46) and mineral
trioxide aggregate (MTA) (ProRoot; Dentsply Tulsa Dental, Tulsa, OK).
Pulp capping with resin composites in monkeys produced the lowest
incidence of bacterial microleakage, pulpal inflammation, and incidence of pulpal necrosis when compared with calcium hydroxide and
glass ionomer cement (46).
When compared with calcium hydroxide, MTA produced significantly more dentinal bridging in a shorter time with significantly less
inflammation and less pulpal necrosis (47 49). MTA has been shown
to be cementoconductive, with attachment of cementoblasts to the material (49). Sarkar et al. (50) studied the interactions of MTA, a synthetic tissue fluid, and dentin of extracted teeth. They concluded that
calcium from the MTA reacted with phosphate in tissue fluid, producing
hydroxyapatite. The sealing ability, biocompatibility, and dentinogenic
activity of the material occur because of these physiochemical reactions.
Once considered taboo, vital pulpal treatment of symptomatic permanent teeth with MTA has been reported (5, 51, 52) to be successful,
allowing continued root development. Stronger roots with greatly improved prognosis for permanent retention are now possible.
Loss of pulpal vitality in open apex teeth in the past led to protracted treatment and often ended in early tooth loss caused by fracture
of weak roots. Apical barrier techniques with MTA now allow timely
completion of apexification and have eliminated the use of calcium
hydroxide, except as a temporary canal disinfectant. The use of MTA as

an apical barrier has become the standard for treatment of the open
apex pulpless tooth (Fig. 6). The development of bonded composite
techniques now allows strengthening of these weak roots to levels of
intact, fully formed roots and has virtually ended root fractures (5356)
(Fig. 6C).
Revascularization of teeth with necrotic infected canals has been
reported by using combinations of antibiotics (57, 58). The canals are
accessed and disinfected with copious irrigation of sodium hypochlorite. The canals are not instrumented. A paste of metronidazole, ciprofloxacin, and minocycline is placed in the canals and left for 1 month.
The tooth is re-entered, and endodontic files are inserted through the
apices to stimulate bleeding to produce a blood clot at the level of the
CEJ. After clotting, MTA is placed over the blood clot, and a permanent
external seal is placed. The clot is then revascularized, producing thickening of the canal walls and apical closure.
Stem cell research holds great hope for the future, with the aim of
healing impaired dental tissues including dentin, pulp, cementum, and
periodontal tissues. By stimulating the bodys intrinsic capacities, we
will be able to regenerate tissues, allowing further development of teeth
and bone or possibly the formation of new teeth to replace those ravaged by decay or lost to traumatic injuries.
References
1. Flores MT, Holan G, Borum M, Andreasen JO. Injuries to the primary dentition. In:
Andreasen JO, Andreasen F, Andersson L, eds. Textbook and color atlas of traumatic
injuries to the teeth. 4th ed. Oxford, UK: Blackwell Munksgaard, 2007.
2. Starkey PE. Management of deep caries of pulpally involved teeth in children. In:
Goldman HM, Forrest SP, Byrd DL, et al, eds. Current therapy in dentistry. vol 3. St
Louis, MO: Mosby, 1968.
3. Mass E, Zilberman U, Fuks AB. Partial pulpotomy: another treatment option for
cariously exposed permanent molars. J Dent Child 1995;62:3425.
4. Orban BJ, ed. Oral histology and embryology. 4th ed. St Louis, MO: CV Mosby Co,
1957.
5. Camp JH, Fuks AB. Pediatric endodontics: endodontic treatment for the primary and
young, permanent dentition. In: Cohen S, Hargreaves K, eds: Pathways of the pulp. 9th
ed. St Louis, MO: Mosby, 2006:822 82.
6. Kamijo Y. Studies on morphological change in the alveolar region of the jaw bone
with development of the permanent tooth from the standpoint of clinical anatomy.
Bull Tokyo Dent Coll 1967;8:41.
7. Zurcher E. The anatomy of the root canals of the teeth of the deciduous dentition and
of the first permanent molars. New York: William Wood & Co, 1925.
8. Hibbard E, Ireland RL. Morphology of the root canals of the primary molar teeth.
J Dent Child 1957;24:250.
9. Finn SB. Morphology of the primary teeth. In: Finn SB, Caldwell RC, Cheraskin E,
et al, eds. Clinical pedodontics. 3rd ed. Philadelphia: WB Saunders, 1967.
10. Ireland RL. Secondary dentin formation in deciduous teeth. J Am Dent Assoc
1941;28:1626.
11. Bevelander G, Benzer D. Morphology and incidence in secondary dentin in human
teeth. J Am Dent Assoc 1943;30:1079.
12. Guthrie TJ, McDonald RE, Mitchell DF. Dental hemogram. J Dent Res 1965;
44:678 82.
13. Evans D, Reid J, Strang R, Stirrups D. A comparison of laser Doppler flowmetry with
other methods of assessing the vitality of traumatized anterior teeth. Endod Dent
Traumatol 1999;15:284 90.
14. McDonald RE, Avery DR. Treatment of deep caries, vital pulp exposure, and pulpless
teeth in children. In: McDonald RE, Avery DR, eds. Dentistry for the child and adolescent. 7th ed. St Louis, MO: Mosby, 1999.
15. Pinkham JR. Diagnosis. In: Pinkham JR, ed. Pediatric dentistry: infancy through
adolescence. Philadelphia: WB Saunders, 1988.
16. Andreasen JO, Ravn JJ. Epidemiology of traumatic dental injuries to primary and
permanent teeth in a Danish population sample. Int J Oral Surg 1972;1:2359.
17. Glendor U. On dental trauma in children and adolescents: incidence, risk, treatment,
time, and cost. Swed Dent J 2000;140(Suppl):152.
18. Robertson A, Lundgren T, Andreasen JO, Dietz W, Hoyer I, Noren JG. Pulp calcifications in traumatized primary incisors: a morphologic and inductive analysis study.
Eur J Oral Sci 1997;105:196 206.
19. Holan G. Tube like mineralizations in the dental pulp of traumatized primary incisors.
Endod Dent Traumatol 1998;14:279 84.
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20. Borum MK, Andreasen JO. Sequelae of trauma to primary maxillary incisors:
I complications in the primary dentition. Endod Dent Traumatol 1998;14:31 44.
21. Andreasen JO, Ravn JJ. The effect of traumatic injuries to primary teeth on their
permanent successors: IIa clinical and radiographic follow-up study of 213 teeth.
Scand J Dent Res 1971;79:284 94.
22. Selliseth N. The significance of traumatized primary incisors on the development and
eruption of permanent teeth. Eur Orthodont Soc Trans 1970;46:443.
23. Holan G, Fuks AB. The diagnosis value of coronal dark-gray discoloration in primary
teeth following traumatic injuries. Pediatr Dent 1996;18:224 7.
24. Holan G. Development of clinical and radiographic signs associated with dark discolored primary incisors following traumatic injuries: a prospective controlled study.
Dent Traumatol 2004;20:276 87.
25. Schrder U, Wennberg E, Granath LE, Moller H. Traumatized primary incisors: follow-up program based on frequency of periapical osteitis related to tooth color. Swed
Dent J 1977;1:95 8.
26. Croll TP, Pascon EA, Langeland K. Traumatically injured primary incisors: a clinical
and histological study. J Dent Child 1987;54:40122.
27. Andreasen JO, Riis I. Influence of pulp necrosis and periapical inflammation of
primary teeth and their permanent successors: combined macroscopic and histological study in monkeys. Int J Oral Surg 1978;7:178 87.
28. Cvek M. Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta-percha: a retrospective clinical study. Endod Dent Traumatol 1992;8:4555.
29. Klein H. Pulp responses to electric pulp stimulator in the developing permanent
anterior dentition. J Dent Child 1978;45:199 202.
30. Fulling HJ, Andreasen JO. Influence of maturation status and tooth type of permanent
teeth upon electrometric and thermal pulp testing procedures. Scand J Dent Res
1976;84:286 90.
31. Fuss Z, Trowbridge H, Bender IB, Rickoff B. Assessment of reliability of electrical and
thermal pulp testing agents. J Endod 1986;12:3015.
32. Fulling HJ, Andreasen JO. Influence of splints and temporary crowns upon electric
and thermal pulp-testing procedures. Scand J Dent Res 1976;84:291 6.
33. Ehrmann EH. Pulp testers and pulp testing with particular reference to the use of dry
ice. Aust Dent J 1977;22:2729.
34. Ohman A. Healing and sensitivity to pain in young replanted human teeth: an experimental clinical and histologic study. Odontol Tidskr 1965;73:166 227.
35. Bhaskar SN, Rappaport HM. Dental vitality tests and pulp status. J Am Dent Assoc
1973;86:409 11.
36. Yanpiset K, Vongsavan N, Sigurdsson A, Trope M. Efficacy of laser Doppler flowmetry
for the diagnosis of revascularization of reimplanted immature dog teeth. Dent Traumatol 2001;17:6370.
37. Sigurdsson A. Pulpal diagnosis. Endod Top 2003;5:1225.
38. Heithersay GS, Hirsch RS. Tooth discoloration and resolution following a luxation
injury: Significance of blood pigment in dentin to laser Doppler flowmetry readings.
Quintessence Int 1993;24:669 76.
39. Karibe H, Ohide Y, Kohno H, et al. Study on thermal pulp testing of immature permanent teeth. Shigaku Odontol 1989;77:1006 13.
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40. Bakland LK. Endodontic considerations in dental trauma. In: Ingle JI, Bakland
LK, eds. Endodontics. 5th ed. Hamilton, Ontario, Canada: BC Decker Inc, 2002:
795 843.
41. Jacobsen I. Criteria for diagnosis of pulpal necrosis in traumatized permanent incisors. Scand J Dent Res 1980;88:306 12.
42. Andreasen F. Transient apical breakdown and its relation to color and sensibility
changes. Endod Dent Traumatol 1986;2:9 19.
43. Cohenca N, Karni S, Rotstein I. Transient apical breakdown following tooth luxation.
44. Mackie IC, Hill FJ. A clinical guide to the endodontic treatment of nonvital immature
permanent teeth. Br Dent J 1999;186:54 8.
45. Cox CF, Suzuki S. Re-evaluating pulpal protection: calcium hydroxide liners vs cohesive hybridization. J Am Dent Assoc 1994;125:82331.
46. Murray PE, Hafez AA, Smith AJ, Cox CF. Identification of hierarchical factors to guide
clinical decision making for successful long-term pulp capping. Quintessence Int
2003;34:6170.
47. Junn DJ, McMillan P, Bakland LK, Torabinejad M. Quantitative assessment of dentin
bridge formation following pulp-capping with mineral trioxide aggregate (MTA). J
Endod 1998;24:278.
48. Pitt-Ford TR, Torabinejad M, Abedi HR, Bakland LK, Kariyawasam SP. Using
mineral trioxide aggregate as a pulp-capping material. J Am Dent Assoc
1996;127:1491 4.
49. Thomson TS, Berry JE, Somerman MJ, Kirkwood KL. Cementoblasts maintain expression of osteocalcin in the presence of mineral trioxide aggregate. J Endod
2003;29:40712.
50. Sarkar NK, Caicedo R, Ritwik R, Moiseyeva R, Kawashima I. Physiochemical basis of
the biologic properties of mineral trioxide aggregate. J Endod 2005;31:97100.
51. Schmitt D, Lee J, Bogen G. Multifaceted use of Pro Root MTA root canal repair
material. Pediatr Dent 2001;23:326 30.
52. Mejare I, Cvek M. Partial pulpotomy in young permanent teeth with deep carious
lesions. Endod Dent Traumatol 1993;9:238 42.
53. Hernandez R, Bader S, Boston D, Trope M. Resistance to fracture of endodontically
treated premolars restored with new generation dentin bonding systems. Int Endod
J 1994;27:281 4.
54. Katebzadeh N, Dalton BC, Trope M. Strengthening immature teeth during and after
apexification. J Endod 1998;24:256 9.
55. Lawley GR, Schindler WG, Walker WA, Kolodrubetz D. Evaluation of ultrasonically
placed MTA and fracture resistance intracanal composite resin in a model of apexification. J Endod 2004;30:16772.
56. Goldberg F, Kaplan A, Roitman M, Manfre S, Picca M. Reinforcement effect of a resin
glass ionomer in the restoration of immature roots in vitro. Dent Traumatol
2002;18:70 2.
57. Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth with
apical periodontitis and sinus tract. Dent Traumatol 2001;17:1857.
58. Banchs F, Trope M. Revascularization of immature permanent teeth with apical
periodontitis: new technique protocol? J Endod 2004;30:196 200.
Pulp Symposium

Martin Trope, DMD
Abstract
The regenerative potential of dental pulp, particularly in
mature teeth, has been considered extremely limited.
However, our improved understanding of pulpal inflammation and repair and improved dental materials and
technologies make vital pulp therapy a viable alternative to root canal treatment. This article explores our
knowledge in this regard and the future potential of
saving or even regenerating the pulp as a routine
dental procedure. (J Endod 2008;34:S13-S17)
Key Words
Pulp, regeneration, revascularization, vital
From private practice, Philadelphia, Pennsylvania.

Address requests for reprints to Martin Trope, DMD, 1601
Walnut St, Suite 402, Philadelphia, PA 19102. E-mail address:
martin_trope@dentistry.unc.edu.
Conflict of Interest: Martin Trope, DMD, reports no financial interests or potential conflicts of interest.
doi:10.1016/j.joen.2008.04.001
The Importance of Vital Pulp

Although it is easy to understand the value of a vital pulp when the tooth is
immature and underdeveloped, it is also important to understand its value in a fully
formed tooth. Endodontic disease is apical periodontitis, and as such, the biologic
rationale for endodontics is the prevention or treatment of apical periodontitis. For
apical periodontitis to be present, the root canal must contain a necrotic infected pulp
(1). Therefore, the vital (noninfected) pulp ensures no apical periodontitis. Thus,
maintaining the vital pulp prevents apical periodontitis, and the potential to regenerate
an injured or necrotic pulp would be the best root filling possible.
The Pulps Regenerative Potential

The Unexposed Pulp
The inflamed pulp unexposed by caries or trauma always has the potential to be
repaired. Although our diagnostic ability to differentiate a vital from a necrotic pulp is
good, differentiating between reversibly and irreversibly inflamed pulp remains an
educated guess at best (2). We do know, however, that the younger the pulp, the better
its repair potential.
The Exposed Pulp
Treatment of the exposed pulp remains quite controversial, with different approaches endorsed by different dental specialties. Vital therapy (ie, pulp capping, partial or full pulpotomy) on traumatically exposed pulps is very successful (3), whereas
vital pulp therapy on the cariously exposed tooth is not nearly as successful (4). The
difference in success rates is explained by the status of the pulp at the time of the
procedure (Fig. 1). Capping the healthy pulp gives very high success rates, whereas
capping the inflamed pulp results in lower and less predictable success (Fig. 2) (5, 6, 7).
On the other hand, with a carious exposure the area and depth of inflammation are very
unpredictable, and pulp capping at the superficial exposure site is popular. Thus, it is
very likely that we would be capping an inflamed pulp, and more failures (necrotic
pulps) would result.
Another extremely important factor in the success of treating a vital exposure is the
coronal seal after the pulp capping/pulpotomy (8). Cox et al. (8) showed that the pulp
can withstand the toxicity of most dental materials, and that what was previously interpreted as toxicity was, in fact, due to the material not sealing adequately. Therefore, it is
considered essential that a well-sealed coronal seal be placed over the vital pulp therapy. This is considered much more important than the material used on the vital pulp.
Approaches to Treatment of Carious Exposure

in the Immature Tooth
Pediatric Dentistry
Because the young vital pulp has such good potential for repair, it is considered
reasonable to perform an indirect or direct pulp cap on a carious exposure as long as
a good coronal restoration can be placed (9). The rationale for this approach is that
most young pulps can heal as long as the coronal restoration does not allow leakage of
additional inflammatory stimulants or microorganisms.
Endodontics
Pulpal inflammation is usually superficial and is unlikely to extend past the canal
orifices, and the healing potential is good if a healthy pulp is treated. Hence, the optimal
approach is to perform a full pulpotomy (thus removing the coronally inflamed pulp)
and treating the presumably healthy pulp at the canal orifices. When the root canal has
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Figure 1. Histologic section of a pulp after a traumatic exposure 24 hours

previously. Only about 1 mm of superficial pulp is inflamed.
developed thick dentinal walls and the apices are closed, a full pulpectomy can be performed (Fig. 3).
Revascularization of Infected Pulp Space

Pulp Revascularization
Revascularization of an immature necrotic tooth has many potential advantages.
It has been shown that under certain conditions revascularization
can be achieved in young teeth that have been traumatically avulsed,
leaving a necrotic but uninfected pulp. Skoglund et al. (10) demonstrated that in extracted dog teeth, pulpal revascularization started immediately after reimplantation and was completed after approximately
45 days (Fig. 4). It is important to understand the biologic features
permitting revascularization in young avulsed teeth, so that we might
attempt to reproduce these unique conditions when the pulp space is
infected. The immature avulsed tooth has an open apex, short root, and
intact but necrotic pulp tissue. Therefore, the new tissue has easy access
to the root canal system and a relatively short distance for proliferation
to reach the coronal pulp horns. It has been experimentally shown that
the apical portion of a pulp might remain vital and proliferate coronally
after reimplantation, replacing the necrotized coronal portion of the
pulp (1113). The speed with which the tissue completely revascularizes the pulp space is important because bacteria from the outside are
continually attempting to enter the pulp space, and the presence of vital
pulpal tissue greatly slows or prevents the bacterial penetration into this
tissue compartment. The ischemically necrotic pulp that is unique to an
avulsion injury acts as a scaffold into which the new tissue grows, and the
fact that the crown is usually intact (rather than carious or with an access
cavity) slows bacterial penetration because their only access to the pulp is
through cracks (14) or enamel defects. Thus, the race between proliferation of new tissue and infection of the pulp space favors the new tissue.
Revascularization of the pulp space in a necrotic, infected tooth
with apical periodontitis was attempted by Nygaard-Ostby and Hjortdal
(15) in the 1960s but was mostly unsuccessful. However, the materials
and instruments available 40 50 years ago were probably not sufficient
to create an environment similar to the avulsed tooth, ie, a canal that is
free of bacteria, containing a scaffold for new tissue to grow and to be
largely resistant to further bacterial penetration. With currently available technologies it could be possible to effectively disinfect an infected
pulp, artificially place a scaffold, and then effectively seal the access
cavity to resist subsequent infection.
A recent case report by Banchs and Trope (16) has reproduced
results in cases reported by others, indicating that it might be possible to
replicate the unique circumstances of an avulsed tooth to revascularize
the pulp in infected necrotic immature roots (1113). Our case (Fig. 5)
described the treatment of an immature second lower right premolar
with radiographic and clinical signs of apical periodontitis with the
presence of a sinus tract. The canal was disinfected without mechanical
instrumentation but with copious irrigation with 5.25% sodium hypochlorite and the use of a mixture of ciprofloxacin, metronidazole, and
minocycline (17), mixed as described in Fig. 6.
A blood clot was produced to the level of the cementoenamel
junction to provide a scaffold for the ingrowth of new tissue followed by
a double seal of mineral trioxide aggregate in the cervical area and a
bonded resin coronal restoration above it. Clinical and radiographic
evidence of healing was observed as early as 22 days. The large radiolucency had disappeared within 2 months, and at the 24-month recall
it was obvious that the root walls were thick, and the development of the root
below the restoration was similar to the adjacent and contralateral teeth.
The antibacterial effectiveness of the triantibiotic paste reported by
Hoshino et al. (17) was confirmed by our group in a dog model with
infected immature roots (18). In addition, our group demonstrated in
dogs that the potential for revascularization does exist (Fig. 7), and that
the blood clot was essential as a scaffold (19). At this point, we are
unsure of which factors in the blood clot are important. When these
factors are isolated, they can be incorporated into a synthetic scaffold
that will be easier to for clinicians to manipulate compared with a blood
clot.
The procedure described in this section can be attempted in most
cases. If no signs of regeneration are present after 3 months, then more
traditional treatment methods can be initiated.
Figure 2. Carious exposure caused by caries. The underlying inflamed pulp is removed, and a partial pulpotomy is performed on the remaining healthy pulp with
calcium hydroxide (Courtesy Dr. Francisco Banchs).
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Figure 3. In this case a full pulpotomy was performed (thus removing the coronally inflamed pulp) and treating the presumably healthy pulp at the canal orifices. When
the root canal has developed thick dentinal walls and the apices are closed, a full pulpectomy can be done (Courtesy Dr. Francisco Banchs).
Figure 4. Revascularization of immature dog teeth during period of 45 days. The teeth were extracted and immediately replanted. During the course of 45 days the
blood supply moves into the pulp space.
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Figure 5. Immature tooth with a necrotic infected canal with apical periodontitis. The canal is disinfected with copious irrigation with sodium hypochlorite
and triantibiotic paste. After 4 weeks the antibiotic is removed, and a blood clot is created in the canal space. The access is filled with a mineral trioxide
aggregate base and bonded resin above it. At 7 months the patient is asymptomatic, and the apex shows healing of the apical periodontitis and some closure
of the apex. Reproduced with permission from Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: new treatment
protocol? J Endod 2004;30:196-200.
Figure 6. Composition and mixing instructions for the triantibiotic paste (adapted from Hoshino et al. (17)).
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Pulp Symposium
Figure 7. Revascularization of an immature dog tooth with apical periodontitis. The root was artificially infected, producing apical periodontitis. After treatment
similar to that described in Fig. 5, revascularization has occurred.
There has been a great deal of discussion as to the correct terminology for what has been called pulp revascularization in this article.
Some have used the cases shown as examples of pulp regeneration and
the beginning of stem cell technology in endodontics. It is clearly not
apexification because not only the apex is closed, but the canal walls are
thicker as well. Apexogenesis accomplishes a closed apex and thicker
dentinal walls but by definition uses remaining vital root pulp to attain
this goal, which is not the case here. Guided tissue regeneration has
been used in periodontics and has some merit. However, guided tissue
regeneration in periodontics assumes regeneration of periodontal
structures, yet this is not the case for pulp. In the present cases, we must
distinguish between revascularization and pulp regeneration. Presently,
we can only say with certainty that the pulp space has returned to a vital
state. On the basis of research in avulsed teeth and a recent study on
infected teeth, however, it is more likely that the tissue in the pulp space
is similar to a periodontal ligament than to pulp tissue (19). It appears
that there is approximately a 30% chance of pulp tissue reentering the
pulp space (20). Future research will need to be performed to stimulate
pulp regeneration from the pluripotential cells in the periapical region
(21).
References
1. Bergenholtz G. Micro-organisms from necrotic pulps of traumatized teeth. Odont
Revy 1974;25:34758.
2. Dummer PM, Hicks R, Huws D. Clinical signs and symptoms in pulp disease. Int
Endod J 1980;13:2735.
3. Cvek M. A clinical report on partial pulpotomy and capping with calcium hydroxide in permanent incisors with complicated crown fracture, J Endod
1978;4:2327.
4. Barthel CR, Rosenkranz B, Leuenberg A, Roulet JF. Pulp capping of carious exposures: treatment outcome after 5 and 10 years: a retrospective study. J Endod
2000;26;525 8.
5. Tronstad L, Mjor IA. Capping of the inflamed pulp. Oral Surg 1972;34:477 83.
6. Mjor IA, Tronstad L. The healing of experimentally induced pulpitis. Oral Surg
1974;38:1159.
7. Cvek M, Cleaton-Jones PE, Austin JC, Andreasen JO. Pulp reactions to exposure
after experimental crown fractures or grinding in adult monkeys, J Endod
1982;8:3919.
8. Cox CF, Keall HJ, Ostro E, Bergenholtz G. Biocompatibility of surface-sealed dental
materials against exposed pulps. Prosthet Dent 1987;57:19.
9. Sato T, Hoshino E, Uematsu H, Noda T. In vitro antimicrobial susceptibility to combinations of drugs on bacteria from carious and endodontic lesions of human deciduous teeth. Oral Microbiol Immunol 1993;8:172 6.
10. Skoglund A, Tronstad L, Wallenius K. A microradiographic study of vascular changes
in replanted and autotransplanted teeth in young dogs. Oral Surg Oral Med Oral
Pathol 1978;1:172 8.
11. Barrett AP, Reade PC. Revascularization of mouse tooth isografts and allografts using autoradiography and carbon-perfusion. Arch Oral Biol 1981;26:
5415.
12. Rule DC, Winter GB. Root growth and apical repair subsequent to pulpal necrosis in
children. Br Dent J 1966;120:586 90.
13. Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth with apical periodontitis and sinus tract. Dent Traumatol 2001;17:
1857.
14. Love RM. Bacterial penetration of the root canal of intact incisor teeth after a simulated traumatic injury. Endod Dent Traumatol 1996;12:289 93.
15. Nygaard-Ostby B, Hjortdal O. Tissue formation in the root canal following pulp
removal. Scand J Dent Res 1971:79:333 48.
periodontitis: new treatment protocol? J Endod 2004;30:196 200.
17. Hoshino E, Kurihara-Ando N, Sato I, et al. In-vitro antibacterial susceptibility of
bacteria taken from infected root dentine to a mixture of ciprofloxacin, metronidazole and minocycline. Int Endod J 1996;29:12530.
18. Windley W III, Teixeira F, Levin L, Sigurdsson A, Trope M. Disinfection of immature
teeth with a triple antibiotic paste. J Endod 2005;6:439 43.
19. Thibodeau B, Teixeira F, Yamauchi M, Caplan DJ, Trope M. Pulp revascularization of
immature dog teeth with apical periodontitis. J Endod 2007;33:680 9.
20. Ritter AL, Ritter AV, Murrah V, Sigurdsson A, Trope M. Pulp revascularization of
replanted immature dog teeth after treatment with minocycline and doxycycline
assessed by laser Doppler flowmetry, radiography, and histology. Dent Traumatol
2004;20:75 84.
21. Sonoyama W, Liu Y, Yamaza T, et al. Characterization of the apical papilla and its
residing stem cells from human immature permanent teeth: a pilot study. J Endod
2008;34:166 71.
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Vital Pulp Therapy with New Materials for Primary Teeth:

New Directions and Treatment Perspectives
Anna B. Fuks, CD
Abstract
Vital pulp therapy aims to treat reversible pulpal injury
and includes 2 therapeutic approaches: (1) indirect pulp
treatment for deep dentinal cavities and (2) direct pulp
capping or pulpotomy in cases of pulp exposure. Indirect pulp treatment is recommended as the most appropriate procedure for treating primary teeth with
deep caries and reversible pulp inflammation, provided
that this diagnosis is based on a good history, a proper
clinical and radiographic examination, and that the
tooth has been sealed with a leakage-free restoration.
Formocresol has been a popular pulpotomy medicament in the primary dentition and is still the most
universally taught pulp treatment for primary teeth.
Concerns have been raised over the use of formocresol
in humans, and several alternatives have been proposed. Controlled clinical studies have been critically
reviewed, and mineral trioxide aggregate and ferric
sulfate have been considered appropriate alternatives
to formocresol for pulpotomies in primary teeth with
exposed pulps. In most of the studies reviewed, the
caries removal method has not been described. The use
of a high-speed handpiece or laser might result in an
exposure of a normal pulp that would otherwise not
be exposed. (J Endod 2008;34:S18-S24)
Key Words
Ferric sulfate, formocresol, mineral trioxide aggregate,
primary teeth, pulp therapy
Professor Emeritus, Department of Pediatric Dentistry, Hadassah School of Dental Medicine, Hebrew University, Jerusalem, Israel.
Address requests for reprints to Dr Fuks at fuks@cc.huji.
ac.il.
Conflict of Interest: Anna B. Fuks, CD, reports no financial
interests or potential conflicts of interest.
doi:10.1016/j.joen.2008.02.031
he aim of vital pulp therapy is to treat reversible pulpal injuries in both permanent
and primary teeth, maintaining pulp vitality and function (1). In addition to these, in
primary teeth it is important to preserve the tooth until its natural exfoliation time, thus
preserving arch integrity (2). Vital pulp therapy includes 2 therapeutic approaches:
indirect pulp treatment (IPT) in cases of deep dentinal cavities and direct pulp capping
(DPC) or pulpotomy in cases of pulp exposure (1).
Advances in biomedical research open avenues for the design of new methods of
dental treatment, aiming at regeneration of the dentin-pulp complex. New approaches
have been based on the understanding of the molecular and cellular mechanisms
regulating dentinogenesis during dental tissue repair and their potential for clinical
exploitation (1).
The dental pulp possesses the ability to form a dentin-like matrix (tertiary dentin)
as part of the repair in the dentin-pulp organ (3). Vital pulp therapy aims to treat
reversible pulpal injury in cases in which dentin and pulp are affected by caries, restorative procedures, or trauma. Whenever the dentin-pulp complex is affected by injury, 3
different physiopathologic conditions might be observed at the dentin-pulp border:
1. In the case of mild injuries as in noncavitated enamel caries or slowly progressing
dentinal caries, the odontoblasts might survive, and the odontoblastic layer is
stimulated to form a tertiary dentin matrix beneath the injury (reactionary dentin). Reactionary dentin shows many similarities to the primary and secondary
dentin and can effectively oppose exogenous destructive stimuli to protect the
pulp (4).
2. With severe dentinal injuries without pulp exposure as in rapidly progressing
carious lesions or in severe tissue damage caused by cavity preparation, odontoblasts are destroyed subjacent to the affected dentin (5, 6). In an appropriate
metabolic state of the dentin-pulp complex, a new generation of odontoblast-like
cells might differentiate and form tubular tertiary dentin (reparative dentinogenesis) (3, 7). It must be emphasized that under clinical conditions, the matrix
formed at the pulp-dentin interface often comprises reactionary dentin, reparative dentin, or fibrodentin formation. It is impossible to distinguish these processes at the in vivo level, and the process might also be indistinguishable from a
biochemical and molecular point of view.
3. In the case of pulp exposure, the amputated pulp can be repaired by itself or after
application of capping materials (8 10). Pulp exposure caused by caries shows
very limited potential for pulp recovery as a result of bacterial infection of the pulp
for a substantial period of time, which compromises the defense reaction (11).
As part of the wound healing process in the repairing pulp, the dentinogenic
potential of pulp cells can be expressed. Proliferation, migration, and differentiation of progenitor cells can give rise to a new generation of reparative dentinforming cells (odontoblast-like cells), reconstituting the lost continuum at the
pulp-dentin border (12, 13).
Indirect Pulp Treatment

After this brief review of the cellular changes during tooth development and how
they are mimicked during tissue repair, we are able to assess the biologic validity of the
various vital pulp treatments. In this light, IPT, contrary to what was believed in the past,
can also be an acceptable procedure for primary teeth with reversible pulp inflammation, provided that the diagnosis is based on a good history and proper clinical and
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Pulp Symposium
radiographic examination, and the tooth has been sealed with a leakage-free restoration (2).
In a recent systematic review on complete or ultraconservative
removal of decayed tissue, Ricketts et al. (14) concluded that in deep
lesions, partial caries removal is preferable to complete caries removal
to reduce the risk of carious exposure.
Several articles reported the success of this technique in primary
teeth (1519). On the basis of the biologic changes previously described and the growing evidence of the success of IPT in primary teeth,
we can recommend IPT as the most appropriate treatment for symptomfree primary teeth with deep caries, provided that a proper, leakage-free
restoration can be placed. This issue will be discussed in greater detail
further in this symposium.
Direct Pulp Capping

DPC is carried out when a healthy pulp has been inadvertently
exposed during an operative procedure. The tooth must be asymptomatic, and the exposure site must be pinpoint in diameter and free of oral
contaminants. A calcium hydroxide medicament is placed over the exposure site to stimulate dentin formation and thus heal the wound and
maintain the pulps vitality (20).
DPC of a carious pulp exposure in a primary tooth is not recommended but can be used with success on immature permanent teeth.
DPC is indicated for small mechanical or traumatic exposures when
conditions for a favorable response are optimal. Even in these cases, the
success rate is not particularly high in primary teeth. Treatment failure
might result in internal resorption or acute dentoalveolar abscess (20).
Presently, DPC should still be looked on with some reservations in
primary teeth. This treatment, however, could be recommended for
exposed pulps in older children 1 or 2 years before normal exfoliation.
In these children, a failure of treatment would not imply the need for a
space maintainer after extraction, as it would in younger children.
In a recent article, Caicedo et al. (21) demonstrated good pulp
response in primary teeth after DPC or pulpotomy with MTA and concluded that MTA might be a favorable material for pulp capping and
pulpotomy in primary teeth.
Pulpotomy
Pulpotomy is still the most common treatment for cariously exposed pulps in symptom-free primary molars. The aim of this treatment
is to preserve the radicular pulp, avoiding pain and swelling, and ultimately to retain the tooth, preserving arch integrity (2). Formocresol
(FC) has been a popular pulpotomy medicament in the primary dentition for the past 70 years since its introduction by Sweet in 1932, and it
is still considered the most universally taught and preferred pulp treatment for primary teeth (2224). Concerns have been raised over the
use of FC in humans, mainly as a result of its toxicity and potential
carcinogenicity (2532).
The International Agency for Research on Cancer classified formaldehyde as carcinogenic for humans in June 2004, leaving the profession to look for other alternatives to FC (31). On the basis of the information available, an expert working group has determined that there is
now sufficient evidence that formaldehyde causes nasopharyngeal cancer in humans, a rare cancer in developed countries, limited evidence
for cancer of the nasal cavity and paranasal sinuses, and strong but not
sufficient evidence for leukemia.
There has been a significant amount of discussion in the dental
literature about the appropriateness and safety of using aldehyde-based
products in pediatric dentistry (29). FC is no longer used in some
countries, mainly as a result of safety concerns.
Milnes (33) published an extensive and detailed review of the

more recent research on the metabolism, pharmacokinetics, and carcinogenicity of formaldehyde and concluded that formaldehyde is not a
potent human carcinogen under conditions of low exposure. He concluded that extrapolation of these research results to pediatric dentistry
suggests an inconsequential risk of carcinogenesis associated with
formaldehyde use in pediatric pulp therapy.
In a case-control study in which FC pulpotomies were performed
in 5- to 10-year-old children, blood samples were taken before (control) and after treatment to observe the mutagenic potential of FC on
lymphocytes cultures. No statistically significant differences could be
observed in the cultured lymphocytes. FC was mutagenic for one patient,
however, leading the authors to raise doubts about the desirability of
using this technique in children (34).
No correlation between FC pulpotomies and cancer has ever been
demonstrated. Nevertheless, several studies have reported that the clinical success of FC pulpotomies decreases with time, and the histologic
response of the primary pulp is capricious, ranging from chronic
inflammation to necrosis (35).
Presently, there are several pulp dressing medicaments that have
been proposed to maintain radicular pulp vitality that are equal to, if not
better than, FC and can be used as alternatives to pulpotomies in primary teeth. The pulp dressing materials and techniques proposed include: electrosurgery (36, 37), laser (38, 39), glutaraldehyde (GT)
(40 44), calcium hydroxide (CH) (45 47), freeze-dried bone (48),
bone morphogenetic protein (49), osteogenic protein (50), ferric sulfate (FS) (5156), mineral trioxide aggregate (MTA) (24, 5759), and
sodium hypochlorite (60).
Although a considerable number of clinical trials and laboratory
animal studies have been published on this subject, the Cochrane review
found that evidence is lacking to conclude which is the most appropriate
technique for pulpotomies in primary teeth (61). The Cochrane review
assessment is extremely rigorous, and with the exception of 3 articles,
none of the articles evaluated could meet the criteria and were excluded.
Evidence-Based Analysis of Pulpotomy Literature

Loh et al. (62) published an evidence-based assessment of FC
versus FS by using a different sieving system including all suitable clinical trials, not only randomized ones. They concluded that both materials were likely to produce similar clinical/radiographic success.
Following Cochranes criticism regarding the paucity of appropriately designed, statistically assessed investigations and the lack of longterm outcomes, many studies have been reported, and several others
have begun to contribute to the literature (32).
Fuks and Papagiannoulis (63) assessed the relevant articles that
have appeared after the aforementioned reviews by using the clinically
based criteria listed by Curzon and Toumba (64). In this review, the
MEDLINE search used generated a total of 358 citations, and the sieving
of these articles was conducted by examining the article title and assessing its relevance (62).
All articles were graded according to the aforementioned criteria
and classified as A if the article met 90% or more of the criteria; B1 if an
article scored from 75% 89%; B2 if it scored between 60%74%; and
C if it scored 59% or less, which meant that it had to be excluded. Even
with different weights attributed to the evaluated articles, no conclusion
could be reached as to the optimum treatment or technique for pulpally
involved primary teeth. In a meta-analysis to compare the clinical and
radiographic effects of MTA with FC, Peng et al. (65) reported that MTA
was superior to FC. These authors claimed that MTA induces less undesirable responses and might be a suitable replacement for FC.
Vital Pulp Therapy with New Materials for Primary Teeth
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Pulp Symposium
TABLE 1. Articles Directly Comparing MTA and FC
Direct comparison
articles: MTA FC
Molars,
FC (N)
Molars,
MTA (N)
Success
(clinical), FC
N (%)
Success
(clinical), MTA
N (%)
Success
(x-ray), FC
N (%)
Success
(x-ray), MTA
N (%)
Follow-up
(mo)
Cuisia et al. (2001)

Agamy et al. (2004)
Jabbarifar et al. (2004)
Farsi et al. (2005)
Holan et al. (2005)
Naik and Hegde (2005)
30
20
32
36
29
23
30
19
32
38
33
24
28 (93)
18 (90)
29 (91)
35 (97)
24 (83)
23 (100)
29 (97)
19 (100)
30 (94)
38 (100)
32 (97)
24 (100)
23 (77)
18 (90)
29 (91)
31 (86)
24 (83)
23 (100)
28 (93)
19 (100)
30 (94)
38 (100)
32 (97)
24 (100)
6
12
12
24
74
6
FC, formocresol.
In another meta-analysis that included clinical trials and randomized, clinical trials, Deery (66) concluded that pulpotomies performed
with either FS or FC were likely to produce similar results.
Although meta-analysis generally pools data from randomized,
clinical trials, they are regarded as observational studies of evidence
(67 69). Usually the reviewer identifies the relevant studies from the
literature and decides whether to include or exclude them. Therefore,
the strength of conclusions drawn from a meta-analysis might only be
comparable to that drawn from observational studies, which are open to
various forms of bias. Problems, including publication bias and the
variable quality of the primary studies, can threaten the validity of metaanalysis (70). Another limitation of meta-analyses is that they all search
for relevant articles in electronic databases and are limited to the English language. Most databases date only from 1965. For this reason
articles that could have been relevant, particularly on CH or FC pulpotomies, were not included. Language bias can also occur because researchers whose native language is not English are more likely to publish nonsignificant results in non-English journals and significant results
in English journals (70).
One of the aims of evidence-based dentistry is to reach an evidence-based conclusion and then translate it into a clinical decision that
would result in a better treatment outcome. With these points in mind,
this article will consist of critically assessing the randomized and nonrandomized human clinical trials that resulted from a MEDLINE search.
This search generated a total of 358 citations, as described by Fuks and
Papagiannoulis (63), with the addition of the relevant studies published
after that date. Duplicate publications of the same study were excluded.
The articles assessed will be limited to the comparisons of FS, MTA, and
CH with FC and are presented in Tables 13.
Studies Comparing MTA With FC

Cuisia et al. (2001)71
This randomized, clinical trial compared MTA with FC, but the
randomization method was not reported. Only asymptomatic molars
without clinical and/or radiographic evidence of pulp degeneration
were included. Pulpotomies were performed in 60 molars by 1 pediatric dentist using a local anesthetic and restored with a stainless steel
crown, but there was no mention of the use of a rubber dam. The results
were assessed by 2 pediatric uncalibrated dental residents at 6-month
follow-up; the clinical success rate was 93% for FC and 97% for MTA,
whereas the radiographic success was 77% for FC and 93% for MTA.
Agamy et al. (2004)57

This randomized, clinical trial compared gray MTA, white MTA,
and FC in 72 molars of 24 children. Only restorable molars without
clinical and/or radiographic evidence of pulp degeneration were included. Each child had at least 3 molars with severe carious involvement
and received pulpotomies with all 3 medicaments. An additional 15
carious teeth planned for serial extractions after 6 months were selected
for the histologic part of the study. All pulpotomies were performed by
the same pediatric dentist, and outcome assessment after 12 months
was done by 2 blinded pediatric dentists. Four children (12 molars)
dropped out, and of the remaining 60 teeth in 20 patients, 1 (gray MTA)
exfoliated normally, and another 6 teeth (4 white MTA and 2 FC) failed
as a result of abscesses. The remaining 53 teeth appeared to be clinically
and radiographically successful. In the histologic study, both types of
MTA formed thick dentin bridges, but the gray MTA appeared to be
better than white MTA and FC as a pulp dressing, because it presented
the closest to normal pulp architecture.
Jabbarifar et al. (2004)72
This randomized, clinical trial compared MTA with FC in 64 molars assigned to 2 groups by the toss of a coin. The number of pediatric
dentists who performed the treatments was not specified, rubber dam
isolation was not reported, and all the teeth were restored with SSCs. Outcome assessment of 64 molars remaining at 12 months was done by 2
blinded pediatric dentists. The number of molars treated at the baseline
and the number of dropouts were not reported. Clinical and radiographic
success for MTA was 94% and for FC was 91%.
Farsi et al. (2005)59
This randomized, clinical trial compared MTA with FC in 120 molars of 100 children assigned to 2 groups by the toss of a coin. Only
restorable molars without clinical and/or radiographic evidence of pulp
TABLE 2. Articles Comparing Directly FS and FC

Direct comparison
articles: FC FS
Molars,
FC (N)
Molars, FS
(N)
Success
(clinical), FC
N (%)
Success
(clinical), FS
N (%)
Success
(x-ray), FC
N (%)
Success
(x-ray), FS
N (%)
Follow-up
(mo)
Fei et al. (1991)

Fuks et al. (1997)
Aktoren and Gencay (2000)
Papagiannoulis (2002)
Ibrevic and Al-Jame (2003)
Huth et al. (2005)
Markovic et al. (2005)
27
37
24
60
80
48
33
29
55
24
73
84
49
37
26 (96)
31 (84)
21 (88)
58 (97)
78 (97)
46 (96)
30 (91)
29 (100)
51 (93)
21 (88)
66 (90)
81 (96)
49 (100)
33 (89)
22 (81)
27 (73)
19 (80)
47 (78)
75 (94)
43 (90)
28 (85)
28 (97)
41 (93)
20 (84)
54 (74)
77 (92)
42 (86)
30 (81)
12
35
24
36
4248
24
18
FC, formocresol; FS, ferric sulfate.
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Fuks
Pulp Symposium
TABLE 3. Articles Directly Comparing CH and FC
Direct comparison
articles: FC CH
Molars,
FC (N)
Molars,
CH (N)
Success
(clinical), FC
N (%)
Success
(clinical), CH
N (%)
Success
(x-ray), FC
N (%)
Success
(x-ray), CH
N (%)
Waterhouse et al. (2000)

Huth et al. (2005)
Markovic et al. (2005)
44
48
33
35
38
34
37 (84)
46 (96)
30 (91)
27 (77)
33 (87)
28 (82)
37 (84)
43 (90)
28 (85)
27 (77)
25 (66)
26 (76)
Follow-up (mo)
To exfoliation
24
18
FC, formocresol; CH, calcium hydroxide.
degeneration were included. The number of pediatric dentists who performed the treatments was not specified, rubber dam isolation was not
reported, and all the teeth were restored with SSCs. At 24 months, 46
molars (38%) were lost, leaving 74 molars for evaluation. All the MTAtreated molars were successful clinically and radiographically (100%). For
the FC, clinical and radiographic success was 97% and 86%, respectively.
the pulpotomies under a local anesthetic and with a rubber dam, but
outcome assessors were not reported. Molars with pulp canal obliteration (PCO) were not considered failures. The dropout rate was 4%
(4/96 molars) after 6 34 months. Clinical success for FC was 84% and
for FS was 93%; radiographic success was 80% for FC and 93% for FS.
No statistical difference was observed between the 2 groups.
Holan et al. (2005)24

This randomized, clinical trial compared MTA with FC in 64 molars of 35 children assigned to 2 groups by the toss of a coin. The
number of operators was not specified, and in 56 molars SSCs were
placed, 1 molar received a composite restoration, and the other 7 teeth
were restored with amalgam. Clinical outcomes were assessed by 1
pediatric dentist without blinding. Radiographs were assessed by 3
blinded pediatric dentists using a standardized evaluation form for
calibration (complete agreement for all cases). Internal resorption was
considered a failure only when it reached the bone. Arrested internal
resorption, calcific metamorphosis, and pulp canal obliteration were
not considered failures.
At 74 months, 2 molars (3%) were lost, leaving 62 molars for
evaluation. Clinical and radiographic success was 97% for MTA and
83% for FC, respectively.
Aktoren and Gencay (2000)73

This randomized, clinical trial compared FS, FC, and GT. Only
asymptomatic and restorable molars without clinical and radiographic
signs of pulp degeneration were included. Clinicians performing the
pulpotomies and outcome assessors were not described. At 24 months,
clinical success rates for 72 molars were reported to be 88% for both FC
and FS, and radiographic success was 80% for FC and 84% for FS.
Naik and Hegde (2005)58

This randomized, clinical trial compared MTA with FC in 50 molars assigned randomly (method not specified) to 2 groups. The inclusion criterion was asymptomatic deep carious lesion with no frank
exposure. Pulpotomies were performed by a postgraduate dentist under local anesthesia and rubber dam. It was not clear whether preoperative radiographs were taken and SSCs were placed 24 hours later.
Three teeth were lost to follow-up (2 FC and 1 MTA), and all the remaining teeth were clinically and radiographically successful at the
6-month follow-up.
Studies Comparing FS With FC

Fei et al. (1991)51
This randomized, clinical trial compared FS wth FC in 83 molars in
62 children assigned by a table of random numbers to 2 groups. Only
restorable molars without clinical or radiographic signs of pulpal degeneration were included. Teeth with pulpal hemorrhage persisting
after 2 applications of FS or FC were eliminated. A pediatric dentistry
postgraduate student performed all pulpotomies, and 2 pediatric dentists were blinded and calibrated before radiographic assessment. At
12 months, 27 molars were lost, leaving 56 molars for assessment.
Clinical success for FC was 96% and for FS was 100%; radiographic
success was 81% for FC and 97% for FS.
Fuks et al. (1997)52
This randomized, clinical trial compared FS with FC in 96 molars
in 72 children assigned to 2 groups by a toss of a coin. Only asymptomatic and restorable molars without clinical and radiographic signs of
pulp degeneration were included. Three pediatric dentists performed
Papagiannoulis (2002)74
This randomized, clinical trial compared FS with FC in 133 molars
in 90 children assigned to 2 groups by a toss of a coin. Only asymptomatic and restorable molars without clinical and radiographic signs of
pulp degeneration were included. Pulpotomies were performed by 3
pediatric dentists; most molars were restored with SSCs, and a few
received composite resin restorations. Outcomes were assessed by a
separate blinded pediatric dentist. Molars with PCO or nonprogressive internal resorption were not considered failures. Clinical success
was 97% for FC and 90% for FS, and radiographic success was 78% for
FC and 74% for FS.
Ibrevic and Al-Jame (2003)54
This randomized, clinical trial compared FS with full-strength FC in
194 molars in 70 patients allocated alternately to 2 groups. Only restorable molars without clinical and radiographic signs of pulp degeneration were included. Pulpotomies were performed by 1 pediatric dentist,
and most molars received SSCs; a few molars were restored with amalgam. Clinical outcomes were assessed by the operator, but radiographic
outcomes were assessed by both the operator and another blinded
evaluator. Calibration was not reported, but both assessors reached
consensus on radiographic outcomes. Ten patients (30 molars)
dropped out after 42 months. Clinical success rates were 97% in the FC
group and 96% in the FS group. The radiographic success rate was 94%
in the FC group and 92% in the FS group. No statistical differences were
found between the radiographic assessments of both pulpotomy agents.
Huth et al. (2005)47
This randomized, clinical trial compared FS, FC, CH, and laser in
107 children. A power calculation estimated the numbers of molars
required to achieve statistical significance. Randomization was done by
casting a concealed lot from a box of 4 50 lots, such that 200 molars
were allocated to 4 groups. Only asymptomatic restorable molars without clinical and radiographic signs of pulp degeneration were included.
The molars received SSCs or composite resin restorations. Two pediatric dentists performed the pulpotomies under local or general anesthesia and rubber dam, and 2 other blinded experienced dentists perVital Pulp Therapy with New Materials for Primary Teeth
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Pulp Symposium
formed outcome assessments. Intraexaminer and interexaminer
reproducibility was optimal (K 1.0). The dropout rate was 8% (16/
191 molars), and the remaining participants were examined after 24
months. Clinical success rate was 96% for FC and 100% for FS, and
radiographic success was 90% for FC and 86% for FS.
Markovic et al. (2005)56

This randomized, clinical trial compared FS, FC, and CH in 104
molars in 104 children assigned randomly to 3 groups. Vital cariousexposed molars with no radiographic signs of pulpal degeneration were
included. Pulpotomies were performed by 3 pediatric dentists, and
outcomes were assessed by a separate evaluator. The intraexaminer
agreement was moderate (K 0.70). The number of molars at baseline
and the number of dropouts were not reported. The clinical success rate
at 18 months for FC was 91%, for FS was 89%, and for CH was 82%. The
radiographic success was 85% for FC, 82% for FS, and 76% for the CH
group. These differences, however, were not statistically significant.
Studies Comparing CH With FC

Three articles compared directly CH with FC. Two of them have
been summarized previously (47, 56).
Waterhouse et al. (2000)75

This randomized, clinical trial compared FC and CH in 84 molars
in 52 children assigned to 2 groups by the toss of a coin. Only healthy
children with restorable molars without clinical and radiographic signs
of pulp degeneration were included. Pulpotomies were performed by
clinicians under rubber dam or cotton roll isolation; SSCs were placed
where indicated (indications not described), and other molars were
restored with amalgam, glass ionomer, or compomer. Outcomes were
assessed by a separate pediatric dentist, blinded and calibrated in a
parallel study (77% interexaminer agreement). At 22 months, 5 molars
in 3 patients dropped out, leaving 79 molars in 49 children. Clinical and
radiographic success was 84% for FC and 77% for CH.
Studies Comparing Laser With FC

Saltzman et al. (2005)39
This randomized single-blind, split-mouth clinical trial compared
a diode laser pulpotomy with MTA with a conventional FC/zinc oxide
eugenol (ZOE) pulpotomy. A total of 26 pairs of teeth from 16 patients
between 3 8 years old were selected on the basis of clinical and radiographic criteria. All teeth were followed up clinically and radiographically for 15 months. A total of 7 laser-MTAtreated teeth were radiographic failures, as opposed to 3 FC/ZOE-treated teeth at 15.7 months;
however, these results were not statistically significant. The authors suggested that an improved success rate among a larger patient sample and a
longer follow-up period would be required for the laser-MTA pulpotomy to
be considered a suitable alternative to conventional FC pulpotomy.
Liu JF (2006)76
This clinical study compared the effects of Nd:YAG laser pulpotomy
with FC on human primary teeth. Patients without any medically compromised disease were selected from the patient population at a hospital-based dental clinic in Taiwan. Primary teeth that required pulpotomy
because of carious pulp exposure were selected for this study. Fifty
children with an average age of 5 years, 3 months (range, 4 7 years)
participated in the study group, and a total of 68 primary molars were
treated with the Nd:YAG laser. Forty-four children participated in the
control group, and 69 primary molars were treated with diluted FC.
Follow-up time was between 6 64 months. In the Nd:YAG laser group,
clinical success was achieved in 66 of 68 teeth (97%), and 94% were
S22
Fuks
radiographically successful. In the control group, 85% and 78%

achieved clinical and radiographic success, respectively. The success
rate of the Nd:YAG laser was significantly higher than that of the FC
pulpotomy. The permanent successors of the laser-treated teeth erupted
without any complications.
Study Comparing Sodium Hypochlorite With FS

Vargas et al. (2006)60
This prospective randomized, clinical study compared the effectiveness of 5% sodium hypochlorite (NaOC1) with that of FS as a pulpotomy medicament in decayed primary molars. Twenty-three healthy
patients between 4 and 9 years old with at least 2 primary molars
needing a pulpotomy were included in the study. The teeth were clinically and radiographically examined, and the signs/symptoms were recorded at 0, 6, and 12 months. Six-month results were based on the first
32 teeth in the NaOC1 group and 28 teeth in the FS group. Twelve-month
results were based on 13 teeth in the FS group and 14 in the NaOC1
group. At 6 months, 100% clinical success was found in both the FS and
NaOC1 groups. Radiographic success for FS was 68%, with internal
resorption being the most common finding. The NaOC1 showed 91%
radiographic success. At 12 months, FS had 85% clinical success and
62% radiographic success. NaOC1 had 100% clinical success and 79%
radiographic success. The authors concluded that preliminary evidence
showed that NaOC1 can be used successfully as a pulpotomy medicament.
Summary
From this review of the randomized, clinical trials, one can observe that all the studies comparing MTA with FC showed that MTA
presented better results, even though in some of them there was no
statistical difference as a result of the small number of teeth tested. FS
was also better than FC in some studies and similar to FC in others, whereas
the 3 studies with CH showed inferior outcomes. It should be emphasized,
however, that in most of the studies the method of caries removal has not
been described. The use of a high-speed handpiece or laser might result in
an exposure of a normal pulp that would otherwise not be exposed and
not need a pulpotomy or that could be alternatively treated by IPT.
As previously mentioned, one of the aims of evidence-based dentistry is to reach an evidence-based conclusion and then translate it into
a clinical decision that would result in a better treatment outcome. It
should be kept in mind, however, that improving patient care requires
the consideration of other factors including the cost and technique
sensitivity of the new medicament.
From the studies previously presented, MTA showed better results
in all cases and should be recommended as an alternative to FC. One of
the drawbacks of this material, however, is its high cost, and its use in
pediatric dentistry practice can become almost prohibitive in some
circumstances. Hence, FS can still be considered a valid and inexpensive solution for pulpotomies in primary teeth (2).
A recent preliminary evaluation of sodium hypochlorite showed
promising results when compared with FS. The follow-up time, however, is only 1 year. Longer follow-up and more clinical studies are
needed to confirm these results.
References
1. Tziafas D. The future role of a molecular approach to pulp-dentinal regeneration.
Caries Res 2004;38:314 20.
2. Fuks AB. Current concepts in vital primary pulp therapy. Eur J Paediatr Dent
2002;3:11520.
3. Baume LJ. The biology of pulp and dentine. In: Myers HM, ed. Monographs in oral
science. Basel, Switzerland: Karger, 1980:67182.
4. Smith AJ, Sloan AJ, Matthews JB, Murray PE, Lumley P. Reparative process in dentine
and pulp. In: Addy M, Embery G, Edgar WM, Orchardson R, eds. Tooth wear and
sensitivity. London, UK: Dunitz, 2002:53 66.
Pulp Symposium
5. Bjorndal L, Mjor IA. Pulp-dentin biology in restorative dentistry: 4 dental caries:
characteristics of lesions and pulpal reactions. Quintessence Int 2001;32:71736.
6. Kitamura C, Kimura K, Nakayama T, Toyoshima K, Terashita M. Primary and secondary induction of apoptosis in odontoblasts after cavity preparation of rat molars. J
Dent Res 2001;80:1530 4.
7. Bjorndal L, Darnnavan T. A light microscopic study of odontoblastic and nonodontoblastic cells involved in tertiary dentinogenesis in well-defined cavitated carious
lesions. Caries Res 1999;33:50 60.
8. Nyborg H. Healing process in the dental pulp on capping: a morphologic
study experiments on surgical lesions of the pulp in dog and man. Acta Odontol
Scand 1955;13(Suppl 16):1130.
9. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposure on dental
pulps in germ-free and conventional laboratory rats. Oral Surg Oral Med Oral Pathol
1965;20:340 9.
10. Yamamura T. Differentiation of pulpal cells and inductive influences of various matrices with reference to pulpal wound healing. J Dent Res 1985;64:530 40.
11. Bergenholz G. Factors in pulpal repair after oral exposure. Adv Dent Res 2001;15:84.
12. Fitzegerald M, Ghiego JD Jr, Heis R. Autoradiographic analysis of odontoblasts replacement following pulp exposures in primate teeth. Arch Oral Biol 1990;
35:70715.
13. Mjor IA, Dahl E, Cox CF. Healing of pulp exposure: an ultrastructural study. J Oral
Pathol Med 1991;20:496 501.
14. Ricketts DNJ, Kidd EAM, Innes N, Clarkson J. Complete or ultraconservative removal
of decayed tissue in unfilled teeth. Cochrane Database Syst Rev 2006;CD003808.
15. Farooq NS, Coll JA, Kuwabara A, Shelton P. Success rates of formocresol pulpotomy
and indirect pulp treatment of deep dentinal caries in primary teeth. Pediatr Dent
2000;22:278 86.
16. Straffon LH, Loos P. The indirect pulp cap: a review and commentary. Isr J Dent Sci
2000;17:714.
17. Falster CA, Araujo FB, Straffon LH, Nor JE. Indirect pulp treatment: In vivo outcomes
of am adhesive resin system vs calcium hydroxide for protection of the dentin-pulp
complex. Pediatr Dent 2002;24:241 8.
18. Al-Zayer MA, Straffon LH, Feigal RJ, Welch KB. Indirect pulp treatment of primary
posterior teeth: a retrospective study. Pediatr Dent 2003;25:29 36.
19. Marchi JJ, de Araujo FB, Froner AM, Straffon LH, Nor JE. Indirect pulp capping in the
primary dentition: a 4-year follow-up study. J Clin Pediatr Dent 2006;31:68 71.
20. Fuks AB. Pulp therapy for the primary dentition. In: Pediatric dentistry: infancy
through adolescence. St Louis, MO: Elsevier, 2005:11830.
21. Caicedo R, Abbott PV, Alongi DJ, Alarcon MY. Clinical, radiographic and histological
analysis of the effects of mineral trioxide aggregate used in direct pulp capping and
pulpotomies of primary teeth. Aust Dent J 2006;51:297305.
22. Primosch RE, Glom TA, Jerrell RG. Primary tooth pulp therapy as taught in predoctoral pediatric dental programs in the United States. Pediatr Dent 1997;19:118 22.
23. Vij R, Coll JA, Shelton P, Farooq NS. Caries control and other variables associated with
success of primary molar vital pulp therapy. Pediatr Dent 2004;26:214 20.
24. Holan G, Eidelman E, Fuks AB. Long-term evaluation of pulpotomy in primary molars
using mineral trioxide aggregate and formocresol. Pediatr Dent 2005;27:129 36.
25. Auerbach C, Moutschen-Damen M, Moutschen M. Genetic and cytogenetical effects of
formaldehyde and related compounds. Mutat Res 1977;39:317 61.
26. Pruhs RJ, Olen GA, Sharma PS. Relationship between formocresol pulpotomies on
primary teeth and enamel defects on their permanent successors. J Am Dent Assoc
1977;94:698 700.
27. Block RM, Lewis RD, Sheats JB, Burke SG. Antibody formation to dog pulp tissue
altered by formocresol within the root canal. Oral Surg 1978;45:28292.
28. Myers DR, Shoaf HK, Dirksen TR, Pashley DH, Whitford GM, Reynolds KE. Distribution of 14c formaldehyde after pulpotomy with formocresol. J Am Dent Assoc
1978;96:80513.
29. Judd PL, Kenny DJ. Formocresol concerns: a review. J Can Dent Assoc 1987;
53:401 4.
30. Sun HW, Feigal RJ, Messer HH. Cytotoxicity of glutaraldehyde and formaldehyde in
relation to time of exposure and concentration. Pediatr Dent 1990;12:3037.
31. International Agency for Research on Cancer. Press release no. 153. Available at:
http://www.iarc.fr/ENG/Press_Releases/archives/pr153a.html. Accessed June 15,
2004.
32. Srinivasan V, Patchett CL, Waterhouse JP. Is there life after Buckleys formocresol?
part I: a narrative review of alternative interventions and materials. Int J Paediatr Dent
2006;16:11735.
33. Milnes AR. Persuasive evidence that formocresol use in pediatric dentistry is safe.
J Can Den Assoc 2006;72:247 8.
34. Zarzar PA, Rosenblatt A, Takahashi CS, Takeuchi PL, Costa Junior LA. Formocresol
mutagenicity following primary tooth pulp therapy: an in-vivo study. J Dent
2003;31:479 85.
35. Rolling I, Thylstrup A. A 3-year follow-up study of pulpotomized primary molars
treated with the formocresol technique. Scand J Dent Res 1975;83:4753.
36. Fishman SA, Udin RD, Good DL, Rodef F. Success of electrofulguration pulpotomies
covered by zinc oxide and eugenol or calcium hydroxide: a clinical study. Pediatr
Dent 1996;18:38590.
37. Sasaki H, Ogawa T, Koreeda M, Ozaki T, et al. Electrocoagulation extends the indication of calcium hydroxide pulpotomy in the primary dentition. J Clin Pediatr Dent
2002;26:2757.
38. Elliot RD, Roberts MW, Burkes J, Phillips C. Evaluation of carbon dioxide laser on
vital human primary pulp tissue. Pediatr Dent 1999;21:32731.
39. Saltzman B, Sigal M, Clokie C, et al. Assessment of a novel alternative to conventional
formocresol-zinc oxide eugenol pulpotomy for the treatment of pulpally involved
human primary teeth: diode laser-mineral trioxide aggregate pulpotomy. Int J Paediatr Dent 2005;15:437 47.
40. Alacam A. Long-term effects of primary teeth pulpotomies with formocresol, glutaraldehyde-calcium hydroxide, and glutaraldehyde-zinc oxide eugenol on succedaneous teeth. J Pedod 1989;18:12332.
41. Prakash C, Chandra S, Jaiswal JN. Formocresol and pulpotomies in primary teeth.
J Pedod 1989;13:314 22.
42. Fuks AB, Bimstein E, Klein H, Guelmann M. Assessment of a 2% buffered glutaraldehyde
solution in pulpotomized primary teeth of schoolchildren. J Dent Child 1990;57:3715.
43. Shumayrikh NM, Adenubi JO. Clinical evaluation of glutaraldehyde with calcium
hydroxide and glutaraldehyde with zinc oxide eugenol in pulpotomy of primary
molars. Endod Dent Traumatol 1999;15:259 64.
44. Araujo FB, Ely LB, Pergo AM, Pesce HF. A clinical evaluation of 2% buffered glutaraldehyde in pulpotomies of human deciduous teeth: a 24-month study. Braz Dent J
1995;6:41 4.
45. Schroder U. A 2-year follow-up of primary molars, pulpotomized with a gentle technique and capped with calcium hydroxide. Scand J Dent Res 1978;86:273 8.
46. Gruythuysen RJ, Weerheijm KL. Calcium hydroxide pulpotomy with a light-cured,
cavity-sealing material after two years. J Dent Child 1997;64:2513.
47. Huth KC, Paschos E, Hajek-Al-Khatar N, et al. Effectiveness of 4 pulpotomy techniques: Randomized controlled trial. J Dent Res 2005;84:1144 8.
48. Fadavi S, Anderson AW. A comparison of the pulpal response to freeze-dried bone,
calcium hydroxide, and zinc oxide-eugenol in primary teeth in two cynomolgus
monkeys. Pediatr Dent 1996;18:52 6.
49. Nakashima M. Induction of dentine formation on canine amputated pulp by recombinant human bone morphogenetic proteins (BMP)-2 and 4. J Dent Res 1994;
73:151522.
50. Rutherford RB, Wahle J, Tucker M, Roger D, Charette M. Induction of reparative
dentine formation in monkeys by recombinant human osteogenicprotein-1. Arch
Oral Biol 1993;38:571 6.
51. Fei AL, Udin RD, Johnson R. A clinical study of ferric sulfate as a pulpotomy agent in
primary teeth. Pediatr Dent 1991;13:32732.
52. Fuks AB, Holan G, Davis JM, Eidelman E. Ferric sulfate vs dilute formocresol in
pulpotomized primary molars: long-term follow-up. Pediatr Dent 1997;19:32730.
53. Smith NL, Seale NS, Nunn ME. Ferric sulfate pulpotomy in primary molars: a retrospective study. Pediatr Dent 2000;22:1929.
54. Ibrevic H, Al-Jame Q. Ferric sulfate as pulpotomy agent in primary teeth: twentymonth clinical follow-up. J Clin Pediatr Dent 2000;24:269 72.
55. Burnett S, Walker J. Comparison of ferric sulfate, formocresol, and a combination of
ferric sulfate/formocresol in primary tooth vital pulpotomies: a retrospective radiographic survey. J Dent Child 2002;69:44 8.
56. Markovic D, Zibojinovic V, Bucetic M. Evaluation of three pulpotomy medicaments in
primary teeth. Eur J Paediatr Dent 2005;6:133 8.
57. Agamy HA, Bakry NS, Mounir MM, Avery DR. Comparison of mineral trioxide aggregate and formocresol as pulp-capping agents in pulpotomized primary teeth. Pediatr
Dent 2004;26:3029.
58. Naik S, Hegde AM. Mineral trioxide aggregate as a pulpotomy agent in primary
molars: an in vivo study. J Indian Soc Pedod Prev Dent 2005;23:13 6.
59. Farsi N, Alamoudi N, Balto K, Mushayt A. Success of minerals trioxide aggregate in
pulpotomized primary molars. J Clin Pediatr Dent 2005;29:30711.
60. Vargas KG, Packam BS, Lowman D. Preliminary evaluation of sodium hypochlorite for
pulpotomies in primary molars. Pediatr Dent 2006;28:5117.
61. Nadin G, Goel BR, Yeung CA, Glenny AM. Pulp treatment for extensive decay in
primary teeth. Cochraine Database Syst Rev 2003;CD0033220.
62. Loh A, OHoy P, Tran X, et al. Evidence-based assessment: evaluation of the formocresol vs ferric sulfate primary molar pulpotomy. Pediatr Dent 2004;26:4019.
63. Fuks AB, Papagiannoulis L. Pulpotomy in primary teeth: review of the literature according
to standardized assessment criteria. Eur Arch Paediatr Dent 2006;7:64 71.
64. Curzon MJ, Toumba KJ. Restoration of primary teeth: criteria for assessment of the
literature. Eur Arch Paediatr Dent 2006;7:48 52.
65. Peng L, Ye L, Tan H, Zhou X. Evaluation of the formocresol vs mineral trioxide
aggregate primary molar pulpotomy: a meta-analysis. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 2006;102:e40 4.
66. Deery C. Formocresol and ferric sulfate have similar success rates in primary molar
pulpotomy: in carious primary molars does a pulpotomy performed with ferric
Vital Pulp Therapy with New Materials for Primary Teeth
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Pulp Symposium
67.
68.
69.
70.
71.
sulphate, compared with formocresol, result in greater clinical/radiographic

success? Pediatr Dent 2004;26:4019.
What is meta-analysis? Available at: http://www.evidence-based-medicine.co.uk. Accessed February 27, 2008.
Egger M, Davey Smith G, Phillips AN. Meta-analysis: principles and procedures. Br
Med J 1997;315:15337.
Norbert V. The challenge of meta-analysis: discussion, indication, and contraindications for meta-analysis. J Clin Epidemiol 1955;48:5 8.
Sutton AJ, Abrams KR, Johns DR. An illustrated guide to the methods of meta-analysis.
J Eval Clin Pract 2001;7:135 48.
Cuisia ZE, Musselman R, Schneider P, Dummet CJR. A study of mineral trioxide
aggregate pulpotomies in primary molars (abstract). Pediatr Dent 2001;23:168.
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Fuks
72. Jabbarifar SE, Khadeni DD, Ghaseni DD. Success rates of formocresol pulpotomy vs
mineral trioxide aggregate in human primary molar tooth. J Res Med Sci
2004;6:55 8.
73. Aktoren O, Gencay K. A two-year clinical-radiographic follow-up of the pulpotomies
in primary molars (abstract). J Dent Res 2000;79:543.
74. Papagiannoulis L. Clinical studies on ferric sulphate as a pulpotomy medicament in
primary teeth. Eur J Paediatr Dent 2002;3:126 32.
75. Waterhouse PJ, Nunn JH, Whitworth JN. An investigation of the relative efficacy of
Buckleys formocresol and calcium hydroxide in primary molars vital pulp therapy.
Br Dent J 2000;188:32 6.
76. Liu JF. Effects of Nd:YAG laser pulpotomy on human primary molars. J Endod
2006;32:404 7.
Pulp Symposium
Vital Pulp Therapy with New Materials: New Directions

and Treatment PerspectivesPermanent Teeth
David E. Witherspoon, BDS, MS
Abstract
Pulp necrosis in immature teeth subsequent to caries
has a major impact on long-term tooth retention. The
aim of vital pulp therapy is to maintain pulp viability by
eliminating bacteria from the dentin-pulp complex and
to establish an environment in which apexogenesis can
occur. A complicating factor in treating immature teeth
is the difficulty predicting the degree of pulpal damage.
The ability of the clinician to manage the health of the
remaining pulpal tissue during the procedure is paramount. Currently, the best method appears to be the
ability to control pulpal hemorrhage by using sodium
hypochlorite. Mineral trioxide aggregate (MTA) currently is the optimum material for use in vital pulp
therapy. Compared with the traditional material of
calcium hydroxide, it has superior long-term sealing
ability and stimulates a higher quality and greater
amount of reparative dentin. In the medium-term clinical assessment, it has demonstrated a high success
rate. Thus, MTA is a good substitute for calcium hydroxide in vital pulp procedures. (J Endod 2008;34:
S25-S28)
Key Words
Apexogenesis, direct pulp cap, mineral trioxide aggregate, pulpotomy
Private practice, Plano, Texas.

Address requests for reprints to Dr David Witherspoon at
dewspoon@ntendo.com.
Conflict of Interest: David E. Witherspoon, BDS, MS, has
acted as a Workshop Coordinator for the annual session of the
American Association of Endodontists.
doi:10.1016/j.joen.2008.02.030
ental caries is one of the greatest challenges to the integrity of the developing tooth.
It can result in irreversible pulpal damage, eventually causing necrosis of the pulpal
tissues and associated arrested development of the tooth root. Ultimately, abnormal
root development will impact the long-term prognosis for tooth retention (1 4). Thus,
the primary goal when treating immature permanent teeth should be to maintain pulp
vitality so that apexogenesis can occur (5 8). Direct pulp caps and pulpotomies in
teeth with incomplete root formation promote normal development of the root complex. There are long-term prognostic advantages of this treatment outcome over apexification treatment. The tooth structure formed is of a great quantity, and its composition
appears to have greater structural integrity (3). The result is that the fully developed
tooth is more resistant to vertical root fractures (4).
The classic study by Kakehashi et al. (9, 10) eloquently established the role of
bacteria in pulpal health and necrosis. In a germ-free environment, the pulp demonstrated the ability to heal and deposit additional dentin material. In the presence of
bacteria, pulpal demise was inevitable. This fundamental premise is integral to the
success of all vital pulp procedures. Thus, the basic principle of vital pulpal treatment
can be broken down into 2 broad phases. The initial phase involves removing the
diseased and bacterially contaminated tissue. The second phase involves establishing an
environment that will prevent any further and future bacterial contamination. The principal procedures aimed at maintaining pulpal vitality include direct pulp caps and
pulpotomies. By removing the affected coronal pulp tissue and leaving the unaffected
radicular pulp tissue in situ, sealed from the oral environment, normal root development can take place.
Historically, a number of materials (1113) have been advocated to induce normal root development. To date, the material of choice has been calcium hydroxide
(Ca(OH)2) (14 20). Most recently, an alternative material, mineral trioxide aggregate (MTA), has become available for use in pulpal procedures. Several properties are necessary when choosing a material to be used in vital pulp treatment. These
include the ability of the material to kill bacteria, induce mineralization, and establish
a tight bacterial seal. The ideal material for vital pulp treatment should be able to resist
long-term bacterial leakage and stimulate the remaining pulp tissue to return to a
healthy state, promoting the formation of dentin. The early data for MTA suggest that it
is the optimum material for fulfilling these goals when vital pulp therapy is the treatment
of choice.
MTAs Physical and Chemical Properties

MTA is composed of tricalcium silicate, bismuth oxide, dicalcium silicate, tricalcium aluminate, and calcium sulfate dihydrate. MTA might also contain up to 0.6%
insoluble residue, including free crystalline silica. Other trace constituents might include calcium oxide, free magnesium oxide, potassium, and sodium sulfate compounds
(21). Hydration of the powder results in the formation of a finely crystalline gel of the
hydrated forms of the components, with some Ca(OH)2 also being formed. This solidifies to a hard structure in less than 3 hours (22). It has a compressive strength equal
to intermediate restorative material (IRM) and Super-EBA IRM but less than that of
amalgam. MTA has been shown to have an antibacterial effect on some of the facultative
bacteria and no effect on strict anaerobic bacteria (23). This limited antibacterial effect
is less than that demonstrated by Ca(OH)2 pastes. MTAs ability to resist the future
penetration of microorganisms appears to be high. In in vitro leakage studies (24, 25),
MTA has resisted leakage predictably and repeatedly. MTA frequently performs better
Vital Pulp Therapy with New Materials
S25
Pulp Symposium
than amalgam IRM or Super EBA (26 30). Compared with composite
resins placed under ideal conditions, MTAs leakage patterns are similar (31, 32). Furthermore, the presence of blood has little impact on the
degree of leakage (29, 33). It is commercially available as ProRoot MTA
(Dentsply Tulsa Dental, Tulsa, OK) and has been advocated for use in
vital pulp therapy (34 38).
Mineralization
MTA has demonstrated the ability to induce hard tissue formation
in pulpal tissues when used as either a direct pulp capping or pulpotomy
material (34, 36, 39 45). MTA promotes rapid cell growth in vitro
(46). Compared with Ca(OH)2, in animal studies, MTA consistently
induces the formation of dentin at a greater rate with a superior structural integrity. It develops more complete dentin bridges and demonstrates an improved ability to maintain pulp tissue integrity (34, 39).
Histologic evaluation in animal and human studies has shown that MTA
stimulates reparative dentin formation, with thick dentinal bridging,
minimal inflammation, and nominal hyperemia. The net result is that
vital pulp therapy with MTA produces negligible pulpal necrosis (34,
41 43, 47).
MTA also appears to induce the formation of a dentin bridge at a
faster rate than Ca(OH)2 (48). In 1 case report (52) partial pulpotomies were conducted on 2 cases of dens evaginatus. After 6 months, the
teeth were removed as part of planned orthodontic treatment. Histologic examination of these teeth showed an apparent continuous dentin
bridge formation in both teeth, and the pulps were free of inflammation.
The process by which MTA acts to induce dentin bridge formation is not
known. It has been theorized (49) that the tricalcium oxide in MTA
reacts with tissue fluids to form Ca(OH)2, resulting in hard tissue formation in a similar manner to Ca(OH)2.
Clinical Outcomes
The initial response reported in case reports has been very positive
(50 52). Several human clinical studies with MTA for direct pulp capping and pulpotomies have recently been published.
Direct Pulp Capping

The clinical data available on MTA pulp capping of cariously exposed permanent teeth are limited to 2 studies. Both of these studies
have reported a high rate of success, which ranges from 93%98% (53,
54). In 1 study (54), 53 teeth with carious exposures that had been
diagnosed with reversible pulpitis and normal periradicular tissue were
treated with MTA pulp caps. A total of 40 patients between 7 and 45 years
old were treated. Briefly, the treatment consisted of caries removal with
the aid of an operating microscope and extensive use of caries detector
dye. Pulpal bleeding was controlled with 5.25% 6.00% NaOCl applied
for up to 10 minutes. After hemostasis was achieved, the pulps were
capped with MTA, and the teeth were temporized with unbonded composite Photocore (Kuraray Co Ltd, Osaka, Japan) and a moistened cotton pellet placed directly over the MTA. The teeth were restored with a
bonded composite 510 days later. Forty-nine of the 53 teeth were
available for recall at the 1-year time frame, with an average recall
period of 3.94 years.
The maximum period of observation was 9 years. During that time,
98% of the cases presented a favorable outcome, with a normal radiographic appearance, no symptoms, and a normal response to cold
testing. In addition, of the 15 teeth in younger patients that were not fully
formed at the time of treatment, all subsequently demonstrated continued normal apexogenesis to complete root formation (54). In the second study, a 93% clinical and radiographic success rate was reported at
the 24-month recall period. The study used a similar protocol to direct
S26
Witherspoon
pulp cap 30 young, permanent, cariously exposed asymptomatic teeth

with MTA. All the teeth showed signs of vitality and absence of periapical
radiolucency, with evidence of continued root growth and no reported
symptoms (53).
Pulpotomy
The human clinical data available on MTA pulpotomies in cariously exposed permanent teeth have reported high success rates, which
ranged from 93%100%. In a prospective clinical trial comparing success rates of partial pulpotomies with treated cariously exposed permanent molars by using Ca(OH)2 or MTA, there was no statistically significant difference in the success rate between each group (Ca(OH)2
91%, MTA 93%). Fifty-one teeth in 34 patients were available for
recall. The patients ranged from 6.8 13.3 years old, and the follow-up period was from 25.4 45.6 months, with an average of 34.8
months (55).
When comparing MTA and Ca(OH)2 pulpotomies within the same
patient at the 12-month recall time frame, 2 of the 15 teeth in the
Ca(OH)2 group were considered failures, whereas none of the teeth
treated with MTA failed (0 of 15 teeth). Calcific metamorphosis was
evident radiographically in 2 teeth treated with Ca(OH)2 and in 4 teeth
treated with MTA (56).
The use of gray MTA for partial pulpotomy in cariously exposed
young permanent first molars diagnosed with reversible pulpitis and
normal periradicular tissue has resulted in a very high success rate.
Exposed pulp tissue was removed with a diamond bur, and after hemostasis, 2 4 mm of gray MTA was placed against the fresh wound and
then covered with a layer of glass ionomer cement. The teeth were
restored with amalgam or stainless steel crowns. At the 24-month recall
period, 22 of 28 teeth showed no signs of clinical or radiographic
failure and responded within normal limits to pulp vitality tests. Although 6 of 28 teeth did not respond to vitality testing at the final followup, the radiographic appearance was within normal limits, and the teeth
were asymptomatic. The patients ages ranged from 7.213.1 years,
with an average age of 10 years (57).
In a case series outcomes report that used MTA pulpotomies to
treat cariously exposed immature permanent teeth (first or second molars) that had been diagnosed with irreversible pulpitis, a success rate of
92% was reported (58). The key factor in deciding whether to complete
a pulpotomy as opposed to a pulpectomy was the ability to control
pulpal hemorrhage. In cases in which pulpal hemostasis could be
achieved with NaOCl, a pulpotomy was completed. The patients ages
ranged from 715 years, with an average age of 10 years. The recall
period ranged from 6 53 months, with an average recall period of 21
months. The single tooth that required nonsurgical root canal treatment
had completed normal root development before requiring nonsurgical
root canal treatment.
Technique
With the vital pulp therapy technique, the patient is anesthetized
with a standard local anesthetic protocol. In all cases, a rubber dam is
used to isolate the tooth being treated. The affected enamel is removed
by using a high-speed bur with copious irrigation. The gross caries can
be removed with either a sharp spoon excavator or a large, round,
slow-speed tungsten carbide bur. As the pulp is approached, the cavity
is flushed with NaOCl to decrease the bacterial load. The remaining
affected tissue is removed by using a coarse, high-speed diamond bur
with copious irrigation. In the case of a pulpotomy, the pulp is removed
to a level where adequate hemostasis can be achieved. Hemostasis is
achieved by irrigating with 6% sodium hypochlorite (59) for up to 10
minutes. Care should be taken to avoid the application of pressure to the
Pulp Symposium
References
Figure 1. (A) Preoperative radiograph of a symptomatic cariously exposed

mandibular second premolar. (B) Postoperative radiograph showing an MTA
pulpotomy completed and restored with bonded composite resin. (C) Recall at
2.7 years showing continued root formation (apexogenesis). The tooth responds within normal limits to pulp tests. (D) Recall at 3.4 years showing the
tooth continuing to respond within normal limits to pulp tests.
pulp. Having achieved hemostasis, a layer of MTA should be placed and

mixed according to the manufacturers recommendations over the exposed pulpal tissue. The thickness of the material should be approximately 2 mm. Once the MTA is in place, a small amount of flowable
compomer (or an equivalent light-cured resin or glass ionomer liner)
should be applied to cover the MTA material. The remainder of the
cavity can then be etched, bonded, and restored (Fig. 1).
Conclusion
The major difficulty in treating permanent immature teeth is the
ability to predictably diagnose the state of pulpal health and, therefore,
the ability of predicting it to heal. The current tests available to the
clinician make it difficult to accurately predict the degree of pulpal
degeneration before commencing treatment. Therefore, the clinicians
ability to assess the health of the remaining pulpal tissue during the
procedure is paramount. Currently, the best method appears to be the
ability to control pulpal hemorrhage with NaOCl.
The current data available on the use of MTA in vital pulp therapy
indicate that it is the optimum material and better than the traditionally
used material Ca(OH)2. It has a greater long-term sealing ability and
stimulates a high quality and a great amount of reparative dentin. In
clinical outcomes evaluation, it has demonstrated a high success
rate. MTA is, thus, a good substitute for Ca(OH)2 in vital pulp procedures.
1. Robertson A, Andreasen FM, Andreasen JO, Noren JG. Long-term prognosis of crownfractured permanent incisors: the effect of stage of root development and associated
luxation injury. Int J Paediatr Dent 2000;10:1919.
2. Rabie G, Trope M, Tronstad L. Strengthening of immature teeth during long-term
endodontic therapy. Endod Dent Traumatol 1986;2:437.
4. Cvek M. Prognosis of luxated nonvital maxillary incisors treated with calcium hydroxide and filled with gutta-percha: a retrospective clinical study. Endod Dent
Traumatol 1992;8:4555.
5. Love RM. Effects of dental trauma on the pulp. Pract Periodontics Aesthet Dent
1997;9:42736, 38 (quiz).
6. Shabahang S, Torabinejad M. Treatment of teeth with open apices using mineral
trioxide aggregate. Pract Periodontics Aesthet Dent 2000;12:31520, 22 (quiz).
7. Webber RT. Apexogenesis versus apexification. Dent Clin North Am 1984;28:
669 97.
8. Massler M. Preventive endodontics: vital pulp therapy. Dent Clin North Am
1967;Nov:66373.
9. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposures of dental
pulps in germ-free and conventional laboratory rats. Oral Surg Oral Med Oral Pathol
1965;20:340 9.
10. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposures of dental
pulps in germ-free and conventional laboratory rats. J South Calif Dent Assoc
1966;34:449 51.
11. Horsted-Bindslev P, Vilkinis V, Sidlauskas A. Direct capping of human pulps with a
dentin bonding system or with calcium hydroxide cement. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2003;96:591 600.
12. Trope M, McDougal R, Levin L, May KN Jr, Swift EJ Jr. Capping the inflamed pulp
under different clinical conditions. J Esthet Restor Dent 2002;14:349 57.
13. Kiba H, Hayakawa T, Nakanuma K, Yamazaki M, Yamamoto H. Pulpal reactions to two
experimental bonding systems for pulp capping procedures. J Oral Sci
2000;42:69 74.
14. Ulmansky M, Sela J, Langer M, Yaari A. Response of pulpotomy wounds in normal
human teeth to successively applied Ledermix and Calxyl. Arch Oral Biol
1971;16:1393 8.
15. Schroder U, Granath LE. Scanning electron microscopy of hard tissue barrier following experimental pulpotomy of intact human teeth and capping with calcium hydroxide. Odontol Revy 1972;23:21120.
16. Schroder U. Evaluation of healing following experimental pulpotomy of intact human
teeth and capping with calcium hydroxide. Odontol Revy 1972;23:329 40.
17. Holland R, de Souza V, de Mello W, Nery MJ, Bernabe PF, Otoboni Filho JA. Healing
process after pulpotomy and covering with calcium hydroxide, Dycal, or MPC: histological study in dog teeth. Rev Fac Odontol Aracatuba 1978;7:18591.
18. Holland R, de Souza V, de Mello W, Nery MJ, Bernabe PF, Otoboni Filho JA. Permeability of the hard tissue bridge formed after pulpotomy with calcium hydroxide: a
histologic study. J Am Dent Assoc 1979;99:4725.
19. Stanley HR. Criteria for standardizing and increasing credibility of direct pulp capping studies. Am J Dent 1998;11(special issue):S1734.
20. Haskell EW, Stanley HR, Chellemi J, Stringfellow H. Direct pulp capping treatment: a
long-term follow-up. J Am Dent Assoc 1978;97:60712.
21. Dentsply, Tulsa-Dental. Material safety data sheet: ProRoot MTA root canal repair
material. Tulsa, OK: Dentsply, 2002:12.
22. Torabinejad M, Hong CU, McDonald F, Pitt Ford TR. Physical and chemical properties
of a new root-end filling material. J Endod 1995;21:349 53.
23. Torabinejad M, Hong CU, Pitt Ford TR, Kettering JD. Antibacterial effects of some root
end filling materials. J Endod 1995;21:403 6.
24. Wu MK, Kontakiotis EG, Wesselink PR. Long-term seal provided by some root-end
filling materials. J Endod 1998;24:557 60.
25. Roy CO, Jeansonne BG, Gerrets TF. Effect of an acid environment on leakage of
root-end filling materials. J Endod 2001;27:7 8.
26. Torabinejad M, Rastegar AF, Kettering JD, Pitt Ford TR. Bacterial leakage of mineral
trioxide aggregate as a root-end filling material. J Endod 1995;21:109 12.
27. Fischer EJ, Arens DE, Miller CH. Bacterial leakage of mineral trioxide aggregate as
compared with zinc-free amalgam, intermediate restorative material, and Super-EBA
as a root-end filling material. J Endod 1998;24:176 9.
28. Lee SJ, Monsef M, Torabinejad M. Sealing ability of a mineral trioxide aggregate for
repair of lateral root perforations. J Endod 1993;19:541 4.
29. Martell B, Chandler NP. Electrical and dye leakage comparison of three root-end
restorative materials. Quintessence Int 2002;33:30 4.
30. Tang HM, Torabinejad M, Kettering JD. Leakage evaluation of root end filling materials using endotoxin. J Endod 2002;28:57.
31. Adamo HL, Buruiana R, Schertzer L, Boylan RJ. A comparison of MTA, Super-EBA,
composite, and amalgam as root-end filling materials using a bacterial microleakage
model. Int Endod J 1999;32:197203.
Vital Pulp Therapy with New Materials
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Pulp Symposium
32. Fogel HM, Peikoff MD. Microleakage of root-end filling materials. J Endod
2001;27:456 8.
33. Torabinejad M, Higa RK, McKendry DJ, Pitt Ford TR. Dye leakage of four root end
filling materials: effects of blood contamination. J Endod 1994;20:159 63.
34. Pitt Ford TR, Torabinejad M, Abedi HR, Bakland LK, Kariyawasam SP. Using mineral
trioxide aggregate as a pulp-capping material. J Am Dent Assoc 1996;127:1491 4.
35. Torabinejad M, Chivian N. Clinical applications of mineral trioxide aggregate. J Endod
1999;25:197205.
36. Andelin WE, Shabahang S, Wright K, Torabinejad M. Identification of hard tissue after
experimental pulp capping using dentin sialoprotein (DSP) as a marker. J Endod
2003;29:646 50.
37. Bakland LK. Management of traumatically injured pulps in immature teeth using
MTA. J Calif Dent Assoc 2000;28:855 8.
38. Schmitt D, Lee J, Bogen G. Multifaceted use of ProRoot MTA root canal repair material. Pediatr Dent 2001;23:326 30.
39. Faraco IM Jr, Holland R. Response of the pulp of dogs to capping with mineral
trioxide aggregate or a calcium hydroxide cement. Dent Traumatol 2001;17:163 6.
40. Holland R, de Souza V, Murata SS, et al. Healing process of dog dental pulp after
pulpotomy and pulp covering with mineral trioxide aggregate or Portland cement.
Braz Dent J 2001;12:109 13.
41. Dominguez MS, Witherspoon DE, Gutmann JL, Opperman LA. Histological and scanning electron microscopy assessment of various vital pulp-therapy materials. J Endod
2003;29:324 33.
42. Aeinehchi M, Eslami B, Ghanbariha M, Saffar AS. Mineral trioxide aggregate (MTA)
and calcium hydroxide as pulp-capping agents in human teeth: a preliminary report.
Int Endod J 2003;36:22531.
43. Tziafas D, Pantelidou O, Alvanou A, Belibasakis G, Papadimitriou S. The dentinogenic
effect of mineral trioxide aggregate (MTA) in short-term capping experiments. Int
Endod J 2002;35:24554.
44. Parirokh M, Asgary S, Eghbal MJ, et al. A comparative study of white and grey mineral
trioxide aggregate as pulp capping agents in dogs teeth. Dent Traumatol
2005;21:150 4.
45. Iwamoto CE, Adachi E, Pameijer CH, Barnes D, Romberg EE, Jefferies S. Clinical and
histological evaluation of white ProRoot MTA in direct pulp capping. Am J Dent
2006;19:8590.
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Witherspoon
46. Mitchell PJ, Pitt Ford TR, Torabinejad M, McDonald F. Osteoblast biocompatibility of
mineral trioxide aggregate. Biomaterials 1999;20:16773.
47. Chacko V, Kurikose S. Human pulpal response to mineral trioxide aggregate (MTA):
a histologic study. J Clin Pediatr Dent 2006;30:2039.
48. Junn DJ, McMillan P, Bakland L, Torabainejad M. Quantitative assessment of dentin
bridge formation following pulp-capping with mineral trioxide aggregate (MTA)
(abstract). J Endod 1998;24:278.
49. Holland R, de Souza V, Nery MJ, Otoboni Filho JA, Bernabe PF, Dezan Junior E.
Reaction of rat connective tissue to implanted dentin tubes filled with mineral trioxide
aggregate or calcium hydroxide. J Endod 1999;25:161 6.
50. Karabucak B, Li D, Lim J, Iqbal M. Vital pulp therapy with mineral trioxide aggregate.
51. Patel R, Cohenca N. Maturogenesis of a cariously exposed immature permanent tooth
using MTA for direct pulp capping: a case report. Dent Traumatol 2006;22:328 33.
52. Koh ET, Ford TR, Kariyawasam SP, Chen NN, Torabinejad M. Prophylactic treatment
of dens evaginatus using mineral trioxide aggregate. J Endod 2001;27:540 2.
53. Farsi N, Alamoudi N, Balto K, Al Mushayt A. Clinical assessment of mineral trioxide
aggregate (MTA) as direct pulp capping in young permanent teeth. J Clin Pediatr Dent
2006;31:72 6.
54. Bogen G. Direct pulp capping with mineral trioxide aggregate: an observational study.
J Am Dent Assoc 2008;139:30515.
55. Qudeimat MA, Barrieshi-Nusair KM, Owais AI. Calcium hydroxide vs mineral trioxide
aggregates for partial pulpotomy of permanent molars with deep caries. Eur Arch
Paediatr Dent 2007;8:99 104.
56. El-Meligy OA, Avery DR. Comparison of mineral trioxide aggregate and calcium
hydroxide as pulpotomy agents in young permanent teeth (apexogenesis). Pediatr
Dent 2006;28:399 404.
57. Barrieshi-Nusair KM, Qudeimat MA. A prospective clinical study of mineral trioxide
aggregate for partial pulpotomy in cariously exposed permanent teeth. J Endod
2006;32:7315.
58. Witherspoon DE, Small JC, Harris GZ. Mineral trioxide aggregate pulpotomies: a case
series outcomes assessment. J Am Dent Assoc 2006;137:610 8.
59. Hafez AA, Cox CF, Tarim B, Otsuki M, Akimoto N. An in vivo evaluation of hemorrhage
control using sodium hypochlorite and direct capping with a one- or two-component
adhesive system in exposed nonhuman primate pulps. Quintessence Int 2002;
33:26172.
Pulp Symposium

Lars Bjrndal, DDS, PhD
Abstract
Various treatment concepts have been suggested to
solve the deep carious lesion dilemma. Recent systematic reviews are presented. Their conclusions are based
on very few studies, and the main message is that
optimal randomized clinical studies are lacking. Observational studies on indirect pulp treatment and stepwise excavation demonstrate that these treatments
avoid pulp exposures, but it cannot be said which
approach is best. A less invasive modified stepwise
excavation approach is described, focusing on changing
an active lesion into an arrested lesion even without
performing an excavation close to the pulp. In Denmark
and Sweden a randomized clinical multi-center trial is
currently taking place, the Caries and Pulp (CAP) trial.
This trial is investigating the effects of stepwise excavation over 2 visits versus 1 complete excavation of
deep caries in permanent teeth. Guidelines for treatment are presented. (J Endod 2008;34:S29-S33)
Key Words
Caries, dentin, indirect pulp treatment, pulp, randomized clinical trial, stepwise excavation, tertiary dentin
From the Department of Cariology and Endodontics,

School of Dentistry, Faculty of Health Sciences, University of
Copenhagen, Copenhagen, Denmark.
Address requests for reprints to Dr Bjrndal at lb@odont.
ku.dk.
Conflict of Interest: Lars Bjrndal, DDS, PhD, is a Grant
Recipient from the Danish Agency for Science Technology and
Innovation.
doi:10.1016/j.joen.2008.02.035
Introducing Thoughts about Level of Evidence in Clinical Research

A demanding trend in clinical research is to perform a randomized clinical trial
(RCT) to compare 2 interventions. Why is RCT so important, or in particular the
randomization? The level of evidence is the short answer to that question. Expert opinion is allocated to the lowest level of evidence, with the next level being observational
studies. At the top of the hierarchy is the systematic review of high-quality RCTs. A more
extended answer deals with the largest problem in studies that are nonrandomized,
which is that of confounding variables. Many factors cannot be controlled for if a simple
comparison is made between 2 studies in which the same treatment has been provided.
The distribution of prognostic factors might differ between the 2 studies. Are the 2
studies, in fact, treating the very same stage of diseases? With regard to caries, how deep
are the lesions? Finally, we cannot exclude the psychological phenomenon that investigators tend to see what they want to see. The perceived effect might in reality differ
between the 2 studies.
There is a great deal of difference between RCTs and observational studies, but this
does not mean that the thousands of clinical studies that have been carried out with a
non-RCT design do not indicate relevance, but they simply do not have the highest level
of evidence.
The following is a list of factors that characterize a high-quality RCT:
1. the presence of well-defined inclusion and exclusion criteria;
2. prognostic factors are equally distributed between the 2 interventions that are
going to be compared;
3. the number of treatments needed to show a difference between control and
experimental groups is calculated;
4. adequate allocation sequences: for example, the randomization of patients to
control or experimental groups is generated by a computer;
5. adequate allocation concealment: the randomization is carried out with a central
independent unit;
6. follow-up examination is done by an investigator(s) who is blinded as to the
patients group assignment;
7. ideally, the RCT should be carried out in a number of trial centers.
The Latest Systematic Reviews from the Cochrane Collaboration

Regarding Caries Treatment and the Pulp
The Cochrane Collaboration carries out systematic reviews of high-quality clinical studies. The recent reviews of caries and pulp treatments all indicate the lack of RCTs (1, 2). The
Cochrane Collaboration has found fewer than 10 studies that could be compared, and they
are not all high-quality RCTs.
Within the concept of maintaining pulp vitality, treatment modalities that included
indirect pulp treatment (IPT) showed no differences in symptoms at 12 months among
studies using Life, Dycal, and Cavitec formulations of calcium hydroxide (2).
In relation to partial caries removal, the following points were addressed in the
review (1):
1. Partial caries removal in symptomless primary or permanent teeth reduces the
risk of pulpal exposure;
2. No pulpal symptoms were found;
3. Partial caries removal appeared preferable in deep lesions to reduce the risk of
carious exposure of the pulp;
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4. There is insufficient evidence to show whether it is necessary to
re-enter and excavate further in the stepwise excavation technique, but studies that did not re-enter reported no adverse
consequences.
Let us add some comments, which in the future might bring these
conclusions further up the hierarchy of evidence. One problem has
been the definition of the penetration depth of the deep caries lesion.
This point has in many studies been defined as a lesion in which one
would expect a pulpal exposure if all caries was removed. Among the 4
included studies on which the above conclusions are based, the lesions
differed between deep lesions and those extending to half the thickness
of the dentin. In 2 of the studies, a stepwise excavation approach was
used with lesions defined as deep, whereas the other 2 studies did not
re-enter the lesion. The problem in comparing these studies is confounding factors. One of the studies treated less progressed lesions,
which might be important when trying to compare the 2 interventions.
We need high-quality RCTs to compare IPT and stepwise excavation. I will return to this later.
How Deep Is a Deep Caries Lesion?

The definition of deep caries lesions points toward the potential
exposure of the pulp (3). When do clinicians expect that a potential
pulp exposure is close? In a practice-based observational study, general
dentists were asked to judge the penetration depth of caries lesions that
would pose a risk for pulpal exposure (4). The majority of dentists
selected lesions that penetrated to within three fourths of the entire
dentin thickness or more as evaluated on x-rays. This judgment was
made in one case in which only half of the dentin was demineralized,
indicating that this definition varies substantially among practitioners.
Let us adopt the same clinical concern for potential exposures as
did the majority of these general practitioners. A deep caries lesion is
present when the penetration depth is in the range of three fourths of the
entire thickness of the dentin or more when evaluated on an x-ray.
The Biologic Dilemma

On the first day of this symposium, we discussed the understanding
of caries, and that the treatment of deep caries lesions has been placed
in what one could call no mans land, with different schools of opinions as classically given by Tomes (5) and Black (6). Another aspect is
that we do not have any reliable or accurate clinical diagnostic device
for monitoring the degree of pulpal inflammation. The case selection for
a given treatment, whether or not we want to avoid an exposure of the
pulp, is still based on indirect diagnostic procedures. We might try to
divide a few clinical stages of vital pulp problems, depending on the
results from our clinical as well as paraclinical diagnostic procedures,
as described in detail by Reit et al. (7). The diagnostic data should be
collected from the following 3 areas: (i) the patients description of
subjective symptoms, (ii) pulp sensibility testing, and (iii) paraclinical
examinations (radiographs for exclusion of apical pathosis).
Attempts to divide degrees of pulp pathology seem ambitious, because we do not always know in what direction the pulpal inflammation
will turn. It has not been possible to devise an overall applied classification system on this issue. For some practitioners, the clinical diagnosis of the pulp is centered on subjective symptomatic factors, ie, symptomatic or nonsymptomatic pulpitis (8), whereas for others the use of
reversible and irreversible pulpitis is applied (9). Within the latter diagnosticdichotomy, the treatments are guided toward either invasive
pulp therapy or procedures aiming to maintain the pulp integrity. Thus,
the words irreversible and reversible cannot solely be interpreted as the
gold standard expression for the actual state of the pulp, but rather they
represent our best clinical judgment.
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Bjrndal
The Dentist Must Handle the Biologic Dilemma!

The clinical use of the irreversible pulpitis diagnosis as well as
symptomatic pulpitis is essentially the same; the tooth will be managed
with an invasive pulp treatment (9). However, the deep carious lesion
might also be a potential reversible pulpitis case, with confirmed pulpal
sensibility but with no objective signs of apical pathology or subjective
symptoms before start of the treatment. Even though the absence of
clinical symptoms is not a sign of absence of pulp pathology, this approach provides one more chance to maintain the pulps integrity, until
the opposite is proved. An important point after treatment of such cases
must be the maintenance of pulp sensibility, because the finding of no
clinical symptoms could be the result of a silently developing pulp
necrosis.
A Brief Historical Focus on Excavations Methods in

Asymptomatic Deep Caries Lesions
Many pulps have probably been exposed through the years on the
basis of the concept that deep caries lesions are always associated with
inflammation, and diagnoses such as asymptomatic pulpitis or chronic
pulpitis have been made. Various excavation methods have been proposed, such as IPT (10) and the two-stage excavation procedure or
stepwise excavation (11). In recent articles and reviews the expression
partial excavation (1) has emerged to refer to various treatment modalities, but in reality the term has not led to consensus, because it can
mean anything from almost no excavation to excavation very close to the
pulp. The differences between the 2 methods mentioned above are that
the IPT procedure involves almost complete removal of the affected
dentin, leaving a thin layer of demineralized dentin. Re-entry is not
attempted. In contrast, the stepwise excavation technique involves reentry at varying intervals. What did these early clinical articles prescribe
in terms of clinical procedure?
One of the earliest articles describing a step-by-step approach is by
Sowden (12). Carious tissue was removed, and a 1-mm layer of calcium
hydroxide was placed followed by a temporary restoration. No final
excavation was performed within the first visit. Re-entry and final excavation were then made after 23 weeks.
A more rigorous approach was addressed in the article by Magnusson and Sundell (11), who emphasized that a thin soft layer of dentin
should remain on the pulpal wall. The authors did not describe in detail
what was meant by a thin layer. They most likely excavated as close as
possible to the pulp, leaving a thin layer of residual caries. Residual
caries, as defined by Kerhove et al. (10), means that if you apply additional pressure to the dentin with the excavator, the pulp will be exposed. Magnusson and Sundell (11) placed a zinc oxide eugenol cement temporary restoration and performed the final excavation after
4 6 weeks. This stepwise excavation method has been a very common
and widespread approach within the Nordic countries. In 1962, Law
and Lewis (13) accessed all areas of carious dentin and placed calcium
hydroxide and an amalgam restoration. Re-entry was made after 6
months.
Eidelman et al. (14) provided details of the excavation procedures. It is stated that all undermining enamel is removed to gain more
easy access to the carious dentin along the enamel-dentin junction. At
the pulpal wall approximately 1 mm of carious dentin was left behind.
The tooth was re-entered after 1 year, and the final excavation was
performed.
For reasons discussed earlier, we cannot make detailed comparisons among these older studies, because each represents its own decade, and there is a great deal of variation among them. For example, in
the study by Magnusson and Sundell (11), primary teeth were treated,
and no follow-up examination was done after treatment was completed.
Pulp Symposium
Note that it is also difficult to determine whether there are any
differences between the classic IPT and the first excavation step as
performed in the study by Magnusson and Sundell (11). Thus, the
potential risk of creating pulpal exposures following either IPT or during the first step of stepwise excavation might very well be the same.
Observational Data about Indirect Pulp Treatment

In a retrospective study AL-Zayer et al. (15) found that IPT in
primary posterior teeth is a successful technique and should be considered as an alternative pulp therapy. Recently, Gruythuysen et al. (16)
also reported that the IPT technique produces clinical success. Concerning the more detailed treatment procedures, the Cochrane review
indicated that variation in base materials did not produce any differences (2). Also, Marchi et al. (17) concluded that IPT in primary teeth
arrests the progression of the underlying caries, regardless of the material used as a liner.
Use the Knowledge from Caries Pathology to Design

an Excavation Approach
The optimal focus on avoiding a pulpal exposure and using caries
pathology might be demonstrated by the concept of a less invasive or
modified stepwise excavation (Fig. 1) (18, 19). The primary aim of the
first excavation is to change the caries environment and not to remove as

much carious dentin, eventually reaching the residual level close to the
dentin-pulp interface. Microbiologic and clinical studies have shown
that it is possible to decrease the number of bacteria and arrest the
caries process during a treatment interval (19, 20). The active, soft,
yellowish demineralized dentin becomes a darker, harder, and drier
demineralized dentin, resembling a slowly progressing lesion. More
detailed microbiologic observations also indicate that during a treatment interval the flora becomes a type associated with slow lesion
progress in root caries (21). These findings have gained additional
support (22). Whether the presence of such flora can remain inactive
beneath a permanent restoration in a deep cavity needs further investigation.
This aspect of using our knowledge of caries pathology as an
integrated part of caries removal is also reinforced in a new textbook
chapter (23).
Is A Two-step Excavation Necessary?

As shown from a recent survey, 18% of respondents would partially remove caries in a deep lesion in which one would expect that
complete caries removal would lead to pulpal exposure (24). I interpret this technique as the IPT with no re-entry. In the United States IPT
Figure 1. Diagrams demonstrating the less invasive stepwise excavation procedure. A closed lesion environment before and after first excavation (a, b) followed by
a calcium hydroxide containing base material and a provisional restoration. During the treatment interval the retained demineralized dentin has clinically changed
into signs of slow lesion progress, evidenced by a darker demineralized dentin (c, d). After final excavation (e) the permanent restoration is made (f). Red zones
indicate plaque. Reprinted with permission from Blackwell Munksgaard from Bjrndal L. Dentin and pulp reactions to caries and operative treatment: biological
variables affecting treatment outcome. Endodontic Topics 2002;2:10 23. (27)
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has been carried out for years, whereas we in the Scandinavian countries traditionally have applied a stepwise excavation approach. It is
difficult to state which treatment approach is better, because no highquality RCTs have yet been performed to give us the answer.
The clinicians intention is to avoid a pulpal exposure on the basis
of the best possible indications. The main concern is that when excavating to a level close to the pulp, a number of pulpal complications
might arise, as indicated within the various stepwise excavation approaches. Clinically, the changes in dentin appearance during the excavation provide the clinician with information regarding the changes in
caries activity. This is also true in cases in which the changes in color of
the carious dentin are not as clear. The final excavation is safer, because
it is easier to remove the remaining dry carious dentin.
The final step of stepwise excavation is 2-fold: (1) to assess the
tooths reaction and (2) to remove the slowly progressing lesion in
slightly infected discolored demineralized dentin before carrying out
the final restoration.
A Two-step Approach Might Be the First Way of

Changing Clinical Habits
The vast majority of respondents to the aforementioned survey
selected an invasive approach in relation to the deep caries case because they presumably did not believe in leaving carious dentin behind
(24). If the operator leaves infected dentin, it might stimulate obliteration of the root canals, making future endodontic treatment more difficult. It is important to say that such a hypothesis is relevant, but it has not
been proved. In reality, this would favor a second visit. Remember the
second aim, which is to remove the slowly progressing caries in slightly
infected discolored demineralized dentin before carrying out the final
restoration.
However, it is not easy to change a clinical habit from one of
removing all carious dentin to one of leaving caries permanently. One
way to accomplish this would be to experience the strategy of changing
the local caries environment by performing a 2-step procedure next
time a deep caries lesion presents in your practice.
A High-quality RCT Concerning Deep Caries Treatment:

The Caries and Pulp (CAP) Trial
The aim of the CAP trial has been to investigate the beneficial and
harmful effects of stepwise excavation of symptomatic and asymptomatic permanent teeth during 2 visits versus complete excavation of deep
caries in 1 visit. The CAP trial is being performed as a multi-center RCT,
and the status of inclusion has recently been reported, which means that
the enrollment of patients has been discontinued, and the results are
about to be analyzed (25). Preliminary data on the outcome pulp exposure favor the use of stepwise excavation.
ready familiar with the guidelines of the IPT, the following presents
the stepwise excavation technique (27):
1. Deep lesion considered likely to result in pulp exposure if treated
by a single and terminal excavation. Evaluated by x-ray, the dentinal lesion involves three fourths or more of the dentin thickness.
2. No history of pretreatment symptoms such as spontaneous pain
and provoked pulpal pain. However, mild to moderate pain on
thermal stimulation is accepted.
3. Positive pulp sensibility tested by an electric pulp tester, thermal
stimulation, or test cavity.
4. Pretreatment radiographs that rule out apical pathosis.
5. Finish the peripheral excavation of the cavity followed by a central
excavation removing the outermost necrotic and infected demineralized dentin, in order that a provisional restoration can be
properly placed.
6. Do not excavate as closely as possible during the first step,
thereby reducing the risk of pulp exposure.
7. Select a provisional restorative material on the basis of the length
of the treatment interval, ranging between 6 and 8 months.
8. The final excavation is often less invasive than expected, as a
result of the altered dentinal changes gained during the treatment
interval.
Recognize that the procedure appears very similar to the IPT,
except for the less invasive first step. This requires the clinician to
decide before reaching the pulp whether to perform a stepwise
excavation approach before all carious dentin has been removed.
Otherwise, the clinician will not promote local changes in the cariogenic environment.
It Is Not Just a Matter of Selecting a Proper Clinical

Treatment Concept
We do not yet have noninvasive tools for the measurement of the
severity of pulpal inflammation. Thus, the discussion of reversible or
irreversible development of pulpitis is controversial in relation to the
actual state of the pulp. When treating the deep carious lesion, we are
forced to make a choice on the basis of indirect diagnostic methods.
Consequently, different schools of thought exist. Future high-quality
RCTs might reduce this problem. The understanding of clinical treatment concepts also includes knowledge of its limitations. The control
and prevention of further pulpal and periapical damage in relation to
the restored tooth will, besides a sufficient restoration, include proper
oral hygiene procedures for the removal of cariogenic biofilms, which
tend to accumulate where the problem beganin the areas of the
restored tooth surfaces. In addition, follow-up examinations are mandatory for the evaluation of pulp sensibility and the possible presence of
apical pathosis (28).
Clinical Guidelines Based on an Observational Study

and a High-quality RCT
References
Observational studies from dental practice environments have

demonstrated the effectiveness of treating deep carious lesions by
using a less invasive or modified stepwise excavation. Long-term
recall (3.5 4.5 years) has demonstrated a high success rate (92%),
indicating that the method can be carried out in clinical practice
(26). The placement of high-quality temporary and final restorative
materials must be stressed, because failures are most often associated with inadequate restorations (4). Therefore, a 2-step excavation procedure will add to the cost of the treatment. Because of the
possibility of asymptomatic development of irreversible pulp degeneration over time, follow-up examinations are required with regard
to pulp sensibility and apical conditions. Because readers are al-
1. Ricketts DNJ, Kidd EAM, Innes N, Clarkson J. Complete or ultraconservative removal

of decayed tissue in unfilled teeth. Cochrane Database Syst Rev 2006;3:CD003808.
2. Miyashita H, Worthington HV, Qualtrough A, Plasschaert A. Pulp management for caries in
adults: maintaining pulp vitality. Cochrane Database Syst Rev 2007;2:CD004484.
3. Fitzgerald M, Heys RJ. A clinical histological evaluation of conservative pulpal therapy
in human teeth. Oper Dent 1991;16:10112.
4. Bjrndal L, Thylstrup A. A practice-based study on stepwise excavation of deep
carious lesions in permanent teeth: a 1-year follow-up study. Community Dent Oral
Epidemiol 1998;26:122 8.
5. Tomes J. A system of dental surgery. London: John Churchill, 1859:336.
6. Black GV. A work on operative dentistry in two volumes, vol II. The technical procedures in filling teeth. 2nd ed. Chicago: Medico-Dental Publishing Co, 1908.
7. Reit C, Petersson K, Molven O. Diagnosis of pulpal and periapical disease. In: Bergenholtz G, Hrsted-Bindslev P, Reit C, eds. Textbook of endodontology. Oxford:
Blackwell Munksgaard, 2003:9 18.
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8. Tronstad L. Clinical endodontics. 2nd ed. Stuttgard: Thieme, 2003:81.
9. Trope M, Sigurdsson A. Clinical manifestation and diagnosis. In: rstavik D, Pitt Ford
TR, eds. Essential endodontology: prevention and treatment of apical periodontitis.
Oxford: Blackwell Sci. Ltd, 1998:15778.
10. Kerkhove BC, Jr, Herman SC, Klein AI, McDonald RE. A clinical and television densitometric evaluation of the indirect pulp capping technique. J Dent Child 1967;34:192201.
11. Magnusson BO, Sundell SO. Stepwise excavation of deep carious lesions in primary
molars. J Int Assoc Dent Child 1977;8:36 40.
12. Sowden JR. A preliminary report on the recalcification of carious dentin. J Dent Child
1956;23:1878.
13. Law DB, Lewis TM. The effect of calcium hydroxide on deep carious dentin. Oral Surg
Oral Med Oral Path 1961;14:1130 7.
14. Eidelman E, Finn SB, Koulourides T. Remineralization of carious dentin treated with
calcium hydroxide. J Child Dent 1965;32:218 25.
16. Gruythuysen RJM, van Strijp AJP, Gunawan MIM, Ramdas M. Indirect pulp treatment
in primary and permanent teeth with deep carious lesions. Caries Res 2007;41:269.
17. Marchi JJ, de Araujo FB, Frner AM, Straffon LH, Nr JE. Indirect pulp capping in the
primary dentition: a 4 year follow-up study. J Clin Pediat Dent 2006;31:68 71.
18. Massler M. Treatment of profound caries to prevent pulpal damage. J Pedod 1978;2:99105.
19. Bjrndal L, Larsen T, Thylstrup A. A clinical and microbiological study of deep carious
lesions during stepwise excavation using long treatment intervals. Caries Res
1997;31:4117.
20. Pinto AS, de Arajo FB, Franzon R, et al. Clinical and microbiological effect of
calcium hydroxide protection in indirect pulp capping in primary teeth. Am J
Dent 2006;19:382 6.
21. Bjrndal L, Larsen T. Changes in the cultivable flora in deep carious lesions following
a stepwise excavation procedure. Caries Res 2000;34:502 8.
22. Paddick JS, Brailsford SR, Kidd EAM, Beighton D. Phenotypic and genotypic selection
of microbiota surviving under dental restorations. Appl Environ Microbiol
2005;71:246772.
23. Kidd EAM, Bjrndal L, Beighton D, Fejerskov O. Caries removal and the pulpodentinal complex. In: Fejerskov O, Kidd EAM, eds. Dental caries: the disease and
its clinical management. 2nd ed. Oxford: Blackwell Munksgaard, 2008:
367 83.
24. Oen KT, Thompson VP, Vena D, et al. Attitudes and expectations of treating deep
caries: a PEARL network survey. Gen Dent 2007;55:197203.
25. Bjrndal L, Bruun G, Markvart M, et al. The CAP-1 randomized trial: stepwise excavation versus one excavation - status of inclusion. Caries Res 2007;41:270.
26. Bjrndal L: Behanding af profunde carieslsioner med gradvis ekskavering. En praksis
baseret undersgelse (English summary). Tandlgebladet 1999;103:498 506.
27. Bjrndal L. Dentin and pulp reactions to caries and operative treatment: biological
variables affecting treatment outcome. Endodontic Topics 2002;2:10 23.
28. Bjrndal L, Mjr IA. Dental caries: characteristics of lesions and pulpal reactions. In:
Mjr IA, ed. Pulp-dentin biology in restorative dentistry. Chicago: Quintessence Publishing Co, 2002:5575.
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Indirect Pulp Capping and Primary Teeth: Is the Primary

Tooth Pulpotomy Out of Date?
James A. Coll, DMD, MS
Abstract
Formocresol pulpotomy (FP) in the United States is
most frequently used to treat asymptomatic caries near
the pulp in primary teeth. Indirect pulp therapy (IPT) is
also indicated and has a significantly higher long-term
success. Pulpotomy is thought to be indicated for primary teeth with carious pulp exposures, but research
shows the majority of such teeth are nonvital or questionable for treatment with vital pulp therapy. IPT has
a significantly higher success in treating all primary first
molars, but especially those with reversible pulpitis
compared with FP. The purpose of this article was to
review the dental literature and new research in vital
pulp therapy to determine the following: (1) Is a pulpotomy indicated for a true carious pulp exposure? (2)
Is there a diagnostic method to reliably identify teeth
that are candidates for vital pulp therapy? (3) Is primary
tooth pulpotomy out of date, and should indirect pulp
therapy replace pulpotomy? (J Endod 2008;34:S34-S39)
Key Words
Indirect pulp therapy, pulp exposure, pulpotomy
From the Department of Pediatric Dentistry, University of

Maryland Dental School, Baltimore, Maryland.
Address requests for reprints to Dr Coll at www.
dmd1@comcast.net.
Conflict of Interest: James A. Coll, DMD, MS, is a paid
consultant to the Maryland State Dental Board in the review
of dental charts of pediatric patients.
doi:10.1016/j.joen.2008.02.033
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Coll
he guidelines of the American Academy of Pediatric Dentistry (AAPD) on pulp

therapy for primary and young permanent teeth states that a pulpotomy is a procedure in which the coronal pulp is amputated, and the remaining radicular pulp tissue is
treated with a medicament or electrocautery to preserve the pulps health (1). The
guidelines state the objective of a pulpotomy is to keep the remaining pulp healthy
without adverse clinical signs or symptoms or radiographic evidence of internal or
external root resorption. The AAPD guidelines further state that there is only one other
choice for vital pulp therapy in primary teeth where caries approach the pulp. This
choice is indirect pulp therapy (IPT), because the direct pulp cap in a primary tooth is
contraindicated for carious exposures (1). IPT is a procedure in which the caries
closest to the pulp is left in place and covered with a biocompatible material, and the
tooth is restored to prevent microleakage. The objectives of treatment are the same as
for a pulpotomy (1).
For deep caries in primary teeth, the indications for IPT and pulpotomy are
identical for reversible pulpitis or a normal pulp when the pulp is judged to be vital from
clinical and radiographic criteria (1). The difference occurs when the caries removal
process results in a pulp exposure; a pulpotomy is then undertaken. IPT purposely
avoids an exposure by leaving the deepest decay in place. IPT is clearly not indicated
when the pulp is exposed by caries, but is pulpotomy indicated for a carious pulp
exposure? For deep caries with possible radiographic exposures that are asymptomatic,
which is the better choice of treatment, IPT or pulpotomy?
The purpose of this article was to review the dental literature and new research in
vital pulp therapy to determine the following: (1) Is a pulpotomy indicated for a true
carious pulp exposure? (2) Is there a diagnostic method to reliably identify teeth that are
candidates for vital pulp therapy? (3) Is primary tooth pulpotomy out of date, and
should IPT replace pulpotomy?
Is Pulpotomy Indicated for Carious Exposures?

A primary tooth pulpotomy should be performed on a tooth judged to have a vital
pulp (1). After the coronal pulp is amputated, this leaves behind vital radicular pulp
tissue that has the potential for healing and repair in 3 general ways, according to Rodd
(2). First, the remaining radicular pulp can be rendered inert, such as by using formocresol. It fixes or denatures the vital pulp so it is no longer pulp tissue in addition to its
bactericidal properties. Second, the radicular pulp might be preserved through minimal inflammatory insult by using a hemostatic agent such as ferric sulfate to form a clot
barrier to preserve the deeper remaining pulp tissue. The third pulpotomy mechanism
encourages the radicular pulp to heal and form a dentin bridge by using calcium
hydroxide or mineral trioxide aggregate (MTA).
What is the histologic and clinical research that can help dentists determine which
teeth with deep caries are vital and, thus, candidates for pulpotomy? Reeves and Stanley
(3) found that as long as the advancing edge of the carious lesion was 1.1 mm from the
pulp, no significant pathologic changes were evident in permanent teeth. Once the
caries approached within 0.5 mm of the pulp and the reparative dentin was involved,
then significant pathologic changes were noted. Shovelton (4) examined permanent
teeth and showed that as caries approximated 0.25 0.3 mm of the pulp, hyperemia and
pulpitis were seen.
Regarding the effect of pulp exposures on the pulps capacity to repair, Lin and
Langland (5) showed that that when no pulp exposure occurred from caries, the pulps
repair capacity was excellent. After a carious exposure, however, it was questionable
Pulp Symposium
Figure 1. Example of using glass ionomer caries control to diagnose reversible pulpitis or food impaction in a mandibular first primary molar with a history of pain
to chewing sweets and solid foods for 23 weeks. (a) Preoperative view. (b) Preoperative radiograph. (c) View immediately after glass ionomer placement. (d) Two
months after caries control. Pain stopped from day glass ionomer placed. No clinical or radiographic sign of irreversible pulpitis. (e) View of IPT with a glass ionomer
base. (f) Tooth 16 months after treatment without signs of pain or irreversible pulpitis clinically or on the radiograph.
and unpredictable. They also found that in teeth with a history of pain,
the pulp chamber would have an area of necrosis often extending into
the radicular pulp. Others have stated that the dentist risks displacing
infected dentin chips into the pulp when performing total excavation of
deep carious lesions, thus increasing the risk of pulpal inflammatory
breakdown (6).
Stepwise caries removal in permanent teeth thought to have radiographic pulp exposures has been proposed as a method to minimize
pulp exposures and preserve vitality (7, 8). Caries excavation is a 2-appointment procedure. Initially, the lesions periphery is made cariesfree, while the center of the caries is partially removed to leave moist,
soft dentin over the pulp. Then, calcium hydroxide and a temporary
filling are placed for 6 12 months. The lesion is then re-entered, and all
the caries is removed. Bjorndal et al. (7) found no pulp exposures on
re-entry in 31 permanent teeth by using stepwise caries removal. Leskell
et al. (8) tested stepwise caries removal versus conventional in 127
permanent teeth with a patient mean age of 10.2 years. After 8 24
months, stepwise removal resulted in approximately 18% pulp exposure versus 40% for conventional caries removal.
Many of these permanent tooth findings likely apply to primary
teeth. Rodd (2) stated that carious primary and permanent teeth
showed similar neural changes when mounting a pulpal defense to deep
caries. Rodd found that primary and permanent teeth have similar vascularity, except in the midcoronal region, and showed a similar degree
of vasodilatation and new vessel formation with caries progression.
Eidelman et al. (9) studied severely decayed primary incisors with
no pulp pathology in nonrestorable teeth from 20- to 42-month-old
children. After fixation, caries was removed with a slow-speed round
bur. A sharp explorer was used to evaluate total caries removal and
check for a pulp exposure. Teeth without pulp exposures and no total
necrosis likely as a result of trauma were histologically diagnosed as
treatable with vital pulp therapy in 23 of 26 cases (88%). By contrast, 16
of 24 (67%) of the incisors judged to be nontreatable (total necrosis)
or questionable (chronic partial pulpitis) for treatment with vital pulp
Indirect Pulp Capping and Primary Teeth
S35
Pulp Symposium
therapy had a carious pulp exposure, leaving only 33% that were unquestionably vital. Dentists might think they can obtain a 90% level of
pulpotomy success in such a case. The simple mathematics of 33%
(chance of finding a vital pulp) 90% (chance of pulpotomy success),
however, would equal a 30% chance of a cariously exposed tooth having
a successful pulpotomy. From these histologic and clinical findings, the
following conclusions can be drawn:
1. Primary tooth pulpotomy requires a vital radicular pulp, no matter what form or type of pulpotomy procedure is used (1, 2).
Teeth with a carious pulp exposure have a low likelihood of being
totally vital (9) and are, thus, poor candidates for vital pulpotomy.
2. Stepwise caries removal will result in fewer pulp exposures than
total caries removal performed in 1 visit (7, 8).
3. For teeth without carious pulp exposures, performing a pulpotomy likely increases the chance of displacing infected dentin
chips into the pulp and impairing the pulps repair capacity (5,
6).
4. The pulps repair capacity is excellent when the carious lesion
remains 1 mm or more away from the pulp (3).
Is There a Diagnostic Method to Identify Teeth with

Deep Caries That Are Symptomless or Questionable,
Yet Are Candidates for Vital Pulp Therapy?
Identifying those teeth with deep caries that are vital and treatable
with vital pulp therapy leads to this articles second purpose, which was
to describe a new method to reliably diagnose these teeth. Initially
placing an intermediate, therapeutic, temporary restoration by using
glass ionomer caries control (GICC) for 13 months before starting
pulp therapy has been shown to be an excellent method of diagnosing
the pulps vitality. No anesthesia is used to perform minimal caries
excavation with spoon excavators or slow-speed round burs and is a
form of alternative restorative treatment (ART) (10) or stepwise caries
removal (7). This procedure takes less than 5 minutes and can be done
at the initial examination visit of a child presenting with multiple open
carious lesions.
GICC is indicated in cavitated carious lesions to diagnose their
vitality in teeth with signs and symptoms of reversible pulpitis or a
symptomless tooth thought to have no pulpitis before instituting any
pulp therapy (11). The technique involves minimally removing the superficial, nonpainful decay by using a slow-speed no. 4 or 6 round bur
or spoon excavation. A glass ionomer temporary filling is then placed by
using a material such as Fuji IX (GC America Inc, Alsip, IL), Ketac Molar
(3M ESPE, St Paul, MN), Voco Ionofil Molar AC (Voco Gmbh, Cuxhaven,
Germany), or a resin-modified glass ionomer. A matrix band does not
have to be used, but the intermediate therapeutic temporary restoration
should not be in occlusion. After 13 months of GICC, if the tooth has
been asymptomatic and shows no signs of irreversible pulpitis clinically
or on a new radiograph, vital pulp therapy can be instituted by using IPT
or pulpotomy (Fig. 1).
Numerous studies have reported on the biologic effects of a glass
ionomer temporary filling. Bonecker et al. (12) studied dentin samples
in 40 primary molars before and after ART excavation. The total bacterial count and mutans streptococci were significantly reduced from the
excavation process alone. Loyola-Rodriquez et al. (13) showed in vitro
that all glass ionomer liners had good antibacterial activity against
Streptococcus sobrinus and S. mutans associated with their fluoride
release.
Wambier et al. (14) published an in vivo study of 32 primary
molars with open deep carious lesions. Radiographs and examinations
excluded teeth with apical pathosis. Initially, carious dentin samples
were taken, and then minimal caries excavation was performed folS36
Coll
TABLE 1. All Types of Pulpotomy Usually Show Decreased Success over Time
References
Pulpotomy
Dean et al. 2002 (18)

Huth et al. 2005 (19)
Rolling and Thylstrup
1975 (20)
Vij et al. 2004 (11)
Smith et al. 2000 (21)
Casas et al. 2004 (22)
Eidelman et al. 2001 (23)
Jabbarifar et al. 2004 (24)
Holan et al. 2005 (25)
Formocresol
1/5 formocresol
Formocresol
Formocresol
Ferric sulfate
Ferric sulfate
MTA
MTA
MTA
Success
(%)
Time
(mo)
92
85
70
612
24
36
70
7480
67
100
94
91
40
19
36
13
12
38
NOTE. Internal root resorption was not always considered failure; Peng et al. (26) calculated MTA
success at 91%, counting internal resorption.
lowed by a resin-modified glass ionomer temporary filling. After 30 and

60 days of temporization, the second dentin samples showed that total
bacterial counts decreased significantly (P .05), and all bacterial
strains had similar trends in both time periods. Scanning electron microscopy inspection of dentin samples in the same time frames showed
dentin reorganization and narrower dentin tubules. The authors believed the results suggested that sealing the cavitated lesion with glass
ionomer contributes to remineralization. Only the outer carious layer
needs to be removed to accomplish this result. Oliveira et al. (15)
reported on 32 permanent teeth after minimal caries excavation and
temporization for longer time periods. They concluded that total caries
removal did not seem essential to stop caries progression.
Regarding the effect of glass ionomer on the subsequent vital pulp
therapy, Vij et al. (11) reported that GICC temporization for 13 months
increased success of the subsequent vital pulp therapy from 79% to
92%. Teeth temporized with zinc oxide eugenol, however, had a success rate of 67%. They also reported a drying out effect of the moist
caries on re-entry after GICC similar to that reported by Bjorndal et al.
(7) after 6 7 months of stepwise caries removal.
Another recently completed study reported on GICCs diagnostic
success in deeply cavitated carious lesions (16). A group of primary
molars had GICC after minimal caries excavation for a mean time of 3.5
months. The GICC intermediate therapeutic temporary restoration had
to have remained intact without displacement for 1 4 months. Another
group of primary molars had no GICC. Both groups had IPT or formocresol pulpotomy and were restored with an immediate steel crown the
day of treatment and were followed for a mean time of more than 3
years. Diagnostic success was based on the vital pulp therapy success, or
the tooth was successfully diagnosed with irreversible pulpitis after 13
months of GICC. The GICC group showed a significant increase (P
.001) in the subsequent vital pulp therapy success (98%) versus the
non-GICC groups vital pulp therapy success (75%). There was a subgroup of 18 teeth that presented with pain and/or a questionable diagnosis of their vitality. All received GICC initially for 1 4 months to
diagnose the tooths vitality. The GICC produced the correct diagnosis
for all the teeth in that 7 molars returned with signs of irreversible
pulpitis and were extracted. For the other 11, however, the pain was
diagnosed as reversible, and all were treated with vital pulp therapy
successfully.
From these microbiologic and clinical studies, the following conclusions can be made on using glass ionomer caries control:
1. Treating primary teeth with deeply cavitated carious lesions after
minimal excavation with glass ionomer caries control for 13
months initially before instituting pulp therapy causes the bacteria to significantly decrease within the lesion (13, 14). In vital,
symptomless teeth with apparent radiographic exposures or near
Pulp Symposium
Figure 2. Long-term success rates of formocresol pulpotomy and IPT were

statistically different starting in the 2- to 3-year follow-up grouping. Reproduced
with permission from Forooq NS, Coll JA, Kuwabara A, Shelton P. Success rates
of formocresol pulpotomy and indirest pulp therapy in the treatment of deep
dentinal caries in primary teeth. Pediatr Dent 2000;22:278 86.
exposures, treating them with caries control will likely stop caries
progression (15).
2. GICC for 13 months changes the character of the dentin so that
it is drier and harder, and the affected dentin likely remineralizes
similar to dentin after stepwise excavation (7, 11, 14).
3. Using GICC as a diagnostic tool for 13 months in teeth with
symptomless radiographic exposures or ones with pain and questionable vitality will diagnose those that can be treated successfully with vital pulp therapy 98% of the time (16).
Is the Primary Tooth Pulpotomy out of Date for

Treatment of Deep Caries and Should IPT Replace
Pulpotomy?
Knowing the pulpal diagnosis of primary teeth with deep caries by
using GICC should greatly improve the chance of any vital pulp therapy.
This leads to the articles third purpose: Is IPT or pulpotomy the best
choice for vital pulp therapy for deeply cavitated carious lesions?
Most pulpotomy success decreases over time from 90% or more
initially (6 12 months) to 70% or less after 3 years or more (11, 20,
22) (Table 1, Figure 2). The MTA pulpotomy appears to have a higher
long-term success rate (90%) than other pulpotomy types (2325).
Yet these reports generally are of shorter duration (only one 24
months (25)) and have small sample sizes (38 teeth) from which to
draw strong conclusions. Most of these MTA pulpotomy studies were
performed on teeth with symptomless radiographic exposures, and
most had immediate steel crowns placed after pulpotomy. The immediate crown should have minimized microleakage and increased pulpotomy success compared with a large amalgam (27), which had been
used in other pulpotomy studies (17, 27). A recent meta-analysis of

MTA versus formocresol pulpotomy studies suggested that MTA was
superior to formocresol as a result of its lower failure rate (26).
IPT usually shows success rates of 90% or greater no matter the
technique, medicament, or time periods (Table 2, Figure 2). IPTs
long-term success (3 4 years) surpasses all other pulpotomy studies,
with the possible exception of the 1 long-term MTA study (25). There
have been various medicaments used for IPT, from calcium hydroxide
(28 30), glass ionomer (11, 17), to none (30), all of which did not
significantly change IPTs success rates, as shown in Table 2. Even using
dental students of vastly different abilities and likely different techniques, as reported by Al-Zayer et al. (29), did not significantly decrease
IPTs success below 95%. The type of final, immediate restoration did
not alter IPTs success when steel crowns were compared with composite fillings and glass ionomers (11, 30). Even when no medicament was
placed for IPT and the composite filling was bonded to the remaining
decay and decay-free dentin, Falster et al. (30) reported success greater
than 90%.
How are pulpotomy and IPT being taught and practiced in the
United States? Dunston and Coll (31) in 2005 surveyed 48 of the 56
pediatric program directors in the U.S. dental schools and 689 of the
board-certified pediatric dentists. They found that 76% of the dental
schools taught either diluted or full-strength formocresol pulpotomy,
whereas the other 24% taught ferric sulfate. Of the 689 pediatric dentists, 81% used diluted or full-strength formocresol, 18% ferric sulfate,
and 1% some other type of pulpotomy (electrocautery, MTA, etc). Formocresol remains the overwhelming choice for pulpotomy, signifying
the toxic concerns regarding formocresol do not seem to be a concern
for most schools or practicing dentists. The International Agency for
Research on Cancer stated in a 2004 press release that formaldehyde
causes nasopharyngeal cancer (32). Milnes (33) in 2006 disputed the
cancer concern by stating that the amount of formocresol in a pulpotomy was likely such a small amount that formocresol pulpotomy was a
low-exposure condition. Zazar et al. (34) found that when studying the
white blood cells after formocresol pulpotomy in 20 children, 1 child
showed a 6-fold increase in white blood cell chromosomal abnormalities. From a statistical standpoint, they believed formocresol was not
mutagenic, but further studies were needed to verify this.
The 2005 survey (31) also had a clinical scenario question regarding deep caries removal in a primary second molar in a 5-year-old.
Seventy percent of the program directors and more than 80% of the
pediatric dentists reported that a pulpotomy was the treatment of choice
over IPT. It appears that IPT is not emphasized in U.S. dental schools as
a method to treat deep asymptomatic caries, and most dentists practice
the way they were taught. In addition, most pediatric dentists believe it is
best to enter the pulp and do a formocresol pulpotomy, even though
long-term formocresol pulpotomy success is significantly lower than
IPT (11, 17, 20, 30).
Other factors need to be considered when choosing IPT or pulpotomy for deep caries in primary teeth. Vij et al. (11) studied IPT and
pulpotomy success treating molars with reversible pulpitis pain. They
TABLE 2. IPT Studies Show Success Rates of 90% or Greater over Time with Differing Techniques and Medicaments
Nirschl and Avery 1983 (28)
Al-Zayer et al. 2003 (29)
Falster et al.* 2002 (30)
Vij et al. 2004 (11)
Farooqet al. 2000 (17)
IPT medicaments
Success (%)
Time (mo)
Sample (N)
Calcium hydroxide
Calcium hydroxide
Glass ionomer
Glass ionomer
94
95
90
94
93
6
14 (median)
24
40
50
33
187
48
108
55
*Adhesive resin alone without a liner or calcium hydroxide liner and adhesive resin.
Combined success of both groups.
S37
Pulp Symposium
reported that in 20 first primary molars with such pain, IPT success was
85%, which was significantly better (P .04) than the 53% in 19
primary first molars treated with formocresol pulpotomy. They also
found that there was significantly (P .04) low success (61%) when
first primary molars were treated with formocresol pulpotomy compared with the 92% success with IPT in these molars. When the data of
Holan et al. (27) were tested with 2 analysis; it also showed a significantly lowered success for formocresol pulpotomy in primary first molars.
Another concern in the choice of using IPT or pulpotomy is the
early exfoliation of pulpotomized teeth. More than 35% of formocresol
pulpotomies exfoliate significantly earlier (6 months) than nonpulpotomized teeth, whereas IPT-treated teeth exfoliate normally (11, 17).
In addition, pulpotomies cost more than 2.3 times more than IPT, on the
basis of published dental insurance reimbursement for the 2 procedures (35, 36). In the United States, however, most dental insurers do
not cover IPT for primary teeth, which might result in less utilization.
For a tooth with deep caries 1 mm away from the pulp, IPT or pulpotomy
can be performed. The pulpotomy could be more painful, because
profound anesthesia is always needed for a pulpotomy, whereas the IPT
requires no pulpal entry and, therefore, is potentially less painful.
When performing IPT and leaving residual decayed dentin, what
are the concerns of leaving this decay after a 1-visit IPT? Aponte et al.
(37) reported performing indirect pulp capping with calcium hydroxide followed by amalgam restorations in 30 primary molars. After 6 46
months (mean, 29 months), the amalgam and calcium hydroxide were
removed, and the carious dentin that had been left behind cultured. In
28 of 30 teeth (93%), the residual carious dentin was sterile. Oliveira et
al. (15) studied 32 permanent teeth judged by radiographs to have a
pulp exposure. From digitized radiographs taken 6 7 months after
partial caries removal followed by temporary fillings, there was mineralized improvement in the carious dentin over time. Finally, the 10-year
prospective study by Mertz-Fairhurst et al. (38) conclusively showed
that in 85 teeth after obvious occlusal caries was successfully sealed
from microleakage, after 10 years in vivo, there was no progress of the
caries in permanent teeth.
The following conclusions on choosing IPT or pulpotomy can be
drawn from these studies:
1. Formocresol and ferric sulfate pulpotomy have a significantly
lower long-term success for treatment of deep caries compared
with IPT (11, 17, 20, 30). Most U.S. pediatric dentists currently
choose to use formocresol pulpotomy over IPT (31).
2. IPT has been shown to have a significantly higher success rate for
teeth with reversible pulpitis compared with formocresol pulpotomy (11).
3. IPT shows higher long-term success rates than any pulpotomy
other than possibly MTA (Tables 1 and 2). MTA pulpotomy has
not been shown to be effective in treating teeth with reversible
pulpitis.
4. IPT is less expensive, has fewer potential side effects, and does not
exhibit early exfoliation as pulpotomy does (11, 17, 35, 36).
Conclusions
Controversy persists as to the best way to perform vital pulp therapy, and additional research is needed to see whether MTA pulpotomy
performs as well as IPT. From the present review of the literature and
research, the following conclusions can be made:
1. Do not treat carious exposures in primary teeth with pulpotomy
or direct pulp caps. Consider pulpectomy or extraction because
S38
Coll
of the high chance of irreversible pulpitis and failure of vital pulp

therapy after a carious pulp exposure.
2. For deep caries approaching the pulp, the choice of IPT or pulpotomy is up to the treating dentist.
3. Use glass ionomer caries control for deep cavitated lesions to
diagnose the status of the pulp with or without history of pain to
attain the highest success for vital pulp therapy. Stay out of the
pulp by using IPT for a higher long-term chance of success compared with formocresol and ferric sulfate pulpotomy.
4. IPT has been shown to have a lower cost, higher success longterm, better exfoliation pattern, and better success treating reversible pulpitis than pulpotomy.
References
1. American Academy of Pediatric Dentistry. Clinical guidelines on pulp therapy for
primary and young permanent teeth: reference manual 2006-07. Pediatr Dent
2006;28:144 8.
2. Rodd H. A pain in the pulp: innervation inflammation and management of the compromised primary tooth pulpsynopses. Newsl Aust N Z Soc Paediatr Dent
2005;32:35.
3. Reeves R, Stanley HR. The relationship of bacterial penetration and pulpal pathosis in
carious teeth. Oral Surg 1966;22:59 65.
4. Shovelton DS. A study of deep carious dentin. Int Dent J 1968;18:392 405.
5. Lin L, Langeland K. Light and electron microscopic study of teeth with carious pulp
exposures. Oral Surg 1981;51:292316.
6. Bergenholtz G, Spangberg L. Controversies in endodontics. Crit Rev Oral Biol Med
2004;15:99 114.
7. Bjorndal L, Larsen T, Thylstrup A. A clinical and microbiological study of deep
carious lesions during stepwise excavation using long treatment intervals. Caries Res
1997;31:4117.
8. Leskell E, Ridell K, Cvek M, Majare I. Pulp exposure after stepwise vs direct complete
excavation of deep carious lesions in young posterior permanent teeth. Endod Dent
Traumatol 1996;12:192 6.
9. Eidelman E, Ulmansky M, Michaeli Y. Histopathology of the pain in primary incisors
with deep dentinal caries. Pediatr Dent 1992;14:13725.
10. AAPD. Clinical guideline on pediatric restorative dentistry: reference manual 200607. Pediatr Dent 2006;28:136 43.
12. Bonecker M, Toi C, Cleaton-Jones P. Mutans streptococci and lactobaccili in
carious dentin before and after atraumatic restorative treatment. J Dent 2003;
31:423 8.
13. Loyola-Rodriquez JP, Garcia-Godoy F, Lindquist R. Growth inhibition of glass ionomer cements on mutans streptococci. Pediatr Dent 1994;16:346 9.
14. Wambier DS, dos Santos FA, Guedes-Pinto AC, Jacqer RG, Simionato MRL. Ultrastructural and microbiological analysis of the dentin layers affected by caries
lesions in primary molars treated by minimal intervention. Pediatr Dent
2007;29:228 34.
15. Oliveira EF, Carminatti G, Fontanella V, Maltz M. The monitoring of deep caries
lesions after incomplete caries removal: results after 14-18 months. Clin Oral Investig
2006;10:134 9.
16. Campbell A, Coll JA. Thesis: diagnostic success of the glass ionomer sedative filling
determining pulpal vitality in primary molars with deep caries. Baltimore, MD:
University of Maryland Pediatric Dental Department, 2007.
17. Forooq NS, Coll JA, Kuwabara A, Shelton P. Success rates of formocresol pulpotomy
and indirest pulp therapy in the treatment of deep dentinal caries in primary teeth.
Pediatr Dent 2000;22:278 86.
18. Dean JA, Mack RB, Fulkerson BT, Sanders BJ. Comparison of electrosurgical and formocresol
pulpotomy procedures in children. Int J Paediatr Dent 2002;12:17782.
19. Huth KC, Paschos E, Hajek-Al-Khatar N, et al. Effectiveness of 4 pulpotomy techniques: randomized controlled trial. J Dent Res 2005;84:1144 8.
20. Rolling I, Thylstrup A. A 3-year clinical follow-up study of pulpotomized primary
molars treated with formocresol technique. Scand J Dent Res 1975;83:4753.
21. Smith NL, Seale NS, Nunn ME. Ferric sulfate pulpotomy in primary molars: a retrospective study. Pediatr Dent 2000;22:1929.
22. Casas MJ, Kenny DJ, Johnston DH, Judd PL. Long-term outcomes of primary molar
ferric sulfate pulpotomy and root canal therapy. Pediatr Dent 2004;26:44 8.
23. Eidelman E, Holan G, Fuks AB. Mineral trioxide aggregate vs formocresol in pulpotomized primary molars: a preliminary report. Pediatr Dent 2001;23:15 8.
24. Jabbarifar SE, Khademi A, Ghasemi D. Success rate of formocresol pulpotomy vs
mineral trioxide aggregate in human primary molar tooth. J Res Med Sci
2004;6:304 7.
Pulp Symposium
25. Holan G, Eidelman E, Fuks AB. Long-term evaluation of pulpotomy in primary
molars using mineral trioxide aggregate of formocresol. Pediatr Dent 2005;
27:129 36.
26. Peng L, Ye L, Tan H, Zhou X. Evaluation of the formocresol vs mineral trioxide
aggregate primary molar pulpotomy: a meta-analysis. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 2006;102:e40 4.
27. Holan G, Fuks AB, Keltz N. Success of formocresol pulpotomy in primary molars
restored with steel crowns vs amalgam. Pediatr Dent 2002;24:212 6.
28. Nirschl RF, Avery DR. Evaluation of a new pulp capping agent in indirect pulp therapy.
J Dent Child 1983;50:2530.
30. Falster CA, Araujo FB, Straffon LH, Nor JE. Indirect pulp treatment: In vivo outcomes
of an adhesive resin system vs calcium hydroxide for protection of the dentin-pulp
complex. Pediatr Dent 2002;24:241 8.
31. Dunston B, Coll JA. A survey of primary tooth pulp therapy as taught in US dental
schools and practiced by diplomates of the American Board of Pediatric Dentistry.
Pediatr Dent 2008;30:42 48.
32. International Agency for Research on Cancer, World Health Organization. IARC classifies formaldehyde as carcinogenic to humans. Press release no. 153, June 15, 2004.
Available at: http://www.iarc.fr/ENG/Press_Releases/archives/pr153a.html.
Accessed February 27, 2008.
33. Milnes AR. Persuasive evidence that formocresol use in pediatric dentistry is safe. J
Can Dent Assoc 2006;72:247 8.
34. Zazar PA, Rosenblatt A, Takahashi CS, Takeuchi PL, Costa Jr LA. Formocresol mutagenicity following primary tooth pulp therapy: an in vivo study. J Dent
2003;31:479 85.
35. Dental Benefits Plus fee schedule. Available at: http://www.dentalbenefitsplus.com/
FeeSchedule/FeeScheduleDownload.asp. Accessed November 23, 2007.
36. Creighton International dental fee schedule for Pennsylvania. Available at: http://
www.nationalinsurancestore.com/care/jump.htm. Accessed November 23, 2007.
37. Aponte AJ, Hartsook JT, Crowley MC. Indirect pulp capping verified. J Dent Child
1966;33:164 6.
38. Mertz-Fairhurst EJ, Curtis JW, Ergle JW, Rueggeberg FA, Adair SM. Ultraconservative
and cariostatic sealed restorations: results at year 10. J Am Dent Assoc
1998;129:55 66.
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Pulp Symposium
Is Formocresol Obsolete? A Fresh Look at the Evidence

Concerning Safety Issues
Alan R. Milnes, DDS, PhD
Abstract
Concern has been expressed about the safety of formocresol use in pediatric dentistry. Formaldehyde, a
primary component in formocresol, is a hazardous substance and is considered a probable human carcinogen
by the International Agency for Research on Cancer,
Health Canada, the Agency for Toxic Substances and
Disease Registry in the U.S. Department of Health and
Human Services, and the U.S. Environmental Protection
Agency. Humans inhale and ingest formaldehyde daily,
however, and produce formaldehyde during cellular metabolism. The human body is physiologically equipped to
handle formaldehyde through multiple conversion pathways. The resultant single carbon atom released during
metabolism is deposited in the 1-carbon pool, which, in
turn, is used for the biosynthesis of macromolecules
including DNA and RNA. Reevaluation of earlier research that examined potential health risks associated
with formaldehyde exposure has shown that this research was based on flawed assumptions, which resulted in erroneous conclusions. The purpose of this
review was to examine more recent research about
formaldehyde metabolism, pharmacokinetics, and carcinogenicity. These results indicated that formaldehyde
is probably not a potent human carcinogen under low
exposure conditions. Extrapolation of these research
results to pediatric dentistry suggests an inconsequential risk associated with formaldehyde use in pediatric
pulp therapy. (J Endod 2008;34:S40-S46)
Key Words
Carcinogens, chemistry, formaldehyde, formocresol,
pulpotomy, toxicity
Private practice in Kelowna, British Columbia, Canada.

Address requests for reprints to Dr Milnes at
angelmanguel@shaw.ca.
Conflict of Interest: Alan R. Milnes, DDS, PhD, reports no
financial interests or potential conflicts of interest.
doi:10.1016/j.joen.2008.03.008
S40
Milnes
he suggestion has been made recently that formocresol use in pediatric dentistry is
unwarranted because of safety concerns, and consequently, formocresol use in
pediatric pulp therapy is obsolete. As a result, numerous investigations for alternatives
to formocresol, some of which have shown efficacy equivalent to formocresol, have
been completed. There can be no doubt that a reparative, biologic approach to pediatric
pulp therapy is preferable to the absolutist, devitalization approach of formocresol
pulpotomy or primary tooth pulpectomy, and research into alternatives is not only
welcome but absolutely essential. This commentary will demonstrate, through a thorough review of the relevant literature, however, that the evidence for banning this
medicament because of safety concerns has been either misinterpreted or replaced by
better science.
Ubiquity of Formaldehyde
Daily formaldehyde exposure is a fact of life. Formaldehyde is found in the air we
breathe, the water we drink, and the food we eat (1). The World Health Organization
(WHO) (2) has estimated that daily consumption of formaldehyde approximates
1.514 mg/day (mean, 7.8 mg/day), although daily intake from food is difficult to
evaluate. Owen et al (3) estimated that North Americans eating a typical North American
diet ingest 11 mg/day. There are other numerous sources of formaldehyde exposure,
which are summarized in Table 1. In unpopulated areas, outdoor air contains approximately 0.2 parts per billion (ppb) formaldehyde. In populated areas with truck and
automobile traffic, however, air concentrations range between 10 and 20 ppb. There
have also been instances of high concentrations of formaldehyde in the air inside
homes. In 20022003, Health Canada (5) found formaldehyde levels of 2 81 ppb in
homes in Prince Edward Island and Ottawa, Canada. Second-hand cigarette smoke
might contain up to 0.4 ppm of formaldehyde (6). The National Institute for Occupational Safety and Health (7) in the United States has stated that formaldehyde is immediately dangerous to health and life at concentrations of 20 parts per million (ppm) and
higher.
Assuming a contribution of 9.4 mg/day from food, 1 mg/day from inhalation, and
0.15 mg/day from water, an adult takes in 10.55 mg of formaldehyde per day (1). At
present, there are no estimates of pediatric exposure, although it is likely that children
are exposed to lower amounts because of lesser food intake.
The estimated formaldehyde dose associated with 1 pulpotomy procedure, assuming a 1:5 dilution of formocresol placed on a no. 4 cotton pellet that has been squeezed
dry, is approximately 0.02 0.10 mg.
Given the environmental ubiquity of formaldehyde and the recognized daily intake
by humans, it is highly unlikely that the elimination of the microgram quantities of
formaldehyde associated with formocresol pulpotomy will have a significant impact on
a childs daily exposure.
Pharmacokinetics of Formaldehyde
Humans produce endogenous formaldehyde as part of normal cellular metabolism. Hileman (8) has shown that endogenous levels of metabolically produced formaldehyde range from approximately 312 ng/g tissue. Amino acid metabolism, oxidative
demethylation, and purine and pyrimidine metabolism have all been shown to produce
formaldehyde (9). Importantly however, human cells are physiologically equipped to
manage this exposure through multiple pathways for oxidation of formaldehyde to
formate and incorporation into biologic macromolecules via tetrahydrofolate-depen-
Pulp Symposium
TABLE 1. Sources of Human Formaldehyde Exposure (4)
Atmospheric formation: photochemical oxidation of organic
compounds
Internal combustion engine exhaust
Fertilizer production
Hydrogen sulfide scavenger: oil operations
Household products:
Dishwashing liquid
Antiseptics and disinfectants
Carpet cleaners
Carpets
Preservatives and embalming solutions
Cosmetics (maximum concentration, 0.3% v/v):
Fingernail hardeners (maximum concentration, 5% v/v)
Paper products
Adhesives
Tire and rubber manufacturing
Latex paints
Resin production:
Phenolic-formaldehyde resin
Urea-formaldehyde resin
Pentaerythritol resin
Permanent press fabrics
Manufactured wood products
Forest and brush fires
Tobacco products
dent, 1-carbon biosynthetic pathways. The single carbon atom released

during metabolism of formaldehyde and formate is deposited in the
1 carbon atom pool, which, in turn, is used for the biosynthesis of
purines, thymidine, and other amino acids that are incorporated into
RNA, DNA, and proteins during macromolecular synthesis.
Cytosolic alcohol dehydrogenase, mitochondrial aldehyde dehydrogenase, and glutathione-dependent and glutathione-independent
dehydrogenases are important enzymes in the metabolism of formaldehyde in hepatocytes (10), oral mucosa (11), and nasal respiratory
mucosa (12). Formate is the principal oxidative product of formaldehyde, which is further oxidized to carbon dioxide and water by the
action of formyltetrahydrofolate synthetase (13). Formate might be converted to a soluble sodium salt via alternative pathways and excreted in
the urine, or it might be incorporated into the 1-carbon pool for use in
biosynthesis (14, 15).
Exogenous formaldehyde is taken up into the human body via
ingestion, inhalation, and dermal exposure. Inhaled formaldehyde appears to be readily absorbed by the upper respiratory tract, but it is not
distributed throughout the body because it is so rapidly metabolized
(16). Ingested formaldehyde is readily absorbed by the gastrointestinal
tract and exhibits little subacute toxicity after oral exposure (17). Experiments in humans, monkeys, and rats have shown no significant
differences in formaldehyde concentration in the blood before and immediately after exposure by inhalation. Heck et al (16) used gas chromatography and mass spectrometry to measure blood formaldehyde
concentrations in Fischer 344 rats exposed to a very high formaldehyde
concentration (14.4 ppm for 2 hours) and in unexposed controls.
They showed that the blood concentrations of the 2 groups were
virtually identical. In rhesus monkeys, Casanova et al (18) reported
that the formaldehyde concentrations in the blood after prolonged
exposure to a high concentration of inhaled formaldehyde (6 ppm
for 6 hours per day, 5 days per week for 4 weeks) had no significant
effect on the formaldehyde concentration in blood relative to preexposure levels.
Human experiments have also provided compelling evidence that
inhaled formaldehyde has virtually no impact on blood concentrations
of formaldehyde. Heck et al (16) exposed 6 human volunteers for 40
minutes to 1.9 ppm formaldehyde (a concentration that is considered
slightly irritating to the nasal and conjunctival membranes), but the

concentrations before exposure were not significantly different from
those measured immediately after exposure. The average formaldehyde
concentration in the blood of rats, monkeys, and humans was 2.70
0.15 g/g (mean standard error) or approximately 0.1 mmol/L. In
dermal studies, formaldehyde was absorbed less readily by monkeys
than by rats or guinea pigs (19).
The half-life of formaldehyde molecules in monkey blood is about
1.5 minutes after intravenous infusion (20). A concurrent rise in formic
acid levels occurs, indicating formaldehydes metabolism (20). In rats,
formaldehydes metabolism after administration via the pulp chamber is
also rapid, and the majority of conversion reportedly occurs within 2
hours after administration (21). Exogenous formaldehyde has a biologic half-life of 11.5 minutes (22) and is quickly cleared from human
plasma. In dogs, the conversion of formate to carbon dioxide and water
results in a biologic half-life for formate of about 80 90 minutes (13).
In humans, the liver converts formaldehyde to carbon dioxide at a rate
of 22 mg/min (3, 23, 24).
In mice and rats, the metabolites of formaldehyde are eliminated in urine, feces, and expired air, with the relative proportion
depending on the route of administration (25, 26). Higher urine
concentrations of formic acid were found in 3 of 6 workers occupationally exposed to unspecified concentrations of formaldehyde
in air (30.0, 50.5, and 173.0 mg/L, respectively) than in unexposed
workers (17 mg/L) (27).
Formaldehyde also reacts covalently with amino and sulfhydryl
groups in target tissues and with DNA, forming unstable hydroxymethyl
protein adducts (DNA-protein cross-links [DPX]) and, in a second
slower reaction involving recruitment of a second amino group, methylene cross-links (28, 29). In rat and monkey tissues, however, metabolism of formaldehyde and its elimination by pathways other than DPX
formation overwhelmingly predominate (30).
Results from dental pulp studies involving rats, dogs, and monkeys
showed that formaldehyde labeled with radioactive carbon (14C) was
apparently distributed among the muscle, liver, kidney, heart, spleen,
and lungs. The quantities of radiolabeled chemical detected, however,
were very small (1% of the total administered dose) (21, 3133). Myers
et al (32) and Pashley et al (33) concluded that [14C]formaldehyde is
absorbed systemically from pulpotomy sites. These studies have been
widely quoted as evidence that formaldehyde is distributed to distant
sites. The investigators in these studies, however, did not determine
whether the labeling of tissues occurred by metabolic incorporation of
the [14C] moiety of the labeled formaldehyde into macromolecules after
the labeled formaldehyde molecule had been metabolized or by covalent binding (formation of protein adducts) by radiolabeled formaldehyde molecules.
In an unrelated study, Casanova-Schmitz et al (34) sampled the
venous blood of rats after injecting either [14C]formaldehyde or
[14C]formate into the tail vein. They verified that labeling of proteins and
target tissues was due to metabolic incorporation of the radiolabeled
metabolite of formaldehyde, 14C, and not covalent binding. The profiles
of radioactivity in the blood after these injections were similar, regardless of whether [14C]formaldehyde or [14C]formate was the source of
14
C. These results excluded the possibility that the labeling of macromolecules is due to formation of protein adducts by formaldehyde,
because only [14C]formaldehyde is capable of forming protein adducts,
whereas both [14C]formaldehyde and [14C]formate are precursors for
macromolecular synthesis by the 1-carbon pool. Hence, it appears that
the claims of systemic distribution in dental publications have been
overstated and are, in fact, false.
Is Formocresol Obsolete?
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Pharmacokinetics of Cresol
The second active ingredient in formocresol, cresol, has received
little attention in the debate about formocresol safety or in investigations
of formocresol efficacy. Cresol has poor solubility, and because of this,
it has been assumed that it does not enter systemic circulation (35).
Cresol is highly lipophilic, however, and has been shown to completely
destroy cellular integrity, which presumably would allow for deeper
tissue fixation by the formaldehyde component of formocresol (35, 36).
No data exist regarding cresol metabolism or elimination in humans or
other mammals, and there is virtually no information about environmental sources of cresol to which humans might be exposed. Last, no
human studies have been published that have examined plasma concentration after exposure to cresol.
A recent clinical study in Colorado has reexamined the issue of
systemic distribution of formocresol (37). Blood samples were drawn
preoperatively, intraoperatively, and postoperatively from 30 children,
each of whom received comprehensive dental treatment including at
least 1 pulpotomy under general anesthesia. Blood samples were examined for formaldehyde and cresol content by using gas chromatography and mass spectrometry detection. Neither formaldehyde nor
cresol was detected in any blood sample. Benzyl alcohol, however, a
by-product of tricresol oxidation (38), was detected in microgram
quantities in a dose-response fashion in blood samples collected after
placement of formocresol-containing pellets.
Benzyl alcohol is present as a bacteriostatic preservative in many
multidose intravenous drugs and solutions (39). It also occurs naturally
in many plants, including raspberries and tea, and is an essential ingredient in many essential oils (39). Benzyl alcohol is oxidized rapidly to
benzoic acid, conjugated with glycine in the liver, and excreted as hippuric acid. It has no carcinogenic or mutagenic potential, and the allowable daily intake, as established by WHO, is 5 mg/kg (39, 40).
Mutagenicity, Genotoxicity, and Cytotoxicity

Exposure of cells to formaldehyde leads to the formation of DPX
(41). The most common types of DNA damage induced by formaldehyde are clastogenic lesions, including sister chromatid exchanges
(SCEs), micronuclei and chromosomal aberrations (42), and deletions
(43). Levels of formaldehyde-induced DPX are considered to represent
a good molecular dosimeter of formaldehyde exposure at sites of contact and are frequently used for risk modeling and prediction of formaldehyde carcinogenicity for different species (44 46). DPX have been
shown to occur only at the site of initial contact in the nasal mucosa of
rats and in the upper respiratory tract of monkeys exposed to formaldehyde (45, 46).
It has also been proposed that formaldehyde could induce the
development of DPX at distant sites, but no convincing evidence has
been obtained from in vivo experimental studies. The outcomes of these
studies have included the following:
(1) lack of detectable protein adducts or DPX in the bone marrow
of normal rats exposed to formaldehyde labeled with radioactive hydrogen (3H) or carbon (14C) at concentrations as high
as 15 ppm (34);
(2) lack of detectable protein adducts or DPX in the bone marrow
of glutathione-depleted (metabolically inhibited) rats exposed
to [3H]formaldehyde and [14C]formaldehyde at concentrations as high as 10 ppm (22, 47);
(3) lack of detectable DPX in the bone marrow of rhesus monkeys
exposed to [14C]formaldehyde at concentrations as high as 6
ppm (46); and
(4) failure of formaldehyde to induce chromosomal aberrations in
the bone marrow of rats exposed to airborne concentrations as
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high as 15 ppm (41) or of mice receiving intraperitoneal injections of formaldehyde at doses as high as 25 mg/kg (48).
Casas et al (49) have been critical of formocresol use in pediatric
dentistry. They have regularly cited 2 studies as evidence of the genotoxic and mutagenic effects of formaldehyde (50, 51). Those published
articles, in fact, represent the same study, however, with the first article
reporting interim results of nasal tumor development in rodents (50)
and the second (3 years later) (51) reporting the final results for the
same study. Although Kerns et al (51) discussed the formaldehydes
mutagenic potential in their animal model, they did not report results
pertaining to mutagenicity, as was stated by Casas et al.
More recent research by Heck and Casanova (52) has revealed
that the development of DPX in the nasal tissues of rats and the upper
respiratory tracts of primates is associated only with exposure to high
doses of formaldehyde. At ambient concentrations consistent with environmental exposures, DPX are unlikely to occur. Furthermore,
Quievryn and Zhitkovitch (53) have shown that DPX do not persist in
tissues for more than a few hours and undergo either spontaneous
hydrolysis or active repair by proteolytic degradation of cross-linked
proteins. This calls into question the role of DPX in formaldehydeinduced carcinogenesis.
Cytogenetic studies (54) of lymphocytes from rodents after formaldehyde inhalation with exposures ranging from 0.515 ppm for 6
hours per day for 5 days failed to detect either chromosomal aberrations or SCEs at any of the formaldehyde concentrations. The authors
attributed their negative results to formaldehydes pharmacokinetics.
In vitro experiments with a Chinese hamster cell line (43) found
that DPX and SCE, as a result of formaldehyde exposure, were associated
with cytotoxicity, not mutation (55). In addition, no mutagenesis occurred in cultured human lymphocytes below a formaldehyde threshold
of 5 g/mL in the culture medium (56).
Dental studies have not supported the contention that formaldehyde, as used in dentistry, is mutagenic. Zarzar et al (57) performed
formocresol pulpotomy on 20 children by using Buckleys original formula (19% formaldehyde and 35% cresol in a solution of 15% glycerin
and water). Peripheral venous samples were collected from each child
immediately before and 24 hours after the pulpotomy, and lymphocytes
were collected from each blood sample for cell culture and cytogenetic
analysis. No statistically significant differences were found between the
2 groups in terms of chromosomal aberrations, chromatid breaks, or
chromatid gaps. Also, Zarzar et al concluded that formocresol is not
mutagenic. The authors observed chromosomal aberrations in 1 (5%)
of the 20 patients but were unable to determine whether formocresol or
other variables accounted for this finding.
Ribeiro et al (58, 59) reported 2 studies that assessed the mutagenic potential of formocresol as well as several other chemicals commonly used in dentistry. With a mouse lymphoma cell line, cultured
human fibroblasts, and a series of formocresol dilutions similar to
clinical doses, these authors found that formocresol did not produce
detectable DNA damage and should not be considered genotoxic.
Laboratory investigations of root canal sealers containing formaldehyde, which are used in endodontic procedures, have demonstrated
cytotoxicity (60). For several reasons, however, these investigations are
not comparable to formocresol pulp studies. A larger quantity of formaldehyde is released from root canal sealers than during pediatric formocresol pulpotomy because of the large quantity of sealer used. Moreover, contact of formocresol with vital pulp tissue during pulpotomy is
restricted to only a few minutes, whereas root canal sealer remains in
the root canal and forms part of the final restoration, with the potential
for further release of formaldehyde.
Pulp Symposium
In summary, DPXs development has been demonstrated only after
prolonged exposure to formaldehyde at specific contact sites such as the
nasopharynx. Hence, the argument that the microgram quantities of
formaldehyde applied to pediatric pulp tissue for a few minutes will
induce distant-site genotoxicity is not supported by the available evidence.
Carcinogenicity
It is indisputable that cancer develops in experimental animals
after inhalation of air with high concentrations of formaldehyde. These
cancers occur as a result of long-term, direct contact between the formaldehyde and susceptible tissues. The resultant toxic effects at these
initial contact sites include ulceration, hyperplasia, and squamous
metaplasia and are considered to contribute to the subsequent development of cancer (61). These high-dose responses, however, are unlikely to occur at sites distant from the point of initial formaldehyde
contact (such as the bone marrow). This is because, according to a
large body of undisputed evidence, formaldehyde is not delivered to
these distant sites. Those who have argued against the continued use of
formocresol in pediatric dentistry on the basis that formaldehyde
causes cancer have failed to recognize this very important distinction.
Those opposed to formocresol use in pediatric dentistry have cited
the work of Swenberg et al (50) and Kerns et al (51) to support their
argument about carcinogenicity. These 2 studies are, in fact, the same
study, with Swenberg et al reporting interim results after 18 months and
Kerns et al reporting final results for the same study after 30 months.
This group of researchers showed that nasal squamous cell carcinoma
developed in Fischer 344 rats exposed to formaldehyde gas at concentrations of 6 ppm and higher for 6 hours per day, 5 days per week for 24
months. The formaldehyde concentrations that resulted in cancer, however, were more than 1000 times the typical human environmental
exposure and 8 times the U.S. occupational exposure limit (0.75 ppm)
(62). Therefore, they are not representative of human experience.
Moreover, the experimental conditions that resulted in nasal cancers in
rodents in no way resemble the conditions associated with a 5-minute
exposure to microgram quantities of formaldehyde, as experienced by a
child undergoing formocresol pulpotomy.
Until recently, formaldehyde was classified as a probable human
carcinogen by Health Canada (63, 64), the International Agency for
Research on Cancer (IARC) (65, 66), the Agency for Toxic Substances
and Disease Registry (ATSDR) (62, 67) in the U.S. Department of Health
and Human Services, and the U.S. Environmental Protection Agency
(USEPA) (68). Although they lacked sufficient evidence to demonstrate
the development of cancer in exposed humans, these regulators (Health
Canada, ATSDR, and USEPA) and advisory agency (IARC) predicted the
cancer risk posed by low-dose exposure by extrapolating from the laboratory animal data previously cited.
Various researchers, however, have recognized that significant
anatomic and physiologic differences between humans and other animal models have confounded extrapolation of animal data to humans
(29, 69 71). Researchers at the Chemical Industry Institute for Toxicology Centers for Health Research (CIIT) (70, 71) developed dynamic
3-dimensional airflow models that accurately depicted both airflow and
regional deposition of formaldehyde on mucosal surfaces of rodents,
monkeys, and humans. The improved understanding garnered from this
research allowed the researchers to improve the accuracy of computergenerated predictions of the uptake and absorption of formaldehyde in
each animal model. The CIIT researchers also developed a biologically
motivated computational model, on the basis of combined rodent and
primate data from the computer-generated nasal cavity airflow models,
cell proliferation data, and DPX data. This model allowed them to math-
ematically evaluate the cancer risks associated with formaldehyde inhalation (71).
Finally, with input from the USEPA, Health Canada, and peer reviewers, the CIIT researchers published a thorough evaluation of potential cancer risk from formaldehyde, integrating toxicologic, mechanistic, and dosimetric data (55). These new experimental data, derived
from sophisticated mathematical models, replaced the inaccurate default assumptions that had been used by the regulatory authorities.
On the basis of these investigations (55, 71), CIIT suggested that
cancer risk is negligible until formaldehyde exposure reaches the levels
associated with cytotoxicity (in the range of 600 1000 ppb). The resulting estimates of cancer risk are many orders of magnitude lower
than the 1987 and 1991 USEPA estimates (55, 71). The model developed by CIIT overcomes problems associated with the standard risk
assessment methods cited by the USEPA and the IARC.
A 2004 IARC press release (66) reclassified formaldehyde from a
probable to a known human carcinogen and has been cited as
evidence that formaldehyde should be eliminated from pediatric dentistry (49). Some clarification of the press release is required, however,
or readers will be left with the impression that the IARC classification is
definitive and binding. The IARC classification is not an assessment of
risk but merely an attempt to answer the question of whether, under any
circumstances, a substance could produce cancer in humans. Clearly,
for formaldehyde the answer to this question is yes. In fact, the author
requested clarification from the head of the IARC Monographs Programme regarding a threshold dosage for carcinogenicity of formaldehyde. Dr Vincent Cogliano responded the evaluations at IARC Monograph meetings concern only whether an agent can increase the risk of
cancer at some dose. We do not undertake dose-response analyses,
consequently, we did not discuss a possible threshold (personal communication, August 5, 2005).
Thus, the IARC classification serves as a hazard identification, the
first step in a multilevel risk assessment process. More importantly, the
IARC reclassification was based primarily on the results of a single
National Cancer Institute (NCI) study (44) among workers in formaldehyde industries. That study included many workers at several plants,
but only a small number of people working at a single plant were found
to have a rare form of cancer. Clearly, confounding variables might have
affected the results. Recognizing these uncertainties, the NCI has agreed
to update the study.
Health Canada has stated that it considers the CIIT dose-response
model (71) to provide the most defensible estimates of cancer risk, on
the basis that it encompasses more of the available biological data,
thereby offering considerable improvement over default (72). The
Organization for Economic Cooperation and Development has stated,
on the basis of the CIIT research models, that taking into account the
extensive information on its mode of action, formaldehyde is not likely
to be a potent carcinogen to humans under low exposure conditions
(73). Pediatric pulp therapy with formocresol as recommended would
be considered a low exposure condition. The USEPA Office of Air
Quality Planning and Standards has stated, The dose response value in
the EPA Integrated Risk Information System (for formaldehyde) is
based on a 1987 study and no longer represents the best available
science in the peer-reviewed literature. We believe that the CIIT modeling effort represents the best available application of mechanistic and
dosimetric science on the dose-response for portal of entry cancers due
to formaldehyde exposure (74).
The possibility that inhaled or ingested formaldehyde might induce
cancers at sites distant from the respiratory or gastrointestinal tracts has
been investigated in numerous long-term toxicity studies performed in
rodents (61). Leukemia was not observed in any of 7 long-term inhalation bioassays in rodents, and it was not observed in 3 drinking water
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Pulp Symposium
studies in which rodents were exposed to doses as high as 1.9 5 g/L.
Leukemia was observed in a single drinking water study (75), in which
Wistar rats were exposed to doses as high as 1.5 g/L. That study, however, is regarded by the Cancer Assessment Committee of the U.S. Food
and Drug Administration (76) as questionable, and the data are unreliable because of a lack of critical detail and questionable histopathologic conclusions.
Evidence from epidemiology investigations of industrial workers
with exposure to formaldehyde provides weak and inconsistent evidence that such exposure is associated with leukemia. Importantly, the
researchers in each instance failed to use recognized epidemiologic
criteria to evaluate the hypothesis that formaldehyde exposure leads to
cancer. The results of 2 large American studies, one from the NCI (44)
and the other from the National Institute of Occupational Safety and
Health (77), did not support a strong causal relation between formaldehyde exposure and leukemia. The strength of associationthe extent
to which a collective body of data indicates a positive association between a disease, in this case leukemia, and a suspected causative agent,
in this case formaldehyde was weak (standardized mortality ratio,
0.86). Moreover, a study of British chemical workers, sponsored by the
Medical Research Council Environmental Epidemiology Unit in the
United Kingdom (78) and involving the highest chronic formaldehyde
exposures and highest peak exposures of all 3 investigations, showed no
causal relationship between formaldehyde and leukemia.
Therefore, evidence from both experimental investigations and
epidemiologic research does not support the hypothesis that inhaled or
ingested formaldehyde might induce distant-site toxicity. The abundant
negative evidence mentioned previously is undisputed and strongly suggests that there is no delivery of inhaled, ingested, or topically applied
formaldehyde to distant sites. The facts are that formaldehyde occurs
naturally throughout the body, there are multiple pathways for detoxification, and only microgram quantities of formaldehyde are applied to
pulp tissues during pulpotomy procedures for mere minutes. Considering these facts, the negative findings provide convincing evidence that
exposure of children to the formaldehyde component of formocresol
during a pulpotomy is insignificant and inconsequential.
Immune Sensitization
Despite evidence from dogs that formocresol can produce antigenic activity in dental pulp tissue (79), Rolling and Thulin (80) found
no increase in either immune response or allergic reactions in 128
children who had undergone formocresol pulpotomy.
More recent evidence supports the work of Rolling and Thulin
(80). A Canadian study (81) of urea formaldehyde foam insulation from
products in the homes of asthmatic subjects found that long-term exposure had no effect on immunologic parameters. Doi et al (82) found
that the prevalence of immunoglobulin E sensitization to formaldehyde
was very low among Japanese children, regardless of whether they had
asthma; furthermore, they found no clinical relevance of formaldehydespecific immunoglobulin E. Hence, the suggestion that formocresol
sensitizes children has not been supported.
Where Do We Go From Here?

On the basis of the evidence presented in this review, it is highly
unlikely that formocresol, judiciously used, is genotoxic or immunotoxic or poses a cancer risk to children who undergo one or more
formocresol pulpotomy procedures. Definitive data to support this hypothesis are lacking, however, and such evidence is needed before
definitive conclusions can be reached.
In keeping with accepted therapeutic principles, pediatric dentists
who wish to continue to use formocresol should apply the lowest dose
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Milnes
possible for the shortest time possible to obtain the desired effect. To
that end, a 1:5 dilution of Buckleys formocresol is recommended. The
dilution should be performed in the local pharmacy to ensure accuracy.
Recent research (83) has indicated that a minority of pediatric dentists
use diluted formocresol because it is not available commercially, so
perhaps it is time for the formocresol product manufacturers to develop
and market a 1:5 dilution of this medicament to replace the fullstrength formulations now available, especially given that the effects of
the 2 formulations are equivalent (83).
No data exist to verify the actual amount of formocresol delivered
to the pulp during the performance of a formocresol pulpotomy. Results
from a yet to be published study in Colorado of systemic formocresol
distribution in children receiving at least 1 pulpotomy while under
general anesthesia determined that the mean dose of formocresol
within a cotton pellet was 0.013 mg (37). This study used full-strength
formocresol. Presumably, if a 1:5 dilution had been used, the mean
milligram dose per pellet would have been 0.0026 mg. The actual dose
that interacts with the pulp tissue is probably much smaller in both
cases, however, because most of the formocresol will remain in the
cotton pellet. Determining the actual doses delivered to the pulp represents an important area for further investigation. In addition, efforts are
needed to disseminate information about dose delivered to both the
profession and the public.
Evidence continues to accumulate that supports the successful
application of indirect pulp treatment (IPT) procedures to primary
teeth as well as the use of mineral trioxide aggregate (MTA) in pulpotomy procedures. A Cochrane systematic review by Nadin et al (84) in
2003 suggested that the paucity of randomized controlled trials in pediatric pulp therapy made it virtually impossible to make recommendations regarding pulpotomy procedures. Nevertheless, numerous randomized controlled trials examining both IPT and MTA have since been
published. These investigations have shown that both IPT and MTA have
clinical and radiographic results that are equivalent to or better than
those produced by formocresol over time. The reader is referred to
articles in this issue by Fuks and Coll for more detail about these promising alternatives.
It is important to put this discussion into a broader perspective.
Antibiotics are used in dentistry at least as often as formocresol, and
each year numerous children and adults are injured or die as a result of
allergic or anaphylactic reactions to antibiotics (85), yet there has been
no call for the elimination of antibiotics from dental practice. In fact,
there is an acceptance that an allergic reaction is both a possibility and
a risk in the treatment of dental infection. Peroxides for dental bleaching, bonding agents, and solvents used in adhesive dentistry all demonstrate cytotoxicity in vitro (86), yet they form an important part of every
dentists restorative armamentarium. These chemicals are used in pediatric dentistry without warnings to parents and patients of the associated risks. Diagnostic radiation is an indispensable component of every
dental office, yet irrefutable evidence (87) exists showing that radiation
exposure can induce the development of cancers. Singling out one
chemical such as formocresol for elimination from practice protocols
in the face of a complete lack of human experimental data identifying a
clear risk is intellectual tomfoolery.
On the basis of the evidence presented in this review, the risk of
cancer, mutagenesis, or immune sensitization associated with the
proper use of formocresol in pediatric pulp therapy can be considered
inconsequential. Until a superior alternative is developed or there is
definitive evidence substantiating a cancer risk, there is no reason to
discontinue its use. When used judiciously, formocresol is a safe medicament.
Pulp Symposium
Conclusions
Evidence presented in this review of the literature indicates that
formocresol, when used judiciously, is unlikely to be genotoxic, immunotoxic, or carcinogenic in children when used in pulpotomy procedures. Until a biologic and reparative alternative has been identified that
is clearly and reproducibly superior to formocresol, there are no scientific or toxicologic reasons to abandon formocresol in pediatric dentistry.
References
1. Federal-Provincial-Territorial Committee on Drinking Water. Formaldehyde: guidelines for Canadian drinking water qualitysupporting documents. Available at:
www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/doc_sup-appui/index_e.html. Accessed
March 13, 2006.
2. World Health Organization. Formaldehyde: environmental health criteria 89, International Programme on Chemical Safety, Geneva, 1989. Available at: www.who.int/
ipcs/publications/ehc/ehc_numerical/en/. Accessed March 13, 2006.
3. Owen BA, Dudney CS, Tan EL, Easterly CE. Formaldehyde in drinking water: comparative hazard evaluation and an approach to regulation. Regul Toxicol Pharmacol
1990;11:220 36.
4. Canadian Environmental Protection Act, 1999. Priority substances list assessment
report: formaldehyde. Environment Canada, Health Canada. Available at: www.hcsc.gc.ca/ewh-semt/pubs/contaminants/psl2-lsp2/formaldehyde/index_e.html. Accessed July 22, 2007.
5. Health Canada. Its your health: formaldehyde and indoor air. Available at: www.hcsc.gc.ca/iyh-vsv/environ/formaldehyde_e.html. Accessed March 13, 2006.
6. Manitoba Federation of Labour Occupational Health Centre, Inc. Formaldehyde.
Available at: www.mflohc.mb.ca/fact_sheets_folder/formaldehyde.html. Accessed
March 13, 2006.
7. The National Institute for Occupational Safety and Health. Formaldehyde. Available
at: www.tricornet.com/nioshdbs/idlh/50000.htm. Accessed March 13, 2006.
8. Hileman B. Formaldehyde: assessing the risk. Environ Sci Technol 1984;18:
216a21a.
9. Squire RA, Cameron LL. An analysis of potential carcinogenic risk from formaldehyde. Regul Toxicol Pharmacol 1984;4:10729.
10. Teng S, Beard K, Pourahmad J, et al. The formaldehyde metabolic detoxification
enzyme systems and molecular cytotoxic mechanism in isolated rat hepatocytes.
Chem Biol Interact 2001;130:28596.
11. Hedberg JJ, Hoog JO, Nilsson JA, Xi Z, Elfwing A, Grafstrom RC. Expression of alcohol
dehydrogenase 3 in tissue and cultured cells from human oral mucosa. Am J Pathol
2000;157:174555.
12. Dahl A. Possible consequences of cytochrome P-450-dependent monoxygenases in
nasal tissues. In: Barrow C, ed. Toxicology of the nasal passages. Washington, DC:
Hemisphere Publishing, 1986:26373.
13. Malorny G, Rietbrock N, Schneider M. [Oxidation of formaldehyde to formic acid in
blood, a contribution to formaldehyde metabolism.] Naunyn Schmiedenbergs Arch
Exp Pathol Pharmakol 1965;250:419 36.
14. Bardana EJ, Montanaro A. Formaldehyde: an analysis of its respiratory, cutaneous,
and immunologic effects. Ann Allergy 1991;66:44158.
15. Kitchens JF, Castner RE, Edwards GS, Harward III WE, Macri BJ. Investigation of
selected potential environmental contaminants: formaldehyde. Washington, DC: US
Environmental Protection Agency, 1976: EPA-560/2-76-009.
16. Heck HD, Casanova-Schmitz M, Dodd PB, Schachter EN, Witek TJ, Tosun T. Formaldehyde (CH2O) concentrations in the blood of humans and Fischer-344 rats exposed
to CH2O under controlled conditions. Am Ind Hyg Assoc J 1985;46:13.
17. Johannsen FR, Levinskas GJ, Tegeris AS. Effects of formaldehyde in the rat and dog
following oral exposure. Toxicol Lett 1986;30:1 6.
18. Casanova M, Heck H, Everitt JI, Harrington WW Jr, Popp JA. Formaldehyde concentrations in the blood of rhesus monkeys after inhalation exposure. Food Chem Toxicol 1988;26:715 6.
19. Jeffcoat AR, Chasalow F, Feldman DB, Marr H. Disposition of [14C] formaldehyde
after topical exposure to rats, guinea pigs and monkeys. In: Gibson JE, ed. Formaldehyde toxicity. Washington, DC: Hemisphere Publishing, 1983:38 50.
20. McMartin KE, Martin-Amat G, Noker PE, Tephly TR. Lack of a role for formaldehyde
in methanol poisoning in the monkey. Biochem Pharmacol 1979;28:6459.
21. Ranly DM. Assessment of the systemic distribution and toxicity of formaldehyde
following pulpotomy treatment: part one. J Dent Child 1985;52:4331 4.
22. Bhatt HS, Lober SB, Combes B. Effect of glutathione depletion on aminopyrine and
formaldehyde metabolism. Biochem Pharmacol 1988;37:15819.
23. Waydhas C, Weigl K, Seis H. The disposition of formaldehyde and formate arising from
drug N-demethylations dependent on cytochrome P-450 in hepatocytes and perfused
rat liver. Eur J Biochem 1978;89:14350.
24. McMartin KE, Martin-Amat G, Makar AB, Tephly TR. Methanol poisoning: Vrole of
formate metabolism in the monkey. J Pharmacol Exp Ther 1977;201:564 72.
25. Galli CL, Ragusa C, Resmini P, Marinovich M. Toxicological evaluation in rats and
mice of the ingestion of a cheese made from milk with added formaldehyde. Food
Chem Toxicol 1983;21:3137.
26. Upreti RK, Farooqui MY, Ahmed AE, Ansari GA. Toxicokinetics and molecular interaction of [14C]-formaldehyde in rats. Arch Environ Contam Toxicol 1987;16:
26373.
27. Srivastava AK, Gupta BN, Gaur JS, Bihari V. Clinical evaluation of workers handling
melamine formaldehyde resin. Clin Toxicol 1992;30:677 81.
28. Bolt HM. Experimental toxicity of formaldehyde. J Cancer Res Clin Oncol
1987;113:3059.
29. Nilsson JA, Zheng X, Sundqvist K, et al. Toxicity of formaldehyde to human oral
fibroblasts and epithelial cells: influences of culture conditions and role of thiol
status. J Dent Res 1998;77:1896 903.
30. Heck H, Casanova M. The implausibility of leukemia induction by formaldehyde: A
critical review of the biological evidence on distant-site toxicity. Regul Toxicol Pharmacol 2004;40:92106.
31. Myers DR, Pashley DH, Whitford GM, McKinney RV. Tissue changes induced by the
absorption of formocresol from pulpotomy sites in dogs. Pediatr Dent 1983;5:6 8.
32. Myers D, Shoaf K, Dirksen T, Pashley DH, Whitford GM, Reynolds KE. Distribution of
14
C-formaldehyde after pulpotomy with formocresol. J Am Dent Assoc 1978;
96:80513.
33. Pashley E, Myers D, Pashley DH, Whitford G. Systemic distribution of
14
C-formaldehyde from formocresol-treated pulpotomy sites. J Dent Res 1980;
59:602 8.
34. Casanova-Schmitz M, Starr TB, Heck HD. Differentiation between metabolic incorporation and covalent binding in the labeling of macromolecules in the rat nasal
mucosa and bone marrow for inhaled 14C- and 3H-formaldehyde. Toxicol Appl Pharmacol 1984;76:26 44.
35. Ranly D. Formocresol toxicity: current knowledge. Acta Odontol Pediatr 1984;
5:93 8.
36. Loos P, Hans SS. An enzyme histochemical study of the effect of various concentrations of formocresol on connective tissues. Oral Surg Oral Med Oral Pathol
1971;31:571 85.
37. Kahl J, Personal communication, August 2006; http://www.thechildrenshospital.org/
news/publications/practiceupdate/2007/formocresol.aspx. Accessed November 12,
2007.
38. Gruber C. The pharmacology of benzyl alcohol and its esters. J Lab Clin Med
1923;9:15.
39. International Programme on Chemical Safety. Environmental health criteria 89:
formaldehyde. Available at: http://www.inchem.org/documents/ehc/ehc/ehc89.htm.
Accessed March 13, 2007.
40. U.S. Environmental Protection Agency. Integrated risk information system: tricresol
(CASRN 1319-77-77-3). Available at: http://www.epa.gov/iris/subst/0030.htm. Accessed November 12, 2007.
41. Heck HD, Casanova M, Starr TB. Formaldehyde toxicity: new understanding. Crit Rev
Toxicol 1990;20:397 426.
42. Merk O, Speit G. Significance of formaldehyde-induced DNA-protein crosslinks for
mutagenesis. Environ Mol Mutagen 1998;32:260 8.
43. Crosby RM, Richardson KK, Craft TR, Benforad KB, Liber HL, Skopek TR. Molecular
analysis of formaldehyde-induced mutations in human lymphoblasts and E. coli.
Environ Mol Mutagen 1988;12:155 66.
44. Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A. Mortality from hematopoietic
malignancies among workers in formaldehyde industries. J Natl Cancer Inst
2003;95:161523.
45. Casanova M, Deyo DF, Heck HD. Covalent binding of inhaled formaldehyde to DNA in
the nasal mucosa of Fischer 344 rats: analysis of formaldehyde and DNA by highperformance liquid chromatography and provisional pharmacokinetic interpretation. Fundam Appl Toxicol 1989;12:397 417.
46. Casanova M, Morgan KT, Steinhagen WH, Everitt JI, Popp JA, Heck HD. Covalent
binding of inhaled formaldehyde to DNA in the respiratory tract of rhesus monkeys:
pharmacokinetics, rat-to-monkey interspecies scaling, and extrapolation to man.
Fundam Appl Toxicol 1991;17:409 28.
47. Casanova M, Heck H. Further studies of the metabolic incorporation and covalent
binding of inhaled [3H]- and [14C]-formaldehyde in Fischer-344 rats: effects of
glutathione depletion. Toxicol Appl Pharmacol 1987;89:10521.
48. Natarajan AT, Darroudi F, Bussman CJM, van Kesteren-van Leeuwen AC. Evaluation of
the mutagenicity of formaldehyde cytogenetic assays in vivo and vitro. Mutat Res
1983;122:355 60.
49. Casas MJ, Kenny DJ, Judd PL, Johnston DH. Do we still need formocresol in pediatric
dentistry? J Can Dent Assoc 2005;71:749 51.
50. Swenberg JA, Kerns WD, Mitchell RI, Gralla EJ, Pavkov KL. Induction of squamous cell
carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor.
Cancer Res 1980;40:3398 402.
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51. Kerns WD, Pavkov KL, Donofrio DJ, Gralla EJ, Swenberg JA. Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure. Cancer Res
1983;43:438292.
52. Heck H, Casanova M. Pharmacodynamics of formaldehyde: application of a model for
the arrest of DNA replication by DNA-protein cross-links. Toxicol Appl Pharmacol
1999;160:86 100.
53. Quievryn G, Zhitkovich A. Loss of DNA-protein crosslinks from formaldehyde exposed cells occurs through spontaneous hydrolysis and an active repair process
linked to proteosome function. Carcinogenesis 2000;21:1573 80.
54. Kligerman AD, Phelps MC, Erexson GL. Cytogenetic analysis of lymphocytes from rats
following formaldehyde inhalation. Toxicol Lett 1984;21:241 6.
55. Chemical Industry Institute for Technology. Formaldehyde: hazard characterization
and dose-response assessment for carcinogenicity by the route of inhalation: position
paper. Research Triangle Park, NC: CIIT; 1999.
56. Kreiger RA, Garry VF. Formaldehyde-induced cytotoxicity and sister-chromatid exchanges in human lymphocyte cultures. Mutat Res 1983;120:515.
57. Zarzar PA, Rosenblatt A, Takahashi CS, Takeuchi PL, Costa Junior LA. Formocresol
mutagenicity following primary tooth pulp therapy: An in vivo study. J Dent
2003;31:479 85.
58. Ribeiro DA, Marques ME, Salvadori DM. Lack of genotoxicity of formocresol, paramonochlorophenol, and calcium hydroxide on mammalian cells by comet assay. J
Endod 2004;30:593 6.
59. Ribeiro DA, Scolastici C, De Lima PL, Marques ME, Salvadori DM. Genotoxicity of
antimicrobial endodontic compounds by single cell gel (comet) assay in Chinese
hamster ovary (CHO) cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
2005;99:637 40.
60. Huang TH, Ding SJ, Hsu TZ, Lee ZD, Kao CT. Root canal sealers induce cytotoxicity and
necrosis. J Material Sci Mater Med 2004;15:76771.
61. International Agency for Research on Cancer. Formaldehyde. IARC Monogr Eval
Carcinog Risks Hum 1996;62:217375.
62. US Department of Labor, Occupational Safety & Health Administration. Safety and
health topics: formaldehyde. Available at: www.osha.gov/SLTC/formaldehyde. Accessed March 13, 2006.
63. Canadian Environmental Protection Act. Priority substances list assessment report:
formaldehyde. Available at: www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/
pubs/contaminants/psl2-lsp2/formaldehyde/formaldehyde_e.pdf. Accessed March
13, 2007.
64. Health and Welfare Canada. Exposure guidelines for residential indoor air quality.
Ottawa, Ontario, Canada: Department of National Health and Welfare, 1987.
65. International Agency for Research on Cancer. World Health Organization, Suppl 7.
Overall evaluations of carcinogenicity: an updating of IARC monographs volumes 1 to
42, 1987.
66. IARC, WHO. IARC classifies formaldehyde as carcinogenic to humans: press release
no. 153. Available at: www.iarc.fr/ENG/Press_Releases/archives/pr153a.html. Accessed March 13, 2006.
67. Agency for Toxic Substances and Disease Registry. Toxicological profile for formaldehyde: US Department of Health and Human Services, Public Health Service. Available at: www.atsdr.cdc.gov/toxprofiles/tp111.html. Accessed March 13, 2006.
68. US Environmental Protection Agency. Integrated risk information system. IRIS database for risk assessment. Washington, DC. Available at: www.epa.gov/iris. Accessed
March 13, 2006.
S46
Milnes
69. Schlosser PM, Lilly PD, Conolly RB, Janszen DB, Kimbell JS. Benchmark dose risk
assessment for formaldehyde using airflow modeling in a single-compartment: DNAprotein cross-link dosimetry model to estimate human equivalent doses. Risk Anal
2003;23:473 87.
70. Kimbell JS, Subramaniam RP, Gross EA, Schlosser PM, Morgan KT. Dosimetry modeling of inhaled formaldehyde: comparisons of local flux predictions in the rat,
monkey, and human nasal passages. Toxicol Sci 2001;64:100 10.
71. Conolly RB, Kimbell JS, Janszen D, et al. Human respiratory tract cancer risks of
inhaled formaldehyde: dose response predictions derived from biologically motivated computational modeling of a combined rodent and human dataset. Toxicol Sci
2004;82:279 96.
72. Environment Canada and Health Canada. Existing substances evaluation: assessment
reportformaldehyde. Available at: www.ec.gc.ca/substances/ese/eng/psap/final/
formaldehyde.cfm. Accessed March 13, 2006.
73. Organization for Economic Development and Cooperation. Screening information
data set, initial assessment profile. Available at: www.oecd.org/dataoecd/24/22/
31744923.pdf. Accessed March 13, 2007.
74. U.S. Evironmental Protection Agency Office of Air Quality Planning and Standards,
EPA Office of Air and Radiation. Rule issued under maximum achievable control
technology provisions of the Federal Clean Air Act. 69 Federal regulation 18333, April
7, 2004. Fed Regist 2004;69:18333 4.
75. Soffritti M, Maltoni C, Maffei F, Biagi R. Formaldehyde: an experimental multipotential carcinogen. Toxicol Ind Health 1989;5:699 730.
76. United States Food and Drug Administration. Indirect food additives, adjuvants, production aids, and sanitizers. Fed Regist 1998;63:35134 5.
77. Pinkerton LE, Hein M, Stayner LT. Mortality among a cohort of garment workers
exposed to formaldehyde: an update. Occup Environ Med 2004;61:193200.
78. Coggon D, Harris EC, Poole J, Palmer KT. Extended follow-up of a cohort of British
chemical workers exposed to formaldehyde. J Natl Cancer Inst 2003;95:1608 15.
79. Block RM, Lewis RD, Sheats JB, Burke SG. Antibody formation to dog pulp tissue
altered by formocresol within the root canal. Oral Surg Oral Med Oral Pathol
1978;45:28292.
80. Rolling I, Thulin H. Allergy tests against formaldehyde, cresol, and eugenol in children with pulpotomized primary teeth. Scand J Dent Res 1976;84:3457.
81. Pross HF, Day JH, Clark RH, Lees RE. Immunologic studies of subjects with asthma
exposed to formaldehyde and urea-formaldehyde foam insulation off products. Allergy Clin Immunol 1987;79:797 810.
82. Doi S, Suzuki S, Morishita M, et al. The prevalence of IgE sensitization to formaldehyde in asthmatic children. Allergy 2003;58:668 71.
83. King SR, McWhorter AG, Seale NS. Concentration of formocresol used by pediatric
dentists in primary tooth pulpotomy. Pediatr Dent 2002;24:1579.
84. Nadin G, Goel B, Yeung C, Glenny A. Pulp treatment for extensive decay in primary
teeth. Cochrane Database Syst Rev 2003;1:CD003220.
85. Pumphreys RS. Fatal anaphylaxis in the UK, 1992-2001. Novartis Found Symp
2004;257:116 28.
86. Darmani H, Al-Hiyasat A, Milhem M. Cytotoxicity of dental composites and their
leached components. Quintessence Int 2007;38:789 95.
87. Rice H, Frush D, Farmer D, Waldhausen J. Review of radiation risks from computed
tomography: essentials for the pediatric surgeon. J Pediatr Surg 2007;42:6037.
Pulp Symposium
New Age Pulp Therapy: Personal Thoughts

on a Hot Debate
Paula Jane Waterhouse, BDS, PhD
Abstract
This article outlines the counterpoint delivered in the debate Is Formocresol Obsolete? It addresses the opinion
supporting the need to move away from formaldehydecontaining preparations in the dental care of children. It
is suggested that such a move should be made not just
because of concerns relating to the possible toxicity of
formaldehyde but to reflect a more contemporary, biologic approach to pulp therapy in the primary
dentition. (J Endod 2008;34:S47-S50)
Key Words
Formocresol, primary teeth, pulp therapy, pulpotomy
From the Department of Paediatric Dentistry, School of

Dental Sciences, Newcastle University, Newcastle upon Tyne,
United Kingdom.
Address requests for reprints to Dr Paula Jane Waterhouse,
The School of Dental Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4BW UK. E-mail
address: p.j.waterhouse@ncl.ac.uk.
Conflict of Interest: Paula Jane Waterhouse, BDS, PhD, has
research interests with Newcastle University through an internal fund and also supervises several graduate students at
Newcastle University. She is also a Council Member of the
British Society of Paediatric Dentistry.
doi:10.1016/j.joen.2008.03.019
he debate over the use of formocresol solution and other formaldehyde-containing

preparations in childrens dentistry continues. This is welcomed and should be
regarded as a positive activity that will benefit ultimately those for whom we provide
dental care. Discussion at meetings and within peer-reviewed and nonpeer-reviewed
publications has stimulated both specialist pediatric dentists and general dentists, not
only on both sides of the Atlantic but worldwide, to consider their stance over this issue.
Should we, as providers of healthcare in the 21st century, continue to use formaldehyde-containing medicaments in endodontic therapy?
This counterpoint will provide my personal thoughts on an undoubtedly controversial topic. These thoughts will be presented within the following sections:
History: Where were we?

A perspective from the United Kingdom (UK) on formocresol preparations
Recent advances in primary tooth pulp biology
Formocresol: Saint or sinner?
Treatment
Evidence-based practice
The current UK guidelines.
History: Where Were We?

Debate centered on clinical technique is not a product of modern medicine. The
varying treatments for the tooth pulp during the last 3 centuries illustrate this clearly.
During the 1700s and early 1800s, metal foils were used to cap exposed pulp tissue (1),
which would one use, gold or lead? Would you also prefer to cauterize the exposed
tissue with a red-hot iron wire before placing the foil?
From the mid-1800s to the early 1900s, the use of medicaments in pulp therapies
emerged and involved wide-ranging substances such as asbestos fibers, cork, beeswax,
pulverized glass, calcium compounds, and others based on eugenol. Interestingly, even at a
relatively early time in medical and surgical knowledge, it is documented that there was great
debate between those who believed a pulp was capable of healing and those who did not (2).
During this period of innovation and discovery, the first recorded use of a formaldehyde-containing medicament was published. In 1874, Nitzel applied a tricresolformalin tanning agent to 8000 exposed pulps (3). The technique appeared to be
unpopular until Buckleys method of treating putrescent pulps was published in 1904,
suggesting the use of equal parts of tricresol and formalini (an aqueous solution of
formaldehyde gas equivalent to 38% w/w formaldehyde).
In 1908, the use of a mummifying paste with a preparation including solid formaldehyde was advocated (4). One year later, the International Dental Congress was
devoted to the pulp and its treatment, and it was here that Boennecken (5) suggested his
preparation of 40% formalin, thymol, and cocaine to be superior to Buckleys solution
in pulp amputation procedures.
By the late 1920s, there was disagreement between clinicians from Europe and the
United States of America (USA) on treatment criteria and medicaments. In general,
clinicians from Europe favored Gysis Triopaste with paraformaldehyde, and in the USA,
pulp amputation was followed by application of Buckleys formocresol solution (1).
In the middle of the last century there were many debates on the merits of different
medicaments, and several variations of formocresol existed. The defining time for
pulpotomy for the extensively carious primary tooth was the work published during a
period of 25 years by Sweet (6, 7). During this time, multiple applications of Buckleys
formocresol were reduced to 2, and an additional application of formocresolized zinc
New Age Pulp Therapy
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oxide eugenol cement was suggested. Since then, the technique for a
single visit, 5-minute application formocresol pulpotomy was developed by using an as effective but weaker strength solution (8, 9). It was
reported that the formocresol addition to zinc oxide eugenol cement
could be omitted (10).
It has been suggested that these later developments were driven by
the impetus from concerns regarding the safety of formocresol (1).
The UK Perspective on Formocresol Preparations

In the UK, Buckleys formocresol solution (38% w/w formaldehyde) and other formocresol preparations are not available for purchase on the general market. It is classed as a medicament, but it does
not have a medicine license. It is prepared from its raw constituents in
hospital-based pharmacy departments. In the late 1990s and early this
century fewer and fewer hospital pharmacists were willing to prepare
Buckleys formocresol solution, even in its diluted form.
Compounding this problem, there appears to have been confusion
within pharmacy services when preparing the medicament in its dilute
form (1). In particular, which formulation should be used to produce a
1:5 dilution? This is reinforced by the Extra Pharmacopoeia stating that
. . . there is often confusion about the terminology and strength of
formaldehyde (1).
Buckleys original formula appears to have contained 50% of a
38% solution of formaldehyde (equivalent to 19% formaldehyde). In
Newcastle, since 1979 the following formulation has been used: formaldehyde solution BP (formalin), 19 mL; tricresol, 35 mL; glycerol, 15
mL; and water to 100 mL. This contains 19% of a 38% solution of
formaldehyde (equivalent to 7% formaldehyde) and is then diluted to a
1:5; thus the final product contains 1/13 the concentration of formaldehyde (gas). This is inarguably a small amount of formaldehyde.
The apparent confusion over its formulation might make comparison of studies problematic. Further uncertainty related to shelf life was
raised. Laboratories making up these solutions have not only a certain
reticence in handling these relatively toxic materials, but also have difficulty in determining a shelf-life for the product (1).
Full-strength Buckleys formocresol solution is considered to have
a shelf life of approximately 2 months if stored in brown glass bottles,
but in its diluted form it is considered unstable and should be diluted
just before use, which is impractical. Despite this, the use of pharmacydiluted Buckleys formocresol was effective, even under strict criteria
for success (11). I believe that in the UK the move away from Buckleys
formocresol has, in part, been driven by increasing difficulties in obtaining the medicament and the increasing reticence of pharmacy staff
to prepare the formulation (1, 12).
Recent Advances in Primary Tooth Biology

Dental pulp is a richly innervated tissue, and recent research has
evaluated neuropeptide-containing nerve fibers. Nerves that express
substance P have provided insight into pulp nerve function. Studies have
shown that within a tooth the nerve fibers are predominantly nociceptive.
These have an obvious pain receptive role, but they also play a primary role
in immunoregulation and healing (13). Both the permanent and primary
dentitions show similar increases in innervation density with caries progression, and Substance P is increased in painful caries cases.
In addition to this, during my own undergraduate days, despite few
published data, I was taught that in response to caries, primary tooth
pulps present a more pronounced and widespread inflammatory reaction compared with permanent teeth and might have been instrumental
in continuing with the amputation procedures (14). This response is
refuted by more recent immunohistochemical work that demonstrates
equality between dentitions for the degree of vasodilation and angiogenS48
Waterhouse
esis in relation to caries insult, with responses predominantly in the

region of the pulp horns. Although primary teeth contain more immune
cells in both intact and carious states, they appear to localize in a
manner similar to permanent teeth (12).
It appears that the primary tooth pulp has good potential for tissue
repair and healing. In light of these contemporary findings, we as a
collective professional body should be re-evaluating our approaches to
pulp therapy in the primary dentition as our colleagues within adult
restorative dentistry have already begun to do. We should be directing
our research energies toward compiling a sound evidence base for
therapies that favor pulp regeneration.
Formocresol: Saint or Sinner?

Despite formocresols undoubted clinical record of success and
its position as the gold standard medicament in both vital and nonvital
pulp therapy techniques in the primary dentition, in a recent British
survey of 184 specialists in pediatric dentistry, 54% expressed concern
over the safety of formocresol (15).
As clinicians, we all know from our own experience and from the
reported literature that a pulpotomy performed with a 5-minute application of a 20% dilution of Buckleys formocresol has a good prognosis,
irrespective of whether the radicular pulp is viable. By virtue of the
formaldehyde and cresol moieties, the solution has tissue fixative and
antimicrobial properties and will fix and devitalize an irreversibly inflamed radicular pulp.
I agree with other pediatric dentists in that the overall amount of
formaldehyde in a working solution is small, but whether that amount
might cause problems should be explored further.
How many pulpotomies with formocresol would a child receive in
1 visit? How many pulpotomies with formocresol might a pediatric dentist undertake during the course of 1 day?
According to data sheets and a large base of published evidence for
animal and human studies, formaldehyde, a volatile organic compound,
is toxic and corrosive, particularly local to the point of contact. Fewer
findings appear to be available for cresol, but it too is a known irritant
and corrosive substance in its own right (16).
The UKs Health and Safety Executive (HSE) presently rates exposure limits for formaldehyde for both long-term and short-term periods
in the workplace to be 2 ppm or 2.5 mg per cubic meter. There appear
to be no data published related to the possible levels of formaldehyde
vapor and indeed cresol vapor in the dental working environment. The
amount of vapor exposure (ppm) to a child undergoing a formocresol
pulpotomy is unknown, and the degree and potential effect of accumulative formaldehyde exposure to dental professionals are unknown.
In the UK in 2005, the HSEs Working Group on Action to Control
Chemicals (WATCH) published findings from an Advisory Committee on
Toxic Substances (ACTS) related to the carcinogenicity of formaldehyde
(17). In Annex 2 of the report the toxicologic profile of formaldehyde is
discussed, and in Annex 3 the carcinogenicity of formaldehyde is presented
by a summary of the human epidemiologic data mainly relied on by the
International Agency for Research into Cancer (IARC) Working Group in
reaching its conclusion relating to formaldehyde exposure and cancer (18).
Formaldehyde is a known and accepted direct-acting irritant. But
what happens once it has contacted a tissue? This has been investigated
mainly in rats (which are obligate nasal breathers). Formaldehyde will
pass into tissues such as mucous membranes rapidly, but uptake into
skin is poor. Once within tissues, formaldehyde will react directly with
proteins and nucleic acids. To put this into the context of formocresol,
tricresol is said to decrease the solubility and diffusion properties of
formaldehyde, thus reducing movement out of the root canal (19).
However, tricresol has been shown to increase the permeability of cell
Pulp Symposium
membranes by disrupting cell membranes lipid components (20). Disrupting cell membranes might potentiate further local toxic effects. Alternatively, formaldehyde can enter a rapid metabolic pathway, converting
ultimately to formate that is excreted in urine as formic acid, or enters
normal metabolic pathways, or is oxidized to carbon dioxide and exhaled
(2123). However, studies have shown that concentrations of 3 ppm formaldehyde gas can saturate detoxification pathways in nasal epithelial cells,
thus allowing free formaldehyde to cause damage locally (24).
Formaldehydes acute toxic effects are considered real and can
occur in humans from both the vapor and solution (25). In 2005, a
dental clinic in California was evacuated after spillage of a 1-ounce
bottle of Buckleys formocresol solution and was closed for the rest of
the day. According to press reports, 10 people had difficulty breathing
and required emergency room treatment (26).
Formaldehyde is an irritant to the eyes and respiratory tract in
amounts as low as 0.1 ppm in some humans. Workers chronically
exposed to mean levels of 0.22 ppm formaldehyde exhibited mild
nasal epithelial lesions (loss of cilia, goblet cell hyperplasia, and mild
dysplasia) when compared with nonexposed controls (21).
Repeat dose inhalational studies with rodents and monkeys demonstrated that length of exposure and the concentration of formaldehyde vapor (ppm) are related to the degree of histopathologic
change observed, ranging from slight hyperplasia to squamous cell
metaplasia of ciliated and non-ciliated respiratory epithelium. The
levels that produced no observed adverse effect for long-term inhalation studies with rodents were in the range of 12 ppm (21, 23).
When formaldehyde was given to rats in drinking water, a 2-year
study showed local effects on gastric tissue, but no signs of systemic
toxicity were reported (22, 25).
The WATCH group suggest that formaldehyde is toxic at the site of
initial contact.
It is generally accepted that formaldehyde is genotoxic in vitro,
inducing mutations and DNA damage in bacteria and in humans, monkeys, and rodent cells (2731).
Results from human and animal in vivo studies showed that findings indicate that formaldehyde acts as a mutagen at the site of contact
(17). Formaldehyde has been shown to be an experimental animal
carcinogen in rats, producing nasal tumors at high levels of exposure
(time and concentrations) (31). The carcinogenic potential of formaldehyde is less evident in other rodents.
Nasal tumors in rats are thought to arise by a combination of severe
chronic local irritation and local genotoxicity. It is clearly stated by
WATCH, . . . By extrapolation, a combination of these circumstances in
humans would be of concern in relation to cancer (17).
With respect to humans, many different regulatory authorities have
assessed the data published before 2004 (22, 23). Since the IARC findings, the HSE has appraised the epidemiologic studies considered
within the IARC report and stated that sufficient evidence exists that
formaldehyde has caused nasopharyngeal cancer in humans (32). The
HSE interpretation of the data from the studies considered is that
they justify increased concern for the carcinogenic potential of
formaldehyde in humans, particularly in relation to nasopharyngeal

cancer, but that the data fall short of providing conclusive evidence.
Doubts were raised concerning inconsistencies in some prominent
new studies (17).
In the context of formocresol vapor in a dental setting, what might the
combined effect of formaldehyde and cresol be? Would the added local
toxicity of cresol aid the local genotoxicity of formaldehyde? Are the levels of
these substances so low in the air around a dental chair that this does not
constitute a risk? Clearly, these need further investigation with models that
replicate the nasal and oral breathing patterns of humans.
Treatment
Applying formocresol to the radicular pulp of a cariously exposed
tooth will render the pulp in its most part nonvital. In many instances
does this relate to our present understanding of primary pulp biology
and pathophysiology? If one considers a carious exposure in a permanent tooth, it should be appreciated that much effort is directed at
preserving the pulp. Recent UK-based publications are beginning to
reflect this approach for the primary dentition. On the basis of the
classification system of Ranly (33), the treatment of the extensively
carious primary tooth can be divided into devitalization, preservation,
and remineralization. The latter two are where we can move away from
formocresol and reflect a more modern, biologic approach to treatment, irrespective of whether formocresol is carcinogenic.
To present the alternatives that are presently clinically viable as
succinctly as possible, the techniques are tabulated by using a single
example of related clinical research (Table 1).
With all the techniques/medicaments listed in Table 1 excluding
indirect pulp therapy (IPT), care must be taken in assessing the status of
the radicular pulp after coronal amputation. If the techniques are used
on healthy or reversibly inflamed pulp tissue, then a high degree of
success has been recorded. These alternative techniques for vital pulp
therapy might not provide such good success rates if used when radicular pulps are irreversibly inflamed. In such a situation other than
pulpectomy, there is not an equivalently successful pulpotomy medicament as formocresol solution (38, 39). I concur that it is in this area
where formocresol, if removed completely, would be missed the most
and, in addition, for teeth exhibiting hyperalgesia or those without local
analgesia where in the past one would have used a paraformaldehyde
preparation such as Millers paste to devitalize the tooth over time. If we
wish to move away from such preparations, then treatment of such teeth
needs further research and development.
IPT of symptom-free but extensively carious teeth shows great
promise but should only be undertaken on teeth without signs of pulpal
degeneration. Not withstanding this, it is certainly an area worthy of
further study.
Evidence-based Practice
Considering all the options we have, what works best? Unfortunately, the Cochrane Systematic Review of pulp treatment for the exten-
TABLE 1. Overview of Some Alternatives to Formocresol for Vital Pulp Therapy

Material
Clinical Success %
Human Clinical
Studies
Tested Against
Formocresol
IPT
Ferric sulphate
MTA
Calcium hydroxide
Lasers
94% during period of mean 3.4 y (34)

92% 4 y (35)
100% 1 y (gray), 84.2% 1 y (white) (36)
77.1% at 22.5 mo (11)
100% 90 days (37)
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Effect (Animal Studies)

Preservation and remineralization
Preservation
Preservation
Preservation and remineralization
Preservation
IPT, Indirect Pulp Therapy; MTA, Mineral Trioxide Aggregate; y, years; mo, months.
New Age Pulp Therapy
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sively decayed primary tooth showed a paucity of acceptable related
clinical research but did draw conclusions, despite including only 3
prospective randomized controlled trials (40). From the review it was
demonstrated that formocresol, ferric sulfate, electrosurgical pulpotomy, and zinc oxide eugenol pulpectomy all performed equally well. A
recent meta-analysis of formocresol versus ferric sulfate found ferric
sulfate to be as effective as formocresol (41).
The Current UK Guidelines

The British Society of Paediatric Dentistry has produced a range of
clinical guidelines. The update reflects a shift in treatment modalities
away from formocresol, discussing IPT, vital pulpotomy, desensitizing
pulpotomy, and pulpectomy (12). However, a 1:5 dilution of Buckleys
formocresol solution remains listed as a medicament within the guidelines. This is an acknowledgment that the debate is far from over.
Summary
In light of the findings presented, I would recommend that pediatric dentists should be engaged in further good quality research and
debate relating to vital and nonvital pulp therapy for the primary dentition. This should include studies to increase our awareness of the possible formaldehyde and cresol vapor exposure in the clinical environment. In some instances, however, there might be difficulties obtaining
ethical approval for such work in certain countries.
At the beginning of this 21st century, we have greater understanding of the pulp biology, pathophysiology, and its powers of healing; we
should reflect this in our approach to clinical management and aim to
preserve what pulp we can. This in itself might lead to a natural reduction in the use of formocresol and herald a new age of pulp therapy.
Acknowledgments
Grateful thanks to Professor Helen Rodd and Dr. Vidya Srinivasan for allowing use of their research and clinical materials.
References
1. Nunn JH, Smeaton I, Gilroy J. The development of formocresol as a medicament for
primary molar pulpotomy procedures. J Dent Child 1996;63:513.
2. Glass RL, Zander HA. Pulp healing. J Dent Res 1949;28:97107.
3. Schwartz EA. Formocresol vital pulpotomy on the permanent dentition. J Canad Dent
Assoc 1980;46:570 8.
4. Bennette B. The preparation of mummifying paste. Br J Dent Sci 1908;51:02 4.
5. Boennecken H. Pulp amputation. Br Dent J 1909;30:1348 9.
6. Sweet CAJ. Procedure for treatment of exposed and pulpless deciduous teeth. J Am
Dent Assoc 1930;17:1150 3.
7. Sweet CAJ. Treatment of vital primary teeth with pulpal involvelment. J Col Dent Assoc
1955;33:381 6.
8. Straffon LH, Han SS. Effects of varying concentration of formocresol on RNA synthesis
of connective tissues in sponge implants. Oral Surg Oral Med Oral Pathol
1970;29:91525.
9. Morawa AP, Straffon LH, Han SS, Corpron RE. Clinical evaluation of pulpotomies
using dilute formocresol. J Dent Child 1975;42:360 3.
10. Beaver HA, Kopel HM, Sabes WR. The effect of zinc oxide-eugenol cement on a
formocresolised pulp. J Dent Child 1966;33:381 6.
11. Waterhouse PJ, Nunn JH, Whitworth JM. An investigation of the relative efficacy of
Buckleys Formocresol and calcium hydroxide in primary molar vital pulp therapy.
Br Dent J 2000;188:32 6.
12. Rodd HD, Boissonade FM. Immunocytochemical investigation of immune cells within
human primary and permanent tooth pulp. Int J Paediatr Dent 2006;16:29.
13. Rodd HD, Boissonade FM. Substance P exposure in human tooth pulp in relation to
caries and pain experience. Eur J Oral Sc 2000;108:476 84.
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Waterhouse
14. Rayner J, Southam JC. Pulp changes in deciduous teeth associated with deep carious
dentine. J Dent 1979;7:39 42.
15. Hunter ML, Hunter B. Vital pulpotomy in the primary dentition: attitudes and practices of Specialists in Paediatric Dentistry practising in the United Kingdom. Int J
Paediatr Dentistry 2003;13:246 50.
16. Physical and Theoretical Chemistry Laboratory, Oxford University, 2006. Available at:
http://physchem.ox.ac.uk/MSDS/CR/cresol.html. Accessed August 15, 2007.
17. WATCH (2005). Working Group on Action to Control Chemicals. Committee paper
2005/6. The carcinogenicity of formaldehyde. Available at: http://www.hse.gov.uk/
aboutus/hsc/iacs/acts/watch/130105/p6.pdf. Accessed June 10, 2007.
18. International Agency for Research on Cancer. Monographs on the evaluation of
carcinogenic risks to humans: volume 88: 2006; formaldehyde, 2-butoxyethanol and
1-tert-butoxypropan-2-ol. Geneva, Switzerland: WHO.
19. s Gravenmade EJ. Some biochemical considerations of fixation in endodontics. J
Endod 1975;1:2337.
20. Ranly DM, Lazzari EM. The formocresol pulpotomy: the past, the present, and the
future. J Pedod 1978;2:11527.
21. Agency for Toxic Substances and Disease Registry, Department of Health and Human
Services, 1999. Toxicological profile for formaldehyde. Available at: http://www.
atsdr.cdc.gov.toxprofiles/tp111.html. Accessed June 10, 2007.
22. International Agency for Research on Cancer. Monographs on the evaluation of
carcinogenic risks to humans: volume 62wood dust and formaldehyde. Geneva,
Switzerland, WHO, 1995.
23. HCN-DECOS (Health Council of the Netherlands-Dutch Expert Committee on Occupational Standards) 2003. Formaldehyde: health-based recommended occupational
exposure limit. Publication number 2003/020SH; The Hague.
24. Casanova M, Heck HAD. Further studies on the metabolic incorporation and covalent
bonding of inhaled [3H] and [14C] formaldehyde in Fischer-344 rats: effects of
glutathione depletion. Toxicol Appl Pharmacol 1987;89:10521.
25. Organisation for Economic Cooperation and Development. SIDS Initial Assessment Report:
2002. Available at: http://www.chem.unep.ch/irptc/sids/OECDSIDS/FORMALDEHYDE.pdf.
Accessed August 14, 2007.
26. San Jose Mercury News 2005. Actual spill intrudes on medical center drill. Available
at: http://publicsafety.com/article/article.jsp?id2460&siteSection3. Accessed
June 3, 2007.
27. Wilkins FJ, Macleod HD. Formaldehyde induced DNA-protein crosslinks in Escherichia coli. Mutat Res 1976;36:11 6.
28. Orstavik D, Holgslo JK. Mutagenicity of endodontic sealers. Biomaterials
1985;6:129 32.
29. Goldmacher VS, Thilly WG. Formaldehyde is mutagenic for cultured human cells.
Mutat Res 1983;116:41722.
30. Nocentini S, Moreno G, Coppey J. Survival, DNA synthesis and ribosomal RNA transcription in monkey kidney cells treated by formaldehyde. Mutat Res
1980;70:231 40.
31. Swenberg JA, Kerns WD, Mitchell RI, Gralla EJ, Pavkov KL. Induction of squamous cell
carcinomas of the rat nasal cavity by inhalational exposure to formaldehyde vapor.
Cancer Res 1980;40:3398 401.
32. International Agency for Research on Cancer. IARC classifies formaldehyde as carcinogenic to humans. Press release no. 153, June 2004. Available at: http://www.
iarc.fr/pageroot/PRELEASES/pr153a.html. Accessed August 20, 2004.
33. Ranly DM. Pulpotomy therapy in primary teeth: new modalities for old rationales.
Pediatr Dent 1994;18:4039.
35. Ibricevic H, Al-Jame Q. Ferric sulphate and formocresol in pulpotomy of primary
molars: long tern follow-up study. Eur J Paediatr Dent 2003;4:28 32.
36. Agamy HA, Bakry NS, Mounir MMF, Avery DR. Comparison of mineral trioxide aggregate and formocresol pulp capping agents in pulpotomized primary teeth. Pediatr
Dent 2004;26:3029.
37. Elliott RD, Roberts MW, Burkes J, Phillips C. Evaluation of the carbon dioxide laser on
vital human primary pulp tissue. Pediatr Dent 1999;21:32731.
38. Patchett CL, Srinivasan V, Waterhouse PJ. Is there life after Buckleys Formocresol?
part 2: evelopment of a protocol for the management of extensive caries in the
primary molar. Int J Paediatr Dent 2006;17:199 206.
39. Srinivasan V, Patchett CL, Waterhouse PJ. Is there life after Buckleys Formocresol?
part 1: a narrative review of the literature. Int J Paediatr Dentistry 2006;16:11727.
40. Nadin G, Goel BR, Yeung CA, Gleny AM. Pulp treatment for extensive decay in primary
teeth. Cochrane Database Syst Rev 2003;1:CD003220.
41. Loh A, OHoy P, Tran X, et al. Evidence-based assessment: evaluation of formocresol
versus ferric sulphate primary molar pulpotomy. PediatDent 2004;26:4019.
Pulp Symposium
Regeneration Potential of the Young Permanent Tooth:

What Does the Future Hold?
Kenneth M. Hargreaves, DDS, PhD,* Todd Geisler, DDS,* Michael Henry, DDS, PhD,*
and Yan Wang, DDS, PhD
Abstract
During the last 10 15 years, there has been a tremendous increase in our clinical tools (ie, materials,
instruments, and medications) and knowledge from the
trauma and tissue engineering fields that can be applied to regeneration of a functional pulp-dentin complex. In addition, recent case reports indicate that biologically based endodontic therapies can result in
continued root development, increased dentinal wall
thickness, and apical closure when treating cases of
necrotic immature permanent teeth. The purpose of this
review was to summarize these findings and illustrate
a path forward for the development and evaluation of
regenerative endodontic therapies. (J Endod 2008;34:
S51-S56)
Key Words
Endodontics, pulp biology, regeneration, revascularization, tissue engineering
From the *Department of Endodontics, University of Texas

Health Science Center, San Antonio, Texas; and Department
of Endodontics, School of Stomatology, Shandong University,
Jinan, China.
Address requests for reprints to Dr K. M. Hargreaves,
University of Texas Health Science Center, Mail Code 7982,
7703 Floyd Curl Dr, San Antonio, TX 78229-3900. E-mail
address: Hargreaves@uthscsa.edu.
Conflicts of Interest: Kenneth M. Hargreaves, DDS, PhD, is
a Grant Recipient from the National Institutes of Health and is
the Editor-in-Chief of the Journal of Endodontics. Todd Geisler,
DDS, is a Grant Recipient from the AAE Foundation. Michael
Henry, DDS, PhD, is a Grant Recipient from the National
Institutes of Health. Yan Wang, DDS, PhD, reports no financial
interests or potential conflicts of interest.
doi:10.1016/j.joen.2008.02.032
reatment of the young permanent tooth with a necrotic root canal system and an
incompletely developed root is fraught with difficulty. Not only is the root canal
system often difficult to fully debride, but the thin dentinal walls increase the risk of a
subsequent fracture. Historically, acceptable endodontic results have been achieved
through apexification procedures with use of long-term calcium hydroxide. Concerns
have been raised, however, that long-term calcium hydroxide therapy might alter the
mechanical properties of dentin. Recent treatment strategies include 1-step creation of
an artificial apical barrier by using mineral trioxide aggregate (MTA) with or without an
apical matrix followed by compaction of obturating material and placement of a coronal
restoration. MTA has been shown to produce good sealing effects under these conditions (1, 2). In addition, bonded composite resins have been reported to increase
fracture resistance under some (3, 4) but not all experimental conditions (5). Unfortunately, even after treatment, these teeth have an elevated risk for fracture (6).
An alternative approach is to provide treatment under conditions where continued
dentin formation is promoted. Several reports document that under conditions where at
least some pulp tissue appears vital, a pulp cap treatment permits continued dentin
formation, described as either continued root development (maturogenesis) or apical
closure (apexogenesis) (7). Although these findings and an emphasis for continued
research on vital pulp therapy are important (8), in many clinical cases the dental pulp
has already undergone tissue necrosis before specialist consultation. Moreover, conventional endodontic therapy is not expected to result in continued dentin formation in
these circumstances. Thus, there is continued need to develop biologically based treatment regimens that offer the potential for continued hard tissue formation of the young
permanent tooth with a necrotic root canal system and an incompletely developed root.
Regenerative Endodontic Procedures

Several groups recently have published preclinical research or case reports that
offer a biologically based alternative to conventional endodontic treatment of these
complex clinical cases. In general, these studies have evolved from the trauma literature, where the following precepts have been established:
1. Revascularization occurs most predictably in teeth with open apices (9 12).
2. Instrumentation with NaOCl irrigation is not sufficient to reliably create the conditions necessary for revascularization of the infected necrotic tooth (13).
3. Placement of Ca(OH)2 in root canal systems prevents revascularization coronal
to the location of the Ca(OH)2 (14).
4. The use of the 3 mix-MP triple antibiotic paste, developed by Hoshino and
colleagues and consisting of ciprofloxacin, metronidazole, and minocycline, is
effective for disinfection of the infected necrotic tooth, setting the conditions for
subsequent revascularization (1519).
This triple antibiotic mixture has high efficacy. In a recent preclinical study on
dogs, the intracanal delivery of a 20-mg/mL solution of these 3 antibiotics via a Lentulo
spiral resulted in a greater than 99% reduction in mean colony-forming unit (CFU)
levels, with approximately 75% of the root canal systems having no cultivable microorganisms present (19). Taken together, these studies provide a strong foundation level
of knowledge from the trauma literature that permits subsequent research to focus on
developing clinical methods for regeneration of a functional pulp-dentin complex.
Regeneration Potential of the Young Permanent Tooth
S51
Pulp Symposium
Although the trauma literature has used the term revascularization to describe this treatments outcome, the goal from an endodontic
perspective is to regenerate a pulp-dentin complex that restores functional properties of this tissue, fosters continued root development for
immature teeth, and prevents or resolves apical periodontitis. Thus,
using the term revascularization for regenerative endodontic procedures has been questioned (20). Therefore, this review will focus on the
concept of regenerating a functional pulp-dentin complex and will restrict the use of the term revascularization to trauma studies.
It should be appreciated that research on regeneration of a pulpdentin complex has a long history. For example, during the last 30 50
years, Nygaard-stby and others have reported a series of preclinical
studies and case studies on patients attempting to regenerate pulp-like
tissue in teeth with either vital or nonvital diagnoses (2124). Connective tissue was demonstrated to grow as much as several millimeters into
the apical portion of the root canal system in teeth with necrotic pulpal
diagnoses (23). The results were variable, however, and histologic
analysis failed to reveal regeneration of a functional pulp-dentin complex. This lack of outcome is not surprising, however, given the level of
materials, instruments, and medications and the knowledge base available at the time. Instead, current research in regenerative endodontics
uses greatly improved materials, instruments, and medications and applies many principles from the fields of trauma research and tissue
engineering (2528).
In part on the basis of this expanding base of tools and knowledge,
several recent case reports have been published describing regenerative
endodontic procedures applied to cases of necrotic immature permanent teeth. Key features of these published cases (20, 29 32) are summarized in Table 1.
There are several common factors observed in these cases. First,
although structurally weak, it is important to realize that the immature
permanent tooth in general has a very wide apical opening that likely is
conducive to tissue ingrowth. Second, these patients are young (8 13
years old), and several (3337), but not all (38), studies suggest that
younger ages have greater healing capacity or stem cell regenerative
potential. Third, none of the cases used instrumentation of the root
canal walls, whereas all of the studies used NaOCl as an irrigant. Fourth,
both Ca(OH)2 paste and combinations of multiple antibiotics have been
used in these patients. Outcome differences between these 2 medicaments might reveal an important aspect of regenerative methods, because many of the reported cases treated with Ca(OH)2 display intracanal calcifications that appear to impede the continued thickening of
the dentinal walls of these immature teeth (20). In addition, other
investigators (30) have suggested that the use of Ca(OH)2 might kill any
remaining pulpal cells, including stem or progenitor cells known to be
present in dental pulp tissue (39 41), or possibly disrupt the apical
papilla (30) and its resident stem cells (42, 43), which is critical for
continued root development. Fifth, the formation of a blood clot might
serve as a protein scaffold, permitting 3-dimensional ingrowth of tissue.
Sixth, nearly all of these studies report continued thickening of the
dentinal walls and subsequent apical closure. It should be appreciated,
however, that the radiographic finding of continued dentinal wall thickness does not address the cellular nature of this calcified material.
Largely on the basis of preclinical studies, it is possible that the
radiographic presentation of increased dentinal wall thickness might be
due to ingrowth of cementum, bone, or a dentin-like material (23, 24,
44 48). This diversity in cellular response is not surprising, given that
human dental pulp cells can develop odontogenic/osteogenic, chondrogenic, or adipogenic phenotypes, depending on their exposure to
different cocktails of growth factors and morphogens (49, 50). One
advantage of case reports is that they are based on outcomes observed
in actual patients and therefore might have great value in stimulating the
S52
Hargreaves et al.
development of subsequent treatment methods; indeed, the discovery of

fluoride emerged from the keen observations of a practicing clinician.
We now recognize, however, the critical importance of subjecting these
initial findings to prospective randomized clinical trials to generate
objective measures of treatment efficacy and the potential liability for
adverse events.
Thus, these and other case reports (51) should be viewed as
generating a strong impetus for developing future prospective clinical
trials. Taken together, these recent case studies support the hypothesis
that the immature necrotic permanent tooth might be particularly responsive to biologically based endodontic therapies. Not only do these
treatments provide an important alternative in a clinical situation with
an otherwise poor prognosis, but equally important, these cases might
serve as an important clinical model to evaluate the application of tissue
engineering concepts to the regeneration of a functional pulp-dentin
complex.
Application of Tissue Engineering Concepts to

Regenerative Endodontics
The field of tissue engineering has literally exploded during the last
decade, and extensive reviews on dental applications are available for
the interested reader (25, 26, 5257). Here we briefly review 3 major
components of tissue engineering from the concept of developing regenerative endodontic treatment regimens. Although basic research has
applied nearly all of the tools of molecular biology for engineering of
dental tissues, including transfections and knockout animals, we will
adopt a different perspective: What concepts of tissue engineering are
most likely to be available to clinicians when treating their patients with
regenerative endodontic techniques? We have used this rather practical
perspective to shape our review of this field and to suggest a path
forward for developing and evaluating regenerative endodontics.
The first component of tissue engineering is a cell source. Odontoblasts are of mesenchymal origin, and under appropriate conditions,
cells from dental pulp, the apical papilla, and possibly other tissues can
form odontoblast-like cells (49, 50, 56, 58 61). Controversies exist
among several of these studies, because measuring only 1 or 2 characteristics of a cell might not be sufficient to conclusively determine
whether the resulting cell is a true odontoblast. Indeed, even among
odontoblasts, the phenotype varies in cells located in the apical versus
coronal dentin. Recent molecular studies have identified many of the
genes selectively expressed in odontoblasts (62, 63), however, and this
is likely to aid future studies characterizing the conditions necessary for
mesenchymal cells of multiple origins to differentiate into the odontoblast phenotype. To date, the precise cell source(s) supporting the
continued root development of the cases described in Table 1 are unknown. It is possible that: residual pulp cells might have remained vital
in some of the cases, cells from the apical papilla underwent proliferation, or bleeding-induced angiogenesis might have recruited stem/
progenitor cells from apical tissues including the apical papilla. The
clinical challenge will be to find a reliable cell source capable of differentiating into odontoblasts, convenient for harvesting, and autogenous
to avoid tissue rejection or introduction of foreign pathogens (25).
Moreover, a delivery method must be developed that permits controlled
application of a known amount of cells into the apical region of the root
canal system. Clearly, these are critical areas for future research.
The second component of tissue engineering is a physical scaffold.
Tissues are 3-dimensional structures, and an appropriate scaffold is
needed to promote cell growth and differentiation. It is known that
extracellular matrix molecules control the differentiation of stem cells
(64, 65), and an appropriate scaffold might selectively bind and localize
cells (66), contain growth factors (67), and undergo biodegradation
Pulp Symposium
TABLE 1. Key Features of Case Reports of Regenerative Endodontic Treatment Applied to Necrotic Immature Permanent Teeth
Tooth Patient Patient
no.
age (y)
sex
29
13
Female
Preoperative
pulpal
diagnosis
Necrosis
Preoperative
periradicular
diagnosis
Chronic apical
abscess
Treatment1
29
11
Male
Necrosis
Chronic apical
abscess
20
10
Female
(Partial)
pulpal
necrosis
Chronic
periradicular
abscess
29
10
Male
Necrosis
Acute
periradicular
abscess
20
10
Female
(Partial)
pulpal
necrosis
Chronic
periradicular
periodontitis
Outcome
5 weekly visits, no
instrumentation, irrigation
with 5% NaOCl and 3%
H2O2. Tooth left open
between first and second
appointments to permit
drainage. Interappointment
medicament: metronidazole
and ciprofloxacin.
6 weeks later: Broach
probed vital tissue in canal.
Applied Ca(OH)2 paste, glass
ionomer cement, bonded
composite resin.
First appointment: Rubber
dam and access. No
instrumentation. Deep
irrigation with 10 mL 5.25%
NaOCl and 0.12%
chlorhexidine.
Interappointment
medicament: metronidazole,
minocycline, and
ciprofloxacin (Lentulo
spiral). Cavit.
1 month: Irrigate 20 mL
5.35% NaOCl. Bleeding
initiated with endo explorer.
Stopped bleeding 3 mm
from cementoenamel
junction. MTA, wet pellet,
Cavit.
2 weeks later: Composite
restoration.
dam and access. No
instrumentation. Irrigate
with 20 mL 2.5% NaOCl.
Interappointment
medicament: Ca(OH)2 paste.
Caviton/IRM.
2 weeks later: Repeat.
3 months: Replace Ca(OH)2
11 months: Remove IRM and
replace with amalgam.
dam and access. No
instrumentation. Irrigate
with 2.5% NaOCl.
Interappointment
1 month: Irrigate with 2.5%
NaOCl. Interappointment
2 months: Replace Ca(OH)2.
7 months: Restore with
Caiton/Ketac Silver.
Formocresol pulpotomy.
9 days: Rubber dam and
access. No instrumentation.
Irrigate with 2.5% NaOCl.
Interappointment
1 month: Replace Ca(OH)2.
2 months later and every
23 months for 11 months:
Replace Ca(OH)2.
amalgam.
Reference
no.
Sixth appointment: Vital

tissue observed 5 mm
apical to canal orifice.
15 months: Positive
response to electrical
pulp test.
30 months: Apical
closure with thickening
of dentinal walls.
29
26 days: Vital tissue

present 15 mm into
canal system.
6 24 months: Gradual
apical closure with
thickening of dentinal
walls.
Positive response to
pulpal cold test.
30
3 months: Found hard

tissue at Ca(OH)2 site.
Asymptomatic.
11 months: Thickening
of dentinal walls.
35 months: Continued
thickening of dentinal
walls and apical closure.
20
2 months: Found hard

tissue at Ca(OH)2 site.
Asymptomatic.
7 months: Apical
closure, thickening
dentinal walls, calcified
coronal one third root
canal system.
20
1 month: Found hard

tissue at mid-root.
1154 months: Gradual
apical closure,
thickening dentinal
walls in apical half of
root canal system.
20
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Pulp Symposium
TABLE 1. (Continued)
Tooth Patient Patient
no.
age (y)
sex
29
Male
Preoperative
pulpal
diagnosis
Necrosis
Preoperative
periradicular
diagnosis
Chronic
periradicular
periodontitis
Treatment1
Male
Necrosis
Chronic
periradicular
abscess
Male
Necrotic
Acute apical
abscess
Tooth left open for drainage

at an emergency clinic.
Rubber dam and access. No
instrumentation. Irrigate 40
mL 2.5% NaOCl.
Interappointment
2 weeks and 5 weeks:
Repeat.
5 months: Repeat.
amalgam to calcified bridge.
First appointment:
Consultation.
Second appointment:
Rubber dam and access. No
instrumentation. Deep
irrigation with 10 mL 5.25%
NaOCl and 0.12%
chlorhexidine.
Interappointment
minocycline, and
ciprofloxacin. Cavit.
Third appointment: Irrigate
with 5.25% NaOCl, induce
bleeding with endo
explorer. Cotton pellet
placed 3 mm below
cementoenamel junction for
15-minute control location
of a blood clot. MTA, wet
cotton pellet, Cavit.
Fourth appointment:
Remove Cavit and place
bonded composite.
Trauma 2 years previously
treated with Cvek
pulpotomy procedure.
Incision for drainage.
Disinfect tooth surface with
Betadine. Rubber dam and
access. No instrumentation.
Irrigate copiously with
1.25% NaOCl.
Interappointment
minocycline, and
ciprofloxacin (Lentulo
spiral). IRM.
11 weeks: Irrigate with 10
mL 1.25% NaOCl and 10 mL
sterile water. Induce
bleeding with endodontic
file inserted beyond the
apex. 15 minutes allowed
for blood clot to reach
cementoenamel junction.
Place MTA over blood clot
with moist cotton pellet.
Remove cotton pellet 1 hour
later and place bonded
composite.
Outcome
Reference
no.
5 weeks: Hard tissue

found at mid-root.
5 60 months: Gradual
development of root
length, thickening of
dentinal walls, apical
closure.
20
8 months:
Asymptomatic. Apical
closure with thickening
dentinal walls.
31
3 months:
Asymptomatic. Diffuse
radiopacities noted in
root canal system. No
response to pulp test
(CO2 ice).
6 12 months:
Asymptomatic. Diffuse
radiopacities noted in
root canal system. No
response to pulp test
(CO2 ice). Gradual apical
development and
closure.
32
IRM, intermediate restorative material; MTA, mineral trioxide aggregate.
S54
Hargreaves et al.
Pulp Symposium
over time (68). Thus, a scaffold is far more than a simple lattice to
contain cells. From our perspective of focusing on practical clinical
applications, we believe that platelet-rich plasma (PRP) satisfies many
of these criteria. PRP is autologous, fairly easy to prepare in a dental
setting, rich in growth factors, degrades over time, and forms a 3-dimensional fibrin matrix (69 72). Interestingly, the case reports from
Table 1 all include formation of a blood clot. The use of PRP as an
alternative source for a fibrin clot might have several advantages, including increased concentration of growth factors and removal of erythrocytes that would be expected to undergo necrosis shortly after clot
formation. To date, however, no publications have evaluated PRP for
scaffold generation in regenerative endodontic applications. This and
other potential scaffolds require future research.
The third component of tissue engineering to consider for regenerative endodontics is signaling molecules. Both growth factors and
other compounds are capable of stimulating cellular proliferation and
directing cellular differentiation. As aforementioned, the observed radiographic thickening of the dentinal walls might be due to production
of cementum, bone, or dentin. It is likely that the cell source and the
available signaling molecules play major roles in guiding the development of cells in the regenerating tissue. For example, the same cultures
of human dental pulp cells can differentiate into cells resembling odontoblasts/osteoblasts, adipoyctes, or chondrocytes, depending on the
combination of signaling molecules such as dexamethasone (49).
Other investigators have shown that dentin or application of a dentin
extract rich in growth factors will promote formation of an odontoblast
phenotype (50, 62, 73). Extracts of dentin promote growth, because
many growth factors are embedded into the dentin matrix during dentinogenesis. Interestingly, ethylenediaminetetraacetic acid (EDTA) very
effectively releases growth factors from human dentin (74). It is not yet
known, however, whether root canal irrigation with EDTA would promote the development of odontoblast proliferation in a regenerative
endodontic procedure. It is likely that intracanal delivery of known
signaling molecules or the solubilization of endogenous signaling molecules will promote the formation of dentin in regenerative endodontic
methods.
A Path to the Future

Collectively, there has been a tremendous increase in our clinical
tools (ie, materials, instruments, and medications) and knowledge
from the trauma and tissue engineering fields during the last decade.
Moreover, recent case reports from multiple investigators support the
feasibility of developing biologically based regenerative endodontic
procedures designed to restore a functional pulp-dentin complex. Although these case reports primarily involve treating the immature permanent tooth, it is quite possible that knowledge gained from this clinical application will have value in developing regenerative endodontic
procedures for the fully developed permanent tooth. In short, the question is no longer can regenerative endodontic procedures be successful? Instead, the important question facing us is what are the issues
that must be addressed to develop a safe, effective, and consistent
method for regenerating a functional pulp-dentin complex in our patients?
In our opinion, the path to the future should focus on translational
research models that simulate likely clinical procedures. For example,
although of clear scientific importance in understanding cellular mechanisms, we do not believe that gene transfection is likely to have major
application in clinical endodontic procedures. Similarly, if natural tooth
development takes several years to occur, then we are not convinced
that the growth of artificial teeth with cells of allogenic or even xeongenic origin (42, 75) is likely to have major clinical application. In-
stead, we believe that research modeling clinical procedures designed

to regenerate a functional pulp-dentin complex is likely to have the
greatest impact. On the basis of current concepts, one approach would
be to focus on methods permitting the delivery of known cells, signaling
molecules, and a scaffold such as PRP into the apical 12 mm of a root
canal system and then backfilling the root canal system with a solution
of PRP and signaling molecules. Because most cells must be less than 1
mm away from a blood vessel to survive (76), research focusing on the
initiation of pulpal regeneration at the apex is likely to have major
impact in developing other clinically useful procedures. Cellular proliferation could then occur along the backfill scaffold.
One possible approach is to develop a model system resembling
clinical application. For example, the revascularization of root canal
systems has been evaluated in human tooth slices after implantation into
nude mice (who are immunocompromised, thus avoiding tissue rejection) (77). Similarly, it might be possible to evaluate the initiation of
pulpal regeneration after various treatments by implanting the apical
510 mm of sectioned human roots into nude mice. This approach has
particular advantages, because it permits rapid evaluation of conditions
necessary to initiate tissue regeneration and could be extended in future
research by evaluating conditions necessary to optimally disinfect necrotic root canal systems before tissue regeneration.
A recent editorial has suggested that little progress has been
made in the years since the Nygaard-stby studies on the regrowth of
dental pulp (8). From many perspectives, this statement is accurate. We
believe, however, that the last decade has produced a critical mass of
knowledge and methods that are likely to result in the generation of
biologically based endodontic therapies that will answer the challenge
issued decades ago.
References
1. Hachmeister DR, Schindler WG, Walker WA III, Thomas DD. The sealing ability and
retention characteristics of mineral trioxide aggregate in a model of apexification. J
Endod 2002;28:386 90.
2. Pace R, Giuliani V, Pini Prato L, Baccetti T, Pagavino G. Apical plug technique using
mineral trioxide aggregate: results from a case series. Int Endod J 2007;40:478 84.
3. Wilkinson KL, Beeson TJ, Kirkpatrick TC. Fracture resistance of simulated immature
teeth filled with resilon, gutta-percha, or composite. J Endod 2007;33:480 3.
5. Stuart CH, Schwartz SA, Beeson TJ. Reinforcement of immature roots with a new resin
filling material. J Endod 2006;32:350 3.
6. Cvek M. Prognosis of luxated nonvital maxillary incisors treated with calcium hydroxide and filled with gutta-percha: a retrospective clinical study. Endod Dent
Traumatol 1992;8:4555.
7. Weisleder R, Benitez CR. Maturogenesis: is it a new concept? J Endod
2003;29:776 8.
8. Spangberg L. Who cares about the dental pulp? Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2007;104:587 8.
9. Kling M, Cvek M, Mejare I. Rate and predictability of pulp revascularization in therapeutically reimplanted permanent incisors. Endod Dent Traumatol 1986;2:839.
10. Johnson WT, Goodrich JL, James GA. Replantation of avulsed teeth with immature
root development. Oral Surg Oral Med Oral Pathol 1985;60:420 7.
11. Laureys W, Beele H, Cornelissen R, Dermaut L. Revascularization after cryopreservation and autotransplantation of immature and mature apicoectomized teeth. Am J
Orthod Dentofacial Orthop 2001;119:346 52.
12. Andreasen JO, Borum MK, Jacobsen HL, Andreasen FM. Replantation of 400 avulsed
permanent incisors: 2factors related to pulpal healing. Endod Dent Traumatol
1995;11:59 68.
13. Cvek M, Nord CE, Hollender L. Antimicrobial effect of root canal debridement in teeth
with immature root: a clinical and microbiologic study. Odontol Revy 1976;27:110.
14. Schroder U, Granath LE. Early reaction of intact human teeth to calcium hydroxide
following experimental pulpotomy and its significance to the development of hard
tissue barrier. Odontol Revy 1971;22:379 95.
15. Hoshino E, Kurihara-Ando N, Sato I, et al. In vitro antibacterial susceptibility of
bacteria taken from infected root dentine to a mixture of ciprofloxacin, metronidazole, and minocycline. Int Endod J 1996;29:12530.
S55
Pulp Symposium
16. Sato T, Hoshino E, Uematsu H, Noda T. In vitro antimicrobial susceptibility to combinations of drugs on bacteria from carious and endodontic lesions of human deciduous teeth. Oral Microbiol Immunol 1993;8:172 6.
17. Sato I, Ando-Kurihara N, Kota K, Iwaku M, Hoshino E. Sterilization of infected rootcanal dentine by topical application of a mixture of ciprofloxacin, metronidazole, and
minocycline in situ. Int Endod J 1996;29:118 24.
18. Takushige T, Cruz EV, Asgor Moral A, Hoshino E. Endodontic treatment of primary
teeth using a combination of antibacterial drugs. Int Endod J 2004;37:132 8.
19. Windley W III, Teixeira F, Levin L, Sigurdsson A, Trope M. Disinfection of immature
teeth with a triple antibiotic paste. J Endod 2005;31:439 43.
20. Chueh LH, Huang GT. Immature teeth with periradicular periodontitis or abscess
undergoing apexogenesis: a paradigm shift. J Endod 2006;32:120513.
21. Nygaard-Ostby B, Hjortdal O. Tissue formation in the root canal following pulp
removal. Scand J Dent Res 1971;79:333 49.
22. Horsted P, Nygaard-Ostby B. Tissue formation in the root canal after total pulpectomy
and partial root filling. Oral Surg Oral Med Oral Pathol 1978;46:275 82.
23. Nygaard-stby B. The role of the blood clot in endodontic therapy: An experimental
histologic study. Acta Odontol Scand 1961;19:32353.
24. Nevins AJ, Finkelstein F, Borden BG, Laporta R. Revitalization of pulpless open apex teeth
in rhesus monkeys, using collagen-calcium phosphate gel. J Endod 1976;2:159 65.
25. Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative endodontics: A review of
current status and a call for action. J Endod 2007;33:37790.
26. Nakashima M, Akamine A. The application of tissue engineering to regeneration of
pulp and dentin in endodontics. J Endod 2005;31:711 8.
27. Thibodeau B, Teixeira F, Yamauchi M, Caplan DJ, Trope M. Pulp revascularization of
immature dog teeth with apical periodontitis. J Endod 2007;33:680 9.
28. Flores MT, Andersson L, Andreasen JO, et al. Guidelines for the management of traumatic
dental injuries: IIavulsion of permanent teeth. Dent Traumatol 2007;23:130 6.
29. Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth with
apical periodontitis and sinus tract. Dent Traumatol 2001;17:1857.
periodontitis: new treatment protocol? J Endod 2004;30:196 200.
31. Petrino JA. Revascularization of necrotic pulp of immature teeth with apical periodontitis. Northwest Dent 2007;86:335.
32. Thibodeau B, Trope M. Pulp revascularization of a necrotic infected immature permanent tooth: case report and review of the literature. Pediatr Dent 2007;29:4750.
33. Lei L, Liao W, Sheng P, Fu M, He A, Huang G. Biological character of human adiposederived adult stem cells and influence of donor age on cell replication in culture. Sci
China 2007;50:320 8.
34. ODriscoll SW, Saris DB, Ito Y, Fitzimmons JS. The chondrogenic potential of periosteum decreases with age. J Orthop Res 2001;19:95103.
35. DIppolito G, Schiller PC, Ricordi C, Roos BA, Howard GA. Age-related osteogenic
potential of mesenchymal stromal stem cells from human vertebral bone marrow.
J Bone Miner Res 1999;14:111522.
36. Amler MH. The age factor in human extraction wound healing. J Oral Surg
1977;35:1937.
37. Murray PE, Stanley HR, Matthews JB, Sloan AJ, Smith AJ. Age-related odontometric
changes of human teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
2002;93:474 82.
38. Stenderup K, Justesen J, Eriksen EF, Rattan SI, Kassem M. Number and proliferative
capacity of osteogenic stem cells are maintained during aging and in patients with
osteoporosis. J Bone Miner Res 2001;16:1120 9.
39. Liu H, Gronthos S, Shi S. Dental pulp stem cells. Methods Enzymol 2006;
419:99 113.
40. Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human
bone marrow and dental pulp. J Bone Miner Res 2003;18:696 704.
41. Gronthos S, Brahim J, Li W, et al. Stem cell properties of human dental pulp stem
cells. J Dent Res 2002;81:5315.
42. Sonoyama W, Liu Y, Fang D, et al. Mesenchymal stem cell-mediated functional tooth
regeneration in swine. PLoS ONE 2006;1:e79.
43. Sonoyama W, Liu Y, Yamaza T, et al. Characterization of the apical papilla and its
residing stem cells from human immature permanent teeth: a pilot study. J Endod
2008;34:166 71.
44. Ritter AL, Ritter AV, Murrah V, Sigurdsson A, Trope M. Pulp revascularization of
replanted immature dog teeth after treatment with minocycline and doxycycline
assessed by laser Doppler flowmetry, radiography, and histology. Dent Traumatol
2004;20:75 84.
45. Nevins A, Finkelstein F, Laporta R, Borden BG. Induction of hard tissue into pulpless
open-apex teeth using collagen-calcium phosphate gel. J Endod 1978;4:76 81.
46. Skoglund A, Tronstad L. Pulpal changes in replanted and autotransplanted immature
teeth of dogs. J Endod 1981;7:309 16.
47. Sheppard PR, Burich RL. Effects of extra-oral exposure and multiple avulsions on
revascularization of reimplanted teeth in dogs. J Dent Res 1980;59:140.
S56
Hargreaves et al.
48. Kvinnsland I, Heyeraas KJ. Dentin and osteodentin matrix formation in apicoectomized replanted incisors in cats. Acta Odontol Scand 1989;47:4152.
49. Wei X, Ling J, Wu L, Liu L, Xiao Y. Expression of mineralization markers in dental pulp
cells. J Endod 2007;33:703 8.
50. Huang GT, Shagramanova K, Chan SW. Formation of odontoblast-like cells from
cultured human dental pulp cells on dentin in vitro. J Endod 2006;32:1066 73.
51. Shah N, Logani A. Evaluation of revascularization to induce apexification/apexogensis
in infected, nonvital immature teeth (abstract). In: IFEA Meeting; August 2007; Vancouver, British Columbia, Canada.
52. Risbud MV, Shapiro IM. Stem cells in craniofacial and dental tissue engineering.
Orthod Craniofac Res 2005;8:54 9.
53. Rahaman MN, Mao JJ. Stem cell-based composite tissue constructs for regenerative
medicine. Biotechnol Bioeng 2005;91:261 84.
54. Modino SA, Sharpe PT. Tissue engineering of teeth using adult stem cells. Arch Oral
Biol 2005;50:255 8.
55. Feinberg SE, Aghaloo TL, Cunningham LL Jr. Role of tissue engineering in oral and
maxillofacial reconstruction: findings of the 2005 AAOMS Research Summit. J Oral
Maxillofac Surg 2005;63:1418 25.
56. Shi S, Bartold PM, Miura M, Seo BM, Robey PG, Gronthos S. The efficacy of mesenchymal stem cells to regenerate and repair dental structures. Orthod Craniofac Res
2005;8:1919.
57. Sloan AJ, Smith AJ. Stem cells and the dental pulp: potential roles in dentine regeneration and repair. Oral Dis 2007;13:1517.
58. Zhang W, Walboomers XF, Wolke JG, Bian Z, Fan MW, Jansen JA. Differentiation
ability of rat postnatal dental pulp cells in vitro. Tissue Eng 2005;11:357 68.
59. Alliot-Licht B, Bluteau G, Magne D, et al. Dexamethasone stimulates differentiation of
odontoblast-like cells in human dental pulp cultures. Cell Tissue Res 2005;321:391 400.
60. Kikuchi H, Suzuki K, Sakai N, Yamada S. Odontoblasts induced from mesenchymal
cells of murine dental papillae in three-dimensional cell culture. Cell Tissue Res
2004;317:173 85.
61. Miura M, Gronthos S, Zhao M, et al. SHED: Stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 2003;100:580712.
62. Liu J, Jin T, Chang S, Ritchie HH, Smith AJ, Clarkson BH. Matrix and TGF-beta-related
gene expression during human dental pulp stem cell (DPSC) mineralization. In Vitro
Cell Dev Bio 2007;43:120 8.
63. Paakkonen V, Vuoristo JT, Salo T, Tjaderhane L. Comparative gene expression profile
analysis between native human odontoblasts and pulp tissue. Int Endod J
2008;41:11727.
64. Bi Y, Ehirchiou D, Kilts TM, et al. Identification of tendon stem/progenitor cells and
the role of the extracellular matrix in their niche. Nature Med 2007;13:1219 27.
65. Yamamura T. Differentiation of pulpal cells and inductive influences of various matrices
with reference to pulpal wound healing. J Dent Res 1985;64(Special issue):530 40.
66. Vacatello M, DAuria G, Falcigno L, et al. Conformational analysis of heparin binding
peptides. Biomaterials 2005;26:320714.
67. Yamada Y, Ueda M, Naiki T, Takahashi M, Hata K, Nagasaka T. Autogenous injectable
bone for regeneration with mesenchymal stem cells and platelet-rich plasma: tissueengineered bone regeneration. Tissue Eng 2004;10:955 64.
68. Young CS, Terada S, Vacanti JP, Honda M, Bartlett JD, Yelick PC. Tissue engineering
of complex tooth structures on biodegradable polymer scaffolds. J Dent Res
2002;81:695700.
69. Ito K, Yamada Y, Nagasaka T, Baba S, Ueda M. Osteogenic potential of injectable tissueengineered bone: a comparison among autogenous bone, bone substitute (Bio-oss),
platelet-rich plasma, and tissue-engineered bone with respect to their mechanical properties and histological findings. J Biomed Mater Res 2005;73A:6372.
70. Anitua E, Andia I, Sanchez M, et al. Autologous preparations rich in growth factors
promote proliferation and induce VEGF and HGF production by human tendon cells
in culture. J Orthop Res 2005;23:281 6.
71. Anitua E, Sanchez M, Nurden AT, Nurden P, Orive G, Andia I. New insights into and novel
applications for platelet-rich fibrin therapies. Trends Biotechnol 2006;24:22734.
72. Ogino Y, Ayukawa Y, Kukita T, Koyano K. The contribution of platelet-derived growth
factor, transforming growth factor-beta 1, and insulin-like growth factor-I in plateletrich plasma to the proliferation of osteoblast-like cells. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2006;101:724 9.
73. Smith AJ. Vitality of the dentin-pulp complex in health and disease: growth factors as
key mediators. J Dent Ed 2003;67:678 89.
74. Graham L, Cooper PR, Cassidy N, Nor JE, Sloan AJ, Smith AJ. The effect of calcium
hydroxide on solubilization of bioactive dentine matrix components. Biomaterials
2006;27:286573.
75. Sharpe PT, Young CS. Test-tube teeth. Sci Am 2005;293:34 41.
76. Helmlinger G, Yuan F, Dellian M, Jain RK. Interstitial pH and pO2 gradients in solid
tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med
1997;3:177 82.
77. Goncalves SB, Dong Z, Bramante CM, Holland GR, Smith AJ, Nor JE. Tooth slice-based
models for the study of human dental pulp angiogenesis. J Endod 2007;33:811 4.
Pulp Symposium
Contemporary Perspectives on Vital Pulp Therapy: Views

From the Endodontists and Pediatric Dentists
N. Sue Seale, DDS, MSD,* and Gerald N. Glickman, DDS, MS
Abstract
The purpose of this study was to determine the level of
agreement between pediatric dentists and endodontists
at a pulp therapy symposium conjointly sponsored by
the American Association of Endodontists (AAE) and
the American Academy of Pediatric Dentistry (AAPD) on
November 23, 2007. Presymposium and postsymposium tests were administered, and respondent answers
were compared between pediatric dentists and endodontists. Opinions on 3 areas were sought: pulp therapy for cariously involved primary teeth; indirect pulp
treatment (IPT) for cariously involved immature permanent teeth; and innovative treatment options including
pulpal revascularization and regeneration. Results were
analyzed with 2 tests. Comparisons of presymposium
and postsymposium responses and between the 2
groups of attendees indicated that the pediatric dentistry and endodontic communities agree that formocresol will be replaced as a primary tooth pulpotomy
agent, that mineral trioxide is the first choice to take
its place, that IPT in primary teeth holds hope as a replacement for pulpotomy, and that IPT is an acceptable
pulp therapy technique for cariously involved young permanent teeth. Both groups believe that pulp revascularization and regeneration will be viable treatment
modalities in the future. The AAE and the AAPD are
positioned to begin preparation of best practice guidelines that share common language and treatment recommendations for pulp therapies performed by both
specialties. (J Endod 2008;34:S57-S61)
Key Words
Indirect pulp capping, pulp therapy, pulpotomy
From the *Department of Pediatric Dentistry and Department of Endodontics, Baylor College of Dentistry, Texas A&M
University Health Science Center, Dallas, Texas.
Address requests for reprints to Dr Seale at sseale@bcd.
tamhsc.edu.
Conflict of Interest: N. Sue Seale, DDS, MSD, reports no
financial interests or potential conflicts of interest. Gerald N.
Glickman, DDS, MS, reports no financial interests or potential
conflicts of interests.
doi:10.1016/j.joen.2008.02.034
his symposium was intended to bring together 2 different disciplines, pediatric

dentistry and endodontics, to hear and evaluate the best evidence surrounding the
pulpal therapy treatments they commonly perform. One anticipated outcome of the
symposium was to begin preparation for working together to produce best practice
guidelines that share common language and treatment recommendations. Such an
outcome would require both disciplines to agree with interpretation of the evidence
presented concerning the shared treatments.
Because this was the first such endeavor to bring these 2 specialties together, it was
anticipated that there would be a diverse cross-section of opinions, both within each
individual specialty and across the 2 specialties. Therefore, the planning committee
sought to determine, through a brief pretest administered before the first speaker, the
baseline opinions of the attendees concerning the various topics to be presented.
The planning committee also needed to determine what effect, if any, the conference presentations had on attendees opinions, specifically regarding reaching agreements on the
evidence presented to support the treatments being discussed. To that end, a more
in-depth post-test was created and administered to the attendees via a real-time electronic audience response system (ARS).
The purpose of this article was to present the results of the opinion surveys and
report the current status of agreement of the 2 specialties concerning the 3 major areas
of interest: pulp therapy for the cariously involved primary tooth; indirect pulp treatment (IPT) for the cariously involved, immature permanent tooth; and innovative treatment options including pulpal revascularization and pulpal regeneration, both currently under investigation.
Methods
An 8-question pretest was prepared and administered to attendees before the first
presentation. The first 3 questions asked for demographic data, including dental discipline, age, and current situation (pediatric or endodontic practitioner, pediatric or
endodontic resident, or academician). Five additional questions used a 5-point Likert
scale with the choices of strongly agree, agree, neutral, disagree, and strongly disagree
and queried about primary tooth pulpotomy and primary and permanent tooth IPT.
Frequency tables of responses to the pretest questions were calculated for all respondents and compared by discipline, age group, and current career position by using 2
analysis, with a significance level of P .05.
After the last speaker, a more detailed set of 20 questions about the same topics
was presented to the audience for their opinion via an electronic ARS. The same 3
demographic questions that were asked in the pretest were repeated, so that attendees
responses could be identified by discipline, age group, and current career position.
Additional questions used the Likert scale or allowed the attendees to choose a single
best answer from a list of options and patient scenarios. Six questions addressed primary tooth pulpotomy, including medicament choice and opinions about formocresol
as a primary tooth pulpotomy agent. Four questions asked for opinions about indirect
pulp capping (IPC)/stepwise excavation in primary teeth, and an additional 5 questions
asked about the same procedure in permanent teeth. Five questions addressed pulpal
revascularization and the potential for stem cell research for pulpal regeneration.
Frequency tables of responses to the ARS questions were calculated for all respondents
and compared by discipline (pediatric dentist or endodontist) by using 2 analysis, with
a significance level of P .05.
Contemporary Perspectives on Vital Pulp Therapy
S57
Pulp Symposium
Results
A total of 376 individuals provided responses, and they were divided as follows: 79 endodontists, 23 endodontic residents, 231 pediatric dentists, 21 pediatric dental residents, and 22 other. The numbers
of residents and nonspecialists were small. Therefore, 2 analyses were
only performed on responses from pediatric dentists and endodontists.
One of the major areas addressed by the speakers was pulp treatment for the cariously involved primary tooth. Issues covered included
the controversy surrounding the use of formocresol as a pulpotomy
agent in primary teeth and the level of evidence supporting either discontinuing its use or maintaining it as a viable pulpotomy agent; the
status of different pulpotomy agents for primary teeth and the level of
evidence that supports them; and the use of IPT as an alternative to
pulpotomy for cariously involved primary teeth.
Pretest responses concerning the acceptability of formocresol as a
contemporary technique for primary tooth pulpotomy were significantly
more positive (P .001) from pediatric dentists, with 80% agreeing or
strongly agreeing compared with only 29% of endodontists. Three of the
postseminar ARS questions revisited this issue, primarily concerning
formocresols safety. When attendees were asked to respond to the
statement formocresol, when used as a primary tooth pulpotomy
agent, presents documented danger to the patient, pediatric dentists
(5%) were significantly (P .001) less likely than endodontists (15%)
to agree or strongly agree. When asked whether the fact that formocresol is a potential carcinogen should contraindicate its future usage in
pediatric pulp therapy, however, 18% of pediatric dentists agreed or
strongly agreed, compared with 37% of endodontists. Again, these differences were significant (P .001; Fig. 1). Attendees were asked their
opinion about the statement formocresol will be replaced as a primary
tooth pulpotomy agent, not because of its danger to patients, but because there is much controversy about its potential to be dangerous.
Pediatric dentists and endodontists were unified in their opinions, with
78% and 76%, respectively, agreeing or strongly agreeing.
Pulpotomy agents or treatment alternatives for cariously involved
primary teeth were addressed in 2 post-symposium ARS questions. Attendees were asked to give their opinions of the best treatment for a
reversibly inflamed primary molar with a large carious lesion encroaching on the pulp. They did this by choosing from a list that included an IPT
or a pulpotomy with formocresol, ferric sulfate, mineral trioxide aggregate (MTA), or sodium hypochlorite. MTA was the favorite pulpotomy
agent, chosen most often by both pediatric dentists (30%) and endodontists (34%), whereas 20% of pediatric dentists and 4% of endodontists chose formocresol. The second question dealt with choices of
Fact that is a
carcinogen
contraindictes
its use
0%
18%
NaOCl
MTA
FeSO4
0%
30%
20%
40%
60%
40%
% of respondents who agreed or strongly agreed (P<.001)
80%
100%
% of respondents who chose each treatment option
Figure 2. Comparison by specialty of responses to the question: If cost were not

an issue, which is the recommended medicament for primary tooth pulpotomy?
agents for pulpotomy and asked, If cost were not an issue, which is the
recommended medicament for pulpotomies in primary teeth? MTA
was the overwhelming winner, with pediatric dentists and endodontists
in agreement, choosing it 85% of the time. Only 15% of pediatric dentists and 3% of endodontists chose formocresol (Fig. 2).
IPT in primary teeth was addressed in the pretest by asking attendees whether IPT was an acceptable substitute technique to replace pulpotomy to maintain vitality of cariously involved primary teeth. Endodontists were significantly (P .003) more likely at 47% to agree or
strongly agree, compared with pediatric dentists (32%). The postsymposium ARS used 5 questions to further explore opinions of attendees concerning the subject of IPT in primary teeth. IPT was offered as a
treatment option in cariously involved primary teeth in a question that
asked attendees to choose from a list the best treatment for a reversibly
inflamed primary molar with a large carious lesion encroaching on the
pulp. Forty-seven percent of pediatric dentists and 58% of endodontists
chose IPT (Fig. 3).
A second question asked attendees to respond to the statement
there is convincing evidence that IPT is as successful as a pulpotomy in
primary teeth with reversible pulpitis. Seventy-four percent of pediatric
dentists and 70% of endodontists agreed or strongly agreed. When
asked to respond to the statement there is convincing evidence that
primary teeth with reversible pulpitis should all be treated by step-wise
excavation for 3 months and only receive a pulpotomy if exposure
occurs on re-entry to remove remaining caries, attendees were divided
58%
47%
4%
2%
34%
30%
MTA
pulpotomy
FeSO4
pulpotomy
5%
20%
Endodon
Ped Den
Formocresol
NaOCl
pulpotomy
15%
10%
Chlorhexidine
IPC
37%
Endodon
Ped Den
Documented
danger to
patient
Calcium
Hydroxide
Formo
pulpotomy
0%
Endodon
Ped Den
0
1%
4%
20%
20%
40%
60%
% of respondents who chose each treatment option
Figure 1. Comparison by specialty of responses to the statements: The fact that

formocresol is a potential carcinogen should contraindicate its future usage in
pediatric pulp therapy; and when used as a primary tooth pulpotomy agent,
formocresol presents a documented danger to the patient.
S58
Seale and Glickman
Figure 3. Comparison by specialty of responses to the question: Which is the

best treatment choice for a reversibly inflamed primary molar with a large
carious lesion encroaching on the pulp?
Pulp Symposium
in their opinions. Forty percent of pediatric dentists and 63% of endodontists agreed or strongly agreed. A scenario question asked what
they would do for a 5-year-old child with a second primary molar in
which they had removed nearly all of the decay, knowing that if they
removed the remaining decay, a pulp exposure would be imminent.
More than half of the pediatric dentists (55%) and 71% of endodontists
would stop caries removal and do an IPT.
The final question about IPT in primary teeth in the postsymposium ARS asked attendees to choose from a list their main reason
for not performing an IPT in a primary tooth with reversible pulpitis.
The most frequently chosen answers in descending order by pediatric
dentists were pulpotomy is supported by evidence to have a better,
more predictable outcome (40%), there is inadequate reimbursement by third party payers for the procedure (32%), there is insufficient evidence to support its efficacy and success (19%), and I dont
believe IPT is successful in primary teeth (9%). Endodontists had
slightly different rankings of their choices, with there is inadequate
reimbursement by third party payers for the procedure (35%), pulpotomy is supported by evidence to have a better, more predictable
outcome (28%), there is insufficient evidence to support its efficacy
and success (18%), and I dont believe IPT is successful in primary
teeth (20%) (Fig. 4).
A second major area addressed by the speakers was management
of the carious lesion encroaching on the pulp of an immature permanent tooth, including those with an open apex. Two pretest questions
dealt with attendees opinions about IPT for these teeth. The first asked
for reactions to the statement indirect pulp capping is an acceptable
contemporary technique for maintaining the vitality of asymptomatic,
cariously involved young permanent teeth. Pediatric dentists were
overwhelmingly positive and significantly (P .001) more likely at
94% to agree or strongly agree, compared with endodontists (69%).
The second pretest question asked for reactions to the statement
symptoms of reversible pulpitis are contraindications to IPT in young
permanent teeth. Endodontists were significantly (P .02) more
likely to agree or strongly agree at 31% than pediatric dentists at 26%.
The post-symposium ARS used the exact same question to assess opinions after the presentations, and there was a significant difference in
how the attendees responded to this question by the end of the conference. When the endodontists pretest responses (31%) were compared
with their ARS responses, significantly fewer (P .001) agreed or
strongly agreed (8%) that symptoms of reversible pulpitis were a contraindication to IPT. The same trend was true for pediatric dentists, with
I don't believe
IPC works in
primary teeth
20%
8%
ARS postsymposium
7%
Endodon
Ped Den
31%
Presymposium
26%
0%
10%
20%
30%
40%
% of respondents who agreed or strongly agreed
Figure 5. Comparison by specialty of presymposium and postsymposium responses to statement: Symptoms of reversible pulpitis are contraindications to
IPT in young permanent teeth with open apices.
significantly fewer (P .001) at 7% agreeing or strongly agreeing that

symptoms of reversible pulpitis were a contraindication to IPT, compared with their pretest responses (26%) (Fig. 5).
Additional post-symposium ARS questions asked attendees opinions of the stepwise, 2-appointment version of IPT in permanent teeth.
One question asked about agreement with step-wise excavation as a
practical treatment modality for IPT in young permanent teeth. Pediatric dentists were significantly (P .03) more likely to agree or
strongly agree at 71%, compared with 59% of endodontists. Another
question asked attendees to choose from a list their main reason for not
performing stepwise excavation in a permanent tooth with an open
apex. Pediatric dentists chose in descending order: patient compliance
for 2 appointments might be questionable (52%); MTA pulpotomy is
supported by evidence to have a better outcome (20%); there is more
evidence to support the efficacy of the 1-step indirect pulp cap (18%);
and inadequate reimbursement by third party payers for the procedure
(10%). Endodontists expressed different preferences for their answers,
with their first choice being: MTA pulpotomy is supported by evidence to
have a better outcome (61%); patient compliance for 2 appointments
might be questionable (27%); there is more evidence to support the
efficacy of the one-step indirect pulp cap (6%); and inadequate reimbursement by third party payers for the procedure (6%) (Fig. 6).
Finally, attendees were asked to choose from a list their strongest
argument for performing stepwise caries excavation in a young permanent tooth. Responses from pediatric dentists included patient recall to
assess symptoms and vitality (41%); patient recall to assess evidence of
root maturation (31%); re-entry to ensure dentin remineralization
9%
18%
Insufficient IPC
evidence
Endodon
Ped Den
28%
Pulpotomy
better
40%
35%
Inadequate
reimbursement
32%
0%
10%
20%
30%
40%
% of respondents who chose each option
Figure 4. Comparison by specialty of responses to the statement: My main

reason for not performing a pulpotomy in a primary tooth with reversible
pulpitis.
6%
More evidence
for IPC
19%
48%
61%
MTA pulp better

evidence
20%
Endodon
Ped Den
6%
Inadeq
reimbursement
10%
27%
Questionable pt
compliance
52%
0%
20%
40%
60%
80%
Figure 6. Comparison by specialty of responses to the question: What is your

main reason for not performing stepwise excavation in a permanent tooth with
an open apex?
S59
Pulp Symposium
Low cost
Tx/Access to
care
Payment for
2nd visit
point whether they believed the future use of stem cells for pulp regeneration in permanent teeth would be an acceptable treatment. All of the
endodontists (100%) and 96% of pediatric dentists agreed or strongly
agreed.
3%
4%
6%
0%
41%
Pt recall/root
maturation
31%
Pt recall for
symptoms &
vitality
25%
14%
25%
Re-entry for
dentin remin
0%
Endodon
Ped Den
24%
10%
20%
30%
40%
50%
Figure 7. Comparison by specialty of responses to the question: Which of the

following would be your strongest argument for performing stepwise caries
excavation in young permanent teeth?
(24%); and provides low-cost treatment for patients needing access to

care (4%). Endodontists responded differently, listing in order: patient
recall to assess evidence of root maturation (41%); patient recall to
assess symptoms and vitality (25%); re-entry to ensure dentin remineralization (25%); payment to practitioner for a second appointment
(6%); and provides low-cost treatment for patients needing access to
care (3%) (Fig. 7).
Root canal revascularization via blood clotting in necrotic young
teeth has been reported in the literature through documented case
reports. A major aspect of this technique is usage of disinfecting irrigants such as sodium hypochlorite and chlorhexidine followed by the
placement of a special antibiotic mixture. Respondents opinions expressed through the ARS indicated that the vast majority of pediatric
dentists (87%) and endodontists (86%) agreed or strongly agreed that
this will be a viable treatment modality for permanent teeth with apical
periodontitis within the next 10 years. When asked to choose from a list
their major concerns about the procedures, pediatric dentists gave the
following responses in descending order: no major concerns at this
time (34%); current evidence is based primarily on case reports
(33%); unpredictability (18%); complex case selection criteria (13%);
and use of antibiotic paste within the canal (2%). Endodontists gave
slightly different ordering to their choices: no major concerns at this
time (32%); unpredictability (26%); current evidence is based primarily on case reports (16%); use of antibiotic paste within the canal
(14%); and complex case selection criteria (12%). The greatest disagreement between the 2 groups came when asked whether general
dentists should perform such procedures if properly educated and
trained. Pediatric dentists were favorably inclined, with 74% agreeing or
strongly agreeing compared with only 45% of endodontists.
Regeneration of pulp tissue involves tissue engineering therapies
by using stem cells, growth factors, and gene therapies. Although this
exciting concept is at its early stages of development, the American
Association of Endodontists has made regenerative endodontics and
revascularization high priority areas for further investigation. ARS questions asked for opinions about whether, from a public health perspective,
the future use of stem cells for pulp regeneration in permanent teeth would
be an acceptable treatment. Endodontists were more likely to agree or
strongly agree at 64%, compared with pediatric dentists at 37%. This
question had the highest percentage of uncommitted responders, with
33% of pediatric dentists and 21% of endodontists choosing neutral as
a response. Finally, the ARS asked for opinions from an ethical standS60
Seale and Glickman
Discussion
Evidence of a merging level of agreement between pediatric dentists and endodontists concerning important issues addressed by the
presenters was needed for the symposium planning committees goal to
be met for the collaborative production of pulp therapy guidelines.
Pretest responses indicated significant differences in opinions between pediatric dentists and endodontists concerning the acceptability
of most of the pulp therapy treatments under consideration. Beginning
with primary tooth pulpotomy agents and formocresol in particular, the
vast majority of pediatric dentists initially viewed formocresol pulpotomy as an acceptable pulp treatment for cariously involved primary
teeth. Although the pretest question did not ask respondents to choose
formocresol from among other pulpotomy agents, as did the ARS questions, 80% of the pediatric dentists favored its use at that point. Comparing the large number of positive responses initially to formocresol
with the ARS responses appears to indicate a changing attitude by pediatric dentists. In the post-symposium ARS questions, only 20% chose
formocresol as the best treatment for a primary tooth with reversible
pulpitis, and only 15% chose it as the recommended medicament for
primary tooth pulpotomy. The way the questions were phrased does not
allow direct comparisons between presymposium and postsymposium
responses, but these results certainly appear to suggest that formocresol
lost popularity. The trend away from formocresol would place pediatric
dentists more in agreement with endodontists, who did not favor formocresol either pre- or post-symposium.
There was a different trend apparent when pediatric dentists were
asked to comment on the safety of formocresol. Their responses to ARS
questions about its documented danger to the patient and whether its
potential as a carcinogen should contraindicate its use indicated that
they do not believe the case that formocresol is dangerous has been
made; only 5% of pediatric dentists and 18% of endodontists agreed.
They did appear convinced, however, that it will be replaced because it
is too controversial. In that respect, they were in complete agreement
with the endodontists. When applying these data to the production of
practice guidelines, it is probably most important that the 2 groups be
together in their opinions about the need to find and endorse a replacement for formocresol.
Continuing with the issue of primary tooth pulp therapy and with
respect to agents used for pulpotomy, post-symposium ARS data indicated that pediatric dentists and endodontists are unified in their overwhelming favor of MTA as the pulpotomy agent of choice. This finding is
interesting in light of the fact that there are few well-designed studies
examining MTA as a primary tooth pulpotomy agent, even though those
studies that are available report positive outcomes in favor of MTA. A
second option being examined to replace formocresol pulpotomy as the
treatment of choice for cariously involved primary teeth is IPT. Pretest
data indicated poor acceptance by the pediatric dentistry respondents,
with less than one third agreeing that it was an acceptable substitute
technique for pulpotomy. Their post-symposium ARS responses appeared to indicate a marked trend toward a more positive attitude about
IPT for primary teeth. More than half would stop caries excavation and
perform an IPT rather than a pulpotomy, and 75% agreed that there is
evidence that IPT is as successful as pulpotomy in primary teeth. Endodontists started out more positively than pediatric dentists about the
procedure for primary teeth and remained that way. The gap between
Pulp Symposium
them narrowed, however, as pediatric dentists more frequently expressed positive opinions in their responses after the symposium.
The issue where pediatric dentists and endodontists have the most
potential to both be treating the same kinds of teeth is the management
of cariously involved young permanent teeth with immature or open
apices. This is also the issue where there has previously been the most
divergence of opinion between the 2 groups concerning the appropriateness of IPT for these teeth. The pretest question responses bore out
this divergence. Almost all of the pediatric dentists (94%) opined that
IPT was an acceptable technique for the asymptomatic cariously involved young permanent tooth, compared with only approximately two
thirds of the endodontists.
Most pediatric dentists and endodontists, however, agreed to a
pretest question concerning reversible symptoms of pulpitis contraindicating IPT. By the end of the conference, their opinions about whether
such symptoms were a contraindication to IPT changed dramatically.
The post-symposium ARS question was worded exactly the same way as
in the pretest. Only 8% of endodontists and 7% of pediatric dentists
agreed that symptoms of reversible pulpitis were a contraindication to
IPT, indicating agreement on this important diagnostic issue.
The IPT procedure in permanent teeth presented at the symposium
was the variant called stepwise excavation. The variant involves 2 appointments and aims to eventually remove all affected dentin rather than
leave a small amount in the tooth as is performed in the 1-appointment
IPT. The procedure has not received wide exposure in the United States
because most of the publications on its use and success have appeared
in journals not widely read by the practicing community. The postsymposium ARS questions dealt mainly with the stepwise excavation
version of IPT and appeared to indicate similar favorable agreement on
its use in permanent teeth by both pediatric dentists and endodontists.
It is this topic of the more conservative, cost-effective treatment

modality of IPT for cariously involved young permanent teeth that is the
most important issue for which the 2 communities must reach agreement and formulate practice guidelines with common language and
intent. Many children and young adults who have the highest risk for
caries and lesions and who are candidates for IPT have either no payer
sources or sources with limited participation by individuals who perform endodontic treatment (general dentists and endodontists). In fact,
many cariously involved teeth in these young individuals have open
apices and are simply not candidates for complete endodontic treatment. They need to be treated with the more complex and lengthy
procedure of vital pulpotomy to obtain root closure followed by complete root canal treatment. The length of time involved in completing the
2 procedures might make them impractical for patients on some payment programs such as Medicaid, where their eligibility might vary
during the time period required. The issue of access to care mandates
that the 2 groups be unified in agreeing that IPT is an evidence-based
and appropriate pulp therapy modality for young permanent teeth with
immature or open apices.
Conclusions
In summary, what do endodontists and pediatric dentists agree on?
These survey data appear to indicate that the pediatric dentistry and
endodontic communities alike agree that formocresol will be replaced
as a primary tooth pulpotomy agent, that MTA is the overwhelming first
choice to take its place, that IPT in primary teeth holds hope as a
replacement for pulpotomy, and that IPT is an acceptable pulp therapy
technique for cariously involved young permanent teeth with open apices. In addition, both the endodontists and pediatric dentists believe that
pulp revascularization and regeneration will be potentially new exciting
treatment modalities in the near future.
S61

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Journal of Endodontics

July 2008, Volume 34, Number 7S

AAE and AAPD Symposium Overview: Emerging Science in Pulp Therapy

Diagnosis Dilemmas in Vital Pulp Therapy: Treatment for the Toothache Is

Regenerative Potential of Dental Pulp

Indirect Pulp Therapy and Stepwise Excavation

Is Formocresol Obsolete? A Fresh Look at the Evidence Concerning Safety Issues

New Age Pulp Therapy: Personal Thoughts on a Hot Debate

Contemporary Perspectives on Vital Pulp Therapy: Views From the Endodontists

AAE and AAPD Symposium Overview: Emerging Science

vidence-based best practices are yet to be established for the

JOE Volume 34, Number 7S, July 2008

N. Sue Seale, DDS, MSD

AAE and AAPD Symposium Overview

From the Department of Cariology and Endodontics,

Can We Obtain Consensus on Caries Pathology?

Some Opinions about the Approach to Dental Caries

JOE Volume 34, Number 7S, July 2008

An Update of Caries Pathology: The Non-cavitated

JOE Volume 34, Number 7S, July 2008

provides the possibility for understanding the subjacent pulpal-dentinal

Examples of Improved Laboratory Methods That Have

The Sequence of the Carious Development in

The Caries Process and Its Effect on the Pulp

Lesion Activity and Pulpal Response

blast necrosis (25), eventually followed by the presence of atubular

JOE Volume 34, Number 7S, July 2008

Understanding of Caries Pathology Creates the

JOE Volume 34, Number 7S, July 2008

The Caries Process and Its Effect on the Pulp

Diagnosis Dilemmas in Vital Pulp Therapy: Treatment for

From private practice of endodontics, Charlotte, North

JOE Volume 34, Number 7S, July 2008

Diagnosis of Pulpal Status in Primary Teeth

Figure 1. Silicone models of the pulps of 2 primary mandibular second molars.

JOE Volume 34, Number 7S, July 2008

ered. A child with systemic disease might necessitate different treatment

Diagnosis Dilemmas in Vital Pulp Therapy

canals indicative of cessation of root formation and pulpal necrosis; and

Near universal agreement exists that avulsed primary incisors

Diagnosis of Pulpal Status in Permanent

Figure 3. Internal resorption (arrow), as seen in this primary maxillary second

JOE Volume 34, Number 7S, July 2008

is greatly diminished. Loss of vitality before completion of root length

JOE Volume 34, Number 7S, July 2008

derstand or communicate accurately. Consequently, most diagnoses

Figure 5. Dark gray discoloration of the crown of this permanent maxillary

Diagnosis Dilemmas in Vital Pulp Therapy

JOE Volume 34, Number 7S, July 2008

JOE Volume 34, Number 7S, July 2008

hydroxide, except as a temporary canal disinfectant. The use of MTA as

Diagnosis Dilemmas in Vital Pulp Therapy

JOE Volume 34, Number 7S, July 2008

Regenerative Potential of Dental Pulp

From private practice, Philadelphia, Pennsylvania.

The Importance of Vital Pulp

The Pulps Regenerative Potential

Approaches to Treatment of Carious Exposure

JOE Volume 34, Number 7S, July 2008

Regenerative Potential of Dental Pulp

Figure 1. Histologic section of a pulp after a traumatic exposure 24 hours

Revascularization of Infected Pulp Space

JOE Volume 34, Number 7S, July 2008