Effects of Calcium Hydroxide-containing Pulp-capping Agents on Pulp Cell Migration,
Proliferation, and Differentiation
U. SCHRODER
Department of Pedodontics. University of Lund, School of Dentistry. 214 21 Malmo. Sweden
The findings from the recent literature on pulpal cell responses to the
application of calcium hydroxide to exposed pulps are described. The
effect of calcium hydroxide on healthy and inflamed pulp is discussed.
The effect of incorporation of calcium hydroxide in various pulp-capping
agents is presented.
The initial effect of calcium hydroxide applied to exposed pulp is the
development of a superficial three-layer necrosis. The beneficial effect of
calcium hydroxide is regarded as the result of the chemical injury caused
by the hydroxyl ions. limited by a zone offirm necrosis against the vital
tissue. and the toleration of calcium ions by the tissue. The firm necrosis
causes slight irritation and stimulates the pulp to defense and repair. The
observed sequence of tissue reactions is that which is expected when con-
nective tissue is wounded. It starts with vascular and inflammatory cell
migration and proliferation. to control and elimination of the irritating
agent. This is followed by the repair process. including migration and
proliferation of mesenchymal and endothelial pulp cells and formation of
collagen. When the pulp is protected from irritation. odontoblasts differ-
entiate. and the tissue formed assumes the appearance of dentin. i.e.. the
function of the pulp is normalized.
The mineralization of the collagen starts with dystrophic calcification
of both the zone offirm necrosis and the degenerated cells in the adjacent
tissue. leading to deposition of mineral in the newly-formed collagen. The
presence of calcium ions stimulates precipitation of calcium carbonate in
the wound area and thereby contributes to the initiation of mineralization.
Hard tissue formation in contact with some hard-setting calcium hy-
droxide cements has been reported. indicating a less-extensive initial
chemical injury than that produced by calcium hydroxide alone. The dif-
ferences in tissue response to various calcium hydroxide-containing ce-
ments are related to such factors as differences in pH and rates of release
of hydroxyl ions and calcium ions. Other components of the cements.
leading to different chemical reactions. may inactivate calcium hydroxide
or be noxious to the pulp and thereby interfere with healing. Decisive
factors for healing of the inflamed pulp are the degree of inflammation.
the time of irritation and infection. and the location of the exposure. The
effect of calcium hydroxide is not a factor.
Internal dentin resorption. observed in pulpotomizedprimary teeth capped
with calcium hydroxide, occurs when chronically inflamed pulp is present
at the time of treatment and/or is induced by improper wound treatment.
such as leaving a blood clot between the wound surface and the calcium
hydroxide.
Concerning the addition of corticosteroids to calcium hydroxide-con-
taining pulp-capping agents. no biologically acceptable histological re-
sults have been reported so far.
J Dent Res 64(Spec Iss):541·548, April 1985
Introduction.
The pulp consists of connective tissue. Difrere~ces compared to
other connective tissues include a lack of epithelium and the pres-
ence of odontoblasts. The pulp is a terminal organ in terms of
neural and vascular functions.
Ever since Hermann (1930) introduced calcium hydroxide to
dentistry, it has been used extensively in the treatme~t of exposed
pulps. When calcium hydroxide, with a pH of 12, IS applied .to
pulp tissue, a caustic effect is observed that leads to superficial
necrosis (Glass and Zander, 1949; Schroder and Granath, 1971a)
and, under certain conditions, to formation of a hard tissue barrier.
Many investigations have been performed to elucidate the well-
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© 1985 International & American Associations for Dental Research
known phenomenon of barrier formation following application of
calcium hydroxide to the exposed pulp.
The effect of calcium hydroxide has been studied in animals
and man for different indications, with different degrees of anti-
septic precautions, and with different operative techniques and
wound treatment. Nevertheless, there is still no fully accepted
explanation for the tissue reactions following application of cal-
cium hydroxide to pulp tissue regarding cell migration, prolifer-
ation, and differentiation. This paper is an attempt to compile
and analyze current knowledge of the subject.
Based on a thorough review of earlier literature, Schroder and
Granath (1971a) decided to perform a clinical and experimental
investigation with the aim of clarifying the effect of calcium hy-
droxide per se on amputated intact human dental pulp. The ma-
terial consisted of pre-molars which were to be extracted for
orthodontic reasons. By eliminating, as far as possible, interfering
factors - such as inflamed pulp, traumatic surgical technique,
contamination by micro-organisms, effects of local anesthesia,
and extra-pulpal blood clots - they were able to study histolog-
ically the tissue reactions leading to the hard tissue formation
following vital amputation and capping with calcium hydroxide
under optimal conditions. The intervals between treatment and
extraction varied from five min to six mo, in order to demonstrate
the sequence of tissue changes leading to wound healing.
The effect on healthy pulp tissue.
Calcium hydroxide per se: Initial reactions. - The initial tissue
reaction was a superficial three-layered necrosis, which was es-
tablished within an hour, with a zone of coagulation necrosis
demarcating against the vital tissue (Fig. I). These results agreed
rather well with those reported by Glass and Zander (1949).
The first effect of calcium hydroxide on pulpal cells was de-
struction. Thrombosis was seen within the zone of firm necrosis.
Schroder and Granath (1971a) explained the zones of the initial
necrosis in the following way: The superficial zone was a result
of application pressure and pressure due to edema in the inter-
mediate zone. The latter zone showed edema and liquefaction
necrosis, resulting from chemical injury. In this zone, tissue and
plasma proteins partly neutralized the hydroxyl ions, giving a
weaker chemical effect in the apical zone and resulting in a co-
agulation necrosis. The concentration of hydroxyl ions was con-
sidered to be responsible for these initial tissue changes.
The alkaline effect is immediate and short. Experiments on pulp
cells in vitro (Das, 1981; Hanks et al., 1983) showed that calcium
hydroxide was compatible with pulp cells, did not have any lasting
~egative effect on cell proliferation, and the pH reached the range
suitable for cell growth after about 24 hr.
Migration of inflammatory cells into the wound area occurred
between six hr and a few days after the treatment and resulted in
slight to moderate inflammation. Thereafter, migration and pro-
liferation of pulpal cells, most probably mesenchymal and endo-
thelial cells, were observed adjacent to the necrotic zone.
Matrixformation. - New collagen was observed in association
with the zone of firm necrosis after four days. After seven days,
the collagen tissue had cellular inclusions and lining marginal
541
542 SCHRODER
Fig. I-Ten min after application of Ca(OHh. Note the compressed su-
perficial zone. the edema in the intermediate zone. and the intravascular
coagulation zone against the vital pulp tissue; polychromic, x 109.
Fig. 2-Seven days after application of Ca(OHh. In contact with the
superficial necrotic zone, a broad zone of newly-formed collagen with
lining cells is seen; polychromic, x 109. [from Schroder and Granath
(1971), Odont Revy 22:379)
cells; it was also radiopaque (Fig. 2). Harrop and Mackay (1968)
made similar observations in rat pulp.
Fitzgerald (1979) observed an increased DNA synthesis in fi-
broblasts and endothelial cells in the monkey pulp, following ex-
posure and application of a hard-setting calcium hydroxide cement.
A corresponding histologically-demonstrable increase of these cell
populations was also seen. Torneck et al. (1983) made the same
observation when applying calcium hydroxide to pulp cells in vitro
and suggested that the cellular proliferation might be due to the
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© 1985 International & American Associations for Dental Research
J Dent Res April 1985
increase of available calcium ions. However, Uitto et al. (1975)
showed that the exposure, as such, of the human pulp led to an
increase in collagen synthesis, and that application of calcium
hydroxide meant an additional increase in collagen formation.
These studies concerning DNA synthesis in pulpal cells, following
application of calcium hydroxide, thus supported the microscop-
ical findings of increased cellular activity in connection with the
application of calcium hydroxide to pulp.
Mineralization of the barrier and cellular differentiation.-In
a TEM study (Schroder and Sundstrom, 1974) of a seven-day
case, spherical foci of mineralization in the deepest layer of the
initial necrosis and adjacent pulp tissue was seen. The foci coa-
lesced to an almost homogeneous calcification front against the
vital tissue (Fig. 3). Nearest the necrotic zone, degenerated pulp
cells were seen, with spherical bodies, and somewhat more api-
cally, the amount of collagen was increased. Membrane-bound
bodies, i.e., matrix vesicles (Fig. 4), were observed at this time
but not later, which indicated initial mineralization. This finding
agrees with earlier as well as later investigations concerning the
role of matrix vesicles in the initial calcification process in car-
tilage (Anderson, 1969), in dentin (e.g., Bernard, 1972; Eisen-
mann and Glick, 1972; Larsson and Bloom, 1973), in bone (Sela
et al., 1978), and in wound healing following pulpotomy of dog
pulp (Hayashi, 1982).
After one month, the barrier was found to consist of a coronal
layer of irregular bone-like tissue with cellular inclusions. The
pulpal part consisted of pre-dentin-like tissue and was lined with
odontoblast-like cells (Schroder and Granath, 1971a; Schroder,
1973a). In the TEM study (Schroder and Sundstrom, 1974), the
one-month barrier showed mineralization of the collagen-rich tis-
sue with cellular inclusions. Along the pulpal surface, cells were
seen which had a well-developed, rough-surfaced endoplasmic
reticulum. Adjacent parts of the barrier were pre-dentin-like, i.e.,
they contained densely packed collagen fibrils and cellular exten-
sions (Fig. 5).
Fig. 3-Seven days after applicationof Ca(OHh. N = superficialnecrotic
zone, P = vital pulp tissue, SC = spherical calcification, DC = degen-
erated cells with spherical bodies (S8), CC = calcification front; TEM x
10,600. [from Schroder and Sundstrom (1974). Odont Revy 25:57)
 Vol. 64 Special Issue EFFECTS OF CALCIUM HYDROXIDE ON PULP CELLS 543

Fig. 4--Seven days after application of Ca(OHh. Pulp tissue adjacent and
apical to the region in Fig. 3; NC = new collagen fibrils; C with arrows
= membrane-bound bodies, matrix vesicles; TEM x 12,600. [from Schroder
and Sundstrom (1974), Odont Revy 25:57]

After three months, the barrier was two-layered, consisting Cor-

onally of irregular tissue and pulpally of dentin-like tissue with
irregular tubuli, and lined by new odontoblasts. In the TEM study,
the three-month case confirmed the light-microscopic findings.
The tissue nearest the vital pulp was identical with pre-dentin and
contained densely packed colIagen fibrils and celIular extensions
(Fig. 6). Based on the structure of the cells, t.e., the well-devel-
oped, rough-surfaced endoplasmic reticulum, and the function of
the celIs and their location in direct contact with the barrier, it
was concluded that they were new odontoblasts. Thus, the TEM
study corroborated earlier results and contributed new knowledge
about the mineralization of the barrier. The mineralization started
with dystrophic calcification of the coagulation zone as welI as
the degenerated cells in the adjacent tissue, leading to deposits of
mineral in the vital tissue containing the newly formed colIagen.
The presence of matrix vesicles during the initial phase of min-
eralization indicated that the initial calcification was similar to
that seen in normal and pathological calcified tissues, as referred
to above.
When the surfaces of the hard tissue barriers were studied in
the scanning electron microscope (Schroder and Granath, 1972),
further confirmation of the light-microscopical studies was ob-
tained. The coronal surface resembled unorganized precipitate be-
fore demineralization and consisted of calcified necrotic tissue.
The appearance was the same after demineralization, but irregular
collagen structures were revealed in deeper parts of the surface
(Fig. 7). The pulpal surface 'Of the barrier contained tubular open-
ings whose morphology closely resembled the arrangement of col-
lagen bundles 'around dentinal tubuli in pre-dentin (Figs. 8 & 9).
Ulmansky et at (l'm~ reported similar findings.
In theabovernentloned studies, the differentiation of pulp cells
Fig. 5-One month afterapplication of Ca(OHh. Top:barrier withlining
cells, x 370. Bottom: lining cells with a well-developed, rough-surfaced
e~doplasmic reticulum (RER); NC = new collagen, PD = pre-dentin
WIth densely-packed collagen and cellular extension (CE); TEM x 8800.
[from Schroder and Sundstrom (1974), Odont Revy 25:57]
into odontoblasts could not be explained. The type of celI pre-
v~iling a! t~e site of operation might be responsible for the specific
differentiation, Cvek and Sundstrom (1974), in a TEM study of
the hard tissue barrier induced by calcium hydroxide and formed
apically of immature roots, observed a similar tissue response, a
two-layered hard tissue formation with calcified tissue nearest the
site of appl~cati~n of calcium h~dr?xide, followed apically by a
cem~ntu~.like tlssu.e. In ~e per~aplcal region, the migrating and
proliferating celIs differentiated into cementoblast-like cells.
The role of calcium.-The role of calcium ions is not well
understood. Calcium ions are well tolerated by the tissue and are
essential for cell proliferation, blood coagulation, mineralization,
and other functions of importance in this context.
Ear1i~r aut~radiogr~phic studies in animals (Sciaky and Pisanti,
1960.; Plsantl. and ~CI~y, 1964) showed that the calcium taking
part 10 the mineraltzation of the barrier came from the tissue and

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© 1985 International & American Associations for Dental Research

544 SCHRODER J Dm! Res April 1985

Fig. 7-Three months after application of Ca(OH2 ) . Coronal surface of

the barrier after demineralization; structureless tissue on the surface; col-
lagen structures and canal-like openings in deeper parts; SEM x 5600.
[from Schroder and Granath (1972), Odont Revy 23:211)

Fig. 6-Three months after application of Ca(OHh. Top: barrier with pre-
dentin zone and lining odontoblast-like cells; x 480. Bottom: pre-dentin
(PD) with cellular extensions (CE); TEM x 12,800. [from Schroder and
Sundstrom (1974), Odom Revy 25:57]

not from the calcium hydroxide used as a medicament. However,

Holland et al. (1982) used calcium, barium, and strontium hy-
droxides in histochemical studies of dog pulp following pulpotomy
and found similar results with the three pulp-capping agents, i.e.,
a necrotic zone followed by a layer of large von Kossa-positive
granulations, which were birefringent to polarized light. Subjacent
to and among these large granulations were many tiny von Kossa-
positive, but not birefringent, granules. The large granulations
consisted of calcium, barium, and strontium carbonates, which
indirectly proved that the calcium was derived from the calcium
hydroxide and not from the pulp tissue. These carbonate granu- Fig. 8-Dentin canal from pre-dentin in one young intact pre-molar; SEM
lations might play a role in stimulating the precipitation of the x 22,000. [from Schroder and Granath (1972), Odont Revy 23:211]
tiny von Kossa-positive calcium salt granulations in the same pulp
area, thus starting the mineralization of the collagen. Tomeck et sponse and should be taken into account when considering the
al, (1983) suggested that the presence of calcium ions in vivo initial mineralization following application of calcium hydroxide.
might have the ability to activate ATP, which is important in the
mineralization process. The ability of calcium ions to stimulate
cellular proliferation might also be important for the proliferative Calcium hydroxide-containing hard-setting ce-
tissue response to the initial injury by the surgical trauma and/or ments.
the medicament (Swierenga et al., 1976). The significance of the vehicle with which calcium hydroxide
Thus, calcium carbonate formation is an immediate tissue re- is mixed has been studied in several investigations. The release

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© 1985 International & American Associations for Dental Research

Vol. 64 Special Issue EfFECTS OF CALCIUM HYDROXIDE ON PULP CELLS
Fig. 9-Three months after application of Ca(OHh. Pulpal surface of the
barrier; SEM x 5800. [from Schroder and Granath (1972), Odont Revy
23:211]
of calcium hydroxide will depend on the composition and the
solubility in water of the material. Anthony et al. (1982), among
others, investigated the effect on the pH when calcium hydroxide
is mixed with camphorated parachlorophenol (CMCP), cresatin,
or saline. Because of chemical reactions between calcium hy-
droxide and cresatin, the pH decreased and reached acid values.
The reaction between calcium hydroxide and CMCP did not lead
to a decrease of pH. Shubich et al. (1978) studied the release of
calcium ions in vitro from five different calcium hydroxide-con-
taining capping agents. They found differences in the amount of
calcium available as well as in the percentage of calcium released.
Different calcium hydroxide-containing pulp-capping agents have
been tested experimentally on exposed human (e.g., Sawusch,
1963; Phaneuf et al., 1968; Stanley and Lundy, 1972; Negm et
al., 1980; Jerrell et al., 1984) and monkey pulp (e.g., Tronstad,
1974; Fitzgerald, 1979; Heys et al., 1980 and 1981; Cox et al.,
1982), and various pulpal responses have been observed. Some
materials proved to be ineffective in inducing wound healing, and
the result was chronic inflammation and necrosis. A correlation
between the inflammatory response and the barrier formation was
noted: The slighter the inflammation, the higher the frequency of
bridging. Furthermore, barrier formation was reported to occur in
close contact with two of the cements, i.e., without a visible
intermediate necrotic layer under the light microscope. This in-
dicates that less tissue damage occurred compared to that caused
by calcium hydroxide mixed in saline, but that sufficient damage
occurred to stimulate healing of the pulp wound. These two ce-
ments contain comparable amounts of calcium hydroxide and sa-
licylate esters. There are, however, differences in pH change and
content of tricalcium phosphate and calcium tungstate (de Freitas,
1982). In an in vitro study, Hanks et al. (1983) showed that the
rate of protein synthesis rose to control levels by the presence of
one of the cements, while the other cements depressed the rate of
synthesis. The differences in tissue response to different calcium
hydroxide-containing cements are thus related to such factors as
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© 1985 International & American Associations for Dental Research
545
different pH and varying release of hydroxyl ions and calcium
ions. Other components of the cements leading to different chem-
ical reactions might also inactivate calcium hydroxide or be nox-
ious to the pulp and thereby interfere with healing. Thus, there is
a great diversity of characteristics among the present calcium hy-
droxide cements, necessitating development of appropriate stan-
dards for pulp-capping cements of this type.
Conclusions.
The observed sequence of tissue reactions, following capping
with calcium hydroxide, is the same as that expected when con-
nective tissue is wounded. First, there are vascular and inflam-
matory cell migration and proliferation to control and eliminate
the irritating agent. Second, the repair process occurs, with mi-
gration and proliferation of mesenchymal and endothelial pulp
cells and formation of collagen, i.e., scar formation. When the
pulp is protected from irritation, the tissue formation decreases,
odontoblasts differentiate from pulp cells, and the tissue formed
assumes the appearance of dentin. In other words, the function of
the pulp is normalized.
Such a sequence of tissue reactions has also been reported in
experimental studies on germ-free rats where pulp wounds healed
with a hard tissue barrier, but without the influence of any active
medicament (Kakehashi et al., 1965). This might be explained as
a result of the operative trauma and the optimal environmental
conditions. Further, it should be noted that the rat pulp is more
reactive than the human pulp. Granath and Hagman (1971) left
gently amputated, healthy human pulps, without any extrapulpal
blood clots, covered with a waxed Teflonv disc, after which the
cavity was filled with a zinc phosphate cement for four weeks.
They observed only mild inflammatory changes, no signs of tissue
destruction, and no signs of hard tissue formation. In spite of the
favorable environmental conditions, the slight, almost negligible,
operative trauma proved to be insufficient to induce wound healing
with hard tissue formation. However, any medicament or opera-
tive procedure causing irritation as slight as or somewhat slighter
than the firm necrosis can be expected to stimulate the pulp to
such a response. Regarding the production of collagen, it could
hardly be a result of any unique property of calcium hydroxide as
mentioned by Mitchell and Shankwalker (1958).
The beneficial effect of calcium hydroxide is to be regarded as
the net result of: (I) the chemical injury caused by the hydroxyl
ions; (2) the firm, limiting, necrosis against the vital tissue; and
(3) the tolerance of calcium ions by the tissue.
The firm necrosis causes slight irritation of the pulp and stim-
ulates the pulpal cells to defense and repair. Some of the hard-
setting calcium hydroxide cements have been reported to induce
a hard tissue barrier in contact with the medicament. There is no
reason to believe, however, that the effect of such cements should
be biologically different from that induced by the calcium hy-
droxide as such. Owing to the composition of some of these ce-
ments, they lead to a less-extensive initial chemical injury, i.e.,
less serious tissue damage which, according to Tronstad (1974)
and Fitzgerald (1979), results in re-organization of the superficial
pulp layer, thereby permitting hard tissue formation in contact
with the medicament. This is not a consistent finding, however,
and the presence of a necrotic zone has also been reported with
these cements (Stanley and Lundy, 1972; Tronstad, 1974; Jerrell
et al., 1984).
Furthermore, the firm necrosis attracts minerals from the tissue
fluid and becomes calcified. This process and precipitation of
calcium carbonate granulations then initiate mineralization of the
newly-formed collagen and differentiation of new odontoblasts,
leading to the two-layered hard tissue barrier. Observations made
during wound healing after application of calcium hydroxide sup-
546 SCHRODER
port the opinion that the differentiation of new odontoblasts de-
pends on the types of pulpal cells and not on calcium hydroxide
as such.
The effect of calcium hydroxide on inflamed pulp
tissue.
Hitherto, only the effect on healthy pulp has been discussed.
The effect of calcium hydroxide on inflamed pulp tissue has been
suggested to be beneficial because of its high pH, which might
modify the environmental pH to levels more favorable for cellular
activity and thus for the repair process. Investigations on cariously
exposed pulp have not confirmed any positive effect of calcium
hydroxide (Nyborg, 1958). Tronstad and Mjor (1972) reported no
beneficial effect on healing when applying calcium hydroxide to
exposed monkey pulp with experimentally induced pulpitis. Cox
et al. (1982) studied the healing capacity of mechanically exposed
and orally contaminated monkey pulp capped with calcium hy-
droxide. After from zero to 24 hours' exposure to the oral envi-
ronment, and five weeks after application of calcium hydroxide,
the healing rate was favorable. Most pulp samples showed no, or
only a slight, inflammatory response, soft tissue re-organization,
and varying amounts of hard tissue formation. Pulp exposed for
seven days, and thereafter capped with calcium hydroxide, showed
a great variability in tissue responses. Complete healing as well
as pulp necrosis was noted. Presumably, this difference in re-
sponse did not depend on the medicament but on the state of the
pulp at the time of treatment, ranging from moderate inflammation
to total necrosis.
Following partial pulpotomy and capping with calcium hydrox-
ide of traumatically exposed healthy human pulp, Cvek (1978)
and Cvek and Lundberg (1983) reported very favorable clinical,
roentgenological, and histological results. The healing did not
seem to be influenced by such factors as exposure time, size of
exposure, or stage of root development. Histological studies of
accidentally exposed pulp in man (Smukler and Tagger, 1976)
and monkeys (Cvek et al., 1982; Heide and Mjor, 1983) showed
only superficial inflammation following exposure for up to seven
days. This was said to be due to the free exposure that permitted
salivary rinsing and excluded impaction of debris.
Thus, the environmental conditions are more favorable for the
accidentally exposed healthy pulp compared to the cariously ex-
posed, which is surrounded by carious tooth substance and im-
pacted food debris. These conditions favor further bacterial growth
and infection and lead to a variety of pulpal changes at the time
of treatment, thus explaining the different outcome of treatment.
A superficial inflammation is eliminated by the initial effect of
calcium hydroxide, leaving a pulp tissue capable of healing. On
the contrary, a more pronounced and widespread pulpal inflam-
mation will be enhanced by the inflammatory response initially
elicited by calcium hydroxide, thus inhibiting or delaying the heal-
ing process. In neither case can the result of treatment be ascribed
to the effect of calcium hydroxide.
The degree of inflammation, the time of irritation and infection,
and the location of the exposure must thus be regarded as decisive
factors for the healing of the inflamed pulp rather than the effect
of calcium hydroxide as such.
Another pulp cell response, internal dentin resorption, has been
reported to occur with high frequency in connection with pulpo-
tomy, particularly in primary teeth, and the use of calcium hy-
droxide as a medicament (Via, 1955). This tissue response is
generally ascribed to an effect of calcium hydroxide. Schroder
and Granath (1971b) suggested, in a study of pulpotomized pri-
mary molars, that internal resorption depended on the presence of
an extra-pulpal blood clot, between the wound surface and the
calcium hydroxide, that interfered with the healing. In order to
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© 1985 International & American Associations for Dental Research
J DellI Res April 1985
investigate the effect of an extra-pulpal blood clot on healing, an
experimental pulpotomy study was performed (Schroder, 1973b)
in which a blood clot was left between the wound surface and the
calcium hydroxide. Healing was found to be seriously impaired,
with chronic inflammation present in most cases, adjacent to mainly
incomplete barriers consisting of necrotic tissue and bone-like tis-
sue (Fig. 10). Dentin-like tissue was an inconsistent finding in the
barriers. All cases showed signs of the initial necrosis induced by
calcium hydroxide. Therefore, the reason for failure to heal was
not that the clot had prevented the initial effect of calcium hy-
droxide by neutralizing the hydroxyl ions. One possible expla-
nation might be that the chemotactic effect on polymorphonuclear
leucocytes of the fibrin in the clot potentiated the slight inflam-
matory reaction initially induced by calcium hydroxide. In studies
where a clot was left on the exposed human pulp and capped with
an inert material, no healing was reported (Masterton, 1966; Gran-
ath and Hagman, 1971). Furthermore, use of a gentle amputation
technique, avoidance of a blood clot on the wound surface, and
application of calcium hydroxide, in tissue contact with the wound
surface under therapeutic conditions in the primary dentition, pro-
vided a considerable decrease in the frequency of internal resorp-
tions (Schroder, 1978).
The blood clot on the surface of the pulp may also act as a
bacterial substrate which attracts micro-organisms and infection
to the wound area. Preliminary results from bacterial staining of
selected sections from histological tooth specimens showing pres-
ence of a blood clot and/or internal dentin resorption after pul-
potomy and capping with calcium hydroxide do not support such
an assumption (Schroder, unpublished data), but further studies
are needed.
Thus, internal dentin resorption of primary teeth does not seem
to depend on the effect of calcium hydroxide, but on chronically
inflamed pulp, i.e., infiltration of mononuclear inflammatory cells
that are present at the time of treatment or induced by improper
wound treatment (such as leaving a blood clot between the wound
surface and the calcium hydroxide).
Conclusion.
The therapeutic use of calcium hydroxide should be restricted
to conditions where the residual pulp tissue is judged to be without
Fig. 1O-0ne month after application of Ca(OHh, after leaving a blood
clot between the wound surface and Ca(OHh. From top: blood clot, rem-
nants of the superficial necrosis, discontinuous hard tissue barrier, necrotic
area in the adjacent pulp, and moderate cellular infiltration; Weigert-
vanGiesen, x 85. [from Schroder (1973), Odont Revy 24:257)
Vol. 64 Special Issue EFFECTS OF CALCIUM HYDROXIDE ON PULP CELLS
chronic inflammation, since calcium hydroxide has not been shown
to have any beneficial effect on chronically inflamed pulp tissue.
Calcium hydroxide in anti-inflammatory and anti-
infectious drugs.
Various corticosteroids have been incorporated into calcium hy-
droxide cements or pastes in order to prevent or reduce pulpal
inflammation and to relieve pain. Various indications for use of
these pulp-capping agents have been suggested, and differing
opinions about their effects have been expressed based on studies
on animal (Bhaskar et al., 1969; Gardner et al., 1971; Schmid et
al., 1974) and on human pulp samples (Barker and Ehrmann,
1969; Hansen, 1969; Schroeder and Asal, 1971; Ulmansky et al.,
197\). Corticosteroids cause degenerative changes in the tissue
(e.g., Uitto et al., 1975) and reduce the pulpal ability to form a
hard tissue barrier in the presence of calcium hydroxide. A two-
step procedure has therefore been suggested and performed on
inflamed pulp (Eifinger, 1968) and on healthy pulp (Schroeder
and Asal, 1971; Ulmansky et al., 1971). The anti-inflammatory
drug is used first, and, after some days, when the pulpal inflam-
mation is supposed to have disappeared, the calcium hydroxide is
applied to the hard tissue barrier to induce wound healing. So far,
positive clinical and roentgenological results have not been fol-
lowed by biologically acceptable histological findings when these
drugs have been used on chronically inflamed pulp. Further in-
vestigations under more standardized conditions are therefore needed
before any definite conclusions can be drawn about the use of
corticosteroids in the endodontic clinic.
There is little information regarding topically applied antibiotics
in combination with calcium hydroxide. The risk of a local cy-
totoxic effect and of hypersensitivity reactions must be taken into
consideration.
Areas for future research.
The role of calcium ions must be clarified in penetrating bio-
chemical studies, based on strictly standardized experiments on
human or comparable animal pulp tissue.
The induction mechanism for mineralization of the collagen
must also be investigated. Based on current knowledge, it may be
concluded that there must be a certain degree of stimulation to
induce deposition of mineral in the barrier, at least in human pulp
tissue. A firm necrosis exerts such a stimulatory action by attract-
ing minerals from the tissue and tissue fluids. Investigations on
monkey pulp with two commercial calcium hydroxide hard-setting
cements have reported hard tissue formation in direct contact with
the capping agent, indicating a less destructive but still sufficiently
strong stimulatory effect to induce mineralization. The great di-
versity of characteristics of the present calcium hydroxide cements
necessitates development of appropriate standards for pulp-cap-
ping agents of this type.
It must, however, be pointed out that testing of different pulp-
capping agents requires strictly controlled conditions, such as
elimination, as far as possible, of interfering factors such as in-
flamed pulp, traumatic surgical technique, contamination by mi-
cro-organisms, effects of local anesthesia, and extra-pulpal blood
clot.
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