You are on page 1of 7

Dental Materials Journal 2017; 36(1): 1–7

Review

Cytotoxicity and biocompatibility of resin-free and resin-modified direct pulp


capping materials: A state-of-the-art review
Liang CHEN and Byoung In SUH

Department of Research and Development, Bisco Inc., 1100 W Irving Park Road, Schaumburg, IL, 60193, USA
Corresponding author, Liang CHEN; E-mail: lchen@bisco.com, lchenchem@yahoo.com

Direct pulp capping is the placement of a dental material directly over exposed pulp to prevent dental pulp from dying and avoid
the need for root canal treatments. Calcium hydroxide and calcium silicates/mineral trioxide aggregates (MTA) have been commonly
used for direct pulp capping with great success clinically. In recent years, resin-modified calcium hydroxide and calcium silicates have
been developed with the advantages of precise placement, command set, and superior physical strength. As pulp capping materials
would be in direct contact with the pulp, the cytotoxicity and biocompatibility is of particular importance in order to avoid pulp
irritation and maintain pulp vitality. Therefore, this review article will summarize the cytotoxicity and biocompatibility of direct pulp
capping materials, particularly resin-modified materials.

Keywords: Cytotoxicity, Pulp capping, Calcium hydroxide, MTA, Calcium silicates

strength, better handling, easier to use and more


INTRODUCTION
precise placement. Although some resins released
Pulp exposures may result from caries removal during from dental restorations may be cytotoxic in sufficient
restorations, large caries, or trauma such as a sports concentrations4), resin-based materials, which are not in
injury. A pulp exposure could cause inflammation of the direct contact with dental pulp have been successfully
dental pulp (pulpitis), which may become irreversible, used in dental restorations for several decades. As pulp
causing pain, pulp necrosis, and eventually may require capping materials would be in direct contact with pulp,
an extraction or root canal treatment1). Clinically, the the cytotoxicity and biocompatibility is of particular
treatment of a pulp exposure includes a direct pulp importance in order to avoid pulp irritation and
capping or pulpotomy. A direct pulp capping is the maintain pulp vitality. The purpose of this review article
placement of a dental material directly over an exposed is to summarize the cytotoxicity and biocompatibility
pulp, to protect the dental pulp and preserve its vitality; of direct pulp capping materials, particularly resin-
a pulpotomy involves the removal of a portion of the pulp modified materials.
before the placement of a material. The goal of direct
pulp-capping is to prevent the dental pulp from dying CALCIUM HYDROXIDE AND RESIN-MODIFIED
and avoid the need for a root canal treatment. CALCIUM HYDROXIDE
A number of materials, such as zinc oxide eugenol,
glass ionomer/resin-modified glass ionomer, and Calcium hydroxide was introduced in dentistry in
adhesive systems, have been used in direct pulp capping, 1920s, and has been used with great clinical success
but they normally have poor clinical outcomes due to the as a direct pulp capping material for several decades2).
cytotoxicity to the dental pulp2). Calcium hydroxide has Calcium hydroxide is a strong base with a high pH of
a long track record of clinical success, and is considered approximately 12. It is slightly soluble in water, releasing
the “gold standard” of direct pulp capping materials2). In Ca2+ and OH− ions through the ionic dissociation5). The
recent years, calcium silicates, such as mineral trioxide high pH of OH− ion provides excellent antibacterial
aggregates (MTA) have generated great interest as direct properties, minimizing bacterial penetration to the
pulp capping materials. MTA is suggested to be superior pulp2). On the other hand, the high pH causes irritation
to calcium hydroxide and could be “a more predictable of the pulp tissue and develops a superficial three-layer
pulp capping material than calcium hydroxide”3). necrosis on exposed pulp, stimulating and forming
Although both calcium hydroxide and MTA have been mineralization directly against the necrotic zone6,7). The
well accepted clinically, they both have some Ca2+ ion provides a source of calcium for initiating and
disadvantages, including long-setting times (or lack of stimulating mineralization6,7). Three types of calcium
setting), poor handling, weak physical strength, high hydroxides have been used for direct pulp capping,
solubility, and/or gradual resorption. Resin-modified including one-paste non-setting calcium hydroxide, two-
calcium hydroxide and calcium silicates/MTA have paste self-setting calcium hydroxide, and resin-modified
been recently developed with the aim of improving calcium hydroxide.
the materials. They can be immediately light cured, Historically, calcium hydroxide was used in a
providing advantages including stronger mechanical powder form directly on exposed pulp. Currently,

Received Mar 22, 2016: Accepted Jul 11, 2016


doi:10.4012/dmj.2016-107 JOI JST.JSTAGE/dmj/2016-107
2 Dent Mater J 2017; 36(1): 1–7

pre-mixed calcium hydroxide pastes (one-paste non- such as UltraCal XS, caused an intense inflammatory
setting system) are commercially available, such as reaction and a coagulative necrosis at 7 days, but the
Calcicur (Voco, Cuxhaven, Germany) and UltraCal XS inflammatory process was significantly reduced at 30
(Ultradent Products, South Jordan, UT, USA) (Table 1). days9). This study also showed that different solvents
These products may also contain a radiopacifier, such as used to make calcium hydroxide pastes (water or
barium sulfate. The major disadvantages of one-paste polyethylene glycol), or different radiopacifiers (barium
calcium hydroxide systems include: lack of setting, weak sulfate, barium oxide, or zinc oxide) did not interfere in
physical properties, gradual resorption/dissolution, and their tissue reaction9). The clinical success rate of calcium
the so-called “tunnel effects” (the porosities in the newly hydroxide pastes for direct pulp capping over a 10-year
formed dentin)1). Although calcium hydroxide has been period of time was reported to be 59.0% (59 teeth total).
widely accepted in clinical practice, studies have shown The failures included subsequent root canal treatment
it may be cytotoxic due to high alkalinity. It was reported (15 teeth), pulp necrosis (1 tooth), asymptomatic apical
that Calcicur (21% cell vitality in 3-day MTT test) was periodontitis (2 teeth), clinical signs and symptoms (1
more cytotoxic than MTA or the negative control (26– tooth), and extractions (5 teeth)10). Another clinical study
35% cell vitality in the same test)8). Another study using showed that the success rate of direct pulp capping of
rat subcutaneous tissue showed that calcium hydroxide, 1,075 permanent teeth with calcium hydroxide was 80.1,

Table 1 Compositions of representative direct pulp-capping materials

Material Type Materials Compositions Manufacturer

Ultradent Products,
One-paste UltraCal XS Calcium hydroxide, water, barium sulfate South Jordan,
non-setting UT, USA
calcium
hydroxide Calcium hydroxide, water, cellulose derivatives Voco, Cuxhaven,
Calcicur
and barium sulfate Germany

Base paste: calcium phosphate, calcium tungstate, zinc


Dentsply
oxide, iron oxide pigments, 1,3-butylene glycol disalicylate
Tulsa Dental,
Dycal Catalyst paste: calcium hydroxide, zinc oxide,
Johnson City,
Two-paste zinc stearate, titanium oxide, iron oxide pigments,
TN, USA
self-setting N-ethyl-o/p-toluene sulphonamide
calcium
hydroxide Base paste: calcium hydroxide, zinc oxide, calcium oxide,
zinc stearate, N-ethyl-o(or p)-toluenesulphonamide Kerr, Orange,
Life
Catalyst paste: titanium dioxide, barium sulfate, methyl CA, USA
salicylate

Prisma VLC Dentsply


Calcium hydroxide, barium sulfate, UDMA, TEGDMA
Dycal Tulsa Dental
Resin-modified
calcium Ultra-Blend Calcium hydroxide, tricalcium phosphate, diurethane
Ultradent Products
hydroxide Plus dimethacrylate, TEGDMA

Calcimol LC Calcium hydroxide, fumed silica, UDMA, TEGDMA Voco

Dentsply
ProRoot MTA Portland cement, bismuth oxide
Tulsa Dental

Tricalcium silicate, dicalcium silicate, tricalcium aluminate, Angelus, Londrina,


MTA-Angelus
Calcium tetracalcium aluminoferrite, bismuth oxide PR, Brazil
silicates/MTA
Powder: tricalcium silicate, calcium carbonate
Septodont,
and zirconium oxide
Biodentine Saint-Maurdes-
Liquid: water, calcium chloride (accelerator)
Fosses, France
and modified polycarboxylate

Resin-modified Portland cement (calcium silicates), fumed silica, Bisco, Schamburg,


TheraCal LC
calcium silicates Bis-GMA, polyglycol dimethacrylate IL, USA

TEGDMA: Triethylene glycol dimethacrylate; Bis-GMA: bisphenol A diglycidyl methacrylate; UDMA: urethane
dimethacrylate
Dent Mater J 2017; 36(1): 1–7 3

68.0 and 58.7% after 1, 5 and 9 years, respectively11). polymerization, superior physical properties, minimally
Because of the disadvantages of high solubility affected by phosphoric acid, and low water solubility/does
and the lack of setting of one-paste calcium hydroxide not dissolve over time. It is known that un-polymerized
systems, a curable two-paste calcium hydroxide system resins/monomers are toxic to pulp cells17). For example,
has been developed and widely used in clinical practice. it was reported that Calcimol LC presented the higher
Commercial products include Dycal (Dentsply Tulsa cytotoxicity to MDPC-23 cells than the resin-free non-
Dental, Johnson City, TN, USA) and Life (Kerr, Orange, setting calcium hydroxide paste Calcicur, but it showed
CA, USA) (Table 1). Two-paste calcium hydroxide similar or lower cytotoxicity than two-paste self-setting
systems normally contain a base paste and catalyst paste. calcium hydroxide Dycal (vitality with MTT test after 72
One of the pastes contains active ingredient calcium h: Calcicur 21%, Calcimol LC 15%, Dycal 9%; number
hydroxide, and the other paste contains disalicylate. The of vital cells with Alamar blue tests after 72 h: Calcicur
setting reaction occurs between the calcium hydroxide 262000, Calcimol LC 33000, Dycal 30000). However,
and disalicylate, forming calcium disalicylate. Two- the composite resin presented mild to no toxic effects to
paste calcium hydroxide system may also contain the odontoblast-like MDPC-23 cells, as long as it was
other components, such as zinc oxide (a reactant, but polymerized18). A study showed resin-modified calcium
not a principle reactant), zinc stearate (accelerator), hydroxide VLC Dycal was not more cytotoxic than the
radiopacifier (calcium tungstate, or barium sulfate etc.), control calcium hydroxide. When VLC Dycal was cured
pigments, plasticizer and/or oil (to make a paste form), sufficiently with a longer curing time, the cytotocixity of
and/or an antibacterial agent. The setting time for a two- the resin in VLC Dycal disappeared. At the same time,
paste calcium hydroxide system is normally 2–6 min. OH− was released and started to cause cytotoxicity19). An
The physical strengths, such as compressive strength, in vitro study indicated that Ultra-Blend Plus had no
tensile strength, and modulus of elasticity, are usually increase of adult human dermal fibroblast cytotoxicity
low. Although two-paste calcium hydroxide systems levels, compared to negative control20). It is worth to note
have setting characteristics, they are still soluble and that a typical 70% of polymerization degree of conversion
could dissolve over time12). Two-paste calcium hydroxide of dimethacrylate monomers does not mean 30% of
systems have been shown to be more toxic than the non- free monomers. It means 30% of methacrylate groups
setting one-paste calcium hydroxide systems, possibly are still available for polymerization, but among those
due to the added toxicity of the additional components 30%, most of them are already in the polymer matrix.
such as disalicylate, accelerator, and/or plasticizer. For Approximately, only 9% of monomers are free monomers
example, in a 3-day MTT assay test with odontoblasts (i.e. both methacrylate groups in one monomer are un-
cells, two-paste calcium hydroxide (Dycal) demonstrated cured), and most of that 9% free monomers are located
the lower cell vitality rate than other types of direct inside the polymer matrix (would not leach out).
pulp capping materials, such as one-paste calcium
hydroxide and MTA8). Dycal also showed significantly CALCIUM SILICATES AND RESIN-MODIFIED
greater toxicity to human dental pulp cells than resin CALCIUM SILICATES
composites13). It was reported that the toxicity of the
two-paste calcium hydroxide system was not able to be Mineral trioxide aggregates (MTA), such as ProRoot
altered by six different growth factors (bone morphogenic MTA (Dentsply Tulsa Dental) has been widely used as a
peptide-2 and 7, fibroblast growth factor-2, epidermal direct pulp capping material (Table 1). MTA is a mixture
growth factor, transforming growth factor-β, and insulin- of tricalcium silicate, dicalcium silicate, and tricalcium
like growth factor-I) which have been shown to alter aluminate. Bismuth oxide (roughly 20%) is also included
pulp cell growth or differentiation. In contrast, some of in MTA for radiopacity. Because of the success of MTA,
the specific growth factors can make pulp cells resistant new versions of calcium silicate-based materials (such as
to the toxicity of composite materials13). The success Biodentine (Septodont, Saint-Maurdes-Fosses, France))
rate for Dycal in direct pulp capping was reported to be have also been developed (Table 1). The mechanism
73% (15 cases) after 6-month follow-up14). The success of action of MTA/calcium silicatse is similar to that of
rates for another two-paste calcium hydroxide (Life, calcium hydroxides. Calcium hydroxide is the by-product
Kerr) after 3-year direct pulp capping were reported as of the primary reaction (hydration) of MTA/calcium
92.2% with mechanical exposure and 33.3% with carious silicates with water. The hydration slowly results in a
exposure15). In another clinical study, the success rate gel which solidifies after several hours. MTA/calcium
for Life in 132 pulp caps was 37% (18% questionable and silicates are believed to have better sealing ability,
45% failure) in the 5-year group and 13% (80% failing biocompatibility and higher physical strength than
and 7% questionable) in the 10-year group16). calcium hydroxide1,21). For instance, the compressive
Light-curable resin-modified calcium hydroxide strength of Biodentine (calcium silicates) was reported
materials, such as Prisma VLC Dycal (Dentsply Tulsa to be 49 MPa after 7 days, while Dycal (two-paste self-
Dental), Calcimol LC (Voco), and Ultra-Blend Plus setting calcium hydroxide) was only 16 MPa21). Compared
(Ultradent Products) (Table 1) have been used for direct to calcium hydroxide, MTA/calcium silicates produce
pulp-capping. Compared to the conventional one-paste more uniform and thicker dentin bridge formations with
or two-paste calcium hydroxide systems, the resin- less inflammatory response and less necrosis of pulp
modified version has several advantages, including light- tissue22,23), possibly due to its ability to increase bone
4 Dent Mater J 2017; 36(1): 1–7

morphogenetic protein (BMP-2 protein) production24) capping. Compared to conventional calcium silicates/
and induce reparative dentinogenesis25). MTA materials, the resin-modified version has several
Many studies have demonstrated that MTA/calcium advantages, including immediate light-polymerization,
silicates were less toxic than calcium hydroxides. In preventing wash out of material, and superior physical
one study, MTA exhibited no cytotoxicity to rat dental properties30). One study showed that TheraCal LC
pulp cells after 72 h, whereas the two-paste calcium presented higher calcium release than MTA (ProRoot)
hydroxide (Dycal) killed almost all cells24). Another and calcium hydroxide (Dycal) throughout a 28-day test
study also suggested that calcium silicates (ProRoot period, while its solubility was significantly lower31).
MTA, MTA-Angelus (Angelus, Londrina, PR, Brazil), The pH profile of the medium conditioned by TheraCal
Biodentine) were less cytotoxic to odontoblasts cells LC was similar as that of ProRoot MTA (from 11 to
than two-paste calcium hydroxide (Dycal) and one-paste 8) during the 28-day test31). Similar to other types of
calcium hydroxide (Calcicur)8). An in vitro adult human calcium hydroxides or calcium silicates materials (Dycal,
dermal fibroblast cytotoxicity study showed that MTA Calcicur, Calcimol LC, MTA Angelus, and Biodentine),
materials (MTA-Angelus, Brasseler Endosequence Root TheraCal LC exhibited valuable antibacterial activity32).
Repair Putty) and resin-modified Ca(OH)2 (Ultra-Blend It was reported that TheraCal LC stimulated apatite
Plus) had cytotoxicity levels statistically similar to the formation after 24 h immersion in Dulbecco’s Phosphate
negative control, which was statistically less cytotoxic Buffered Saline (DPBS) solution33). It is worth noting
than the two-paste calcium hydroxide (Dycal)20). MTA that there is a major difference between TheraCal LC
also showed less toxic to human tooth germ stem cells and resin-modified calcium hydroxide (such as Calcimol
than Dycal26). An in vivo study (60 days) with dogs LC, VLC Dycal, and Ultra-Blend Plus). TheraCal
showed that none or mild inflammatory response LC contains a hydrophilic monomer/polymer matrix,
occurred beneath the pulpal wound capped with calcium while Calcimol LC, VLC Dycal, and Ultra-Blend Plus
hydroxide saline paste or Pro-Root MTA. MTA and contain a hydrophobic monomer/polymer matrix. The
calcium hydroxide presented no statistical difference hydrophilic matrix allows higher calcium and hydroxide
in terms of the pulpal response, but the teeth capped release, which are very important in protecting pulp
with calcium hydroxide had greater healthy pulp loss27). their ability to stimulate dentin formation and provide
One study compared MTA (ProRoot) with two-paste antibacterial action (high alkalinity), respectively6,31,33).
calcium hydroxide system (Dycal) when used as pulp- Both TheraCal LC and resin-modified calcium hydroxide
capping materials in 11 pairs of human teeth. After were shown to be more cytotoxic to murine odontoblasts
1 week, 2, 3, 4, and 6 months, MTA groups presented cells and human dental pulp stem cells than resin-free
less inflammation, less hyperaemia, less necrosis, more calcium silicates, such as Biodentine, MTA Angelus,
frequent odontoblastic layer formation, and thicker and ProRoot MTA, but they showed similar or lower
dentinal bridging (0.19–0.43 mm for ProRoot, and cytotoxicity than Dycal (vitality with MTT test after 72
0.02–0.15 mm for Dycal from 3–6 months) than the h: resin-modified materials: 14–15%, resin-free MTA
calcium hydroxide group23). Another in vivo study also 28–35%, Dycal 9%; number of vital cells with Alamar
demonstrated that MTA caused less inflammation, blue tests after 72 h: resin-modified materials: 33000–
less necrosis, and faster dentin bridge formation, than 35000, resin-free MTA 333000–533000, Dycal 30000)8,34).
calcium hydroxide Dycal28). An in vitro study from the However, this cytotoxicity might be due to the uncured
same paper demonstrated that calcium hydroxide monomers in the oxygen inhibition layer on the surface
(29.4% decrease of cell metabolic activity) caused of TheraCal LC test samples during sample preparation
higher cytotoxic effects to the MDPC-23 cells than MTA in the laboratory (exposure to air/oxygen). Research
(9.9% decrease)27). The success rate of MTA (ProRoot) studies suggested that uncured monomers/resins were
for direct pulp capping was reported to be 80.3% (195 toxic to pulp cells, while cured resins presented no
cases) after 2 year-recall, which was higher than that toxic effects17,18). However, it is worth noting that an
of calcium hydroxide (Life, Kerr) (68.5%, 181 cases)29). oxygen inhibition layer is not clinically relevant, since
Another clinical trial showed the overall success rate the pulp capping materials are placed inside teeth
for MTA (ProRoot) was 80.5% (170 teeth total), with with no oxygen present. It would be more clinically
33 failed teeth (19.5%) in 10 years10). The success rate relevant to remove the oxygen inhibition layer prior to
was higher than that of calcium hydroxide (59%). The cytotoxicity tests. Covering the materials with a Mylar
failure included subsequent root canal treatment (25 strip may reduce the oxygen inhibition layer, but it does
teeth), pulp necrosis (2 teeth), asymptomatic apical not completely remove it. A rinse of the surface with
periodontitis (4 teeth), and extraction (2 teeth)10). In ethanol or acetone may remove the oxygen inhibition
another paper, 98% of teeth (49 teeth total) capped layer. A 14-day in vivo study with rats indicated that
with MTA received favorable outcomes on the basis of the tissue responses and temporospatial localization
radiographic appearance, subjective symptoms, and cold of dentin matrix protein 1 and osteopontin in pulps
testing, over an observation period of nine years3). capped with TheraCal LC were similar to those capped
Similar to resin-modified calcium hydroxides, with calcium hydroxide or ProRoot MTA35). Compared
light-curable resin-modified calcium-silicate based to the resin-containing calcium hydroxide (Ultra-Blend
materials (such as TheraCal LC, Bisco, Schaumburg, Plus) and resin-modified Glass Ionomer (Vitrebond, 3M,
IL, USA) have been developed and used for direct pulp ESPE), the resin-containing calcium silicates (TheraCal
Dent Mater J 2017; 36(1): 1–7 5

LC) presented lower cytopathic effects to cultured pulp and the control (102–155 ppb) groups39). It is likely that
cells36). In a 4-week in vivo study on primate pulp capped TheraCal LC released less Al because of its lower
with 4 different materials, both the Portland cement solubility31) and shorter setting time (immediately light-
and TheraCal LC groups presented more frequent and cured) which reduces the chance of Al-release prior to
thicker hard tissue bridge formation than the GIC and the setting of the material39).
VLC Dycal groups37). A 2-year in vivo study demonstrated
that TheraCal LC had higher success rate (93.3%) for OTHER MATERIALS FOR PULP-CAPPING
direct pulp capping than antibacterial adhesive system
(Protect Bond, Kuraray) (83.3%) and Glass Ionomer Several other types of materials have been reported
cement (Fuji IX, GC) (66.6%)38). Another clinical study as direct pulp-capping materials, including zinc oxide
indicated that the success rate for TheraCal LC was not eugenol (ZOE), glass ionomer/resin-modified glass
significantly different from that for Dycal (~70% in 15 ionomer (GI/RMGI), and adhesive systems. Similar
cases) in direct pulp capping after 6-month follow-up14). to calcium hydroxide and calcium silicates, ZOE has
The success rate went up to 100% with a pre-treatment bactericidal effects. However, ZOE releases sufficient
of laser irradiation to the exposed pulp14). amounts of eugenol to be highly cytotoxic. A study
Calcium silicates/MTA-based materials and showed ZOE causes chronic inflammation, with no pulp
Portland cements contain trace amount of heavy healing and no dentin bridge formation after 12-weeks
metals, such as lead (Pb), arsenic (As), cadmium (Cd), direct pulp-capping, while calcium hydroxide showed
nickel (Ni), iron (Fe), copper (Cu), manganese (Mn), pulpal healing2). ZOE is not recommended for direct pulp
and zinc (Zn)39). It was reported that the MTA/Portland capping.
cements materials, such as CPM (Egeo, Buenos Aires, GI/RMGIs are less cytotoxic than ZOE. In addition,
Argentina), CPM Sealer (Egeo), Gray MTA-Angelus they are able to chemically bond to teeth. However,
(Angelus), ProRoot-MTA (Dentsply Tulsa Dental), and unlike calcium hydroxide/calcium silicates, GI/RMGIs
Gray Portland cement (Votorantim Cimentos, Cubatão, are acidic and lack anti-bacterial effects. This initial
SP, Brazil) contained arsenic levels higher than the acidity of GI/RMGI with a prolonged period at low pH,
ISO-recommended limit for water-based cements of 2 in addition to cytotoxicity of other components, may
mg arsenic/kg material (ISO 9917-1 standard). Only cause damaging effects on the pulp48). It was reported
White Portland cement (Cimento Rio Branco, Rio de that direct pulp-capping with RMGI showed chronic
Janeiro, RJ, Brazil), MTA-Obtura (Angelus) and White inflammation and no dentin bridge formation after 10
MTA-Angelus (Angelus) presented arsenic levels below months of restoration, while calcium hydroxide showed
the limit set in the ISO standard40). Other studies significantly better pulpal healing2). GI/RMGIs should
demonstrated that MTA-based materials, such as not be used for direct pulp capping.
ProRoot, MTA-Angelus, and/or Biodentine, contained Due to their excellent bonding ability, resin adhesive
low level of arsenic41-43), aluminium44), beryllium44), systems were suggested for pulp capping 20 years ago.
cadmium44), chromium43,44) iron44), and lead42,43). During However, similar to GI/RMGI, adhesives are acidic and
the long setting periods of MTA/calcium silicates, toxic have no bactericidal effects. Dental adhesives exhibited
chemicals could leach out, causing cytotoxicity. It was poor pulpal healing, chronic inflammation, and lack
reported that a calcium phosphate silicate-based sealer of dentin bridge formation, while the control calcium
(EndoSequence BC Sealer, Brasseler, Savannah, hydroxide demonstrated good pulpal healing, dentin
GA, USA) required 168 h to reach the final set, and it bridge formation and no or slight inflammation2,49-53).
exhibited severe cytotoxicity at 24 h, which gradually It is interesting to note that pulp capped directly with
decreased to moderate cytotoxicity over the 6-week non-acidic bonding resin or resin composite showed a
period45). Other evidence was shown that low levels of trend towards better pulp response than the ones capped
heavy metals like chromium, arsenic and lead leached with acidic primers or adhesives51). Dental adhesive
out from the solid MTA-based materials, such as should be avoided for direct pulp capping.
ProRoot and MTA-Angelus in water and simulated body
fluid41,46). It is important to note that “the dose makes CONCLUSIONS
the poison”. In the other words, all substances could be
poisonous, depending upon dosage47). The low levels of Based on this review, the following can be concluded
concentration were believed to be safe for use in clinical regarding direct pulp capping:
practice41,43). An in vivo study using rats compared the 1. Resin adhesive systems, zinc oxide eugenols, and
release of heavy metal (aluminium) from three different glass ionomers/resin-modified glass ionomers
type of calcium silicate-based materials: MTA Angelus, have been shown to have cytotoxic effects on
MTA Fillapex (containing MTA, salicylate resin, natural pulp cells. When used for direct pulp capping,
resin, bismuth oxide, and silica), and resin-containing they exhibited chronic inflammation, poor pulpal
TheraCal LC. After 6, 30, and 60 days of restorations healing, and lack of dentin bridge formation, and
with these materials, the levels of aluminium (Al) in should be avoided for direct pulp capping.
the plasma in which MTA Angelus (322–529 ppb) and 2. Calcium hydroxide-base products include one-
MTA Fillapex (299–468 ppb) were implanted, were paste non-setting calcium hydroxide systems,
around twice as high as Theracal LC (143–226 ppb) two-paste self-setting calcium hydroxide systems,
6 Dent Mater J 2017; 36(1): 1–7

and light-curable resin-modified calcium with calcium hydroxide. Quintessence Int 2011; 42: 165-171.
hydroxides. They all demonstrate antibacterial 12) Prosser HJ, Groffman DM, Wilson AD. The effect of
composition on the erosion properties of calcium hydroxide
properties and the ability to stimulate dentin
cements. J Dent Res 1982; 61: 1431-1435.
bridge formation. Calcium hydroxide has the 13) Furey A, Hjelmhaug J, Lobner D. Flow Line, Durafill VS, and
longest track record of clinical success and is Dycal toxicity to dental pulp cells: effects of growth factors. J
still considered the gold standard for direct pulp Endod 2010; 36: 1149-1153.
capping. Two-paste calcium hydroxide systems 14) Cengiz E, Yilmaz HG. Efficacy of erbium, chromium-doped:
contain toxic components other than calcium yttrium, scandium, gallium, and garnet laser irradiation
hydroxide, resulting in the higher cytotoxicity combined with resin-based tricalcium silicate and calcium
hydroxide on direct pulp capping: a randomized clinical trial.
than one-paste calcium hydroxide system. J Endod 2016; 42: 351-355.
3. Compared to calcium hydroxide, MTA/calcium 15) Al-Hiyasat AS1, Barrieshi-Nusair KM, Al-Omari MA. The
silicate materials have been shown to have less radiographic outcomes of direct pulp-capping procedures
cytotoxicity and better or comparable clinical performed by dental students: a retrospective study. J Am
outcomes for direct pulp capping. Dent Assoc 2006; 137: 1699-1705.
4. In vitro testing showed that light-curable resin- 16) Barthel CR1, Rosenkranz B, Leuenberg A, Roulet JF. Pulp
capping of carious exposures: treatment outcome after 5 and
modified calcium hydroxides or calcium silicates
10 years: a retrospective study. J Endod 2000; 26: 525-528.
did exhibit the higher cytotoxic effects than resin- 17) Jontell M, Hanks C.T., Bratell J, Bergenholtz G. Effects of
free version possibly because oxygen inhibition unpolymerized resin components on the function of accessory
layers were not first removed which may not be cells derived from the rat incisor pulp. J Dent Res 1995; 74:
clinically relevant since the tooth interface which 1162-1167.
these materials come into contact with is oxygen 18) Aranha AM, Giro EM, Hebling J, Lessa FC, Costa CA.
Effects of light-curing time on the cytotoxicity of a restorative
free. Light-curable resin-modified products have
composite resin on odontoblast-like cells. J Appl Oral Sci
the advantages of precise placement, command 2010; 18: 461-466.
set, superior physical strength, less solubility, 19) Kaga M, Seale NS, Oikawa K. Evaluation of cytotoxicity of
and reduced heavy metal release. Light-curable VLC Dycal in tissue culture for clinical use. Shoni Shikagaku
products with hydrophilic polymer matrix Zasshi 1989; 27: 313-316.
allowed the high release of calcium and hydroxide 20) Hirschman WR, Wheater MA, Bringas JS, Hoen MM.
ions. They are promising materials for dental Cytotoxicity comparison of three current direct pulp-capping
agents with a new bioceramic root repair putty. J Endod
treatment of direct pulp capping. 2012; 38: 385-388.
21) Natale LC, Rodrigues MC, Xavier TA, Simões A, de Souza
REFERENCES DN, Braga RR. Ion release and mechanical properties of
calcium silicate and calcium hydroxide materials used for
1) Komabayashi T, Zhu Q, Eberhart R, Imai Y. Current status pulp capping. Int Endod J 2015; 48: 89-94.
of direct pulp-capping materials for permanent teeth. Dent 22) Ford TR, Torabinejad M, Abedi HR, Bakland LK, Kariyawasam
Mater J 2016; 35: 1-12. SP. Using mineral trioxide aggregate as a pulp-capping
2) Hilton T. Keys to clinical success with pulp capping: a review material. J Am Dent Assoc 1996; 127: 1491-1494.
of the literature. Oper Dent 2009; 34: 615-625. 23) Aeinehchi M, Eslami B, Ghanbariha M, Saffar AS. Mineral
3) Bogen G, Kim J, Bakland L. Direct pulp capping with mineral trioxide aggregate (MTA) and calcium hydroxide as pulp-
trioxide aggregate. J Am Dent Assoc 2008; 139: 305-315. capping agents in human teeth: a preliminary report. Int
4) Yoshii E. Cytotoxic effects of acrylates and methacrylates: Endod J 2003; 36: 225-231.
relationships of monomer structures and cytotoxicity. J 24) Yasuda Y, Ogawa M, Arakawa T, Kadowaki T, Saito T. The
Biomed Mater Res 1997; 37: 517-524. effect of mineral trioxide aggregate on the mineralization
5) Mohammadi Z, Dummer PM. Properties and applications of ability of rat dental pulp cells: an in vitro study. J Endod
calcium hydroxide in endodontics and dental traumatology. 2008; 34: 1057-1060.
Int Endod J 2011; 44: 697-730. 25) Okiji T, Yoshiba K. Reparative dentinogenesis induced by
6) Chen L, Shen H, Suh BI. Bioactive dental restorative mineral trioxide aggregate: a review from the biological and
materials: a review. Am J Dent 2013; 26: 219-227. physicochemical points of view. Int J Dent 2009; 464280.
7) Schröder U. Effects of calcium hydroxide-containing pulp- 26) Guven EP, Yalvac ME, Sahin F, Yazici MM, Rizvanov AA,
capping agents on pulp cell migration, proliferation, and Bayirli G. Effect of dental materials calcium hydroxide-
differentiation. J Dent Res 1985; 64: 541-548. containing cement, mineral trioxide aggregate, and enamel
8) Poggio C, Ceci M, Dagna A, Beltrami R, Colombo M, Chiesa matrix derivative on proliferation and differentiation of
M. In vitro cytotoxicity evaluation of different pulp capping human tooth germ stem cells. J Endod 2011; 37: 650-656.
materials: a comparative study. Arh Hig Rada Toksikol 2015; 27) de Souza Costa CA, Duarte PT, de Souza PP, Giro EM, Hebling
66: 181-188. J. Cytotoxic effects and pulpal response caused by a mineral
9) Andolfatto C, da Silva GF, Cornélio AL, Guerreiro-Tanomaru trioxide aggregate formulation and calcium hydroxide. Am J
JM, Tanomaru-Filho M, Faria G, Bonetti-Filho I, Cerri PS. Dent 2008; 21: 255-261.
Biocompatibility of intracanal medications based on calcium 28) Swarup SJ, Rao A, Boaz K, Srikant N, Shenoy R. Pulpal
hydroxide. ISRN Dent 2012; 904963: 1-6. response to nano hydroxyapatite, mineral trioxide aggregate
10) Mente J, Hufnagel S, Leo M, Michel A, Gehrig H, Panagidis and calcium hydroxide when used as a direct pulp capping
D, Saure D, Pfefferle T. Treatment outcome of mineral agent: an in vivo study. J Clin Pediatr Dent 2014; 38: 201-
trioxide aggregate or calcium hydroxide direct pulp capping: 206.
long-term results. J Endod 2014; 40: 1746-1751. 29) Hilton TJ, Ferracane JL, Mancl L. Comparison of CaOH with
11) Willershausen B, Willershausen I, Ross A, Velikonja S, Kasaj MTA for direct pulp capping: a PBRN randomized clinical
A, Blettner M. Retrospective study on direct pulp capping trial. J Dent Res 2013; 92(7 Suppl): 16S-22S.
Dent Mater J 2017; 36(1): 1–7 7

30) Nielsen MJ, Casey JA, VanderWeele RA, Vandewalle KS. and Portland cement. Oral Surg Oral Med Oral Pathol Oral
Mechanical properties of new dental pulp-capping materials. Radiol Endod 2005; 99: 648-650.
Gen Dent 2016; 64: 44-48. 42) Camilleri J, Kralj P, Veber M, Sinagra E. Characterization
31) Gandolfi MG, Siboni F, Prati C. Chemical-physical properties and analyses of acid-extractable and leached trace elements
of TheraCal, a novel light-curable MTA-like material for pulp in dental cements. Int Endod J 2012; 45: 737-743.
capping. Int Endod J 2012; 45: 571-579. 43) Chang SW, Baek SH, Yang HC, Seo DG, Hong ST, Han SH,
32) Poggio C, Arciola CR, Beltrami R, Monaco A, Dagna A, Lee Y, Gu Y, Kwon HB, Lee W, Bae KS, Kum KY. Heavy
Lombardini M, Visai L. Cytocompatibility and antibacterial metal analysis of ortho MTA and ProRoot MTA. J Endod
properties of capping materials. Sci World J 2014; 181945: 2011; 37: 1673-1676.
1-10. 44) Kum KY, Kim EC, Yoo YJ, Zhu Q, Safavi K, Bae KS,
33) Gandolfi MG, Siboni F, Taddei P, Modena E, Prati C. Apatite- Chang SW. Trace metal contents of three tricalcium silicate
forming ability of theracal pulp-capping material. J Dent Res materials: MTA Angelus, Micro Mega MTA and Bioaggregate.
2011; 90 (Spec Iss A): 2520. Int Endod J 2014; 47: 704-710.
34) Bortoluzzi EA, Niu LN, Palani CD, El-Awady AR, Hammond 45) Loushine BA, Bryan TE, Looney SW, Gillen BM, Loushine
BD, Pei DD, Tian FC, Cutler CW, Pashley DH, Tay FR. RJ, Weller RN, Pashley DH, Tay FR. Setting properties and
Cytotoxicity and osteogenic potential of silicate calcium cytotoxicity evaluation of a premixed bioceramic root canal
cements as potential protective materials for pulpal sealer. J Endod 2011; 37: 673-677.
revascularization. Dent Mater 2015; 31: 1510-1522. 46) Schembri M, Peplow G, Camilleri J. Analyses of heavy metals
35) Yoshiba K, Takei E, Edanami N, Hinata G, Yoshiba N, in mineral trioxide aggregate and Portland cement. J Endod
Shigetani Y, Okiji T. Reparative dentinogenesis after pulp- 2010; 36: 1210-1215.
capping with a lightcured calcium silicate based material. J 47) Rozman K, Doull J. Paracelsus, Haber and Arndt. Toxicology
Dent Res 2015; 94A: 2794. 2001; 160: 191-196.
36) Hebling J, Lessa FC, Nogueira I, Carvalho RM, Costa CA. 48) Smith DC, Ruse ND. Acidity of glass ionomer cements during
Cytotoxicity of resin-based light-cured liners. Am J Dent setting and its relation to pulp sensitivity. J Am Dent Assoc
2009; 22: 137-142. 1986; 112: 654-657.
37) Cannon M, Gerodias N, Viera A, Percinoto C, Jurado 49) Cui C, Zhou X, Chen X, Fan M, Bian Z, Chen Z. The adverse
R. Primate pulpal healing after exposure and TheraCal effect of self-etching adhesive systems on dental pulp after
application. J Clin Pediatr Dent 2014; 38: 333-337. direct pulp capping. Quintessence 2009; 40: e26-34.
38) Petrolo F, Comba A, Scansetti M, Alovisi M, Pasqualini D, 50) Lu Y, Liu T, Li X, Li H, Pi G. Histologic evaluation of direct
Berutti E, Scotti N. Effects of light-cured MTA like material pulp capping with a self-etching adhesive and calcium
on direct pulp capping. Dent Mater 2014; 30s: e1-e180. hydroxide in beagles. Oral Surg Oral Med Oral Pathol Oral
39) Demirkaya K, Can Demirdöğen B, Öncel Torun Z, Erdem Radiol Endod 2006; 102: e78-84.
O, Çetinkaya S, Akay C. In vivo evaluation of the effects of 51) Accorinte Mde L, Loguercio AD, Reis A, Muench A, de Araújo
hydraulic calcium silicate dental cements on plasma and liver VC. Adverse effects of human pulps after direct pulp capping
aluminium levels in rats. Eur J Oral Sci 2016; 124: 75-81. with the different components from a total-etch, three-step
40) Monteiro Bramante C, Demarchi AC, de Moraes IG, adhesive system. Dent Mater 2005; 21: 599-607.
Bernadineli N, Garcia RB, Spångberg LS, Duarte MA. 52) Sübay RK, Demirci M. Pulp tissue reactions to a dentin
Presence of arsenic in different types of MTA and white and bonding agent as a direct capping agent. J Endod 2005; 31:
gray Portland cement. Oral Surg Oral Med Oral Pathol Oral 201-204.
Radiol Endod 2008; 106: 909-913. 53) Hebling J, Giro EM, Costa CA. Biocompatibility of an adhesive
41) Duarte MA, De Oliveira Demarchi AC, Yamashita JC, Kuga system applied to exposed human dental pulp. J Endod 1999;
MC, De Campos Fraga S. Arsenic release provided by MTA 25: 676-682.

You might also like