Article Wjpps 1443595849

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
Ramamoorthi et al.
World Journal of Pharmacy and Pharmaceutical Sciences
SJIF Impact Factor 5.210
Volume 4, Issue 10, 239-266.
Review Article
ISSN 2278 4357
CYTOTOXIC EFFECTS OF RESTORATIVE BIOMATERIALS ON

DENTAL PULP A SYSTEMATIZED REVIEW
Dr. Aparna Narvekar1, Dr. Andamuthu Sivakumar2, Dr. Murali Ramamoorthi3
1
MDS, Prosthodontist. Canada. 2MDS, Professor, Dept of Conservative Dentistry &

Endodontics, Vivekananda Dental College for Women, Namakkal, India.
3
Article Received on
09 Aug 2015,
Revised on 30 Aug 2015,
Accepted on 21 Sep 2015
MDS, MS. Canada.
ABSTRACT
Background: The most important cause of pulpal damage due to
restorative procedures/ materials is the toxic substances release from
the material. Understanding the cytotoxicity and various tests to
determine these effects helps in validating and better decision making
*Correspondence for
Author
Dr. Murali Ramamoorthi
MDS, MS. Canada
in
day to
day dental
practice,
Objectives:
To assess the
cytocompatibility of commonly used restorative materials and methods

to detect the cytotoxic effects on dental pulp. Methods: An electronic
database search [ MEDLINE, EMBASE, PUBMED] complimented by
journal database [Elsevier, science direct, SAGE] and manual search was conducted to
identify the reviews, systematic reviews and meta-analysis reporting cytotoxic tests or
cytotoxic effects of restorative materials pertinent to dental pulp. No language restrictions or
date were used initially. Results: The initial search provided 1572 titles, complimented with
285 titles from manual search and journal database. Following the final filtering process 69
studies were finally selected and included in this review. No systematic reviews or metaanalysis were found. Conclusion: Among the various cytotoxicity tests, dentin barrier test and
tooth slice culture methods are promising in detecting the cytotoxic effects of the dental
materials on pulp. Most of the currently used dental materials are not cyto compatible to pulp
if placed directly on pulp or the remaining dentin thickness is less than 0.5mm.
KEYWORDS: Biocompatibility, Dental materials, Invitro test, Cytocompatibility,
Cytotoxicity assay, Preclinical tests.
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INTRODUCTION
Restorative dental materials are the foundation for replacing diseased tooth or lost tooth
structure. The primary objective of using restorative material is to restore form and function.
All four major classes of biomaterials: Metals, Polymers, Ceramics, Composites are used for
restoration. Various classification systems are used to categorize the restorative dental
materials [based on use, fabrication, longevity]. The most commonly used classification of
restorative dental material is as follows
Table 1: Classification on Restorative materials
The selection of material for clinical use is based on mechanical, physical, biological
properties of the material intent to use. Three major factors are considered as foundation for
the success of restorative dental material, they are 1. Material properties, 2. Design, 3.
Biocompatibility.
Williams (2008) defined Biocompatibility as the ability of a biomaterial to perform its
desired function with respect to a therapy, without eliciting and undesirable local or systemic
effects in the recipient or beneficiary of that therapy, but generating the most appropriate
beneficial cellular or tissue response in that specific situation and optimizing the clinically
relevant performance of that therapy. Biocompatibility (lack of harmful effects) is a measure
of bodys biological response to a material used in specific application. It is a property of a
material interacting with its environment. The biological response to a material will change if
change occurs in the host or the application of the material.
Biocompatibility testing is an important part of obtaining regulatory body approval to market
any medical device or materials intent to use in human body. Three basic categories of testing
is done to ensure that the material is biocompatible, they are Cytotoxicity test, sensitization,
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irritation & intracutaneous reactivity. Among this three cytotoxicity is the most sensitive of
biocompatibility test. It is said that if a sample fails only one of Biocompatibility test 90% of
time cytotoxicity test fails. Cytotoxic effects is the quality of the material being toxic to cells.
It is the degree to which the material possess a specific destructive action on certain cells.
Cytotoxic effects of restorative dental materials are evaluated by series of test like
comparative analysis, surface degradation tests, cell culture tests, clinical testing in humans
and animal models. Several factors determine the cytotoxic effects of restorative materials.
This includes chemical nature of its components, physical nature of the components, type and
location of tooth that exposed to restorative material, duration of exposure, surface
characteristics, amount and nature of substances eluted from the material, oral & host
environment, and depth of the restoration. It is hypothesized that restorative materials may
directly affect plural tissue or play an auxiliary role in causing sub lethal changes to pulpal
tissues. The exact and complete biological effects of restorative material on dental pulp are
still not clear. Thus the objective of this report is to systematically review the literature that
described Cytocompatibility, of commonly used restorative biomaterials on dental pulp and
various cytotoxicity test to detect the cytotoxic effects.
MATERIALS AND METHODS
Review Protocol: The PICO question used for this systematic reviews was to investigate the
various cytotoxic effects, cytocompatibility, biocompatibility of restorative materials and
methods to test cytotoxicity. The focused review question used in this review was shown in
the table-1.
Search strategy: A comprehensive literature search published up to March 6th 2015 was
performed on the article databases: Ovid Medline [from 1946], EMBASE [from 1947]
PubMed. The search strategy used a combination of medical subject headings (MeSH) terms
and keywords for Medline, PubMed and EMBASE. The keywords and MeSH terms used for
the search were shown in the table-1.Further the main search was complimented by searching
in additional journal databases[ Elsevier, science direct, SAGE] to identify additional
literatures. In addition, a hand search strategy was performed by the authors from the citation/
reference list of the primary studies and reviews. No restrictions were applied in the search
initially. Later filters [reviews, systematic reviews, Meta-analysis] were used.
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Inclusion & Exclusion criteria: Systematic reviews, meta-analysis, reviews were included
in this review provided that the study presented or reported cytotoxic effects/cytotoxicity
tests/biocompatibility/biocompatibility test of restorative materials on dental pulp and the
study was reported in English and peer reviewed literature. Original research reports, nonEnglish
literature,
studies
reported
on
endodontic
materials/dental
implants/bleaching/whitening are excluded from this review. The comprehensive list of

included and excluded criteria were shown in table-2.
Table-2. Search Strategy
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Screening methods and data extraction: Data were extracted based on authors, y e a r of
publication, characteristics (type of restorative materials, type of tests, type of preclinical
models, main observation of the study, limitations of the study).
Study Quality Assessment: Selected systematic reviews, and meta-analysis were subjected
to AMSTAR [Assessing the methodological quality of systematic reviews] tools to
qualitatively score the reviews.
RESULTS
Table-3: Flow chart of search Methodology

The titles and abstracts of 1857 articles [initial search] were screened to assess their
suitability for full text review. After removing the duplicates [n= 421], 1168 articles were
excluded based on the title review. Thus 268 articles were eligible for the abstract screening.
Of those 115 articles were excluded based on the exclusion criteria. Among the 153 full text
articles reviewed, 84 were excluded [The details of the excluded articles and the reason for
exclusion were shown in supplemental table-2] leaving 69 full text articles to be included in
this review. The flow chart describing the screening process based on PRISMA guidelines
was shown in table -3. Due to the paucity of the systematic reviews and meta-analysis [0
studies] quality assessment was not undertaken. Because most of the selected studies are
narrative reviews no characteristic table is used in this literature review. Observations from
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the selected full text articles are synthesized and presented in discussion as follows:
cytotoxicity test, screening methods, material-cell interface, cell lines, endpoints and current
status.
DISCUSSION
Biocompatibility testing of any materials involves four sequential phases of evaluation. Phase
1and 2 [cytotoxicity tests] are considered as foundation test. The material which successfully
pass through this tests are considered for phase 3 and phase 4. Restorative dental materials
are constantly evolving throughout the years with dispelling several myths like acid etching
of vital dentin will devitalize underlying pulp to calcium hydroxide is the only pulp
protecting material. The pulpal response to any dental materials depends on various factors
like size and concentration of molecules, density, length, diameter of the dentinal tubules,
effect of temperature, remaining dentin thickness and longevity of the restoration. The life
span of commonly used restorative materials are shown in the table 4.
Table: 4 Longevity of the commonly used restorative materials
Dental Amalgam approximately 14 years
Cast gold 20 years
Ceramic crowns - 15 years
Ceramic inlays- 10 years
Gold foil, mat gold 24 years
Compomer- 10 years
PFM crowns-20 years
GIC- 8 years
Resin composites class1, 2: 10 years, class 3, 4,5: 15 years
On an average restorative materials are expected to be in service for at least ten years. Any
restorative materials that are placed adjacent to vital pulp can induce biological effects. These
effects are controlled by the components that are released from the material and the pulpal
response to those components. The fig-1 shows three possible ways a cytotoxins/ substance
release from restoration follows. The three possible pathways a restoration can Thus the
cytotoxicity effects of these materials on dental pulp is more vital in choosing an appropriate
restorative material for a given clinical situation. The details of various methods to determine
cytotoxicity/cyto compatibility, factors in choosing appropriate test and current status of the
commonly used restorative materials are discussed in the following paragraphs.
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Fig:1 Possible pathways a leached/ released components from a restoration can happen.
[black arrow- to pulp, blue arrow to oral cavity, green arrow- to periodontium]
1. Cytotoxicity tests
The term cytotoxicity is used to describe the cascade of molecular events that cause
functional and structural damage to cells. Throughout the years various assays and protocols
were developed to test the cytotoxic effects of biomaterials. The rationale behind doing a
cytotoxicity test is to determine how a material sample affects a particular cell type. The
primary criteria of these tests are the material must not affect the cell number, cell growth,
genetic integrity, membrane integrity, genetic expression and enzymatic activity of the cells.
The cytotoxicity tests are broadly categorized into viability assays, survival assays, metabolic
assays, transformation assays, and inflammation assays. Different assays currently in use are
showed in the table-5.
Table: 5 Various currently use assays that measure cytotoxic effects
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
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Assays based on membrane integrity.

Dye exclusion assays.
Dye uptake assays.
Chromium uptake assays.
Enzyme release assays.
Assays based on cellular respiration.
Assays based on radioisotope incorporation.
Assays using labelled nucleotides.
Assays using labelled phosphatases.
Assays based on calorimetric test.
Assays based on luminescence test.
Assays based on apoptosis
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Among the various cytotoxicity assays the most commonly used one is the tests that based on
membrane integrity. The membrane integrity can be evaluated by the uptake of dyes. Dye
such as naphthalene blue, trypan blue, erythrosine, neutral red, diacetyl fluorescin were
commonly used in such assays.
2. Screening methods
ISO 10993-5: 2009 presents the general guidelines for cytotoxic screening. The ISO
7405:2008 details the screening protocol pertinent to restorative dental materials. Based on
the regulatory body guidelines, four screening methods are recommended. They are 1. Direct
cell culture and culture extract testing [barrier screening assays], 2.Agar diffusion testing
[Tissue culture overlay test], 3.Filter diffusion testing [Millipore cellulose acetate method], 4.
Dentin barrier testing [Model cavity method].
About twenty different cell culture techniques were used to assess the cytotoxic effects of
biomaterials using the barrier screening assays. The main strategy behind this screening
method is to test the cytotoxicity of individual components of restorative material by placing
them directly onto cells in a monolayer culture for short duration usually more than 24 hours.
Using the dose response curve, the cytotoxic potential of each ingredient in the material is
calculated.
However the disadvantages in using this method are time consuming, technique sensitive,
troublesome in interpretation, subjective judgement so often not clinically relevant. The
direct use of cell and colony counting are the least reliable method to evaluate the cytotoxic
effects.
Agar diffusion testing is the most established testing methods since it is used for more than
50 years. The method uses permanent cell lines and test the ability of leachable components
of restorative material to diffuse through dentinal tubules. This is assessed by staining the
permanent cell lines with neutral red vital stain dye covered with a layer of agar and on which
the test material is incubated for 24 hours. Fig-2 shows the agar overlay test illustration. The
presence of leachable toxic substance is confirmed by the loss of dye within the cells. Though
the screening method costs less, the accuracy of the test depends on the material components
to diffuse through agar monolayer thus jeopardizing the outcome of test results.
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Fig:2 Agar overlay assay

In the Millipore cellulose acetate method 0.45m filters are used. On one side of the filter
cells are grown and on the other side test materials were placed. Based on the appearance of
filters at the material and cell interface, scoring were done based on ISO 7405 guidelines to
classify the cytotoxic response. The test method is based on enzyme activity. Glucose 6
phosphatase dehydrogenase, cytochrome oxidase, lactate dehydrogenase are used as assay
endpoints.
Dentin barrier test or model cavity method was based on the idea by Outwaitte et al [1974].
This method mimics the invivo oral environment and test the ability of the material to diffuse
through dentinal tubules. Thus ideal for testing cytotoxic effects of the material on dental
pulp. The first dentinal barrier test was devised by Tyass [1977]. The author simulated dental
cavity consist of Pyrex cylinder projecting through the lid of 30 mm petri dish. This method
later [1989] become British standard for testing restorative materials. The DBT [Dentin
barrier test] is the ideal test for evaluating the restorative material components that are
responsible for pulpal effects. This is highly recommended method to test the
cytocompatibility of any new restorative material. The schematic illustration of dentin barrier
test is showed in the figure3.
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Fig: 3 Illustrative diagram of dentin disk barrier test.

3. Material-Cell Interface in cytotoxicity test
There are three major possible ways to design the material-cell contact in invitro test. 1.
Direct, 2. Indirect or through an 3.eluate. In direct method cells can be placed onto
material/around the material/ materials onto cells. In the indirect method a barrier is used to
separate cells and test material. The schematic illustration of the direct and indirect design is
shown in the figure-4.
Fig-4: Material Cell Interface

The material-cell interface plays a major role in invitro cytotoxicity test outcomes and its
clinical importance. The classical example is Zinc oxide eugenol [ZOE] based cements. Early
invitro tests had reported that they are severe toxic to pulp. However it was disproved by the
successful clinical use in restoring cavities. The invivo pulpal studies reported low toxicity.
The non-direct placing of ZOE by using dentin barrier in invitro test demonstrated the
apparent low toxicity of this material. The design plays a vital role in implication of the
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invitro test. The following table-6 shows the recommended cell-material interface based on
the nature of test material.
Table: 6 Recommended cell- biomaterial interface
Biomaterial Form
Cell- material interface
Solid
Direct/indirect
Liquid, powder, fibers
Indirect
Based on the material-cell interface, the cytotoxicity tests can be categorized as direct tests
and indirect tests. The following table-7 shows the different tests used in each categories.
Table: 7 Cytotoxicity tests based on material-cell interface
Direct
MTT assay
NBT assay
XTT assay
WST assay
Alamar blue assay
Indirect
Agar overlay test
Millipore filter test
Dentin barrier test
4. Cell Lines used in cytotoxicity test: Two types of cell lines can be used to determine the
cytotoxic effects of the restorative biomaterials: primary cell lines [grow for only limited time
in culture] and permanent cell lines [grow more or less indefinitely in culture]. The choice of
cell line is a controversial and so far no clear recommendations are guidelines are available.
ISO 10993:1999 preferred the use of established cell lines like mouse fibroblasts [clone
L929], Balb/3T3, WI-38 for cytotoxicity tests.
Various commonly used cell lines are shown in following table-8
Table: 8 Commonly used cell lines in cytoxicity tests
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However these cell lines dont represent oral tissues. Ideally odontoblast cells should be used
for cytotoxicity screening of restorative materials, but it is very difficult in growing this cells
separated from dentin matrix. Various researches had attempted to transform primary oral
explanted cells in culture into permanent cell lines but their phenotypic resemblance are
questionable. The pulp fibroblasts are readily cultured, the drawback is their greater
variability from culture to culture in the means of growth characteristics and sensitivity to
cytotoxins. To overcome this existing drawbacks tooth slice culture method was introduced.
It has the benefit of maintaining identical experimental conditions similar to oral
environment. Further it allows to evaluate the restoration procedures and restoration
variables. So, far these variables were not able to be measured in animals and clinical trials.
Murray (2000) further suggested that tooth slice culture eliminates bacterial contamination
the factor that often exaggerate the toxic effects of test materials. However tooth slice culture
method requires further development and optimization.
5. Endpoints of cytotoxicity assays
Assay endpoints are categorized into metabolic impairment assay and membrane integrity
assay. Various endpoints measured are as follows: assessment of cell damage by
morphological means, measurement of cell damage, measurement of cell growth,
measurement of specific aspects of cell metabolism.
6. Current cytotoxic status of commonly used restorative materials
A. Amalgam: Amalgam is been used for restoration for more than 150 years despite various
controversies and speculations over these years. Dental amalgam are considered as either
inert or mildly irritating to dental pulp. These was demonstrated by manly 1942, schroff
1946, 1947, schour 1955, siberkweit 1955, masler 1956, welder 1956 by conducting
experiments in dogs, rats and humans.
Later cell culture screening tests demonstrated that free mercury in amalgam and copper is
toxic to cells. Various experiments concluded that mercury from amalgam in humans and
dogs do not reach pulp. Stanley in 1991 confirmed with his experiment that any pulpal
response to amalgam is due to the insertion procedure [pressure of condensation] rather than
the material itself. This was further confirmed by the usage tests, that the pulpal response to
amalgam in shallow, deep cavities that are appropriately lined shows minimal response and
amalgams rarely cause irreversible damage to the pulp. The current recommendation is
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cavities with 0.5mm to 1 mm remaining dentine on cavity floor should be appropriately lined
before placing amalgam restoration.
B. Resin Based composites.
Resin based composites are combination of organic and inorganic phase. Invitro cytotoxicity
tests had demonstrated moderate cytotoxic effects. Composite materials has shown chronic
inflammatory response in invivo and cytotoxic in cell culture. Past two decades the pulp and
dentin reactions to composites are attributed to bacterial leakage rather than cytotoxic effects.
Pulp studies of individual components by Stanley et al showed slight but varied response.
Though early researches showed severe pulp reaction to composites, most studies after
1985s shown no or moderate reaction. Almost all of the major components of composites are
cytotoxic in invitro tests. But they are tested as bulk monomer. Histologic studies confirmed
that even low concentration of residual monomer molecules show moderate degree of
cytotoxicity on pulpal tissues. Goldberg (2008) confirmed that low to moderate pulpal
inflammatory response after 3 days to chemically and light cure resin composite in cavities
with approximately 0.5mm remaining dentin thickness. However the reaction was not seen
after 5-8 weeks. Further it is accompanied by reparative dentin formation. Invivo studies in
recent past had suggested that complete or incomplete cured resins caused little irritation to
pulp if an adequate marginal seal is present. The cytotoxicity of the cured composite is based
on the extent of release of these components from the composites and dentin barrier
effectively reduces the ability of the released components to reach the pulp. Current
recommendation is to place a protective liner or bonding agent if resin composite material is
used as restoration.
C. Glass ionomer cement
Glass ionomer cement [GIC] were first introduced in dentistry since 1969. The
cytocompatibility and stability over time makes this material to be used in neurologic surgery
[fixing ossicular chain prosthesis, cochlear implants and repair of tegmen and posterior canal
wall defects]. Screening tests shown that freshly prepared GIC is mildly cytotoxic but its
effects reduced over the time. High molecular sized of the polyacrylic acid makes it
impossible to diffuse through dentine. Studies shown that GIC appears to be bland to pulp
when used as restorative material but induce pulpal response when used as luting agents. The
viscosity and hydraulic pressure are attributed to this difference. Light cured GIC [resin
modified GIC]has been introduced by including bis-phenol-A-glycidyl methacrylate[BiS-
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GMA] or other monomers/oligomers as pendant chains .Any modifications of GIC is shown

to be cytotoxic. Several studies demonstrated that Metal modified GIC, Resin modified GIC
leaches and diffuse through dentinal tubules and reach dental pulp cells. The magnitude of
damage to pulp cells is inversely related to the remaining dentin thickness between the pulp
tissue and the material. Stainlawski in 1999 further analyzed the reason for the cytotoxic
effects of metal reinforced GIC and confirmed that Zinc along with copper and silver are
responsible for cytotoxicity. Lan WH in 2003 compared nine types of GIC cultured on human
dental pulp cells and confirmed that resin modified GIC is more toxic than conventional GIC.
However in 2003 and 2007, Costa CAS demonstrated with an invivo study in human teeth
that resin modified GIC liner didnt cause any pulpal response in deep class V cavity. In any
case GIC or modified GICs should not be placed directly on living pulp tissue.
D. Zinc oxide eugenol cement [ZOE]
Both invivo and invitro test proved that eugenol released from zinc oxide cement fixes the
cell, depresses cell respiration and reduces nerve transmission upon direct contact. These
effects are dose dependent and the magnitude of diffusion through dentinal tubules. I t forms
temporary seal against bacterial invasion. It cause slight to moderate inflammatory reaction in
the first week followed by reparative dentin formation within 5-8 weeks. It has anodyne and
obtundant effect on pulp, facilitates pulpal healing but it is irritant on direct contact.
E. Zinc polycarboxylate
Zinc polycarboxylate shows similar pulpal response like ZOE. However reparative dentin
formation is very minimal. Concentration of polyacrylic acid above 1% is cytotoxic in invitro
test but long term invivo test failed to prove this claim. It was hypothesized that buffering and
protein binding might neutralize these effects in long term.
F. Zinc phosphate
It is a combination of zinc and orthophosphoric acid. Invitro tests shown that zinc phosphate
cement exhibit strong to moderate cytotoxic effects on pulp but decrease with time. Focal
necrosis were seen in test that injected zinc phosphate cement into rat dental pulp. The
cytotoxic effects are mainly attributed to its initial low p H [4.2 in 3 min]. Current
recommendation is to use a protective liner/varnish beneath the zinc phosphate restoration.
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G. Bonding agents
It is well established that dentin is an efficient buffer of protons, as a result most of the acid
never reaches the pulp. This also depends on remaining dentine thickness and 0.5mm is
considered as an adequate remaining dentin thickness [RDT]. Although acids do not reach
pulp invitro studies demonstrated that bonding agents may penetrate up to 0.5 mm into
dentine thus causing significant suppression of cellular metabolism for 4 weeks after its
application. Smith et al in 1986 confirmed that 40% of orthophosphoric acid remained in
tooth even after rinsing. Thus the cytotoxic effects of acid etching and bonding agents on
dental pulp depends on following factors: remaining dentin thickness, degree of etching and
strength of acid.
H. Liners, varnishes
Generally liners are high alkaline pH (>12) suspension. The high pH leads to extreme
cytotoxicity in invitro tests. The initial pulp tissue reaction to this high alkaline pH is the
necrosis to a depth of >1mm. within weeks to months those necrotic zone is replaced by
dystrophic calcification and act as a stimulus for dentine bridge formation. The high pH
provides bactericidal activity and promotes tertiary dentin formation if used as pulp capping
agents.
I. Other restorative materials
Metal ions of chromium, cobalt, copper, mercury, tin, nickel and zinc cause cell death
/damage in invitro tests. All these metals are used in dental material as base metal alloys,
dental amalgam, titanium alloys. However these metals are not found as metal ions in
restorations. Further alloying of these metal reduces ion production. The insertion of gold foil
may result in pulpal reaction but this is because of condensation force, thermal conductivity,
dehydration of dentinal tubules, and micro leakage not because of cytotoxic effects.
Conventional dental ceramics are considered to be most inert of all dental material. The
pulpal response to inlays, onlays, crowns, bridges are determined by the luting agents used
not by the components of casting alloys /ceramics. Almost all luting agents are cytotoxic in
invitro tests but with variable differences.
Altering water: powder ratio, viscosity, are some of the measures advised to decrease these
cytotoxic effects on dental pulp. Pulpal protection is mandatory if acrylic resin cement is
used.
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Limitations
The major drawback with classical invitro cytotoxicity test is it does not reflect the long term
in vivo behavior of restorative material. Many factors affects the release of components from
restorative material such as bacterial metabolic products, water, enzymes, polar and non polar
solvents. Current cytotoxicity tests are not exhaustive enough to accommodate all or some of
the confounding factors mentioned early. Improving these limitations along with
comprehensive database to identify the cytotoxic effects of individual components of
commonly used dental materials would be an attractive option for material scientist to design
new and effectively redesign existing questionable restorative materials.
Clinical guidelines
Based on the literatures reviewed, the following guidelines are suggested. However it should
be followed with caution as it is based on narrative reviews not systematic review or Metaanalysis.
Table-9 Flowchart for clinical guidelines in using restorative biomaterial

7. CONCLUSION
From the literatures eugenol, BiS-GMA, TEGDMA, HEMA, BPA, UDMA, gold, copper,
cobalt, mercury, tin, nickel, zinc, chromium, and ortho phosphoric acid are considered to be
cytotoxic to dental pulp if placed directly. Acid dental materials have the ability to
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demineralize dentin and possibly increases biological effects on dental pulp. Remaining
dentin thickness, dentine permeability, duration of exposure influences the cytotoxic effects
of the restorative dental material on dental pulp. Tooth slice culture assay shows promising in
determining the cytotoxic effects of restorative materials pertain to dental pulp. With the
revolution of new materials around, immortalized odontoblasts, developing new cell lines,
three dimensional tooth slice culture, are some of the interesting avenues to be explored to
improve the reliability of current invitro cytotoxicity tests. Despite various limitations,
current invitro cytotoxicity tests guided us in providing materials for safe clinical use.
Knowing the cytotoxic effects of each components helps the clinician in proper decision
making to choose appropriate pulp friendly restorative material.
REFERENCES
1. Schmalz G. Determination of Biocompatibility. Biocompatibility of Dental Materials:
Springer Berlin Heidelberg; 2009; 13-43.
2. Chapter 6 - Biocompatibility and Tissue Reaction to Biomaterials. In: Powers RLSM,
editor. Craig's Restorative Dental Materials (Thirteenth Edition). Saint Louis: Mosby;
2012; 109- 33.
3. ISO 7405, 1997 ISO 7405, 1997. International Standard 7405 Dentistry Preclinical
evaluation of biocompatibility of medical devices in dentistryTest methods for dental
materials. International Organization for Standardization, Geneva, 1997
4. ISO 10993 part 12, 1996 ISO 10993 part 12, 1996. International Standard 10993
Biological evaluation of medical devices Part 12: Sample preparation and reference
materials. International Organization for Standardization, Geneva, 1996
5. ISO 10993 part 5, 1999. ISO 10993 part 5, 1999. International Standard 10993
Biological evaluation of medical devicesPart 5: Tests for in vitro cytotoxicity. British
Standard Institute, 1999.
6. ISO 7405, 2008 ISO 7405, 2008. International Standard 7405 Dentistry Preclinical
evaluation of biocompatibility of medical devices in dentistryTest methods for dental
materials. International Organization for Standardization, Geneva, 2008.
7. ISO 10993 part 5, 2009. ISO 10993 part 5, 2009. International Standard 10993
Biological evaluation of medical devicesPart 5: Tests for in vitro cytotoxicity. British
Standard Institute, 2009.
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8. engn A, Yaln M, lker HE, ztrk B, Hakk SS. Cytotoxicity evaluation of dentin
bonding agents by dentin barrier test on 3-dimensional pulp cells. Oral Surgery, Oral
Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2011; 112(3): e83-e8.
REFERENCES
A. Included articles
9. al-Dawood, A. and A. Wennberg, Biocompatibility of dentin bonding agents. Endod Dent
Traumatol, 1993; 9(1): 1-7.
10. Barnett, F., Pulpal response to restorative procedures and materials. Current Opinion in
Dentistry, 1992; 2: 93-8.
11. Ben-Amar, A. and H.S. Cardash, The fluid-filled gap under amalgam and resin composite
restorations. Am J Dent, 1991; 4(5): 226-30.
12. Bergenholtz, G., Evidence for bacterial causation of adverse pulpal responses in resin
based dental restorations. Crit Rev Oral Biol Med, 2000; 11(4): 467-80.
13. Bouillaguet, S. and J.C. Wataha, Future directions in bonding resins to the dentine-pulp
complex. J Oral Rehabil, 2004; 31(4): 385-92.
14. Browne, R.M., Animal tests for biocompatibility of dental materials--relevance,
advantages and limitations. J Dent, 1994; 22(20: S21-4.
15. Brune, D. "Metal release from dental biomaterials." Biomaterials.1986; 7(3): 163-175
16. Costa, C.A., J. Hebling, and C.T. Hanks, Current status of pulp capping with dentin
adhesive systems: a review. Dent Mater, 2000; 16(3): 188-97.
17. Cox, C.F., Effects of adhesive resins and various dental cements on the pulp. Oper Dent,
1992; Suppl 5: 165-76.
18. Cox, C.F. and A.A. Hafez, Biocomposition and reaction of pulp tissues to restorative
treatments. Dent Clin North Am, 2001; 45(1): 31-48; v.
19. Cox, C.F. and S. Suzuki, Re-evaluating pulp protection: calcium hydroxide liners vs.
cohesive hybridization. J Am Dent Assoc, 1994; 125(7): 823-31.
20. Cox, C.F., et al., Technique sensitivity: biological factors contributing to clinical success
with various restorative materials. Adv Dent Res, 2001; 15: 85-90.
21. de Souza Costa, C.A., J. Hebling, and C.T. Hanks, Current status of pulp capping with
dentin adhesive systems: a review. Dental Materials, 2000; 16(3): 188-197.
22. de Souza Costa, C.A., et al., Methods to evaluate and strategies to improve the
biocompatibility of dental materials and operative techniques. Dental Materials, 2014;
30(7): 769-784.
www.wjpps.com
Vol 4, Issue 10, 2015.
256
Ramamoorthi et al.
23. Fratamico, F.C. and C. Prati, Biocompatibility of dentinal adhesive systems in

conservative dentistry]. Dental Cadmos, 1990; 58(4): 66-70.
24. Geurtsen, W., Biocompatibility of resin-modified filling materials. Crit Rev Oral Biol
Med, 2000; 11(3): 333-55.
25. Gilmore, H.W., Recent consensus on the pulpal reaction to restorative materials. The
Journal of prosthetic dentistry, 1970; 23(4): 434-440.
26. Goldberg, M., In vitro and in vivo studies on the toxicity of dental resin components: a
review. Clin Oral Investig, 2008; 12(1): 1-8.
27. Habsha, E., The incidence of pulpal complications and loss of vitality subsequent to full
crown restorations. Ontario dentist, 1998; 75(1): 19-21, 24.
28. Hanks, C.T., J.C. Wataha, and Z. Sun, In vitro models of biocompatibility: A review.
Dental Materials, 1996; 12(3): 186-193.
29. Hilton, T.J., Can modern restorative procedures and materials reliably seal cavities? In
vitro investigations. Part 2. American journal of dentistry, 2002; 15(4): 279-289.
30. Hume, W.R. and T.M. Gerzina, Bioavailability of components of resin-based materials
which are applied to teeth. Crit Rev Oral Biol Med, 1996; 7(2): 172-9.
31. Kafrawy, A.H., Biologic considerations in the selection and use of restorative materials.
Dent Clin North Am, 1983; 27(4): 645-56.
32. Kanca, J., 3rd, Pulpal studies: biocompatibility or effectiveness of marginal seal?
Quintessence Int, 1990; 21(10): 775-9.
33. Ketley, C.E. and J.R. Goodman, Formocresol toxicity: is there a suitable alternative for
pulpotomy of primary molars? Int J Paediatr Dent, 1991; 1(2): 67-72.
34. Krifka, S., et al., A review of adaptive mechanisms in cell responses towards oxidative
stress caused by dental resin monomers. Biomaterials, 2013; 34(19): 4555-63.
35. Kugel, G., Direct and indirect adhesive restorative materials: a review. American Journal
of Dentistry, 2000; 13(Spec No): 35D-40D.
36. Lam, C.W. and P.R. Wilson, Crown cementation and pulpal health. Int Endod J, 1999;
32(4): 249-56.
37. Mallineni, S.K., et al., Biocompatibility of various dental materials in contemporary
dentistry: a narrative insight. Journal of investigative and clinical dentistry, 2013; 4(1):
9- 19.
38. Marigo, L., et al., Pulpo-dentin protection: the biocompatibility of materials most
commonly used in restorative work. A literature review. Minerva Stomatol, 1999; 48(9):
373-95.
www.wjpps.com
Vol 4, Issue 10, 2015.
257
Ramamoorthi et al.
39. Milia, E., et al., Current dental adhesives systems. A narrative review. Current
Pharmaceutical Design, 2012; 18(34): 5542-5552.
40. Missias, P., Biocompatibility of dental amalgam]. Odontostomatol Proodos, 1990; 44(5):
307-17.
41. Mjor, I.A. and M. Ferrari, Pulp-dentin biology in restorative dentistry. Part 6: Reactions
to restorative materials, tooth-restoration interfaces, and adhesive techniques.
Quintessence Int, 2002; 33(1): 35-63.
42. Mjor, I.A. and D. Odont, Pulp-dentin biology in restorative dentistry. Part 2: initial
reactions to preparation of teeth for restorative procedures. Quintessence international
(Berlin, Germany : 1985), 2001; 32(7): 537-551.
43. Modena, K.C., et al., Cytotoxicity and biocompatibility of direct and indirect pulp
capping materials. J Appl Oral Sci, 2009; 17(6): 544-54.
44. Murray, P.E. and A.J. Smith, Saving pulps--a biological basis. An overview. Prim Dent
Care, 2002; 9(1): 21-6.
45. Murray, P.E., et al., Analysis of pulpal reactions to restorative procedures, materials, pulp
capping, and future therapies. Crit Rev Oral Biol Med, 2002; 13(6): 509-20.
46. Murray PE, Garcia Godoy C, Garcia Godoy F. How is the biocompatibilty of dental
biomaterials evaluated? Med Oral Patol Oral Cir Bucal. 2007; 12(3):E258-66.
47. Nicholson, J.W. and B. Czarnecka, The biocompatibility of resin-modified glass-ionomer
cements for dentistry. Dent Mater, 2008; 24(12): 1702-8.
48. Nowicka, A., et al., Response of dental pulp to self-etching adhesive systems used in
indirect capping. A literature review]. Annales Academiae Medicae Stetinensis, 2009;
55(1): 79- 83.
49. Oilo, G., Luting cements: a review and comparison. Int Dent J, 1991; 41(2): 81-8.
50. Pashley, D.H., The effects of acid etching on the pulpodentin complex. Oper Dent, 1992;
7(6): 229-42.
51. Polyzois, G.L., In vitro evaluation of dental materials. Clinical Materials, 1994; 16(1): 2160.
52. Radovic, I., et al., Self-adhesive resin cements: A literature review. Journal of Adhesive
Dentistry, 2008; 10(4): 251-258.
53. Santini, A., Biocompatibility of dentine-bonding agents. 2. Pulpal considerations. Prim
Dent Care, 1998; 5(2): 69-72.
www.wjpps.com
Vol 4, Issue 10, 2015.
258
Ramamoorthi et al.
54. Santini, A., Biocompatibility of dentine-bonding agents. 1. Factors associated with

function. Primary dental care : journal of the Faculty of General Dental Practitioners
(UK), 1998; 5(1): 15-19.
55. Schmalz, G., The biocompatibility of non-amalgam dental filling materials. Eur J Oral
Sci, 1998; 106(2 Pt 2): 696-706.
56. Schmalz, G. and P. Garhammer, Biological interactions of dental cast alloys with oral
tissues. Dental Materials, 2002; 18(5): 396-406.
57. Schuster, G.S., et al., Biocompatibility of posterior restorative materials. Journal of the
California Dental Association, 1996; 24(9): 17-31.
58. Schuurs, A.H., R.J. Gruythuysen, and P.R. Wesselink, Pulp capping with adhesive
resinbased composite vs. calcium hydroxide: a review. Endod Dent Traumatol, 2000;
16(6): 240-50.
59. Schweikl, H., G. Spagnuolo, and G. Schmalz, Genetic and cellular toxicology of dental
resin monomers. J Dent Res, 2006; 85(10): 870-7.
60. Seltzer, S., Advances in biology of the human dental pulp. Newer restorative materials
and the pulp. Oral surgery, oral medicine, and oral pathology, 1971; 32(3): 454-460.
61. Shovelton, D.S., Pulp protection. Journal of the British Endodontic Society, 1976;9(2):
57-66.
62. Sidhu SK, Schmalz G. The biocompatibility of glass-ionomer cement materials. A status
report for the American Journal of Dentistry. American journal of dentistry. 2001;
14(6):387- 96.
63. Sidhu, S.K. and G. Schmalz, The biocompatibility of glass-ionomer cement materials. A
status report for the American Journal of Dentistry. Am J Dent, 2001; 14(6): 387-96.
64. Sidhu, S.K. and T.F. Watson, Resin-modified glass ionomer materials. A status report for
the American Journal of Dentistry. American journal of dentistry, 1995; 8(1): 59-67.
65. St. John, K.R., Biocompatibility of Dental Materials. Dental Clinics of North America,
2007; 51(3): 747-760.
66. Stanley, H.R., Pulpal response to dental techniques and materials. Dental clinics of North
America, 1971; 15(1): 115-126.
67. Stanley, H.R., Pulpal responses to ionomer cements--biological characteristics. J Am
Dent Assoc, 1990; 120(1): 25-9.
68. Stanley, H.R., Local and systemic responses to dental composites and glass ionomers.
Adv Dent Res, 1992; 6: 55-64.
www.wjpps.com
Vol 4, Issue 10, 2015.
259
Ramamoorthi et al.
69. Stanley, H.R., Pulpal consideration of adhesive materials. Operative dentistry, 1992;
Suppl 5: 151-164.
70. Stanley, H.R., Effects of dental restorative materials: local and systemic responses
reviewed. J Am Dent Assoc, 1993; 124(10): 76-80.
71. Stanley, H.R., Pulpal responses to conditioning and bonding agents. Journal of esthetic
dentistry, 1993; 5(5): 208-214.
72. Swift, E.J., Jr., Pulpal effects of composite resin restorations. Oper Dent, 1989;14(1): 207.
73. Tenorio de Franca, T.R., et al., Arsenic content in Portland cement: a literature review.
Indian J Dent Res, 2010; 21(4): 591-5.
74. Upadhyay, D., et al., Corrosion of alloys used in dentistry: A review. Materials Science
and Engineering: A, 2006; 432(12): 1-11.
75. Wataha, J.C., et al., Cytotoxicity of components of resins and other dental restorative
materials. J Oral Rehabil, 1994; 21(4): 453-62.
76. Wataha JC. Biocompatibility of dental casting alloys: a review. The Journal of prosthetic
dentistry. 2000; 83(2):223-34.
77. Wataha JC. Principles of biocompatibility for dental practitioners. The Journal of
prosthetic dentistry. 2001; 86(2):203-9.
Excluded Articles [ N= 84]
A.
No
information
on
cytotoxic
effects,
on
dental
pulp/
Cytoxicity
of
bleaching/whitening.
1. Alani, A. H. and C. G. Toh. "Detection of microleakage around dental restorations: a
review." Oper Dent 1997; 22(4): 173-185
2. Bagby, M., et al. "Metal ceramic compatibility: a review of the literature." Journal of
Prosthetic Dentistry 1990; 63(1): 21-25.
3. Bergenholtz, G. "Advances since the paper by Zander and Glass (1949) on the pursuit of
healing methods for pulpal exposures: Historical perspectives." Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 100(2 SUPPL.) 2005; S102-S108.
4. Berger, J. E. "A review of the erroneously labeled "mummification" techniques of pulp
therapy." Oral Surg Oral Med Oral Pathol 1972; 34(1): 131-144.
5. Bergmans, L., et al. "Cervical external root resorption in vital teeth." J Clin Periodontol
2002; 29(6): 580-585.
6. Berman, L. H. "Dentinal sensation and hypersensitivity. A review of mechanisms and
treatment alternatives." J Periodontol 1985; 56(4): 216-222.
www.wjpps.com
Vol 4, Issue 10, 2015.
260
Ramamoorthi et al.
7. Bettencourt, A. F., et al. "Biodegradation of acrylic based resins: A review." Dental

Materials 2010; 26(5): e171-e180.
8. Bjorndal, L. and I. A. Mjor. "Pulp-dentin biology in restorative dentistry. Part 4: Dental
caries--characteristics of lesions and pulpal reactions." Quintessence Int 2001; 32(9): 717736.
9. Blunck, U. "Improving cervical restorations: a review of materials and techniques." J
Adhes Dent, 2001 3(1): 33-44
10. Bowen, R.L. and W.A. Marjenhoff, Dental composites/glass ionomers: the materials. Adv
Dent Res, 1992; 6: 44-9.
11. Burgess, J. O. "Dental materials for the restoration of root surface caries." Am J Dent
1995; 8(6): 342-351.
12. Burke, F. J., et al. "Assessing restorative dental materials: I. Test methods and assessment
of results." Dent Update 2002; 29(4): 188-194.
13. Burke, F. M. and D. Y. Samarawickrama. "Progressive changes in the pulpo-dentinal
complex and their clinical consequences." Gerodontology 1995; 12(12): 57-66.
14. Che Ghazali, F. B. "Permeability of dentine." Malaysian Journal of Medical Sciences
2003; 10(1): 27-36.
15. Ciarlone, A. E. and D. H. Pashley. "Medication of the dental pulp: a review and
proposals." Endod Dent Traumatol 1992; 8(1): 1-5.
16. Correa, J.M., et al., Silver nanoparticles in dental biomaterials. International Journal of
Biomaterials, 2015; 2015(485275).
17. Cox, C. F. "Microleakage related to restorative procedures." Proc Finn Dent Soc, 1992 88
Suppl 1: 83-93.
18. Cox, C. F. "Evaluation and treatment of bacterial microleakage." Am J Dent 1994; 7(5):
293-295
19. Dadoun, M. P. and D. W. Bartlett. "Safety issues when using carbamide peroxide to
bleach vital teeth--a review of the literature." Eur J Prosthodont Restor Dent 2003; 11(1):
9-13.
20. Dahl, J. E. and U. Pallesen. "Tooth bleaching--a critical review of the biological aspects."
Crit Rev Oral Biol Med 2003; 14(4): 292-304.
21. D'Alpino, P. H., et al. "Use of fluorescent compounds in assessing bonded resinbased
restorations: a literature review." J Dent 2006; 34(9): 623-634.
22. Davidson, C. L. and A. J. Feilzer. "Polymerization shrinkage and polymerization
shrinkage stress in polymer-based restoratives." J Dent 1997; 25(6): 435-440.
www.wjpps.com
Vol 4, Issue 10, 2015.
261
Ramamoorthi et al.
23. Davis, M. "Problems with amalgam: physical and chemical instability." Dent Today
2000; 19(7): 94-96, 98-96101.
24. Diniz, I. M. A., et al. "Evaluation of antibacterial photodynamic therapy effects on human
dental pulp cell cultures." Photodiagnosis and Photodynamic Therapy, 2014; 11(3): 300306.
25. Donovan, T. E. and G. C. Cho. "Contemporary evaluation of dental cements."
Compendium of Continuing Education in Dentistry 1999; 20(3): 197-199.
26. Elshahawy, W., et al. "Cytotoxic effect of elements released clinically from gold and
CAD-CAM fabricated ceramic crowns." Tanta Dental Journal 2014; 11(3): 189-193.
27. Emmler, J., et al. "Cytotoxicity of the dental composite component TEGDMA and
selected metabolic by-products in human pulmonary cells." Dental Materials 2008;
24(12): 1670- 1675.
28. Ferracane, J. L., et al. "Can interaction of materials with the dentin-pulp complex
contribute to dentin regeneration?" Odontology 2010; 98(1): 2-14.
29. Ferrari, M. and F. Garcia-Godoy, Sealing ability of new generation adhesive-restorative
materials placed on vital teeth. Am J Dent, 2002; 15(2): 117-28.
30. Fron Chabouis, H., et al. "Clinical efficacy of composite versus ceramic inlays and
onlays: A systematic review." Dental Materials 2013; 29(12): 1209-1218.
31. Gale, M. S. "Coronal microleakage." Ann R Australas Coll Dent Surg 2000; 15: 299- 305.
32. Gao, W., et al. "Demineralisation and remineralisation of dentine caries, and the role of
glass-ionomer cements." Int Dent J 2000; 50(1): 51-56.
33. Goldberg, A. J. "Deterioration of restorative materials and the risk for secondary caries."
Adv Dent Res 1990; 4: 14-18.
34. Goldberg, M., et al. "Undesirable and adverse effects of tooth-whitening products: A
review." Clin Oral Investig 2010; 14(1): 1-10.
35. Goldberg, M., et al. "The impact of bioactive molecules to stimulate tooth repair and
regeneration as part of restorative dentistry." Dent Clin North Am 2006; 50(2): 277-298.
36. Hamilton, A.I., et al., Special report: Report of the Committee on Scientific Investigation
of the American Academy of Restorative Dentistry. The Journal of prosthetic dentistry,
1980; 43(6): 663-686.
37. Hamilton, A.I., et al., Report of the Committee on Scientific Investigation of the
American Academy of Restorative Dentistry*. The Journal of prosthetic dentistry, 1975;
34(1): 86- 110.
www.wjpps.com
Vol 4, Issue 10, 2015.
262
Ramamoorthi et al.
38. Hilton, T.J., Cavity sealers, liners, and bases: current philosophies and indications for use.
Operative dentistry, 1996; 21(4): 134-146.
39. Holland GR. Morphological features of dentine and pulp related to dentine sensitivity.
Archives of oral biology. 1994; 39 Suppl: 3s-11s.
40. Markowitz, K., et al., Biologic properties of eugenol and zinc oxide-eugenol. A clinically
oriented review. Oral Surg Oral Med Oral Pathol, 1992; 73(6): 729-37.
41. Melo, M.A.S., et al., Nanotechnology-based restorative materials for dental caries
management. Trends in Biotechnology, 2013; 31(8): 459-467.
42. Minguez, C. and K. Lyons, Failure of crowns and bridges - A review of the literature.
New Zealand Dental Journal, 2007; 103(1): 7-13.
43. Peng, J.J.Y., M.G. Botelho, and J.P. Matinlinna, Silver compounds used in dentistry for
caries management: A review. Journal of Dentistry, 2012; 40(7): 531-541
44. Strang, R., et al., Dental materials: 1996 literature review. Part 2. Journal of Dentistry,
1998; 26(4): 273-91.
45. Stanley, H.R., Dental iatrogenesis. Dent Today, 1994; 13(11): 66, 68, 70-3.
46. Stanley, H.R., Dental iatrogenesis, Part 2. Dent Today, 1995; 14(2): 76-81.
47. Van Landuyt, K.L., et al., How much do resin-based dental materials release? A
metaanalytical approach. Dental Materials, 2011; 27(8): 723-747.
48. Weiner, R.S., Liners, bases, and cements: a solid foundation. Gen Dent, 2002; 50(5): 4426
B. Endodontic Perspective.
1. Brodin, P. "Neurotoxic and analgesic effects of root canal cements and pulpprotecting
dental materials." Endod Dent Traumatol 1988; 4(1): 1-11.
2. Cerqueira, D. F., et al. "Cytotoxicity, histopathological, microbiological and clinical
aspects of an endodontic iodoform-based paste used in pediatric dentistry: a review." J
Clin Pediatr Dent 2008; 32(2): 105-110.
3. Chala, S., et al. "Apexification of immature teeth with calcium hydroxide or mineral
trioxide aggregate: Systematic review and meta-analysis." Oral Surgery, Oral Medicine,
Oral Pathology, Oral Radiology and Endodontology 2011; 112(4): e36-e42.
4. Darvell, B. W. and R. C. T. Wu. "MTAAn Hydraulic Silicate Cement: Review
update and setting reaction." Dental Materials 2011; 27(5): 407-422.
C. Non English.
1. Bonte, E. "[Biocompatibility of glass-ionomers: review of the literature]." Chir Dent Fr
1989; 59(469): 55-56.
www.wjpps.com
Vol 4, Issue 10, 2015.
263
Ramamoorthi et al.
2. Cadenaro, M. and G. Gregorig, [Enamel-dentinal adhesives in amalgam restorations.

Review of the literature]. Minerva Stomatol, 2000; 49(6): 313-21.
3. Cesar Sampaio, J. E., et al. "[Importance of cavity varnishes in clinical restorative
dentistry]." Odontologia Clinica 1987; 1(2): 22-24, 27.
4. Fratamico, F. C. and C. Prati. "Biocompatibility of dentinal adhesive systems in
conservative dentistry. [Italian]." Dent Cadmos 1990; 58(4): 66-70.
5. Girard, C. and J. Holz (1985). "[Short and long-term follow-up in the treatment of
category IV pulp diseases with calcium hydroxide]." Schweiz Monatsschr Zahnmed
1984; 95(3): 169-182.
6. Gohring, K. S., et al. "[Indications for use of MTA, a review. Part 1: Chemical, physical
and biological properties of MTA]." Schweiz Monatsschr Zahnmed 2004; 114(2): 143153.
7. Heyeraas KJ, Sveen OB, Mjor IA. Pulp-dentin biology in restorative dentistry. Part 3:
Pulpal inflammation and its sequelae. Quintessence international (Berlin, Germany:
1985). 2001; 32(8):611-25
8. Holz J, Baume LJ. Biological testing for compatibility of intermediate filling materials
with the dental pulp and dentin. [French]. Schweizerische Monatsschrift fur
Zahnheilkunde = Revue mensuelle suisse d'odonto-stomatologie / SSO. 1973; 83(12):
1369-458.
9. Imai Y. A chemist's view on toxicity of dental materials. [Japanese]. Kokubyo Gakkai
zasshi The Journal of the Stomatological Society, Japan. The Journal of the
Stomatological Society, Japan, 1987; 54(2): 341-8.
10. Kojima S. [Clinico-pathological studies on the modification of alpha-cyanoacrylate as
pulp protective materials on vital human teeth (author's transl)]. Shika gakuho Dental
science reports. 1982; 82(1): 61-128.
11. Miani C, Deli R. Biological properties of materials in conservative dentistry. I. Pulp
reactivity. [Italian]. Minerva stomatologica. 1983; 32(6): 879-81.
12. Mjor IA. Pulp-dentin biology in restorative dentistry. Part 7: The exposed pulp.
Quintessence international (Berlin, Germany: 1985). 2002; 33(2):113-35.
13. Mjor IA, Ferrari M. Pulp-dentin biology in restorative dentistry. Part 6: Reactions to
restorative materials, tooth-restoration interfaces, and adhesive techniques. Quintessence
international (Berlin, Germany : 1985). 2002; 33(1): 35-63.
www.wjpps.com
Vol 4, Issue 10, 2015.
264
Ramamoorthi et al.
14. Mjor IA, Odont D. Pulp-dentin biology in restorative dentistry. Part 2: initial reactions to
preparation of teeth for restorative procedures. Quintessence international (Berlin,
Germany : 1985). 2001; 32(7): 537-51.
15. Mjor IA, Sveen OB, Heyeraas KJ. Pulp-dentin biology in restorative dentistry. Part 1:
normal structure and physiology. Quintessence international (Berlin, Germany: 1985).
2001; 32(6): 427-46.
16. Minoux M, Serfaty R. Vital tooth bleaching: biologic adverse effects-a review.
Quintessence international (Berlin, Germany : 1985). 2008; 39(8): 645-59.
17. Missias P. [Biocompatibility of dental amalgam]. Odontostomatologike proodos. 1990;
44(5): 307-17.
18. Wauters T, Wauters J. Should the dentin smear layer be preserved or eliminated? (Review
of the literature). [French]. Revue belge de medecine dentaire. Belgisch tijdschrift voor
tandheelkunde. 2000; 55(2): 93-103.
19. Zmener O, Dominguez FV. [Corrosion of silver cones: current status]. Revista de la
Asociacion Odontologica Argentina. 1987; 75(2): 38, 40-1.
D. Original research, Technical reports, Letter to editor, short communication, Non
indexed.
1. Bayne, S. C. "Correlation of clinical performance with 'in vitro tests' of restorative dental
materials that use polymer-based matrices." Dental Materials 2012; 28(1): 52-71.
2. Boland, E. J., et al. "In vitro cytotoxicity of a remineralizing resin-based calcium
phosphate cement." Dental Materials 2006; 22(4): 338-345.
3. Cabrera, S., et al. "Effects of growth factors on dental pulp cell sensitivity to amalgam
toxicity." Dental Materials 2007; 23(10): 1205-1210.
4. Camps, J., et al. "In vitro cytotoxicity of dental adhesive systems under simulated pulpal
pressure." Dental Materials 1997; 13(1): 34-42.
5. Chang, M.-C., et al. "The role of reactive oxygen species and hemeoxygenase- expression
in the cytotoxicity, cell cycle alteration and apoptosis of dental pulp cells induced by
BisGMA." Biomaterials 2010; 31(32): 8164-8171
6. Chang, Y.-C. and M.-Y. Chou. "Cytotoxicity of fluoride on human pulp cell cultures in
vitro." Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology
2001; 91(2): 230-234.
7. Chang, H.-H., et al. "Urethane dimethacrylate induces cytotoxicity and regulates
cyclooxygenase-2, hemeoxygenase and carboxylesterase expression in human dental pulp
cells." Acta Biomaterialia 2014; 10(2): 722-731.
www.wjpps.com
Vol 4, Issue 10, 2015.
265
Ramamoorthi et al.
8. Chen, R.-S., et al. "Cytotoxicity of three dentin bonding agents on human dental pulp
cells." J Dent 2003; 31(3): 223-229.
9. Cox, C. F., et al. "Biocompatibility of dental adhesives." J Calif Dent Assoc 1995; 23(8):
35-41.
10. de Souza Costa, C. A., et al. "In vitro cytotoxicity of five glass-ionomer cements."
Biomaterials 2003; 24(21): 3853-3858.
11. Demirci, M., et al. "The induction of oxidative stress, cytotoxicity, and genotoxicity by
dental adhesives." Dental Materials 2008; 24(3): 362-371.
12. Huang F-M, Chang Y-C. Cytotoxicity of resin-based restorative materials on human pulp
cell cultures. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and
Endodontology. 2002; 94(3): 361-5.
13. Jan Y-D, Lee B-S, Lin C-P, Tseng W-Y. Biocompatibility and cytotoxicity of two novel
low-shrinkage dental resin matrices. Journal of the Formosan Medical Association. 2014;
113(6):349-55.
www.wjpps.com
Vol 4, Issue 10, 2015.
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CYTOTOXIC EFFECTS OF RESTORATIVE BIOMATERIALS ON

MDS, Prosthodontist. Canada. 2MDS, Professor, Dept of Conservative Dentistry &

MDS, MS. Canada.

cytocompatibility of commonly used restorative materials and methods

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implants/bleaching/whitening are excluded from this review. The comprehensive list of

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Table-3: Flow chart of search Methodology

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Assays based on membrane integrity.

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World Journal of Pharmacy and Pharmaceutical Sciences

Vol 4, Issue 10, 2015.

World Journal of Pharmacy and Pharmaceutical Sciences

Fig:2 Agar overlay assay

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World Journal of Pharmacy and Pharmaceutical Sciences

Fig: 3 Illustrative diagram of dentin disk barrier test.

Fig-4: Material Cell Interface

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World Journal of Pharmacy and Pharmaceutical Sciences

Cell- material interface

Liquid, powder, fibers

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World Journal of Pharmacy and Pharmaceutical Sciences

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World Journal of Pharmacy and Pharmaceutical Sciences

GMA] or other monomers/oligomers as pendant chains .Any modifications of GIC is shown

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World Journal of Pharmacy and Pharmaceutical Sciences

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World Journal of Pharmacy and Pharmaceutical Sciences

Table-9 Flowchart for clinical guidelines in using restorative biomaterial

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World Journal of Pharmacy and Pharmaceutical Sciences

23. Fratamico, F.C. and C. Prati, Biocompatibility of dentinal adhesive systems in

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World Journal of Pharmacy and Pharmaceutical Sciences

54. Santini, A., Biocompatibility of dentine-bonding agents. 1. Factors associated with

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World Journal of Pharmacy and Pharmaceutical Sciences