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BIOCOMPATIBILITY OF DENTAL MATERIALS
Introduction
History
Requirement of dental materials
Biologic response in the dental environment
Enamel
Dentin
Pulp
Pediodntium
Gingival and mucosa
The oral immune system
Adverse Effects from dental materials
Toxicity
Inflammation
Allergy
Mutagenic radians.
Local and systemic effects of materials
Measuring the biocompatibility of materials
Types of Tests
In Vitro tests
Cytotoloxicity assays
Cell number and growth
Membrane permeability tests
Tests for cell metabolism or cell function
Tests that USC barriers.
Other Assays for cell functions
Mutagenesis assays
Animal tests
Usage tests
Dental implants in bone
Using in vitro, animal and usage tests together.
Standards that regulate the measurement of biocompatibility.
Biocompatibility of dental materials
Reaction of pulp
Microleakage
Amalgam
Direct filling gold
Dental casting alloys
Non metallic restorative materials
Bonding agents
Composite resins
Liners and varnishes
Ceramics
Conclusion
INTRODUCTION
When a biomaterial is placed in contact with the tessiues and fluids of the
human body, there is inivariable some form of interaction between the material and
biological environment this interaction is referred to as biocompatibility.
Biocompatibility is defined as the ability of a material to function in a specific
application in the presence of an appropriate host response.
Dentistry shares concerns about biocompatibility as with other fields of
medicine, such as orthopedics, cardiology and vascular biology among others. In the
development of any biomaterial, one must consider the strength, esthetics and
functional aspects of the material, as well as its biocompatibility furthermore,
demands for appropriate biological responses are increasing as we requires that
materials perform more sophisticated functions in the body for longer time periods
Thus, considerations of biocompatibility. sophisticated functions in the body for
longer time periods. Thus considerations of biocompatibility are important to
manufacturers practitioners, scientists and patients.
The field of biocompatibility, is interdisciplinary and draws on knowledge
from materials science, bioengineering biochemistry, molecular biology tissue
engineering and other fields.
Biocompatibility HISTORICAL BACKGROUND
Although the concept of ethical treatment of patients extends back to the line
of Hippocrates ( 460 – 377 B.C) the idea that new materials must be tested for safety
and efficacy before clinical use is more recent. As late as the mid 1800’s dentists tried
new materials for the first time by putting patients mouths.
Even G.V.Black used patients to test many of his new ideas for restorative
materials such as early amalgams. The concept of protecting the patient as a research
subject is only 30-40 years old and many of the regulations and ethics in this area are
still being challenged and defined today. In most cases a committee of clinicians,
basic scientists and laypersons regulate and oversee the testing of new materials in
humans.
Using humans as research subjects today without some previous testing or
knowledge of the biological proportions is unethical and illegal still over new material
must be inserted into a human for the first time at same point. Therefore many
alternative tests have been developed to try to minimize the risks to humans. The
current philosophy about testing the biological properties of dental materials in a
systematic way evolved in the 1960’s as the need to protect patients became
politically acute and the number of new materials increased.
The oversight for this testing in U.S now rests largerly with the Food and Drug
Administration ( FDA), but these activities are regulated by the American National
Standards Institute ( ANSI). American Dental Association ( ADA) Biological testing
of materials has significantly evolved over the past 40 years. Since initially being used
on animal models. Many studies between the 1950’s and the 1970’s involved the use
at premolar teeth that were scheduled for orthodontic extraction. As well as cell
solutions techniques and biological responses to material today the field of
biocompatibility has reached a point where some prediction of biological properties is
possible and the future will likely provide the ability to design materials that elicit
customized biological responses. Some of the pioneering works are
Use of in vitro techniques to study the toxicity of various synthetic
materials began some 30 yrs. After tissue culture was first established as a
technique in 1926.
Various investigators began to apply organ and tissue culture techniques to
toxicological problems in 1950’s and 1960’s.
Kawahara;s lab began to use cell culture methods to investigate dental
materials in the 1950’s these investigators reported the cytotoxicity of pure
metals, dental cements and medicaments.
Leirskar and Helgeland (1972) did the first study of cell culture tests using
human epithelial cells on and around standard size disks of dental
materials, including silver amalgam and copper amalgam resins silicate
and gold alloy.
One of the earliest quantitative in vitro tests was a membrane permeability
assay for release using L- 929 cells by spangbeng in 1973.
Schmalz in 1982 was one of the first dental investigators to apply the agar
overlay techniques to test the cyloloxicity of dental materials.
REQUIREMENT OF DENTAL MATERIALS
Be nontoxic
Be non irritant to the oral or other tessiues
It should not produce allergic reactions.
It should not be mutagenic or Coriogenicity
Classification of materials
Matrials may be classified into following types from the perspective of
biological compatibility
a) those which contact the soft tissue within the mouth.
b) Those which could affect the health or vitality of the dental pulp/
c) Those which are used as used as root eanal filling materials.
d) Those which affect the hard tessuies of the mouth.
e) Those used in the dental laboratory, which though not used I the mouth,
are handled and may be accidentally engisted or inhaled.
Examples of hazards
a) some dental cement components are acidic and may cause irritation.
b) Polymer based filling materials may contain irritating chemicals such as
unreacted monomers.
c) Mercury is used in dental amalgam, and mercury vapour is toxic.
d) Dust from alginate impression materials may be inhaled,some products
contain lead compounds/
e) Some people show allergic reactions to alloy containing nickel.
f) Some dental porcelain powder contain uranium.
g) Laboratory materials have their hazards,such as cyanaids solution for
electroplating,vapoures from low fucing metal dies, silicious particles in
investment materials and fleeces containing fluorides.
Evaluation of the biocompatibilities-before adopting any methods for
biocompatibility fests the following aspects must be careful considred:
1. location of the material
2. nature of the tessiues-soft or meniralized hard tessuie
3. exposure of the materials to the oral situations,salvia blood
4. type of contacts, direct or indirect through a barriears like a epithelvies
5. chemical nature –compositions ,degradations.
6. physical condition –like stresses,fatigue resistancs.
ANATOMICAL AND PATHOLOGICAL ASPECTS OF ORAL TESSUIES
Oral anatomy influencing the biologic response
Several aspects of oral anatomy influence the biocompatibility of dental
restorative materials. The full effects of the oral anatomy on the biocompatibility of
materials are not known but these effect will be a major focus of anatomy of the tooth,
the periodontal attachment and to the peripical environment that have influences on
the biologic response to materials and all are sites of interface between materials and
tissue in dentistry.
ENAMEL
Mature human enamel is highly meneialyid enamel rods have a specific
orientation with each other,and the orientation provides maximal strength because of
its high mineral (hydroxylapatile) content, enamel is much more bittele than dentin
and is soluibied to a greater extent by acid solution this property is used to advantage
with bonding agents, when acids are used to etch the enamel to provide
micromechanical retention of resin composites. The differential etching that occurs is
a consequence of the different orientation of enamel rods. permeability of enamel to
most oral molecules is quite low, and it seals the tooth to outside agents.
However recent evidence indicates that enamel is not totally emperineable.
Peroxides in bleaching agents has been shown to penetrate intact enamel in just a few
seconds.
Dentin and pulp:
The dentin and pulp to be a single tissue the dentinial matrix (both ciassified
and unclassified forms the greatest bulk of the tooth collagen constitutes
approximately 85% of the organic portion of dentin and hydroxy apatite is the main
unorganic compound the dentenail matrix contains protein type 1 type 5 collagens,
osteoclasin and osteopontien, phosphoryjns dentinsealoprotien and dentin matrix
protein.
The dentin matrix surrounds dentenial tubles that are filled with odontoblastic
processes. The tubules traverse the region between the dentino enameljunction (DEJ)
and the pulp.
A serum like fluid fills the dentenial tubules this fluid has conteneity with the
extracellular of the pulp tissue. pulpal circulation maintains an intercellular hydraulic
pressure, which causes fluid flow into tubules to be directed from the pulp outward
towards the DEJ when enamel is removed.external hydrostatic and osmotic pressure
can also cause fluid movement toward or from the pulp. The positive or negative
displacement of this fluid through exposed denture tubules is capable of affecting
either odontoblasts or pulpal nerve endings. These effects are the basis of
hydrodynamic theory of hyperlagesisa (pulpal hypersensitivity).
Smear layer is formed by the action of the beer or hand instruments on the
classified dentin matrix. this occludes the dentinal tubules to some extent and it is
quite effective in reducing hydrostatin pressures but less effective in reducing
hydrosstative pressures but less effective in reducing diffusion.
The smear layer can be removed by acid etching. Which also deminiralyses
the openings of the tubules. The dentenial tubules establish continuity with the pulpal
fluid to facilitate the diffusion of molecules both natural or from materials into and
out of the pulp. The smear layer ,dentenial tubules and dentenial matrix are all
important in the application of dentenial bonding agents and the ability of components
of the bonding agents to reach and affects pulpal tessuies.
The pulp of the tooth is a connective tessuie containing normal elements such as
fibroblasts,collages,capillarises and nerve pulp supplies the cells, which replace any
odontoblasts desriyed during cavity preparation or material placement and allowes the
tooth to form secondary or separation dentin.
PERIODONICAL ATTACHMENT:
Junction between the outside of the body (oral cavity) and the inside of the
body. The dentin of the root of the tooth is covered by a thin layer of the root of the
tooth is covered by a thin layer of cementum that may seal the dentenial tubules
cementum attaches the collages fubers of the periodontal ligament the genguia
normally extends above the level of the cementum and forms a potential space against
the enamel called periodontal pochet.the gingivial epithelium is also attached to the
cementum of the tooth by a specialized junctional epithelium. The periodontial pocket
is the site of the development of periodontal pocket is the site of the development of
periodontal desease,which can destroy the junctional ipetheluim,periodontal ligament
and supporting aluolar bone.
Because many dental restorations are near or in the periodontal attachment area the
biocompatibility of these materials may influence the normal periodontal
architecture,the periodontal desease process or the body,s ability to defend against
bacteria that cause periodontal desease periodontal desease periodontal pocket is a
unique microenvironment that allow concentration of components from materials to
reach higher levels than are seen in the rest of the oral cavity the influence of dental
materials on the periodontal disease and the biting forces that strain the periodontal
ligament and supporting bone. It is often difficult to determine with certainty whether
inflammation in this area is caused by periodontal disease, occlusal trauma, the
material or some combination of these factors. the periodontal pocket has also been
used as a site to place materials that release therapeutic agents to combat periodontal
disease. It is likely that this approach will expand as better drug delivery materials are
developed.
PERIAPICAL AREA:
Another interface between materials and the inside of the body. The apex of the tooth
is the junction of the pulp of the tooth and the alueolar bone nerves and blood vessels
entire through the apical foramen. When the pulp of the tooth is destroyed by
infection or during restoration of a tooth, endodontic materials are placed in the
pulpal space and these materials interface with the body through the apex of the tooth.
If the endodontic procedure is not performed correctly the filling materials may
extruded from the apex into the periapical area and cause additional physical damage.
The ability of the root canal material toward the apex is also an important
consideration.
The use of the retrograde approach to seal the apical foramen, the filling materials
will be in direct contact with the perapical tessuies. Thus biological responces to these
materials must be critically examined. As with the periodontal attachment area, the
release of substances from root canal filling materials may cause adverse responses
around the apex or may alter the body’s reaction to bacterial products that have
contaminated the area.
The delineation between the bacterial and material threats are not clear , and the
ability of materials to influence the body’s immunological response in the perapical
area has only recently been studied.
SPECIAL BIOLOGICAL INTERFACE WITH DENTAL MATERIALS:
Dentin rein interface
Implant bone interface
Dentin resin interface:-when resin based restorations material bonds to dentin. The
composite nature of the denture allows the mineralized matrix to be dissolved away
by acids which preserving the collagen network. If the network doesnot collapse,
which may happen if the dentin is dessicated it may be embedded by a resin –
containing material thereby mechanically bonding the resin material to dentin.
If the resin material doesnot penetrate the collgenous network or debonds from it as
the resin shrinks during polymerization, a gap will form between the resin and the
dentin. this also occurs in enamel this few missions wide gap allows bacteria and oral
fluids to pucolate from the pulp outward or from the oral cavity onward. This leakage
is termed as microleakage.
The bio compatibility of a restoration is altered by the leakage process which
may cause a number of undesirable events:-
1. It may allow bacteria or bacterial products to reach the pulp and cause
infection.
2. It encourages the breakdown then exposes the margins of the restorations
making the tooth restoration complex aesthetically unacceptable.
If the resin penetrate the collagen network of the dentin but does not penetrate it
completely a much smaller gap will exist between the mineralized matrix of the
dentin and collagen resin hybrid layer. Nanoleakage.
Although nanoleakage probably doesnot allow bacteria or bacterial
products to penetrate the marginal gaps of the restoration and the pulp,fluid exchange
most likely occurs that can degrade the resin or the collagen network. That has been
uncompletely embedded with resin, thereby reducing the longevity of the dentin resin
bond this degradation process may also gradually increase the gap size until
microleakage begins to occur.
Osseointegration:
The use of endosseous dental implants has uncriased tremendulously over the past
decade. the success of these implants relieves on the ability of the material to promote
osseointegration and allow a close approximation of bone with the material..the
ability of a material to allow osseointegration is closely related to its biocompatibility
in dentistry, relatively few materials allow osseointegration
1.they are commercially purelitanum.
2. titanium-aluiminium-vanaduim alloy.
3.tantalum
4. several types of ceramics.
Materials that allow osseointegration have very low osseointegration have very low
degradation rates,and they tend to form surface oxides that promote bony
approximation some materials such as bioglass-ceramics, promote an integration
between the bone and material with no intervening space at all.when this integration
occurs,the material is said to biointegrate with the bone.biointegration appears to
require a degradation of the ceramic to promote bone formation .no known desirabily
of osseointegration over biointegration has been established.like all biocompatibility
phenomena osseointegration and biointegration are dynamic processes that may be
altered by changes in the host,fatigue of the materials or function of the implant.it is
also important to understand that neither osseointegration nor bio integration munic
the normal ligamentous connection between a tooth root and alerolar bone.
Oral immuno system:
It plays an important role in the biological response to any material.it appears to
behave some what differently in oral epitheluium and connection tessuie than in the
rest of the body and the biological responses to materials in the mouth may not always
parallel those seen in other locations the oral environment is not always equivalent in
structure or function to other areas of the body and that differences may alter the
biological response to materials
ADVERSE EFFECT FROM DENTAL MATERIALS
TOXICITY
Material release certain substances which in convert concentration can lead to the
toxicity. It in the first screening test used for all dental materials. This is a close-
related potential of a material resulting in cell or tissue death. Example-some
substances like mercury ,,nickel, berylluim released into the body, which can cause
overt bixicity above a certain amount.
INFLAMMATION
It is a second fundamental type of biological response to a material. it
involves the activation of the host immune system inflammation may result toward off
some threat. toxicity or from allergy and often the inflammatory response precedes
toxicity.the inflammation may be caused by toxic or allergic materials. And
sometimes may preceed toxicity. The pulpal and periodontal disease are largely
chronic inflammatory responses to long term infections.
HYPERSENSITIVELY AND ALLERGY
Hypersensitively is the abnormal reaction that occurs when the body is exposed to a
foreign material this materials sensitive the immune system, so that when the person
is repiately exposed to the same material the body responds with a hypersensitivity
reaction which is not dose dependent.
The allergic or hypersensitive reaction developes only in persons whose immune
system recognize the material as foreign the allergic reactions can manifest as
localized reaction in the tessuie which is directly in contact with the material allergy
can be a systemic manifestations in the form of itching skin
eruptions,sneezing,erythema,breathing difficulties.
According to gell and coomb’s classifications the allergic reaction or immune
responses can be-:
Type I-immedaite
TypeII-cyto-toxic hypersensitivity
TypeIII-immune complex hypersensitivity
Type 4 delayed, cell-medicated hypersensitivity
The allergic reaction are due to there individuals emmuine systems,recognizing a
substance as foreign and are initially dose dependent
Mutagenic Reactions
These are caused by the materials or its components,altering the base-pair
sequence of DNA in cell (mutation) some resin-based restoration,realants,cons of
metals (Ni,Be,Cu) are found to be mutagens.fortunately these may not be
(arcinogenic,as the immune system supplies lot of cellular energies and mechanics to
repair the mutated DNA.
Oestroginicity-
It is the ability to produce materials like xeno-istrogens,to act in the body as
estrogens.the resin,bisphenol A,the starting substance of BISGMA,composite
restoratibe materials and few other series are found to be esteogenic.
In most cases the surface characterstics such as composition,roughness and
corrosion degradation products affect the biocompatibility.
Osseo integration and bio integration
It is the dynamic interaction between the body and materials.it is the key
phenomena in the implantology.
Osseointegration-
Formation of living body tissues with in 10 mm space from the implant materials
surface without any fibrous connection tessuis
Eg: Tantalum ceramics.
Biointegration :
Certain materials like bioglasses which undergo biointegration with the bone directly
any intervening space.
Immunotoxicity:
it is due to the alteration in the cells of immune system by the matrials.this cause
either increase or decrease of cellular of functions.
Eg-mercury,palladium,HEMA
EVALUATION TEST OF BIOCOMPATIBILITY:
Historically new materials were simply tested in human to assess their
biocompatibility, this practice has not been acceptable for many years and current
materials must be extensively screened for biocompatibility before they are used in
humans. Several varieties of tests are currently used to unsure that new materials are
biologically acceptable.
These are classified as
a) in vitro test
b) animal test usage test
a) in vitro test: these tests are performed outside of an organism. These tests maybe
conducted in a test tube, cell culture dish, flash, or other contains but they are
performed separately from an intact organisms. The biological system may
consist of mammalian cells, cellular organelles, tessuies ,bacteria or some text of
enzyme. The contact involves the exposure of a material and biological system
are a)direct
b) indirect
direct contact involves the exposure of a material or an extract from a material
directly with the biological system where as indirect contact occurs through a barrier
of some sort such as agar, a membrane filter, or dentin.
In vitro test can be subdi
MEASURING THE BIOCOMPATABILITY OF MATERIALS
Measuring the biocompatibility of a material is not simple and the methods of
measurement are evolving rapidly as more is known about the interactions between
dental materials and oral tissues as technologies for testing improve. Historically new
materials were simply tested in humans to assess their biocompatibility. However this
practice has not been acceptable for many years and current materials must be
extensively screened for biocompatibility before they are used in humans several
varieties of tests are currently used to ensure that new materials are biologically
accepted.
Types of Tests
There are three basic types of tests : the in vitro test, the animal test, and the
usage test performed either in animals or in humans.
In vitro tests are performed outside f an organism historically, in vitro tests
have been used as the first screening test to evaluate a new material. These tests may
be conducted in a test tube, cell culture dish, flask or other containers, but they are
performedseperately from an intact organism, which is placed in contact. With some
biologic system the biologic system may consist of mammalian cells, cellular
organells tissue bacteria or some sort of enzyme. The contact between the biological
system and the material may be direct or indirect. Direct contact involves the
exposure of a material or an extract from a material directly with the biological
system where as indirect contact occurs through a barrier of some sort. Such as agar a
membrane filter or death. In vitro tests can be subdivided into tests that measure cell
growth or death, those that determine cellular function of some type, and those that
evaluate the integrity of the genetic materials of the cell.
ADVANTAGES
Relatively fast
Less expensive
Can be standardized
Large scale screening
Good experiment control
Tightly controlled conditions for quality.
Disadvantages
Relevance to in vivo is questionable
Lack of complex co-ordination of systems that is present in an organism
such as immune, inflammatory and circulatory system.
IN VITRO TESTS
SYTOTOXICITY ASSAYS
By these tests the effect of the material or its leachable products are studied on
the metabolic functions of the test cell system. In general cytotoxicity tests measure
the effect of a material on
Cell number or growth
Integrity of cell membranes
Biosynthesis or enzyme activity or
The genetic material of the cell.
Advantages of cytotoxicity assays are
Testing for a specific function of cell metabolism in isolation from other
events.
Screening large number of samples quickly and inexpensively
Quantifying results
Having potential for standardization of test methods
Disadvantages include
Limitation of testing to only one cell type at a time
Dissimilarity of test cells to host cells
Lack of inflammatory and other tissue protective mechanism in tissue
culture.
The biological systems used in vitro cytotoxicity tests may be
Organ cultures
Cells in culture or
Cell organelles.
The most widely used biological systems for in vitro toxicity testing of dental
materials are cells in culture. Two types of cells can be used for in vitro assays.
Primary cells are those cells taken directly from an animal and cultured. These
cells will grow for only a limited time in culture but retain many of the characteristic
of cells in vivo.
Continuous cells or cell lines are primary cells that have been transformed
previously to allow them to grow more or less indefinitely in culture because of this
transformation. These cells do not retain all in vivo characteristic but they do
consistently exhibit any features that they do retain.
In all cytotoxicity tests the test system itself must be nontoxic, sterile and
reproducible so as not to interfere with the analysis of the material.
MEMBRANE PERMEABILITY TESTS
Membrane permeability is the ease with which a dye can pass through a cell
membrane. This test used on the basis that a loss in membrane permeability is
equivalent to or very nearly equivalent to cell death. The main advantage of
membrane permeability is
It identifies cells that are dead or alive under the microscope. This feature is
important because it is possible for cells to be physically present but dead (when
materials fix the cell.)
There are two basic types of dyes used, vital dyes are actively transported into
viable cells where they are retained unless cytotoxic efforts increase the permeability
of the membrane. It is important to establish that the dye itself does not exhibit
cytotoxicity during this frame of the test. Eg. Neutral red Na2 Cr o4
Non vital dyes are not actively transports and are only taken up if membrane
permeability has been compromised by cytotoxic. Eg. Trypan blue and propidium
iodine.
The main disadvantages of this test is the managing of radioactive isotopes (a
gamma radiation emitter.
CELL NUMBER AND GROWTH TESTS
These assess the cytotoxicity of a material by measuring cell number or
growth after exposure to a material cells are plated in a well of a cell culture dish
where they attach. The material is then placed in the test system if the material is not
cytotoxic, the cells will remain attached to the well and will proliferate with time. If
the material is cytotoxic, the cells may stop growing exhibit cytopathic features or
detach from the well. If the material is a solid, then the density of cells may be
assessed at different distances from the material and a zone of inhibited cell growth
may be described. The cell density can be assessed either quantitatively, semi
quantitatively or quantitatively substances such as Teflon can be used as negative
( non cytotoxic) controls where as materials such as plasticized polyvinyl chloride can
be used as positive cytotoxic controls.
TESTS FOR CELL METABOLISM OR CELL FUNCTION
Some in vitro tests for biocompatibility, use the biosynthetic or enzymatic
activity of cells to assess cytotoxic response. Tests that measure DNA or protein by
cells is usually analyzed by adding radio isotope labeled precursors to the medium
and quantifying the radioscope incorporated into DNA or protein. (eg. 3H –
thymidine)
A commonly used enzymatic test for cytotoxicity is the MTT test. This test
measures the activity of cellular dehydrogenases, which converts a chemical MTT,
via several cellular reducing agents, to a blue, insoluble formazan compound. If the
dehydrogenases are not active because of the cytotoxic effects, the formazan will not
form. Production of Formazan is quantified by dissolving if and measuring the optical
density of the resulting solution, they can also be localized around the test sample by
light or electron microscopy.
Recently developed indicator dyes such as alam blue have been formulated to
quantitatively measure cell proliferation using and oxidation reduction (redox)
indicator that yields a calorimelic change and fluorescent signal in response to
metabolic activity and permit continous monitoring of cells overtime.
TESTS THAT USE BARRIERS
Indirect tests researches have long recognized that in vivo direct contact does
not exist between cells and the materials separation of cells and materials may occur
from keratinized epithelium dentin or extracellular matrix. Thus several in vitro
barrier tests have been developed to mimic in vivo conditions.
One such test is the agar overlay method in which a monolayer of cultured
cells is established before adding 1% agar plus a vital stain such as neutral red to a
fresh culture media. The agar forms a barriers between the cells and the material
which is placed on top of the agar sold test sample or liquid samples adsorbed onto
filter paper can be tested with this assay upto 24 hrs.
However the agar may not adequately represent barriers that occur in vivo,
furthermore because of variability of the agar’s diffusion properties, it is difficult to
correlate the intensity of color or width of the zone around or material with the
concentration of leachable toxic products.
A second barriers assay is the Millipore filter assay. This technique establishes
a mondayer of cells on filters made of cellulose esters. The culture medium is then
replaced with medium containing 1% agar and this mixture is allowed to get over the
cells, finally the filter monolay get is detached and turned over so that the filter is on
top for placement of solid or soluble test samples for 2 or more hours. After exposure
to the test samples the filter is removed and an assay is used to determine the effect of
the sample on acellular metabolic activity toxicity in the Millipore filter test is
assessed by the width of the cytotoxic zone around each test sample.
It has the drawback of arbitrarily influencing the diffusion of leachable
products from the test materials.
Dentin barriers tests have shown improved correlation with the cytotoxicity of
dental materials in usage tests in teeth and are gradually being developed for
screening purpose. A number of studies have shown that dentin forms a barrier
through which toxic materials must diffuse to reach pulpal tissue.
The thickness of the dentin correlates directly with the protection offered to
the pulp thus assays have been developed that incorporate dentin disks between the
test sample and the cell assay system.
The use of dentin disks offers the added advantage of directional diffusion
between the restorative material and the culture medium.
OTHER ASSAYS FOR CELL FUNCTIONS
In vitro assays to measure immune functional or other tissue reaction have also
been used. These assays measure cytokine production by lymphocytes macrophages,
lymphocyte, proliferation, chemotaxis or T- cells. Other tests measure the ability of a
material to alter cell cycle or activate complement. Material that activate complement
may generate inflammation or thrombi and may propagate a chronic inflammatory
response whereas concerns about complement activation by dental materials are
fewer, it is possible that activation of complement by resins or metals or their
corrosion products may prolong inflammation in the gingival or pulp.
MUTAGENESIS ASSAYS
They assess the effect of materials on a cells genetic material. There is a wide
range of mechanisms by which materials can affect the genetic material of the cell.
Genotoxic mutagens directly alter the DNA of the cell through various types of
mutations. Each chemical may be associated with a specific type of DNA mutation
Genotoxic chemicals may be mutagens in their native states or may require activation
or biotransformation to be mutagens, in which case they are called promutagens
mutagens may or may not be carcinogens and carcinogens may or may not be
mutagens. Thus the qualification and relevance of tests that attempt to measure
mutagenesis and carcinogensis are extremely complex.
The Ames test is the most widely used short term mutagenesis test and the
only short term test that is considered thoroughly validated. It uses mutant stocks of
salmonella typhimurium that require exogenous histidine native stocks of bacteria do
not require expgenous histidine. Exclusion of histidine from the culture medium
allows a chemical to be tested for its ability to convert the mutant strain to a native
strain. Chemicals that significantly increase the frequency of reversion back to the
native state have a reportedly high probability of being carcinogenic in mammals
because they significantly alter genetic material performance of this test requires
experience in the field and special strains of salmonella to produce meaningful results.
A second test for mutagenesis is the styles cell transformation test. This test on
mammaion cells was developed to offer an alternative to bacterial tests ( Ames test)
which may not be relevant to mammation systems. This assay quantifies the ability of
potential carcinogens to transform standard cell lines so that they will grow in soft
agar untransformed fibroblasts normally will not grow within an agar get whereas
genetically transformed cells will grow below the gel surface. This characteristic that
correlate with the ability of cells to produce tumors in vivo. However there has been
some difficulty in reproducing these results.
ANIMAL TESTS
After screening by initial tests of the materials developed for a specific use
animal tests for biocompatibility are used in mammals such as mice rats hamsters or
guinea pigs. Animal tests are distinct from usage tests in that the material is not placed
in the animal with regard toxic use. The use of an animal allows many complex
interactions between the material and a functioning complete biological system to
occur. The biological responses in animal tests are more comprehensive and may be
more relevant than in vital tests.
Disadvantage include
They can be difficult to interpret and control
Expensive
Time consuming
Often involve significant ethical concerns and paperwork
Relevance of the test to the in vivo use of a material can be quite unclear,
especially in estimating the appropriateness of an animal species to
represent a human.
Mucous membrane Irritation test
This determines a material causes inflammation to mucous membrane or
abraded skin. This test is conducted by placing the test materials and positive and
negative controls into contact with hamster’s cheek pouch tissue or rabbit oral tissue.
After several weeks of contact the control and test sites are examined and the
gross tissue reaction in the living animals are recorded and photographed in color. The
animals are then sacrificed and biopsy, specimens are prepared for histological
evaluation of inflammatory, changes.
Skin sensitization Test ( Guinea pig maximization test)
Used in guinea pigs, the materials are injected intradermally to test for the
development of skin hypersensitivity reactions. This injection is followed by
secondary treatment with adhesive patches containing the test substance.
If hypersensitivity develops from the initial injector, the patch will elicit an
inflammatory response. The skin patch test can result in a spectrum from no reaction
to intense redness and swelling. The degree of reaction in the patch test and the
percentage of animals that show a reaction are the basis for estimating the
allergenicity of the material.
IMPLANTATION TESTS
These tests are used to evaluate materials that will contact subcutaneous tissue
or bone. The location of the implant site is determined by the use of the material and
may include connective tissue, bone or muscle. Although amalgams and alloys are
tested because the margins of the restorative materials contact the gingival most
subcutaneous tests are used for materials that will directly contact soft tissue during
implantation endodontic or periodontal treatment.
Short term implantation is studied by aseptically placing controls are placed at
separate sites and allowed to remain for 1 – 11 weeks. Alternatively an empty tube is
embedded first and the inflammatory reaction from surgery is allowed to subside. The
implant site is then reopened and the test material is placed into this healed site or is
packed into the tube and the test material is placed into this healed site or is packed
into the tube that was placed previously. At the appropriate time, the areas are excised
and prepared for microscopic examination and interpretation. The tissue response can
be evaluated by normal histological, histochemical, or immunohistochemical
method. Implantation tests of larger duration, for identification of either chronic
inflammation or tumor formation are performed in a manner similar to that of short
term tests except the materials remains in place for 1 to 2 years before examination.
Animal tests that measure the mutagenic and carcinogenic properties of
materials have been developed by toxicologists. Those tests are employed with a
strategy tests are applied in a specific order and testing is stopped when any indicates
mutagenic potential of the material or chemical. The validity of any of these tests may
be affected by tissue of species tissue gender and other factors. Tests are generally
divided into
Limited in vivo tests that measure altered lives function or increased tumor
induction when animals are exposed to the chemicals for a fraction of their
lifetimes.
Long term invivo tests are performed by keeping the chemical in contact
with the animals over the majority of its lifetime.
Fidelity, with which the test mimics
USAGE TESTS
These tests may be done in animals or human volunteers. They are distinct
from other animal tests because they require the material be placed in a situation
identical to its intended clinical use. The usefulness of a usage test for predicting
biocompatibility is directly proportional to the fidelity with which the test mimics the
clinical use of the material in every regard include time location environment and
placement techniques. For this reason usage tests in animals employ larger animals
that have similar oral environment to humans such as dogs or monkeys. If humans are
used, the usage test is dentical to the clinical trial.
In dentistry dental pulp periodontium and gingival or mucosal tissue are
generally the largest of usage tests.
These tests are gold standard in that they give the ultimate to whether or not a
material will be biocompatibility.
Advantage
Relevance to use of material is assured.
Disadvantage
Very expensive
Very time consuming
Major legal / ethical issues
Can be difficult to control
Difficult to interpret and quantify.
Dental pulp irritation tests
Materials to be tested on the dental pulp are placed in class V cavity
preparations in intra noncarious teeth of monkeys or other suitable animals. After
careful uniformly sized cavity preparations under sterile conditions the compounds
are placed in equal number of anterior and posterior teeth of the maxilla and mandible
to ensure uniform distribution in all types of teeth. The materials are left in place from
1 to 8 weeks. Zinc oxide eugenol and silicon cements have been used as negative and
positive control materials respectively.
At the conclusion of the study, the teeth are removed and sectioned for
microscopic examination. The tissue sections are evaluated by the investigation
without knowledge of the identity of the materials and necrotic and inflammatory
reaction are classified.
According to the intensity of the response the thickness of the remaining
dentin and reparative dentin for each histological specimen is measured with a
phalomicrometer and recorded. The response of the pulp is evaluated based on its
appearance after treatment. The severity of the lesion is based on disruption of the
structure and the number of inflammatory cells present.
Pulpal response is classified as either
Slight
Mild hyperemia, few inflammatory cells slight hemorrhage in the
odontoblastic zone.
Moderate
Definite increase in number of inflammatory cells hyperemia slight disruption
of odontoblastic zone.
Severe
Decided inflammatory infiltrate hyperemia total disruption of odontoblastic
lay and even localized abscesses
Efforts have been made to develop techniques that identify bacterial insults to
pulp. Usage tests that study teeth with induced pulpils allow evaluation of types and
amount of reparative dentin formed.
MUCOSA AND GINGIVAL USAGE TESTS
Since various dental materials contact gingival and mucosal tissues, the tissue
response to these materials must be measured. Materials are placed in cavity
preparation with subgingival extensions. The materials effects on gingival tissues are
observed at 7 days and again after 30 days. Responses categorized as
Slight characterized by a few mononuclear inflammatory cells (mainly
lymphocytes) in the epithelium and adjacent connective tissue.
Moderate characterized by numerous mononuclear cells in the connective
tissue and a few neutrophils in the epithelium.
Severe evokes a significant mononuclear and neutrophilic infiltrate and
thinned or absent epithelium
Difficulties include
Presence of some degree of preexisting inflammatory in gingival tissue.
Bacterial plaque
Secondary factors are the surface roughness of the restorative material open or
overhanging margins and over contouring or under contouring of the restoration.
DENTAL IMPLANTS IN BONE
The best estimations of the success and failure of implants are gained from
three tests.
1. Penetration of periodontal probe along the side of the implant.
2. Mobility of the implant
3. Radiographs indicating either osseous integration or radiolucency around
the implant.
Previously investigators argued that formation of a fibrous connective tissue
capsule around a subperiosteal implant or root cylinder was the natural reaction of the
body to a material. They argued that this was actually an attachment similar to the
periodontal ligament and should be considered a sign of an acceptable material.
However, in most cases it resembled the wall of a cyst, which is the body’s attempt to
isolate the implanted material as the material slowly degrades and leaches its
components into tissue.
Currently for implants in bone, implants should be completely encased in bone
the most differentiated slab of that tissue fibrous capsule formation is a sign of
irritation and chronic inflammation.
Using in vitro Animal and Usage Tests Together
Generally no single test is used to evaluate the biocompatibility of a new
material. The ways by which these tests are used together however are controversial
and have evolved over the years as knowledge has increased and new techniques
developed.
Early combination schemes proposed a pyramid testing protocol in which all
materials were tested at the bottom of the pyramid and materials were weekend out as
the testing continued towards the top of the pyramid. Tests at the bottom of the
pyramid were unspecific toxicity tests of any type with conditions that did not
necessarily reflect those of the material use. The next layer shows specific toxicity
that presumably death with conditions more relevant to the use of the material. The
final lie was a clinical trial of the material.
Number of tests Number of tests
Later another pyramid schemes was proposed that divided tests into initial
secondary and usage tests. The philosophy was similar to the first scheme except the
types of tests were broadened to encompass biological reactions other than toxicity
such as immunogenicity and mutagenicity. The concept of a usage test in an animal
was also added first only materials that passed the first lier of tests were graduates to
the second lier and only those that passed the second lier were graduated to the
clinical trials.
Two newer schemes have evolved in the recent past with regards to using
combinations of biocompatibility tests to evaluate materials.
Firstly all tests continue to be of value in assessing biocompatibility of a
material during its development and even in its clinical service.
Eg. Tests in animals for inflammatory response may be useful not only during
development of a material but also if a problem is noted with the material after it has
been on the marked for a time.
Secondly these new schemes recognize the inability of current test methods to
accurately and absolutely screen in or out a material.
They incorporate the philosophy that assessing the biocompatibility is an
ongoing process.
STANDARDS THAT REGULATE THE MEASUREMENT OF
BIOCOMPATABILITY
The first efforts of the ADA to establish guidelines for dental materials came
in 1926 when scientists at the national Bureau of standards development
specifications for dental amalgam. Since then standardization has been difficult and a
length, process made more difficult by disagreement on the appropriateness and
significance of particular tests. In 1972, the council on dental materials, instruments
and equipments of ANSI / ADA approved document no 41 for recommended standard
practices for biological evaluation of dental materials. The committee that developed
this documents recognized the need for standardized methods of testing and for
sequential testing of materials to reduce the number of compounds that would need to
be tested clinically.
ANSI / ADA DOCUMENT 41
The original ANSI/ ADA documents 41 for biological testing was updated in
1982 to include tests for mutagencity. This specification uses the linear paradigm for
materials screening and divides testing into initial secondary and usage tests.
The initial tests include in vitro assays for cytotoxicity red blood cell
membrane lysis mutagenesis and carcinogenesis as well as animal tests for
inflammatory or immune responses secondary tests include animal tests for
inflammatory or immune responses. Usage tests include tests for pulpal and bone
response.
The required tests for a given material are not listed specifically, rather it is up
to the manufacturer to select the tests and defined the selection to the ANSI /ADA and
later FDA when applying for approval of the materials.
ISO STANDARD 10993
The ISO 10993 document is the international standard for testing the
biocompatibility of materials unlike ANSI / ADA documents 41, it is not restricted to
dental materials. This document is periodically documents. In 2002 consisted of 16
parts each addressing a different area of biological testing.
Two types of tests for cytotoxicity, sensitization and systemic toxicity and
supplementary tests for chronic toxicity carcinogenicity and biodegradation. In
addition some specialized tests for devices are addressed such as the dentin barrier
test for restorative dental materials. In this standard usage tests are part of
supplementary tests. As the ANSI/ADA standard the selection of test is left to the
manufacturer who must defined the selection upon application for approval.
BIOCOMPATABILITY OF DENTAL MATERIALS
Reaction of pulp
Dentin protects the pulp and owes its validity and its sensitivity to
stimulation of the dental pulp. This intimate relationship has far reaching
clinical application.
The nature of pulp reaction that follows peripheral injury of the dentin
which depends on
The nature of the causative agent
It’s proximity to the pulp.
1 Attrition abrasion
Responses
Mild irritation
Reparative dentin
2. Progressive dental caries
Inflammation of pulp
3. Iatrogenic injuries
May result in inflammation of pulp
As pulp inflammation can also be iatrogenic in origin Do not Harm is the basic
principal should be followed by all members of the health profession.
Iatrogenic pulp injury can develop
During the preparation of a tooth for a restoration
During the insertion of the restorative material
It can be due to inherent irritational properties of the material either.
Clinical components of the material
Injurious products generated during setting of the material
Pulpal reactions can also be caused by Bacterio
Either residual bacteria left behind in the cavity.
Or by the bacteria that gain access to the cavity after restoration as a
result of microleakage.
Pulpal response to cast metal restoration, porcelains etc mainly
depends on the comenting agents, proximation of the pulp and
techniques of cementation.
MICROLEAKAGE
There is evidence that restorative materials may not bond to enamel or dentin
with sufficient strength to resist the forces of contraction during polymerization wear
or thermal cycling when debonding occurs, bacteria, food debris or saliva may be
drawn into the gap between the restoration and the tooth by capillary action. This
effect has been termed microleakage. The importance of microleakage in pulpal
irritation has been extensively studied early studies reported that various dental
restoration materials irritated pulp tissue in animal tests.
However, several recent studies hypothesized that it was often the products of
microleakage, not the restorative materials that caused pulpal irritation. Subsequently
numerous studies should that bacteria were present under restoration and in dentinal
labours which might be responsible for pulpal irritation.
Microleakage can lead to
Secondary caries
Stains or discoloration
Pulpal pathology
Post operative sensitivity
Restorative materials depending on their chemical nature can be grouped as
Metallic restorative materials Non- metal restorative materials
Amalgam Different restorative materials
Direct filling Gold Acrylic
Dental casting Alloys Composite
Techniques Alloys Gold Porcelain
Base metal alloys
AMALGAM
Dental amalgam has been used extensively for dental restoration
Biocompatability of amalgam is thought to be determined largely by the correction
products released while in service. Corrosion in turn depends on the type of amalgam
whether it contains the y2 phase and its composition In cell culture screening tests,
free or non leaded mercury from amalgam is toxic with the addition of copper
amalgams become toxic to cells in culture but low copper amalgam that has set for 24
hrs. does not inhabit cell growth. Implantation tests show that low copper amalgams
are well tolerated but the high copper amalgams can cause severe radiations when in
direct contact with tissue. In usage tests, the response of the pulp to amalgam in
shallow or in deeper but lined cavities is minimal and amalgam rarely causes invisible
damage to the pulp however, pain results from using amalgam is deep unlined cavity
preparations( 0.5 mm or less)
Firstly because of its thermal conductivity
Secondly margins of newly placed amalgam restorations show significant
microleakage marginal leakage of corrosion and microbial products is probably
enhanced by the natural daily thermal cycle in the oral cavity.
Lichenoid reaction representing a long term effect in the oral mucous
membrane adjacent to amalgam restoration is quite often Buccal mucosa and lateral
border of the longer being the areas affected.
For many years a controversy has raged over the biocompatibility at amalgam
restoration because of the presence of element hg. The symptoms of chronic Hg.
Poisoning ( elemental) are
Weakness
Fatigue
Anorxia
Weightloss
Insomnia
Irrilability
Tremois in extremities
Shyness
The signs and symptoms of meth Hg poisoning ( Sea food)
Alaxia (gait disturbances)
Paresthesia of extremities lips and tongue
Constriction of visual fields
Amalgams based on gallium rather than mercury have been developed to
provide direct restorative materials that are mercury free, but appeared to be more
cytotoxic than high copper amalgams chemically these materials show much higher
corrosion rates than standard amalgam leading to roughness and discolouration.
Accepted Hg levels
Patient with amalgam – over Hg level
Normal 0.7 mg/ml
DIRECT FILLING GOLD
The pulp responses from the insertion of cohesive and compacted gold are
associated with condensation, whether with hand instrument / with mechanical
pneumatic instrument.
The responses develop when the condensation occurs over freshly cut dentinal
lubules.( minimum of 2 mm sapiapulpal dentin thickness) but not when the dentinal
tubules are lined with pre-operatively formed reparative dentin induced from previous
episodes of disease / restorative procedures.
Apparently it was found that when compact properly into sound tooth
structure produce only minimal pulp response showing least marginal leakage.
Under extremely rare conditions patients have been reported with
Burning sensation
Lichenoid lesions of oral mucosa
Generalized systemic reactions.
DENTAL CASTING ALLOYS
We have to select alloys based on individual patients specific functional and
economics requirement – There is no one alloy suitable for all applications e.g certain
base metal alloys contain Be, Ni, Co, Cr. And the biocompatibility of each metal
varies to different degree of tissue tolerance.
1) Beryllium : To date there have been no documented cases of Be toxicity at
dental origin.
However, under controlled conditions, when inhalation of dust and fumes can
be anticipated, the presence of be constitutes recognized health hazard.
It may result in
Acute form
Response vary from contact dermatitis to severe chemical
Chronic form
Symptoms range from coughing, chest pain and general weakness
To pulmonary dysfunction
Chronic inflammatory condition - Berylliosis
Which result in lung cancer.
2) NICKEL : Epidermiologic studies on workers in non dental industries have
identified Ni. And Ni. Compound as carcinogenic. The major hazardous route
is aspiration. The use of nickel has been controversial for many years because
of the biological properties of nickel ions and compound.
There is no experimental evidence that Ni. Compounds are carcinogenic when
admixture by oral cutaneous route.
It causes dermatitis ( contact) because it is a potential sensitizing agent and in
sensitized patients intra orally.
Burning and tingling sensation during the first 24 hours and.
Later exhibited a slight erythematous reaction in the mucosa.
However there is no correlation found between the incidence of Ni
hypersensitivity and the presence of intra oral Ni alloy restoration.
Cobalt alloys have a potential for
Dermatologic
Systemic effect that may result from patient and personal exposure to
cobalt alloys.
Inhibition of cell metabolism is reversible in tissue culture by high levels of
serum proteins suggesting that protein binding or buffering in inflamed pulp tissue
may play an important role in detoxifying these materials in vivo. The initial
response after exposing pulp tissue to these highly alkaline pulp capping agents is
necrosis to a depth of 1 mm or more. The alkaline pH also helps to coagulate any
hemorrhagic exudates of the superficial pulp shortly after necrosis occur neutrophils
infiltrate into the subnecrotic zone. After 5-8 weeks only a slight inflammatory
response remains within weeks to months however the necrotic zone undergoes
dystrophic calcification which appears to be a stimulus for dentin bridge formation.
When resins are incorporated, the Ca(OH2) become less irritating and are able
to stimulate reparative dentin bridge formation mere quickly than Ca(OH)2 suspension
alone with no zone of necrosis and reparative dentin is laid down adjacent to the liner.
This indicates that replacement odontoblasts form the dentin bridge in contact with
the liner.
The liners such as copal vanishes and polystyrenes are not generally used
under resin based materials, because resin components dissolve the film of vanish.
Because liners are used in such thin layers, they do not provide thermal
insulation but do initially isolate the dentinal tubule contents from the
cavity preparation.
They may also reduce penetration of bacteria or chemical substances for a
time.
The vanish also prevent penetration of corrosion products of amalgams
into the dentinal tubules.
CERAMICS
Among the most biocompatible materials used for dental restorations are
ceramics and the use of dental constructions manufactured using ceramics has
increased during the past few decades, new ceramics materials have been used both as
high strength care materials and as veneers.
This biocompatibility of dental ceramics has been largely assumed on the
basis of studies of traditional feldspathic porcelains and the low corrosion rates of
feldspathic materials studies showed clearly that all ceramics materials are not
equivalent in their initial state of fabrication with aging after polishing procedure.
GROUP II
ZINC PHOSPHATE CEMENT
It has an irritational potential intermediate to Z no E and silicate cement
As a base it is not highly toxic
As a lulling agent on pressure causes a widespread three dimensional
lesion involving all the coronal pulp tissue as the phosphoric acid within
the mix of 2n phosphate cement is forced in the dentinal tubules.
A young tooth with wide open dentinal tubules is more susceptible to
such an intense inflammatory response compared to an older tooth which
has sclerotic / Reparative dentin that blocks dentinal tubules and prevent
the acid from reaching the pulp.
The P-11 of the cement 3 minute after mixing is 3.5 the P-11 rapidly
increases thereafter approaches neutrality in 24 hours. Thus damage to the
pulp occurs during the first few hours after insertion of the cement, this
can be prevented by using appropriate varnishes and dentin bonding
agents.
Tendency to form complexes with proteins would limit its diffusion
through the tissues
In this regard polycarboxylate cements are equivalent to ZOE cements.
Post operative sensitivity effects are negligible for cements.
GLASS IONOMER CEMENT
Glass ionomers have been used as both cement ( luting agent) and as a
restorative material light cured ionomer systems have been introduced these systems
use BISGMA or other oligomers as pendant chains on the polyacrylate main chain.
In screening tests freshly prepared ionomer is mildly cytotoxic but this
effect is reduced over time.
The fluoride release from these materials is of therapeutic value
The overall pulpal biocompatibility of glass ionomer cement has been
attributed to the weak nature of the polyacrylic acid. It is unable to diffuse
through dentin due to its high molecular weight.
Histological studies in usage tests show that any inflammatory intitrak
from ionomer is minimal or absent after a month.
GROUP III
SILICATE CEMENT
It has high irritational potential
It is an ideal material for the control in studies that evaluate pulp reactions
to restorative materials.
The ptt is below 3 at the time of insertion and the ptt remains below
neutrality even after 1 month calcium hydroxide base provides adequate
pulp protection from the cement.
RESINS
Those is no indication that commonly used acrylic resins produce systemic
effects in humans.
The amount of residual monomer in processed polymethyl is externally
low.
The oral mucosa and underlying tissues function as barriers that
significantly diminish the volume of monomer reaching the blood stream.
Residual monomer that reaches the blood stream is rapidly hydrolyzed to
methacrylic acid and excerted.
Clinical experience indicates that true allergic reactions to acrylic resins
seldom occurs in the oral cavity.
Theoretically, such reaction( toxic and allergic) could occur after contact
with polymer residual monomer benzyl peroxide hydroquinone.
Clinically most patients reported denture induced SORE MOUTH which
on evaluation indicates tissue irritation which is generally related to
unhygiene conditions / trauma caused by ill fitting prosthesis.
Repeated prolonged contact with monomer may result in contact
dermatitis.
Finally inhalation of monomer vapour may be detrimental therefore, the
use of monomers should be restricted to well ventilated areas.
COMPOSITE RESINS
The material whether conventional / microfilled auto polymerizing photo
activated (UV/VL) are found irritating to the pulp. In vitro, freshly set chemically
cured and light cured resins often cause moderate cytotoxic reaction in cultured cells
over 24 to 72 hrs. of exposure although several newer systems seem to have minimal
toxicity. The cytotoxicity is significantly reduced 24-48 hrs. after setting and by the
presence of a dentin barrier.
Cytotoxicity is thought to be medicated by resin compounds released from the
materials. It appears likely that reactive radicals generated during polymerization of
the resin are responsible for pulp injury.
Evidence indicates that the light cured resins are less cytotoxic than
chemically cured systems, but this effect is highly dependent on curing efficiency of
the light and the type of resin system used.
BONDING AGENTS
Numerous bonding agents have been developed and are applied to cut dentin
during restoration of the tooth. Many of these reagents are cytotoxic to cells if tested
alone, however when placed on dentin and rinsed with water between applications of
subsequent reagents as prescribed by the manufacturer the cytotoxicity is reduced.
Long term in vitro studies suggest that compounds of the bonding agent may
penetrate upto 0.5 mm of dentin and cause significant suppression of cellular
metabolism for upto 4 week after application suggesting that residual unbound
reagents may cause adverse effects.
Hydroxyethyl methacrylate (HEMA) a hydrophilic resin contained in several
bonding systems is at least 100 times less toxic in tissue culture than BIS GMA
studies using long term in vitro systems have shown, however that adverse effects of
resins occur at much lower concentrations when exposure times are increased to 4-6
weeks. Many cytotoxic effects of resin compounds are reduced significantly by the
presence of a dentin barrier studies have shown that combinations of HEMA and
other resins found in dentin bonding agents may ad synergistically to cause cytotoxic
effects in vitro.
LINERS AND VARNISHES
Calcium hydroxide cavity liner come in many forms, ranging from saline
suspensions with a very alkaline PH( above 12) to modified forms containing Zinc
oxide, titanium dioxide and resins.
The high PH of calcium hydroxide in suspensions leads to extreme
cytotoxicity in screening tests calcium hydroxide cements containing resins cause
mild to moderate cytotoxic effects in both cut and long term set conditions.
CONCLUSION
Biocompatibility of a dental material depends o its composition location and
interaction within the oral cavity. Diverse biological response to these materials
depends on whether they release their components and whether those components are
toxic immunogenic or mutagenic at the released concentrations. The location of a
material in the oral cavity. Partly determinesits biocompatibility finally the
interactions between the material and the body influence the biocompatibility of the
material. In the end, no material can be shown to be 100% safe or risk free, further
more the clinician must rely on clinical judgement, data available and analyze the risk
benefit ration before choosing a dental material.
Elements such as potassium and sodium appear to be the most liable from the
ceramics but these elements are not particularly hazardous. In cytotoxicity assays by
siogren et al in 2000, there was no evidence of cytotoxicity in dental ceramics
indicating good biocompatibility in vitro break down in products of dental ceramics
have not been reported to have known toxic effects and several of the ions in dental
ceramics are considered non toxic.
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