Biocompatibility

presented By
Dr. V. Chakradhar
1st year post graduate student
Dept. of prosthodontics & crown and bridge
Contents 2

• Definition

• Historical background

• Biocompatibility requirements

• Biocompatibility tests

• Correlation among different tests

• Adverse effects from exposure to dental materials

• Biocompatibility of dental materials

• Review of literature

• Conclusion

• References
Definition 3

• Biocompatibility is the ability of a material to elicit an appropriate

biological response in a given application in the body. [Craig]
• Capability of existing in harmony with surrounding biologic
environment. [ GPT 9 ]
• Biocompatibility is not a property of just a material, but rather a
property of how a material reacts with its environment.
HISTORICAL BACKGROUND 4

 Although the concept of the ethical treatment of patients extends back to the
time of Hippocrates (460-377 BC.), the idea that new dental materials must
be tested for safety and efficacy before clinical use is much more recent.

 As late as the mid 1800s,dentists tried new materials for the first time by
putting them into patients' mouths
 5

 Many exotic formulations were used.

For example, Fox developed a "fusible metal“ that consisted of bismuth, lead, and tin, which
he melted and poured into the cavity preparation at a temperature of approximately 100 C.

 Even G.V. Black used patients to test many of his new ideas for restorative materials, such
as early amalgam

 The current philosophy about testing the biological properties of dental materials in a
systematic way evolved in the 1960s as the need to protect patients became politically
acute and as the number of new materials increase.
BIOCOMPATIBILITY REQUIREMENTS 6

1. They should not sensitize and produce allergic reactions.

2. They should not be mutagenic.

3. They should not be carcinogenic.

4. They should not contain any toxic diffusible substances which get
released and enter into the circulatory system.

5. They should not be harmful to soft & hard tissues of the oral cavity in
particular and the whole body in general.
 DEFINING THE USE OF A MATERIAL 7

T h e r e are several factors that must be considered when trying to measure the
biological response.

The most important factors include :

 Location of material

 The duration of material in the body

 Stresses placed on material

Location of material 8

 The location of a material is important to its overall biological response.

 In general, materials that communicate through the epithelium or lie

completely beneath it will need closer scrutiny when assessing the
biological response than materials that do not penetrate the epithelium.

 Similarly, materials that penetrate tooth enamel will need more scrutiny
than materials than do not.
 The duration of material in the body 9

 The duration of the presence of a material is an important factor, because

many interactive effects between the body and material take some time to
develop.

 In general, the most stringent tests to measure biocompatibility are required

for materials that are present for the longest times.

 Long durations give sufficient time for the material to affect the body and for
the body to affect the material in many complex ways
Stresses placed on material :
10

 stresses placed on the material are important to the biological

response

 These stresses may be physical, chemical, or thermal in nature.

 Short-term, long-term, and fatigue stresses all need to be considered

when assessing the effect of stress on the biological performance of
material.
Biocompatibility tests
 12

• Autian (1970) was the first to propose a structured approach in

biocompatibility testing:

• 1. Non specific toxicity (Cell culture or small laboratory animals)

• 2. Specific toxicity (Usage tests e.g. in sub-human primates)
• 3. Clinical testing in humans.
 13

• In 1984, it was Langeland who proposed a sequence which was later

adopted as the ISO technical report 7405:
• Primary tests – cytotoxicity tests , genotoxicity tests
• Secondary tests – sensitization tests
- Mucosal irritation tests
-implantation tests
Preclinical usage tests – pulp and dentine usage test
-Pulp capping and pulpotomy usage tests
- Endodontic usage test
- acc to phillips 14

In vitro Animal Usage

tests tests tests
Invitro tests
In vitro tests 16

Tests are done in test tube, cell culture dish, or other wise out side a living organism

Invitro
tests

Direct Indirect
test test
Direct tests: 17

 Material contacts the cell system without barrier.

further subdivided into :

• Those in which the material is physically present with the cells
• Extract from the material contact the cell system
Indirect tests {Tests That Use Barriers} 18

• when there is a barrier of some sort between the material and the
cell system.

• Agar overlay method

• Millipore filter assay

• Dentin barrier tests

 AGAR OVERLAY METHOD 19

• The cell layer, which has been previously stained with neutral red (NR), is
covered with a thin layer of agar .

• Samples are placed on top of the agar for a time.

• If the material is cytotoxic, it will injure the cells and the neutral red will be
released, leaving a zone of inhibition
 Millipore filter assay 20

• A monolayer of cells is grown on a filter Cell layer

filter
• That is turned over so that test materials are placed on the filter
and leachable diffusion products are allowed to interact with the
Materials tested
cells.
filter

• After exposure the toxicity in the Millipore filter test is assessed Cell layer

by the width of the cytotoxic zone around each test sample.

 Dentin disk barrier test method 21

• A dentin disk is used as a barrier

• The material is placed on one side (A) of the dentin disk (B)

• Collection fluid (cell culture medium or saline) is on the other side of the disk (C).

• Cells can also be grown on the collection side.

• Components of the material may diffuse through the dentin

• and the effect of the medium on cell metabolism can then be measured.

• To assess the rate of diffusion, the collection fluid can be Circulated into and out of the
collection chamber (C).
 22

In vitro tests can be roughly subdivided into those

• that measure cytotoxicity or cell growth

• measure some metabolic or other cell function, and

• those that measure the effect on the genetic material in a cell

(mutagenesis assays).
Cells used for in vitro tests 23

1. primary cells:

• taken directly from animals and cultured .

• These cells will grow for only a limited time in culture but usually retain many of
the characteristics of cells in vivo
 24

2. Continuously grown cells or cell lines :

• These are 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

characteristics

• but they do consistently exhibit those features that they do retain.

Cytotoxicity tests 25

• Cytotoxicity tests assess cell death caused by a material

• by measuring cell number or growth before and after exposure to
that material
 Membrane permeability tests 26
• Membrane permeability tests are used to measure cytotoxicity by the ease with
which a dye can pass through a cell membrane,

• because membrane permeability is equivalent to or very nearly equivalent to cell

death

The fibroblasts are rounded and detached ,

Light microscopic indicating that they are either dead
view of a noncytotoxic interaction between a material (dark or dying. The material is a type of calcium
image at bottom of the picture) and periodontal ligament fibroblasts hydroxide pulp-capping agent
in a cell culture (in vitro) test.
 Tests for Cell Metabolism or Cell Function 27

• use the biosynthetic or enzymatic activity of cells to assess cytotoxic response.

• A commonly used enzymatic test

- MTT (MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide]test

- NBT (nitroblue tetrazolium),

- Alamar Blue tests

• all being colorimetric assays quantitatively measure cell proliferation using a

fluorescent indicator that allows continuous monitoring of cells over time.
 28

other assays for cell function :

• measures cytokine production by lymphocytes and macrophages.

• Tests measure the ability of a material to alter the cell cycle or

activate complement system.
 Mutagenesis Assays: 29

Assess the effect of a biomaterial on a cell’s genetic material:

• Ames test:

• The Ames test is a widely employed method that uses bacteria to test whether a given chemical can
cause mutations in the DNA of the test organism

• Mutant strains of the bacteria Salmonella tymphimurium were used

• These bacteria contain mutations in the enzyme that synthesize histidine

• Histidine is responsible for further synthesis of proteins

• A positive test indicates that the chemical is mutagenic

 30

• A second test for mutagenesis is the Styles’ cell transformation test.

• This test on mammalian cells offers an alternative to bacterial

tests(Ames test).

• However, the Ames test is widely used.

Advantages Disadvantages 31

• Quick to perform • Relevance to in vivo is questionable

• Least expensive • Another significant disadvantage includes

• Can be standardized the lack of inflammatory and other tissue-

• Large-scale screening protective mechanisms in the in vitro

• Good experimental control environment.

• Excellence for mechanisms of • cannot predict the overall biocompatibility

interactions of a material
Animal tests
 Animal tests 33

• Animal tests for biocompatibility, usually involving mammals such as mice, rats, hamsters, or guinea
pigs.

DISADVANTAGES
ADVANTAGES

• Relevance to use of material is

• Allows complex systemic interactions
• Response more comprehensive than in vitro questionable
• Expensive
tests
• Time consuming
• More relevant than in vitro test
• Legal/ethical concerns
• Difficult to control
• Difficult to interpret and quantify
 34

• Mucous membrane irritation test –

• Determines whether a material causes inflammation to mucous membranes or

abraded skin

• Skin sensitization test- materials are injected intradermally

• test for development of skin hypersensitivity reactions, followed by secondary

treatment with adhesive patches containing the test substance.
 35

Implantation tests are

• used to evaluate materials that will contact subcutaneous tissue or bone.

• The location of the implantation site is determined by the use of the material
and may include connective tissue, bone, or muscle.
Usage tests
 Usage Tests 37

• Usage tests may be done in animals or in human study participants.

• They are distinct from other animal tests because they require that the material be placed in
a situation identical to its intended clinical use.

• The usefulness for predicting biocompatibility is directly proportional to the fidelity with
which the test mimics the clinical use of the material in every regard, including time,
location, environment, and placement technique.

• For this reason, usage tests in animals usually employ larger animals that have similar oral
environments to humans, such as dogs, mini-swine or monkeys
 38

ADVANTAGES DISADVANTAGES

• Relevance to use of material is • Very expensive

assured • Very time consuming

• Major legal/ethical issues

• Can be difficult to control

• Difficult to interpret and quantify

 Dental Pulp Irritation Tests 39

• In dentistry, dental pulp, periodontium, and gingival or mucosal tissues are the main
targets of usage tests.

• Generally, materials to be tested on the dental pulp are placed in class 5 cavity
preparations in intact, non-carious teeth.

• At the conclusion of the study, the teeth are removed and sectioned for microscopic
examination

• Tissue necrotic and inflammatory reactions classified according to the intensity of

the response.
 40

• Although most dental-pulp irritation tests non-carious teeth, without inflamed

pulps, there has been increased concern that inflamed dental pulp tissue may
respond differently to liners, cements, and restorative agents.

• So, usage tests on teeth with induced pulpitis, will allow evaluation of the
type and amount of reparative dentin formed.
 Dental Implants in Bone 41

• At present ,the best predictors for success of implants are careful patient selection and
ideal clinical conditions.

• As such, there are three commonly used tests to predict implant success:

(1) penetration of a periodontal probe along the side of the implant,

(2) mobility of the implant, and

(3) radiographs indicating either osseous integration or radiolucency around the implant.
 42

• A bone implant is considered successful if it exhibits no mobility, no

radiographic evidence of peri-implant radiolucency, has minimal vertical bone
loss and is completely encased in bone,

• Has an absence of persistent peri-implant soft tissue complications.

• Any fibrous capsule formation is a sign of irritation and chronic inflammation,

• which is likely to lead to micromotion of the implant and ultimately to

loosening and failure
Mucosa and Gingival Usage Tests 43

• Tissue response to materials with direct contact of gingival and mucosal

tissues is assessed by placement in cavity preparations with subgingival
extensions

• The material’s effect on gingival tissues are observed

• and responses are categorized as slight, moderate, or severe, depending

on the number of mononuclear inflammatory cells (mainly lymphocytes
and neutrophils) in the epithelium and adjacent connective tissues.
 44

A difficulty with this type of study is

• the frequent presence of some degree of preexisting inflammation
in gingival tissue due to the presence
• of bacterial plaque,
• surface roughness of the restorative material,
• open or overhanging margins, and
• over- or under-contouring of the restoration.
Correlation Among In Vitro, Animal, and Usage Tests 45

• In the field of biocompatibility, some scientists question the usefulness of in vitro

and animal tests in light of the apparent lack of correlation with usage tests and
the clinical history of materials.

• However, lack of correlation is not surprising

• Because in vitro and animal tests often measure aspects of biological response
that are more subtle or less prominent than those observed during a material’s
clinical use.
 46

• Thus it is important to remember that

• each type of test has been designed to measure different aspects of

biological response to a material, and correlation is not always to be
expected.
 47

• Three methods were used to evaluate the following materials: ZOE

(zinco-xide eugenol) cement; resin composite; and silicate cement

(1) four different cell culture tests,

(2) an implantation test,

(3) a usage test in class 5 cavity preparations in monkey teeth.

48
 Using In Vitro, Animal, and Usage Tests
Together 49
• Pyramid testing protocol, in which all materials were
tested at the bottom of the pyramid and materials were
“weeded out” as the testing continued toward the top of
the pyramid.

• “unspecific toxicity” tests of any type (in vitro or animal)

• specific toxicity tests

• final tier was a clinical trial of the material.

• philosophy was similar to the first scheme, except that

the types of tests were broadened to encompass
biological reactions other than toxicity, such as
immunogenicity and mutagenicity.
 Non Linear Progression of tests 50

•Mjör in 1977 he modified the linear paradigm to a non-

linear pattern, where simultaneously all three tests would be
performed on the tested material.
ADVERSE EFFECTS FROM EXPOSURE
TO DENTAL MATERIALS
ADVERSE EFFECTS FROM EXPOSURE
TO DENTAL MATERIALS 52

• Any biomaterial that is placed adjacent to a natural tissue in the

body can induce local or systemic biological effects.

• These effects are controlled by the substances that are released

from the material and the biological responses to those substances.
 Local effects 53

• Form dental materials, local effects might occur in the pulp tissue, in
the periodontium, at the root apex, or in nearby oral tissues such as
the buccal mucosa or tongue

• These local effects depends on:

• (1) the ability of substances to be distributed to these sites,

• (2) their concentrations, and

• (3) exposure times, which may range from seconds to years.

 systemic effects 54
Their routes of entry into the body include
• (1) ingestion and absorption
• (2) inhalation of vapor
• (3) leakage through the tooth apex; and
• (4) absorption through the oral mucosa
The ultimate systemic response depends on four key variables:
• (1) concentration of the substance;
• (2) time of exposure;
• (3) excretion rate of the substance; and
• (4) organ of importance or site at which exposure occurred
INFLAMMATORY AND ALLERGIC REACTIONS: 55

• Inflammation may result from trauma (excessive force, laceration, and abrasion), allergy, or toxicity

• Leads to the activation of the host’s immune system

• Histologically, the inflammatory response is characterized by edema of the tissue caused initially by
an infiltration of inflammatory cells such as neutrophils and, later in the chronic stage, to the action of
monocytes and lymphocytic cells.

• Eg: metal ions first interact with a host molecule to produce a delayed Type IV hypersensitivity
reaction, which is modulated by monocytes and T cells.

• This type is often associated with contact dermatitis

 56

• Some materials such as latex, can cause allergy directly by activating

antibodies to the material.

• These are classified as Type I, II, or III reactions, according to the Gell and
Coombs

• These reactions occur quickly and are modulated by antibody-producing

eosinophils, mast cells, or B lymphocytes
ALLERGIC REACTIONS 57

• Allergic contact dermatitis or stomatitis

• This is most common adverse reaction to dental materials

• The interval between exposure to the causative agent and the occurrence of
clinical feature varies between 12-48 hrs.

• It usually occurs where body surface makes direct contact with the allergens.

• E.g.: - monomers of bonding agent, acrylic components of dental cements.

• Industry workers who handle these materials are also affected

 58
• allergic reactions to nickel-containing metals:

prostheses with copings and

a severe reaction of lips to
framework made from
nickel-containing wire
nickel-alloy (crown on left
a watchband buckle
and three-unit FDP on right
 IMMUNOTOXICITY 59

• The principal concept of immunotoxicity is that substances leached from materials can
alter immune system cells.

• Monocytes control chronic inflammatory and immune responses, and they also
secrete many substances that alter the actions of other cells.

• Thus, if substances leached from a biomaterial change the monocyte’s ability to

secrete these substances, the biological response can be greatly influenced and this
may greatly impair cellular defense mechanisms against bacteria (Schmalz et al.,
2011).
 TOXICITY 60

• The adverse reactions of tissues to selected foreign substances resulting in

unacceptable invivo interactions (GPT 9).

• It can be at the local or systemic level depending on the amount ,rate of

release, specific type of substance available to tissues.(dose dependent)
GENOTOXICITY, MUTAGENICITY,
61
AND CARCINOGENICITY

• Genotoxicity refers to any adverse effect on the DNA of an organism.

• If the adverse effect is transferred to the next (heritable) generation of cells, the effect is
called mutagenicity

• Mutagenic reactions occur when a physical or chemical agent changes the genetic
material of an organism, (DNA) permanently.

• Several metal ions from dental materials—such as

• beryllium, copper, and nickel and some components of root canal sealers are mutagenic.
 62

• Genotoxic effects have been reported for beryllium and gallium salts (Kuroda
et al., 1991).

• Occupational data indicate that beryllium may increase the risk of lung cancer
and other tumors in humans.(Aller, 1990; Ashby et al., 1990;Hayes, 1997)

• No genotoxic effects were found for several titanium-containing alloys, CP Ti,

and one Ni-Cr−based alloy according to studies by Wang and Li, 1998.
Biocompatibility among
dental materials
 INTERFACES WITH DENTAL MATERIALS 64

• Although several interfaces may be present in the restorations, the dentin–

cement or dentin–resin interfaces are the most important in transition areas
for transfer of leached substances into dentinal fluid

• incomplete bonding or resin penetration into the collagen mesh of acid-etched

dentin can lead to fluid ingress along gaps wider than 1 μm, which is referred
to as MICROLEAKAGE.
 65

• The bacteria that migrate to the pulp may initiate an infection of pulp tissue

• The gap also promotes material breakdown along the unsupported margin.

• This breakdown increases the gap width, which allows larger particles and
molecules to progress toward the pulp chamber

• Causes marginal staining and compromised esthetics

 66
• If the resin penetrates the collagen network of dentin but does not penetrate it completely
• then a much smaller gap (less than 0.1 μm in most cases) will exist between the mineralized matrix
of dentin and the collagen–resin hybrid layer
• This much smaller gap has been claimed to allow NANOLEAKAGE
• does not allow bacteria or bacterial products to penetrate the marginal gaps of the restoration and the
pulp.
• However, fluid exchange most likely occurs, and this may degrade the resin or the collagen network
• thereby reducing the longevity of the dentin–resin bond.
• one must be aware of potential immune responses in the pulp and periapical tissues that may occur
independently of leakage phenomena
DENTAL - AMALGAM 67

• Biocompatibility of amalgam is thought to be determined largely by the corrosion products released

• Unreacted mercury or copper leaching out from these high-copper alloys has usually been the
constituent leading to adverse response

• Cell damage was seen in treated cultures exposed to particulate γ1 (Ag2Hg3)

• Bacterial tests on the high copper amalgam pellets have revealed little inhibitory effect on serotypes of
Streptococcus mutans, thus suggesting that metallic elements were not released in amounts
necessary to kill these microorganisms.

• Although the high-copper amalgams seem biologically acceptable in usage tests, liners are suggested
for all deep cavities
 68

• Amalgams based on gallium rather than mercury

• Clinically, these materials show much higher corrosion rates than
standard amalgams.
• This leads to surface roughness and discoloration
 BONDING AGENTS AND RESIN BASED
COMPOSITES 69
• Hydroxyethyl methacrylate (HEMA), a hydrophilic resin contained in several bonding systems, is at least

100 times less cytotoxic in tissue culture than Bis-GMA.

• Longer-term in vitro studies suggests that the components of the bonding agents may penetrate up to

0.5 mm of dentin and cause significant suppression of cellular metabolism for up to 4 weeks after

application.

• However, when placed on dentin and rinsed with water between applications as prescribed by the

manufacturer, cytotoxicity is reduced.

• If the dentin in the floor of the cavity preparation is thin (<0.1 mm), there is some evidence that HEMA is

cytotoxic in vivo.
 ESTROGENICITY 70

• Estrogenicity is the ability of a chemical to act as the hormone estrogen does in

the body. If these chemicals are not indigenous to the body, the substance is
called a xenoestrogen.

• The concern about estrogens in dentistry centers around a chemical called

bisphenol A (BPA), which is a synthetic starting point for bis-GMA (bisphenol-A-
glycidyldimethacrylate) composites in dentistry.
 71

• One test commonly used to assess xenoestrogenic activity is the E-screen assay.

• Studies have shown that BPA is probably 1000-fold less potent as an estrogen than
the native estrogen hormone.

• If bis-GMA is used, the amount released after placement of a restorative filling is too
small to be of concern.

• To overcome any concerns, products free of bis-GMA can be used.

 GLASS IONOMERS 72

• In screening tests, freshly prepared GIC is mildly cytotoxic, but this effect is reduced over time.

• In usage tests the pulp reaction to these cements is mild, and histological studies show that any
inflammatory infiltrate from ionomer is minimal or absent after 1 month.

• There have been several reports of pulpal hyperalgesia for short periods (days) after placing
glass ionomers in cervical cavities.

• The overall pulpal biocompatibility has been attributed to the weak nature of the polyacrylic acid,
as well as to its high molecular weight.
 CALCIUM HYDROXIDE 73

• Calcium hydroxide cements containing resins cause mild-to-moderate cytotoxic effects

in tissue culture in both the freshly set and long-term set conditions.

• The initial response after exposing pulp tissue to these highly alkaline aqueous pulp-
capping agents is necrosis to a depth of 1 mm or more.

• When resins are incorporated into the compound, these calcium hydroxide compounds
become less irritating and are able to stimulate reparative dentin bridge formation.
 ZINC PHOSPHATE CEMENT 74

• In vitro screening tests indicate that zinc phosphate cement elicits strong-to-moderate cytotoxic
reactions that decrease with time.

• Focal necrosis, observed in implantation tests with zinc phosphate cements injected into rat pulp,
confirm the cytotoxic effects of this cement when it contacts pulp tissue.

• In usage tests in deep cavity preparations, moderate-to-severe localized pulpal damage is

produced within 3 days, probably because of the initial low pH (4.2 at 3 minutes).

• By 5 to 8 weeks, only mild chronic inflammation is present, and reparative dentin has usually
formed.
 ZOE CEMENTS 75

• The effects of eugenol are dose dependent and diffusion through dentin dilutes eugenol by
several orders of magnitude.

• In cavity preparations in primate teeth (usage tests), ZOE caused only a slight to-moderate
inflammatory reaction within the first week. This was reduced to a mild, chronic inflammatory
reaction, with some reparative dentin formation (within 5 to 8 weeks), when cavities were deep.
 ZINC POLYACARBOXYLATE CEMENT 76

• In short-term tissue culture tests, cytotoxicity of freshly set and completely set cements has
correlated with both the release of zinc and fluoride ions into the culture medium and with a
reduced pH.

• subcutaneous and bone implant tests over a 1-year period have not indicated long-term
cytotoxicity of these cements.

• These cements evoke a pulpal response similar to that caused by ZOE, with a slight-to-
moderate response after 3 days and only mild, chronic inflammation after 5 weeks.

• Reparative dentin formation is minimal with these cements.

 BASE METAL ALLOYS 77

• Metal ions can be leached from cast metal restorations or wrought appliances into the oral cavity.

• Metallic ions released through corrosion processes are responsible for much of the metal–protein
or metal–cell interaction behavior of dental metals and alloys. Ions released from the superficial
layers of cast alloys may be quite cytotoxic.

• The amount and nature of released cations varies depending on the type of alloy, the environment,
and the corrosion mechanism.

• Nickel is known to be highly allergenic, especially in females. It has been reported that 34% to
65% of patients who are allergic to nickel are also allergic to palladium.
 78

• Some base metals, such as nickel-chromium-beryllium (Ni-Cr-Be)

alloys, exhibit increased corrosion in low-Ph environments.

• Some evidence suggests that metal appliances can lead to gingivitis

or periodontitis. (Schmalz and Garhammer, 2002)

• High-noble (HN) and noble (N) alloys are corrosion resistant so

negligible level of leaching is seen.
 TITANIUM AND TITANIUM ALLOYS 79

• In vitro evaluation of titanium biocompatibility, percentage attachment

efficiency, and proliferation of human fetal fibroblasts and human gingival
fibroblasts reveals that a surface layer of titanium oxide (Ti2O3) has the ability
to coexist with living tissues and organisms.

• Based on these studies one can conclude that titanium is relatively nontoxic,
non-injurious, and not physiologically reactive.

• However, it is susceptible to attack by acidic fluoride products.

 DENTAL CERAMICS 80

• Ceramic materials are known for their high levels of biocompatibility

• glazed ceramics were less irritating than resin-based composite or gold

• minor observed irritations may be attributed to mechanical irritation, e.g., from roughened surfaces.

• Metal oxides such as Al2O3, BaO, , K2O, Li2O, Na2O and ZrO2 are components of either dental

core ceramics or dental veneering (layering) ceramics, and

• These oxides and related compounds in dental ceramics exhibit minimal dissolution in normal oral

fluids and beverages

 81

• highly acidic environments can increase the release rates of certain

metal and silicon ions. For example, acidulated phosphate fluoride
(APF) is known to corrode the surfaces of veneering porcelains as
well as glaze and stain ceramics.

• most dental ceramics do not induce an adverse effect when they

contact the oral mucous membrane
ZIRCONIA - BIOCOMPATIBILITY 82

• The biocompatibility of zirconia has been evaluated extensively.

• No local or systemic cytotoxic effects or adverse reactions have been traced to zirconia.

• The bone response of zirconia in vivo and the inflammation adjacent to zirconia have
been shown to be satisfactory.

• Furthermore, bacteria and pathogen seem to adhere to zirconia to the same extent as to
other materials
 Denture base materials 83

• Denture base materials, especially methacrylates, have been associated with immune
hypersensitivity reactions of gingiva and mucosa more than any other dental material

• In addition to hypersensitivity, visible light-cured denture base resins and denture base
resin sealants have been shown to be cytotoxic to epithelial cells in culture

• However, most of these materials have undergone the polymerization reaction, and
the incidence of hypersensitization is quite low
Denture adhesives 84

• Denture adhesives have been evaluated in vitro and show severe cytotoxic
reactions.

• Several had substantial formaldehyde content.

• The adhesives also allowed significant microbial growth.

• Newer formulations that add antifungal or antibacterial agents have not yet been
shown to be clinically effective.
Review of literature
 Review of literature 86

• Rivard CH et al in the year 2002 conducted a In vivo biocompatibility

testing of peek polymer for a spinal implant system in rabbits

• Observed neither necrosis nor swelling of the dura mater and nerve roots
was observed.

• Concluded that the PEEK polymer is harmless to the spinal cord; thus it
might be used as component in the spinal implant system.
Rivard CH, Rhalmi S, Coillard C. In vivo biocompatibility testing of peek polymer for a spinal implant system:
a study in rabbits. Journal of Biomedical Materials Research. 2002 Dec 15;62(4):488-98.
 87

• Wang L et al in 2014 conducted several invitro and invivo studies on peek

and concluded

• There is increased biocompatibility and antibacterial activity in vitro, and

promoted osseointegration in vivo, which suggests that it holds potential to
be applied as dental implant material in dental tissue engineering
applications.

Wang L, He S, Wu X, Liang S, Mu Z, Wei J, Deng F, Deng Y, Wei S. Polyetheretherketone/nano-fluorohydroxyapatite

composite with antimicrobial activity and osseointegration properties. Biomaterials. 2014 Aug 1;35(25):6758-75
 88

• KIZILDAG A et al in 2019 on Autogenous Tooth Bone Graft Combined with

Platelet-Rich Fibrin in Calvarial Defects

• suggested that ATBG combined with PRF significantly increased the new
bone formation and enhanced bone healing in cranial defects(peri-implant
surfaces) .

Kizildag A, Taşdemir U, Arabacı T, Aksu KIZILDAG C, Albayrak M, Şahin B. Effects of Autogenous Tooth Bone Graft
And Platelet-Rich Fibrin in Peri-İmplant Defects: An Experimental Study in An Animal Model. Journal of Oral
Implantology. 2019 ; 30( 6 ) 1662-66
 89

• Endang W in the year 2019 conducted invivo animal study on the new Bone
Graft Substitute in Bone Tissue Regeneration

• Concluded that the local hydroxyapatite combined with extracted sea

cucumber (Stichopus hermanni) collagen could potentially enhance
osteoblast formation in promoting bone healing and regeneration.

Endang W, Hsu LC, Lan WC, Wen SC, Ou KL, Chou HH, Huang MS, Sugiatno E. Application of a Promising Bone Graft
Substitute in Bone Tissue Regeneration: Characterization, Biocompatibility, and In Vivo Animal Study. BioMed
Research International.2019
conclusion 90

• It is the duty of each dentist to do the treatment planning after evaluating

whether the benefits of the material being used outweigh the risks for the
patient under consideration.

• However, if restorative treatment is essential to restore occlusion and function,

these risks may be accepted, although informed consent procedures must still
be satisfied before treatment is begun.
 References 91

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 93

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