BIOCOMPATIBILITY OF DENTAL

MATERIALS

PRESENTED BY- DR. BALPREET KAUR

MDS 1st year
Department of Prosthodontics and Crown & Bridge
CONTENTS
• Introduction
• Definitions
• Biocompatibilitiy requirements
• Adverse effects
• Tests for evaluation of biocompatibility
• Progression of biocompatibility tests
• Standards that regulate the measurement of biocompatibility
• Various dental materials considered for biocompatibility
• Physical factors affecting pulp health
• Conclusion
• References
Introduction

• Biocompatibility refers to the study of interaction of various materials

with human tissues
• Materials used in dentistry come in direct contact of the hard tisssues
of teeth, the oral mucosa, the pulp, and the periapical tissues
• Due to this intimate long term contact, the materials should exhibit a
high degree of biocompatibility
• For the biocompatibility of a biomaterial, it is not only important that
minimal diffusible substances are released but when it is in body
contact, but the material must also solve the purpose for which it has
been designed.
Definitions

• Biocompatible - Capable of existing in harmony with the surrounding

biologic environment (GPT 10)

• Biomaterial - refers to any nonvital material intended to interact with

biological systems within or on the human body

• Biocompatibility is formally defined as the ability of a material to elicit

an appropriate biological response in a given application in the body
Biocompatibility Requirements

• They should not sensitize and produce allergic reactions

• They should not undergo biodegradations
• They should not be carcinogenic
• They should not contain toxic diffusible substances which gets
released and enters into the circulatory system
• They should not be harmful to soft and hard tissues of the oral cavity
in particular and the whole body in general.
Adverse Effects of Dental Materials
Health effects can be subdivided into-:
• Systemic toxicity

• Local reactions

• Allergic reactions

• Other reactions
Systemic toxicity
• Almost all dental materials release substances into the oral cavity, from
where they may enter the human body through different routes,
including swallowing of saliva and inhalation, with subsequent passage
of the epithelial barriers in the gastrointestinal tract or the lungs.
• These substances may, via the blood circulation, be transported to
different organs
• According to the time frame-:
- acute (up to an exposure period of 24 h)
- subacute (up to 3 months)
- chronic toxicity
Local reactions

• Substances released from dental materials may generate a reaction

(e.g., inflammation or necrosis) in adjacent tissues, such as oral
mucosa/gingiva, pulp, or alveolar bone

Inflammation of the gingiva in contact Pulp necrosis after application of

with a porcelain-fused-to-metal crown resin fillings
Local reactions

• Factors other than substances released from dental materials may

cause a local tissue reaction

- The presence of bacteria that accumulates at the surface, at the

margin, or under a material is the most important factor

- Mechanical/physical irritation, such as pressure caused by dentures,

can also cause local tissue reactions
Allergic reactions
• An allergic reaction to a substance can be triggered if the organism
was previously sensitized to this compound

• Dental materials may cause allergies of type I (immediate reaction)

and type IV (delayed reaction)
Allergic contact dermatitis on the
fingertip of a dentist after contact
with resin-based composite
a. Pronounced gingivitis of an orthodontic patient
(nickel-containing device) who revealed a positive reaction in a
patch test. The most important differential diagnosis would be
“plaque-associated” inflammation. b Persisting perioral and
labial eczema of an orthodontic patient (copper–nickel–
titanium wires). The patient had no intraoral symptoms, and
there was complete regression after replacement with titanium
wires
Other Reactions

Mutagenicity- Carcinogenicity-
It is the ability of a substance It is the ability of the material or
to pass on the genetic damage substance released from it to
to next generation induce malignant tumors

Genotoxicity- Teratogenicity-
Refers to the ability of a It is the ability of certain
substance released from substance to cause
materials to cause alterations of malformation during embryonic
the genome DNA development
Tests For Evaluation of Biocompatibility

Biocompatibility tests are classified on three levels (tiers) :-

Group I : In Vitro tests

Group II : In Vivo tests
Group III : Usage tests
In Vitro tests
• It is done outside a living organism
• Requires placement of a material or a component of a material in
contact with a cell, enzyme, or some other isolated biological system
Classification of in vitro tests

Direct Indirect
( when the material (when there is a barrier of
contacts the cell system some sort between the
without barriers) material and the cell system)

Material is physically Extract from the material

present within the cells contacts the cell system
Cytotoxicity tests

• Cytotoxicity tests assess cell death caused by a material by

measuring cell number or growth before and after exposure to
that material

Noncytotoxic interaction Cytotoxic interaction

• 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

a.The size of the zone of neutral red decolorization around the

sample is indicative of cell damage. b The cell morphology (e.g.,
rounding, disintegration) indicates the extent of damage
Tests for cell metabolism and cell function

• It uses the biosynthetic or enzymatic activity of cells to assess cytotoxic response

• Tests that measure DNA synthesis or protein synthesis are common examples of
this type of test
- MTT test-: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
- NBT test-: nitroblue tetrazolium
- XTT test-: 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-
carboxanilide
- WST test-: water-soluble tetrazolium
• Alamar Blue test- quantitatively measure cell proliferation using a fluorescent
indicator that allows continuous monitoring of cells over time.
_x0002_
Tests that use barrier (Indirect)

• Because direct contact often does not exist between cells and
materials during in vivo use, several in vitro barrier tests have been
developed to mimic in vivo conditions
1. Agar overlay method- it uses agar to form a barrier between the
cells and the material

The cell layer, which has been previously stained with neutral red (NR), is covered
with a thin layer of agar (A).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
2. Millipore filter assay- in which a monolayer of cells is grown on
a filter that is turned over so that test materials are placed on the
filter and leachable diffusion products are allowed to interact
with the cells
3. Dentin disk barrier test- A dentin disk forms a barrier between
the test material and target cell

The material is placed on one side (A) of the dentin disk (B) in the device used to hold the dentin disk. 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
Mutagenesis assays

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

• Ames test -: is the most widely used short-term mutagenesis test. It
looks at the conversion of a mutant stock of Salmonella typhimurium
back to a native strain, because chemicals that increase the frequency
of reversion back to the native state have a high probability of being
carcinogenic in mammals
• Styles’ cell transformation test-: This test is done on mammalian cells
which offers an alternative to bacterial tests
In Vivo tests ( Animal tests)
• Usually involving mammals such as mice, rats, hamsters, or guinea
pigs
1. Mucous membrane irritation
test- determines whether a
material causes inflammation to
mucous membranes or abraded
skin

2. Skin sensitization test- materials

are injected intradermally to test
for development of skin
hypersensitivity reactions, followed
by secondary treatment with
adhesive patches containing the
test substance
3. Implantation tests- used to evaluate materials that will contact
subcutaneous tissue or bone.

Formation of an abscess at the interface between material

and connective tissue (arrows mark the location of the open
ends of the Teflon tube containing the test material, which
was implanted into the tissue)
Usage test

• May be done in animals or in human study participants

• They require that the material be placed in a situation identical to its

intended clinical use

• Also termed as clinical trial

• Gold standard
1. Dental pulp irritation test-

• Materials to be tested on the dental pulp are placed in class 5 cavity

preparations in intact teeth without caries

• The teeth are removed and sectioned for microscopic examination

• Tissue necrosis and inflammatory reactions are classified according to

the intensity of the response.
2. Dental implants in bone -
• Materials used for dental implants are inserted into the jaw
• Criteria for implant sucess-:
- Early implant success- 1 to 3 years,
- Intermediate implant success- 3 to 7 years
- Long-term implant success- more than 7 years

• Tests to predict implant success-:

- Penetration of a periodontal probe along the side of the implant
- Mobility of the implant
- Radiographs indicating either osseous integration or radiolucency
around the implant
3. Mucosa and gingival usage tests-
-Tissue response to materials with direct contact of gingival and
mucosal tissues is assessed by placement in cavity preparations with
subgingival extensions.
- Material’s effect on gingival tissues is observed and responses are
categorized as slight, moderate, or severe, depending on the number of
mononuclear inflammatory cells
- Disadvantages
• presence of bacterial plaque
• surface roughness of the restorative material
• open or overhanging margins
• overcontouring or undercontouring of the restoration
Classical progression of biocompatibility tests
Newer schemes for biocompatibility testing
Standards that regulate the measurement of biocompatibility

1. ANSI/ADA Specification 41-

- Three categories of tests are described in the 2005 American National
Standards Institute (ANSI)/ADA specification: initial, secondary, and usage
tests.

2. ISO 10993-
- Several multinational working groups, including scientists from ANSI and
the ISO, were formed to develop standard ISO 10993, published in 1992.
- The standard divides tests into initial and supplementary tests to assess
the biological reaction to materials
Various dental materials considered for biocompatibility

Metals : Amalgam & mercury

Nickel
Beryllium
Gold
Cobalt, Chromium, Platinum
Resins : Acrylic Resins
Chemically cured composite resins
Light cured composite resins
Bonding agents
Soft liners
Cements : Silicate cement
Zinc Phosphate cement
Glass ionomer cement
Zinc oxide Eugenol cement
Resin based composite cements
Miscellaneous : Impression materials
Implant materials
Conditioning agents
Rubber dam
Gingival Retraction cords
Bleaching agents
Laboratory materials
Amalgam & Mercury

-Pulp response is related to condensation pressure

-Rate of diffusion into enamel & dentin-inversely related to degree of

mineralization

-Amalgams release sufficient vapor to cause absorption of between 1

and 3 microgram per day of mercury.
Mercury

- Occurs in 4 forms - metal, inorganic ion, as a component of silver

mercury phase & Methyl or ethyl mercury

- Methyl mercury :-formed by bacteria or other biological systems

acting on metallic mercury. Absorbed 90-95% from the gut. Most
toxic

- Ingested metallic mercury is poorly absorbed by gut (0.01%)

- 65% to 85% of mercury vapor that is inhaled, is retained in body

Mercury levels in blood

- Subjects with amalgam restoration : 0.7ng/mL

- Subjects without amalgam restoration : 0.3ng/mL

- Lowest level at which earliest : 35ng/mL

non-specific symptoms occur

- Therefore, widespread removal of amalgam restorations is

unwarranted
Mercury Hazard to Dental Personnel

- Via inhalation & skin contact (allergic contact dermatitis)

- Accidental spillage
- Handling with bare fingers
- Improper storage
- Improper retrieval of spilled mercury or waste amalgam
- Faulty equipment
Nickel

-Most common cause of allergic dermatitis (10- 20%)

-Female : Male - 10 : 1

- Nickel ions are a documented mutagen in humans, but there is no

evidence of carcinogenic response intraorally.
Beryllium

- Used in Ni- Cr alloys to increase the castability of these alloys

- Documented carcinogen in metallic or ionic state

-Berylliosis : inflammatory lung disease due to inhalation of beryllium

dust or fumes

-Highest risk to dental technicians during melting & trimming of alloy

Beryllium

-Prevention :

Confirm allergy by Patch test

Avoid base metal restorations in patients with known allergy

Good ventilation & exhaust

Gold

-Pure gold is inert

-Allergy to gold is very rare (1 in 1 million)

Platinum, Cobalt & Chromium

- No documented evidence of any allergy or toxicity

Acrylic Resin
- Cause allergic reactions (denture stomatitis) when used as denture base material or
provisional fixed partial denture resin

- Highest risk for dental professionals due to frequent exposure to unpolymerized monomer
 Chemically Cured Resin Composites

-Polymerization of composites is never complete

-Require use of matrix pressure to enhance adaptation to cavity walls : thus a

potential pulp irritant

-Chronic pulpitis : persists for indefinite period, after 2 to 3 weeks, develop

massive pulp lesion

-Thin coating of hard setting Ca(OH)2 cement recommended for deep cavities
Light-Cured Resin Composites

- Visible light cured systems : greater depth of cure, shorter curing

time, less porosity & more wear-resistant restorations than UV light
cured systems less pulp response

- Use twice the recommended time exposure to light

- Conservative cavity preparation & incremental curing . Thus, there is

no need for matrices & pressure, to gain adaptation and less toxicity
to pulp
Bonding Agents

-Reduce expected pulp responses induced by subsequent placement of

more toxic resin-based composite materials

-Low to average inflammatory cellular response values despite small to

average remaining dentin thickness values
Soft Liners

- Candidiasis due to fungal colonization

Silicate Cement

- Pain on cementation due to low pH

- High osmotic pressure : movement of fluids into dentinal tubules

Zinc Phosphate Cement

-Prevention :-

-High P/L ratio

-Coating dentin with varnish, dentin bonding agent, liner, hydrophilic

resin primer or thin wash of Ca(OH)2 mechanical plugging of
tubules & neutralization of acids
- (pH below 4 after 1 hr)
Glass Ionomer Cement

- Polyacrylic is weak acid & has high molecular wt.

Weaker penetration

Pulpal response is less

- Water hardening (water setting) GIC is more satisfactory

Zinc Oxide Eugenol Cement

- Obtundant effect on pulp

- Free eugenol can irritate soft

tissues

- Eugenol : potent allergen

Resin Based Composite Cements

- Dual cure : light-cured & chemically self-cured

- Resin based cementing agents : low viscosity

- If light curing is inadequate, self curing not effective to complete

polymerization causing pulpal responses
Impression Materials

- Irreversible hydrocolloids :- Inhaling fine airborne particles (dust) can

cause silicosis & pulmonary hypersensitivity. Therefore
dustless/dustfree alginate is preferred

- Elastomers :- Cellular toxicity levels

• Polyether > Addition Silicone > Polysulphide

• Hypersensitivity potential of polyether catalyst system

Implant Materials

- Commercially pure Titanium & its alloys are the most biocompatible
restorative materials

- Bio-glass ceramics used as implant materials also exhibit good

biocompatibility
Implant Materials
- Osseointegration :- Materials that allow
osseointegration have very low degradation
rates,and they tend to form surface oxides that
promote bony approximation within 100Ao space
eg. Titanium, tantalum, several forms of
ceramics,Bio-glass ceramics

- Biointegration :-Involves the adaptation of bone or

other tissue to the implanted material without any
intervening space along the tissue material interface
eg. Hydroxyapatite(HA), tricalcium phosphate (TCP)
and other calcium phosphates
Latex

• It is obtained from rubber tree

• Ammonia is added as preservative, but can cause allergic reaction
• Vulcanization is done to form rubber which is done using chemicals
like sulphur which are also allergens
• Oedema, chest pain and a rash on neck and chest of severely allergic
persons
• Both patients and dentists are highly exposed to this allergen
Rubber Dam

- Cause allergy to some patients due to latex content

- Rubber dam clamps can injure gingival tissues

Gingival Retraction Cords

- Can injure gingival soft tissues during placement

Bleaching Agents

-Like sodium per borate & hydrogen peroxide :- cause periodontal soft
tissue injury

Laboratory Materials

-Cyanide solution : used as an electrolyte for the electroplating of cast &

dies is very poisonous

-Siliceous particles : used in silica bonded investment materials can cause

silicosis
 Physical factors affecting Pulp Health
Microleakage

-Free penetration of fluids, micro-

organisms & oral debris along interface
between restoration & tooth,
progressing down the walls of cavity
preparation
-It can result in :
•Secondary/Recurrent caries,
acute/chronic pulpitis, pulp abscess, etc.
•Staining or discoloration

•Sensitivity due to continuing pulpal

irritation
 Microleakage

-Prevention :-
• Use bonding/adhesive techniques for better adaptation of
restoration to tooth surface

• Regular monitoring of restoration

•Use cavity varnish below amalgam restoration

(leakage space filled by corrosion products thereby sealing cavity :
but requires much time)
 Thermal Changes

• Temperature fluctuations in oral cavity may crack restorative material

or produce undesirable dimensional changes Microleakage

• Metals are good conductors of heat, causing sensitivity with large

metallic restorations eg. Amalgam or gold inlays.
 Galvanism
Flow of current when two dissimilar metallic restorations
oppose each other in oral cavity

Due to different electromotive potentials of opposing metals

Saliva acts as electrolyte

Contact Short-circuit current flows through pulp

causing pain and discomfort
Prevention :-
- Placement of insulating base
- Applying varnish on cavity walls
- Proper planning of restoration
 Estrogenicity
• It is the ability of a chemical to act as the hormone estrogen
does in the body

• bisphenol A ( BPA) can act on estrogenic receptors in cells

• The fear is that, release of these substances might alter normal

cellular development
 Conclusion
• Due to rise in number of patients with allergies from different
materials, the practicing dentists should be aware about the
allergies documented to known materials

• For establishing diagnosis, it is essential to obtain proper history

related to allergy, clinical examination and confirmatory tests

• It is mandatory for the clinician to know and understand the

biocompatibility of the dental materials, so as to provide
maximum advantage and minimum risk to the patient
 References

• Anusavice KJ, Chiayi Shen, H Ralph Rawls. Phillip’s Science of Dental

Materials Kenneth J. Anusavice, PhD, DMD ; Chiayi Shen, PhD ; H.
Ralph Rawls, PhD. St. Louis, Missouri Elsevier; 2013

• Dental Materials – Properties & Manipulation- Craig

• Biocompatibility of Dental Materials- Gottfried Schmalz, Dorthe

Arenholt-Bindslev
THANK YOU