Biological Properties of Dental Materials 1-General Dentistry / Orthodontic Courses by Indian Dental Academy

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Contents
Introduction
Biocompatibility v/s Biological properties
Components of biocompatibility
Adverse effects of dental materials
Toxicity
Inflammation
Allergy
Mutagenicity
Carcinogenicity
Local & Systemic effects of materials
Key principles that determine adverse effects from materials
Concept of Immunotoxicity
Oral anatomy that influences the biological response
Enamel
Dentine & Pulp
Bone
Measuring the biocompatibility
Invitro tests
Animal tests
Usage tests
Clinical trials
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Advantages & disadvantages of biocompatibility tests
Correlation among the tests
How tests are used together ?
Regulatory standards for measurement of biocompatibility
Current biocompatibility issues in dentistry
Reaction of pulp to different materials
Dentine bonding & Dentine bonding agents
Dental amalgam
Dental cements
Bleaching agents
Latex
Impression materials
Biocompatibility of metals
Reaction of other oral soft tissues to restorative materials
Denture base material
Soft denture liner & adhesives
Reactions of bone & soft tissues to Implant materials
Conclusion
List of references

Introduction
Biological properties of Dental
materials
Biocompatibility = Lack of interaction
Biocompatible material = list of negatives
Non degradable
Non irritant
Non toxic
Non allergic
Non carcinogenic
Non mutagenic
Total inactivity = Passive ignorance ?
More appropriate active acceptance
Biocompatibility : ability of a material to perform with an
appropriate host response, in a specific application.

Components
Initial Physiochemical interaction
Effect of the tissue environment
Local host response
Transport of products Systemic effects
Establishment of solid-liquid interface as any material is
implanted into the tissue
Protein absorption is the first event
Immediate response to injury is inflammation
Very few is know about the factors
Condition of the host
Properties of the material
Context in which the material is used
Eg: Biocompatible as Crown & Bridge but not as an implant material

Adverse effects from Dental
materials
Toxicity
Placement of a foreign material in the body carries the possibility
of toxicity
Toxicity can be of 2 types
Acute toxicity.
Chronic toxicity.
Type 1: requires prolonged or repeated administration
Type 2: requires very few or one dose but long lasting effects
Type 1 chronic toxicity is a possibility with Biomaterials
Eg: metal ions released by gradual corrosion of an implant
According to J.J.Jacobs et al (1991)
Vanadium lungs
Aluminium surrounding tissues
Fortunately, materials causing over toxicity are no longer used in
dentistry.

Inflammation
May result from toxicity or allergy and often it
precedes toxicity.
Oedema, inflammatory cell infiltrate
Current biocompatibility research
Allergy
Allergy
Body specifically recognizes material as foreign &
reacts disproportional to the amount of material
Gell & Coombs classification of immune responses
Type 1: Atopic or anaphylactic reaction
Type 2: Cytotoxic hypersensitivity reaction
Type 3: Immune complex disease
Type 4: Delayed or cell mediated hypersensitivity
Type 5: Stimulating antibody reaction
Type 6: antibody dependent, cell mediated Cytotoxic
reaction

Type 1, 2, 3 quickly. Eosinophils, Mast cells & B
lymphocytes
Type 4 delayed. Monocytes & T cells
Allergic response individuals immune system
recognizes a substance as foreign
Allergic reactions initially dose independent,
disproportionate
Toxic / inflammatory reactions dose dependant,
proportionate
Mutagenic reactions
Alteration in base pair sequence (mutation)
2 types
Alteration in cellular process that maintain DNA integrity
Direct interaction
Can occur from radiations, chemicals, errors in DNA
replication process
Examples
Metal ions nickel, copper, beryllium
Few components of root canal sealers
Resin based materials to some extent
Carcinogenic response
Currently no dental material has been shown to be
carcinogenic for dental applications in patients
However, carcinogenesis is often exceedingly
difficult to prove or disprove conclusively
Local & Systemic effects of
materials
Local effects
Pulp
Periodontium
Root apex
Oral tissues buccal mucosa, tongue
Systemic effects
Function of the distribution of substances released from the materials
Simple diffusion
Lymphatics
Blood vessels
Access to the body by
Ingestion & absorption in gut
Inhalation
Release at tooth apex
Absorption into mucosa
Systemic response depends on
Duration & concentration of the exposure
Excretion rate of the substance
Site of the exposure

Key principles that determine
adverse effects from materials
A) various types of metal corrosion & other types of
material degradation :
Biocompatibility depends on the degradation process
Corrosion is determined not only by material composition
but also by the biological environment
Many ways for release of products in host
Metal prosthesis releases metal ions by
Electrochemical force
Particles dislodged by mechanical forces
Resin composites
Cyclic stresses
Salivary esterases

B) Surface characteristics :
Surface is quite different from interior
Examples
Dental casting alloy containing 70% gold may have 95%
gold at its surface
Relative unpolymerized state of a sealant at its surface

The surface composition, roughness, mechanical &
chemical properties are critical to the biocompatibility

Concept of
Immunotoxicity
Concept of Immunotoxicity
Based on the principle that small alteration in
the cells of immune systems by materials can
have significant biological consequences
Examples:
Mercury ions increase the Glutathione but
Palladium decreases Glutathione content of
Monocytes
HEMA may change the ability of Monocytes to
direct an immune response once challenged by
plaque or others agents
Oral anatomy that influences
the Biological response
Enamel : seals the
tooth
Peroxides permeate
intact enamel
Dentine & Pulp :
Smear layer
Effective in reducing the
hydrostatic pressure but
not diffusion
Acid etching

Bone : Osseointegration & Biointegration
Osseointegration
Implant & bone closely approximate to each other
Approximation less than 100 A
No fibrous tissue in intervening space
Titanium alloys
Biointegration
Implant & bone are fused to one another & are
continuous
Occurs with Ceramic & Ceramic coated metal implants
Eg: Calcium & Tri calcium phosphate, Hydroxyapatite,
Bioglass
Measuring the
Biocompatibility
Is not simple and methods of measurement are
evolving rapidly as more is know about the
interactions between dental materials and oral
tissues & as technologies for testing improves
Classified as
In Vitro test
Animal test
Usage test
Clinical trial special case of a usage test in humans
In Vitro test
Placement of a material
or component of it in
contact with cell,
enzyme or some other
isolated biological
system
Direct
Material in contact
Physically present or
extract from material
Indirect
Some sort of barrier
Types of cells used in In-vitro
assays
Primary cells :
Directly from an animal into culture
Grows for only a limited time

Continuous cells :
Primary cells transformed to allow them to grow
indefinitely

Testing procedures & extent of
testing
Manufacturers responsibility to test new material
A) Initial tests :deals with general biocompatibility & systemic
effects of a material
Short term systemic toxicity test
Short time oral administration
Toxicity profile
Acute systemic toxicity test
I.V administration
Inhalation toxicity test
Dental remedies that have significant volatility under usage condition
Hemolysis test
In vitro evaluation of hemolytic activity of materials intended for
prolonged tissue contact
Emes mutagenicity & the dominant lethal test
To asses the potential carcinogenic activity

Cytotoxicity tests
Measures cell count or growth after exposure to a
material
Method 1 :
Place the cells in the well of a cell culture dish
If Cytotoxic - cell may stop growing, exhibit cytopathic
features or detach from the cell
Method 2 :
Measurement of cytotoxicity by a change in membrane
permeability
Loss in membrane permeability is equivalent or very nearly
equivalent to cell death
Identifies the cells that are alive or dead
Tests
Sensitization test
Oral mucous membrane irritation test
Subcutaneous implant test
Bone implant test
Usage tests
Pulp &Dentine test
Response of dentine & pulp
Minimum experimental variables
Pulp capping & Pulpotomy test
Endodontic usage test
Assess response of the pulp wound & the periapical tissue
Influenced by level at which the pulp tissue is cut off &
total removal of pulp tissue
Bone implant usage test
To evaluate all materials that, during their intended use,
penetrate the oral mucosa and the adjacent bone
Correlation among the tests
Lack of correlation
Less prominent biological response
Barriers may exist
Measure different aspects of the biological
response to the material
Advantages & disadvantages
of Biocompatibility tests
In-Vitro test
Advantages
Quick to perform
Least expensive
Standardized
Large scale screening
Excellent for mechanisms of interaction
Disadvantages
Relevance to In-Vivo questionable
In- Vivo test
Advantages
Allows complex systemic interactions
More comprehensive
More relevant
Disadvantages
Relevance to use ?
Expensive
Time consuming
Ethical concern
Difficult to control
Difficult to interpret & quantify
Usage test
Advantages
Relevance to use of material is assured

Disadvantages
Very expensive
Time consuming
Major legal / ethical

usage progression

secondary of

primary testing

Linear paradigm, relies on the accuracy of the primary tests (challenged by
Major et al 1977)
No prediction of results in usage tests
Lack of correlation in In-Vitro tests
How the tests are used together
to measure the Biocompatibility

Non linear thinking

U Progression
S of
P Testing

All the 3 tests are done
As test progresses Usage test predominates
Most common progression

Usage
Recognizes
Primary Secondary complexity
Standards that regulate the
measurement of Biocompatibility
ANSI / ADA : earliest attempt in 1933
1972 The Council on dental material,
instruments & equipment of ANSI / ADA approved
document no. 41 for recommended standard
practices for biological evaluation of dental
materials
In 1982 updated to include test for mutagenicity
Uses linear paradigm
ISO Standard 10993 :
Not restricted to dental materials only
First published in 1992
In 2002 ISO 10993 consisted of 16 parts
2 types of tests
Initial Cytotoxicity, sensitization & systemic toxicity.
In Vitro / animal test
Supplementary chronic toxicity, carcinogenicity &
bio-degradation. Animals / Humans
Specialized tests Eg: dentine barrier test

Current Biocompatibility
issues in dentistry
Reactions of pulp to
different materials
Micro leakage :
If a material does not
bond or debonds at
enamel or dentine
Previous belief
Concept of nano leakage
Between mineralized
dentine & bonded
material. In very small
spaces of
demineralized matrix
into which material did
not penetrate
Hydrolytic degradation
of dentine material
bond
Dentine bonding :
Bonding to dentine is
difficult composition,
wetness, low minerals
Smear layer formation &
removal
Many studies have
shown
0.5mm of RDT is
adequate
Dentine is a buffers of
protons
Penetration of acids <
100 micrometers
Dentine bonding agents :
HEMA is 100 times less cytotoxic in tissue culture
than Bis GMA
Bis GMA, TEGDMA, UDMA

Amalgam
Dental amalgam :
Toxic or not ?
In usage test response of
pulp to amalgam in shallow
or deep lined cavities
Gallium based amalgam
Excessive gallium release,
roughness, discolor
Significant foreign body
reaction
Absorption : 1 3
micrograms / day
Minimum dose to produce
observable toxic effect is 3
micrograms / kg body
weight

Dental cements

Resin based materials :
Resin composites
luting or restorative
Light cured < cytotoxic
than chemically cured
Pulpal reaction
diminishes after 5 8
weeks
Protective liner or
bonding agent minimizes
Pulpal reaction

Glass ionomers :
Luting agent &
restorative material
Weaker polyacrylic acid
Fluoride release
Histological studies in
usage test shows that
any inflammatory
infiltrate to ionomer is
minimal or absent after 1
month

Zinc phosphate :
Luting agent & base
Thermal conductivity closer
to enamel
Pulpal damage in first 3
days due to initial low
PH(4.2), reaches neutrality
in 48 hours
When placed in deep
cavities ?
Inclusion of Ca- OH to the
powder or lowering the
concentration of phosphoric
acid
Calcium hydroxide :

Suspension form Resin containing

Highly cytotoxic Mild to moderate cytotoxic

Necrosis 1mm or > No necrotic zone
shortly
Neutrophil infiltration Dentine bridge formation
5 to 8 weeks is quick
Slight inflammatory response
wks - months
Dystrophic calcification

Dentine bridge
Zinc oxide eugenol :

Suppresses the nerve transmission
Inhibit synthesis of Prostaglandins & Leukotriens

Hammesfahr 1987, initiated the search for a
biocompatible resin base system incorporating
Calcium hydroxide PRISM VLC DYCAL

Soft tissue response to the
luting cements
Apply petroleum jelly

Clean the excess

Any residues of cement
Bleaching agents :
Usually contain some form of peroxide
In-Vitro traverses the dentine & in sufficient
conc. can be cytotoxic
Penetrates intact enamel & reaches the pulp in
few min.
May burn gingiva
Latex
Latex :
6% to 7% of surgical personnel may be allergic
42% adverse reactions to occupational materials
Hypersensitivity may be due to true latex allergy or reaction
to accelerator & antioxidants
White, milky sap

Addition of ammonia

Hydrolyses & degrades the sap proteins to produce allergens
Liquid vulcanization solid
latex sulphur + heat rubber

Soaked in hot water leaches out allergens
Allergenicity depends on collecting, preservation
& processing
Impression materials
Impression materials :
Price & Whitehead
(1972) Allergic
contact stomatitis &
Foreign body response
Sydiskis & Gerhardt
(1993) some degree
of toxicity in cell culture
Gabriela Mazzanti et al
(2005) no significant
evidence of diffuse
inflammation or local
skin reaction
Casting alloys
Dental casting alloys :
John c. Wataha 2000
Release of elements is essential for adverse effects
Identifying & quantifying the elements that are
released is most relevant measure from stand point of
Biocompatibility
a) Release of elements from casting alloys
Multiple phases
Inherent tendency to release elements lability
Eg: Cu, Ni, Cd, Zn & Ga highly labile
Environmental conditions - PH
b) Systemic toxicity
Released metals may not be inside the body
Route of access I.V < Peritoneal < Oral
Distribution there is no documented proof that
these material cause Systemic toxicity

c) Local toxicity
Micro environment exists around casting alloys
Metal ions can cause local toxicity
Increased exposure causes increased toxicity

d) Allergy to dental casting alloys

Elemental release is essential for allergy
Metal ions Haptens
Allergy & Toxic reaction difficult to distinguish

Patch test for metals controversial
Application of metal ion to skin in the form of patch
Injecting small amount of ion below the skin
Assessment of the response is difficult
Salt of metal ions important for response
Eg: chloride, sulphate, nitrate salts
Vehicle whether its water, oil or petrolatum can vary
the response
Grimaudo N.J 2001 true allergic hypersensitivity to
dental casting alloys is rare

Nickel :
Common component
Incidence of allergy 10% 20%
Cross reactivity between nickel & palladium (33%
& 100%)
Nickel ions induces ICAMs in the endothelium
release of cytokines
It may contribute to any intraoral inflammation
around nickel containing crowns
Beryllium :
Used in Ni-Cr alloys in conc. of 1 2 wt%
Forms thin adherent oxides
Documented carcinogen
Berylliosis
Individual is hypersensitive
Inhalation of beryllium dust, salts, fumes
Reaction of other oral soft tissues
a) Denture base
materials
Methacrylates
Greatest potential for
hyper sensitization
Acrylic & diacrylic
monomers, curing
agents, antioxidants,
amines, formaldehydes
For the patients most of
these materials have
been reacted in
polymerization and thus
less prone
True allergy of oral mucosa to denture base
material is very rare

Residual monomer (methyl methacrylate)

Allergic acrylic stomatitis

Heat cured is better

b) Soft denture liners &
adhesives
Release of plasticizers
Extremely cytotoxic
Effects are masked by
the inflammation
Denture adhesives show
severe cytotoxic
reactions In-Vitro
Large amount of
formaldehyde
Allowed significant
microbial growth

Denture cleansers
Used to cleanse the prosthesis
Eg : Hypochlorite, mild acids, etc.
Biocompatible & cause no harm to the patient

Artificial teeth
Acrylic & Porcelain teeth

Acrylic teeth is preferred in poor ridges
Implants
Reaction of bone & soft
tissues to implant material
Materials Ceramics, Metals, Carbons & Polymers
a) Reaction to ceramic implant material
Very low toxic effects. Oxidized state, corrosion resistant
Used as a porous or dense coating
Root surface porosities > 100microns (firmly bound )
Root surface porosities < 100microns (fibrous ingrowth)
b) Hydroxyapatite
Relatively non resorbable form of calcium phosphate
Coating material & ridge augmentation material
c) Beta -Tricalcium phosphate
Another form of calcium phosphate, has been used in
situations where resorption of the material is desirable
d) Reaction to pure metals & alloys
Metal oldest type of oral implant material
Shares the quality of strength
Initially selected on the basis of the Ease of
fabrication
Stainless Steel, Chromium-Cobalt-Molybdenum,
Titanium and its alloys
Most commonly used is Titanium
Titaniums Biocompatibility is associated with its
fast oxidizing capacity.
Corrosion resistant & allows Osseointegration
Soft tissue :
Epithelium forms bond
with implant similar to
that of tooth
C.T apparently does not
bond to the titanium, but
forms a tight seal that
seems to limits ingress of
bacteria & its products
Conclusion
List of references
Restorative dental materials by Craig & Powers
Phillips Science of dental materials
Chemistry of medical & dental materials by J.W.Nicholson
Concise Encyclopedia of medical & dental materials by David Williams
Dental biomaterials by Arturo N. Natali
Dent material 2005;21(4):371-74
JPD 2001 Aug;86(2):203-9
Gen Dent 2001 Sep-Oct;49(5):498-503
JPD 2000 Feb;83(2):223-34
JPD 1998 Sep;80(2):203-9
JPD 1993;69;431-5
J Biomater Appl 1987 Jan;1(3):373-81
BDJ 1972;133:9-14

Precautions to be taken in the
Lab
Make certain the ventilation system in room is
properly functioning
During operation of the dental lathe wear a
protective eyewear & a mask
Clean & disinfect the dental lathe at least
once daily
Use sterile rag wheels, stones & fresh
pumice for each patient's prosthesis
Leader in continuing dental education

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