Bio compatibility/prosthodontic courses

BIOCOMPATIBILITY TESTS
INDIAN DENTAL ACADEMY
Leader in Continuing Dental Education
www.indiandentalacademy.com

 CONTENTS
1. Introduction:
2. Def of biocompatibility
3. Key words
4. Biocompatibility: historical background
5. Measuring The Biocompatibility Of Material
6. Defining the Use of a Material
7. Types of tests: advantages and disadvantages

`
8. Standards : Advantages and Disadvantages
9. ANSI/ ADA Document 41
10. ISO Standard 10993
11. Current Bio-compatibility Issues In Dentistry
12. Summary :
13. References :

INTRODUCTION

 The biocompatibility of dental materials is a
complex topic that draws on knowledge from
biology, the patient risk factors, clinical experience,
and engineering.
 Biocompatibility is now recognized as a
fundamental requirement for any dental material.
 Now specifications and criteria are to be met for
every new material that is released into market .
 As the knowledge about the adverse effects of any
material has gone to the common man these
biocompatibility tests have become a must


 Def of biocompatibility:
 Ability of a material to elicit an appropriate
biological response in a given application in the
body

 KEY WORDS

 Allergy: abnormal antigen and antibody reaction to
a substance that is harmless to most of individuals
 Estrogenicity: ability of a chemical to act in the
body in a manner similar to that of estrogen, the
female sex harmone
 Toxicity : dose related potential of a material to
cause cell or tissue death
 Xenoestrogen: a chemical, not indigenous to the
body, that acts in the body in a manner similar to
that of estrogen

 BIOCOMPATIBILITY
HISTORICAL BACKGROUND

 Although the concept of the ethical treatment of
patients extends back to the time of Hippocrates
(460-377 b.c) 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
 Using humans as research subjects today without
some previous testing or knowledge of the
biological properties of a material is unethical and
illegal. Still, every new material must be inserted
into a human for the first time at some point.
Therefore, many alternative tests have been
developed to try to minimize the risks to humans.

 Biological testing of materials have evolved
significantly over past 40 yrs.
 Most biological reactions to materials were
categorized empirically and relied on animal
models .
 many studies between 1950’s and 1970’s
involved the use of premolar teeth that were
scheduled for orthodontic extraction.
 As cell culture techniques developed, research
focused on the mechanisms that affected
biological response to materials.

 Defining the Use of a Material
 The function or use of a material in the body has
an important influence on the nature of the
biological response it induces.
 There are several factors that must be
considered when trying to measure the
biological response.
 Fist the location of a material is important to its
overall biological response

 Materials that penetrate tooth enamel will need
more scrutiny than materials that do not.
 The duration of the material in the body is important
to be biological response.
 For the material to affect the body and for the body
to. Affect the material in many complex ways.
 Finally, the stresses placed on the material are
important to the biological response. These stresses
may be physical, chemical or thermal in nature.

 Types of tests: advantages and disadvantages
 There are three basic types of tests used to
measure the biocompatibility of dental
materials: the in vitro test, the animal test, and
the usage test performed either in animals or in
humans Each of these tests has advantages and
disadvantages

 IN VITRO TEST

 Are performed outside of an organism.
Historically in vitro tests have been used as the
first screening test to evaluate a new material.
 This test may be conducted in a test tube, cell
culture dish, flask or other container, but an
extract of a material is placed into contact with
some biological system.
 The biological system may consist of
mammalian cells, cellular organelles, tissues,
bacteria or some sort of enzyme

 In vitro tests have several advantages over
animal or usage tests.
 They are relatively fast, inexpensive and easily
standardized.
 Further more they may be used for larger scale
screening than can either animal or usage tests.
 Conditions for these tests can be tightly
controlled to provide the highest quality of
scientific rigor.

 The greatest disadvantage of in vitro test is their
potential lack of relevance to the in vivo use of
the material

 ANIMAL TESTS

 Place a material into an intact organism of some
type. Common animals for this type of test are
mice, rats, hamsters, ferrets, or guinea pigs, but
many other types of animals tests are distinct
from in vitro tests..

 Animal tests are distinct from usage tests in that
animal tests expose the animal to the material
without regard to the material’s final use.
 Animal tests may also be subdivided into
several types including short term or long term
systemic toxicity exposure to intact or abraded
membranes and immune sensitization or bone
response.
 There are also animal tests for mutagencity and
other specialized conditions.

 Regardless of the type of test used the advantage
of an animal test is its ability to allow an intact
biological system to respond to a material.

 However animal tests are expensive and difficult
to control, and they may take many months or
even years to complete depending on the species
used.
 These tests are also controversial because of
ethical concerns about proper animal treatment.

 Furthermore the relevance of an animal test is
often questioned because of concerns about the
ability of any animal species used to adequately
represent the human species

 Despite their advantages animal tests provide an
important bridge between the in vitro
environment and the clinical use of the material

 USAGE TESTS

 These are performed in animals or humans.
 A usage test requires that the material be placed
in an environment clinically relevant of the use
for the material in clinical practice.
 If test is performed in human it is called a
clinical trial rather than a usage test.
 The choice of animals for a usage test will be
more limited than for an animal test because not
all species can be used for all clinical situations
often because of the size or anatomy that more
closely resembles that of humans.

 The relevance of a usage test depends directly
on the quality with which the test mimics the
clinical use of the material in terms of time,
area, clinical environment and placement
technique.
 The human clinical trial is therefore the “gold
standard” of usage tests and is the standard by
which in vitro and animal tests are judged.

 Usage tests also have a number of
disadvantages.
 These tests are extremely complex and difficult
to perform in terms of experimental control and
interpretation.
 The tests are exceptionally expensive thousands
of dollars may be needed for a single subject.
 If human are to be used, approval for clinical
trail must be obtained by law, from an
Institutional Review Board.

 The time required for these tests may stretch
from months to years if data on the long term
performance of a material are desired.
 Finally human usage tests may involve many
legal liabilities and issues that are not factor for
animal and in vitro tests.

 Generally no single test is used to evaluate the
biocompatibility of a new material.
 Rather in vitro animal and usage tests are used
together.
 However the role of each of these basic tests in
the overall testing scheme is controversial and is
still evolving..

 Three phases are generally recognized in the
testing of a new biomaterial primary, secondary
and usage

 Primary test are performed initially in the
testing of a new material; these tests are often in
vitro in nature. .

 Secondary test are almost always conducted in
animals. For example tests to measure dermal
irritation chronic toxicity or response upon
implantation are selected to observe the immune
response.
 The usage phase of testing is largely the same as
described previously because the material must
be tested in a clinical relevant situation.

 The testing of a new material is a linear
progression from primary to secondary to usage
test.
 Primary tests are conducted first and only
materials that “pass” these primary tests are
tested in the secondary phase.
 Similarly, only materials that have favorable
results in the secondary tests are subjected to
usage tests

 In the late 1970’s and early 1980’s several
studies by Mjor et al (1977) were published
comparing invitro, animal and usage tests for
materials used clinically in dentistry for many
years.
 The results showed that the in vitro and animal
tests did not necessarily predict the results tests
or the successful Clinical experience with the
material.

Standards : Advantages and Disadvantages
 Although the earliest attempts at formally
developing standardized tests for the
biocompatibility of materials came in 1933 it
was not until 1972 that the council on Dental
Materials Instruments and Equipments (later
called the Council on Scientific Affairs) of the
American National Standards Institute /
American Dental Association (ANSI/ ADA)
approved Document No.41 for Recommended
Standard Practices for Biological Evaluation of
Dental Materials

ANSI/ ADA Document 41
 The original ANSI/ ADA Document No.41 for
biological testing of dental materials (released in
1972) was updated in 1982 to include tests for
mutagenicity. 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 systemic toxicity by oral ingestion.
 Secondary tests include animal tests for
inflammatory or immune responses.
 Usage tests include tests for pulpal and bone
response.

ISO Standard 10993:
 The ISO 10993 document is the international
standard for testing the biocompatibility of
material Unlike ANSI/ADA Document No. 41,
the ISO 10993 standard is not restricted to
dental material. This document was first
published in 1992,
 But modified version are updated periodically in
2002, ISO 10993 consisted of 16 parts each
addressing a different area of biological testing
for example part3 governs tests for genotoxicity
carcinogenicity and reproductive toxicity
whereas Part 4 covers tests for material that
interact 'with blood

 Two types of tests are covered in the standard initial
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.
 The initial tests may be in vitro or animal test
whereas the supplementary tests are performed on
animals or humans.
 In this standard usage tests are part of the
supplementary tests

 The standardization of biocompatibility testing
of materials has done much to advance
understanding of biocompatibility and to
protect the public.
 Because the nature of biologic testing involves
innumerable, standardization is critical to the to
the unbiased comparison of results from
different studies. In this sense, standards are
very important

 however standards also have disadvantages
Most standards cannot keep pace with the
development of new scientific information such
as the rapid advance of cellular and molecular
biological techniques.
 By their nature standards represent a
compromise among manufacturers,
academicians, and the lay public therefore they
tend to be developed slowly.

LATEX
 Exposure to latex comes from many resources
including toys, balloons ,condoms, swim
goggles, dishwashing gloves, hairnet elastics,
clothing elastics, footwear, cervical diaphragms,
and hot water bottles.
 Of particular interest in dentistry is the use of
latex rubber dam, which exposes patients and
dental personnel.

 In the early 197Os when the AIDS Virus
became known, dental personnel began to
routinely wear gloves to reduce the risk of
disease transmission. Since that time, the
incidence of latex hypersensitivity
reactions has increased dramatically.
 In 1991, the FDA estimated that about 6%
to 7% of surgical personnel may be
allergic to latex.

 Hypersensitivity to latex-containing products may
represent a true latex allergy or a reaction to -
accelerators and antioxidants used in latex
processing.
 Reactions to latex vary from localized rashes and
swelling to more serious wheezing and anaphylaxis
,Dermatitis of the hands (eczema) is the most
common adverse reaction.
 A history if eczema and a familial history of
allergies are predisposing factors and repeated
exposure and duration of exposure playa role in the
degree of response

 Such exposures may result in angioneurotic
allergic reactions oedema, chest pain, and a rash
on the neck and chest of severely allergic
persons,
 Asthmatic reactions and other respiratory
reactions have also been reported to components
of the latex that are released into the air carried
by the powdered coating on many latex
products.

 Natural latex products are made from a white, milky
sap harvested from a tree that grows in tropical
regions.
 Ammonia added to the sap to preserve it, but at the
Same time the ammonia hydrolyzes and degrades
the sap proteins to produce allergens.
 “Vulcanization” is the process by which liquid
latex is hardened into rubber through the use of
sulfur compounds and
 Allergenicity of a given batch of latex will be highly
dependent on how the sap was collected, preserved,
and processed.

Nickel
 is a common component of many dental alloys
including those used for crowns, fixed partial
dentures, removable dentures and some
orthodontic appliances. Nickel is also used in
many types of endodontic files, although the
duration of exposure through this route is far
shorter.
 Nickel is the most allergenic metal known, with
an incidence of somewhere between 10 % to
20% depending on the study.

 Hypersensitivity to nickel is more
common among women presumably
because of chronic exposure through
jewelry.
 These reactions are probably
underreported because the reactions are
often subtle, and they resemble
periodontal inflammation.

Beryllium:
 is used in Ni-Cr alloys in concentration of 1wt%
to 2wt % to increase the castability of these
alloys and lower their melting range.
 Beryllium also tends to form thin adherent
oxides that are required to promote chemical
bonding of porcelain.
 The use of beryllium in dental alloys is
controversial because of its biological effects.
 First beryllium is a documented carcinogen in
either the metallic (Beo) or ionic (Be2+) state
although there are no studies showing that
dental alloys containing beryllium cause cancer
in humans.

Mercury and Amalgam
 The controversy over biocompatibility of
amalgam has waxed and waned several times in
the 170 plus year history of its dental use in the
United States. Most of the controversy stems
from the know toxicity of mercury and the
debate over.
 Whether mercury from amalgams has toxic
effects. Mercury occurs in three forms as the
metal from (Hg0) as an inorganic ion (Hg2+) or
in one several organic forms, such as methyl or
ethyl mercury.

 Metallic mercury gains access to the body
via the skin or as a vapour through the
lungs.
 Ingested metallic mercury is poorly
absorbed from the gut (0.01%) so the
primary portal into the body is through
inhalation of mercury vapor

 Methyl mercury is the most toxic form of
mercury and is also very efficiently absorbed
from the gut (90% to 95%). The primary source
of methyl mercury is in the diet, with fish.


Estrogenicity:
 In 1996 a research group claimed that dental
sealants estrogenic substances in sufficient
quantities to warrant concern.
 “Estogenicity” is the ability of a chemical to act as
the harmone estrogen does in the body. If these
chemicals are not indigenous to the body, the
substances is called xenoestrogen.
 The concern about estrogens in dentistry center
around a chemical called bisphenol A (or BPA).
 There is fairly convincing evidence that BPA and
BPA dimethacrylate (also known as BAD) may act
on the estrogenic receptors in cells.

 One test commonly used to assess
xenoestrogenic activity is called the “E-Screen
assay”. This in vitro test relies on the growth
response of breast cancer cells

 The E-Screen test has several problems that
make its accuracy doubtful.
 First the test does not confirm that the
chemicals acts on the estrogenic receptor a
requirement for true
 Second the test uses cell growth to define
estrogenicity but many factors other than
estrogenicity can cause such cell growth.
 Finally several other problems exists with
the test such as reliability and sensitivity of
the cell lines used and difficulties in
controlling variables.

Other biological effects of resins
 The primary risk of these materials appears to be
allergy and the risk is highest for dental
personnel because of frequent exposure to
unpoymerized material.
 The Allergenicity of methylmethacrylate is well
document and the use of gloves is not effective
in preventing contact because most monomers
pass easily through gloves.
 Also allergic reactions to other methacrylates
have been reported .

 The allergic reactions are primarily
contact dermatitis with the resins acting as
“haptens” via delayed hypersensitivity
mechanisms
 Resins also have significant toxic effect as
demonstrated through the use of in vitro
tests often comparable and sometimes
exceeding the potency of metals .

 Summary :
 Every doctor should be thorough with the
allergicity and side effects of any drug and any
material used on patient because of the growth
in the knowledge of consumer acts .

 References :
 1. Phillips science of dental materials – 11th
edition – Anusavice
 2. Restorative Dental Materials – 10th Edition –
Robert Craig
 3. Dental Materials – E. C. Coombe
 4. Applied Dental Materials – 8th Edition –
McCabe

 THANK YOU

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