Placement of materials in the body can lead to immune responses. In vitro and in vivo tests are used to evaluate the biocompatibility of dental materials. In vitro tests involve direct or indirect exposure of materials to cells in controlled conditions, while in vivo tests in animals or humans provide a more clinically relevant environment. A variety of animal and human clinical trials involving low doses and increasing numbers of subjects are used to evaluate safety and efficacy of new materials.
2. INTRODUCTION
• Placement of a material in the body creates an interface that must exhibit
BIOLOGICAL and STRUCTURAL stability during the life time of the implanted
device.
• The dynamics of the interfacial interaction depends on the shape, size, and
location of the material, its physical properties, its composition and the stresses
that develop during function.
2
3. IMMUNITY
• Resistance exhibited by the host against any foreign antigen including microorganisms.
- Textbook of Microbiology(C.P. Baweja)
• A state of protection from infectious diseases
- Kuby’s Immunology (Jenni Punt, Sharon Stranford, Patricia Jones)
3
4. Immunity
Miscellaneous
Acquired immunity
Innate Immunity
Species Immunity
Racial Immunity
Individual Immunity
Passive immunity
Active immunity
Natural Natural
Artificial Artificial
Herd immunity
Local immunity
Adoptive immunity
Combined immunity
Cell mediated immunity
Humoral immunity
Vaccination Transfer of
antibodies
from mother
to foetus
Parentral
administr
ation of
antibodie
s
Textbook of Microbiology. C P Baveja 6th e 4
5. INNATE IMMUNITY
1. Species immunity- the resistance to a pathogen shown by a
specific species. Eg. B anthracis infects humans but not chicken.
2. Racial Immunity- When different races in one species have
immunity. Eg. Mediterranean coast are immune to P. Falciparum.
3. Individual Immunity- Resistance of an individual in the same
species and in the same race. Eg. homozygous twins exhibit similar
degree of resistance to tuberculosis.
5
6. ACQUIRED IMMUNITY
The resistance acquired by an individual during life.
• Natural - through clinical and sub clinical infections
• Artificial -induced by vaccines
Acquired Active Immunity
6
9. HOW DOES THE IMMUNE RESPONSE TAKES PLACE
Hypersensitivity reaction
Normal reaction
Humoral response
Cell mediated response
Type 2 hypersensitivity
Type 3 hypersensitivity
Type 4 hypersensitivity
Type 1 hypersensitivity
9
Textbook of Microbiology. C P Baveja 6th e
10. • The immunity derived from soluble
mediators or body fluids.(body humorals)
• The fluid contained antibodies.
• B Lymphocytes are associated
• Antibodies are produced in plasma cells.
• The result is destruction of the antigen,
removal via phagocytosis
Cell-Mediated Immunity (Metchnikoff)
• The immunity is derived from special cells
• The cells act on the foreign body.
• T lymphocytes are associated
• Cells destroy the foreign object.
• Intracellular parasitism is seen eg herpes
,Tb
Humoral Immunity (Behering et al)
10
Textbook of Microbiology. C P Baveja 6th e
11. ANTIBODIES
• An antibody is defined as a protein that is produced
by B lymphocytes in response to the presence of an
antigen.
• Antibody is γ-globulin in nature and it is also called
• immunoglobulin (Ig)
11
Textbook of Microbiology. C P Baveja 6th e
12. • Functions of Different Antibodies
• IgA plays a role in localized defense mechanism in external secretions
like tear
• IgD is involved in recognition of the antigen by B lymphocytes.
• IgE is involved in allergic reactions
• IgG protects body fluids.
• IgM protects blood stream.
12
Textbook of Microbiology. C P Baveja 6th e
13. WHAT IS BIOCOMPATIBILITY ?
• The ability of a biomaterial to perform its desired function with respect to a
medical (or dental) therapy, without eliciting any undesirable local or systemic
effects in the recipient or beneficiary of that therapy, but generating the most
appropriate beneficial cellular or tissue response in that specific situation, and
optimizing the clinically relevant performance of that therapy - Philip’s science of
dental materials 12th edition
• BIOCOMPATIBLE :Capable of existing in harmony with the surrounding biologic
environment - GPT 9
13
14. • Placement of material in the body creates an interface that is normally not present.
• This interface is not static – a site for many dynamic interactions between the
body and the material through which the body may alter the material or the
material may alter the body.
• The activity of this interface determines the biocompatibility of the material.
14
15. • The biocompatibility of a material depends on several factors:
• The chemical nature of its components
• The physical nature of the components
• The types and locations of patient tissues that will be exposed to the device
• The duration of the exposure
• The surface characteristics of the material
• The amount and nature of substances eluted from the material
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 15
16. At risk – patients, dentists, lab technicians
16
17. ADVERSE EFFECTS FROM DENTAL MATERIALS
• A critical adverse effect is the first event that is observed at the lowest
exposure level
• The location of this effect is called the critical tissue, or critical organ,
and the concentration of a substance that produces this effect is the
critical concentration
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 17
18. • Health effects can be subdivided into the following:
• Systemic toxicity
• Local reactions
• Allergic reactions
• Other reactions
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 18
20. SYSTEMIC TOXICITY
• Systemic effects from dental materials are a function of the distribution of
substances released from dental materials
• Their routes of entry into the body include the following sources:
(1) ingestion and absorption;
(2) inhalation of vapor;
(3) leakage through the tooth apex;
(4) absorption through the oral mucosa.
• Their migration to other sites can occur by diffusion through tissues or by flow
through lymphatic channels or blood vessel
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 20
21. • 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
• When substances are excreted slowly, their critical concentrations are reached more
rapidly than are those concentrations of substances that are excreted quickly.
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 21
22. LOCAL REACTIONS
• Substances released from the dental material and biological responses to those
substances may cause reaction in the adjacent tissue
• Cell death due to apoptosis or necrosis release of proinflammatory mediators
• Bacterial accumulation on the surface of the material
• Mechanical or physical irritation
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 22
23. • 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 are a function of
• the ability of substances to be distributed to these sites,
• their concentrations, and
• exposure times, which may range from seconds to years
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 23
24. Inflammation of the gingiva in relation to porcelain
fused to metal crown
24
25. ALLERGY
• An altered state of reactivity to an antigen , and includes both type of immune
responses, protective as well as injurious - Dr. Clemens Von Pirquet
• Hypersensitivity reactions have been classified traditionally into 2 types, based on
the time required for a sensitised host to develop clinical reaction on exposure to
the antigen.
• Immediate
• Delayed
25
26. Coombs and Gell (1963) classified hypersensitivity reactions into 4 types, based on
different mechanism of pathogenesis.
TYPE OF REACTION CLINICAL
SYNDROME
TIME REQUIRES
FOR
MANIFESTATION
MEDIATORS
Type I: Ig E type 1. Anaphylaxis
2. Atopy
Minutes Ig E
Type II : cytolytic and
cytotoxic
Antibody mediated damage
– thrombocytopenia-
agranulocytosis, haemolytic
anemia
Hours to days Ig G, Ig M
Type III : Immune complex 1. Arthus reaction
2. Serum sickness
Hours to days Ig G, Ig M, leucocytes.
Type IV : Delayed
hypersensitivity.
1. Tuberculin
2. Contact dermatitis
Hours to days T cells, lymphokines,
macrophages
Textbook of Microbiology. C P Baveja. 6th e 26
27. Allergic contact dermatitis
• Usually occurs where body surface makes direct contact with allergen.
• e.g. Monomers of bonding agent, Acrylic component of dental cements, nickel &
resin monomers, latex gloves.
• Distal part of fingers & palmer aspect of fingertips
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 27
28. Allergic contact stomatitis
• Most common adverse reaction to Dental Materials.
• A) Local/contact type lesions
• B) Systemic/distant lesions
• Common allergens :- chromium, cobalt, mercury, eugenol, components of resin
based materials, & formaldehyde
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 28
29. Allergic contact dermatitis on the
fingertip of a dentist after contact
with resin-based composite
Pronounced gingivitis of an
orthodontic patient (nickel-
containing device) who revealed a
positive reaction in a patch test.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 29
30. INFLAMMATION
• The inflammatory response involves the activation of the host’s immune system to
ward off some challenge or threat
• Inflammation may result from trauma (excessive force, laceration, and abrasion),
allergy, or toxicity
• 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.
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 30
31. Inflammation adjacent to the metal margin of a
metal- ceramic crown due to potential allergy
to one of the metal components
31
32. OTHER REACTIONS
• MUTAGENESIS : Production of genetic alteration through use of chemicals or
radiation.
• CARCINOGENESIS : The process of initiating and promoting cancer.
• TERATOGENESIS : Disturbed growth processes involved in the production of
malformed neonate.
• ESTROGENECITY: It is the ability of a chemical to act as the hormone Estrogen
in the body. substance is called XENOESTROGEN, can alter the reproductive
cycle and developmental process
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 32
33. TEST REQUIREMENTS
1) The test should be performed under conditions that simulate the actual use of the
material in the body
2) The test conditions should reflect the effects of the material’s time in the body
on the biological response.
3) The stresses induced in the material under its intended function should be
considered in the interpretation of the biological response.
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 33
34. TEST CONDITIONS
• The test conditions should reflect whether or not the material will
(1) Contact soft tissue or mineralized tissue
(2) Be external to the oral epithelium
(3) Serve as an endosseous Implant
(4) Be exposed directly to bone, tissue fluid, blood, and saliva
(5) Be separated by some barrier such as dentin between the material and living
cells
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 34
35. TYPES OF TESTS
(1) an in vitro test
(2) an in vivo test
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 35
36. INVITRO
• Direct contact exposes a material or an extract of a
material directly to the biological environment,
biological systems may consist of mammalian cells,
cellular organelles, tissues, bacteria, or certain
enzymes.
• Indirect contact involves a barrier such as agar, a
membrane filter, or dentin. Conducted in cell culture
dishes, test tubes, or other containers
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 36
37. Advantages -
1. Done in controlled experimental condition
2. Rapid, economical & easily standardized
3. Large scale screening possible
Disadvantages -
1. Lack of relevance to in vivo use of material
2. Lack the ability to simulate complex interactions of immune, inflammatory &
circulatory system
37
38. Usage tests
• Usage tests are the most clinically relevant tests
• Performed either in animals or humans
• Requires that the material be placed in a clinically relevant environment similar
to that to which the material would be exposed in clinical practice.
• Larger animals with anatomy similar to that of humans
• In animals : usage tests
• In humans : clinical trials
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 38
39. Advantage -
1. Material placed in an environment clinically relevant to its use in clinical
practice
Disadvantages -
1. Extremely complex & difficult to perform
2. Exceptionally expensive & very time consuming
3. Ethical concerns
39
40. Animal Tests
• Carried out in baboons, cats, dogs, ferrets, guinea pigs, hamsters, mice, monkeys,
pigs, rats, and sheep.
Advantages -
1. Intact biologic system to respond to a material.
2. Provide important bridge between in vitro environment & clinical use of
material
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 40
41. • Disadvantages -
• More expensive & difficult to control
• Time consuming
• Ethical concerns
41
43. Phase 0
• Phase 0 trials are the first clinical trials done among people.
• They aim to learn how a drug is processed in the body and how it affects the
body. In these trials, a very small dose of a drug is given to about 10 to 15 people.
American Cancer Society 43
44. Phase I
• Phase I trials aim to find the best dose of a new drug with the fewest side effects.
The drug will be tested in a small group of 15 to 30 patients.
• Doctors start by giving very low doses of the drug to a few patients. Higher doses
are given to other patients until side effects become too severe or the desired
effect is seen.
• The drug may help patients, but Phase I trials are to test a drug’s safety. If a drug
is found to be safe enough, it can be tested in a phase II clinical trial.
44
45. Phase II
• Phase II trials further assess safety as well as if a drug works. The drug is often
tested among patients with a specific type of cancer.
• Phase II trials are done in larger groups of patients compared to Phase I trials.
Often, new combinations of drugs are tested. Patients are closely watched to see
if the drug works.
• However, the new drug is rarely compared to the current (standard-of-care) drug
that is used. If a drug is found to work, it can be tested in a phase III clinical trial
45
46. Phase III
• Phase III trials compare a new drug to the standard-of-care drug.
• These trials assess the side effects of each drug and which drug works better.
Phase III trials enroll 100 or more patients.
46
47. Phase IV
• Phase IV trials test new drugs approved by the FDA. The drug is tested in several
hundreds or thousands of patients.
• This allows for better research on short-lived and long-lasting side effects and
safety.
47
48. IMPLANTATION TEST
• Materials are implanted subcutaneously, intramuscularly, or in the bone of an
experimental animal (rats, rabbits, etc).
• After different periods of implantation of the material in the tissues (between 1 week
and several months), the adjacent tissue is investigated macroscopically and
microscopically.
• After a short implantation time (1–2 weeks), degrees of inflammation surrounding the
implant will primarily be assessed.
• In the case of an extended implantation period, the nature and quantity of the
connective encapsulation will be evaluated, too.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 48
49. • Implantation studies also provide information about the removal of toxic substances
from the tissue and about the defense reaction of the entire organism, such as via an
inflammatory reaction.
• Thus, this type of study is closer to the patients than cell culture experiments are.
• However, a good correlation was found between cell culture data and findings from
implantation tests regarding certain dental filling materials
49
50. MUCOSAL DAMAGE AND MUCOSA USAGE TEST
• Various cell cultures and animal models have been described in the literature for
testing mucosal compatibility.
• A relatively new model consists of in vitro grown skin equivalents and is already
being applied for test purposes in the cosmetics industry.
• Based on the experience of the cosmetics industry, in vitro grown mucosa equivalents
may offer an interesting perspective, but experiences with dental materials are still
minor
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 50
51. INTRAEOSSEOUS IMPLANT TEST
• Materials used for dental implants are inserted into the jaw of test animals.
• For this, penetration of the epithelial barrier, equivalent to the treatment of patients, is
simulated on experimental animals.
• Tissue reaction is assessed histologically, with the tissue in contact with the implant
being of particular interest
• Many factors, including surgical technique, biomechanics, anatomical conditions, and
oral hygiene, play an extremely important role in the clinical success of implant
materials.
• Preclinical intraosseous implant tests are only a prerequisite for the use of dental
implants
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 51
52. ALLERGY TESTS
• The patch test, originally developed and described by Jadassohn , is the most
important allergy test regarding dental materials.
• This test can be applied to identify delayed type hypersensitivity (type IV reactions)
as the cause for an allergic contact dermatitis.
• Immediate reactions (type I reaction, such as asthma) can be diagnosed by the prick
test.
• The radio allegro sorbent test (RAST) may be used as an alternative or supplement to
the prick test.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 52
53. PATCH TEST
• Adhesive tapes containing the potential allergens at concentrations that are just high
enough to trigger the allergic reaction (but which are non irritating) are adhered to the
clinically sound skin of the patient’s back.
• The most important allergens are combined in so-called standard series at ready-made
concentrations and are commercially available.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 53
54. • The patient should avoid excessive sweating or exposure to sun as well as
scratching of the back, and should not have a shower or bath.
• During the following days, after the tape has been removed, the skin is evaluated
for test reactions: redness, itching, blisters, etc.
• Skin reactions are assessed after 2 and 3 days and after 5 and 7 days to detect late
reactions, since immunocompetent T lymphocytes occasionally require several
days before they cause a visible allergic reaction.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 54
55. ADHESIVE TAPES
EVALUATION OF SKIN REACTION
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 55
56. PRICK TEST
• This test is used to detect “immediate-type” allergies – type I reactions.
• The allergen is applied as a drop to the skin, and then the skin is “pricked” through
the drop.
• After 5–30 min, the skin reaction is assessed - redness, formation of weals
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 56
57. RADIO ALLERGO SORBENT TEST (RAST)
• It is an in vitro test
• It is used to diagnose immediate-type allergies (IgE mediated) by identifying an
allergen-specific IgE in the patient’s blood.
• Because the RAST is an in vitro test, the patient will not be exposed to the risk of
sensitization by the test itself.
• However, with atopic patients or through other circulating antibodies, this test may
render results that are inconsistent with clinical findings.
• This test can be used for diagnosing suspected allergies, potentially in combination
with the prick test
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 57
59. GUIDELINES FOR SELECTING BIOCOMPATIBLE MATERIALS
• Unconditional biocompatibility will often be claimed by manufacturers
• However with knowledge of biocompatibility issues clinicians can make
reasonable judgements about biological safety.
• Several critical steps will ensure an informed decision.
• These steps are as follows :
• Defining the use of material
• Defining how the material was tested
• Risk versus benefit
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 59
60. DEFINING THE USE OF A MATERIAL
• The use of a material plays a major role in determining its biocompatibility and vice
versa.
• The clinician must look into whether the materials proposed use is new and whether it has
been tested in its proposed use.
• A second consideration is the composition of the material.
• A small change in composition of material can alter its biocompatibility.
• A new material’s composition must always be analysed.
• DEFINING HOW THE MATERIAL WAS TESTED
• The methods by which the material was tested must be analysed for relevant conditions
and duration.
Philips’ Science of Dental Materials. Anusavice, Shen, Rawls. 12th e 60
61. RISK vs BENEFIT
• The use of a material in the body requires a risk benefit analysis.
• The degree of risk assumed must be carefully weighed against possible benefits.
• The material with benefit overweighing risk must be chosen.
• Possible risk must always be explained to the patient.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 61
63. LATEX
• NATURAL RUBBER LATEX (NRL) has a wide variety of uses in health care
departments due to its strength, elasticity, flexibility, tear resistance and barrier
properties
• obtained from a white, milky sap harvested from Hevea brasiliensis (rubber tree)
and has a composition cis 1,4 polyisoprene
• known to cause Type I and Type IV allergic reactions, as well as irritant contact
dermatitis.
• The first known case of NRL anaphylaxis in a dental professional was recorded in
1987 by Axelsson and colleagues
The dental team and latex hypersensitivity – ADA council on scientific affairs – JADA 1999 63
64. • Hypersensitivity to latex containing products may represent a true latex
allergy or a reaction to accelerators and anti oxidants used latex
processing.
• Reactions to latex vary from localised rashes and swelling to more
serious wheezing and anaphylaxis.
• Dermatitis of the hands is the most common reaction.
• Contact of latex gloves or rubber dam may result in angioneurotic
edema, chest pain, rashes on skin and chest of allergic patients.
• Asthmatic reactions and other respiratory reactions may also occur.
64
65. • IRRITANT DERMATITIS : A condition often confused with the two allergic
conditions described above, is very common among frequent users of both latex
and synthetic gloves and is characterized by dry, itchy, irritated areas of the skin
confined to the area of glove contact.
65
66. LATEX-FRUIT SYNDROME
• People who have latex allergy also may have or develop an allergic response to
some plants and/or products of these plants such as fruits.
• This is known as the latex-fruit syndrome.
• Fruits (and seeds) involved in this syndrome include banana, pineapple, avocado,
chestnut, kiwi fruit, mango, passionfruit, fig, strawberry, and soy.
• Some, but not all of these fruits contain a form of latex
Latex-fruit syndrome": frequency of cross-reacting IgE antibodies - Brehler R, Theissen U, Mohr C, Luger T. - Allergy 1997 66
67. ALTERNATIVES
• Condition should be allowed to resolve – avoiding further exposure.
• Seek physician consultation
• The following recommendations are based on those issued by the National
Institute of Occupational Health and Safety in June 1997
• Synthetic latex such as elastane, neoprene, nitrile and artificially synthesized
polyisoprene latex do not contain the proteins from the Hevea brasiliensis tree.
Preventing allergic reactions to natural rubber latex in the workplace. -Department of Health and Human Services, Public Health Service, Centers for Disease Control
and Prevention, National Institute for Occupational Safety and Health; 1997.
67
68. • Products made from guayule natural rubber emulsions also do not contain the
proteins from the Hevea rubber tree, and do not cause allergy in persons sensitized
to Hevea proteins.
• Chemical treatment to reduce the amount of antigenic proteins in Hevea latex has
yielded alternative materials, such as Vytex, which reduce exposure to latex
allergens while otherwise retaining the properties of natural rubber.
Preventing allergic reactions to natural rubber latex in the workplace. -Department of Health and Human Services, Public Health Service, Centers for Disease Control
and Prevention, National Institute for Occupational Safety and Health; 1997.
68
70. • Allergic reactions have mainly been reported in the context of ZOE pastes and a
polyether-based material
• SYMPTOMS :
• mucosal burning directly after impression,
• reddening,
• swelling,
• blister formation were observed 24 h later in the area of the affected intraoral
mucosa and the tongue
• EXTRAORALLY, swollen lips and extensive exanthemas of the face and the neck
were observed.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 70
71. FATAL ANAPHYLACTIC SHOCK DUE TO A DENTAL
IMPRESSION MATERIAL
• Gangemi, Spangnolo, Cardia, Minciullo
• International journal of prosthodontics – 2009
• Materials used for dental impressions are usually safe. This study describes a case
of fatal anaphylaxis that appeared immediately after the oral mucosa came into
contact with an alginate paste used for dental impressions.
• The cadaveric examination and the post mortem toxicology report confirmed that
the cause of death was anaphylactic shock. The patient was affected by both
cardiovascular and lung diseases that worsened the condition and forbade the use
of epinephrine.
Gangemi, S, Cardia G, Minciullo PL. Fatal anaphylactic shock due to a dental impression material. International Journal Of Prosthodontics 2009; 22(1):33-4 71
72. DENTALALLOYS
• An alloy is any mixture of two or more metals
• Alloys are used in almost every aspect of dentistry.
• More than 3,000 alloys are available that put them into long-term direct or indirect
contact with epithelium, connective tissue, or bone
• The complexity and diversity of today’s dental alloys make understanding their
biocompatibility difficult because any element in an alloy may be released and
influence vital tissue.
• Elements that are released from dental alloys into the oral cavity may only gain
access to the body through the epithelium in the gut, the gingiva, or, for elements
that form vapors (such as mercury), through the lungs (absorption)
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer
72
73. • Metals such as nickel and copper have been reported to cause gingivitis when they are
released from alloys into adjacent oral tissues
73
74. Some patients who indicated complaints related to dental alloys revealed an alteration
of the tongue, usually a fissured or geographic tongue.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 74
75. • Palatal erythema underneath a metal base has been observed on various occasions
• The causes for these reactions may be toxic or allergic in nature, an insufficient fit
of a denture, or bacterial or fungal infection
• If oral hygiene measures does not resolve the condition then an elimination test (not
wearing the restoration for a specific period of time) or insertion of a metal-free
temporary restoration is recommended.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer
75
76. BERYLLIOSIS
• Berylliosis is an occupational lung disease
• Continued exposure to beryllium vapours causes the
development of small inflammatory nodules, called
granulomas, leading to restrictive lung disease.
• The symptoms include cough and shortness of breath,
chest pain, joint aches, fever, weight loss.
• There is no cure for berylliosis; the goals of treatment are
to reduce symptoms and slow the progression of disease
76
77. AMALGAM TOXICITY
• Dental amalgams consist of metals that may cause concerns about the risk of
systemic toxic and local reactions if released in sufficiently high quantities.
• Immediate allergic reactions (type I) to components of dental amalgam are
extremely rare.
• Delayed allergic reactions (type IV) may occur in the oral mucosa.
• They are usually limited to the area in contact with an amalgam filling.
• Body burden of mercury can be studied by analysis of urine, blood and hair.
• Urine analysis is the best long term indicator of the total metallic mercury body
burden, normalized to grams of creatine clearance from the kidney
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 77
78. COMPOSITES
• Resin-based composites are primarily used as anterior and posterior filling
materials, applied as pit and fissure sealants, luting composites, crown build ups
and the bonding of brackets and orthodontic bands.
• Most of the resins are polymerized by light, with a wavelength between 400 and
500 nm according to the light initiators used.
• Traditional QTH lights are now replaced by LEDs
• Resin-based composites release residual monomers
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 78
79. • Released compounds can directly cause biological reactions. Polymerization
shrinkage is a material property that may indirectly influence the tissue
compatibility
• Also these components undergo biodegradation thus releasing elements.
• Resin-based composites are cytotoxic before polymerization and immediately
thereafter, whereas almost no reaction is caused by set specimens
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 79
80. • Resin-based composites may promote bacterial growth due
to the surface topography and lack of marginal adaptation.
• Acids (such as phosphoric acid or citric acid) or complexing
agents (such as ethylene-diamine-tetra acetic acid, or
EDTA) can increase the permeability of dentin by removing
the smear layer and expanding the orifices of the dentin
tubules.
Loss of marginal adaptation.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 80
81. LIGHT CURING UNITS
• The temperature rise that may be associated with polymerization of a resin and the
thermal radiation of a curing unit, is an issue of concern
• Taken together, a temperature rise of 15.5–18.6°C was found in resin-based
composite during the application of a QTH curing unit, and an increase of 8.2–
12.1°C was found when an LED unit had been used and the irradiation time had
been the same.
• Overall rise 0f 5.5 degree Celsius will cause irreversible pulpal damage.
• Dentin is, however, an excellent thermal insulator, that protects the pulp
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 81
82. • Blue light ranging between 400 and 500 nm is used for curing
• Mutagenic effects of polymerization lights in bacterial cultures were also shown
after long irradiation times.
• However, in the dental practice, acute tissue damage seems to be rather unlikely
because the exposure times are much shorter.
• Reversible damage to eyes (e.g., afterimages) may occur, especially after direct
glare.
• To prevent any adverse effects on the eyes, protective glasses should be used, or
protective shields should be attached to the end of the light guide of the
polymerization lamp.
82
83. • Acids that are used to etch ceramics may cause severe chemical burn of soft
tissues after unintentional contact.
• Thus, proper isolation of soft tissue is very important.
Chemical burn after
inadvertent contact of
phosphoric acid with
gingiva
83
84. RESINS
• Polymethylmethacrylates (PMMAs) are used primarily for dentures, custom trays,
making artificial teeth
• They can be classified based on curing mechanism as :
• Heat activated
• Self activated
• Light activated
84
85. • Two aspects are of particular importance that influences the leaching of elements
are:
• Monomer– polymer conversion and residual monomer content.
• The concentration of residual monomers should be as low as possible because
leaching of substances is primarily responsible for unwanted side effects.
• Heat-polymerizing acrylic resins generally reveal a higher rate of polymerization
and thus a lower level of residual monomers compared with autopolymerizing
products
85
86. • MMA may irritate the eyes, skin, and respiratory system, microbial proliferation
• Candida albicans plays an important role in the etiology of “denture stomatitis”
• Irritation of the oral mucosa beneath or adjacent to resin restorations is certainly
the most severe local clinical adverse effect.
• A clear association between irritation of the mucosa beneath dentures and the
release of residual monomers was documented
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 86
87. • Skin and mucosal contact with MMA and PMMA may result in allergic reactions
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 87
88. DENTAL CEMENTS
• ZINC PHOSPHATE CEMENTS
• Zinc phosphate cement is primarily used for the cementation of indirect
restorations, such as crowns and bridges, and is also applied for temporary fillings,
cavity bases, and build ups of teeth beneath crowns
• The acidity of the cement during application is very high due to the presence of
phosphoric acid
after 24 hours pH
increases to 5.5
2 minutes after
mixing pH is 2
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 88
89. • When a luting procedure is performed with zinc phosphate cement, the patient
may complain almost immediately of a stinging sensation that lasts a short time.
• This sensation is supposedly due to excess phosphoric acid reaching the pulp
through patent dentin tubules
• The application of calcium hydroxide is recommended in the deepest areas of the
cavities that are close to the pulp before the restoration is cemented.
89
90. GLASS IONOMER CEMENT (GIC)
• GICs are used as filling material for cavity bases and buildups as well as for root
canal fillings and as luting agents for indirect restorations such as inlays, crowns,
and bridges
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 90
91. • 3 main factors affecting the biocompatibility of GIC :
• The heat evolved during the earliest stages of the setting of GIC - This is small
and considered unlikely to cause thermal damage in dental or orthopaedic
applications.
• The presence of aqeuous polymeric acids - these are relatively weak, with a pK,
of 4.5-5.0. The initial step in the neutralization reaction is rapid so the amount of
free carboxylic acid is low early in the setting process
• The substances leached from the set cement - different initial constituents of
the cements release different species.
Sasanaluckit P, Albustany KR, Doherty PJ, Williams DF. Biocompatibility of Glass ionomer cements. Biomaterials 1993;14(12) 906-16 91
92. • Glass ionomer cements are, in general, cytotoxic shortly after mixing but are
inactive when set. They can be applied on vital dentin if one is certain that the
pulp is not exposed
• Deep cavities are always associated with the risk of a unrecognized pulp exposure.
Therefore, it is recommended to cover areas close to the pulp (and pulp exposures)
with a calcium hydroxide-based material.
• When GICs are used as luting agents for restorations, the tooth should not be
excessively dried
Sasanaluckit P, Albustany KR, Doherty PJ, Williams DF. Biocompatibility of Glass ionomer cements. Biomaterials 1993;14(12) 906-16 92
93. ZINC OXIDE EUGENOL (ZOE)
• Zinc oxide and eugenol cements are primarily used as temporary filling material,
for temporary luting of cast restorations, for indirect pulp capping, and as root
canal sealers .
• Allergy to ZOE is found commonly in many patients.
• Common symptoms include redness, swelling, or pain of the oral mucosa,
gingiva, and lips .
• Burning mouth and swelling of the tongue, nausea, abdominal pain, urticaria, and
hot flushes was reported in a rare case.
• Dentist can also develop contact dermatitis due to allergy to eugenol
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 93
94. • Eugenol, which is a phenol derivative, is highly cytotoxic in vitro
• However, if dentin is present as a barrier between ZOE and cells, no or only slight
cytotoxic effects have been observed.
• Thus, dentin possesses a protective effect that may be related to an adsorption of
eugenol to calcium apatite and to certain proteins, such as albumin, in dentin.
• A direct application of ZOE cements on the exposed vital pulp will cause a severe
inflammatory reaction and pulp necrosis
• Deepest areas should be covered by a calcium hydroxide preparation, to avoid a
pulp necrosis
• The powder–liquid ratio should be as high as possible to reduce the quantity of
unbound and leachable eugenol.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 94
96. CALCIUM HYDROXIDE
• Calcium hydroxide cements are used for direct and indirect pulp capping. The
long-term goals of these procedures are a vital and pain-free pulp
• The calcium-hydroxide-triggered coagulation necrosis seems to be a stimulus that
is sufficient to initiate healing in the subjacent vital pulp tissue.
• This process will then initiate the differentiation of cells to odontoblast-like pulp
cells (secondary odontoblasts), which will finally result in a bridging
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 96
97. CERAMICS
• Dental ceramics comprise a comprehensive palette
of different nonmetallic, inorganic materials.
• They are primarily used for inlays, veneers, partial
crowns, full crowns, and for copings.
• They are also used for frame works and for
veneering of metal/ceramic copings and
frameworks, artificial teeth, and for root canal
posts.
Biocompatibility Of Dental Materials. Gottfried Schmalz, Dorthe Arenholt-Bindslev. Springer 97
98. • Dental ceramics are commonly regarded as insoluble or only very slightly soluble
at best.
• However, their initial strength decreases significantly because of permanent load
and the aqueous media.
• Thus, degradation occurs, which may be of a chemical nature (solubility in an
acidic, neutral, or alkaline environment), a mechanical nature (wear), or a
combination of the two.
98
99. • In general, the systemic toxicity and the allergenic potency of ceramics are
considered to be extremely low.
• Ceramics are usually nontoxic in patients
• Only dental laboratory technicians might be exposed to an inhalation of ceramic
dust due to processing and finishing of dental ceramics that may cause silicosis.
99
100. • Silicosis – lung disease marked by inflammation and scarring in the form of
nodular lesions in the upper lobes of the lungs.
• Symptoms – shortness of breath, cough, fever and cyanosis
• Commonly accepted occupational protective measures in the dental laboratory,
such as suction units and mouth guards, should be used as protection against dust
during the processing of dental ceramics
• It is essential to wear gloves and eye protection when handling hydrofluoric acid
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101. REFERENCES
• Biocompatibility of dental materials – Gottrified Schmaltz, Dorthe Arenholt
• Philip’s science of dental materials 11th edition, 12th edition.
• Textbook of microbiology – C P Baveja 6th edition
• GPT – 9th edition
• The dental team and latex hypersensitivity – ADA Council On Scientific Affairs –
JADA 1999
• Latex-fruit syndrome": frequency of cross-reacting IgE antibodies - Brehler R,
Theissen U, Mohr C, Luger T. - Allergy 1997
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102. • Preventing allergic reactions to natural rubber latex in the workplace. -Department
of Health and Human Services, Public Health Service, Centers for Disease Control
and Prevention, National Institute for Occupational Safety and Health; 1997
• Biological interactions of dental cast alloys with oral tissues – Gottfried schmaltz
–Dental material 2002
• Hironori T, Yoshiyuki H, Katsushi T. Leaching and cytotoxicity of formaldehyde
and methyl methacrylate from acrylic resin denture base materials. J Prothet Dent
1994; 71(6):618-24
• Gangemi, S, Cardia G, Minciullo PL. Fatal anaphylactic shock due to a dental
impression material. International Journal Of Prosthodontics 2009; 22(1):33-4
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Editor's Notes
Igm and igd distributed intravascularyly
VERY RARE
Atopy – asthma – occurring in a region that is not in contact with the allergen
Anaphylaxis – acute onset of itching, edema , shortness of breath.
Thrombocytopenia – deficiency of platelets
Agranulocytosis – deficiency of granulocytosis increasing the chance of infection
Hemolytic anaemia - early destruction of red blood cells. This means that red blood cells are destroyed and removed from the bloodstream before their normal lifespan is over
An Arthus reaction is a local vasculitis associated with deposition of immune complexes and activation of complement mainly in the vascular walls.
rarely reported after vaccination and can occur after tetanus toxoid–containing or diphtheria toxoid–containing vaccines
Serum sickness – allergic reaction characterised by rashes, itching, fever
Tuberculin, also known as purified protein derivative, is a combination of proteins that are used in the diagnosis of tuberculosis. This use is referred to as the tuberculin skin test and is recommended only for those at high risk. Injection is done into the skin
Contact dermatitis is a rash caused by your skin reacting to a substance it has come into contact with. You may need patch testing to identify the causative substance. A steroid cream or ointment will usually clear the rash.
an animal test, and
(3) a usage test performed clinically in animals or humans
3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide. water soluble tetrazolium
a purple, water insoluble formazan compound.
XTT {2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide }
ground and fed to the animals. seldom used for
testing dental materials
To the authors' knowledge, dental impression materials, and alginate in particular, have not been reported previously as being a cause of anaphylaxis.
Thus, it may be concluded that potential pulp damage caused by acid attacks from the zinc phosphate cement is possible only during the first hours after application