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Biocompatibility of Dental Materials:
Introduction
Historical Background
Importance Of Biocompatibility
Regulatory Approval Of Dental Materials
Definition
Requirement
Adverse effect
Toxicity
Hypersensitivity and Allergy
Inflammation
Mutagenic reaction 3
Estrogenicity
Osseointegration and Biointegration
Immunotoxicity
Anatomy and pathological aspect of oral tissues
Enamel
Dentin and pulp
Dentin permeability
Bone
Periodontium
Gingiva and Mucosa 4
Measuring biocompatibilty
Invitro test
Animal test
Usage test
Using invitro,animal and usage tests together
Selection of biocompatible material
Biocompatibility of dental materials
Review of literature
Conclusion
 Reference
5
 “Our objective should be the perpetual
preservation of what remains rather than
the meticulous restoration of what is
missing”
MULLAR M.DE VAN
6
7(J Prosthet Dent 2001;86:203-9.)
 Although the concept of the ethical treatment of
patients extends back to the time of Hippocrates (460-
377 KC.), 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.
 Many exotic formulations were used. For example,
Fox developed a "fusible metal“ that consisted of
bismuth, lead, and tin, which he melted and poured
into the cavity preparation at a temperature of
approximately 100" C.
 Even G.V. Black used patients to test many of his new
ideas for restorative materials, such as early
amalgams.
 The current philosophy about testing the biological
properties of dental materials in a systematic way
evolved in the 1960s as the need to protect patients
became politically acute and as the number of new
materials increase.
 The concept of protecting the patient as a research
subject is only 30 to 40 years old, and many of the
regulations and ethics in this area still being
challenged and defined today.
Dentists potential concerns about biocompatibility can be
organized in to 3 areas :
 1) Safety of the patient.
Primary concern - avoid any harm to the patient.
 2) Safety of Dental staff
The risk of adverse effects of biomaterials is much higher
for dental staff than for the patient. The staff may be chronically
exposed to materials when they are being manipulated or setting.
Eg:- i) Amalgam – Mercury vapour.
ii) Chronic exposure to latex and resin based materials.
11
iii) Regulatory compliance issues
Biocompatibility issues are closely linked to regulations that
affect dental practice.
Ex: Dental amalgam.
3) Legal Liability.
 Biocompatibility issues also influence liability issues that affect
dental practitioners.
12
Two regulations currently govern the use of dental materials:
ANSI/ADA document No.41(1979) & addendum
No41A(1982)
ISO10993document(1993) although these documents are
different , ANSI/ADA document is currently under
revision to coordinate with the ISO document.
13
 Biocompatible
Capable of existing in harmony with surrounding
biological environment
GPT(9)
 Biocompatibility
Property of the material which remain harmoniously with the
living tissues.
Shama Bhat-2nd edition
Ability of a material to elicit on appropiate biological response
in a given application in the body.
Craig -12 edition
14
Biomaterial
Any substance other than a drug that can be used for
any period of time as part of a system that treats, augments, or
replaces any tissue, organ, or function of the body.
GPT(8)
 Bioinert
These allow close apposition of bone on their surface
leading to intact osteogenesis.
Metals –commerically pureTi
Ti alloy (Ti6Al-4V)
Al2O3,Zr2O3
15
 Biodegradation
The series of processes by which living systems render
chemicals less noxious to the environment.
GPT(8)
 Bioactive
Having an effect on or causing a reaction in living tissue
16
 Should not be harmful to pulp and soft tissues
 Should not contain toxic diffusible substance
 Should not produce allergic responses
 Should not be carcinogenic
 Should not undergo biodegradation
 Should not show estrogenecity and contain xenoestrogens
17
18
 Paracelus(1493-1541)- father of toxicology and first
modern medical scientist said that.
“All things are poison and nothing is without poison only
the dose permits something not to be poisonous”.
Latter phrase-right dose differentiates a poison for remedy.
19
 Test organism such as cells and selected bacteria through
higher order plants and animals.
 A specific response or biological endpoint.
 Exposure or test period.
 A dose or dose curve.
20
21
 Hypersensitivity is abnormal reaction
that occurs when the body is exposed
to a foreign material.
 Develops only in person whose
immune system recognise the material
as foreign.
 Allergic reaction can manifest as a
localised reaction in tissues which is
directly in contact with material.
 Systemic manifestation are skin
eruption, itching, sneezing,
erythema,breathing difficulties.
Textbook of Pathology :Harsh Mohan :4th edition :jaypee brothers 22
 Allergic contact dermatitis
 Allergic contact stomatitis
 Allergic to latex products
23
24
 Altering the base pair sequence of DNA in cells
 Resin based restorative
 Sealants
 Ions of metal(Ni,Be,Cu) found to be mutagens.
25
 Ability to produce material like xenoestrogens to act in
body as estrogens
 Resin
 bisphenolA-starting substance of BisGMA
 Restorative material and few other resin are estrogenic
26
27
 Osseointegration –formation
of living body tissues within
10mm space from the
implant material surface
without any fibrous
connective tissues.
 Material –CpTi,Ti6Al-4v
alloy,tantalum and few
ceramics.
 These material does not
undergo biodegradation
easily.
 Certain material like bioglasses which undergo
biointegration with the bone.
 Directly without any interviewing space.
 This material should undergo degradation.
28
29
 Alteration in cells of
immune system.
 Mercury
 Palladium
 Dentin bonding agents
 HEMA may indirectly
cause change in cellular
function.
30
31
• Highly mineralised.
• More brittle than dentin.
• Solubilised to a greater extent by acid solution.
• Helps for bonding agents to provide micromechanical
retention.
Essential of Oral Histology and Embrology A Clinical Approach-James k Avery|Daniel j ChiegJ-Mosby
Elsevier
32
Essential of Oral Histology and Embrology A Clinical Approach-James k Avery|Daniel j ChiegJ-Mosby
Elsevier 33
34
 Under positive hydraulic pressure-
Movement of fluid in the dentinal tubules
stimulates the A-fibers producing sharp
localised pain.
 Under negative hydraulic pressure- fluid
convection is away from the pulp when
concentrated solution such as sucrose, or
saturated calcium chloride are exposed to
open dentinal tubules producing sensitivity.
Eg, cervical abrasion.
 Presence of smear layer, cavity liners,
sealers, debri can reduce fluid convection.
35
 Diffusion is proportional to
the length of the dentinal
tubules & roughly to the
thickness of dentin between
cavity preparation & pulp.
 Ions & molecules can diffuse
even against positive
hydraulic pressure.
 Smear layers are better than
cavity liners & sealers.
 Extacellular matrixwith cells and tissues .
 Mineralised tissue-23%organic substance (86%typeI collagen)
77%hydroxyapatite(small and less well dentin)
 Vascularity of bone serve mineral phase as a major reservoir
of calcium and phosphate ions for body’s metabolic processes.
 Synthesized by osteoclast .
 It have excellent self repair capacity.
36
37
38
 Consist of PDL,cementum and
alveolar bone.
 Cementum and alveolar bone –
extracellular matrices.
 Cells are destroyed during injury
and have no source of progenitor
cells ankylosis –bone and teeth
 Researchers have investigated that
chemical and surgical methods to
limit epithelial down growth of
gingiva to enhance PDL
reattachments to tooth and bone
surface,
 Gingiva –attached and free gingiva.
 Oral mucosa –loose fibroelastic connective tissuewith a well
vascularised and innervated lamina propria and submucosa and
covered by parakeratinized stratified squamous epithelium.
 Dental material chemically and physically injury OMM
 Gingival tissues reaction to oral implant.
39
 Transmucosal implant –special problem-epithelial
growth,encystification and exfoliation of implant.
 Inflammatory disease around implant is implantits.
 Perimplantitis-response to bacteria that attached to
implant and exist near the gingiva.
40
41
 Outside body
 In vitro – Interaction of any
material on cell, enzyme or
any biological substance
isolated from organism.
42
 Direct – material physically in contact with cell
 Indirect – extract from the material in contact with the cell
 Subdivided into measuring
Cell growth / cytotoxicity
Effect on genetic material in cell
Metabolic / other cell function
43
 Advantages
 Quick
 Inexpensive
 Easy
 Standardized
 Well suited for large scale screening
 Disadvantage
 Questionable relevance to final in-vivo study.
 Lack of inflammatory and other tissue protective
measures.
44
 Primary cells – direct from animal into culture
- limited period of growth
- maintains characteristics of cell
- to measure cytotoxicity
 Continuous cells – transformed primary cells
- growth is in definitive
- no in vivo characteristics
- genetically and metabolically
stable ( easy to standardize)
45
46
 Assess by measuring the cell number/
growth after exposing to material
 Liquid- cells are placed in well of
culture dish
- then places in sample
- if cell detach and stop
growth –
cytotoxic
- if remains in contact with
well – non
cytotoxic.
Eg; bonding agent,
formocresol
 Solid –
eg; Tablets
zone of inhibition
47
Membrane permeability
Na51CrO4
(vital dyes)
Neutral Red
(vital dyes)
Trypan Blue
(non-vital dyes)
48
 Usually dyes contain auxochromes.
 An auxochrome is a group of atoms attracted to a
chromophore, which are present in cells.
 Vital dyes are basic dyes they contain amino group, that
helps in cell permeability.
 The basic dyes bind to negative ions to stain the cell.
 Acid ions in non-vital dyes reduce the ability of the dyes
to stain the vital cells.
 Eg – chemicals, injecting drugs
49
 The biosynthesis or enzymatic activity of cells to assess
cytotoxicity
 Measures – DNA synthesis
- Protein synthesis
 They are analyzed by adding radioisotope labeled
precursors to the medium and quantifying them on DNA
and protein
 Radioisotope - 3H-thymidine
50
51
 It is a colorimetric assays
 This measures the activity
of cellular dehydrogenases
 XTT(2-methoxy-4-nitro-
5-sulfophenyl),MTS( 4,5-
dimethylthiazol-2-yl),
WST( water soluble
Tetrazolium salt)
 Which converts the MTT chemical to a purple, insoluble
formazan dyes
 If dehydrogenases are not active because of cytoxic effect
the formazan will not form
 Helps in assay the viability & proliferation of cell
 Quantified using spectrophotometer(500-600nm
wavelength)
 Enzyme that oxidizes a substrate by transferring hydrogen
to an acceptor that is either NAD(Nicotinamide Adenine
Dinucleotide or a flavin enzyme.
52
 Since there is no direct contact between cell and material
in vivo ( epithelium/dentin)
 AGAR OVERLAY METHOD:
AGAR NUTRIENTS, GAS, SOLUBLE TOXIC
NEUTRAL RED / FRESH CULTURE MEDIA
53
 Effect of materials on a cell’s genetic material
 Genotoxic mutagens directly alter the DNA of the cell
through mutation
 Genotoxic chemical may be mutagens in native state or
may require activation or biotransformation to be
mutagens, in which case they are called promutagens
54
 Epigenetic mutagens do not alter the DNA themselves, but
support tumor growth by altering the cell's biochemistry,
altering the immune system, acting as hormones, or other
mechanisms.
 Carcinogenesis is the ability to cause cancer.
 Mutagens may or may not be carcinogens, and
carcinogens may or may not be mutagens.
55
 The test uses several strains of the bacterium Salmonella
typhimurium that carry mutations in genes involved in
histidine synthesis
 It is a auxotrophic mutant, so that they require histidine
for growth.
 The variable being tested is the mutagen's ability to cause
a reversion to growth on a histidine-free medium
 The plate is incubated for 48 hours
 Eg ; amalgam & drugs
56
57
 Non- mammalian test
 This assay quantifies the ability of potential carcinogens
to transform standardized cell lines so they will grow in
soft agar
 Untransformed fibroblasts normally will not grow within
an agar gel, whereas genetically transformed cells will
grow below the gel surface
58
59
 Mammals such as mice, rats, hamsters, or guinea pigs,
although many types of animals have been used.
 The use of an animal allows many complex interactions
between the material and a functioning, complete
biological system to occur.
60
Advantage :
 More comprehensive.
 More relevant than in vitro tests.
Disadvantages :
 Difficult to interpret and control
 Expensive
 Time consuming
Significant ethical concerns
 Paperwork.
61
62
 Material causes inflammation to mucous
membrane or abraded skin.
 Postive and negative controls are placed in
contact with hamster cheek pouch tissue
or rabbit oral tissue.
 Several week later it is examined and
gross tissue reaction in living animals are
recorded.
 Animal sacrificed and biopsy specimen
are prepared for histological evaluation.
 Guinea pigs –intradermally test solution is injected for
development of skin hypersensitivity reaction.
 Result-no reaction to redness and swelling.
63
 Tests are applied in a specific order, and testing is stopped
when anyone indicates mutagenic potential of the material
or chemical.
64
65
 To evaluate materials that will contact
subcutaneous tissue or bone.
 Amalgams and alloys are tested
because the margins of the restorative
materials contact the gingiva.
 Short term tests (  12 weeks) 
Mice, rats, guinea pigs
 Long term tests (  Weeks)  dogs,
rabbits, sheep, goats.
 Usage tests may be done in animals or in human
volunteers.
 The material be placed in a situation identical to its
intended clinical use
 Larger animals that have similar oral environments to
humans, such as dogs or monkeys are used.
66
 Advantages
 Relevance to use of material is assured
Disadvantages
 Very expensive
 Very time consuming
 Major legal/ethical issues
 Can be difficult to control
 Difficult to interpret and quantify
67
 Monkeys are suitable animal.
 Class V cavity preparation done with minimal trauma.
 ZOE and silicate cements used with positive and negative
control material respectively and left for 1-8 weeks.
 Tooth is removed and examined under microscope and a
photomicrometer for reparative dentin evaluation.
68
 Failure of implants are gained from three tests:
 Periodontal probing
 Mobility
 Radiolucency around the implant.
69
70
 Implant is considered successful if
it
 No mobility
No peri-implant radiolucency
Minimal vertical bone loss
Absence of persistent peri-implant
soft tissue complications
Fibrous capsule formation is a
sign of irritation and chronic
inflammation.
 Materials are placed in cavity preparations with subgingival
extensions.
 Observed at 7 days and again after 30 days.
 Responses are categorized as slight, moderate,
or severe.
 A slight response is characterized by a few mononuclear
inflammatory cells (mainly lymphocytes) in the epithelium and
adjacent connective tissue.
 A moderate response is indicated by numerous mononuclear
cells in the connective tissue and a few neutrophils in the
epithelium.
 A severe reaction evokes a significant mononuclear and
neutrophilic infiltrate and thinned or absent epithelium.
71
 Difficulties
 Degree of preexisting inflammation in gingival tissue
 The surface roughness of the restorative material
 Overcontouring or undercontouring of the restoration.
 8 – 14 days of healing time should be given after oral
prophylaxis.
72
Using In Vitro, Animal, And Usage
Tests Together
73
74
75
76
Selection of biocomptible materials
1.Define the use of the material
Material play crucial role.
composition of material.
2. Define how the material has been tested
Usage test –fidelity of reproducing the clinical use
Animal or invitro test-structure of test and method are
employed.
3.Risks and benfits
No material is 100% safe/risk free.
depends on clinical judgement,common sense and data available.
Use require risk benefit analysis.
77
78
 Contraction on polymerization, wear, or thermal cycling.
 Amalgam, composite, zincphosphate cement, and silicate
cement
TEST MATERIAL PLACED
ZOE
79
 The leakage of saliva, bacteria, or material components
through the interface between a material and tooth
structure.
 Nanoleakage refers specifically to dentin bonding, and
may occur between mineralized dentin and a bonded
material in the very small spaces of demineralized
collagen matrix into which the bonded material did not
penetrate.
80
81
 1- to 2-µm layer of organic and inorganic debris.
 It was said to be impermeable but diffusion of molecules
as large as albumin (66 kDa) has occurred through a smear
layer.
 Ethylenediaminetetraacetic acid (EDTA), sodium
hypochlorite, and proteolytic enzymes.
82
83
 Bonding to dentin is more difficult - its composition (being
both organic and inorganic), wetness, and lower mineral
content.
 Successful bonding of agents creates a "hybrid layer" of resin
and collagen in intimate contact with dentin and dentinal
tubules
 The removal of the smear layer makes any microleakage more
significant.
 The acids used to remove the smear layer are a potential source
of irritation themselves (phosphoric, hydrochloric,citric, and
lactic acids).
84
 . Dentin is a very efficient buffer of protons, and most of
the acid may never reach the pulp if sufficient dentin
remains.
 A dentin thickness of 0.5 mm has proven adequate.
 Citric or lactic acids are less well buffered.
 Many of dentin bonding agents are cytotoxic to cells in
vitro tested alone.
 But when placed on dentin and rinsed with tap water
between applications of subsequent reagents as prescribed,
cytotoxicity is often reduced.
 Bonding agents permeate up to 0.5 mm of dentin to cause
significant suppression of cellular metabolism
85
86
 Hydroxyethyl methacrylate (HEMA), a
hydrophilic resin contained in several
bonding systems, is at least 100 times
less cytotoxic in tissue culture than
Bis-GMA.
 However, if the dentin in the floor of
the cavity preparation is thin (< 0.1
mm), there is some evidence that
HEMA may be cytotoxic in vivo.
 Eg; 1st generation, 2nd generation, 3rd
generation, 4th generation.
87
 Freshly set chemically cured and light-cured resins often cause
moderate cytotoxic reactions in cultured cells.
 The cytotoxicity reduced -24 to 48 hours after setting and by
the presence of a dentin barrier.
 The light-cured resins are less cytotoxic than chemically cured
systems.
 The pulpal inflammatory response to chemically cured and
light-cured resin composites is low to moderate after 3 days
when they were placed in cavities with approximately 0.5 mm
of remaining dentin.
 It is very cytotoxic in in-vitro tests of direct contact with
fibroblasts
 Probably because of unpolymerized components in the air-
inhibited layer that leach out from the materials.
88
 Some of the newer composites with non-BisGMA non-
UDMA matrices have significantly lower cytotoxicity.
 Polished composites show markedly less cytotoxicity in
vitro.
 bis-phenol-A and bis-phenol-A dimethacrylate to cause
estrogen-like responses in vitro.
 The effect on other oral tissues is not significant
89
•90
 Biocompatibility of amalgam is determined
largely by corrosion products released while
in service.
 Unreacted mercury from amalgam is toxic,
but low-copper amalgam that has set for 24
hours does not inhibit cell growth.
 Implantation tests show that low-copper
amalgams are well tolerated than high
copper.
 The cavity preparation should be lined for
two other reasons
 1. Thermal conductivity with amalgam
 2. Margins of newly placed amalgam
restorations show significant microleakage
 Amalgam restorations into the gingival crevice
inflammation of the gingiva as products of corrosion or
bacterial plaque.
 Even after 7 days after placing an amalgam, a few
inflammatory cells appear in the gingival connective
tissue, and hydropic degeneration of some epithelial cells
may be seen.
 Although copper enhances the physical properties of
amalgam and is bactericidal, it is also toxic to host cells
and causes severe tissue reactions in implantation tests.
 Gallium-based alloys that have been used as amalgam
replacements also shows sever reactions. 91
 In- vivo : Materials placed where they are rinsed in saliva,
these cytotoxic agents are probably washed away before
they harm the gingiva.
 Rough surfaces on alloy restorations also caused increased
cytotoxic effects so polishing the restoration is important.
92
 The cavities, with depths of about 2 mm, were placed
halfway between the cementoenamel junction and the root
tip.
93
 Amalgam tattoo is an iatrogenic lesion caused by
traumatic implantation of dental amalgam into soft tissue.
 Common localised pigmented lesion of oral cavity.
 Clinically, amalgam tattoo presents as a dark gray or blue,
flat macule located adjacent to a restored tooth.
 Most are located on the gingiva and alveolar mucosa
followed by the buccal mucosa and the floor of the
mouth.
 The biologic response to the amalgam is related to particle
size, quantity and elemental composition of the amalgam.
 Cosmetic surgery is done for amalgam tattoo.
 If cosmetic surgery is not possible then surgical excision
and tranplantation of oral mucosal tissue is done. 94
95
 Glass ionomers cement -luting agent and as a restorative
material.
 Freshly prepared ionomer is mildly cytotoxic, but effect
reduces with times after setting.
 The fluoride release causes cytotoxicity in in vitro tests
 Histological studies in usage tests shows that any inflammatory
infiltrate from ionomer is minimal or absent after 1 month.
 There have been several reports of pulpal hyperalgesia for
short periods (days) after placing glass ionomers in cervical
cavities.
 This effect is probably the result of increased dentin
permeability after acid etching or the high pH of the
restoration. 96
 Cavity liners of two basic type
saline suspensions with a very alkaline pH (above 12)
modified forms containing zinc oxide, titanium dioxide,
and resins.
 The high pH of calcium hydroxide in suspension leads to
extreme cytotoxicity
 Calcium hydroxide cements containing resins cause mild-
to-moderate cytotoxic effects.
 The inhibition of cell metabolism is reversible in tissue
culture by high levels of serum proteins, suggesting that
protein binding or buffering in inflamed pulpal tissue may
play an important role in detoxifying these materials in
vivo. 97
 The initial response is necrosis to a depth of 1 mm or more,
neutrophils infiltrate into the subnecrotic zone.
 Eventually, after 5 to 8 weeks, only a slight inflammatory
response remains.
 Within weeks to months, the necrotic zone undergoes
dystrophic calcification, which appears to be a stimulus for
dentin bridge formation.
 When resins are incorporated into the formulae, these calcium
hydroxide compounds become less irritating and are able to
stimulate reparative dentin bridge formation more quickly than
the Ca(OH), suspensions, and with no zone of necrosis
98
 Not used under resin-based materials, because resin
components dissolve the thin film of varnish.
 Liners are used in such thin layers, they do not provide
thermal insulation, but they initially isolate the dentinal
tubule contents from the cavity preparation.
 Reduce penetration of bacteria or chemical substances
for a time.
 Thinness of the film and formation of pinpoint holes, the
integrity of these materials is not as reliable
99
100
 Thermal conductivity = Enamel.
 Zinc-phosphate cement elicits strong-to-moderate
cytotoxic reactions that decrease with increased time after
setting.
 Focal necrosis, observed in implantation tests.
 In usage test , moderate-to-severe localized pulpal damage
is produced within the first 3 days, probably because of
the initial low pH on setting (4.2 pH at 3 minutes).
 The pH of the set cement approaches neutrality after 48
hours
101
 Initially painful and damaging effects on the pulp before
cement is placed in deep cavity preparations, protective
layer of a dentin bonding agent, ZOE, varnish, or calcium
hydroxide is recommended under the cement.
 Calcium hydroxide in the powder, lowers the
concentrations of phosphoric acid in the liquid, or
included materials such as copper and fluoride ions that
may function as antimicrobial agents.
 Copper ions have proven extremely toxic in implantation
tests
102
 Developed to combine the strength of zinc phosphate
cements with the adhesiveness and biocompatibility of
zinc oxide eugenol (ZOE).
 Inhibition of cells is seen initially but decreases as the
cement sets.
 Pulpal response similar to that caused by ZOE, with a
slight-to-moderate response after 3 days and only mild,
chronic inflammation after 5 weeks.
 Reparative dentin formation is minimal
103
104
 ZOE fixes cells, depresses cell respiration,
and reduces nerve transmission with direct
contact.
 ZOE has been reported bactericidal.
 This lower concentration reportedly
suppresses nerve transmission and inhibits
synthesis of prostaglandins and leukotrienes
(anti-inflammatory).
 Usage tests - ZOE caused only a slight-to-
moderate inflammation in first week.
 And reduced to a mild, chronic
inflammatory reaction.
 Reparative dentin formation in 5 to 8 weeks.
 Methacrylates, have been associated with immune
hypersensitivity reactions of gingiva and mucosa probably
more than any other dental material.
 Dental and laboratory personnel are in high risk exposed
repeatedly to a variety of unreacted components.
 Visible light-cured denture base resins and denture base
resin sealants have been shown to be cytotoxic to
epithelial cells in culture.
105
 Cell culture tests : have shown that some of these
materials are extremely cytotoxic.
 In animal tests : caused significant epithelial changes.
 In usage : Mild cytotoxity
106
 Severe cytotoxic reactions.
 The adhesives also allowed significant microbial growth
107
Wednesday, October 07, 2015 by Malisano Dental
108
 There are four basic materials used in implant fabrication:
ceramics, carbon, metals, and polymers (and
combinations of the above).
 Have low toxicity, and are nonimmunogenic and
noncarcinogenic.
 Carbon has been used as a coating and in bulk forms for
implants. Although the biologic response to carbon coatings
can be favorable, they have been supplanted by titanium,
aluminum oxide bulk materials, and hydroxyapatite coatings.
 Although titanium and titanium alloy implants have corrosion
rates that are markedly less than other metallic implants, they
do release titanium into the body.
109
 They have generally good record of biocompatibility
 HYPERSENSITIVITY: Nickel ( 10% - 20%) females,
palladium.
 CARCINOGENIC: beryllium, cadmium, cromium(Cr6), nickel
subsulfide (Ni2S3)
 MUTAGEN: Tin, copper, iron
Dental materials 18 (2002) 413-421
110
111
 No local or systemic cytotoxic effect.
 Bone response of ziroconia in vivo and inflammed.
112
 Ceramic material ar known for their high levels of
biocompatibility .
 Metal oxides-Al2O3,BaO,CaO,K2O,Li2O,Na2O,ZnOand
Zro2-dental core ceramics or dental veenering ceramics
andSiO2 are principle matrix phase component of all
veenering ceramics.
 In highly acidic environment increase of rate of release of
certain metals and silicon ions.
113
 Invitro Test Proven - Biocompatible.
 Nontoxic
 Non Injurious
 Not Physiologically Reactive.
 Light Weighted
 High Strength
 Excellent Durability To Chemical Agents.
 Susceptible To Attack Acidic Fluoride Products.
114
115
Beryllium
Although the beryllium concentration in dental alloys rarely
exceeds 2 wt % the amount of beryllium vapor released in to the
breathing space during melting of Ni-Cr-Be alloys may be
significant over an extended period.
· The risk of beryllium vapor exposure is greatest for dental
technicians during alloy melting especially in the absence of an
adequate exhaust and filtration system.
· High levels of beryllium have been measured during finishing
and polishing when a local exhaust system was not used. They
were reduced to levels considered safe when exhaust fan was
used.
· Exposure of beryllium may result in acute and chronic forms of
beryllium disease – BERYLLIOSIS
Clinical features
Symptoms range from coughing, chest pain and
general weakness to pulmonary dysfunction.
- Contact dermatitis
- Chemical pneumonitis
NICKEL
•It is a great concern to dental patients with a known allergy to
this element.
•Dermatitis resulting from contact with nickel solutions was
described as early as 1989.
•Inhalation, ingestion and dermal contact of nickel or nickel
containing alloys are common because nickel is found in
environmental sources such as air, soil and food as well as in
synthetic objects such as coins, kitchen utensils, and jewellery.
120
Nickel allergy was determined by PATCH TEST LUIS-
BLANCO-DALMAN 1982, [JPD.1982: 48; 99-101] described a
standard patch test consisting of 5% Nickel sulfate solution or 5%
Nickel sulfate solution on a petrolatum base, in centre portion of a
square band-aid of good quality. This is applied on medial aspect
of upper arm, which was cleaned with a alcohol swab. This is left
in place for 48hr undisturbed. A band-aid with out any reagent is
placed adjacent to the first acts a control. After 48 hrs, band-aid is
removed and area is cleaned.
It is read after 20 min.
0  no reaction.
+  erythema is seen.
++  erythema, papules are seen.
+++  erythema, papules, vesicles are seen.
++++  edema with vesicles is seen.
122
 No associated chemical or allergic reaction.
 Thermal injury can occur for improper handling of
reversible hydrocolloids
 Silicosis and pulmonary hypersensivity
 Dustless alginate is used.
123
 Reaction between zinc oxide and eugenol
 Used for:
 Surgical dressing
 Bite registration
 Root canal filling materials
 Cementing medium
 Impression of edentulous mouth
 Temporary relining material for denture.
124
 ZOE paste causes burning sensation and stinging.
 Leaching of eugenol .
 Zinc oxide can rect with varoius carboxylic acids.
 Orthoethoxybenzoic acid is used in regards of eugenols.
125
126
 ADA measured toxicity by injecting
material into the oral mucosa of baboons
for 48 h.
 Light-bodied materials were less toxic
and contained less lead, toxicity was not
strongly related to lead content.
 Lead peroxide (pbo2) are used in
materials for radiographic detection.
 But makes it difficult to distinguish from
coagulated blood.
 The method determined that sta-tic X and
imprex are significantly more toxic but
the lead content had no significant result.
127
 Cause allergic problem.
 Decreases by thorough
mixing of the material to
avoid contact of aromatic
sulponic ester catalyst with
mucous membrane.
 Contain some form of peroxide (generally carbamide
peroxide) in a gel form.
 Applied to the teeth either by the dentist or by the patient.
 Is in contact with teeth for several minutes to several
hours depending on the formulation.
 Home bleaching agents is for weeks to even months.
 In vitro study-peroxides can rapidly (within minutes)
traverse the dentin in sufficient concentrations to be
cytotoxic.
 Cytotoxicity depends to a large extent on the
concentration of the peroxide.
128
 Peroxides rapidly penetrate intact enamel and reach the
pulp in a few minutes.
 Tooth sensitivity is very common.
129
 Toxicity is the peak circulation levels of local anesthetics.
 concentration of local anesthetic administered to patients
are varied according to:
Age
Weight
Health.
 Maximum dose -70mg to 500mg
 The amount of dose - solution and vasoconstrictor.
130
Tissue toxicity - Rare
 Can occur if administered
in high enough
concentrations (greater
than those used clinically)
 Usually related to
preservatives added to
solution
Systemic toxicity - Rare
 Related to blood level of
drug secondary to
absorption from site of
injection.
 Range from
lightheadedness, tinnitus
to seizures and
CNS/cardiovascular
collapse
131
 True allergy is very rare
 Most reactions are from ester class - ester hydrolysis
(normal metabolism) leads to formation of PABA - like
compounds
 Patient reports of “allergy” are frequently due to previous
intravascular injections
132
133
 Inhalation and aspiration of various dust and
toxic vapours-heating and melting of certain
alloys causes respiratory and GIT system
irritation.
 Pneumoconiosis is severe fibrotic lung
disease caused by chronic exposure to
inorganic dust.
 Exposure to Co-Cr,Co-Cr-Mo and Ni-Cr-Be
alloys cause pneumoconiosis in techinicians.
 Benign pneumoconiosis –hard metals.
 Malignant pneumoconiosis-dust from
crystalline silics,abestos or beryllium.
 It was only in 1980 dentists started using gloves.
 In March 29, 1991, the FDA issued a bulletin in response
to latex related allergy.
134
Processing of latex :
Natural rubber products
While milky sap from tropical trees
.
Ammonia is added to pressure.
hydrolyzes and degrades the sap proteins to
produce allergens.
 Aerosol –particles are both liquid and solid .
 Particle is less than 100 microns.
 When water evaporates droplet nuclei is formed of 0.5 to
10 microns.
 It can reach to pulmonary alveoli or float in air for several
hours.
 Splatter –air borne particles which are larger than 50
microns in diameter.
 Mixture of air,water and/or solid substance which is
50micron to several millimeter.
136
 Aerosol and splatter production which occur with usage
of ultrasonic scalertips and burs at high speed handpiece is
considered to be very exhastive or intensive.
 Source- Patient
Dental Unit Waterline
Instruments
137
138
Thermal osteonecrosis and bone drilling parameters
revisited: Augustin, G.etal(2007)
 During the drilling of the bone, the temperature could
increase above 47degreeC and cause irreversible
osteonecrosis. The result is weakened contact of implants
with bone and possible loss of rigid fixation.
 The aim of this study was to find an optimal conditions
where the increase in bone temperature during bone
drilling process would be minimal.
. Archives of Orthopaedic and Trauma Surgery, [Epub ahead of print].
139
 Materials and methods-
Influence of different drill parameters was
evaluated on the increase of bone temperature.
1. Diameters-2.5, 3.2 and 4.5 mm
2. Drill speed-188, 462, 1140 and 1820 rpm
3. Feed-rate 24, 56, 84, 196 mm/min
4. Drill point angle 80, 100 and 120degree
5. External irrigation with water of 26 deg C.
140
. Archives of Orthopaedic and Trauma Surgery, [Epub ahead of print].
 Results-
 Combinations of drill speed and diameter with the use
of external irrigation produced temperatures far below
critical.
 Without external irrigation, temperature values for the
same combination of parameters ranged 31.4-55.5degC.
 Temperatures above critical were recorded using 4.5 mm
drill with higher drill speeds (1140 and 1820 rpm).
141
. Archives of Orthopaedic and Trauma Surgery, [Epub ahead of print].
 There was no statistical significance of different drill point
angles on the increase or decrease of bone temperature.
The higher the feed-rate the lower the increase of bone
temperature
142
. Archives of Orthopaedic and Trauma Surgery, [Epub ahead of print].
 Biocompatible Denture Polymers – A Review
Rahul Bhola etal (2009)
 This article reviews various denture polymers for their
properties and provides suggestions on the development of
newer polymers for future clinical use.
 PMMA resin continues to be the universal versatile polymer in
denture dentistry. Depending upon the type of polymerization,
PMMA resins may leach 0.1-5% of the residual monomer and
additives, mainly MMA and formaldehyde, contributing to
localized allergic reactions
143Trends Biomater. Artif. Organs, Vol 23(3),129-3l6 (2010)
 Possible carcinogenic and embryotoxic potency of MMA.
 Allergic reactions has been observed to increase with the
increased use of higher amounts of PMMA resins.
 Development of newer high strength,radio-opaque acrylic
denture materials employing polymer blends, heavy metals and
block co-polymers.
 Development of non-leachable plasticizer or plasticizer free
soft denture liners that could retain their softness permanently.
144
Trends Biomater. Artif. Organs, Vol 23(3),129-3l6 (2010)
 The biocompatibility of a dental material depends on its
composition, location and interactions with oral cavity. Diverse
biological responses to these materials depend on whether they
release their components and whether those components are
toxic, immunogenic, or mutagenic at released concentrations.
 Today, in development of any biomaterial one must consider
not only strength, esthetics, or functional aspects of the
material, but its biocompatibility as well. Furthermore,
demands for appropriate biological responses are increasing as
we ask materials to perform more sophisticated functions in
body. Thus considerations of biocompatibility are important to
manufactures, practitioners, scientists and patients
145
146
 Craig’s Restorative Dental Materials –John M.Power.RonaldL.Sakaguchi-
12th Edition-Elsevier.
 Science of Dental Materials Clinical applications-V Shama.BT Nandish-2nd
edition-CBC publishers and distributors.
 Philips’Science Dental Materials-Anusavice-11th Edition-Elsevier
 Philips’Science Dental Materials-Anusavice|Shen|Rawl-12th Edition-
Elsevier.
 Glossary of Prosthodontics Terms-8th edition.
 Glossary of Prosthodontics Terms-9th edition
 Essential of Oral Histology and Embrology A Clinical Approach-James k
Avery|Daniel j ChiegJ-Mosby Elsevier.
 Archives of Orthopaedic and Trauma Surgery, [Epub ahead of print].
 Trends Biomater. Artif. Organs, Vol 23(3),129-3l6 (2010)
 (J Prosthet Dent 2001;86:203-9.)
 Textbook of Pathology :Harsh Mohan :4th edition :jaypee brothers
147
148

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Biocompatibilty seminar

  • 1.
  • 3. Introduction Historical Background Importance Of Biocompatibility Regulatory Approval Of Dental Materials Definition Requirement Adverse effect Toxicity Hypersensitivity and Allergy Inflammation Mutagenic reaction 3
  • 4. Estrogenicity Osseointegration and Biointegration Immunotoxicity Anatomy and pathological aspect of oral tissues Enamel Dentin and pulp Dentin permeability Bone Periodontium Gingiva and Mucosa 4
  • 5. Measuring biocompatibilty Invitro test Animal test Usage test Using invitro,animal and usage tests together Selection of biocompatible material Biocompatibility of dental materials Review of literature Conclusion  Reference 5
  • 6.  “Our objective should be the perpetual preservation of what remains rather than the meticulous restoration of what is missing” MULLAR M.DE VAN 6
  • 7. 7(J Prosthet Dent 2001;86:203-9.)
  • 8.  Although the concept of the ethical treatment of patients extends back to the time of Hippocrates (460- 377 KC.), 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.
  • 9.  Many exotic formulations were used. For example, Fox developed a "fusible metal“ that consisted of bismuth, lead, and tin, which he melted and poured into the cavity preparation at a temperature of approximately 100" C.  Even G.V. Black used patients to test many of his new ideas for restorative materials, such as early amalgams.
  • 10.  The current philosophy about testing the biological properties of dental materials in a systematic way evolved in the 1960s as the need to protect patients became politically acute and as the number of new materials increase.  The concept of protecting the patient as a research subject is only 30 to 40 years old, and many of the regulations and ethics in this area still being challenged and defined today.
  • 11. Dentists potential concerns about biocompatibility can be organized in to 3 areas :  1) Safety of the patient. Primary concern - avoid any harm to the patient.  2) Safety of Dental staff The risk of adverse effects of biomaterials is much higher for dental staff than for the patient. The staff may be chronically exposed to materials when they are being manipulated or setting. Eg:- i) Amalgam – Mercury vapour. ii) Chronic exposure to latex and resin based materials. 11
  • 12. iii) Regulatory compliance issues Biocompatibility issues are closely linked to regulations that affect dental practice. Ex: Dental amalgam. 3) Legal Liability.  Biocompatibility issues also influence liability issues that affect dental practitioners. 12
  • 13. Two regulations currently govern the use of dental materials: ANSI/ADA document No.41(1979) & addendum No41A(1982) ISO10993document(1993) although these documents are different , ANSI/ADA document is currently under revision to coordinate with the ISO document. 13
  • 14.  Biocompatible Capable of existing in harmony with surrounding biological environment GPT(9)  Biocompatibility Property of the material which remain harmoniously with the living tissues. Shama Bhat-2nd edition Ability of a material to elicit on appropiate biological response in a given application in the body. Craig -12 edition 14
  • 15. Biomaterial Any substance other than a drug that can be used for any period of time as part of a system that treats, augments, or replaces any tissue, organ, or function of the body. GPT(8)  Bioinert These allow close apposition of bone on their surface leading to intact osteogenesis. Metals –commerically pureTi Ti alloy (Ti6Al-4V) Al2O3,Zr2O3 15
  • 16.  Biodegradation The series of processes by which living systems render chemicals less noxious to the environment. GPT(8)  Bioactive Having an effect on or causing a reaction in living tissue 16
  • 17.  Should not be harmful to pulp and soft tissues  Should not contain toxic diffusible substance  Should not produce allergic responses  Should not be carcinogenic  Should not undergo biodegradation  Should not show estrogenecity and contain xenoestrogens 17
  • 18. 18
  • 19.  Paracelus(1493-1541)- father of toxicology and first modern medical scientist said that. “All things are poison and nothing is without poison only the dose permits something not to be poisonous”. Latter phrase-right dose differentiates a poison for remedy. 19
  • 20.  Test organism such as cells and selected bacteria through higher order plants and animals.  A specific response or biological endpoint.  Exposure or test period.  A dose or dose curve. 20
  • 21. 21  Hypersensitivity is abnormal reaction that occurs when the body is exposed to a foreign material.  Develops only in person whose immune system recognise the material as foreign.  Allergic reaction can manifest as a localised reaction in tissues which is directly in contact with material.  Systemic manifestation are skin eruption, itching, sneezing, erythema,breathing difficulties.
  • 22. Textbook of Pathology :Harsh Mohan :4th edition :jaypee brothers 22
  • 23.  Allergic contact dermatitis  Allergic contact stomatitis  Allergic to latex products 23
  • 24. 24
  • 25.  Altering the base pair sequence of DNA in cells  Resin based restorative  Sealants  Ions of metal(Ni,Be,Cu) found to be mutagens. 25
  • 26.  Ability to produce material like xenoestrogens to act in body as estrogens  Resin  bisphenolA-starting substance of BisGMA  Restorative material and few other resin are estrogenic 26
  • 27. 27  Osseointegration –formation of living body tissues within 10mm space from the implant material surface without any fibrous connective tissues.  Material –CpTi,Ti6Al-4v alloy,tantalum and few ceramics.  These material does not undergo biodegradation easily.
  • 28.  Certain material like bioglasses which undergo biointegration with the bone.  Directly without any interviewing space.  This material should undergo degradation. 28
  • 29. 29  Alteration in cells of immune system.  Mercury  Palladium  Dentin bonding agents  HEMA may indirectly cause change in cellular function.
  • 30. 30
  • 31. 31 • Highly mineralised. • More brittle than dentin. • Solubilised to a greater extent by acid solution. • Helps for bonding agents to provide micromechanical retention.
  • 32. Essential of Oral Histology and Embrology A Clinical Approach-James k Avery|Daniel j ChiegJ-Mosby Elsevier 32
  • 33. Essential of Oral Histology and Embrology A Clinical Approach-James k Avery|Daniel j ChiegJ-Mosby Elsevier 33
  • 34. 34  Under positive hydraulic pressure- Movement of fluid in the dentinal tubules stimulates the A-fibers producing sharp localised pain.  Under negative hydraulic pressure- fluid convection is away from the pulp when concentrated solution such as sucrose, or saturated calcium chloride are exposed to open dentinal tubules producing sensitivity. Eg, cervical abrasion.  Presence of smear layer, cavity liners, sealers, debri can reduce fluid convection.
  • 35. 35  Diffusion is proportional to the length of the dentinal tubules & roughly to the thickness of dentin between cavity preparation & pulp.  Ions & molecules can diffuse even against positive hydraulic pressure.  Smear layers are better than cavity liners & sealers.
  • 36.  Extacellular matrixwith cells and tissues .  Mineralised tissue-23%organic substance (86%typeI collagen) 77%hydroxyapatite(small and less well dentin)  Vascularity of bone serve mineral phase as a major reservoir of calcium and phosphate ions for body’s metabolic processes.  Synthesized by osteoclast .  It have excellent self repair capacity. 36
  • 37. 37
  • 38. 38  Consist of PDL,cementum and alveolar bone.  Cementum and alveolar bone – extracellular matrices.  Cells are destroyed during injury and have no source of progenitor cells ankylosis –bone and teeth  Researchers have investigated that chemical and surgical methods to limit epithelial down growth of gingiva to enhance PDL reattachments to tooth and bone surface,
  • 39.  Gingiva –attached and free gingiva.  Oral mucosa –loose fibroelastic connective tissuewith a well vascularised and innervated lamina propria and submucosa and covered by parakeratinized stratified squamous epithelium.  Dental material chemically and physically injury OMM  Gingival tissues reaction to oral implant. 39
  • 40.  Transmucosal implant –special problem-epithelial growth,encystification and exfoliation of implant.  Inflammatory disease around implant is implantits.  Perimplantitis-response to bacteria that attached to implant and exist near the gingiva. 40
  • 41. 41
  • 42.  Outside body  In vitro – Interaction of any material on cell, enzyme or any biological substance isolated from organism. 42
  • 43.  Direct – material physically in contact with cell  Indirect – extract from the material in contact with the cell  Subdivided into measuring Cell growth / cytotoxicity Effect on genetic material in cell Metabolic / other cell function 43
  • 44.  Advantages  Quick  Inexpensive  Easy  Standardized  Well suited for large scale screening  Disadvantage  Questionable relevance to final in-vivo study.  Lack of inflammatory and other tissue protective measures. 44
  • 45.  Primary cells – direct from animal into culture - limited period of growth - maintains characteristics of cell - to measure cytotoxicity  Continuous cells – transformed primary cells - growth is in definitive - no in vivo characteristics - genetically and metabolically stable ( easy to standardize) 45
  • 46. 46  Assess by measuring the cell number/ growth after exposing to material  Liquid- cells are placed in well of culture dish - then places in sample - if cell detach and stop growth – cytotoxic - if remains in contact with well – non cytotoxic. Eg; bonding agent, formocresol
  • 47.  Solid – eg; Tablets zone of inhibition 47
  • 48. Membrane permeability Na51CrO4 (vital dyes) Neutral Red (vital dyes) Trypan Blue (non-vital dyes) 48
  • 49.  Usually dyes contain auxochromes.  An auxochrome is a group of atoms attracted to a chromophore, which are present in cells.  Vital dyes are basic dyes they contain amino group, that helps in cell permeability.  The basic dyes bind to negative ions to stain the cell.  Acid ions in non-vital dyes reduce the ability of the dyes to stain the vital cells.  Eg – chemicals, injecting drugs 49
  • 50.  The biosynthesis or enzymatic activity of cells to assess cytotoxicity  Measures – DNA synthesis - Protein synthesis  They are analyzed by adding radioisotope labeled precursors to the medium and quantifying them on DNA and protein  Radioisotope - 3H-thymidine 50
  • 51. 51  It is a colorimetric assays  This measures the activity of cellular dehydrogenases  XTT(2-methoxy-4-nitro- 5-sulfophenyl),MTS( 4,5- dimethylthiazol-2-yl), WST( water soluble Tetrazolium salt)
  • 52.  Which converts the MTT chemical to a purple, insoluble formazan dyes  If dehydrogenases are not active because of cytoxic effect the formazan will not form  Helps in assay the viability & proliferation of cell  Quantified using spectrophotometer(500-600nm wavelength)  Enzyme that oxidizes a substrate by transferring hydrogen to an acceptor that is either NAD(Nicotinamide Adenine Dinucleotide or a flavin enzyme. 52
  • 53.  Since there is no direct contact between cell and material in vivo ( epithelium/dentin)  AGAR OVERLAY METHOD: AGAR NUTRIENTS, GAS, SOLUBLE TOXIC NEUTRAL RED / FRESH CULTURE MEDIA 53
  • 54.  Effect of materials on a cell’s genetic material  Genotoxic mutagens directly alter the DNA of the cell through mutation  Genotoxic chemical may be mutagens in native state or may require activation or biotransformation to be mutagens, in which case they are called promutagens 54
  • 55.  Epigenetic mutagens do not alter the DNA themselves, but support tumor growth by altering the cell's biochemistry, altering the immune system, acting as hormones, or other mechanisms.  Carcinogenesis is the ability to cause cancer.  Mutagens may or may not be carcinogens, and carcinogens may or may not be mutagens. 55
  • 56.  The test uses several strains of the bacterium Salmonella typhimurium that carry mutations in genes involved in histidine synthesis  It is a auxotrophic mutant, so that they require histidine for growth.  The variable being tested is the mutagen's ability to cause a reversion to growth on a histidine-free medium  The plate is incubated for 48 hours  Eg ; amalgam & drugs 56
  • 57. 57
  • 58.  Non- mammalian test  This assay quantifies the ability of potential carcinogens to transform standardized cell lines so they will grow in soft agar  Untransformed fibroblasts normally will not grow within an agar gel, whereas genetically transformed cells will grow below the gel surface 58
  • 59. 59
  • 60.  Mammals such as mice, rats, hamsters, or guinea pigs, although many types of animals have been used.  The use of an animal allows many complex interactions between the material and a functioning, complete biological system to occur. 60
  • 61. Advantage :  More comprehensive.  More relevant than in vitro tests. Disadvantages :  Difficult to interpret and control  Expensive  Time consuming Significant ethical concerns  Paperwork. 61
  • 62. 62  Material causes inflammation to mucous membrane or abraded skin.  Postive and negative controls are placed in contact with hamster cheek pouch tissue or rabbit oral tissue.  Several week later it is examined and gross tissue reaction in living animals are recorded.  Animal sacrificed and biopsy specimen are prepared for histological evaluation.
  • 63.  Guinea pigs –intradermally test solution is injected for development of skin hypersensitivity reaction.  Result-no reaction to redness and swelling. 63
  • 64.  Tests are applied in a specific order, and testing is stopped when anyone indicates mutagenic potential of the material or chemical. 64
  • 65. 65  To evaluate materials that will contact subcutaneous tissue or bone.  Amalgams and alloys are tested because the margins of the restorative materials contact the gingiva.  Short term tests (  12 weeks)  Mice, rats, guinea pigs  Long term tests (  Weeks)  dogs, rabbits, sheep, goats.
  • 66.  Usage tests may be done in animals or in human volunteers.  The material be placed in a situation identical to its intended clinical use  Larger animals that have similar oral environments to humans, such as dogs or monkeys are used. 66
  • 67.  Advantages  Relevance to use of material is assured Disadvantages  Very expensive  Very time consuming  Major legal/ethical issues  Can be difficult to control  Difficult to interpret and quantify 67
  • 68.  Monkeys are suitable animal.  Class V cavity preparation done with minimal trauma.  ZOE and silicate cements used with positive and negative control material respectively and left for 1-8 weeks.  Tooth is removed and examined under microscope and a photomicrometer for reparative dentin evaluation. 68
  • 69.  Failure of implants are gained from three tests:  Periodontal probing  Mobility  Radiolucency around the implant. 69
  • 70. 70  Implant is considered successful if it  No mobility No peri-implant radiolucency Minimal vertical bone loss Absence of persistent peri-implant soft tissue complications Fibrous capsule formation is a sign of irritation and chronic inflammation.
  • 71.  Materials are placed in cavity preparations with subgingival extensions.  Observed at 7 days and again after 30 days.  Responses are categorized as slight, moderate, or severe.  A slight response is characterized by a few mononuclear inflammatory cells (mainly lymphocytes) in the epithelium and adjacent connective tissue.  A moderate response is indicated by numerous mononuclear cells in the connective tissue and a few neutrophils in the epithelium.  A severe reaction evokes a significant mononuclear and neutrophilic infiltrate and thinned or absent epithelium. 71
  • 72.  Difficulties  Degree of preexisting inflammation in gingival tissue  The surface roughness of the restorative material  Overcontouring or undercontouring of the restoration.  8 – 14 days of healing time should be given after oral prophylaxis. 72
  • 73. Using In Vitro, Animal, And Usage Tests Together 73
  • 74. 74
  • 75. 75
  • 77. 1.Define the use of the material Material play crucial role. composition of material. 2. Define how the material has been tested Usage test –fidelity of reproducing the clinical use Animal or invitro test-structure of test and method are employed. 3.Risks and benfits No material is 100% safe/risk free. depends on clinical judgement,common sense and data available. Use require risk benefit analysis. 77
  • 78. 78
  • 79.  Contraction on polymerization, wear, or thermal cycling.  Amalgam, composite, zincphosphate cement, and silicate cement TEST MATERIAL PLACED ZOE 79
  • 80.  The leakage of saliva, bacteria, or material components through the interface between a material and tooth structure.  Nanoleakage refers specifically to dentin bonding, and may occur between mineralized dentin and a bonded material in the very small spaces of demineralized collagen matrix into which the bonded material did not penetrate. 80
  • 81. 81
  • 82.  1- to 2-µm layer of organic and inorganic debris.  It was said to be impermeable but diffusion of molecules as large as albumin (66 kDa) has occurred through a smear layer.  Ethylenediaminetetraacetic acid (EDTA), sodium hypochlorite, and proteolytic enzymes. 82
  • 83. 83
  • 84.  Bonding to dentin is more difficult - its composition (being both organic and inorganic), wetness, and lower mineral content.  Successful bonding of agents creates a "hybrid layer" of resin and collagen in intimate contact with dentin and dentinal tubules  The removal of the smear layer makes any microleakage more significant.  The acids used to remove the smear layer are a potential source of irritation themselves (phosphoric, hydrochloric,citric, and lactic acids). 84
  • 85.  . Dentin is a very efficient buffer of protons, and most of the acid may never reach the pulp if sufficient dentin remains.  A dentin thickness of 0.5 mm has proven adequate.  Citric or lactic acids are less well buffered.  Many of dentin bonding agents are cytotoxic to cells in vitro tested alone.  But when placed on dentin and rinsed with tap water between applications of subsequent reagents as prescribed, cytotoxicity is often reduced.  Bonding agents permeate up to 0.5 mm of dentin to cause significant suppression of cellular metabolism 85
  • 86. 86  Hydroxyethyl methacrylate (HEMA), a hydrophilic resin contained in several bonding systems, is at least 100 times less cytotoxic in tissue culture than Bis-GMA.  However, if the dentin in the floor of the cavity preparation is thin (< 0.1 mm), there is some evidence that HEMA may be cytotoxic in vivo.  Eg; 1st generation, 2nd generation, 3rd generation, 4th generation.
  • 87. 87
  • 88.  Freshly set chemically cured and light-cured resins often cause moderate cytotoxic reactions in cultured cells.  The cytotoxicity reduced -24 to 48 hours after setting and by the presence of a dentin barrier.  The light-cured resins are less cytotoxic than chemically cured systems.  The pulpal inflammatory response to chemically cured and light-cured resin composites is low to moderate after 3 days when they were placed in cavities with approximately 0.5 mm of remaining dentin.  It is very cytotoxic in in-vitro tests of direct contact with fibroblasts  Probably because of unpolymerized components in the air- inhibited layer that leach out from the materials. 88
  • 89.  Some of the newer composites with non-BisGMA non- UDMA matrices have significantly lower cytotoxicity.  Polished composites show markedly less cytotoxicity in vitro.  bis-phenol-A and bis-phenol-A dimethacrylate to cause estrogen-like responses in vitro.  The effect on other oral tissues is not significant 89
  • 90. •90  Biocompatibility of amalgam is determined largely by corrosion products released while in service.  Unreacted mercury from amalgam is toxic, but low-copper amalgam that has set for 24 hours does not inhibit cell growth.  Implantation tests show that low-copper amalgams are well tolerated than high copper.  The cavity preparation should be lined for two other reasons  1. Thermal conductivity with amalgam  2. Margins of newly placed amalgam restorations show significant microleakage
  • 91.  Amalgam restorations into the gingival crevice inflammation of the gingiva as products of corrosion or bacterial plaque.  Even after 7 days after placing an amalgam, a few inflammatory cells appear in the gingival connective tissue, and hydropic degeneration of some epithelial cells may be seen.  Although copper enhances the physical properties of amalgam and is bactericidal, it is also toxic to host cells and causes severe tissue reactions in implantation tests.  Gallium-based alloys that have been used as amalgam replacements also shows sever reactions. 91
  • 92.  In- vivo : Materials placed where they are rinsed in saliva, these cytotoxic agents are probably washed away before they harm the gingiva.  Rough surfaces on alloy restorations also caused increased cytotoxic effects so polishing the restoration is important. 92
  • 93.  The cavities, with depths of about 2 mm, were placed halfway between the cementoenamel junction and the root tip. 93
  • 94.  Amalgam tattoo is an iatrogenic lesion caused by traumatic implantation of dental amalgam into soft tissue.  Common localised pigmented lesion of oral cavity.  Clinically, amalgam tattoo presents as a dark gray or blue, flat macule located adjacent to a restored tooth.  Most are located on the gingiva and alveolar mucosa followed by the buccal mucosa and the floor of the mouth.  The biologic response to the amalgam is related to particle size, quantity and elemental composition of the amalgam.  Cosmetic surgery is done for amalgam tattoo.  If cosmetic surgery is not possible then surgical excision and tranplantation of oral mucosal tissue is done. 94
  • 95. 95
  • 96.  Glass ionomers cement -luting agent and as a restorative material.  Freshly prepared ionomer is mildly cytotoxic, but effect reduces with times after setting.  The fluoride release causes cytotoxicity in in vitro tests  Histological studies in usage tests shows that any inflammatory infiltrate from ionomer is minimal or absent after 1 month.  There have been several reports of pulpal hyperalgesia for short periods (days) after placing glass ionomers in cervical cavities.  This effect is probably the result of increased dentin permeability after acid etching or the high pH of the restoration. 96
  • 97.  Cavity liners of two basic type saline suspensions with a very alkaline pH (above 12) modified forms containing zinc oxide, titanium dioxide, and resins.  The high pH of calcium hydroxide in suspension leads to extreme cytotoxicity  Calcium hydroxide cements containing resins cause mild- to-moderate cytotoxic effects.  The inhibition of cell metabolism is reversible in tissue culture by high levels of serum proteins, suggesting that protein binding or buffering in inflamed pulpal tissue may play an important role in detoxifying these materials in vivo. 97
  • 98.  The initial response is necrosis to a depth of 1 mm or more, neutrophils infiltrate into the subnecrotic zone.  Eventually, after 5 to 8 weeks, only a slight inflammatory response remains.  Within weeks to months, the necrotic zone undergoes dystrophic calcification, which appears to be a stimulus for dentin bridge formation.  When resins are incorporated into the formulae, these calcium hydroxide compounds become less irritating and are able to stimulate reparative dentin bridge formation more quickly than the Ca(OH), suspensions, and with no zone of necrosis 98
  • 99.  Not used under resin-based materials, because resin components dissolve the thin film of varnish.  Liners are used in such thin layers, they do not provide thermal insulation, but they initially isolate the dentinal tubule contents from the cavity preparation.  Reduce penetration of bacteria or chemical substances for a time.  Thinness of the film and formation of pinpoint holes, the integrity of these materials is not as reliable 99
  • 100. 100
  • 101.  Thermal conductivity = Enamel.  Zinc-phosphate cement elicits strong-to-moderate cytotoxic reactions that decrease with increased time after setting.  Focal necrosis, observed in implantation tests.  In usage test , moderate-to-severe localized pulpal damage is produced within the first 3 days, probably because of the initial low pH on setting (4.2 pH at 3 minutes).  The pH of the set cement approaches neutrality after 48 hours 101
  • 102.  Initially painful and damaging effects on the pulp before cement is placed in deep cavity preparations, protective layer of a dentin bonding agent, ZOE, varnish, or calcium hydroxide is recommended under the cement.  Calcium hydroxide in the powder, lowers the concentrations of phosphoric acid in the liquid, or included materials such as copper and fluoride ions that may function as antimicrobial agents.  Copper ions have proven extremely toxic in implantation tests 102
  • 103.  Developed to combine the strength of zinc phosphate cements with the adhesiveness and biocompatibility of zinc oxide eugenol (ZOE).  Inhibition of cells is seen initially but decreases as the cement sets.  Pulpal response similar to that caused by ZOE, with a slight-to-moderate response after 3 days and only mild, chronic inflammation after 5 weeks.  Reparative dentin formation is minimal 103
  • 104. 104  ZOE fixes cells, depresses cell respiration, and reduces nerve transmission with direct contact.  ZOE has been reported bactericidal.  This lower concentration reportedly suppresses nerve transmission and inhibits synthesis of prostaglandins and leukotrienes (anti-inflammatory).  Usage tests - ZOE caused only a slight-to- moderate inflammation in first week.  And reduced to a mild, chronic inflammatory reaction.  Reparative dentin formation in 5 to 8 weeks.
  • 105.  Methacrylates, have been associated with immune hypersensitivity reactions of gingiva and mucosa probably more than any other dental material.  Dental and laboratory personnel are in high risk exposed repeatedly to a variety of unreacted components.  Visible light-cured denture base resins and denture base resin sealants have been shown to be cytotoxic to epithelial cells in culture. 105
  • 106.  Cell culture tests : have shown that some of these materials are extremely cytotoxic.  In animal tests : caused significant epithelial changes.  In usage : Mild cytotoxity 106
  • 107.  Severe cytotoxic reactions.  The adhesives also allowed significant microbial growth 107
  • 108. Wednesday, October 07, 2015 by Malisano Dental 108  There are four basic materials used in implant fabrication: ceramics, carbon, metals, and polymers (and combinations of the above).  Have low toxicity, and are nonimmunogenic and noncarcinogenic.
  • 109.  Carbon has been used as a coating and in bulk forms for implants. Although the biologic response to carbon coatings can be favorable, they have been supplanted by titanium, aluminum oxide bulk materials, and hydroxyapatite coatings.  Although titanium and titanium alloy implants have corrosion rates that are markedly less than other metallic implants, they do release titanium into the body. 109
  • 110.  They have generally good record of biocompatibility  HYPERSENSITIVITY: Nickel ( 10% - 20%) females, palladium.  CARCINOGENIC: beryllium, cadmium, cromium(Cr6), nickel subsulfide (Ni2S3)  MUTAGEN: Tin, copper, iron Dental materials 18 (2002) 413-421 110
  • 111. 111
  • 112.  No local or systemic cytotoxic effect.  Bone response of ziroconia in vivo and inflammed. 112
  • 113.  Ceramic material ar known for their high levels of biocompatibility .  Metal oxides-Al2O3,BaO,CaO,K2O,Li2O,Na2O,ZnOand Zro2-dental core ceramics or dental veenering ceramics andSiO2 are principle matrix phase component of all veenering ceramics.  In highly acidic environment increase of rate of release of certain metals and silicon ions. 113
  • 114.  Invitro Test Proven - Biocompatible.  Nontoxic  Non Injurious  Not Physiologically Reactive.  Light Weighted  High Strength  Excellent Durability To Chemical Agents.  Susceptible To Attack Acidic Fluoride Products. 114
  • 115. 115
  • 116. Beryllium Although the beryllium concentration in dental alloys rarely exceeds 2 wt % the amount of beryllium vapor released in to the breathing space during melting of Ni-Cr-Be alloys may be significant over an extended period.
  • 117. · The risk of beryllium vapor exposure is greatest for dental technicians during alloy melting especially in the absence of an adequate exhaust and filtration system. · High levels of beryllium have been measured during finishing and polishing when a local exhaust system was not used. They were reduced to levels considered safe when exhaust fan was used. · Exposure of beryllium may result in acute and chronic forms of beryllium disease – BERYLLIOSIS
  • 118. Clinical features Symptoms range from coughing, chest pain and general weakness to pulmonary dysfunction. - Contact dermatitis - Chemical pneumonitis
  • 119. NICKEL •It is a great concern to dental patients with a known allergy to this element. •Dermatitis resulting from contact with nickel solutions was described as early as 1989. •Inhalation, ingestion and dermal contact of nickel or nickel containing alloys are common because nickel is found in environmental sources such as air, soil and food as well as in synthetic objects such as coins, kitchen utensils, and jewellery.
  • 120. 120
  • 121. Nickel allergy was determined by PATCH TEST LUIS- BLANCO-DALMAN 1982, [JPD.1982: 48; 99-101] described a standard patch test consisting of 5% Nickel sulfate solution or 5% Nickel sulfate solution on a petrolatum base, in centre portion of a square band-aid of good quality. This is applied on medial aspect of upper arm, which was cleaned with a alcohol swab. This is left in place for 48hr undisturbed. A band-aid with out any reagent is placed adjacent to the first acts a control. After 48 hrs, band-aid is removed and area is cleaned. It is read after 20 min. 0  no reaction. +  erythema is seen. ++  erythema, papules are seen. +++  erythema, papules, vesicles are seen. ++++  edema with vesicles is seen.
  • 122. 122
  • 123.  No associated chemical or allergic reaction.  Thermal injury can occur for improper handling of reversible hydrocolloids  Silicosis and pulmonary hypersensivity  Dustless alginate is used. 123
  • 124.  Reaction between zinc oxide and eugenol  Used for:  Surgical dressing  Bite registration  Root canal filling materials  Cementing medium  Impression of edentulous mouth  Temporary relining material for denture. 124
  • 125.  ZOE paste causes burning sensation and stinging.  Leaching of eugenol .  Zinc oxide can rect with varoius carboxylic acids.  Orthoethoxybenzoic acid is used in regards of eugenols. 125
  • 126. 126  ADA measured toxicity by injecting material into the oral mucosa of baboons for 48 h.  Light-bodied materials were less toxic and contained less lead, toxicity was not strongly related to lead content.  Lead peroxide (pbo2) are used in materials for radiographic detection.  But makes it difficult to distinguish from coagulated blood.  The method determined that sta-tic X and imprex are significantly more toxic but the lead content had no significant result.
  • 127. 127  Cause allergic problem.  Decreases by thorough mixing of the material to avoid contact of aromatic sulponic ester catalyst with mucous membrane.
  • 128.  Contain some form of peroxide (generally carbamide peroxide) in a gel form.  Applied to the teeth either by the dentist or by the patient.  Is in contact with teeth for several minutes to several hours depending on the formulation.  Home bleaching agents is for weeks to even months.  In vitro study-peroxides can rapidly (within minutes) traverse the dentin in sufficient concentrations to be cytotoxic.  Cytotoxicity depends to a large extent on the concentration of the peroxide. 128
  • 129.  Peroxides rapidly penetrate intact enamel and reach the pulp in a few minutes.  Tooth sensitivity is very common. 129
  • 130.  Toxicity is the peak circulation levels of local anesthetics.  concentration of local anesthetic administered to patients are varied according to: Age Weight Health.  Maximum dose -70mg to 500mg  The amount of dose - solution and vasoconstrictor. 130
  • 131. Tissue toxicity - Rare  Can occur if administered in high enough concentrations (greater than those used clinically)  Usually related to preservatives added to solution Systemic toxicity - Rare  Related to blood level of drug secondary to absorption from site of injection.  Range from lightheadedness, tinnitus to seizures and CNS/cardiovascular collapse 131
  • 132.  True allergy is very rare  Most reactions are from ester class - ester hydrolysis (normal metabolism) leads to formation of PABA - like compounds  Patient reports of “allergy” are frequently due to previous intravascular injections 132
  • 133. 133  Inhalation and aspiration of various dust and toxic vapours-heating and melting of certain alloys causes respiratory and GIT system irritation.  Pneumoconiosis is severe fibrotic lung disease caused by chronic exposure to inorganic dust.  Exposure to Co-Cr,Co-Cr-Mo and Ni-Cr-Be alloys cause pneumoconiosis in techinicians.  Benign pneumoconiosis –hard metals.  Malignant pneumoconiosis-dust from crystalline silics,abestos or beryllium.
  • 134.  It was only in 1980 dentists started using gloves.  In March 29, 1991, the FDA issued a bulletin in response to latex related allergy. 134
  • 135. Processing of latex : Natural rubber products While milky sap from tropical trees . Ammonia is added to pressure. hydrolyzes and degrades the sap proteins to produce allergens.
  • 136.  Aerosol –particles are both liquid and solid .  Particle is less than 100 microns.  When water evaporates droplet nuclei is formed of 0.5 to 10 microns.  It can reach to pulmonary alveoli or float in air for several hours.  Splatter –air borne particles which are larger than 50 microns in diameter.  Mixture of air,water and/or solid substance which is 50micron to several millimeter. 136
  • 137.  Aerosol and splatter production which occur with usage of ultrasonic scalertips and burs at high speed handpiece is considered to be very exhastive or intensive.  Source- Patient Dental Unit Waterline Instruments 137
  • 138. 138
  • 139. Thermal osteonecrosis and bone drilling parameters revisited: Augustin, G.etal(2007)  During the drilling of the bone, the temperature could increase above 47degreeC and cause irreversible osteonecrosis. The result is weakened contact of implants with bone and possible loss of rigid fixation.  The aim of this study was to find an optimal conditions where the increase in bone temperature during bone drilling process would be minimal. . Archives of Orthopaedic and Trauma Surgery, [Epub ahead of print]. 139
  • 140.  Materials and methods- Influence of different drill parameters was evaluated on the increase of bone temperature. 1. Diameters-2.5, 3.2 and 4.5 mm 2. Drill speed-188, 462, 1140 and 1820 rpm 3. Feed-rate 24, 56, 84, 196 mm/min 4. Drill point angle 80, 100 and 120degree 5. External irrigation with water of 26 deg C. 140 . Archives of Orthopaedic and Trauma Surgery, [Epub ahead of print].
  • 141.  Results-  Combinations of drill speed and diameter with the use of external irrigation produced temperatures far below critical.  Without external irrigation, temperature values for the same combination of parameters ranged 31.4-55.5degC.  Temperatures above critical were recorded using 4.5 mm drill with higher drill speeds (1140 and 1820 rpm). 141 . Archives of Orthopaedic and Trauma Surgery, [Epub ahead of print].
  • 142.  There was no statistical significance of different drill point angles on the increase or decrease of bone temperature. The higher the feed-rate the lower the increase of bone temperature 142 . Archives of Orthopaedic and Trauma Surgery, [Epub ahead of print].
  • 143.  Biocompatible Denture Polymers – A Review Rahul Bhola etal (2009)  This article reviews various denture polymers for their properties and provides suggestions on the development of newer polymers for future clinical use.  PMMA resin continues to be the universal versatile polymer in denture dentistry. Depending upon the type of polymerization, PMMA resins may leach 0.1-5% of the residual monomer and additives, mainly MMA and formaldehyde, contributing to localized allergic reactions 143Trends Biomater. Artif. Organs, Vol 23(3),129-3l6 (2010)
  • 144.  Possible carcinogenic and embryotoxic potency of MMA.  Allergic reactions has been observed to increase with the increased use of higher amounts of PMMA resins.  Development of newer high strength,radio-opaque acrylic denture materials employing polymer blends, heavy metals and block co-polymers.  Development of non-leachable plasticizer or plasticizer free soft denture liners that could retain their softness permanently. 144 Trends Biomater. Artif. Organs, Vol 23(3),129-3l6 (2010)
  • 145.  The biocompatibility of a dental material depends on its composition, location and interactions with oral cavity. Diverse biological responses to these materials depend on whether they release their components and whether those components are toxic, immunogenic, or mutagenic at released concentrations.  Today, in development of any biomaterial one must consider not only strength, esthetics, or functional aspects of the material, but its biocompatibility as well. Furthermore, demands for appropriate biological responses are increasing as we ask materials to perform more sophisticated functions in body. Thus considerations of biocompatibility are important to manufactures, practitioners, scientists and patients 145
  • 146. 146
  • 147.  Craig’s Restorative Dental Materials –John M.Power.RonaldL.Sakaguchi- 12th Edition-Elsevier.  Science of Dental Materials Clinical applications-V Shama.BT Nandish-2nd edition-CBC publishers and distributors.  Philips’Science Dental Materials-Anusavice-11th Edition-Elsevier  Philips’Science Dental Materials-Anusavice|Shen|Rawl-12th Edition- Elsevier.  Glossary of Prosthodontics Terms-8th edition.  Glossary of Prosthodontics Terms-9th edition  Essential of Oral Histology and Embrology A Clinical Approach-James k Avery|Daniel j ChiegJ-Mosby Elsevier.  Archives of Orthopaedic and Trauma Surgery, [Epub ahead of print].  Trends Biomater. Artif. Organs, Vol 23(3),129-3l6 (2010)  (J Prosthet Dent 2001;86:203-9.)  Textbook of Pathology :Harsh Mohan :4th edition :jaypee brothers 147
  • 148. 148

Notes de l'éditeur

  1. way.That is,the material maybe affected in some way by the biological environment,and equally the biological environment maybe affected by the material.
  2. Involves activation of the host immune system to overcome external invasions. Pulpal and periodontal disease are mainly due to longterm infections. Histologically - edema of the tissue with infiltration of acute and chronic inflammatory cells.
  3. Involves activation of the host immune system to overcome external invasions. Pulpal and periodontal disease are mainly due to longterm infections. Histologically - edema of the tissue with infiltration of acute and chronic inflammatory cells.
  4. passage of nerve impulses through dentin. At the top, impulses are shown stimulating nerves in dentin; this is termed the direct Theory stimulation theory. In the center, an odontoblast is depicted as receptor passing impulses to nerves in the peripheral pulp in dentin and hence on to the brain, which is the transduction theory. At the bottom, the diagram displays concept of fluid and odontoblast movement. This movement causes ___ 2 pressure on the nerve endings, which stimas receptor ulates them. The odontoblast thus acts as a mechanoreceptor to nerve endings, which, in turn, conduct impulses to the brain. This is termed the hydrodynamic theory.
  5. Tubules from C.S area range from 20,000/mm² near DEJ to 50,000/mm² near the pulp. Tubule diameter varies from 0.5µm at DEJ to 2.5 µm near pulp Pulpal circulation maintains the intercellular hydraulic pressure of about 24mmHg. (32.5 cm H20) Summary oftheories on the passage of nerve impulses through dentin. At the top, impulses are shown stimulating nerves in dentin; this is termed the direct Theory stimulation theory. In the center, an odontoblast is depicted as receptor passing impulses to nerves in the peripheral pulp in dentin and hence on to the brain, which is the transduction theory. At the bottom, the diagram displays concept of fluid and odontoblast movement. This movement causes ___ 2 pressure on the nerve endings, which stimas receptor ulates them. The odontoblast thus acts as a mechanoreceptor to nerve endings, which, in turn, conduct impulses to the brain. This is termed the hydrodynamic theory. (Modified from Bhaskar SN, edi Hydrodynamics ---3 tor: Orban 's oral histoloW and embryolow, ed
  6. PDL fibers extend from cementum above alveolar crest to alveolar cortical bone or cementum of adjacent teeth.
  7. Due to the minimal release of compounds from most materials, systemic toxicity effects caused by dental materials have been considered to occur very seldomly or not at all. Screening tests for systemic toxicity are therefore justified only with certain body contact for long periods of time with a dental product. The international standardization on biological evaluation of medical devices has demonstrated a need for improved screening tests and continuous revision of the standards for testing. It is obvious that certain published studies on systemic effects of dental materials and some proposed test methods do not reflect today's demand for toxicokinetic and organ effect studies. PMID: 7844269
  8. a. along the side of the implant
  9. Biocom
  10.  A. Cross-section of Class I composite restoration. B. Diagram illustrating the concepts of microleakage (right) and nanoleakage (letf) when bonding dental resins (R) to dentin (D). The dentin has been acid-etched in preparation for the application of the resin, which leaves the collagenous matrix of the dentin exposed (unshaded crosshatched area in upper right side). If the resin does not completely penetrate the collagen network (left) then a samll sapce of communication exists between the dentinal tubules (DT) and the external part of the tooth (arrow, left). This situation is called nanoleakage. On the other hand, if the resin fails to penetrate the collagen network at all, or debonds from it, then the space is much larger (arrow, right). This situation is called microleakage. In the ideal situation (center), the resin penetrates the collagen network all the way to the mineralized dentin. Nanoleakage and microleakage are both important factors in the biocompatibility of dental resin materials.
  11. 1 by inhalation of fine particle of alginate. 2is preferred to minimise the risk.
  12. Some common toxic effects: light headedness shivering or twitching seizures hypotension numbness