Biological properties of Dental materials.
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Contents
Introduction Biocompatibility v/s Biological properties Components of biocompatibility Adverse effects of dental materials
Local & Systemic effects of materials Key principles that determine adverse effects from materials Concept of Immunotoxicity Oral anatomy that influences the biological response
Toxicity Inflammation Allergy Mutagenicity Carcinogenicity
Enamel Dentine & Pulp Bone
Measuring the biocompatibility
Invitro tests Animal tests Usage tests Clinical trials www.indiandentalacademy.com
Advantages & disadvantages of biocompatibility tests Correlation among the tests How tests are used together ? Regulatory standards for measurement of biocompatibility Current biocompatibility issues in dentistry Reaction of pulp to different materials
Latex Impression materials Biocompatibility of metals Reaction of other oral soft tissues to restorative materials
Dentine bonding & Dentine bonding agents Dental amalgam Dental cements Bleaching agents
Denture base material Soft denture liner & adhesives
Reactions of bone & soft tissues to Implant materials Conclusion List of references www.indiandentalacademy.com
Introduction
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Biological properties of Dental materials
Biocompatibility = Lack of interaction Biocompatible material = list of negatives Non degradable Non irritant Non toxic Non allergic Non carcinogenic Non mutagenic Total inactivity = Passive ignorance ? More appropriate – active acceptance Biocompatibility : ability of a material to perform with an appropriate host response, in a specific application. www.indiandentalacademy.com
Components
Initial Physiochemical interaction Effect of the tissue environment Local host response Transport of products – Systemic effects Establishment of solid-liquid interface as any material is implanted into the tissue Protein absorption is the first event Immediate response to injury is inflammation Very few is know about the factors Condition of the host Properties of the material Context in which the material is used Eg: Biocompatible as Crown & Bridge but not as an implant material www.indiandentalacademy.com
Adverse effects from Dental materials
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Toxicity
Placement of a foreign material in the body carries the possibility of toxicity Toxicity can be of 2 types Acute toxicity. Chronic toxicity.
Type 1: requires prolonged or repeated administration Type 2: requires very few or one dose but long lasting effects
Type 1 chronic toxicity is a possibility with “Biomaterials” Eg: metal ions released by gradual corrosion of an implant According to J.J.Jacobs et al (1991) Vanadium – lungs Aluminium – surrounding tissues Fortunately, materials causing over toxicity are no longer used in dentistry. www.indiandentalacademy.com
Inflammation
May result from toxicity or allergy and often it precedes toxicity. Oedema, inflammatory cell infiltrate Current biocompatibility research www.indiandentalacademy.com
Allergy
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Allergy
Body specifically recognizes material as foreign & reacts disproportional to the amount of material Gell & Coomb’s classification of immune responses
Type 1: Atopic or anaphylactic reaction Type 2: Cytotoxic hypersensitivity reaction Type 3: Immune complex disease Type 4: Delayed or cell mediated hypersensitivity Type 5: Stimulating antibody reaction Type 6: antibody dependent, cell mediated Cytotoxic reaction www.indiandentalacademy.com
Type 1, 2, 3 – quickly. Eosinophils, Mast cells & B lymphocytes Type 4 – delayed. Monocytes & T cells Allergic response – individual’s immune system recognizes a substance as foreign Allergic reactions – initially dose independent, disproportionate Toxic / inflammatory reactions – dose dependant, proportionate
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Mutagenic reactions
Alteration in base pair sequence (mutation) 2 types
Alteration in cellular process that maintain DNA integrity Direct interaction
Can occur from radiations, chemicals, errors in DNA replication process Examples
Metal ions – nickel, copper, beryllium Few components of root canal sealers Resin based materials to some extent www.indiandentalacademy.com
Carcinogenic response ďƒ˜
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Currently no dental material has been shown to be carcinogenic for dental applications in patients However, carcinogenesis is often exceedingly difficult to prove or disprove conclusively www.indiandentalacademy.com
Local & Systemic effects of materials
Local effects
Pulp Periodontium Root apex Oral tissues – buccal mucosa, tongue
Systemic effects
Function of the distribution of substances released from the materials
Access to the body by
Simple diffusion Lymphatics Blood vessels Ingestion & absorption in gut Inhalation Release at tooth apex Absorption into mucosa
Systemic response depends on
Duration & concentration of the exposure Excretion rate of the substance Site of the exposure www.indiandentalacademy.com
Key principles that determine adverse effects from materials
A) various types of metal corrosion & other types of material degradation :
Biocompatibility depends on the degradation process Corrosion is determined not only by material composition but also by the biological environment
Many ways for release of products in host
Metal prosthesis – releases metal ions by Electrochemical force Particles dislodged by mechanical forces Resin composites Cyclic stresses Salivary esterases www.indiandentalacademy.com
B) Surface characteristics :
Surface is quite different from interior Examples Dental casting alloy containing 70% gold may have 95% gold at its surface Relative unpolymerized state of a sealant at its surface The surface composition, roughness, mechanical & chemical properties are critical to the biocompatibility
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Concept of Immunotoxicity
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Concept of Immunotoxicity “ Based on the principle that small alteration in the cells of immune systems by materials can have significant biological consequences ” Examples:
Mercury ions increase the Glutathione but Palladium decreases Glutathione content of Monocytes HEMA may change the ability of Monocytes to direct an immune response once challenged by plaque or others agents www.indiandentalacademy.com
Oral anatomy that influences the Biological response
Enamel : “seals” the tooth
Peroxides permeate intact enamel
Dentine & Pulp :
Smear layer Effective in reducing the hydrostatic pressure but not diffusion Acid etching www.indiandentalacademy.com
Bone : Osseointegration & Biointegration
Osseointegration
Implant & bone closely approximate to each other Approximation less than 100 A No fibrous tissue in intervening space Titanium alloys
Biointegration Implant & bone are fused to one another & are continuous Occurs with Ceramic & Ceramic coated metal implants Eg: Calcium & Tri calcium phosphate, Hydroxyapatite, Bioglass
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Measuring the Biocompatibility
Is not simple and methods of measurement are evolving rapidly as more is know about the interactions between dental materials and oral tissues & as technologies for testing improves Classified as
In Vitro test Animal test Usage test Clinical trial – special case of a usage test in humans
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In Vitro test
Placement of a material or component of it in contact with cell, enzyme or some other isolated biological system
Direct Material in contact Physically present or extract from material Indirect Some sort of barrier www.indiandentalacademy.com
Types of cells used in In-vitro assays
Primary cells :
Directly from an animal into culture Grows for only a limited time
Continuous cells :
Primary cells transformed to allow them to grow indefinitely
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Testing procedures & extent of testing
Manufacturer’s responsibility to test new material A) Initial tests :deals with general biocompatibility & systemic effects of a material Short term systemic toxicity test
Acute systemic toxicity test
Dental remedies that have significant volatility under usage condition
Hemolysis test
I.V administration
Inhalation toxicity test
Short time oral administration Toxicity profile
In vitro evaluation of hemolytic activity of materials intended for prolonged tissue contact
Emes mutagenicity & the dominant lethal test
To asses the potentialwww.indiandentalacademy.com carcinogenic activity
Cytotoxicity tests
Measures cell count or growth after exposure to a material
Method 1 : Place the cells in the well of a cell culture dish If Cytotoxic - cell may stop growing, exhibit cytopathic features or detach from the cell Method 2 : Measurement of cytotoxicity by a change in membrane permeability Loss in membrane permeability is equivalent or very nearly equivalent to cell death Identifies the cells that are alive or dead www.indiandentalacademy.com
Tests
Sensitization test Oral mucous membrane irritation test Subcutaneous implant test Bone implant test
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Usage tests
Pulp &Dentine test
Pulp capping & Pulpotomy test Endodontic usage test
Response of dentine & pulp Minimum experimental variables
Assess response of the pulp wound & the periapical tissue Influenced by – level at which the pulp tissue is cut off & total removal of pulp tissue
Bone implant usage test
To evaluate all materials that, during their intended use, penetrate the oral mucosa and the adjacent bone www.indiandentalacademy.com
Correlation among the tests
Lack of correlation Less prominent biological response Barriers may exist Measure different aspects of the biological response to the material
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Advantages & disadvantages of Biocompatibility tests
In-Vitro test
Advantages
Quick to perform Least expensive Standardized Large scale screening Excellent for mechanisms of interaction
Disadvantages
Relevance to In-Vivo questionable www.indiandentalacademy.com
In- Vivo test
Advantages Allows complex systemic interactions More comprehensive More relevant Disadvantages Relevance to use ? Expensive Time consuming Ethical concern Difficult to control Difficult to interpret & quantify
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Usage test
Advantages
Relevance to use of material is assured
Disadvantages
Very expensive Time consuming Major legal / ethical
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How the tests are used together to measure the Biocompatibility
usage secondary
primary
progression of
testing
Linear paradigm, relies on the accuracy of the primary tests (challenged by Major et al 1977) No prediction of results in usage tests www.indiandentalacademy.com Lack of correlation in In-Vitro tests
Non linear thinking U S P
Progression of Testing
All the 3 tests are done As test progresses Usage test predominates www.indiandentalacademy.com
Most common progression
Usage Primary
Secondary
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‘Recognizes complexity’
Standards that regulate the measurement of Biocompatibility
ANSI / ADA : earliest attempt in 1933
1972 – The Council on dental material, instruments & equipment of ANSI / ADA approved document no. 41 for recommended standard practices for biological evaluation of dental materials In 1982 updated to include test for mutagenicity Uses linear paradigm www.indiandentalacademy.com
ISO Standard 10993 :
Not restricted to dental materials only First published in 1992 In 2002 ISO 10993 consisted of 16 parts 2 types of tests –
Initial – Cytotoxicity, sensitization & systemic toxicity. In – Vitro / animal test Supplementary – chronic toxicity, carcinogenicity & bio-degradation. Animals / Humans Specialized tests – Eg: dentine barrier test
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Current Biocompatibility issues in dentistry
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Reactions of pulp to different materials Micro leakage :
If a material does not bond or debonds at enamel or dentine Previous belief Concept of nano leakage
Between mineralized dentine & bonded material. In very small spaces of demineralized matrix into which material did not penetrate Hydrolytic degradation of dentine – material bond www.indiandentalacademy.com
Dentine bonding :
Bonding to dentine is difficult – composition, wetness, low minerals Smear layer formation & removal Many studies have shown 0.5mm of RDT is adequate Dentine is a buffers of protons Penetration of acids < 100 micrometers www.indiandentalacademy.com
Dentine bonding agents :
HEMA is 100 times less cytotoxic in tissue culture than Bis – GMA Bis – GMA, TEGDMA, UDMA
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Amalgam
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Dental amalgam :
Toxic or not ? In usage test response of pulp to amalgam in shallow or deep lined cavities Gallium based amalgam
Excessive gallium release, roughness, discolor Significant foreign body reaction
Absorption : 1 – 3 micrograms / day Minimum dose to produce observable toxic effect is 3 micrograms / kg body weight www.indiandentalacademy.com
Dental cements
Resin based materials :
Resin composites – luting or restorative Light cured < cytotoxic than chemically cured Pulpal reaction diminishes after 5 – 8 weeks Protective liner or bonding agent minimizes Pulpal reaction www.indiandentalacademy.com
Glass ionomers :
Luting agent & restorative material Weaker polyacrylic acid Fluoride release Histological studies in usage test shows that any inflammatory infiltrate to ionomer is minimal or absent after 1 month
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Zinc phosphate :
Luting agent & base Thermal conductivity closer to enamel Pulpal damage in first 3 days due to initial low PH(4.2), reaches neutrality in 48 hours When placed in deep cavities ? Inclusion of Ca- OH to the powder or lowering the concentration of phosphoric acid
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Calcium hydroxide : Suspension form
Resin containing
Highly cytotoxic
Mild to moderate cytotoxic
Necrosis 1mm or >
No necrotic zone
shortly
Neutrophil infiltration
Dentine bridge formation is quick
5 to 8 weeks
Slight inflammatory response wks - months
Dystrophic calcification Dentine bridge www.indiandentalacademy.com
Zinc oxide eugenol :
Suppresses the nerve transmission Inhibit synthesis of Prostaglandins & Leukotriens
Hammesfahr 1987, initiated the search for a biocompatible resin base system incorporating Calcium hydroxide “ PRISM VLC DYCAL” www.indiandentalacademy.com
Soft tissue response to the luting cements
Apply petroleum jelly
Clean the excess
Any residues of cement
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Bleaching agents :
Usually contain some form of peroxide In-Vitro – traverses the dentine & in sufficient conc. can be cytotoxic Penetrates intact enamel & reaches the pulp in few min. May burn gingiva www.indiandentalacademy.com
Latex www.indiandentalacademy.com
Latex :
6% to 7% of surgical personnel may be allergic 42% adverse reactions to occupational materials Hypersensitivity may be due to true latex allergy or reaction to accelerator & antioxidants White, milky sap Addition of ammonia
Hydrolyses & degrades the sap proteins to produce allergens
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Liquid latex
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vulcanization sulphur + heat
solid rubber
Soaked in hot water leaches out allergens Allergenicity depends on collecting, preservation & processing
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Impression materials
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Impression materials : Price & Whitehead (1972) – Allergic contact stomatitis & Foreign body response Sydiskis & Gerhardt (1993) – some degree of toxicity in cell culture Gabriela Mazzanti et al (2005) – no significant evidence of diffuse inflammation or local skin reaction
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Casting alloys www.indiandentalacademy.com
Dental casting alloys : John c. Wataha 2000
Release of elements is essential for adverse effects Identifying & quantifying the elements that are released is most relevant measure from stand point of Biocompatibility
a) Release of elements from casting alloys Multiple phases Inherent tendency to release elements – lability Eg: Cu, Ni, Cd, Zn & Ga – highly labile Environmental conditions - PH
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b) Systemic toxicity
Released metals may not be inside the body Route of access – I.V < Peritoneal < Oral Distribution – there is no documented proof that these material cause ‘Systemic toxicity’
c) Local toxicity
Micro environment exists around casting alloys Metal ions can cause local toxicity Increased exposure causes increased toxicity www.indiandentalacademy.com
d) Allergy to dental casting alloys
Elemental release is essential for allergy Metal ions – Haptens Allergy & Toxic reaction – difficult to distinguish
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Patch test for metals – controversial
Application of metal ion to skin in the form of patch Injecting small amount of ion below the skin Assessment of the response is difficult Salt of metal ions important for response Eg: chloride, sulphate, nitrate salts Vehicle – whether its water, oil or petrolatum can vary the response Grimaudo N.J 2001 – true allergic hypersensitivity to dental casting alloys is rare
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Nickel :
Common component Incidence of allergy 10% – 20% Cross reactivity between nickel & palladium (33% & 100%) Nickel ions induces ICAM’s in the endothelium – release of cytokines It may contribute to any intraoral inflammation around nickel containing crowns
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Beryllium :
Used in Ni-Cr alloys in conc. of 1 – 2 wt% Forms thin adherent oxides Documented carcinogen Berylliosis
Individual is hypersensitive Inhalation of beryllium dust, salts, fumes www.indiandentalacademy.com
Reaction of other oral soft tissues
a) Denture base materials
Methacrylates Greatest potential for hyper sensitization Acrylic & diacrylic monomers, curing agents, antioxidants, amines, formaldehydes For the patients most of these materials have been reacted in polymerization and thus less prone www.indiandentalacademy.com
True allergy of oral mucosa to denture base material is very rare
Residual monomer (methyl methacrylate)
Allergic acrylic stomatitis
Heat cured is better www.indiandentalacademy.com
b) Soft denture liners & adhesives
Release of plasticizers Extremely cytotoxic Effects are masked by the inflammation Denture adhesives show severe cytotoxic reactions In-Vitro Large amount of formaldehyde Allowed significant microbial growth www.indiandentalacademy.com
Denture cleansers
Used to cleanse the prosthesis
Eg : Hypochlorite, mild acids, etc.
Biocompatible & cause no harm to the patient
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Artificial teeth
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Acrylic & Porcelain teeth
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Acrylic teeth is preferred in poor ridges
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Implants www.indiandentalacademy.com
Reaction of bone & soft tissues to implant material
Materials – Ceramics, Metals, Carbons & Polymers a) Reaction to ceramic implant material
b) Hydroxyapatite
Very low toxic effects. Oxidized state, corrosion resistant Used as a porous or dense coating Root surface porosities > 100microns (firmly bound ) Root surface porosities < 100microns (fibrous ingrowth) Relatively non resorbable form of calcium phosphate Coating material & ridge augmentation material
c) Beta -Tricalcium phosphate
Another form of calcium phosphate, has been used in situations where resorption of the material is desirable www.indiandentalacademy.com
d) Reaction to pure metals & alloys
‘Metal’ oldest type of oral implant material Shares the quality of ‘strength’ Initially selected on the basis of the ‘Ease of fabrication’ Stainless Steel, Chromium-Cobalt-Molybdenum, Titanium and its alloys Most commonly used is Titanium Titanium’s Biocompatibility is associated with its fast oxidizing capacity. Corrosion resistant & allows Osseointegration www.indiandentalacademy.com
Soft tissue :
Epithelium forms bond with implant similar to that of tooth C.T apparently does not bond to the titanium, but forms a tight seal that seems to limits ingress of bacteria & its products
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Conclusion
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List of references
Restorative dental materials by Craig & Powers Phillips’ Science of dental materials Chemistry of medical & dental materials by J.W.Nicholson Concise Encyclopedia of medical & dental materials by David Williams Dental biomaterials by Arturo N. Natali Dent material 2005;21(4):371-74 JPD 2001 Aug;86(2):203-9 Gen Dent 2001 Sep-Oct;49(5):498-503 JPD 2000 Feb;83(2):223-34 JPD 1998 Sep;80(2):203-9 JPD 1993;69;431-5 J Biomater Appl 1987 Jan;1(3):373-81 BDJ 1972;133:9-14
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Precautions to be taken in the Lab
Make certain the ventilation system in room is properly functioning During operation of the dental lathe wear a protective eyewear & a mask Clean & disinfect the dental lathe at least once daily Use sterile rag wheels, stones & fresh pumice for each patient's prosthesis www.indiandentalacademy.com
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