Biological Properties of Dental Materials 1-General Dentistry / orthodontic courses by Indian dental...

Biological properties of Dental materials.

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Contents Introduction Biocompatibility v/s Biological properties Components of biocompatibility Adverse effects of dental materials

Toxicity Inflammation Allergy Mutagenicity Carcinogenicity

Local & Systemic effects of materials Key principles that determine adverse effects from materials Concept of Immunotoxicity Oral anatomy that influences the biological response

Enamel Dentine & Pulp Bone

Measuring the biocompatibility Invitro tests Animal tests Usage tests Clinical trials


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Advantages & disadvantages of biocompatibility tests Correlation among the tests How tests are used together ? Regulatory standards for measurement of biocompatibility Current biocompatibility issues in dentistry Reaction of pulp to different materials

Dentine bonding & Dentine bonding agents Dental amalgam Dental cements Bleaching agents

Latex Impression materials Biocompatibility of metals Reaction of other oral soft tissues to restorative materials

Denture base material Soft denture liner & adhesives

Reactions of bone & soft tissues to Implant materials Conclusion List of references


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Introduction


Biological properties of Dental materials Biocompatibility = Lack of interaction Biocompatible material = list of negatives

Non degradable Non irritant Non toxic Non allergic Non carcinogenic Non mutagenic

Total inactivity = Passive ignorance ? More appropriate – active acceptance Biocompatibility : ability of a material to perform with an

appropriate host response, in a specific application.


Components Initial Physiochemical interaction Effect of the tissue environment Local host response Transport of products – Systemic effects

Establishment of solid-liquid interface as any material is implanted into the tissue

Protein absorption is the first event Immediate response to injury is inflammation Very few is know about the factors

Condition of the host Properties of the material Context in which the material is usedEg: Biocompatible as Crown & Bridge but not as an implant material


Adverse effects from Dental materials


Toxicity Placement of a foreign material in the body carries the possibility

of toxicity Toxicity can be of 2 types

Acute toxicity. Chronic toxicity.

Type 1: requires prolonged or repeated administration Type 2: requires very few or one dose but long lasting effects

Type 1 chronic toxicity is a possibility with “Biomaterials” Eg: metal ions released by gradual corrosion of an implant According to J.J.Jacobs et al (1991)

Vanadium – lungs Aluminium – surrounding tissues

Fortunately, materials causing over toxicity are no longer used in dentistry.


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Inflammation May result from toxicity or allergy and often it

precedes toxicity. Oedema, inflammatory cell infiltrate Current biocompatibility research


Allergy


Allergy Body specifically recognizes material as foreign &

reacts disproportional to the amount of material Gell & 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


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


http://www.arindammukherjee.com/Ari/6-cell.gif

Mutagenic reactions Alteration in base pair sequence (mutation) 2 types

Alteration in cellular process that maintain DNA integrity Direct interaction

Can occur from radiations, chemicals, errors in DNA replication process

Examples Metal ions – nickel, copper, beryllium Few components of root canal sealers Resin based materials to some extent


Carcinogenic response Currently no dental material has been shown to be

carcinogenic for dental applications in patients However, carcinogenesis is often exceedingly

difficult to prove or disprove conclusivelywww.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

Simple diffusion Lymphatics Blood vessels

Access to the body by Ingestion & absorption in gut Inhalation Release at tooth apex Absorption into mucosa

Systemic response depends on Duration & concentration of the exposure Excretion rate of the substance Site of the exposure


Key principles that determine adverse effects from materials A) various types of metal corrosion & other types of

material degradation : Biocompatibility depends on the degradation process Corrosion is determined not only by material composition

but also by the biological environment Many ways for release of products in host

Metal prosthesis – releases metal ions by Electrochemical force Particles dislodged by mechanical forces

Resin composites Cyclic stresses Salivary esterases


B) Surface characteristics : Surface is quite different from interior Examples

Dental casting alloy containing 70% gold may have 95% gold at its surface

Relative unpolymerized state of a sealant at its surface

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


Concept of Immunotoxicity


Concept of Immunotoxicity “ Based on the principle that small alteration in

the cells of immune systems by materials can have significant biological consequences ”

Examples: Mercury ions increase the Glutathione but

Palladium decreases Glutathione content of Monocytes

HEMA may change the ability of Monocytes to direct an immune response once challenged by plaque or others agents


Oral anatomy that influences the Biological response Enamel : “seals” the

tooth Peroxides permeate

intact enamel Dentine & Pulp :

Smear layer Effective in reducing the

hydrostatic pressure but not diffusion

Acid etching


Bone : Osseointegration & Biointegration Osseointegration

Implant & bone closely approximate to each other Approximation less than 100 A No fibrous tissue in intervening space Titanium alloys

Biointegration Implant & bone are fused to one another & are

continuous Occurs with Ceramic & Ceramic coated metal implantsEg: Calcium & Tri calcium phosphate, Hydroxyapatite,

Bioglass


http://images.google.co.in/imgres?imgurl=http://www.cda.org/cda_member/pubs/journal/jour1101/history_f25.jpg&imgrefurl=http://www.cda.org/cda_member/pubs/journal/jour1101/history.html&h=331&w=206&sz=18&hl=en&start=2&tbnid=vj9AT9iTdi1TzM:&tbnh=119&tbnw=74&prev=/images%3Fq%3Dosseointegration%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DX

Measuring the Biocompatibility Is not simple and methods of measurement are

evolving rapidly as more is know about the interactions between dental materials and oral tissues & as technologies for testing improves

Classified as In Vitro test Animal test Usage test Clinical trial – special case of a usage test in humans


In Vitro test Placement of a material

or component of it in contact with cell, enzyme or some other isolated biological system Direct

Material in contact Physically present or

extract from material Indirect

Some sort of barrier


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Types of cells used in In-vitro assays Primary cells :

Directly from an animal into culture Grows for only a limited time

Continuous cells : Primary cells transformed to allow them to grow

indefinitely


Testing procedures & extent of testing

Manufacturer’s responsibility to test new material A) Initial tests :deals with general biocompatibility & systemic

effects of a material Short term systemic toxicity test

Short time oral administration Toxicity profile

Acute systemic toxicity test I.V administration

Inhalation toxicity test Dental remedies that have significant volatility under usage condition

Hemolysis test In vitro evaluation of hemolytic activity of materials intended for

prolonged tissue contact Emes mutagenicity & the dominant lethal test

To asses the potential carcinogenic activitywww.indiandentalacademy.com

Cytotoxicity tests Measures cell count or growth after exposure to a

material Method 1 :

Place the cells in the well of a cell culture dish If Cytotoxic - cell may stop growing, exhibit cytopathic

features or detach from the cell Method 2 :

Measurement of cytotoxicity by a change in membrane permeability

Loss in membrane permeability is equivalent or very nearly equivalent to cell death

Identifies the cells that are alive or dead


Tests

Sensitization test Oral mucous membrane irritation test Subcutaneous implant test Bone implant test


Usage tests Pulp &Dentine test

Response of dentine & pulp Minimum experimental variables

Pulp capping & Pulpotomy test Endodontic usage test

Assess response of the pulp wound & the periapical tissue Influenced by – level at which the pulp tissue is cut off &

total removal of pulp tissue Bone implant usage test

To evaluate all materials that, during their intended use, penetrate the oral mucosa and the adjacent bone


Correlation among the tests

Lack of correlation Less prominent biological response Barriers may exist Measure different aspects of the biological

response to the material


Advantages & disadvantages of Biocompatibility tests In-Vitro test

Advantages Quick to perform Least expensive Standardized Large scale screening Excellent for mechanisms of interaction

Disadvantages Relevance to In-Vivo questionable


In- Vivo test Advantages

Allows complex systemic interactions More comprehensive More relevant

Disadvantages Relevance to use ? Expensive Time consuming Ethical concern Difficult to control Difficult to interpret & quantify


Usage test Advantages

Relevance to use of material is assured

Disadvantages Very expensive Time consuming Major legal / ethical


usage progression

secondary of

primary testing

Linear paradigm, relies on the accuracy of the primary tests (challenged by Major et al 1977)

No prediction of results in usage tests Lack of correlation in In-Vitro tests

How the tests are used together to measure the Biocompatibility


Non linear thinking

U Progression S of P Testing

All the 3 tests are done As test progresses Usage test predominates


Most common progression

Usage ‘Recognizes Primary Secondary complexity’


Standards that regulate the measurement of Biocompatibility

ANSI / ADA : earliest attempt in 1933 1972 – The Council on dental material,

instruments & equipment of ANSI / ADA approved document no. 41 for recommended standard practices for biological evaluation of dental materials

In 1982 updated to include test for mutagenicity Uses linear paradigm


ISO Standard 10993 : Not restricted to dental materials only First published in 1992 In 2002 ISO 10993 consisted of 16 parts 2 types of tests –

Initial – Cytotoxicity, sensitization & systemic toxicity. In – Vitro / animal test

Supplementary – chronic toxicity, carcinogenicity & bio-degradation. Animals / Humans

Specialized tests – Eg: dentine barrier test


Current Biocompatibility issues in dentistry


Reactions of pulp to different materials

Micro leakage : If a material does not bond or

debonds at enamel or dentine Previous belief Concept of nano leakage

Between mineralized dentine & bonded material. In very small spaces of demineralized matrix into which material did not penetrate

Hydrolytic degradation of dentine – material bond


Dentine bonding : Bonding to dentine is

difficult – composition, wetness, low minerals

Smear layer formation & removal

Many studies have shown 0.5mm of RDT is

adequate Dentine is a buffers of

protons Penetration of acids <

100 micrometers


Dentine bonding agents : HEMA is 100 times less cytotoxic in tissue culture

than Bis – GMA Bis – GMA, TEGDMA, UDMA


Amalgam


Dental amalgam : Toxic or not ? In usage test response of

pulp to amalgam in shallow or deep lined cavities

Gallium based amalgam Excessive gallium release,

roughness, discolor Significant foreign body

reaction Absorption : 1 – 3

micrograms / day Minimum dose to produce

observable toxic effect is 3 micrograms / kg body weight


Dental cements

Resin based materials : Resin composites – luting

or restorative Light cured < cytotoxic than

chemically cured Pulpal reaction diminishes

after 5 – 8 weeks Protective liner or bonding

agent minimizes Pulpal reaction


Glass ionomers : Luting agent &

restorative material Weaker polyacrylic acid Fluoride release Histological studies in

usage test shows that any inflammatory infiltrate to ionomer is minimal or absent after 1 month


Zinc phosphate : Luting agent & base Thermal conductivity closer

to enamel Pulpal damage in first 3

days due to initial low PH(4.2), reaches neutrality in 48 hours

When placed in deep cavities ?

Inclusion of Ca- OH to the powder or lowering the concentration of phosphoric acid


Calcium hydroxide :

Suspension form Resin containing Highly cytotoxic Mild to moderate cytotoxic

Necrosis 1mm or > No necrotic zone shortly

Neutrophil infiltration Dentine bridge formation 5 to 8 weeks is quick Slight inflammatory response wks - months

Dystrophic calcification

Dentine bridge


Zinc oxide eugenol :

Suppresses the nerve transmission Inhibit synthesis of Prostaglandins & Leukotriens

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


Soft tissue response to the luting cements

Apply petroleum jelly

Clean the excess Any residues of cement


Bleaching agents : Usually contain some form of peroxide In-Vitro – traverses the dentine & in sufficient

conc. can be cytotoxic Penetrates intact enamel & reaches the pulp in

few min. May burn gingiva


Latex


Latex : 6% to 7% of surgical personnel may be allergic 42% adverse reactions to occupational materials Hypersensitivity may be due to true latex allergy or reaction

to accelerator & antioxidants White, milky sap

Addition of ammonia

Hydrolyses & degrades the sap proteins to produce allergens


Liquid vulcanization solid latex sulphur + heat rubber

Soaked in hot water leaches out allergens Allergenicity depends on collecting, preservation

& processing


Impression materials


Impression materials : Price & Whitehead (1972) –

Allergic contact stomatitis & Foreign body response

Sydiskis & Gerhardt (1993) – some degree of toxicity in cell culture

Gabriela Mazzanti et al (2005) – no significant evidence of diffuse inflammation or local skin reaction


Casting alloyswww.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 – labilityEg: Cu, Ni, Cd, Zn & Ga – highly labile Environmental conditions - PH


b) Systemic toxicity Released metals may not be inside the body Route of access – I.V < Peritoneal < Oral Distribution – there is no documented proof that

these material cause ‘Systemic toxicity’

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


d) Allergy to dental casting alloys

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


Patch test for metals – controversial Application of metal ion to skin in the form of patch Injecting small amount of ion below the skin Assessment of the response is difficult Salt of metal ions important for responseEg: 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 rarewww.indiandentalacademy.com

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


Beryllium : Used in Ni-Cr alloys in conc. of 1 – 2 wt% Forms thin adherent oxides Documented carcinogen Berylliosis

Individual is hypersensitive Inhalation of beryllium dust, salts, fumes


Reaction of other oral soft tissues a) Denture base

materials Methacrylates Greatest potential for

hyper sensitization Acrylic & diacrylic

monomers, curing agents, antioxidants, amines, formaldehydes

For the patients most of these materials have been reacted in polymerization and thus less prone


True allergy of oral mucosa to denture base material is very rare

Residual monomer (methyl methacrylate) Allergic acrylic stomatitis

Heat cured is better


b) Soft denture liners & adhesives Release of plasticizers Extremely cytotoxic Effects are masked by the

inflammation Denture adhesives show

severe cytotoxic reactions In-Vitro Large amount of

formaldehyde Allowed significant

microbial growth


Denture cleansers

Used to cleanse the prosthesis Eg : Hypochlorite, mild acids, etc.

Biocompatible & cause no harm to the patient


Artificial teeth

Acrylic & Porcelain teeth

Acrylic teeth is preferred in poor ridges


Implants


Reaction of bone & soft tissues to implant material Materials – Ceramics, Metals, Carbons & Polymers a) Reaction to ceramic implant material

Very low toxic effects. Oxidized state, corrosion resistant Used as a porous or dense coating Root surface porosities > 100microns (firmly bound ) Root surface porosities < 100microns (fibrous ingrowth)

b) Hydroxyapatite Relatively non resorbable form of calcium phosphate Coating material & ridge augmentation material

c) Beta -Tricalcium phosphate Another form of calcium phosphate, has been used in

situations where resorption of the material is desirablewww.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


Soft tissue : Epithelium forms bond

with implant similar to that of tooth

C.T apparently does not bond to the titanium, but forms a tight seal that seems to limits ingress of bacteria & its products


Conclusion


List of references Restorative dental materials by Craig & Powers Phillips’ Science of dental materials Chemistry of medical & dental materials by J.W.Nicholson Concise Encyclopedia of medical & dental materials by David Williams Dental biomaterials by Arturo N. Natali Dent material 2005;21(4):371-74 JPD 2001 Aug;86(2):203-9 Gen Dent 2001 Sep-Oct;49(5):498-503 JPD 2000 Feb;83(2):223-34 JPD 1998 Sep;80(2):203-9 JPD 1993;69;431-5 J Biomater Appl 1987 Jan;1(3):373-81 BDJ 1972;133:9-14


Precautions to be taken in the Lab Make certain the ventilation system in room is

properly functioning During operation of the dental lathe wear a

protective eyewear & a mask Clean & disinfect the dental lathe at least

once daily Use sterile rag wheels, stones & fresh

pumice for each patient's prosthesis



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