Biocompatibility of materials for use in the body

• Materials (synthetic or natural) that are used in medical devices that are in contact with tissues • Augments or replaces partially or totally any tissue, organ or function of the body, in order to maintain or improve the quality of life of the individual

-Medical implants Heart valves, artificial joints, dental implants -Repair and healing of human tissues Sutures, clips, staples, stents -Cellular scaffolds for regenerating tissues Biomaterials incorporating cells Bioactive molecules -Molecular probes and nanoparticles Used in imaging for cancer and to deliver therapies at a molecular level -Biosensors Devices that convert biologic responses into electrical signals Blood glucose monitoring devices and brain activity sensors -Drug delivery systems Chemotherapy devices for cancer patients Implantable birth control

-Ability of a material to perform with an appropriate host response in a specific application (must be beneficial to the host)

• Monomers in denture base materials • Allergic reactions to alloys containing nickel • Mercury in dental amalgam • Phosphoric acid used as an etchant on enamel

• Non-toxic to patient and staff • Non-irritant in mouth and other tissues • Minimal inflammation (acute, not chronic) • Tissue integration (implants) • Physical and mechanical properties (for intended application) • Not mutagenic or carcinogenic

-Protein adsorption Dependent on material properties -Environmental Body fluids, pH, cells, proteins -Degradation Breakdown products -Corrosion Metals eg. cobalt-chrome alloys

-Blood clot-equilibrium disturbed Coagulation (platelets) -Inflammatory response Acute (neutrophils) -Chronic inflammation Chronic (lymphocytes and monocytes) -Evokes immune response (activation of macrophages, lymphocytes) -Wound healing (repair/regeneration) Fibroblasts, endothelial cells

-In vitro tests Cytotoxicity screening tests provide an indication of cell death (by material itself or its extracts) Many tests can assess cell number, growth rate, metabolism, gene up regulation -Evaluating biocompatibility of a material in vitro allows prediction of in vivo oral tissues • In vitro allows the prediction of in vivo oral tissues • Not always comparable tho

• Social pressure to reduce animal experimentation • Advance in vitro testing • More sophisticated technology -International Standardization Organisation (ISO) provides guidelines -European Centre Validation Alternative Methods (ECVAM)- 3 R’s Reduction, Refinement, Replacement

• Need to identify a relevant mammalian model • Addressing ethical concerns • Expensive and time consuming • Not always reproducible response BUT -Can obtain a more comprehensive biological response

• Most relevant test • Needs ethical approval and patient consent • All other tests can be measured against this • Expensive and logistically complicate • Lots of variables, difficult to interpret results

-Material to be tested should be representative of either the final product or a component of the final product 3 requirements for biocompatibility testing methods: -Specificity (ability of a test to correctly identify those with a disease) Appropriate cells for a material being tested -Sensitivity (ability of test to correctly identify those without a disease) Methods used should be sensitive and suitable for cell culture medium -Quality controls Both negative and positive and also, material and cell culture control

• Ability of a material to perform with an appropriate host response in a specific application • Involves 2 components: -Biosafety Deals with the exclusion of deleterious effects of a biomaterial on the organism itself -Biofunctionality Concerns and addresses the need of a material not only to be free from damaging effects on the host, but also to elicit a beneficial host-response, for optimal functioning of the medical device

• American National Standard Institute/American Dental Association • International Standards Organization • These regulatory bodies do not require specific biological tests but are guidelines for approval of materials • Responsiblity is therefore placed on the manufacturer to present evidence for approval

-Any material or device that is to be used or placed within the body must be tested for biocompatibility to ensure it is safe for human use • Dental materials used in the oral cavity should be harmless to all oral tissue: gingiva, mucosa, pulp and bone • Materials should contain no toxic, leachable or diffusible substance that can be absorbed into the circulatory system, causing systemic toxic responses/toxicity (including teratogenic or carcinogenic effects) • Materials should be free of agents that could elicit sensitization or an allergic response in a sensitized patient

• Rare • Those reported in resorative materials may show toxic, irritative or allergic reactions • Often greater risk to the practicioner than the patient • Effects range from cumulative irritation to severe allergenic responses • Manifested as local and/or systemic • Local reactions involve the gingiva, mucosal tissues, pulp and hard tooth tissues • Systemic reactions are expressed generally as allergic skin reactions • Side effects may be acute or chronic

• No major adverse responses • Lichenoid episodes reported • Thermal conduction to pulp tissue may cause some tissue damage

• Few documented systemic adverse effects • Minor irritant effect on the pulp • Hydraulic pressure/etching during placement may irritate pulp • Good adhesion, minimal leakage at margins and no gingival reactions reported • Overall excellent biocompatibility

• Few systemic adverse affects documented • Incomplete polymerisation leads to degradation, leaching and imperfect bonding • Polymerisation shrinkage • Adverse local pulp and dentine reactions, development of recurrent caries and pain • Increased plaque adhesion and lichenoid episodes reported

• Critical to the long term success of dental prosthesis • No known severe reactions • Except wear on opposing dentition and resoteation • Strong, wear resistant • Aesthetically pleasing • Good biocompatibility

• Direct toxicity is when a material should be free of substances that cause sensitisation or allergic responses • Indirect toxicity should contain no toxic, leachable or diffusable substances