1) Bacteria and other pathogens enter wound site2) Platelets from blood release blood clotting proteins at wound site3) Mast cells secrete factors that mediate vasodilation and ventricular constriction. Delivery of blood, plasma and cells at injury site increase4) Neutrophils secrete factors that kill and degrade pathogens5) Neutrophils and macrophages remove pathogens by phagocytosis6) Macrophages secrete hormones called cytokines that attract immune system cells and activate cells associated with tissue healing7) Inflammatory response continues until foreign material is eliminated and wound is healed Foreign body response Series of molecular and cellular events that lead to encapsulation and isolation from surrounding tissue1) Foreign surface acquire protein coat in body2) Edema lead to leukocyte emigration from blood and accumulation in biomaterial site3) Together with platelets, leukocytes bind on to protein-coated surfaceThrombogenicity Local and systemic Scenarios1) No thrombus formed2) Thrombus formed and remains attached3) Trombus formed but detaches4) Reaction occurs at the surface but thrombus quickly detaches via microembolismFlow1) High wall shear, rate of platelets reaching surface> rate of interaction thrombus mainly formed of platelets2) Low wall shear, vice versa causes starvingthrombus mainly formed of red cells entrapped in fibrin mesh

In-vitro test Blood placed in direct contact with material or rearticulating blood with known flow regime In-vivo Insert materials in form of tube/ ring in the arteries/veins of animals Questionable to human:1) Time and type of measurements can cause important blood reactions to be missed, local and systemic effects not accurately measured2) Blood reactions in animals differ to those in humans3) Flow unrealistic4) Blood vessel trauma and injury

A-V shunt model in baboons Characterise blood response to tubular materials and vascular graft with respect to:1) Localised thrombus accumulation2) Consumption of circulating platelets and fibrogen 3) Plasma levels of factors released by platelets and coagulation proteins during thrombosis4) Emobilization of micro thrombi to downstream circulatory bedsPacemakerConsists of: - pulse generator which includes a power source and electric circuitry to initiate the electric stimulus and to sense normal activity One or more electrically insulated conductors leading from the pulse generator to the heart muscle Tissue or blood and tissue interface between electrode and adjacent stimulatable myocardial cellsProblems: Layer of non excitable fibrous tissue can form around the electrode Pulse generator output not set sufficiently high in early post implantation (lead to loss of pacing with fatal consequence). Set too high shortens battery life Lead and electrodes (infection, lead fracture, electrode corrosion, insulation failure, high pacing threshold) Pulse generator (erosion due to pressure necrosis of the skin overlying the pulse generator, infection of pacemaker pocket, migration of rotation of the pacemaker pack, failure of electronic component or battery depletion) Complucations of cardiac assist devices1) Hemorrhage2) Thrombosis3) InfectionTissue engineeringStep 1: Differentiated or undifferentiated cells seeded on bioabsorbably scaffold. Construct matured in a bioreactor, maturation means the cellse proliferate and elaborate extracellular matrix form new tissueStep 2: Construct implanted in appropriate anatomical position where remodelling in vivo is intended to recapiltulate the normal tissue/organ functionApplication of scaffolds1) Tissue induction ingrowth of surrounding tissue into porous scaffold, providing substrate and cell proliferation2) Cell transplantation seeded in scaffold, cultured then transplanted 3) Prevascularization to encourage ingrowth of vascular tissue4) In sity polymerization minimal surgical intervention, injectable bioresorbable materials to fill defects. 5) Delivery of bioactive moleculesSterility The absence of all living organism Test for small number of samples by immersing product into a container of sterile liquid microbiological culture medium. If sterile to microbial growth Sterility assurance level (SAL) probability of no more than 1 in a million implant will be nonsterile

Sterilization methods1) Heat (121 degrees,15-30mins not suitable for non metallic implants and packaging materials) Pressure rated sterilization chamber All surface of the product must be in contach with the steam Kill organism by destroying metabolic and structural componentsAdvantage: Efficacy, speed, simple and lack of toxic residuesDisadvantage: high temp and pressure limit the range of compatible materials2) Ethylene oxide gas Used for wide range of productsToxic and carcinogenic residue and release post sterilization cause of concernAdvantage: Efficacy, high penetration and compatible with wide range of materialsDisadvantage: CFC compounds and costly explosion proof equipment3) Radiation sterilizaitionGamma rays from cobalt 60 isotope sourceAdvantage: wide range of materials, easy to controlDisadvantage: PTFE not compatible, high capital cost and continual decay of the isotope even when not in use4) Electron beam sterilization E beam generated using an acceleratorCompared to gamma ray, accelerated electron has less penetrating abilityAdvantage: suitable for wide range of materialsDisadvantage: Penetration distance, suitable only for thin products immediatel after primary packaging5) Low temperature gas plasma and chlorine dioxide