1) Bacteria and other pathogens enter wound site

2) Platelets from blood release blood clotting proteins at wound site

3) Mast cells secrete factors that mediate vasodilation and ventricular
constriction. Delivery of blood, plasma and cells at injury site increase
4) Neutrophils secrete factors that kill and degrade pathogens
5) Neutrophils and macrophages remove pathogens by phagocytosis
6) Macrophages secrete hormones called cytokines that attract immune
system cells and activate cells associated with tissue healing
7) 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 tissue
1) Foreign surface acquire protein coat in body
2) Edema lead to leukocyte emigration from blood and accumulation in
biomaterial site
3) Together with platelets, leukocytes bind on to protein-coated surface

Thrombogenicity
-

Local and systemic

Scenarios
1)
2)
3)
4)

No thrombus formed
Thrombus formed and remains attached
Trombus formed but detaches
Reaction occurs at the surface but thrombus quickly detaches via
microembolism

Flow
1) High wall shear, rate of platelets reaching surface> rate of interaction
thrombus mainly formed of platelets
2) Low wall shear, vice versa causes starving
thrombus 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 measured
2) Blood reactions in animals differ to those in humans
3) Flow unrealistic
4) 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 accumulation
2) Consumption of circulating platelets and fibrogen
3) Plasma levels of factors released by platelets and coagulation proteins
during thrombosis
4) Emobilization of micro thrombi to downstream circulatory beds

Pacemaker
Consists 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 cells

Problems:
-

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 devices

1) Hemorrhage
2) Thrombosis
3) Infection
Tissue engineering
Step 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 tissue
Step 2: Construct implanted in appropriate anatomical position where
remodelling in vivo is intended to recapiltulate the normal tissue/organ function
Application of scaffolds
1) Tissue induction ingrowth of surrounding tissue into porous scaffold,
providing substrate and cell proliferation
2) Cell transplantation seeded in scaffold, cultured then transplanted
3) Prevascularization to encourage ingrowth of vascular tissue
4) In sity polymerization minimal surgical intervention, injectable
bioresorbable materials to fill defects.
5) Delivery of bioactive molecules

Sterility
-

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 methods
1) 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 components
Advantage: Efficacy, speed, simple and lack of toxic residues
Disadvantage: high temp and pressure limit the range of compatible
materials
2) Ethylene oxide gas
Used for wide range of products
Toxic and carcinogenic residue and release post sterilization cause of
concern
Advantage: Efficacy, high penetration and compatible with wide range of
materials
Disadvantage: CFC compounds and costly explosion proof equipment
3) Radiation sterilizaition
Gamma rays from cobalt 60 isotope source
Advantage: wide range of materials, easy to control
Disadvantage: PTFE not compatible, high capital cost and continual decay
of the isotope even when not in use
4) Electron beam sterilization
E beam generated using an accelerator
Compared to gamma ray, accelerated electron has less penetrating ability
Advantage: suitable for wide range of materials
Disadvantage: Penetration distance, suitable only for thin products
immediatel after primary packaging
5) Low temperature gas plasma and chlorine dioxide