In vivo testing of Biomaterials Flashcards
week 4
What are the arguments for animal testing?
Mixture of cells EFFECTS OF VASCULATURE Correct body temp, fluids, pH etc. Long term effects Movement included Can not commercialise a biomaterial without animal toxicity tests
What must be done to do animal experiments?
The head of the lab needs a HOME OFFICE LICENCE
- EACH individual experiment is submitted to university ethics committee for approval
- Can only do SPECIFICALLY what you set out to do in the proposal
- Numbers of animals are STRICTLY controlled have to give statistical evidence for choice of number.
- Need appropriate controls, Surgical/ Materials known to be non-toxic
When are project licences granted?
1) There is no validated alternative to animal tests
2) There is a reasoned, sustainable justification for the generation of new test data
3) The protocols proposed cannot be further refined
4) The protocols will be likely to produce data which will meet the specified objective
How could tissue engineering contribute to replaces animal experiments?
Replacement
Refinement
Reduction
What needs to be tested in vivo assessment of tissue compatibility?
1) materials of manufacture
2) intended additives, process contaminents, residues
3) leachable substances
4) degradation products
5) other components and their interactions in the final product
6) properties and characteristics of the final product
During testing, why do we need to bear in mind eventual use?
Ie when testing material for catheter don’t need to implant it for 6 months
What are the type of reactions that are tested for?
1) Sensitization/ Irritation/ Intracutaneous reactivity
2) Systemic toxicity (acute toxicity) Subchronic toxicity (subacute toxicity)
3) Genotoxicity
4) Implantation
5) Haemocompatibility
6) Chronic toxicity
7) Carcinogenicity
8) Reproductive and Developmental toxicity
9) Biodegradation
10) Immune response
What is the definition of blood compatibility?
The property of a material or device that permits it to function in contact with blood without inducing adverse reactions • Usually want to minimise clotting (exception : haemostatic device)
What does BMI stand for?
blood materials interactions
What is blood incompatibility?
BMI lead to clot or thrombus
- may compromise device by occlusion
- may detach (embolize) and create vessel occlusion downstream
- susceptible devices require use of anti-coagulation drugs (heparin)
What is problem with using heparin?
anti-coagulation drug
bleeding risk
What are platelets?
non nucleated disks
250,000 cells/microlitre
In the absence of injury or forgein materials, what is clotting prevented by?
endothelial cell lining of blood vessels which exhibit heparin on their surface
What does heparin consist of?
polysaccharides w/ SO3- and COO- charged
= provides electrostatic repulsion
How can materials trigger clotting?
Fibrinogen and other plasma proteins bind to exposed surface, platelets adhere to proteins
1) platelet binding triggers release of storage granule contents to extracellular environment (mediated by focal contacts)
2) granule release increases receptor expression on surface and recruits other platelets to site
3) platelet aggregation via fibrogren bridges = plug that initially reduces blood flow
