Topic 5 Blood-biomaterial interactions Flashcards
What happens to proteins that adhere to surfaces and what determines what proteins adhere first?
Adhered proteins usually undergoes some conformation. The Vroman effect will determine which protein adheres first and the protein exchange sequence.
What happens when platelets encounter proteins adhered on biomaterial surfaces?
Platelets adhere to biomaterial surfaces via integration with surface absorbed adhesion proteins. The interaction activates the platelets and they can use paracrine signaling between each other. Some proteins that can interact with the platelet is fibrinogen, VWF, vitronectin and fibronectin.
Explain the activation of the intrinsic coagulation pathway
Through contact activation at the negative biomaterial surface by auto activation of factor 12. The activation can get accelerated by kallikrein. and the high-molecular-weight kininogen (HMWK) functions as a cofactor for kallikrein and factor XI. The goal is to get factor XIa that can further react in the intrinsic pathway.
In an experiment platelets were put on a hydrophilic negatively charged glass surface, what happened?
The single platelets got sticky and started to aggregate. As the clusters are growing (4 min) fibrin molecules are formed and the platelets are getting less smooth and round.
What is the primary underlying mechanism by which biomaterials induce thrombus formation at the surface of the biomaterial?
Composition and conformation of proteins adsorbed at the biomaterial surface.
What is Fibrinolysis?
The enzyme Plasmin degrades fibrin fibers to fibrin degradation products (FDP). For the breakdown of the clot, usually occurs naturally after 24-48 hours. Tissue plasminogen activator is released from endothelial cells => plasminogen in clot to plasmin => fibrin to FDP.
How can the FDP be used?
The FDP (end products of fibrinolysis) can be used for monitoring blood coagulation.
How can heparin influence blood coagulation?
Heparin is a GAG and a very potent molecule to prevent blood clotting, and is naturally occurring on the surface of endothelial cells. Heparin bind to the enzyme antithrombin III, results in a conformational change so it now can bind to and inactivate thrombin (also heparin Xa). Heparin can release and bind another antithrombin as it sits on the endothelial surface and works as a catalyst site.
Describe the role of thrombomodulin in blood clotting
Present on the surface of endothelial cells. Can activate protein C to its activated form, but only if thrombin is present. Activated protein C can prevent the activation of factor V and stimulate endothelial cells to release tissue plasminogen activator - for the degradation of the clot.
Whats the role of Prostacyclin (PGI2)?
Prostacyclin (a prostaglandin) prevents platelet activation and can be given as a drug.
How does the tissue factor pathway inhibitor (TFPI) work?
TFPI prevents the initiation of the extrinsic pathway of blood coagulation. It prevents the activation of factor X to Xa and the factor VIIa complex.
Describe 2 ways to prevent blood clot formation
- Prevent protein adsorption and platelet activation
2. Immobilize or release bioactive anticoagulants
How can one prevent platelet activation by modifying the biomaterial surface?
By non-adhesive surface modification such as mimicking the glycocalyx, which are flexible, neg. charged, hydrophilic sugar chains on the surface of endothelial cells. Can mimic this by the synthetic polymer polyethylene glycol/oxide (PEG/PEO). They are very hydrophilic and with a high coverage they repel each other so they wont fold. The longer the chain the less protein and platelet adhesion.
Heparin can also be immobilized.
