Mechanisms of platelet activation by biomaterials and fluid shear flow

Severe defects in the heart or blood vessels leads to various cardiovascular diseases (CVD) and patients sometimes require biomaterial based implants to replace/overcome these defects. However, introduction of biomaterials into the patient's anatomy leads to bleeding and thrombosis complications. To date, the search for a completely non-thrombogenic surface is not complete. Various factors account for the challenges found in this regard: i. design factors of mechanical devices, especially at the sharp edges and connections, introduce non-physiological flow patterns, ii. blood protein responses to the biomaterial vary based on the specific biomaterial used in the vascular grafts; iii. multiple pathways are stimulated due to biomaterial-blood interactions which include interactions both at the protein and the cellular levels; iv. the pathways are intricate and inter-linked due to which perturbing a single reaction does not usually eliminate the problem; and v. the exact molecular mechanisms that trigger these thrombogenic processes is still not fully understood. Platelets are the key cellular players in both the hemostatic and thrombotic processes in blood. In this review, we describe an overall view of some of the thrombogenic processes initiated due to biomaterial-blood interactions, with focus on the role of von Willebrand factor in shear induced platelet activation and aggregation processes.