| Description |
Platelet surface interactions play a critical role in the hemocompatibility of blood contacting biomaterials. When blood leaves the natural vessel and contacts a synthetic material, the body senses this change. Immediately, a host of responses occur at the blood material interface including plasma protein adsorption and platelet adhesion and activation. Platelet activation stimulates local coagulation factors eventually leading to the formation of a blood clot. Clot formation on vascular implants can have many adverse effects and ultimately lead to the failure of these devices. To date, an extensive amount of research has been focused on controlling surface induced platelet adhesion and activation. Although a number of studies have shown promising in vitro results, the translation to successful hemocompatible biomaterials has been somewhat limited. This is largely due to the complexity behind the mechanisms driving the platelet response. In this dissertation, well defined microenvironments, as a function of both surface chemistry and protein immobilization, were used to characterize and understand the molecular mechanisms of surface induced platelet responses. Specifically, molecular gradients were investigated as a high throughput technique in which the platelet response could be rapidly screened over a variety of surface chemistries. Here, it was discovered that the upstream environment affected the downstream platelet response and that upstream surface interactions may actually prime platelets for downstream adhesion and activation. This phenomenon was further explored using microcontact printing to prepare test samples with covalently immobilized fibrinogen "priming" regions. The downstream platelet response was characterized and found to be dependent on the presence of an upstream priming region. The use of microcontact printing was also investigated as a tool to control platelet adhesion and morphological characteristics using random micropatterns of fibrinogen at varying relative coverage areas. The experiments described in this dissertation provided well controlled environments in which specific surface-induced platelet adhesion and activation mechanisms were examined and will serve as a foundation for future fundamental studies. |
