Blood Coagulation Inducing Synthetic Polymer Hydrogel
Casey, Brendan John
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Uncontrolled hemorrhaging, or blood loss, accounts for upwards of 3 million deaths each year and is the leading cause of preventable deaths after hospital admission around the world. Biological-based hemostatics are quite effective at controlling blood loss, but prohibitively expensive for people in developing countries where over 90 % of these deaths are occurring. Synthetic-based hemostatics are less expensive, yet not nearly as effective as their biological counterparts. A better understanding of how synthetic materials interact with and affect the body's natural clotting response is vital to the development of future hemostatic material technology which will help millions around the world. Initial in vitro experimentation focused on investigating the key chemical and structural material properties which affect Factor VII (FVII) activation in citrated human plasma. Enzyme-linked assays were utilized to confirm the ability of specifically formulated charged hydrogels to induce FVII activation and provided insight into the critical material parameters involved in this activation. Dynamic mechanical analysis was used to establish a correlation between polymeric microstructure and FVII activation. Experiments utilizing coagulation factor depleted and inhibited plasmas indicated that FVII, FX, FII, and FI are all vital to the process outlining the general mechanism of fibrin formation from the onset of FVII activation. The ability of the polymer to induce fibrin formation in "artificial plasma" explicitly lacking calcium, TF, and platelets suggested that a specifically designed material surface has the capability to substitute for these vital cofactors. Clinical diagnostic experimentation using sheep blood indicated that hydrogels containing higher amounts of electrostatic positive charge and lower cross-link density were able to induce faster, more robust clot formation in the presence of a coagulation cascade activator. Subsequent in vivo animal experimentation clearly demonstrated the ability of such hydrogels to aggregate platelets and erythrocytes promoting the formation of an effective hemostatic seal at the wound site. Moreover, in vivo testing confirmed the viability of such a charged polymer hydrogel to effectively control blood loss in a clinically relevant model.