Grant: Project Grant

This project is to develop and validate biodegradable blood clots by design, called bioengineered blood clots (BBC), as a safe and effective therapy to manage hemorrhage. Hemorrhage is recognized as the most important unaddressed area in trauma care. Existing hemostatic technologies reliant on native blood clots and coagulation cascades are inadequate to manage hemorrhage. The efficacy is observed to plateau and linked with a fundamental material constraint: native blood clots are relatively slow to form and vulnerable to rupture. Motivated by our recent studies, the hypothesis of this project is that the limited hemostatic function of native blood clots could be remedied with a design strategy of bioengineered blood clots for rapid, robust, and effective hemostasis. The BBC will be designed and tested for biocompatibility, biodegradability, and blood compatibility. To test these hypotheses, this project contains three aims: (1) synthesize, characterize, and refine bioengineering blood clots with click clotting strategy; (2) study the fracture of blood clots with physiological relevance in vitro, in silico, and ex vivo; (3) develop and validate BBC as hemostatic sealants in animal hemorrhage models. To accomplish these objectives, this project will draw upon expertise from leading researchers in biomaterials, biomechanics, hemostasis, hematology, and trauma surgery. This project is expected to substantially advance the fundamental understanding of blood clot fracture and its implications on hemostasis and lead to next-generation hemostatic technologies based on bioengineered blood clots for controlling hemorrhage, which is responsible for 30-40% of trauma-associated deaths. The proposed technologies could help treat severe bleeding and reduce death and related complications from uncontrolled bleeding in Canada and abroad.