Sliding microgel-based synthetic platelets for managing traumatic bleeding

University Of Texas Dallas, Richardson TX

Investigators

Abstract

Proposal Summary/Abstract Uncontrolled bleeding following trauma is the major cause of death in both civilian and military settings, responsible for approximately 2 million deaths per year worldwide. Rapidly addressing life-threatening hemorrhages at trauma scenes is crucial for reducing preventable trauma deaths, yet it remains a significant challenge. The overall goal of this project is to develop a hemostatic agent suitable for systemic administration to trauma patients in prehospital settings. Our approach in designing this agent is inspired by the pivotal role of platelets in identifying bleeding sites and arresting hemorrhage. Specifically, we propose sliding hydrogel-based microparticles as synthetic platelets to replicate the adhesion and shape-changing behaviors of platelets. This is important because platelets after adhering at vascular injury sites experience dramatic morphologic changes, facilitating hemostatic plug formation and clot stabilization. However, mimicking their dynamic morphologic changes and the underlying hemostatic functions in synthetic materials systems has been a difficult task. We chose the sliding hydrogel because of its unique topological structure, consisting of linear polymer chains threaded through and crosslinked by bicyclic rings. These sliding crosslinks make the hydrogel highly deformable. We will further functionalize these sliding rings with multiple bleeding-site-binding peptides. Our central hypothesis is that after intravenous injection, these highly deformable sliding microgels with bleeding-site-binding moieties accumulate at vascular injury sites and adapt morphologically to promote clot formation and stabilization, ultimately halting traumatic bleeding. In this work, we will fabricate sliding microgels with injury-targeting and shape-changing ability; and assess their hemostatic efficacy in vitro and in vivo.