Intraosseous administration of lyophilized synthetic platelets renders hemostatic efficacy in rat model of traumatic hemorrhage.

Abstract

BACKGROUND: In traumatic hemorrhage, transfusion of donor-derived platelets improve hemostasis and survival, but their availability is often limited by supply constraints and short shelf-life. To address this, we have developed SynthoPlate (SP), a synthetic platelet nanotechnology that mimics the primary hemostatic functions of natural platelets, and have recently advanced its manufacturing into a shelf-stable, lyophilized powder for rapid aqueous-reconstitution and on-demand use. OBJECTIVES: We aimed to evaluate the feasibility, safety, and efficacy of administering SP intraosseously in a rat model of traumatic hemorrhage, considering the critical clinical relevance of intraosseous access in prehospital and combat medicine. METHODS: We first assessed SP's hemostatic cooperativity with rat platelets using a microfluidic assay. Next, SP was administered intraosseously in rats to evaluate safety and biodistribution. Finally, 0.5 mg/kg of SP was administered intraosseously in a rat liver laceration model to assess effects on hemodynamics, blood loss, and survival. RESULTS: Microfluidic studies confirmed SP's hemostatic capability in platelet-depleted rat plasma. In pilot safety studies, intraosseously administered SP was well tolerated at doses up to 20 mg/kg, 40 times the proposed effective dose. In efficacy studies, rats treated with SP showed significantly reduced blood loss and improved survival compared with controls. SP-treated rats also exhibited higher mean arterial pressure postinjury, shorter durations of hypotension, and faster mean arterial pressure recovery. CONCLUSION: This first-in-kind study demonstrates the feasibility of administering SP intraosseously to enhance hemostasis and survival in traumatic hemorrhage, supporting its potential as a rapidly deployable, shelf-stable platelet surrogate for use in emergency and austere settings.