Field-Deployable Dried Platelet Surrogate Nanotechnology for Hemorrhage Control in RDCR
Abstract
Topic Area Relevance: The proposed research addresses the Topic Area of Hemorrhage Control. The research proposes to develop, evaluate, and establish a lyophilized (freeze-dried) synthetic platelet (Lyo-SP) technology that can be sterilizable and storage-stable at various environmental conditions for long time periods, easily field-deployable and portable as small volume powder, and rapidly reconstitutable in small-volume saline for intravenous or intraosseous administration to mitigate combat-associated traumatic hemorrhage via mimicking how natural platelets staunch bleeding. Traumatic hemorrhage remains a primary cause of “preventable mortality” in combat trauma for our military. A variety of technologies have been developed in the management of traumatic hemorrhage, e.g., tourniquets, hemostatic powders (e.g., QuikClot), hemostatic dressings (e.g., Combat Gauze), self-expandable polymeric matrices (e.g., ResQFoam) to treat hemorrhage. However, non-compressible hemorrhage (e.g., internal bleeding, polytrauma, blast trauma, etc.) continues to be a significant challenge to Warfighter survival. Several recent clinical studies have established that in such scenarios, transfusion of whole blood or blood components (e.g., platelets/RBC/plasma) can significantly improve survival. Robust efforts are therefore being focused on making whole blood (e.g., the Ranger ROLO program) or blood components (e.g., chilled or freeze-dried platelets) available for far-forward remote damage control resuscitation (RDCR). But there will always be persistent logistical challenges regarding whether enough whole blood or components can be available, due to donor shortage, portability, storage, and shelf-life issues. In this framework, synthetic surrogates of blood components that can be easily lyophilized and sterilized, deployed far forward, stored for a long time at various environment conditions without compromising stability and bioactivity, and reconstituted rapidly in small volume saline for on-field administration can provide significant logistical/functional benefit in RDCR of combat trauma. Lyo-SP addresses this important logistical need as a freeze-dried platelet surrogate that can potentially enable far-forward hemorrhage control in RDCR. Overview of Proposed Research: The central research hypothesis is “Lyo-SP can allow on-demand small-volume rapid aqueous reconstitution and facile intravenous or intraosseous transfusion without affecting particle stability, in vivo systemic safety and injury site-targeted platelet-mimetic hemostatic bioactivity, for mitigating hemorrhage and improving survival in trauma.” This hypothesis will be tested by specific experimental aims: Aim 1: In vitro evaluation of platelet-relevant bioactivity for Lyo-SP compared to freshly made non-lyophilized SP, using biochemical assays, microfluidics, aggregometry, flow cytometry, ROTEM and TEG, utilizing human (healthy donor as well as trauma patient-derived) plasma and whole blood. In this aim, reproducible manufacturing processes, scale-up and rigorous in vitro characterization of Lyo-SP will be established. The characterization will include particle size, morphology, pre- and post-sterilization stability, pre- and post-sterilization capabilities of rendering platelet-mimetic hemostatic bioactivities (adhesion, aggregation, thrombin/fibrin amplification, etc.) and effect on whole blood clot viscoelastic properties (clotting time, clot amplitude, clot lysis, etc.) utilizing healthy human donor blood. Subsequently, the translational potential of Lyo-SP regarding these properties will be evaluated in whole blood and plasma derived from human trauma patients. Aim 2: Evaluation of systemic safety, hemostatic efficacy and survival outcome for reconstituted Lyo-SP compared to non-lyophilized SP, varying dosage and time of administration in rat liver hemorrhage model. Here, a lethal uncontrolled liver hemorrhage model in rats will be used to evaluate s
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010628
Entities
People
- Anirban Sen Gupta
Organizations
- Case Western Reserve University
- United States Army