SymClot: Synthetic Platelet Mimetic Particles for Augmenting Hemostasis in Patients Requiring Extracorporeal Support
Abstract
Topic Area: This proposal centers on the application of SymClot, a synthetic platelet mimetic technology, for the treatment of bleeding in patients requiring extracorporeal life support and directly addresses the CRRP Focus and Topic Areas of (1) Solutions to enhance combat care delivery throughout the far-forward environment, in particular, the Topic Areas of (a) Blood products, including freeze-dried platelets and plasma, and (b) Extracorporeal life support, and (2) Wound care solutions for complex trauma and tissue regeneration that span the operational medical care continuum or roles of care, i.e., multi-modal wound care solutions that provide a combination of hemostasis and wound healing. Research Problem: Extracorporeal life support (ECLS), including cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), is a commonly used clinical treatment for patients undergoing bleeding shock, severe cardiac distress or failure, or acute respiratory failure/acute respiratory distress syndrome (ARDS). During normal bleeding events, the body’s native platelets become activated and work to form blood clots, stemming blood loss and supporting downstream wound healing processes. However, ECMO greatly inhibits platelet function and significantly impedes clotting and wound healing processes. Blood or blood product transfusions, including platelet transfusions, are the current primary strategy for managing bleeding in ECMO patients. This strategy is not ideal, as frequent blood product transfusions raise the risk of adverse off-target blood clot formation in these patients; as a result, patients on ECMO additionally require anticoagulant treatment to mitigate adverse clotting risk, further exacerbating bleeding risks. Approximately 30% of ECMO patients experience adverse bleeding events, which are associated with significant risks of morbidity and mortality. Reducing the usage of blood products is linked to lower risk of off-target clot formation and improved patient outcomes. We have developed synthetic platelet mimetic particles, known as SymClot, that are capable of recapitulating key features of native platelets (namely, specific homing to injury sites and integration with developing clot networks to stem bleeding and stabilize the clot networks to facilitate subsequent stages of wound healing). As SymClot is a synthetic technology, it is easy to manufacture and scale up, has a longer shelf life than native platelets, and can be easily transported to austere settings for use in rural and field hospitals as needed. Additionally, the targeted nature of SymClot reduces risks of off-target adverse clot formation. To facilitate translation of this technology out of the laboratory and into the clinic, we must further optimize SymClot formation for storage and ease of intravenous administration and validate efficacy in a relevant, preclinical, large-animal (sheep) ECMO model to enable regulatory filing with FDA and clinical trials. Specific Aims: The specific aims of this project are as follows: Specific Aim 1. Evaluation of optimal SymClot formulation for storage and intravenous administration. Specific Aim 2. In vitro analysis of clot augmentation in blood samples obtained from sheep on ECMO. Specific Aim 3. In vivo analysis of SymClot hemostatic efficacy in an ovine ECMO model of ECLS. Long-Term and Military Impact: The long-term impact of this project is the development of a novel synthetic platelet that is optimized for use in combat environments and rural settings, enabling better point-of-care outcomes for Service Members and civilians who require extracorporeal support. SymClot can be freeze-dried, allowing for ease of storage and transportation compared to natural blood products, and can administered intravenously to specifically target injury sites, lowering risk of adverse off-target clotting associated with blood and blood products. SymClot can also be mass-produced, help
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310977
Entities
People
- Seema Nandi
Organizations
- United States Army