SBIR-STTR Award

This SBIR Phase I project aims to further the development a novel nanoparticle-based synthetic platelet technology for the treatment of internal, non-compressible hemorrhage after traumatic injury. Trauma is the leading killer of people aged 1-46, and uncontrollable hemorrhage after injury is the cause of 35% of pre-hospital trauma deaths and 90% of military combat casualties. This is because there are currently no pre-hospital treatment options for internal, non-compressible hemorrhage. If the patient reaches a medical treatment facility in time, the current standard of care is transfusion with blood products, including platelets. However, natural platelet products suffer from shortage in supply (due to donor shortage), difficulty in portability, high risk of bacterial contamination, very short shelf life (3-5 days), requirement of blood typing and cross matching, and multiple biologic side effects (e.g. immune response). Therefore, there exists a significant clinical need for a synthetic platelet surrogate that can address the above limitations and can be administered at point-of-injury or during en route care to stop the bleeding earlier and potentially save lives. Beyond the potential clinical and commercial impact, the proposed research will also provide multi-disciplinary educational and research opportunities in major STEM areas at undergraduate level to create future scientists and engineers.A synthetic platelet technology has been developed that can simulate the hemostatic mechanisms and capabilities of natural platelets while allowing large-scale manufacturing, sterilization, long shelf-life and portability. The technology consists of a platelet-mimetic lipid-based nanoparticle, heteromultivalently surface-decorated with three types of small synthetic peptide ligands that render cooperative mechanisms of binding to von Willebrand Factor (vWF) and collagen (platelet-mimetic injury site-selective adhesion mechanisms) and binding to stimulated form of GPIIb-IIIa on active platelets (platelet-mimetic injury site-directed aggregation mechanism). This patented design is unique in that it is currently the only design that combines these adhesion and aggregation properties of natural platelets on a single synthetic platform. Preliminary studies have established the platelet-mimetic functional mechanisms in vitro as well as its significant hemostatic therapy capability in vivo in small (mouse) and large (pig) animal models of hemorrhage in both prophylactic and emergency administration frameworks. Building on these promising results, this project aims to conduct translationally-directed studies to address technical hurdles associated with manufacturing the synthetic platelets with batch-to-batch consistency and long shelf life (>1 year) at a range of storage conditions (widely varying temperatures, altitudes, etc), which would be highly relevant in austere civilian and military applications.

The broader/commercial impact of this Small Business Innovation Research (SBIR) Phase II project aims to advance a technology for the treatment of uncontrolled hemorrhaging (bleeding) after traumatic injury. Uncontrolled hemorrhage from trauma is the a major cause of death, but an estimated 40% are potentially preventable if hemorrhage control can be achieved rapidly. In hospitals, such traumatic bleeding is treated by transfusion of donated blood to assist with clotting to stanch bleeding, but this source suffers from lack of timely availability, high risk of bacterial contamination, and short shelf-life (5-7 days). The proposed technology will rapidly stanch bleeding by adhering to the injury site and amplifying the individual's clotting mechanisms. In addition, it offers advantages of large-scale manufacturing, sterilizability, long shelf life, and easy portability/storage for on-demand use. This project will advance the engineering of this nanotechnology at scale. This SBIR Phase II project will advance the development of a synthetic hemostat nanotechnology for manufacturing at scale. Uncontrolled hemorrhage from trauma is typically managed by transfusion of donor blood-derived platelets, which suffer from many disadvantages. This project will advance the development of a synthetic platelet surrogate nanotechnology with the following technical objectives: 1) Develop and validate lipid-peptide conjugation methods; 2) Develop and validate lipid-peptide characterization methods; 3) Develop and validate liposome manufacture methods; 4) Test at batch scale; 5) Test consistency at scale. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.