The focus of this Phase I proposal is to assess the feasibility of applying our platform of cellular biochemical stabilization with unique freezing and drying engineering design to the goal of generating freeze-dried therapeutic cells. Specifically, this program will target application of ThromboSol, a patented platelet stabilization formula, to the process of freeze-drying platelets, resulting in a stable, off-the-shelf, platelet product. Current long-term platelet storage methods are logistically complex and ineffective for economical stockpiling of transfusable units for emergency care. Our approach is to isolate the discrete components of the freeze-drying process, namely metabolic stabilization, cell freezing, frozen configuration, drying, and rehydration, and to systematically develop instrumentation and cell stabilization formulations to successfully chaperone platelets through these processes. The dried product has multiple potential commercial applications including systemic platelet delivery for correction of hemostatic function and growth factor delivery for enhanced tissue regeneration, either alone or in combination with tissue regenerative matrices. Furthermore, the product will allow a longer time period for enhanced cell-typing to prevent alloimmunization, enhanced transportablity for world-wide distribution, and point-of-need accessibility in ambulatory and far-forward military environments. Finally, the pathway being developed in this proposal will generate a general development pathway for any therapeutic cell type, whether derived directly from human donors or as engineered therapeutic cells. Utilizing ThromboSol stabilized platelets, Phase I development of a freeze-dried platelet product will follow three design steps: 1) application of nebulization technology for microdroplet formation, 2) application of novel variable thermal-gradient freezing technology, and 3) application of standard drying and rehydration technologies. At each stage, the quality of the processed platelets will be analyzed, identifying lesions to target with specific biochemical or physical stabilization. Upon successful completion of the Phase I feasibility program, Phase II will incorporate drying and rehydration model development and optimization, process scale-up, clinical assessment, and commercial equipment engineering focusing on closed-loop processing for product sterility and prevention of lot-to-lot contamination. Successful completion of this program (Phases I and II) will yield a dried platelet product with characteristics of long-term ambient storability, easy transportation to access-limited locations, one-step reconstitution, and effective in vivo hemostatic capabilities and normal circulatory half-life.
