Next Generation Platelet Storage Bags for Better and Safer Transfusions

Platelet transfusion is a lifesaving medical procedure in contexts ranging from hemorrhagic bleeding to chemotherapy. However, platelet supply, shelf life, and quality remain challenging problems for blood banks globally. Platelets have limited shelf lives throughout which their quality rapidly degrades, a phenomenon known as the platelet storage lesion (PSL). Another longstanding and life-threatening complication of platelet transfusion and storage is bacterial contamination and growth, leading to infection and sepsis post-transfusion. These challenges result in high wastage rates of platelets (~20% in Canada) and chronic shortages globally. Furthermore, current state-of-the-art pathogen reduction and antiseptic technologies cannot consistently eliminate all bacteria present in platelet concentrates. To address these challenging problems, this research aims to develop next-generation platelet storage bags capable of self-sterilizing from bacteria while extending platelet shelf life, thereby improving the supply, safety, and efficacy of platelet transfusions. To address these challenging problems, this project aims to develop next-generation blood storage bags capable of eliminating bacteria while extending the blood's shelf life. We have developed a line of universally applicable coatings based on the co-assembly of polydopamine with a library of ultra-high molecular weight hydrophilic polymers (uHHPs) in water that prevent both platelet and bacterial adhesion on storage units. These coatings can be deposited in one step in water, and do not leach, providing a practical approach do developing bioactive coatings with widespread functionality that can be deposited on myriad materials in medical devices, including blood storage bags. Our group has screened a wide library of UHHPs for the polydopamine coatings and identified 3 coatings that demonstrate excellent long-term biocompatibility with platelet concentrates, showing no significant decreases in quality markers when compared to industry-standard storage bags (metrics including CD62P and phosphatidylserine display, blood gas analysis of O2, CO2, pH, glucose, and lactate, rotational thromboelastometry using EXTEM and INTEM, or aggregometry with ADP, thrombin, or TxA2). Proteomic characterization of the protein coronas formed on the surface of the uncoated and coated bags revealed stark differences in surface proteomes, yet notably, these did not manifest in differences in platelet storage quality, suggesting that the species and quantity of proteins adhered does not impact platelet storage quality. Using the platelet-compatible coatings, we have developed blood storage bags conjugated with novel antimicrobial peptides (AMPs), identified through a library screen, that render the blood bags self-sterilizing. Platelet concentrates coated with AMP-coupled coatings using the AMPs E6- and Tet20 eliminated 100 CFU/mL Staphylococcus epidermidis 24 h, with no significant decreases in quality for platelets in coated units, whether the bags were inoculated with bacteria or not. Coated bags containing leukoreduced whole blood reduced S. epidermidis growth and did not demonstrate significant decreases in quality either. Collectively, this data is a proof-of-concept that AMP-coupled coatings can act as a platform for the development of self-sterilizing blood bags. The development of a next-generation platelet storage bag capable of self-sterilization holds immense promise for blood banking systems globally, as platelet shortages remain a chronic challenge and blood contamination persists despite best efforts. Furthermore, this technology may act as the basis for the development of future bioactive platelet storage bags that actively combat the PSL or combat other relevant bloodborne pathogens.