The University of British Columbia Vancouver, British Columbia, Canada
Background/Case Studies: Platelet transfusion is a lifesaving procedure in contexts ranging from hemorrhaging and chemotherapy. However, challenges persist in supply, shelf life, and safety of platelets. Platelets degrade quickly during storage—a process called the platelet storage lesion (PSL)—and are prone to bacterial contamination, which can lead to sepsis. These issues result in high wastage (~20% in Canada) and global shortages. Current pathogen reduction methods cannot fully eliminate bacteria. This research aims to develop next-generation platelet storage bags that self-sterilize and extend platelet shelf life, improving transfusion safety and reliability.
Study
Design/Methods: We developed universally applicable coatings based on polydopamine and ultra-high molecular weight polymers (uHMWPs). These coatings reduce both bacterial and platelet adhesion and are biocompatible with the cells up to 7-day storage (approved limit in Canada). Our goal is to optimize these coatings for platelet storage:
We are screening a library of HMWPs to identify those that best preserve platelet concentrates (PCs) over 7 days, aiming to reduce activation and extend shelf life. I hypothesize that minimizing platelet adhesion improves PSL outcomes.
We are screening >600 antimicrobial peptides (AMPs) to find those with strong antibacterial activity in plasma and PCs when conjugated to our coatings (performed in 96-well plates). In parallel, top candidates from the screen are being conjugated to our coatings in PC bags to validate their activity and test the platelet biocompatibility over long-term storage. I hypothesize that these AMP-coupled coatings will remain biocompatible while eradicating contaminants.
Platelet activation (CD62P) and apoptosis (Annexin V) are measured via flow cytometry; metabolic markers via blood gas; function via thromboelastometry. Bacterial activity is tracked via CFUs in 6 mL PVC mini bags.
Results/Findings: Aim 1: We identified polymer coatings that reduce adhesion without affecting platelet activation. Coatings are being tested in additive solution and pathogen-inactivated units in the future. Aim 2: Miniaturized platelet storage bags have been conjugated with 2 AMP candidates identified from our screen (Aim 2, Fig. 1A). Bags were filled with PCs and either inoculated with 100 CFU/mL Staphylococcus epidermidis or left uninoculated as controls. AMP-functionalized bags (Fig. 1B) eliminated S. epidermidis within 24h (Fig. 1B) and maintained sterility for 7 days, without impacting platelet activation or clotting (Fig. 1C and D)
Conclusions: This data supports that AMP-coupled coatings can form the basis of self-sterilizing, platelet-compatible blood bags—potentially expandable with other bioactive functions.
