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Cold\u2010stored and freeze\u2010dried platelets are being investigated for extending shelf\u2010life, but these still have the inherent challenge of donor\u2010dependency. To address this, we developed a liposome\u2010based synthetic platelet (SP) nanoconstruct that mimics the primary hemostatic mechanisms of platelets, and have previously reported its efficacy. However, a logistical limitation of SP is its susceptibility to environment\u2010induced physico\u2010chemical instabilities that reduces shelf\u2010life when stored as aqueous suspension, impacting its availability and bioactivity. Lyophilization of liposomal nanotherapeutics utilizing anhydrobiosis\u2010inspired lyoprotectants can enhance shelf\u2010life, but this has not been explored for synthetic platelets. With these considerations, we report advancing SP into a lyophilized product (Lyo\u2010SP) that can be rapidly aqueous\u2010reconstituted for on\u2010demand use. Lyo\u2010SP retained morphology, size, and charge in long\u2010term storage at various temperatures, and conserved platelet\u2010mimetic functions in multiparametric assays with human plasma and blood. Lyo\u2010SP demonstrated biosafety in its effect analysis on endothelial cells, neutrophils, RBCs and complement C3. Lyo\u2010SP significantly reduced bleeding in a tail\u2010clip model in thrombocytopenic mice. These studies establish the potential of Lyo\u2010SP as a shelf\u2010stable platelet surrogate for treating bleeding complications.<\/jats:p>","DOI":"10.1002\/advs.202600002","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:59:48Z","timestamp":1776682788000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lyophilized Synthetic Platelets: In Vitro Characterization and In Vivo Evaluation in Mouse Thrombocytopenia Model"],"prefix":"10.1002","volume":"13","author":[{"given":"Ujjal Didar Singh","family":"Sekhon","sequence":"first","affiliation":[{"name":"Haima Therapeutics LLC  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dante","family":"Disharoon","sequence":"additional","affiliation":[{"name":"Case Western Reserve University Department of Biomedical Engineering  Cleveland OH 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