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However, the clinical translation of secretome-based therapies is hindered by the instability of its bioactive components during storage. To address this challenge, we developed a lyophilization strategy using cryoprotectants to produce a stable, powdered form of hUC-MSC-conditioned medium (CM). Our results demonstrated that the lyophilized CM (Lyo-CM), particularly when formulated with specific cryoprotectants, maintained excellent bioactivity of CM while showing superior reproducibility and stability. Furthermore, both in vitro and in vivo experiments revealed that Lyo-CM significantly enhanced wound closure during inflammation and proliferation phases, including inflammation resolution, cell proliferation, angiogenesis, and extracellular matrix remodeling. Our study provides a valuable approach to establishing a clinically viable, shelf-stable formulation of hUC-MSC secretome to advance the field of cell-free regenerative therapy.<\/jats:p>","DOI":"10.1093\/rb\/rbag140","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T16:51:39Z","timestamp":1782751899000},"source":"Crossref","is-referenced-by-count":0,"title":["Advanced lyophilized mesenchymal stem cell-conditioned medium formulation improves therapeutic efficacy in skin wound repair"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3717-9903","authenticated-orcid":false,"given":"Xinjiani","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Medicine, Jiaxing University , Jiaxing 314001,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University , Jiaxing 314006,","place":["China"]},{"name":"Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University , Jiaxing 314006,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxue","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University , Jiaxing 314006,","place":["China"]},{"name":"Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University , Jiaxing 314006,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Medicine, Jiaxing University , Jiaxing 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