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A human mesenchymal stem cell (MSC)-derived ECM biologic was engineered to treat diabetic wounds using xeno- and serum-free components. Hypoxia-primed MSCs in a chemically defined medium produced a pro-angiogenic secretome. Aggregation with dextran sulfate created an ECM-DxS composite (MIPSOS) that enhanced pro-angiogenic bioactivity, accelerated revascularization and closure, improved infiltration and granulation, and reduced macrophage presence compared with GraftJacket®.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/culturing-hypoxia-primed-mesenchymal-stem-cells-in-xeno-and-serum-free-conditions-facilitates-the-synthesis-of-an-extracellular-matrix-based-biologic-with-augmented-therapeutic-potential-for-the-treatment-of-diabetic-wounds/458738/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/culturing-hypoxia-primed-mesenchymal-stem-cells-in-xeno-and-serum-free-conditions-facilitates-the-synthesis-of-an-extracellular-matrix-based-biologic-with-augmented-therapeutic-potential-for-the-treatment-of-diabetic-wounds/458738.png","ImageObject",300,407,{"name":92,"@type":93},"Aldword","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-10","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How does hypoxia priming change MSC behavior for diabetic wound treatment?","Question",{"text":113,"@type":114},"Hypoxia-primed MSCs cultured in a chemically defined medium produce a secretome enriched with pro-angiogenic factors, which is then formulated into the therapeutic biologic.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What is MIPSOS, and how is it assembled?",{"text":118,"@type":114},"MIPSOS is an ECM-DxS composite biologic created by aggregating/coprecipitating the MSC secretome with dextran sulfate (DxS), assembling deposited components into insoluble ECM, and then processing after decellularization into micro-particles of solidified secretome.",{"name":120,"@type":111,"acceptedAnswer":121},"How does MIPSOS perform compared with a clinically used ECM-based product?",{"text":122,"@type":114},"MIPSOS-treated wounds showed almost doubled wound closure rates and improved revascularization, re-epithelization, infiltration, and granulation, outperforming GraftJacket® while reducing macrophage presence.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},458738,1790791489,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},2336478940917,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Lit etal. Stem Cell Research & Therapy (2026) 17:15 [https://doi.org/10.1186/s13287-025-04827-z](https://doi.org/10.1186/s13287-025-04827-z)  \nStem Cell Research & Therapy  \nRESEARCH Open Access  \nCulturing hypoxia-primed mesenchymal  stem cells in xeno-and serum-free conditions facilitates the synthesis of an extracellular matrix-based biologic with augmented therapeutic potential for the treatment of diabetic wounds  \nKwok Keung Lit 1,2,3, Cheuk Kwan Owen Li 1,2, Zhamilya Zhirenova 1,2,3 and Anna Blocki 1,2,3,4*  \nAbstract  \nDiabetic wound healing is severely impaired by poor angiogenesis, neuropathy, chronic inflammation, decreased cell proliferation and dysregulated extracellular matrix (ECM) synthesis. Here, we developed a human mesenchymal stem cell (MSC)-derived ECM-based biologic with augmented pro-angiogenic potential, free of any xeno-and serum-free components, aimed at treating diabetic wounds. Hypoxia-primed MSCs, cultured in chemically defined medium, synthesized a secretome enriched in pro-angiogenic factors. This secretome was aggregated and coprecipitated by a heparan sulfate mimetic, dextran sulfate (DxS), into the pericellular space. MSCs assembled the deposited secretome components into an insoluble ECM, which upon decellularization was processed into MIcroParticles of SOlidified Secretome (MIPSOS), an ECM-DxS composite biologic. This formulation of MIPSOS demonstrated augmented pro-angiogenic bioactivity in vitro and in vivo and accelerated revascularization, reepithelization and wound closure by almost doubling wound closure rate, and outperforming GraftJacket®, a clinically utilized decellularized human dermis-derived biologic. MIPSOS-treated wounds showed enhanced cellular infiltration and granulation tissue formation, along with a reduced presence of macrophages, indicating progression toward inflammation resolution. MIPSOS thus provides a novel treatment alternative that overcomes major limitations of soluble factor-based, tissue-derived ECM-based, as well as cell-based therapies, offering significant improvements in diabetic wound management.  \nKeywords Xeno-free/serum-free, Hypoxic culture, Extracellular matrix, Revascularization, Diabetic wound healing  \n*Correspondence:  \nAnna Blocki  \n[anna.blocki@cuhk.edu.hk](anna.blocki@cuhk.edu.hk)  \n1Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China  \n2School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China  \n3Center for Neuromusculoskeletal Restorative Medicine (CNRM), Hong Kong Science Park, New Territories, Shatin, Hong Kong SAR, China 4Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/.  \nLit et al. Stem Cell Research & Therapy (2026) 17:15  \nIntroduction  \nImpaired re-vascularization is one of the key pathophysiological features of chronic diabetic wound healing [1]. Due to the resulting poor tissue perfusion, ischemic tissues are continuously injured by low oxygen tension and ","cbCaichFWRU1RvxV","https://ap.wps.com/l/cbCaichFWRU1RvxV","pdf",5059506,"English","# Abstract\n# Keywords\n# Introduction\n## Impaired re-vascularization in diabetic wounds\n## Limitations of existing pro-angiogenic therapies\n## MSC and ECM-based alternatives","[{\"question\":\"How does hypoxia priming change MSC behavior for diabetic wound treatment?\",\"answer\":\"Hypoxia-primed MSCs cultured in a chemically defined medium produce a secretome enriched with pro-angiogenic factors, which is then formulated into the therapeutic biologic.\"},{\"question\":\"What is MIPSOS, and how is it assembled?\",\"answer\":\"MIPSOS is an ECM-DxS composite biologic created by aggregating/coprecipitating the MSC secretome with dextran sulfate (DxS), assembling deposited components into insoluble ECM, and then processing after decellularization into micro-particles of solidified secretome.\"},{\"question\":\"How does MIPSOS perform compared with a clinically used ECM-based product?\",\"answer\":\"MIPSOS-treated wounds showed almost doubled wound closure rates and improved revascularization, re-epithelization, infiltration, and granulation, outperforming GraftJacket® while reducing macrophage presence.\"}]","Culturing hypoxia-primed mesenchymal stem cells in xeno- and serum-free conditions facilitates the synthesis of an extracellular matrix-based biologic with augmented therapeutic potential for the treatment of diabetic wounds | PDF",1790754267,48]