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Therefore, a dermal substitute that can induce rapid tissue regeneration and inhibit scar formation is urgently required to address this concern. In this study, we established biologically active dermal substitutes (BADS) by combining novel animal tissue\u2010derived collagen dermal\u2010replacement scaffolds (CDRS) and bone marrow mesenchymal stem cells (BMSCs) for the healing and recurrence treatments of chronic diabetic wounds. The collagen scaffolds derived from bovine skin (CBS) displayed good physicochemical properties and superior biocompatibility. CBS loaded with BMSCs (CBS\u2010MCSs) could inhibit M1 macrophage polarization in vitro. Decreased MMP\u20109 and increased Col3 at the protein level were detected in CBS\u2010MSCs\u2010treated M1 macrophages, which may be attributed to the suppression of the TNF\u2010\u03b1\/NF\u2010\u03baB signaling pathway (downregulating phospho\u2010IKK\u03b1\/\u03b2\/total IKK\u03b1\/\u03b2, phospho\u2010I\u03baB\/total I\u03baB, and phospho\u2010NF\u03baB\/total NF\u03baB) in M1 macrophages. Moreover, CBS\u2010MSCs could benefit the transformation of M1 (downregulating iNOS) to M2 (upregulating CD206) macrophages. Wound\u2010healing evaluations demonstrated that CBS\u2010MSCs regulated the polarization of macrophages and the balance of inflammatory factors (pro\u2010inflammatory: IL\u20101\u03b2, TNF\u2010\u03b1, and MMP\u20109; anti\u2010inflammatory: IL\u201010 and TGF\u2010\u03b23) in db\/db mice. Furthermore, CBS\u2010MSCs facilitated the noncontractile and re\u2010epithelialized processes, granulation tissue regeneration, and neovascularization of chronic diabetic wounds. Thus, CBS\u2010MSCs have a potential value for clinical application in promoting the healing of chronic diabetic wounds and preventing the recurrence of ulcers.<\/jats:p>","DOI":"10.1002\/btm2.10467","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T12:57:21Z","timestamp":1670417841000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Collagen scaffolds derived from bovine skin loaded with\n                    <scp>MSC<\/scp>\n                    optimized\n                    <scp>M1<\/scp>\n                    macrophages remodeling and chronic diabetic wounds healing"],"prefix":"10.1002","volume":"8","author":[{"given":"Hengdeng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Burns, Laboratory of General Surgery The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"},{"name":"Guangdong Provincial Engineering 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