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Hypoxia pretreatment of bone marrow—derived mesenchymal stem cells seeded in a collagen‐chitosan sponge scaffold promotes skin wound healing in diabetic rats with hindlimb ischemia
Authors:Chuan Tong MD  Haojie Hao MD  Lei Xia MD  Jiejie Liu MD  Dongdong Ti MD  Liang Dong MD  Qian Hou MD  Haijing Song MD  Huiling Liu MD  Yali Zhao PhD  Xiaobing Fu PhD  Weidong Han PhD
Affiliation:1. Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing, China;2. Department of Medical Administration, Chinese PLA General Hospital, Beijing, China;3. Central laboratory, Hainan branch of Chinese PLA General Hospital, Sanya, China
Abstract:Bone marrow—derived mesenchymal stem cells (BM‐MSCs) have properties that make them promising for the treatment of chronic nonhealing wounds. The major challenge is ensuring an efficient, safe, and painless delivery of BM‐MSCs. Tissue‐engineered skin substitutes have considerable benefits in skin damage resulting from chronic nonhealing wounds. Here, we have constructed a three‐dimensional biomimetic scaffold known as collagen‐chitosan sponge scaffolds (CCSS) using the cross‐linking and freeze‐drying method. Scanning electron microscopy images showed that CCSS had an interconnected network pore configuration about 100 μm and exhibited a suitable swelling ratio for maintaining morphological stability and appropriate biodegradability to improve biostability using swelling and degradation assays. Furthermore, BM‐MSCs were seeded in CCSS using the two‐step seeding method to construct tissue‐engineered skin substitutes. In addition, in this three‐dimensional biomimetic CCSS, BM‐MSCs secreted their own collagen and maintain favorable survival ability and viability. Importantly, BM‐MSCs exhibited a significant upregulated expression of proangiogenesis factors, including HIF‐1α, VEGF, and PDGF following hypoxia pretreatment. In vivo, hypoxia pretreatment of the skin substitute observably accelerated wound closure via the reduction of inflammation and enhanced angiogenesis in diabetic rats with hindlimb ischemia. Thus, hypoxia pretreatment of the skin substitutes can serve as ideal bioengineering skin substitutes to promote optimal diabetic skin wound healing.
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