title: 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.
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.
authors.affiliation: Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Tong
authors.affiliation: Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Hao
authors.affiliation: Department of Medical Administration, Chinese PLA General Hospital, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xia
authors.affiliation: Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Ti
authors.affiliation: Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.affiliation: Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Hou
authors.affiliation: Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Song
authors.affiliation: Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Liu
authors.affiliation: Central laboratory, Hainan branch of Chinese PLA General Hospital, Sanya, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
authors.affiliation: Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D048271:Chitosan; D003094:Collagen; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D005612:Freeze Drying; D006614:Hindlimb; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007511:Ischemia; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells; D008855:Microscopy, Electron, Scanning; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D017768:Skin, Artificial; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing
chemical_list: D016207:Cytokines; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D003094:Collagen; D048271:Chitosan; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat