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
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
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DOI：
10.1111/wrr.12369
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发表时间：
2016
影响因子：
2.9
通讯作者：
Chuan Tong;Hao-jie Hao-Hao-jie-Hao-2381608;Lei Xia;Jiejie Liu;Dong-dong Ti;Liang Dong;Qian Hou;Hai-jing Song;
中科院分区：
文献类型：
--
作者：
Chuan Tong;Hao-jie Hao-Hao-jie-Hao-2381608;Lei Xia;Jiejie Liu;Dong-dong Ti;Liang Dong;Qian Hou;Hai-jing Song;
骨髓间充质干细胞（BM-MSCs）具有使其有希望用于治疗慢性不愈合伤口的特性。主要的挑战是确保BM-MSC的有效，安全和无痛输送。组织工程皮肤替代品在慢性不愈合伤口引起的皮肤损伤中具有相当大的益处。在这里，我们使用交联和冷冻干燥方法构建了一种三维仿生支架，称为胶原-壳聚糖海绵支架（CCSS）。扫描电子显微镜图像显示，CCSS具有约100 μm的互连网络孔结构，并表现出适当的溶胀比，以保持形态稳定性和适当的生物降解性，以提高生物稳定性，使用溶胀和降解试验。此外，使用两步接种法将BM-MSCs接种在CCSS中以构建组织工程皮肤替代物。此外，在这种三维仿生CCSS中，BM-MSCs分泌自己的胶原蛋白并保持良好的存活能力和活力。重要的是，BM-MSCs在缺氧预处理后表现出促血管生成因子（包括HIF-1α、VEGF和PDGF）的显著上调表达。在体内，低氧预处理的皮肤替代品通过减少炎症和增强下肢缺血的糖尿病大鼠的血管生成显著加速伤口闭合。因此，低氧预处理皮肤替代物可以作为理想的生物工程皮肤替代物，以促进最佳的糖尿病皮肤伤口愈合。
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.