Mesenchymal stem cell-laden anti-inflammatory hydrogel enhances diabetic wound healing

• Published in: Scientific reports Vol. 5; no. 1; p. 18104
• Main Authors: Chen, Shixuan, Shi, Junbin, Zhang, Min, Chen, Yinghua, Wang, Xueer, Zhang, Lei, Tian, Zhihui, Yan, Yuan, Li, Qinglin, Zhong, Wen, Xing, Malcolm, Zhang, Lu, Zhang, Lin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-12-2015; Nature Publishing Group
• Subjects: 13/100; 13/107; 13/21; 13/51; 38/1; 631/532/2074; 631/57/2268; 64/60; 82/51; 82/80; Angiogenesis; Animals; Biocompatible Materials - chemistry; Biocompatible Materials - therapeutic use; Bone healing; Bone marrow; Contraction; Diabetes; Diabetes Complications - pathology; Diabetes Complications - therapy; Diabetes mellitus; Disease Models, Animal; Encapsulation; Extracellular matrix; Fibroblast growth factor 2; Granulation Tissue - metabolism; Granulation Tissue - pathology; Histology; Humanities and Social Sciences; Hydrogel, Polyethylene Glycol Dimethacrylate - chemical synthesis; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogels; Immunohistochemistry; Inflammation; Macrophages; Male; Materials Testing; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; Microenvironments; multidisciplinary; Rodents; Science; Skin; Skin Ulcer - etiology; Skin Ulcer - pathology; Skin Ulcer - therapy; Stem cell transplantation; Stem cells; Temperature effects; Transforming growth factor-b1; Ulcers; Wound Healing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18104

The purpose of this study was to permit bone marrow mesenchymal stem cells (BMSCs) to reach their full potential in the treatment of chronic wounds. A biocompatible multifunctional crosslinker based temperature sensitive hydrogel was developed to deliver BMSCs, which improve the chronic inflammation microenvironments of wounds. A detailed
in vitro
investigation found that the hydrogel is suitable for BMSC encapsulation and can promote BMSC secretion of TGF-β1 and bFGF.
In vivo
, full-thickness skin defects were made on the backs of db/db mice to mimic diabetic ulcers. It was revealed that the hydrogel can inhibit pro-inflammatory M1 macrophage expression. After hydrogel association with BMSCs treated the wound, significantly greater wound contraction was observed in the hydrogel + BMSCs group. Histology and immunohistochemistry results confirmed that this treatment contributed to the rapid healing of diabetic skin wounds by promoting granulation tissue formation, angiogenesis, extracellular matrix secretion, wound contraction and re-epithelialization. These results show that a hydrogel laden with BMSCs may be a promising therapeutic strategy for the management of diabetic ulcers.