International Journal of Nanomedicine (May 2022)
Self-Assembled Nano-Peptide Hydrogels with Human Umbilical Cord Mesenchymal Stem Cell Spheroids Accelerate Diabetic Skin Wound Healing by Inhibiting Inflammation and Promoting Angiogenesis
Abstract
Junshuai Xue,1 Nianfeng Sun,2 Yang Liu3 1Department of General Surgery, Qilu Hospital of Shandong University, Jinan City, Shandong Province, People’s Republic of China; 2Women’s and Children’s Hospital Affiliated to Qingdao University, Qingdao, 266001, People’s Republic of China; 3Department of General Surgery, Vascular Surgery, Qilu Hospital of Shandong University, Jinan City, Shandong Province, People’s Republic of ChinaCorrespondence: Nianfeng Sun; Yang Liu, Tel +86 18561810688 ; +86 18560088317, Email [email protected]; [email protected]: Non-healing skin wounds are a common complication in diabetic patients. Vector biomaterials embedded with mesenchymal stem cells (MSCs) are considered a promising treatment approach. In this study, we presented a novel and effective approach to accelerate diabetic skin wound healing.Methods and Materials: Human umbilical cord mesenchymal stem cells (hUC-MSCs) were shaped into spheres. RADA16-I, KLT, and RGD nanopeptides were selected for self-assembly into hydrogels. hUC-MSCs spheroids (hUC-MSCsp) were combined in vitro with self-assembled nanopeptide hydrogels and subsequently transplanted into a mouse model of diabetic skin trauma.Results: Compared with the PBS, hUC-MSCs, hUC-MSCsp, and hUC-MSCs with hydrogel groups, hUC-MSCsp with hydrogel significantly accelerated wound healing (p< 0.01) and shortened the healing time (10 vs 14 vs 21 days). The expressions of IL-6, IL-10, IL-1β, and TNF-α were significantly decreased (p< 0.001). The expression of VEGF was significantly higher in the hUC-MSCsp with hydrogel group (p< 0.05), and the density of neovascularization in the fresh skin tissue at the wound was also remarkably increased (p< 0.01).Conclusion: Nanopeptide hydrogels loaded with hUC-MSCsp accelerated diabetic skin wound healing by inhibiting inflammation and promoting angiogenesis compared with conventional stem cell transplantation, which deserves further investigation.Keywords: diabetic wound, human umbilical cord mesenchymal stem cell, spheroid, nanopeptide hydrogels, treatment
