International Journal of Nanomedicine (Aug 2020)
Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomes Combined Pluronic F127 Hydrogel Promote Chronic Diabetic Wound Healing and Complete Skin Regeneration
Abstract
Jiayi Yang,1,* Zhiyi Chen,1,* Daoyan Pan,1,* Huaizhi Li,1 Jie Shen1,2 1Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Shunde Hospital of Southern Medical University, Shunde, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Shen; Daoyan PanDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510515, People’s Republic of ChinaEmail [email protected]; [email protected]: Chronic refractory wounds are a multifactorial comorbidity of diabetes mellitus with the characteristic of impaired vascular networks. Currently, there is a lack of effective treatments for such wounds. Various types of mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to exert multiple therapeutic effects on skin regeneration. We aimed to determine whether a constructed combination of human umbilical cord MSC (hUCMSC)-derived exosomes (hUCMSC-exos) and Pluronic F-127 (PF-127) hydrogel could improve wound healing.Materials and Methods: We topically applied human umbilical cord-derived MSC (hUCMSC)-derived exosomes (hUCMSC-exos) encapsulated in a thermosensitive PF-127 hydrogel to a full-thickness cutaneous wound in a streptozotocin-induced diabetic rat model. The material properties and wound healing ability of the hydrogel and cellular responses were analyzed.Results: Compared with hUCMSC-exos, PF-127-only or control treatment, the combination of PF-127 and hUCMSC-exos resulted in a significantly accelerated wound closure rate, increased expression of CD31 and Ki67, enhanced regeneration of granulation tissue and upregulated expression of vascular endothelial growth factor (VEGF) and factor transforming growth factor beta-1 (TGFβ-1).Conclusion: The efficient delivery of hUCMSC-exos in PF-127 gel and improved exosome ability could promote diabetic wound healing. Thus, this biomaterial-based exosome therapy may represent a new therapeutic approach for cutaneous regeneration of chronic wounds.Keywords: angiogenesis, diabetes wound, exosomes, mesenchymal stem cells, thermoresponsive hydrogels
