Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomes Combined Pluronic F127 Hydrogel Promote Chronic Diabetic Wound Healing and Complete Skin Regeneration

Int J Nanomedicine. 2020 Aug 11:15:5911-5926. doi: 10.2147/IJN.S249129. eCollection 2020.

Abstract

Purpose: 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.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetic Foot / drug therapy
  • Diabetic Foot / pathology
  • Exosomes / chemistry*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Poloxamer / chemistry*
  • Rats, Sprague-Dawley
  • Regeneration
  • Skin / drug effects
  • Skin / injuries
  • Skin Physiological Phenomena
  • Streptozocin
  • Umbilical Cord / cytology
  • Vascular Endothelial Growth Factor A / genetics
  • Wound Healing / drug effects*
  • Wound Healing / physiology

Substances

  • Hydrogels
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Poloxamer
  • Streptozocin