Exosome loaded genipin crosslinked hydrogel facilitates full thickness cutaneous wound healing in rat animal model

Drug Deliv. 2021 Dec;28(1):884-893. doi: 10.1080/10717544.2021.1912210.

Abstract

Full thickness cutaneous wound therapy and regeneration remains a critical challenge in clinical therapeutics. Recent reports have suggested that mesenchymal stem cells exosomes therapy is a promising technology with great potential to efficiently promote tissue regeneration. Multifunctional hydrogel composed of both synthetic materials and natural materials is an effective carrier for exosomes loading. Herein, we constructed a biodegradable, dual-sensitive hydrogel encapsulated human umbilical cord-mesenchymal stem cells (hUCMSCs) derived exosomes to facilitate wound healing and skin regeneration process. The materials characterization, exosomes identification, and in vivo full-thickness cutaneous wound healing effect of the hydrogels were performed and evaluated. The in vivo results demonstrated the exosomes loaded hydrogel had significantly improved wound closure, re-epithelialization rates, collagen deposition in the wound sites. More skin appendages were observed in exosomes loaded hydrogel treated wound, indicating the potential to achieve complete skin regeneration. This study provides a new access for complete cutaneous wound regeneration via a genipin crosslinked dual-sensitive hydrogel loading hUCMSCs derived exosomes.

Keywords: genipin crosslinked hydrogel; hUCMSCs derived exosome; rat model; skin tissue regeneration; wound healing.

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Collagen / metabolism
  • Drug Liberation
  • Exosomes / metabolism*
  • Female
  • Hydrogels / chemistry*
  • Hydrogen-Ion Concentration
  • Iridoids / administration & dosage
  • Iridoids / pharmacology*
  • Mesenchymal Stem Cells / drug effects
  • Particle Size
  • Rats
  • Rats, Sprague-Dawley
  • Skin / drug effects*
  • Wound Healing / drug effects*

Substances

  • Hydrogels
  • Iridoids
  • Collagen
  • genipin

Grants and funding

This research was funded by the ‘Special Project for the Transformation of Medical Scientific and Technological Achievements’, the Key R&D Program of Liaoning Province in 2019—‘Applied Study of umbilical Cord Mesenchymal Stem Cells Directed Vascular Endothelial Differentiation in the Treatment of Diabetic Foot’, and Liaoning Province Scientific Research Foundation, Grant Number 20180530017.