Sodium alginate/collagen hydrogel loaded with human umbilical cord mesenchymal stem cells promotes wound healing and skin remodeling

Cell Tissue Res. 2021 Feb;383(2):809-821. doi: 10.1007/s00441-020-03321-7. Epub 2020 Nov 7.

Abstract

Stem cell transplantation is a promising therapy for wound healing, but the low retention and survival of transplanted stem cells limit their application. Injectable hydrogels exert beneficial effects in skin tissue engineering. In this study, an injectable hydrogel composed of sodium alginate (SA) and collagen type I (Col) was synthesized as a tissue scaffold to improve the efficacy of stem cells in a full-thickness excision wound model. Our results showed that SA/Col hydrogel was injectable, biodegradable, and exhibited low immunogenicity, which could promote the retention and survival of hUC-MSCs in vivo. SA/Col loaded with hUC-MSCs showed reduced wound size (p < 0.05). Histological and immunofluorescence results confirmed that SA/Col loaded with hUC-MSCs significantly promoted the formation of granulation, enhanced collagen deposition and angiogenesis, increased VEGF and TGF-β1 expression (p < 0.05), and mitigated inflammation evidenced by lower production of TNF-α and IL-1β and higher release of IL-4 and IL-10 (p < 0.05). Furthermore, SA/Col loaded with hUC-MSCs significantly lowered the expression of NLRP3 inflammasome-related proteins (p < 0.05). Taken together, our results suggest that SA/Col loaded with hUC-MSCs promotes skin wound healing via partly inhibiting NLRP3 pathway, which has potential to the treatment of skin wounds.

Keywords: Injectable hydrogel; Mesenchymal stem cells; NLRP3 inflammasome; Tissue remodeling; Wound healing.

MeSH terms

  • Alginates / pharmacology*
  • Animals
  • Biocompatible Materials / pharmacology
  • Cell Line
  • Cell Proliferation / drug effects
  • Collagen / pharmacology*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Humans
  • Hydrogels / pharmacology*
  • Inflammation / pathology
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Neovascularization, Physiologic / drug effects
  • Skin / drug effects*
  • Umbilical Cord / cytology*
  • Wound Healing* / drug effects

Substances

  • Alginates
  • Biocompatible Materials
  • Hydrogels
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Collagen