PDGF-BB/SA/Dex injectable hydrogels accelerate BMSC-mediated functional full thickness skin wound repair by promoting angiogenesis

J Mater Chem B. 2021 Aug 21;9(31):6176-6189. doi: 10.1039/d1tb00952d. Epub 2021 Jul 23.

Abstract

Wound healing is a well-orchestrated dynamic and interactive process, which needs a favorable microenvironment and suitable angiogenesis. Platelet derived growth factor-BB (PDGF-BB) plays a crucial role in wound healing. However, the short half-life of PDGF-BB limits its efficacy. In the present study, we successfully synthesized an injectable hydrogel with sodium alginate (SA) and dextran (Dex) as a delivery system to simultaneously deliver PDGF-BB and bone marrow-derived mesenchymal stem cells (BMSCs) in the wound. Our work demonstrates that the PDGF-BB protein enhanced the survival, migration and endothelial cell (EC) differentiation of BMSCs in vitro. The PDGF-BB/SA/Dex hydrogels could sustainably release PDGF-BB with excellent biocompatibility in vitro and in vivo. Besides, these composite hydrogels loaded with BMSCs could accelerate wound healing by improving epithelialization and collagen deposition. In addition, the PDGF-BB/SA/Dex hydrogels promoted the EC-differentiation of transplanted BMSCs and proliferation of hair follicle stem cells in the wound. Furthermore, the expressions of angiogenesis-specific markers, PDGFR-β, p-PI3K, p-Akt, and p-eNOS, were obviously increased in the PDGF-BB/SA/Dex/BMSCs group. In conclusion, the PDGF-BB/SA/Dex injectable hydrogels could accelerate BMSC-mediated skin wound healing by promoting angiogenesis via the activation of the PDGF-BB/PDGFR-β-mediated PI3K/Akt/eNOS pathway, which may provide a new therapeutic strategy for stem cell therapy in wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / administration & dosage
  • Alginates / chemistry
  • Alginates / pharmacology*
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology*
  • Dextrans / administration & dosage
  • Dextrans / chemistry
  • Dextrans / pharmacology*
  • Humans
  • Hydrogels / administration & dosage
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Materials Testing
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Neovascularization, Physiologic / drug effects
  • Platelet-Derived Growth Factor / administration & dosage
  • Platelet-Derived Growth Factor / chemistry
  • Platelet-Derived Growth Factor / pharmacology*
  • Skin / drug effects
  • Skin / metabolism
  • Wound Healing / drug effects

Substances

  • Alginates
  • Biocompatible Materials
  • Dextrans
  • Hydrogels
  • Platelet-Derived Growth Factor