Improving Chronic Diabetic Wound Healing through an Injectable and Self-Healing Hydrogel with Platelet-Rich Plasma Release

ACS Appl Mater Interfaces. 2020 Dec 16;12(50):55659-55674. doi: 10.1021/acsami.0c17142. Epub 2020 Dec 1.

Abstract

Diabetic skin ulcer is one of the severe complications of diabetes mellitus, which has a high incidence and may cause death or disability. Platelet-rich plasma (PRP) is widely used in the treatment of diabetic wounds due to the effect of growth factors (GFs) derived from it. However, the relatively short half-life of GFs limits their applications in clinics. In addition, the presence of a large amount of proteases in the diabetic wound microenvironment results in the degradation of GFs, which further impedes angiogenesis and diabetic wound healing. In our study, we fabricated a self-healing and injectable hydrogel with a composite of chitosan, silk fibroin, and PRP (CBPGCTS-SF@PRP) for promoting diabetic wound healing. CBPGCTS-SF@PRP could protect PRP from enzymatic hydrolysis, release PRP sustainably, and enhance the chemotaxis of mesenchymal stem cells. The results showed that it could promote the proliferation of repair cells in vitro. Moreover, it could enhance wound healing by expediting collagen deposition, angiogenesis, and nerve repair in a type 2 diabetic rat model and a rat skin defect model. We hope that this study will offer a new treatment for diabetic nonhealing wounds in clinics.

Keywords: angiogenesis; diabetic wound healing; nerve repair; platelet-rich plasma; sustainable release.

MeSH terms

  • Animals
  • Benzaldehydes / chemistry
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology*
  • Biocompatible Materials / therapeutic use
  • Cell Proliferation / drug effects
  • Chitosan / chemistry
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / pathology
  • Fibroins / chemistry
  • Humans
  • Hydrogels / chemistry*
  • Hydrogels / metabolism
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Nude
  • Neovascularization, Physiologic / drug effects
  • Nerve Fibers / physiology
  • Platelet-Rich Plasma / chemistry
  • Platelet-Rich Plasma / metabolism*
  • Polyethylene Glycols / chemistry
  • Rats
  • Regeneration / drug effects
  • Skin Diseases / drug therapy
  • Skin Diseases / pathology
  • Wound Healing / drug effects*

Substances

  • Benzaldehydes
  • Biocompatible Materials
  • Hydrogels
  • Intercellular Signaling Peptides and Proteins
  • Polyethylene Glycols
  • 4-carboxybenzaladehyde
  • Fibroins
  • Chitosan