Self-assembled polyelectrolyte complexes of chitosan and fucoidan for sustained growth factor release from PRP enhance proliferation and collagen deposition in diabetic mice

Drug Deliv Transl Res. 2022 Nov;12(11):2838-2855. doi: 10.1007/s13346-022-01144-3. Epub 2022 Apr 21.

Abstract

Diabetic wound management is a serious health care challenge due to higher rates of relapse, expensive treatment approaches, and poor healing outcomes. Among cell-based therapies, use of platelet-rich plasma (PRP) has been shown to be effective for diabetic wounds, but its poor shelf-life limits its clinical use. Here, we demonstrate a simple but effective polymer system to increase the shelf-life of PRP by developing a polyelectrolyte complex with dropwise addition of chitosan solution containing PRP by simple mixing at room temperature. Thus, prepared chitosan-fucoidan (CF) carrier complex encapsulated more than 95% of the loaded PRP. The resulting CF/PRP colloids were spherical in shape and ensured extended PRP release up to 72 h at 37 °C. Routine characterization (FT-IR, XRD, SEM) showed the material properties. The biological assays showed that CF complexes were biocompatible while CF/PRP enhanced the proliferation of fibroblasts and keratinocytes via higher Ki67 expression and fibroblast migration. Further investigations using a diabetic mouse model demonstrated significantly higher wound contraction and histopathological observations showed increased fibroblast migration, and collagen and cytokeratin deposition in treatment groups. The results are suggestive of the efficacy of CF/PRP as a cost-effective topical formulation for the sustained delivery of growth factors in treating chronic diabetic wounds.

Keywords: Chitosan; Diabetic wound; Fucoidan; Platelet-rich plasma; Polyelectrolyte complex; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Chitosan*
  • Collagen / metabolism
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Keratins / metabolism
  • Ki-67 Antigen / metabolism
  • Mice
  • Platelet-Rich Plasma* / metabolism
  • Polyelectrolytes
  • Polysaccharides
  • Spectroscopy, Fourier Transform Infrared
  • Wound Healing

Substances

  • Intercellular Signaling Peptides and Proteins
  • Ki-67 Antigen
  • Polyelectrolytes
  • Polysaccharides
  • Keratins
  • Collagen
  • Chitosan
  • fucoidan