Fabrication of In Situ Layered Hydrogel Scaffold for the Co-delivery of PGDF-BB/Chlorhexidine to Regulate Proinflammatory Cytokines, Growth Factors, and MMP-9 in a Diabetic Skin Defect Albino Rat Model

Biomacromolecules. 2021 May 10;22(5):1885-1900. doi: 10.1021/acs.biomac.0c01709. Epub 2021 Apr 26.

Abstract

Diabetes mellitus (DM)-associated impairments in wound healing include prolonged inflammation, the overexpression of matrix metalloproteases (MMPs), and low levels of growth factors at the wound site. To this end, a layer-by-layer scaffold (SL-B-L) made of cross-linked silk fibroin and hyaluronic acid is developed to deliver chlorhexidine, an antimicrobial agent and an MMP-9 inhibitor, along with the PDGF-BB protein. SL-B-L exhibited highly porous morphology. Diabetic rats treated with SL-B-L demonstrated an early wound closure, a fully reconstructed epithelial layer by 14 days, and reduced levels of IL-6, TNF-α, TGF-β1, and MMP-9. Interestingly, SL-B-L treatment increased angiogenesis, the bioavailability of collagen, DNA content, and VEGF-A levels. Furthermore, enhanced keratinocyte-fibroblast interaction along with ordered collagen deposition was observed in SL-B-L-treated rats. Most interestingly, when compared with a clinically used scaffold SEESKIN+, SL-B-L outperformed in promoting wound healing in a diabetic rat model by regulating the inflammation while delivering growth factor and the MMP-9 inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Becaplermin
  • Chlorhexidine
  • Cytokines*
  • Diabetes Mellitus, Experimental* / drug therapy
  • Hydrogels
  • Intercellular Signaling Peptides and Proteins
  • Matrix Metalloproteinase 9
  • Rats
  • Skin
  • Vascular Endothelial Growth Factor A

Substances

  • Cytokines
  • Hydrogels
  • Intercellular Signaling Peptides and Proteins
  • Vascular Endothelial Growth Factor A
  • Becaplermin
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat
  • Chlorhexidine