Preclinical efficacy study of a porous biopolymeric scaffold based on gelatin-hyaluronic acid-chondroitin sulfate in a porcine burn injury model: role of critical molecular markers (VEGFA, N-cadherin, COX-2), gamma sterilization efficacy and a comparison of healing potential to Integra™

Biomed Mater. 2021 Sep 1;16(5). doi: 10.1088/1748-605X/ac1d3e.

Abstract

Development of scaffold from biopolymers can ease the requirements for donor skin autograft and plays an effective role in the treatment of burn wounds. In the current study, a porous foam based, bilayered hydrogel scaffold was developed using gelatin, hyaluronic acid and chondroitin sulfate (G-HA-CS). The fabricated scaffold was characterized physicochemically for pre- and post-sterilization efficacy by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA).In-vitrostudies proved that the scaffold promoted cellular proliferation. The efficacy of G-HA-CS scaffold was compared with Integra™ at different time points (7, 14, 21 and 42 days), in a swine second degree burn wound model. Remarkable healing potential of the scaffold was evident from the wound contraction rate, reduction of IL-6, TNF-αand C3. The expression of healing markers TGF-β1 and collagen 1 revealed significant skin regeneration with regulated fibroblast activation towards the late phase of healing (p< 0.001 at day 21 and 42 vs. control). Expression of Vascular Endothelial Growth Factor A (VEGFA), vimentin and N-cadherin were found to favor angiogenesis and skin regeneration. Mechanistically, scaffold promoted wound healing by modulation of CD-45, cyclooxygenase-2 and MMP-2. Thus, the promising results with foam based scaffold, comparable to Integra™ in swine burn injury model offer an innovative lead for clinical translation for effective management of burn wound.

Keywords: angiogenesis; burn injury; gamma sterilization; gelatin; hyaluronic acid; hydrogel scaffold; swine model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Burns / metabolism*
  • Chondroitin Sulfates* / chemistry
  • Chondroitin Sulfates* / pharmacology
  • Disease Models, Animal
  • Gamma Rays
  • Gelatin / chemistry
  • Gelatin / pharmacology
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / pharmacology
  • Hydrogels / chemistry
  • Hydrogels / pharmacology
  • Male
  • Porosity
  • Swine
  • Tissue Scaffolds / chemistry*
  • Wound Healing / drug effects*

Substances

  • Biocompatible Materials
  • Hydrogels
  • Gelatin
  • Hyaluronic Acid
  • Chondroitin Sulfates