A novel chitosan–collagen bilayer scaffold prevents contraction and accelerates cutaneous repair in a rat splint-skin model

Introduction The treatment of chronic wound is extremely challenging and is often exacerbated by inflammation, poor angiogenesis and recurrent bacterial infections. To address this, we have developed a novel biomimetic bilayer three-dimensional scaffold with a chitosan-collagen upper epidermal layer, on top of a porous collagen-glycosaminoglycan dermal layer. Methods In this study we assess this scaffold’s efficacy in a preclinical wound model. In addition, we examined the scaffold with the addition of plasmid DNA encoding pro-angiogenic stromal derived factor-1α (SDF-1α) and anti-fibrotic β-klotho in a splinted full-thickness skin wound model on young Sprague Dawley rats for 14 days. Results All the scaffold groups showed uniform deposition of extracellular matrix and showed no signs of wound contraction unlike our ‘empty’ defect group. Both the ‘bilayer chitosan- collagen’ group and ‘gene activated group’ showed that the upper chitosan layer was filled with exudate, which dried over time and formed a protective scab that delaminated easily at day 14. Our Chitosan- collagen scaffolds showed a decrease in pro-inflammatory IL-1β, an increase in the pro-angiogenic CD31 and a decrease in pro-fibrotic α-SMA protein expression. We showed enhanced pro-angiogenic and reduced pro-fibrotic expression with the addition of SDF and Klotho plasmids respectively (p < 0.01); however, the rate of wound healing was reduced with gene activation. Discussion While the chitosan layer of the bilayer scaffold does not integrate into the wound bed it does form a protective covering with enhanced anti-inflammatory cues that support the lower integrating dermal collagen layer yielding optimal anti-fibrotic wound healing. These properties highlight the potential of this chitosan-collagen bi-layered scaffold, suggesting its suitability for promoting enhanced healing of chronic wounds in clinical settings.