Comparison of biopolymer scaffolds for the fabrication of skin substitutes in a porcine wound model

This study compared three acellular scaffolds as templates for the fabrication of skin substitutes. A collagen‐glycosaminoglycan (C‐GAG), a biodegradable polyurethane foam (PUR) and a hybrid combination (PUR/C‐GAG) were investigated. Scaffolds were prepared for cell inoculation. Fibroblasts and keratinocytes were serially inoculated onto the scaffolds and co‐cultured for 14 days before transplantation. Three pigs each received four full‐thickness 8 cm × 8 cm surgical wounds, into which a biodegradable temporising matrix (BTM) was implanted. Surface seals were removed after integration (28 days), and three laboratory‐generated skin analogues and a control split‐thickness skin graft (STSG) were applied for 16 weeks. Punch biopsies confirmed engraftment and re‐epithelialisation. Biophysical wound parameters were also measured and analysed. All wounds showed greater than 80% epithelialisation by day 14 post‐transplantation. The control STSG displayed 44% contraction over the 16 weeks, and the test scaffolds, C‐GAG 64%, Hybrid 66.7% and PUR 67.8%. Immunohistochemistry confirmed positive epidermal keratins and basement membrane components (Integrin alpha‐6, collagens IV and VII). Collagen deposition and fibre organisation indicated the degree of fibrosis and scar produced for each graft. All scaffold substitutes re‐epithelialised by 4 weeks. The percentage of original wound area for the Hybrid and PUR was significantly different than the STSG and C‐GAG, indicating the importance of scaffold retainment within the first 3 months post‐transplant. The PUR/C‐GAG scaffolds reduced the polymer pore size, assisting cell retention and reducing the contraction of in vitro collagen. Further investigation is required to ensure reproducibility and scale‐up feasibility.