Development and evaluation of a fish skin-derived acellular dermal matrix for diabetic wound healing: <i>In vitro</i> and <i>in vivo</i> assessment

<b>Introduction:</b> Non-healing diabetic foot ulcers often result in amputation and reduced quality of life. The study objective was to develop and evaluate a novel fish skin-derived acellular dermal matrix (FSADM) for diabetic wound-healing applications, addressing these challenges. <b>Methods:</b> FSADM was fabricated from yellow fin tuna (<i>Thunnus albacares</i>) skin using a decellularization and lyophilization process. The matrix was characterized by Fourier-transform infrared spectroscopy (FTIR). <i>In vitro</i> biocompatibility was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays with L929 fibroblasts and hemocompatibility tests. <i>In vivo</i>, biocompatibility was evaluated through subcutaneous implantation in Sprague-Dawley rats. Wound-healing efficacy was assessed in a streptozotocin-induced diabetic rat model with full-thickness excisional wounds, comparing FSADM with commercial alternatives and untreated controls. <b>Results:</b> FTIR analysis confirmed the preservation of collagen structure in FSADM. <i>In vitro</i> studies demonstrated cytocompatibility with L929 cells and minimal haemolytic activity (0.68 ± 0.034%). Subcutaneous implantation demonstrated good biocompatibility, with a progressive reduction in the inflammatory response. In the diabetic wound model, FSADM-treated wounds exhibited significantly faster closure rates than commercial controls (<i>p</i> < 0.05), achieving 100% closure by day 21, compared to 90% closure in commercial controls. Histological analysis revealed enhanced epithelialization, hair follicle formation, and angiogenesis in FSADM-treated wounds. <b>Conclusion:</b> FSADM demonstrates excellent biocompatibility and superior wound-healing in diabetic conditions compared to commercial alternatives. It presents a promising, sustainable biomaterial for diabetic wound care. Further studies are needed to validate these findings in clinical settings and optimize their therapeutic potential.