Process Integration of Decellularization and Terminal Sterilization for Acellular Piscine Dermal Matrix as a Dermal...

Acellular dermal regeneration templates (ADRTs) are widely employed for wound management; however, most commercial products are derived from mammalian tissues, posing potential risks of zoonotic disease transmission. Acellular piscine dermal matrices (APDMs) have emerged as promising, safer alternatives. Despite their potential, the specific impacts of critical manufacturing parameters, namely source material, decellularization protocol, and terminal sterilization, on APDM performance remain systematically underexplored, hindering their clinical translation. In this study, we systematically investigated the effects of these processing steps on the physicochemical and biological properties of APDMs derived from two representative teleost species (tilapia and salmon). The results demonstrated that both decellularization and sterilization processes profoundly affected the materials' morphological architecture, thermal stability, in vitro/in vivo degradation kinetics, and overall biocompatibility. Specifically, tilapia-derived APDM exhibited superior thermal stability (Ti > 37°C), making it more suitable for mammalian physiological applications. Among the processing variants, alkaline decellularization achieved a more thorough removal of immunogenic cellular components (DNA and glycosaminoglycans (GAGs)) while preserving the collagenous matrix. Furthermore, terminal sterilization via ethylene oxide (ETO) or wet γ-irradiation (γ-W) mitigated the structural destruction and rapid enzymatic degradation typically induced by dry γ-irradiation (γ-D). Notably, the optimized formulation (T-NE: tilapia skin processed via alkaline decellularization and ETO sterilization) presented an ideal balance of structural integrity and controlled biodegradation. In a full-thickness defect model, T-NE supported robust vascularization and accelerated the maturation of granulation tissue, exhibiting optimal wound integration. Collectively, this study establishes a comprehensive process-structure-function framework, confirming T-NE as a highly translatable dermal regeneration scaffold for complex wound therapy.