Fish skin grafts for human wound healing: mechanistic evidence, clinical performance, application strategies and translational challenges - a review.

Marine-derived fish skin grafts, particularly those obtained from tilapia and cod, represent promising biomaterials for the management of chronic and complex wounds. Their extracellular matrix is rich in type I collagen, glycosaminoglycans, bioactive peptides, and other biologically active constituents that provide a supportive microenvironment for cellular proliferation, angiogenesis, immune modulation, and tissue regeneration. The structural and biochemical characteristics of fish skin grafts promote cellular adhesion and migration, extracellular matrix remodeling, granulation tissue formation, and re-epithelialization. Their inherent antimicrobial and anti-inflammatory properties may also contribute to infection control and modulation of the wound microenvironment, particularly in chronic wounds susceptible to persistent microbial colonization. Integration of fish skin-derived scaffolds with advanced hydrogel-based delivery systems may further enable controlled therapeutic release and maintenance of an optimal wound-healing environment. Clinical applications have expanded to include diabetic foot ulcers, venous leg ulcers, burns, surgical wounds, and other complex injuries. Nevertheless, important challenges remain, including variability in processing and sterilization methods, product standardization, potential immunogenicity, regulatory approval, graft integration, and optimization of application protocols. This review critically examines the biological mechanisms, clinical applications, therapeutic outcomes, technological advances, and ethical considerations associated with fish skin grafts and highlights current barriers and future priorities for their broader translation into advanced wound care.