Decellularized fish swim bladder as a dermal graft: Histological, biomechanical, and in vivo characterization

Effective skin substitutes must create a supportive microenvironment that promotes cell attachment, migration, and integration within the scaffold matrix. Decellularized fish swim bladder (DFSB) scaffolds offer a collagen-rich matrix substitute with promising regenerative potential, although species-specific differences in their performance are not yet fully understood. This study aimed to identify the DFSB scaffold that best promotes cellular infiltration and wound healing, with an emphasis on modulating inflammation. In this study, a novel in vivo approach was developed to directly assess cell–scaffold interactions through the integration of cell migration and quantitative infiltration analyses, enabling a physiologically relevant evaluation beyond conventional in vitro methods. To achieve this DFSBs from four fish species were evaluated for mechanical properties, swelling behavior, and porosity. The scaffold with the most favorable structural characteristics was implanted into full-thickness wounds. Wound-healing parameters and quantitative cell infiltration into the scaffold were assessed on days 1, 3, 5, and 7. The results indicated that Rutilus frisii kutum demonstrated the most suitable properties, including preserved collagen architecture, moderate swelling and porosity. Upon implantation, the scaffold adhered firmly to the wound bed and remained stable throughout healing, enabling direct and continuous scaffold–wound interaction. Cells attached within 24 h and significantly infiltrated deeper into the matrix over time, with marked increases in cell density and penetration depth by day 5 ( p < 0.001). This effective interface corresponded with accelerated wound repair, including earlier epithelialization (day 1), reduced inflammation, and enhanced fibroblast recruitment, angiogenesis, and collagen deposition. In conclusion the Rutilus frisii kutum DFSB scaffold provided a supportive matrix for rapid cell attachment and deep infiltration. Its stable integration with the wound bed enabled continuous cell–scaffold interaction, contributing to inflammation modulation and accelerated healing.