Full-Thickness Wounds Treated with FN-Silk to Improve Healing Outcome: An In Vivo Study in Porcine Wounds

The integrity of the skin is essential for protecting the body against external threats and maintaining physiological homeostasis. While several clinical strategies exist for epidermal regeneration, effective methods for dermal regeneration remain limited, often resulting in scar formation and impaired tissue function. This study evaluated the efficacy and safety of fibronectin (FN)-silk, a recombinant spider silk protein functionalized with an FN-derived cell adhesion motif and formulated as a fibrillar foam, in comparison with MatriDerm^®, a clinically available collagen-based dermal matrix, for the treatment of full-thickness wounds. An in vivo porcine wound healing model was used to assess healing outcomes, mechanical properties, and tissue responses following treatment with FN-silk, MatriDerm^®, or NaCl control. A total of 72 wounds were randomly assigned to the three treatment groups. FN-silk foam was extruded to fill the excised wound void, while MatriDerm^® was cut into customized shapes to match each wound. Neither treatment induced signs of tissue toxicity or significant inflammatory responses. FN-silk accelerated early wound healing, demonstrating significantly increased re-epithelialization after 1 week (49% coverage compared to 23% in untreated controls and 34% in MatriDerm^®). Furthermore, FN-silk-treated wounds exhibited significantly higher net elasticity (p < 0.05), indicating improved mechanical properties of the regenerated tissue. Noninvasive measurements revealed comparable skin hydration and temperature across treatment groups, although FN-silk-treated wounds showed a higher melanin index at 12 weeks (p < 0.01). Histological analysis demonstrated gradual FN-silk degradation, with only minor remnants present at the final time point. No significant differences were observed in epidermal thickness or rete ridge formation. Together, these findings indicate that FN-silk is a promising biomaterial for dermal regeneration, promoting accelerated wound healing and favorable mechanical outcomes compared to MatriDerm^®.