A bioactive NGF-functionalized dermal scaffold promotes functional and morphological recovery with favorable hematological profiles after sciatic nerve injury in rats.

Peripheral nerve injuries involving complete nerve transection remain a major clinical challenge due to limited regenerative capacity and insufficient functional recovery after conventional repair strategies. Bioactive nerve guidance scaffolds capable of providing structural support and localized delivery of neurotrophic signals have emerged as promising approaches for enhancing peripheral nerve regeneration. In this work, I developed a tubular nerve repair scaffold from decellularized dermal extracellular matrix and incorporated nerve growth factor (NGF) into the construct to provide localized neurotrophic support following sciatic nerve transection in rats. The regenerative potential of NGF-functionalized dermal collagen-derived scaffolds (DerCS-NGF) was evaluated in a rat sciatic nerve transection model and compared with untreated defects and unloaded scaffold groups. Functional recovery was assessed using behavioral tests, while histological, stereological, molecular, hematological, and biochemical analyses were performed after 12 weeks. Implantation of DerCS-NGF significantly enhanced nerve regeneration, as demonstrated by increased nerve fiber density, improved myelin sheath thickness, preservation of sensory and motor neuronal populations, reduced gastrocnemius muscle atrophy, and superior functional recovery compared with untreated and unloaded scaffold groups. Furthermore, NGF delivery through the dermal scaffold significantly reduced local inflammatory cytokine levels, including TNF-α, IL-1β, and IFN-γ, and upregulated the expression of regeneration-associated genes, including NF200, S100, and βIII-tubulin. Hematological and biochemical parameters, including RBC, HGB, WBC, lymphocytes, neutrophils, MPV, ALT, AST, creatinine, and urea, were additionally assessed at the 12-week endpoint to evaluate systemic responses following scaffold implantation. Overall, this study demonstrates that the NGF-functionalized dermal extracellular matrix-derived scaffold promotes structural and functional recovery after sciatic nerve injury and provides a bioactive platform with a favorable systemic safety profile for the repair of severe peripheral nerve injuries.