Dual-functional DHBA/Zn-hybrid electrospun scaffolds for simultaneous nerve repair and bone regeneration

Abstract Oral and maxillofacial surgeries or trauma (e.g., impacted tooth extraction, jaw fracture, or tumor resection) often lead to concurrent peripheral nerve injury and bone defects, while current collagen/gelatin sponges offer limited therapeutic effects. To address this challenge, we developed innovative electrospun scaffolds (MOF2, MOF4, and MOF6) by in situ synthesis of 3,5-dihydroxybenzoic acid/zinc (DHBA/Zn-MOF) hybrids within a gelatin/polycaprolactone matrix. In vitro, Schwann cells treated with material extracts exhibited enhanced migration, regulated myelin-associated genes (Ngf/Pmp22 upregulated, Ncam downregulated), and increased NGF protein expression via the PI3K pathway. Co-cultured PC12 cells showed increased neurite outgrowth, confirming neural repair potential. Osteoblasts exposed to material extracts showed elevated alkaline phosphatase activity, enhanced mineralization, and upregulated osteogenic genes (Runx2, Alp, and Opg), verifying osteogenic capacity. In vivo, MOF6 scaffolds achieved superior motor function recovery in a rat sciatic nerve crush model (evidenced by increased compound muscle action potentials and reduced gastrocnemius muscle atrophy) and promoted trabecular bone formation in a rat skull defect model (validated by micro-CT and histological analyses). These findings underscore the dual-functional capability of DHBA/Zn-hybrid scaffolds to simultaneously promote nerve repair and bone regeneration, offering a promising therapeutic approach for complex neuro-bone composite injuries in clinical practice.