Dual-delivery of VEGF and NGF by emulsion electrospun nanofibrous scaffold for peripheral nerve regeneration

Controlled delivery of multiple therapeutic agents can be considered an effective approach in nerve injury due to its multifunction. In this study, recombinant human vascular endothelial growth factor (VEGF) and recombinant human nerve growth factor (NGF) were loaded on the surface and in the core of emulsion electrospun poly (L-lactic acid) (PLLA) nanofibrous scaffold, respectively. The in vitro studies showed that VEGF and NGF had a sequential release pattern in which most of the VEFG was released in the first few days but the NGF could be continuously released for > 1 month. The dual-delivery scaffold could enhance the neural differentiation of induced pluripotent stem cells-derived neural crest stem cells (iPSCs-NCSCs) in vitro. Furthermore, this scaffold was applied to a critical sized defect in rat sciatic nerve model. Footprint analysis, electrophysiological tests, and histological analysis revealed that a significant improvement of neovascularization as well as nerve healing after 3 months post-operation could be achieved by dual-delivery of VEGF and NGF. Taken together, the present study indicated that VEGF and NGF in emulsion electrospun nanofibrous scaffold had a synergistic effect on regeneration of vascularized nerve tissue.