Nerve growth factor/angiogenin gene activated dermal bioscaffold for nerve repair in cutaneous wound healing

Patients with extensive and deep skin defects treated with dermal scaffolds usually emphasize the importance of rapid angiogenesis, while overlook the crucial role of skin nerves in regenerative repair. Insufficient early nerve regeneration not only impedes skin reinnervation and angiogenesis, but also damages the synergistic effects among them, eventually hinders healing quality. Nerve growth factor (NGF) has shown potent potential in peripheral nerve regeneration and promotion of angiogenesis. Angiogenin (ANG) is an independent angiogenic factor, supplying microenvironment needed for neurogenesis. This study presents a dermal scaffold with dual gene activity, fabricated by incorporating nanoparticles (NPs) composed of polyethylenimine (PEI)-chimeric plasmids encoding both NGF and ANG (PEI-plasmid NGF/ANG dermal scaffold (NADS)). Specifically, NADS achieves sustained and in situ release of these two factors, and encourages the repair cells to fulfill their regenerative roles. In vivo experiments confirm the efficacy of NADS in promoting fully functional innervated skin regeneration, inducing the fastest healing rates and rapidly facilitating the formation of a mature vascular network, thus resulting in high-quality wound healing. This approach offers an effective and comprehensive strategy for clinical application.