Self-Adaptive All-In-One Delivery Chip for Rapid Skin Nerves Regeneration by Endogenous Mesenchymal Stem Cells

Skin wound therapy aims not only to restore skin protection but also to recover excitation functions through nerve regeneration. During the restoration of skin nerves, the recruitment of endogenous stem cells and promotion of neuronal regeneration on site work stepwise are foundations of in situ regeneration. However, current therapeutic systems usually execute each process separately, leading to limited regeneration and recovery of excitation functions. Herein, a novel self-adaptive all-in-one delivery chip (G:P:Al-Chip) is constructed that combines therapeutic protein release, gene delivery, and electrical conduction in a single microfluidic chip by 3D coaxial printing. G:P:Al-Chip consists of an outer conductive hydrogel shell anchored with chemokine and an inner microchannel filled with enzyme-initiated vector/plasmid DNAs microcomplexes. G:P:Al-Chip delivers chemokine, functional plasmid DNAs, and promotes electrical conduction with a self-adaptive program that significantly enhances the recruitment of endogenous mesenchymal stem cells and promotes neuronal regeneration. G:P:Al-Chip is shown to enhance nerve regeneration with excitation functions within 23 days. G:P:Al-Chip organizes recruitment and neuronal regeneration cues along with bioelectrical signal in one degradable chip for accelerated skin nerve regeneration.