A Bioinspired Force-Inducible Hydrogel Conduit for Peripheral Nerve Regeneration

Long-gap peripheral nerve injury (PNI) presents a significant challenge since the growth cone at the proximal end fails to detect and respond to neurotrophic signals from the distal ends, even when bridging the long-gap with nerve guide conduits (NGCs), impeding the motivated growth of new axons. In this study, a bioinspired force-inducible multichannel nerve guide conduit (FI-MNGC) is developed, constructed from silk fibrin-based hydrogel. By mimicking the gradient capillary architectures in vascular plants, the FI-MNGC utilizes a multichannel design with gradient apertures that can self-generate enhanced capillary forces, which not only promote directed axon growth but also guide the directed delivery of Schwann cells (SCs) toward the distal ends of the injured nerve, without the need for any external stimuli. Implemented in a rat model with a 16 mm and a rabbit model with a 30 mm long-gap sciatic nerve defect, the FI-MNGC significantly accelerates the recovery process, paralleling the efficacy of autografts in nerve regeneration, functional recovery, and repair speed. This innovative approach offers a promising alternative to autografts, enhancing the potential for clinical implementation in long-gap PNI therapies.