Fluffy sponge-reinforced electrospun conduits with biomimetic structures for peripheral nerve repair

Tubulation repair of sciatic nerve transection via nerve guide conduits (NGCs) significantly reduces the risk of axon misdirection, but the single-hollow architecture limits the treatment effect of NGCs. Biomimetic functional conduits can be used to build a microarchitecture that is essential for guiding cell migration and promoting tissue maturation, which is a strategy that motivates the development of neuroengineering by modulating nerve development and regeneration. NGCs for the treatment of peripheral nerve system (PNS) injury have exhibited great potential to imitate the complex PNS architecture. Here, a gelatin-perfused poly (lactic-co-glycolic acid) (PLGA) and collagen-based biomimetic electrospun conduit (Gel@PLGA/Col) were fabricated to mimic the complex PNS structure for regenerative medicine applications involving the sciatic nerve. The Gel@PLGA/Col conduit displayed outstanding nerve regeneration performance in a sciatic nerve defect implantation model with a large gap. Additionally, histological analysis of the new nerve tissue demonstrated that the biomimetic electrospun conduit contributed greatly to inducing axon growth and the recovery of nerve continuity, with increases in myelin tissue positivity in newly formed nerve tissue of 14.43% and 13.81% at 6 weeks and 12 weeks, respectively, which was comparable to autologous nerve implantation. Moreover, functional analyses of nerve and muscle tissue showed that the conduits restored synaptic transmission and significantly improved functional recovery after injury. Thus, the fluffy sponge-reinforced electrospun conduit with a biomimetic structure and excellent nerve regeneration ability holds great potential for peripheral nerve repair.