Peripheral nerve injury is a serious medical problem with limited surgical and clinical treatment options. It is of great significance to integrate multiple guidance cues in one platform of nerve guidance conduits (NGCs) to promote axonal elongation and functional recovery. Here, a multi-functional NGC is constructed to promote nerve regeneration by combining ordered topological structure, density gradient of biomacromolecular nanoparticles, and controlled delivery of biological effectors to provide the topographical, haptotactic, and biological cues, respectively. On the surface of aligned polycaprolactone nanofibers, a density gradient of bioactive nanoparticles capable of delivering recombinant human acidic fibroblast growth factor is deposited. On the graded scaffold, the proliferation of Schwann cells is promoted, and the directional extension of neurites from both PC12 cells and dorsal root ganglions is improved in the direction of increasing particle density. After being implanted in vivo for 6 and 12 weeks to repair a 10-mm rat sciatic nerve defect, the NGC promotes axonal elongation and remyelination, achieving the regeneration of the nerve not only in anatomical structure but also in functional recovery. Taken together, the NGC provides a favorable microenvironment for peripheral nerve regeneration and holds great promise for realizing nerve repair with an efficacy close to autograft.

No abstract

Fibrous scaffolds have shown their advantages in tissue engineering, such as peripheral nerve regeneration, while most of the existing fiber-shaped scaffolds are with simple structures, and the in vitro performance for nerve regeneration lacks systematic analysis. Here, novel nerve-on-a-chip derived biomimicking microfibers for peripheral nerve regeneration are presented. The microfibers with controllable core-shell structures and functionalities are generated through capillary microfluidic devices. By integrating these microfibers into a multitrack-architectured chip, and coculturing them with nerve cells as well as gradient bioactive elements, the nerve-on-a-chip with the capabilities of systematically assessing the performances of nerve fiber formation in the hollow microfibers at in vitro level is constructed. Based on a rat sciatic nerve injury model, the rapid promotion ability is demonstrated of optimized microfibers in nerve regeneration and function recovery in vivo, which implies the credibility of the nerve-on-a-chip on biomimicking microfibers evaluation for peripheral nerve regeneration. Thus, it is convinced that the organ-on-a-chip will undoubtedly open up a new chapter in evaluating biological scaffolds for in vivo tissue engineering.