Anisotropic topographies and biological cues can simulate the regenerative microenvironment of nerve from physical and biological aspects, which show promising application in nerve regeneration. However, their synergetic influence on injured peripheral nerve is rarely reported. In the present study, we constructed a bionic microenvironment-inspired scaffold integrated with both anisotropic micro-nanocomposite topographies and IKVAV peptide. The results showed that both the topographies and peptide displayed good stability. The scaffolds could effectively induce the orientation growth of Schwann cells and up-regulate the genes and proteins relevant to myelination. Last, three signal pathways including the Wnt/β-catenin pathway, the extracellular signal–regulated kinase/mitogen-activated protein pathway, and the transforming growth factor–β pathway were put forward, revealing the main path of synergistic effects of anisotropic micro-nanocomposite topographies and biological cues on neuroregeneration. The present study may supply an important strategy for developing functional of artificial nerve implants.

The surface topographies of artificial implants including surface roughness, surface groove size and orientation, and surface pore size and distribution have a great influence on the adhesion, migration, proliferation, and differentiation of nerve cells in the nerve regeneration process. Optimizing the surface topographies of biomaterials can be a key strategy for achieving excellent cell performance in various applications such as nerve tissue engineering. In this review, we offer a comprehensive summary of the surface topographies of nerve implants and their effects on nerve cell behavior. This review also emphasizes the latest work progress of the layered structure of the natural extracellular matrix that can be imitated by the material surface topology. Finally, the future development of surface topographies on nerve regeneration was prospectively remarked.

Peripheral nerve injury has seriously affected patient’s health and life. Schwann cells play an important role in peripheral nerve regeneration. However, the effect of the current tissue engineered scaffolds for promoting Schwann cells growth is still not as good as that of autologous graft. In this study, new developed three-dimensional gellan gum/starch (GG/ST) scaffolds with various printing gap for Schwann cells growth were prepared by 3D printing technology. Various physiochemical characterizations of the printed scaffolds were performed including morphology, rheological behavior, swelling ratio, and degradation behavior. The cytotoxicity and biocompatibility of the scaffolds were evaluated using L929 fibroblasts and RSC96 Schwann cells, respectively. The results displayed that the GG/ST scaffold exhibited a porous network structure. The cross-sectional pore density of the hydrogel had a tendency to increase with the ascending printing gap. The swelling rate and degradation rate of the hydrogel gradually increased and eventually reached an equilibrium state. The rheological test results showed that the scaffolds had good printability. MTT cytotoxicity test and CCK-8 cell proliferation test displayed that the scaffold was nontoxic, and Schwann cells could grow well on the scaffold after 5 days of culture, whereas the number of cells on the scaffold with the printing gap of 3 mm was the largest. These results indicated that the GG/ST scaffold prepared by 3D printing technology may have a potential application in peripheral nerve regeneration.

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The substrate elasticity and topographical guidance are crucial factors for regulating tissue regeneration. However, the synergistic effects of both cues on peripheral nerve regeneration are still unclear. Herein, the polyacrylamide/chitosan...

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Biocompatible and morphable hydrogels capable of multimode reprogrammable, and adaptive shape changes are potentially useful for diverse biomedical applications. However, existing morphable systems often rely on complicated structural designs involving cumbersome and energy-intensive fabrication processes. Here, we report a simple electric-field-activated protein network migration strategy to reversibly program silk-protein hydrogels with controllable and reprogrammable complex shape transformations. The application of a low electric field enables the convergence of net negatively charged protein cross-linking networks toward the anode (isoelectric point plane) due to the pH gradient generated in the process, facilitating the formation of a gradient network structure and systems suitable for three-dimensional shape change. These tunable protein networks can be reprogrammed or permanently fixed by control of the polymorphic transitions. We show that these morphing hydrogels are capable of conformally interfacing with biological tissues by programming the shape changes and a bimorph structure consisting of aligned carbon nanotube multilayers and the silk hydrogels was assembled to illustrate utility as an implantable bioelectronic device for localized low-voltage electrical stimulation of the sciatic nerve in a rabbit.