Wood-Inspired Bioadaptable Material with Neurite Outgrowth Guidance Structures, Superior Cell Microenvironment, and Long-Term Structural Stability

Abstract

Abstract Nerve injuries present serious clinical challenges worldwide. Autologous nerve transplantation is recognized as the gold standard to treat long-gap peripheral nerve defects, but its application has inherent limitations. This situation highlights the need for innovative repair strategies. Promoting and guiding neurite outgrowth is a key step in nerve regeneration, as directional neurite extension facilitates the reconstruction of neural networks. Inspired by the oriented microstructure and biological properties of natural wood, we developed a structurally stable wood hydrogel by integrating a mechanically robust wood-derived cellulose framework with a soft gelatin methacrylate (GelMA) hydrogel matrix. This biomimetic composite demonstrated enhanced capacity to induce directional neurite outgrowth in vitro, long-term structural stability, and significantly altered gene expression profiles associated with cytoskeletal reorganization and cellular motility. Mechanistic investigations revealed that the synergistic effects of topographical guidance cues and mechanical properties were associated with suppression of the RhoA/ROCK1 pathway. The developed wood hydrogel combines oriented architecture, mechanical compatibility, high water absorbency, and long-term structural stability without sacrificing the intrinsic advantages of hydrogel systems. These findings suggest that this hard–soft hybrid biomimetic strategy provides an effective platform for guiding aligned neurite outgrowth and offers a promising design concept for future nerve tissue engineering applications.