Tunable Wrinkled Topographies Reveal Feature-Size-Dependent Regulation of Neuronal and Glial Spatial Organization

Purpose Mechanical cues presented by biomaterial surfaces are powerful regulators of cellular behavior, yet how topographical feature size differentially regulates neuronal and glial spatial organization remains poorly understood. Although anisotropic surface architectures have been shown to promote neural alignment and neurite outgrowth, systematic comparisons across multiple topographical regimes within a common material platform have been limited. Methods To address this gap, we developed a scalable wrinkle-based nanofabrication platform capable of generating anisotropic MXene topographies spanning characteristic nano-, submicron-, and micron-scale regimes. By varying multilayer thickness, the platform enabled systematic shifts in characteristic wrinkle dimensions while maintaining a common material composition and surface chemistry. Results Using this platform, we found that distinct regenerative processes exhibit different responses across the topographical regimes. While all wrinkled topographies effectively aligned Schwann cells, the nanoscale topographies produced the greatest cellular elongation. In contrast, submicron and microscale topographies showed greater early neuronal alignment, whereas the submicron topography showed the greatest neurite extension while maintaining strong directional guidance following differentiation. Conclusions These findings reveal distinct structure–response relationships between topographical regimes and neural guidance behavior. More broadly, this scalable wrinkle-based platform provides a versatile strategy for investigating topography-mediated cell–material interactions and informing the design of next-generation regenerative neural interfaces.