Cell type-specific response to curvature controls tissue growth dynamics in biomaterial pores

In porous biomaterials, pore diameter and surface curvature are critical parameters governing cell migration, multicellular organization, and subsequent tissue formation, ultimately influencing in vivo performance. However, how different cell types respond to curvature and what determines their specific adaptations remain poorly understood. Here, we expose diverse cell types to precisely controlled, physiologically relevant microgeometries, revealing two distinct cellular strategies for adapting to curvature on channel-like surfaces. We examine how cellular stress modulation and the induction of senescence influence curvature responses and identify a universal predictor of curvature adaptation, linked to focal adhesion distribution across cell types and stress states. Consequently, tissue growth dynamics and final tissue architecture vary significantly between cell types. This mechanistic insight enables the prediction of optimal biomaterial pore diameters for specific cell types, offering a valuable framework for designing biomaterials with tailored cell-instructive properties for targeted tissue engineering applications. • The cellular response to curvature is cell-type dependent, with implications for tissue regeneration and biomaterial design. • Focal adhesion distribution is a key parameter controlling how cells respond and adapt to curvature. • Cell-spanning vs. layer-by-layer growth are alternative mechanisms with consequences for tissue healing speed and structure. • Cell-instructive biomaterials with tailored curvatures can be engineered to address these distinct healing mechanisms.