Crystalline Topographical Construction: Endogenous Grooves As Physical Cues for Stem Cell Regulation in Bone Regeneration

Micro/nano-topographical cues are potent regulators of cellular behavior and function. However, conventional fabrication techniques (e.g., photolithography, nanoimprinting) rely on complex exogenous processing that often induces surface energy loss and impairs biological signal transduction efficiency. Herein, we report a controllable endogenous topographical construction strategy leveraging strain-induced crystalline phase transition in poly(lactide-glycolide-ε-caprolactone) (PLGCL) to spontaneously engineer surface topography. We demonstrate that anisotropic microgrooves-generated via stretch-induced crystal transformation within a critical dimensional range-exert decisive control over bone marrow stromal cell (BMSC) osteogenic differentiation. Mechanistically, an optimal topographical window was identified wherein groove dimensions promote integrin clustering via contact guidance, driving focal adhesion maturation, actomyosin contraction, RhoA/ROCK pathway activation, and YAP nuclear translocation. This cascade enhances BMSC osteogenic differentiation efficiency. Notably, the engineered topography induced heterogeneity within the stem cell population: the early recruitment driven by SDF-1α synergized with the microgroove mediated osteogenic differentiation in the mid to late stage, while mechanical signals dependent on surface curvature/orientation led to differences in differentiation, thereby contributing to stem cell regulation and bone repair. Concomitantly, the film’s rapid early-phase release gradient of SDF-1α effectively recruits endogenous BMSCs to the defect site, replenishing the stem cell pool for repair. In a rat calvarial cranial defect model, SDF-1α-functionalized films exhibited superior regenerative outcomes. Collectively, this work establishes an endogenous topographical construction paradigm, where stretch-induced microgrooves act as physical-mechanical cues instructing stem cell differentiation. Synergizing with chemical cues, this strategy enables precise, cell-free therapeutic repair, offering a new perspective for designing regenerative materials.