3D TPMS curvature accelerated osteogenesis by enhancing permeability and directing cell orientation

Abstract The curvature of cell adhesion substrates has emerged as a critical geometric parameter influencing cellular fate determination. While its regulatory role is increasingly recognized, the osteogenic effects of complex three-dimensional (3D) curved surfaces remain insufficiently explored. In this study, high-precision two-photonic polymerization 3D printing was utilized to fabricate scaffolds with controlled curvature distributions, achieving unprecedented fidelity between manufactured surfaces and their digital models. Comparative analysis of triply periodic minimal surface (TPMS) scaffolds and conventional truss scaffolds revealed distinct osteogenic mechanisms: zero mean curvature enhanced osteogenic differentiation through improved scaffold permeability, while negative Gaussian curvature promoted bone formation through combined effects of permeability controlling and guided cellular organization. Notably, scaffolds exhibiting broader ranges of negative Gaussian curvature demonstrated superior osteogenesis inductive capacity, as evidenced by enhanced new bone formation in both in vitro and in vivo models. These findings provide mechanistic insights into curvature-dependent osteogenesis, quantitative design principles for TPMS-based bone scaffolds, and experimental validation of curvature optimization strategies. The study establishes a geometric framework for rational scaffold design, advancing the development of high-performance regenerative implants. Keyworks. TPMS, Gaussian curvature, two-photonic polymerization, osteogenesis, bone regeneration.