Osteogenic tailoring of oriented bone matrix organization using on/off micropatterning for osteoblast adhesion on titanium surfaces

Titanium (Ti) implants are well known for their mechanical reliability and chemical stability, crucial for successful bone regeneration. Various shape control and surface modification techniques to enhance biological activity have been developed. Despite the crucial importance of the collagen/apatite bone microstructure for mechanical function, antimicrobial properties, and biocompatibility, precise and versatile pattern control for regenerating the microstructure remains challenging. Here, we developed a novel osteogenic tailoring stripemicropatterned MPC-Ti substrate that induces genetic-level control of oriented bone matrix organization. This biomaterial was created by micropatterning 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer onto a titanium (Ti) surface through a selective photoreaction. The stripe-micropatterned MPC-Ti substrate establishes a distinct interface for cell adhesion, robustly inducing osteoblast cytoskeleton alignment through actin cytoskeletal alignment, and facilitating the formation of a bone-mimicking-oriented collagen/apatite tissue. Moreover, our study revealed that this bone alignment process is promoted through the activation of the Wnt/ beta-catenin signaling pathway, which is triggered by nuclear deformation induced by strong cellular alignment guidance. This innovative material is essential for personalized next-generation medical devices, offering high customizability and active restoration of the bone microstructure. Statement of Significance: This study demonstrates a novel osteogenic tailoring stripe-micropatterned MPC-Ti substrate that induces osteoblast alignment and bone matrix orientation based on genetic mechanism. By employing a light-reactive MPC polymer, we successfully micropatterned the titanium surface, creating a biomaterial that stimulates unidirectional osteoblast alignment and enhances the formation of natural bonemimetic anisotropic microstructures. The innovative approach of regulating cell adhesion and cytoskeletal alignment activates the Wnt/beta-catenin signaling pathway, crucial for both bone differentiation and orientation. This study presents the first biomaterial that artificially induces the construction of mechanically superior anisotropic bone tissue, and it is expected to promote functional bone regeneration by enhancing bone differentiation and orientation-targeting both the quantity and quality of bone tissue.