Field-ridge structured bioactive Zn-based scaffold promotes bone regeneration via cellular mechanotransduction.

Abstract

Large bone defects often exhibit impaired healing due to the absence of a favorable osteoinductive microenvironment at the defect core. Drawing inspiration from agricultural field-ridge structures, we developed a Zn-based metallic biomimetic scaffold, designated the "Osteogenic Conditioning Scaffold" (OCS), with a tailored porous architecture and groove-ridge-like surface texture to enhance bone conduction and osteogenesis. Using a rationally designed laser scanning strategy in laser powder bed fusion (L-PBF), we spatially regulated melt-track overlap to generate ordered groove-ridge-like textures, enabling the one-step fabrication of 3D-printed Zn-0.4Li porous scaffolds with oriented surface textures. <i>In vitro</i> evaluations revealed that the OCS promoted the adhesion and spreading of bone marrow mesenchymal stem cells (BMSCs), activated mechanotransduction signaling (upregulated VCL, phosphorylated FAK, and nuclear translocation of YAP), and triggered epigenetic regulator shifts (downregulated KDM5A and upregulated KDM6A), thereby enhancing osteogenic differentiation. In a rabbit critical-sized calvarial defect model, the scaffold significantly accelerated new bone formation and osseointegration, with consistent mechanistic signatures validated <i>in vivo</i>. This robust, stable, and readily tunable fabrication approach enables the synergistic integration of osteogenic bioactivity from Zn²⁺ and Li⁺ ions with the osteoinductive effects of hierarchical porous and groove-ridge-like textures, offering a promising strategy for the repair of large bone defects.