A continuous adhesion-enhanced osteogenic pathway in artificial scaffold drives cellular infiltration and condensed mineralization for rapid bone regeneration

Enhancing the cellular infiltration and mineralization capacity of bone scaffolds can effectively address the challenges of bone nonunion and the prolonged osteogenic repair cycle, particularly in the treatment of critical-sized bone defects. Conventional bone scaffolds, whether composed of inorganic materials or fabricated via 3D-printed titanium alloy, frequently hinder seamless cellular integration due to inherent structural discontinuities, such as granular interfaces or layer-by-layer striations. Here, we address this limitation by employing graphene, not merely as a filler, but as a continuous surface modifier within a 3D scaffold. Through an <i>in-situ</i> reduction-induced phase separation technique, we engineered a long-range, frost-like graphene surface at a low graphene concentration of 3.4 wt% in fabricated scaffold. The resulted unique architecture establishes a continuous pathway for cell migration, leading to significantly enhanced cellular adhesion, accelerated infiltration, rapid calcium deposition and bone ingrowth. We demonstrate that these pro-osteogenic effects are mediated through the modulation of genetic pathways related to ion channels and cell-extracellular matrix interactions. Furthermore, the scaffolds show excellent biocompatibility, integrating seamlessly into nascent bone tissue without eliciting inflammation or immune rejection. Thus, this strategy of constructing continuous cell-migration surfaces presents a promising and scalable platform for the regeneration of critical-sized bone defects.