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 in-situ 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. • A continuous frost-like graphene pathway was constructed via in-situ reduction-induced phase separation. • Enhanced cellular adhesion and deep infiltration enabled by continuous cell migration pathways. • Accelerated calcium deposition and osteogenic mineralization through ion channel and cell-ECM interaction modulation. • Controlled metabolic clearance and excellent biocompatibility of graphene enable safe bone integration.
Yu et al. (2026) studied this question.