Repair of critical-sized bone defects remains a major clinical challenge because many implants lack both the structural guidance and multimodal biological signals necessary for rapid, vascularized regeneration. To address these limitations, we developed and validated a multifunctional bone-tissue engineering scaffold to repair critical-sized bone defects. Using a modified directional freeze-casting method, we fabricated a scaffold with a multiscale biomimetic architecture. The scaffold reproduces structural features of natural bone ranging from the micron-scale Haversian/Volkmann systems to the millimeter-scale cortical–trabecular organization. The scaffold is co-functionalized with β-tricalcium phosphate (β-TCP) nanoparticles and black phosphorus (BP) nanosheets to generate synergistic therapeutic effects. The biomimetic architecture provides physical guidance that directs cell alignment and markedly improves tissue infiltration. Sustained release of osteogenic ions from β-TCP promotes osteogenic differentiation, while BP enables near-infrared (NIR)-mediated mild photothermal stimulation that enhances angiogenesis, which is a key and often limiting step in bone regeneration. In a subcutaneous ectopic osteogenesis model in nude mice, all scaffold components demonstrate clear therapeutic efficacy. Furthermore, in a rabbit radial critical-sized defect model, the functionalized scaffolds significantly promote vascularized bone formation, achieving complete functional bridging of the defect. By integrating precise structural biomimicry with multimodal bioactive synergistic strategies, this scaffold establishes a robust and innovative design paradigm for advanced bone regeneration biomaterials.
Luo et al. (2026) studied this question.