Intelligent 3D bioprinting platforms for complex bone-tissue interfaces: Mechanisms, biofabrication, and regenerative applications
Bone-tissue interfaces—including both anatomically-defined structures (osteochondral, tendon-to-bone, ligament-to-bone) with characteristic compositional gradients, and functional biological interactions (bone-immune, bone-vascular, bone-nerve that regulate systemic regenerative processes)—represent critical repair targets. Traditional strategies fail due to mechanical mismatch and poor integration. 3D bioprinting enables precise, patient-specific construction of multi-gradient scaffolds through co-deposition of diverse biomaterials and cell types, transcending structural mimicry to coordinate multilineage differentiation and microenvironmental regulation. This review systematically synthesizes advances in six interface categories, moving beyond study-by-study description to comparative analysis. We distinguish structural approaches (pore regulation, fiber reinforcement, microchannels) that primarily improve biomimicry from bioactive strategies (growth factors, hypoxia, immunomodulation) that direct cell fate, clarify experimental validation levels (in vitro vs. animal models), and delineate appropriate clinical scenarios. Key bottlenecks include insufficient deep vascularization, temporal immune regulation mismatches, and mechanical integration unpredictability. Future directions encompassing organ-on-chip integration, AI-driven personalization, and organoid-inspired self-organization are outlined. 3D bioprinting emerges as a unified platform for both anatomical interface reconstruction and functional biological orchestration in regenerative medicine.
