Intelligent 3D bioprinting platforms for complex bone–tissue interfaces: Mechanisms, biofabrication, and regenerative applications

Bone–tissue interfaces—including anatomically defined structures (osteochondral, tendon-to-bone, ligament-to-bone interfaces) with characteristic compositional gradients and functional biological interactions (bone–immune, bone–vascular, and bone–nerve interactions) that regulate systemic regenerative processes—represent critical repair targets. Traditional strategies fail due to mechanical mismatch and poor integration. Three-dimensional (3D) bioprinting enables precise, patient-specific construction of scaffolds with multiple spatial gradients through co-deposition of diverse biomaterials and cell types, transcending structural mimicry to coordinate multilineage differentiation and microenvironmental regulation. This review 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 mismatches in immune regulation, and unpredictable mechanical integration. Future directions, including organ-on-chip integration, artificial intelligence-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.