Recent advances in 3D printing biomimetic gradient scaffolds for tendon-bone interface repair

Repair of tendon-bone interface (TBI) injuries remains a major clinical challenge, primarily due to the difficulty in reconstructing the native interface's complex gradient architecture. The emergence of biomimetic gradient scaffolds offers a promising solution by replicating the hierarchical organization and functional heterogeneity of the TBI within a single construct, thereby achieving both structural biomimicry and functional tissue regeneration. With its high controllability and capability for patient-specific customization, 3D printing has become a pivotal technology for the design and fabrication of such gradient scaffolds. This review first outlines the developmental process of the TBI and the characteristic features of its injury-healing mechanism, emphasizing its unique histological and biomechanical requirements. Subsequently, current 3D printing strategies applied in the fabrication of biomimetic gradient scaffolds are systematically summarized, including fused deposition modeling (FDM), selective laser sintering/melting (SLS/SLM), and bioprinting. The suitability and limitations of natural polymers, synthetic polymers, and inorganic metallic materials in scaffold fabrication are also discussed. Furthermore, this review highlights recent advances in multidimensional biomimetic design concepts such as mimicking structural and mineralization gradients, integrating bioactive factors, and employing decellularized extracellular matrix based strategies that collectively promote TBI reconstruction and functional recovery. In summary, this work provides a comprehensive overview of recent advances in 3D-printed biomimetic gradient scaffolds for TBI repair. It highlights key printing technologies, material selection principles, and biomimetic design strategies, with the aim of guiding future research and clinical translation in TBI regeneration. • 3D printing precisely recreates TBI multiscale gradients, enabling spatially controlled structural, compositional, and mechanical transitions. • Natural/synthetic polymers plus bioactive nanoparticles synergistically tune biocompatibility, degradability, and osteo-/teno-induction. • Bioprinting and 4D smart-responsive printing enable spatiotemporal control of cells and remodeling, advancing clinical TBI repair.