Advanced engineering strategies for biomaterial scaffolds application in tendon-bone interface regeneration

Tendon-bone interface injuries, such as rotator cuff tears and anterior cruciate ligament ruptures, remain challenging due to the enthesis's complex structure and poor healing capacity. Conventional repair often fails to restore the fibrocartilaginous transition, causing mismatched integration and high retear rates. Biomaterial-based scaffolds provide biomechanical support and bioactive regulation, showing great promise for regeneration. Recent advances span natural polymers, synthetic polymers, bioceramics, and composites, with designs evolving from monophasic to multiphasic, gradient-based, and functionalized scaffolds. Emerging strategies emphasize immunomodulation, bio-signal delivery, and physical responsiveness, establishing a structure-signal-function paradigm to guide multi-tissue integration. However, translation faces major barriers, including inadequate animal models, manufacturing and scalability challenges, long-term safety concerns, and regulatory complexity, as well as the need to balance personalization with cost. Future directions point to intelligent biomaterials, AI-driven design, and integrated translational frameworks to bridge preclinical research and clinical application. Overall, advanced scaffold engineering offers transformative potential for functional tendon-bone regeneration, but successful translation will depend on close collaboration among biology, materials science, engineering, and medicine.