Trifecta of Tendon Regeneration: 3D Bioprinted Scaffolds Recapitulate Hierarchical Interfaces From Muscle-to-Bone.

Abstract

Functional tendon regeneration faces dual challenges: limited self-healing capacity and the complexity of three hierarchical interfaces-the myotendinous junction (MTJ), tendon proper, and bone-tendon junction (BTJ). Conventional repair strategies often fail to address these critical barriers, resulting in a higher probability of re-tear after the surgery. 3D bioprinting emerges as a transformative approach, enabling recapitulation of these multiscale interfaces through precise structural design, functional material gradients, and bioactive integration. This review comprehensively analyzes recent advances in bioprinted tendon scaffolds, focusing on tripartite structural-biological requirements across MTJ, tendon proper, and BTJ microenvironments. Critical examination is given to the synergistic regulation of bioprinting technologies and material diversity for replicating native mechanobiological cues. Furthermore, innovative scaffold design strategies target each interface's unique regeneration challenges: anisotropic muscle-tendon integration, load-bearing tendon remodeling, and mineralized osteotendinous regeneration. Finally, translational roadblocks and future directions are assessed, emphasizing in vivo functional reintegration of the muscle-to-bone continuum and scalable manufacturing for clinical adoption.