Hierarchy Reproduction: Multiphasic Strategies for Tendon/Ligament-Bone Junction Repair

Tendon/ligament-bone junctions (T/LBJs) are susceptible to damage during exercise, resulting in anterior cruciate ligament rupture or rotator cuff tear; however, their intricate hierarchical structure hinders self-regeneration. Multiphasic strategies have been explored to fuel heterogeneous tissue regeneration and integration. This review summarizes current multiphasic approaches for rejuvenating functional gradients in T/LBJ healing. Synthetic, natural, and organism-derived materials are available for in vivo validation. Both discrete and gradient layouts serve as sources of inspiration for organizing specific cues, based on the theories of biomaterial topology, biochemistry, mechanobiology, and in situ delivery therapy, which form interconnected network within the design. Novel engineering can be constructed by electrospinning, 3-dimensional printing, bioprinting, textiling, and other techniques. Despite these efforts being limited at present stage, multiphasic scaffolds show great potential for precise reproduction of native T/LBJs and offer promising solutions for clinical dilemmas.