Progress on rotator cuff tendon-to-bone interface tissue regeneration and repair.

Abstract

Tendon-bone interface (TBI) injuries, typified by rotator cuff tears, are common musculoskeletal disorders. Their intrinsic healing capacity is limited by pathological conditions such as local hypoxia, oxidative stress, and secondary fatty infiltration, which prevent spontaneous restoration of the native four-zone gradient architecture. As a result, functional tissue is often replaced by fibrovascular scar tissue with inferior mechanical properties. Because surgical repair alone cannot precisely recreate this complex interface, highly biomimetic tissue-engineered regenerative strategies have emerged as a promising alternative. Beginning with the anatomy of the rotator cuff and the key challenges in treating rotator cuff injuries, this review summarizes the spatiotemporal complexity, physiological vulnerability, and rehabilitation challenges of the TBI. It further discusses the structural composition, fabrication methods, mechanisms of action, and clinical applications of tissue-engineered strategies for TBI regeneration. These approaches use scaffolds based on hydrogels, decellularized matrices, polymers, collagen, and nanoparticles, which can be functionally engineered through graded architectures, aligned structures, mineralization cues, and tailored interfacial properties. In parallel, active components such as stem cells, exosomes, and bioactive factors can be incorporated to recreate a three-dimensional microenvironment that supports tissue regeneration, attenuates inflammation, regulates bone metabolic homeostasis, and promotes vascular regeneration. Although substantial progress has been made in tissue-engineered repair of rotator cuff injuries, future studies should place greater emphasis on digitally enabled and coordinated scaffold design, more robust safety assessment, and quantitative evaluation of therapeutic efficacy. Mechanistic studies and translational research will also be essential to bridge the gap between basic research and clinical application.