Low‐Intensity Pulsed Ultrasound Combined With Mild Hyperthermia Can Promote the Healing of Rotator Cuff Injuries in a Rabbit Model

PURPOSE: To investigate the synergistic effects of low-intensity pulsed ultrasound (LIPUS) and mild hyperthermia (MH) on tendon-to-bone healing in a rabbit rotator cuff repair model and to explore underlying cellular mechanisms using bone marrow-derived mesenchymal stem cells (BMSCs). METHODS: In vitro, BMSCs were exposed to various LIPUS intensities and MH temperatures to determine optimal conditions based on proliferation, migration, and chondrogenic differentiation assessed by multiple assays. In vivo, rabbits with infraspinatus tendon detachment and repair were randomly assigned to control, LIPUS, MH, or combined treatment groups. Interventions were applied daily beginning shortly after surgery, and tendon-bone healing was evaluated at defined postoperative intervals using histological, immunohistochemical, micro-CT, and biomechanical analyses. RESULTS: Optimal LIPUS and MH conditions significantly enhanced BMSC proliferation compared with other settings. Combined LIPUS and MH treatment further promoted BMSC proliferation, migration, and chondrogenic differentiation relative to either treatment alone. In vivo, the combined group showed the most organized collagen alignment, robust fibrocartilage regeneration, highest bone volume fraction, and significantly improved biomechanical strength at both time points (P < .01). Micro-CT and histological analyses confirmed superior osteochondral integration in the combined group. CONCLUSIONS: The combination of LIPUS and MH significantly enhanced BMSCs proliferation, chondrogenic differentiation, and tendon-bone healing in a rabbit rotator cuff repair model. Compared with single interventions, the combined treatment led to improved histological organization, increased COL-II expression, and higher biomechanical strength at the tendon-bone interface. CLINICAL RELEVANCE: The combination of LIPUS and MH significantly enhances tendon-to-bone healing in rotator cuff injuries, offering a promising non-invasive therapeutic strategy for improving repair quality and functional recovery.