Low-Intensity Pulsed Ultrasound Stimulated Hydrogel-Polylactic Acid Composite Scaffolds: A Dual-Cue Approach for Enhanced Rotator Cuff Healing

Rotator cuff tear is a prevalent musculoskeletal condition. The complex soft-to-hard transition at the tendon-bone interface (TBI) makes the healing process more challenging than in homogeneous tissues. In this study, low-intensity pulsed ultrasound (LIPUS), a non-invasive modality for bone repair, was employed as an external stimulus in combination with tissue engineering. A composite scaffold, designated as BMP-2/bFGF@GM-PLA, was developed by incorporating a gelatin-methacryloyl (GM) hydrogel loaded with bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) into polylactic acid (PLA) electrospun fibers. Under LIPUS stimulation, the BMP-2/bFGF@GM-PLA scaffold effectively promotes migration, osteogenic and tenogenic differentiation of the bone marrow mesenchymal stem cells through synergistic mechanical and chemical cues. In vivo, the combined system of BMP-2/bFGF@GM-PLA implantation and post-operative LIPUS treatments significantly enhances healing in rat models of rotator cuff tear, as evidenced by enhanced biomechanical properties, accelerated bone defect repair, and improved histological structure of the TBI. This study proposes a novel approach that combines LIPUS stimulus with acoustic-responsive biomaterial scaffolds, thereby coordinating mechanical and chemical cues to facilitate rotator cuff healing.