Beyond the enthesis: Evidence and translational challenges for coordinated multi-tissue repair in rotator cuff tears

Despite advances in surgical techniques, outcomes after rotator cuff repair remain limited by concurrent biological and mechanical deficits involving the proximal muscle, tendon, enthesis, and peri-fixation bone. Structural reattachment alone does not fully address redox dysregulation, context-dependent inflammatory signaling, disorganized matrix remodeling, bone loss, muscle atrophy, or fatty infiltration. This narrative review evaluates compartment-specific interventions and biomaterial strategies designed to address these interacting constraints. Evidence remains predominantly preclinical and is strongest for tendon-enthesis-bone augmentation through injectable and self-healing hydrogels, fibrous or gradient scaffolds, and responsive or sequential delivery systems. By contrast, proximal muscle preservation has largely been studied separately through pharmacological, physical, metabolic, progenitor-directed, and rehabilitation-based interventions. We define coordinated multi-tissue repair as a therapeutic and evaluation framework aligning anatomically appropriate interventions with structural, biological, mechanical, and functional outcomes. Here, integration denotes spatial or compositional organization within a tendon-enthesis-bone construct, whereas coordination aligns anatomically separate treatment domains through timing, rehabilitation, and shared outcomes. Coordination does not require a single construct spanning all affected compartments. We distinguish direct rotator cuff evidence from transferable findings in related musculoskeletal interfaces and from unvalidated design proposals. Representative platforms are compared in terms of intended roles, mechanical limitations, degradation requirements, manufacturing constraints, safety considerations, and validation needs. Future studies should use matched controls, longitudinal assessment, and compartment-resolved outcomes to determine whether spatial organization, sequential delivery, and anatomically separate muscle-directed treatment provide incremental benefit. Translation will require clinically relevant models and prospective, risk-stratified evaluation.