Mitochondrial transfer and transplantation in tendon, ligament, and enthesis repair: current evidence, mechanistic rationale, and regenerative opportunities.

Tendon, ligament, and enthesis injuries often heal through fibrovascular scar rather than restoration of native matrix organization, mechanical function, and graded interface architecture. Mitochondrial dysfunction has emerged as a recurrent feature of these repair failures, linking impaired bioenergetics, oxidative stress, persistent inflammation, cell death, and defective matrix remodeling. In parallel, mitochondria are increasingly recognized as transferable organelles that can move between cells or be delivered therapeutically as isolated mitochondria, mitochondria-rich extracellular vesicles, or engineered mitochondria-based products. This review examines mitochondrial transfer and transplantation as organelle-level mechanisms and therapeutic strategies in tendon, ligament, rotator cuff muscle, and enthesis-related repair. We define key terminology and characterization requirements for verifying mitochondrial identity, integrity, uptake, and function, and synthesize evidence across disease-relevant repair contexts. Direct preclinical support is most developed in tendinopathy/tendon repair and rotator cuff tear-associated muscle degeneration, whereas evidence in anterior cruciate ligament-related repair remains early, and application to enthesis regeneration or tendon-to-bone healing is still largely hypothesis-driven. Further therapeutic development will depend on defined donor sources, product identity, indication-specific potency, tissue retention, dosing strategies, safety assessment, disease-relevant models, and functional endpoints.