Obesity Amplifies the Detrimental Effects of Delayed Repair on Tendon-to-Bone Healing After Rotator Cuff Injury in a Rat Model

Background: Rotator cuff repair outcomes are influenced by systemic metabolic status and tear chronicity. Although obesity and delayed surgery are each linked to poorer healing, whether obesity potentiates the detrimental effects of repair delay on tendon-to-bone healing remains incompletely defined. Hypothesis: Delayed repair would impair tendon-to-bone healing individually, and obesity would exacerbate the consequences of repair delay, resulting in worse structural, functional, and molecular outcomes. Study Design: Controlled laboratory study. Methods: A total of 48 Sprague-Dawley rats were randomly assigned to 4 groups defined by repair timing (early vs delayed) and metabolic status (healthy vs obese). Outcomes were assessed at 4 and 8 weeks postrepair using micro–magnetic resonance imaging (MRI), gait analysis, and histology/immunofluorescence; biomechanical testing and lipidomics were performed at 8 weeks. Results: Across assessments, delayed repair was associated with impaired recovery, and obesity exacerbated these effects, yielding worse outcomes. Specifically, the combined condition exhibited a more unfavorable MRI appearance and gait metrics, collagen architecture, collagen type 3–rich scarring, proteoglycan staining, and cartilage-related marker expression. Notably, lipid infiltration markers FABP4 and perilipin 2 increased by approximately 6-fold ( P < .0001) and 12-fold ( P < .0001), respectively. Lipidomic profiling further revealed a distinct local lipidomic signature. Conclusion: Delayed repair impaired tendon-to-bone healing after rotator cuff tear in this rat model, and obesity further exacerbated the detrimental effects of repair delay, resulting in the weakest structural, functional, and molecular outcomes when both factors co-occur. Clinical Relevance: Once surgery is indicated, repair delay may not carry uniform biological consequences across patient populations. In patients with obesity and a body mass index >30, prolonged delay may impose a disproportionate penalty on tendon-to-bone healing, and therefore heightened consideration of surgical timing is warranted.