Exosome enriched serum enhances engineered ligament mechanics and collagen content with no additional benefit of resistance exercise

Following resistance exercise, systemic changes foster improved functionality of tendons and ligaments. Post-exercise, muscle tissue releases exosomes that are thought to facilitate inter-tissue communication. To determine the potential role of exosomes in the exercise-induced adaptations of tendons and ligaments, we modified our engineered human ligament (EHL) model to work with exosome-enriched serum. Treatment of the EHLs with exosomes enriched from fetal bovine serum (fbEXO) resulted in enhanced ligament mechanics and increased collagen content in a dose-response fashion (maximum tensile load [MTL]: 10 %: 0.196 ± 0.138 N, 20 %: 0.278 ± 0.103 N, 40 %: 0.840 ± 0.092 N; r² = 0.858, <i>P</i> < 0.0001; collagen content: 10 %: 1.073 ± 12.49 µg, 20 %: 86.43 ± 71.65 µg, 40 %: 145.7 ± 84.11 µg; r² = 0.4735, <i>P</i> = 0.0046). After optimizing an exosome enriched feeding protocol using fbEXO, we confirmed that exosomes enriched from human serum (hsEXO) could sustain EHL function. Subsequently, twelve healthy, recreationally active volunteers (22 ± 3 y, 1,68 ± 0.10 m, 65.6 ± 27.8 kg; 6F/6M) performed a single bout of resistance exercise. Serum samples were collected prior to and 15 min post-exercise, and exosomes were enriched from these samples for treatment of EHLs. EHL function and collagen content did not differ when treated with hsEXO obtained at rest or post-resistance exercise (MTL: 1.30 ± 0.36 vs. 1.20 ± 0.36 N, <i>P</i> = 0.3950; collagen content: 424.6 ± 47.68 vs. 425.2 ± 44.46 µg, <i>P</i> = 0.9663). This model provides a novel way to determine the role of exosomes in connective tissue development and adaptation. The identification of circulating exercise factors that enhance tendon and ligament function remains to be fully elucidated.