Rotator Cuff Repair: Lessons from Immune Strategies, 3D Biofabrication and In Vivo Testing

Background: Rotator cuff injuries are the most common type of tendinopathies affecting up to 10% of young adults and more than 60% of the elderly. Tendons have notoriously limited regenerative capacity which is attributed to their low vascularisation and low cell-to-tissue ratio. That leads to an inefficient repair process resulting in fibrotic scar tissue with poorer mechanical properties. Recent advances in tissue engineering and biofabrication techniques have been anticipated with great hope in the field of regenerative medicine. Methods: In this review, we discuss the insights gained from immune-based strategies, 3D biofabrication, and in vivo testing in the context of rotator cuff repair. Particular emphasis is placed on in vivo studies that bridge the gap between laboratory innovation and clinical translation, outlining promising avenues for future therapeutic development. Results : Regardless of the huge progress in in vitro modelling and in vivo healing of RCTs in animals, clinical translation has not yet succeeded because mechanical loading, and chronic inflammation in humans are hard to recapitulate. Biologic variability, regulatory complexity, and poor reproducibility also slow down translation to the clinic. Conclusion : With a number of encouraging results so far, multidisciplinary research will continue to elucidate the complex biological processes in terms of (1) immune and tendon cell engagement and modulation, natural matrix deposition and remodelling; (2) material mimicry regarding topography, anisotropic, gradient continuity, biomechanical properties; and (3) in vivo behaviour in structural reconstruction and functional performance in the long-term. Such integrative approach is essential to overcome today’s limitations in RC repair and to outline next-generation strategies to achieve improved clinical outcomes.