Immunoengineering Biomaterials for Musculoskeletal Tissue Repair across Lifespan

Abstract Musculoskeletal diseases and injuries are among the leading causes of pain and morbidity worldwide. Broad efforts have focused on developing pro‐regenerative biomaterials to treat musculoskeletal conditions; however, these approaches have yet to make a significant clinical impact. Recent studies have demonstrated that the immune system is central in orchestrating tissue repair and that targeting pro‐regenerative immune responses can improve biomaterial therapeutic outcomes. However, aging is a critical factor negatively affecting musculoskeletal tissue repair and immune function. Hence, understanding how age affects the response to biomaterials is essential for improving musculoskeletal biomaterial therapies. This review focuses on the intersection of the immune system and aging in response to biomaterials for musculoskeletal tissue repair. The article introduces the general impacts of aging on tissue physiology, the immune system, and the response to biomaterials. Then, it explains how the adaptive immune system guides the response to injury and biomaterial implants in cartilage, muscle, and bone and discusses how aging impacts these processes in each tissue type. The review concludes by highlighting future directions for the development and translation of personalized immunomodulatory biomaterials for musculoskeletal tissue repair.