Healing of tendon-related diseases: insights from macrophage regulation

Abstract Tendon-related diseases (TRDs) are increasingly common in the current aging society and impose a significant burden on patients. Despite therapeutic advances, the pathophysiology of TRDs remains poorly understood, hindering effective clinical management. The macrophages are highly plastic immune cells involved in the maintenance of in vivo homeostasis and the injury-healing process. Their dual role in TRDs has been widely investigated, either promoting tenogenic and chondrogenic differentiation or amplifying inflammatory response, underscoring their therapeutic potential for TRDs treatment. Therefore, the review aims to summarize the roles of macrophages in the healing of TRDs, characterized by limited regenerative capacity, and examine strategies for the modulation of macrophage phenotypes to accelerate the regeneration process. Finally, we review applications involving macrophage modulation within the context of tissue engineering of TRDs, providing novel insights for the design of biomaterials-based targeted delivery systems.