"Smart Exosomes": A Smart Approach for Tendon Regeneration.

Shoulder tendon injuries are the common musculoskeletal disorder resulting in significant pain and disability. These injuries are characterized by chronic inflammation and tissue degeneration. Tendon pathology exhibits poor innate healing ability, enhanced inflammation, disorganized collagen fibers, calcification, and scar tissue formation affecting the normal healing process. Extracellular vesicle, especially exosomes, treatment has been emerging as a potential regenerative strategy improving the outcomes and biomechanical properties, accelerating tenocyte proliferation and migration, reducing inflammation, and facilitating the healing at tendon-bone interface. In this article, we critically reviewed the potential role of exosomes in tendon regeneration and their applications to accelerate the healing response following injury. In addition, the article provides novel insights on the concept of "Smart Exosomes" by programming/manipulating the secretome contents and functions of exosomes in the management of shoulder tendon injury. Impact statement The exosomes pose tremendous regenerative capacity in otherwise inherently poor tendon healing following shoulder injury. Understanding the exosome biology in the context of tendon injury offers immense opportunities for developing novel regenerative approaches. Herein, we focus on the novel concept of "Smart Exosomes" by programming the regenerative properties of exosomes as a next-generation management strategy for shoulder tendon injury.