Incorporating exosomes in tissue engineering scaffolds: pave the way toward clinical application

In recent years, the use of endosome-derived extracellular vesicles (EVs) in regenerative therapies and tissue repair has attracted much attention. However, local or systemic injection of the free state of extracellular vesicles at the site of action is rapidly cleared and lacks a controlled release mechanism. Incorporation of exosomes into tissue-engineered scaffold materials not only facilitates the prolongation of EVs' retention time at the target site but also enhances their ability to induce cell differentiation, exert anti-inflammatory effects, and modulate immune responses. Thus, in this review, we provide a systematic overview of the biological properties of EVs and discuss the current research progress on specific functional components (nucleic acids, proteins, lipids, and others) of EVs in tissue repair and regeneration. More importantly, we demonstrate the design strategies, therapeutic effects, and mechanisms of action of EV-laden bioscaffolds. We also discuss the challenges and prospects in translating therapies of EV-loaded biomaterials into clinical tissue regeneration and repair.