Cell-free exosome-laden scaffolds for tissue repair

With the development of regenerative medicine, tissue repair at the molecular, cellular, tissue, and organ level has seen continuous improvements over traditional techniques. As the core of tissue repair, seed cells are widely used in various fields of regenerative medicine. However, their use is still associated with problems such as decreased cell survival and regeneration capacity after transplantation, immune rejection, and ethical concerns. Therefore, it is difficult to universally and safely apply stem cell banks for regenerative medicine. The paracrine effects of cells, especially secretion of exosomes, play vital roles in cell communication, immune response, angiogenesis, scar formation, tissue repair, and other biological functions. Exosomes are a type of nanoscale extracellular vesicle that contain biologically active molecules such as RNA and proteins; therefore, exosomes can replicate the functions of their parental cells. Meanwhile, exosomes can be used as nanocarriers to deliver active factors or small molecules to promote tissue repair. Preclinical studies of exosomes in tissue engineering and regenerative medicine have been carried in the fields of bone/cartilage repair, nerve regeneration, liver and kidney regeneration, skin repair, vascular tissue regeneration, etc. This review introduces exosomes from the aspects of biogenesis, composition, identification, and isolation, and focuses on the development status of scaffold materials for exosome delivery. In addition, we highlight examples of exosome-laden scaffolds for preclinical applications in tissue repair. We look forward to the broad application prospects of exosome-laden scaffolds.