Exosomes and exosome-loaded scaffolds: Characterization and application in modern regenerative medicine

Exosomes (EXOs) are extracellular vesicles derived from the endosome. These heterogeneous nanoparticles (30-150 nm) are secreted from various cells and play important biological roles in intercellular communication. EXOs have received much attention for application in regenerative therapies and tissue repair due to their stability, biosafety, and functional versatility. However, in their free forms, "EXOs have poor bioavailability" at the site of action and are devoid of controlled-release mechanisms. These issues have been largely remedied by scaffolding EXOs with appropriate biomaterials such as hydrogels to create EXOs -loaded scaffold (ELS). These biomaterial-based scaffolds can be rationally designed and functionalized to enhance various aspects of ELS including bioavailability, biocompatibility, and loading/release control. Additionally, the ELS are superior to free EXOs due to reduced injection-related side effects. This review article provides a comprehensive and updated account of EXOs and ELS isolation, characterization, and application in regenerative medicine with a focus on soft tissue repair. We also offer insights into the advantages of ELS therapy compared to stem cell therapy towards application in wound healing, cardiac and bone repair. ELS promotes cell migration to the scaffold and will cause better homing of exosomes. Different types of scaffolds are made and each one can be modified based on the repair in the target tissues so that the reactions between the scaffold and exosome take place properly and effective signals are created for tissue repair.