Exploring exosomes in osteoarthritis: biogenesis, functional roles, and recent hydrogel-based delivery strategies

The discovery of exosomes in the early 1980s transformed modern medicine by establishing a new class of cell-free therapeutics. Exosomes, which are classified as diminutive membrane-bound vesicles, are secreted by all cell types in the extracellular space. Functionally, they are involved in intercellular communication and transport bioactive cargoes across the cells. Recently, exosomes have gained attention for their potential in the treatment and diagnosis of osteoarthritis (OA). Stem cell-derived exosomes are known to promote cartilage regeneration and reduce inflammation, while endogenous exosomes from osteoarthritic cells exacerbate the progression of OA. Despite their therapeutic potential, the low retention of exosomes administered intra-articularly in the joint cavity limits their application. Hydrogels, as a delivery vehicle for exosomes, allow them to achieve an increased residence time and sustained and localized release within the osteoarthritic joint. Furthermore, hydrogels protect exosomes from enzymatic degradation, mimic the extracellular matrix, and enhance their bioavailability and regenerative potential. This review provides an overview of the biogenesis of exosomes and key techniques for exosome isolation and characterization. We also discuss their functional role in therapy and the pathogenesis of OA. Additionally, we highlight the diagnostic value of exosomal miRNAs, lncRNAs, and circRNAs as emerging biomarkers for OA. Furthermore, we spotlight recent research in developing exosome-loaded hydrogels for OA treatment, focusing on their therapeutic outcomes, encapsulation, and characterization. Finally, we discuss current difficulties and prospects for translating exosome-loaded hydrogels into clinical settings.