Enhanced exosome biomanufacturing, precision isolation, and advanced engineering: toward mechanistic regulation and biomaterial integration for osteoarthritis therapy

Exosomes (Exos) are nanoscale extracellular vesicles that have gained attention as promising therapeutic agents due to their unique biological attributes, immunomodulatory roles, and potential for targeted drug delivery. This review systematically explores their biological origins, secretion mechanisms, and cellular uptake dynamics of Exos. We explore strategies to enhance Exos production, including genetic modifications and optimized culture conditions, and compare purification methods such as ultracentrifugation and size-exclusion techniques, noting their advantages and disadvantages. Additionally, we discuss the engineering of Exos for drug delivery applications through methods like electroporation and physicochemical modifications. Focusing on osteoarthritis (OA)-a widespread degenerative joint disorder lacking effective clinical treatments for halting its progression or promoting cartilage regeneration-we elaborate on the therapeutic mechanisms of Exos in this context, including regulation of inflammatory responses, enhancement of chondrocyte survival, promotion of matrix synthesis, and inhibition of pathological angiogenesis via bioactive molecules like microRNAs and proteins. To address the challenges of rapid clearance and insufficient targeting in vivo, we propose innovative delivery systems using polymer-based and natural biomaterials to improve Exos retention and stability within the joint cavity. This approach aims to optimize therapeutic outcomes and bridge fundamental biological research with clinical applications, advancing next-generation OA treatment strategies.