Refining the biomanufacturing of microalgae-derived extracellular vesicles as a potential nanotherapeutic for osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease characterized by oxidative stress, chronic inflammation and progressive cartilage degradation. Current treatments remain largely symptomatic and fail to target underlying disease mechanisms. Extracellular vesicles (EVs) have emerged as promising nanotherapeutics; however, mammalian-derived EVs face limitations related to cost, scalability and manufacturing complexity. Microalgae represent a sustainable alternative, yet their potential as EV biofactories for regenerative medicine remains largely unexplored. This study investigates the biomanufacturing and therapeutic potential of microalgae-derived EVs for OA. Four microalgae species ( Chlorella sorokiniana, Synechococcus sp., Leptolyngbya sp. and Chlamydomonas reinhardtii CC1690) were cultured under varying photoperiods (0, 16 and 24 h light/day) to evaluate effects on viability, growth and EV production. EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, protein quantification and immunoblotting. Antioxidant activity and therapeutic efficacy were assessed in a cytokine-induced OA-like in vitro model. All species maintained high viability (>80%), with EV yield strongly dependent on light exposure. Leptolyngbya sp. demonstrated the fastest growth and highest EV production under extended illumination, generating EVs with antioxidant properties. Leptolyngbya-derived EVs enhanced mesenchymal stromal cell proliferation and migration and mitigated cytokine-induced matrix degradation. These findings establish Leptolyngbya as a scalable, cost-effective source of therapeutic EVs for OA.