Biologic and regenerative strategies for osteoarthritis: advances in MSC, exosome, and PRP based therapies

Abstract

Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by progressive cartilage destruction, chronic inflammation, pain, and functional impairment. Conventional therapies primarily focus on symptom management and are unable to restore damaged articular cartilage or effectively modify disease progression. Consequently, increasing attention has been directed toward biologic and regenerative approaches that target the underlying mechanisms of cartilage degeneration and joint dysfunction. This review provides a comprehensive overview of emerging regenerative strategies for articular cartilage repair, including gene- and noncoding RNA-based therapies, platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), mesenchymal stromal cells (MSCs), MSC-derived exosomes, and cell-based interventions. Current evidence indicates that these therapies exert their effects through modulation of inflammatory pathways, enhancement of extracellular matrix synthesis, promotion of chondrocyte survival, and regulation of tissue repair processes. Among them, PRP and BMAC offer minimally invasive approaches with favorable safety profiles, whereas MSCs and exosome-based therapies demonstrate substantial regenerative and immunomodulatory potential. Gene and epigenetic therapies further provide opportunities to target disease-associated molecular pathways and improve cartilage homeostasis. Despite encouraging preclinical and clinical outcomes, significant challenges remain, including heterogeneity in biologic preparations, variability in treatment protocols, limited long-term clinical evidence, and the absence of standardized outcome measures. Future research should focus on mechanistic validation, protocol standardization, optimization of delivery strategies, and large-scale randomized clinical trials to establish the long-term safety and disease-modifying efficacy of these regenerative therapies. Collectively, biologic and regenerative interventions represent promising avenues for advancing cartilage repair and improving clinical outcomes in patients with osteoarthritis.