Hydrogels as drug carriers for cartilage repair in osteoarthritis: Applications and challenges

Osteoarthritis (OA) is a prevalent chronic degenerative joint disease characterized by progressive cartilage degradation, subchondral bone remodelling, synovial inflammation, osteophyte formation, and loss of joint function, resulting in significant pain, disability, and socioeconomic burden worldwide. Despite advances in clinical management, current therapeutic strategies, including nonsteroidal anti-inflammatory drugs, corticosteroids, hyaluronic acid injections, and surgical interventions, primarily provide symptomatic relief and have limited ability to prevent disease progression or regenerate damaged cartilage. In recent years, hydrogel-based drug delivery systems have emerged as promising therapeutic platforms owing to their excellent biocompatibility, biodegradability, injectability, high water content, and structural similarity to the native extracellular matrix. These properties enable hydrogels to serve as effective carriers for a wide range of therapeutic agents, including anti-inflammatory drugs, growth factors, nucleic acids, nanoparticles, exosomes, and stem cells, while providing sustained and localized drug release within the osteoarthritic joint. This review comprehensively discusses the pathophysiology of OA and highlights the major molecular signaling pathways involved in disease progression, including NF-κB, MAPK, Wnt/β-catenin, PI3K/Akt, TGF-β, and JAK/STAT pathways. Furthermore, recent advances in natural, synthetic, hybrid, and stimuli-responsive hydrogels are critically examined, with particular emphasis on their applications in cartilage repair and targeted drug delivery. Emerging approaches involving nanotechnology-enabled hydrogels, gene delivery systems, stem cell-loaded constructs, and immunomodulatory biomaterials are also evaluated for their therapeutic potential and translational prospects. This review provides an integrated and up-to-date perspective on hydrogel-based strategies for cartilage regeneration and disease modification, highlighting their potential as next-generation therapeutic platforms for the long-term management of osteoarthritis.