Recent advances in intra-articular bioactive delivery for the treatment of osteoarthritis.

Osteoarthritis (OA) is among the most prevalent debilitating chronic diseases worldwide, with treatment currently strictly palliative. Intra-articularly administered agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and hyaluronic acid (HA) have an edge over systemic medications as they get localized at the site of inflammation, where they achieve higher concentrations to exert their therapeutic effects. However, the repeated injections of these agents are accompanied by discomfort and pain as well as an increased risk of infections. Furthermore, therapeutic agents are rapidly cleared from the intra-articular (IA) space, compromising their therapeutic efficacy. There is an urgent need for solutions to address these challenges. This review explores and highlights recent advances in IA therapies such as viscosupplementation, targeted corticosteroid formulations, colloidal systems (nano- and microparticles) fabricated from an array of materials, and molecularly imprinted polymer (MIP hydrogels and their potential for OA treatment. Delivery systems showcase their ability to prolong the retention of biologics, improve release profiles, and modulate inflammatory and matrix-degrading mediators in OA models. The review further integrates preclinical and clinical evidence, emphasizing the translational potential of such therapies while assessing the strengths and challenges of various therapeutic approaches. The literature provided can be used to identify future novel approaches to address the gaps in OA treatment with translation to clinical applications.