Oxidative stress in osteoarthritis: From mitochondrial homeostasis to targeted delivery systems

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage degradation, in which oxidative stress and mitochondrial dysfunction play a pivotal role. Excessive reactive oxygen species (ROS) production, driven by inflammation, metabolic reprogramming, and systemic risk factors, leads to mitochondrial damage, impaired mitophagy, and disrupted mitochondrial dynamics, forming a vicious cycle that accelerates OA progression. Although traditional antioxidant molecules show therapeutic potential, their rapid clearance from the joint cavity limits clinical efficacy. Recent advances in tissue engineering and smart delivery systems-such as ROS-responsive hydrogels, microspheres/nanocarriers, and exosome-based platforms-enable targeted, sustained, and on-demand drug release, offering new opportunities to restore redox balance and break the pathological amplification loop. This review systematically summarizes the molecular mechanisms linking oxidative stress to mitochondrial homeostasis in OA and highlights the design principles and application status of emerging delivery strategies, aiming to provide a theoretical foundation for next-generation precision therapies.