Application and progress of smart hydrogel microspheres for regulating oxidative stress in osteoarthritis

Osteoarthritis (OA) is a globally prevalent chronic degenerative joint disease. Patients suffer from severe clinical symptoms, and currently, there are no drugs that can effectively halt the progression of the disease. Oxidation is closely related to energy metabolism in the body, and oxidative stress (OS) occurs when the balance between oxidation and antioxidant systems is disrupted. The pathogenesis of OA caused by OS includes the regulation of cell signaling, inducing mitochondrial dysfunction, inhibition of autophagy, promotion of apoptosis, extracellular matrix (ECM) degradation, microRNA regulation and abnormal mechanical stress. OS plays a crucial role in the occurrence and development of OA. Studies have shown that scavenging reactive oxygen species (ROS) can restore mitochondrial function, activate autophagy, reduce apoptosis, and promote ECM synthesis. Therefore, regulating OS in the body has become a new therapeutic strategy for the treatment of OA. Smart hydrogel microspheres are tiny spherical particles formed by the cross-linking of hydrophilic polymers, and they have become ideal carriers with great potential in drug delivery, minimally invasive treatment, tissue repair, and regeneration. In recent years, research on OS-regulating biomaterials loaded on smart hydrogel microspheres has been increasing. This article comprehensively reviews the OS-related pathological mechanisms for OA, methods for treating OA by regulating OS, smart hydrogel microspheres and their characteristics, as well as the latest developments in biomaterials for OS-regulating OA therapies. This article summarizes the recent research progress and provides future perspectives for the future development in the field.