Osteoarthritis (OA) is a prevalent and debilitating chronic joint disease, creating an urgent need for therapeutic strategies that move beyond symptomatic relief toward disease modification. Nanocomposite hydrogels, which incorporate nanoparticles into a three-dimensional (3D) polymeric network, have emerged as a promising class of biomaterials due to their enhanced and tailorable physical, chemical, and biological properties compared to conventional hydrogels. This review provides a systematic analysis of nanocomposite hydrogels for OA therapy. It begins by outlining the epidemiological burden of OA and limitations of current treatments, establishing the rationale for advanced local drug delivery systems. We then comprehensively examine the preparation strategies of nanocomposite hydrogels, encompassing physical encapsulation, electrostatic assembly, hydrogen bonding, covalent crosslinking, DNA origami, and advanced co-assembly platforms. Subsequently, the resulting systems are classified into three therapeutic paradigms based on their primary action, namely microenvironment-modulating, cartilage-reparative, and target-inhibiting or activating hydrogels. A dedicated section on structure-function engineering deconstructs the design of these materials, focusing on the construction of mechanical networks, the design of pore architectures for mass transport, interface functionalization, and the integration of stimuli-responsive bonds for intelligent therapy. Finally, the review critically evaluates the key translational challenges, including manufacturing scalability, long-term safety, and regulatory pathways. Nanocomposite hydrogels represent a transformative platform capable of integrating multiple therapeutic functions, ranging from sustained drug release and anti-inflammatory action to active tissue regeneration and precise molecular targeting. By rationally engineering their structure across multiple scales, these advanced biomaterials hold significant potential to shift OA management from palliative care to curative and disease-modifying interventions. Overcoming the identified translational hurdles through interdisciplinary collaboration will be crucial for their successful clinical adoption.
He et al. (Sat,) studied this question.