An Advanced Mechanically Active Osteoarthritis‐on‐Chip Model to Test Injectable Therapeutic Formulations: The SYN321 Case Study

Current treatments for osteoarthritis (OA) often fail to address the underlying pathophysiology and may have systemic side effects, particularly associated with long-term use of non-steroidal anti-inflammatory drugs (NSAIDs). Thus, researchers are currently directing their efforts toward innovative polymer-drug combinations, such as mixtures of hyaluronic acid viscoelastic hydrogels and NSAIDs like diclofenac, to ensure sustained release of the NSAID within the joint following intra-articular injection. However, the progress of novel injectable therapies for OA is hindered by the absence of preclinical models that accurately represent the pathology of the disease. The uBeat (R) MultiCompress platform is here presented as a novel approach for studying anti-OA injectable therapeutics on human mechanically-damaged OA cartilage microtissues, in a physiologically relevant environment. This platform can accommodate injectable therapeutic formulations and is successfully tested with SYN321, a novel diclofenac-sodium hyaluronate conjugate under development as a treatment for knee OA. Results indicate the platform's effectiveness in evaluating therapeutic potential, showing downregulation of inflammatory markers and reduction in matrix degradation in OA cartilage micro-tissues treated with SYN321. The uBeat (R) MultiCompress platform thus represents a valuable tool for OA research, offering a bridge between traditional in vitro studies and potential clinical applications, with implications for future drug discovery.