Self-Healing Hydrogels for Material-Assisted Cell therapy in Osteoarthritis

ended

Osteoarthritis (OA) is an incurable and painful disease. Over 70 million Europeans are currently affected by OA – a number that is set to increase with aging population and prevalence of obesity. To date, no clinically-efficient therapy exists to treat this socioeconomically debilitating disease. In this context, innovative regenerative therapies for joints are a pressing medical challenge. Intraarticular mesenchymal stromal cell (MSC) injections hold the great promise of stopping and reversing age-associated inflammation and degeneration of joints by providing the necessary trophic factors to mitigate immune responses. However, translational progress using conventional cell delivery (saline) has been seriously hampered by the limited control over cell survival, location and fate in damaged joints. It is now common knowledge that cell microenvironment plays a crucial role in the success of cell transplantation; and appropriate synthetic matrix design is key to success. To address challenges in intraarticular MSC-based immunomodulation strategies, we have envisioned an original hydrogel-assisted cell therapy. In this strategy, an injectable hyaluronic acid (HA)-based hydrogel with long-lasting viscoelastic properties will allow MSC encapsulation and cytoprotection, ensuring the production of anti-OA soluble factors in vivo. To best mimic synovial environment and support MSCs in vivo, we will synthesize a novel boronic acid-based, self-healing HA hydrogel with unique properties of injectability, stability and fast relaxation under mechanical load. After carefully characterizing the physicochemical properties of this new class of biomaterials, we will investigate the effects of cell encapsulation on adipose stromal cell (ASC) survival, morphology and factor secretion. Then, the preclinical efficacy of intraarticular injections of cell-loaded, self-healing hydrogels will be confirmed in two complementary OA mice models.