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

Descripción del proyecto

Mejora de la terapia celular de la osteoartritis

La osteoartritis, una enfermedad dolorosa, afecta el cartílago protector que proporciona una interfaz suave y lubricada en las articulaciones. Este cartílago se deteriora de forma gradual y deja que el hueso frote otro hueso. Las inyecciones intraarticulares de células madre multipotentes han demostrado ser el tratamiento más prometedor de la enfermedad. Sin embargo, la solución salina fisiológica en la que se administran las células a las articulaciones no ha favorecido adecuadamente unos trasplantes satisfactorios. El proyecto BABHY-CART, financiado con fondos europeos, proporciona un microentorno más favorable para las células. Este imitará su entorno natural, favoreciendo que proliferen y liberen factores antiosteoatríticos «in vivo».

Objetivo

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.