NOVEL THERAPEUTIC APPROACH FOR OSTEOARTHRITIS BASED ON AN INJECTABLE GLYCOSAMINOGLYCAN FOR VISCOSUPPLEMENTATION WITH CHONDROPROTECTIVE EFFECT

Objectives: The recommended procedure to treat osteoarthritis (OA) according to the ESCEO depends on the extent of damage of joint tissues. Treatments based on anti-inflammatory drugs require persistent injections and rarely contains the degeneration over the course of the years. More severe stages involve substituting the articular structure for an artificial prosthesis. Halfway, viscosupplementation therapies are based on the injection of hyaluronic acid (HA) to reduce friction. Here we present a viscosupplement gellable on demand that mimics the actual macrostructure of the proteoglycan, by including biomolecules that support hydration of the cartilage and stimulate its native cells. Methods: By using EDC/NHS chemistry, it is possible to obtain a crosslinkable HA hydrogel with chondroitin sulfate (CS) grafted to it in a straightforward rection in aqueous media and without the need of catalysts. The crosslinking potential and the grafting efficiency has been determined by spectrophotometric or fluorometric reference assays. Conditions under which the SOL-GEL transition happens have been studied with a parallel-plates rheometer. The biological characterization of the grafting macromolecule and the hydrogels, as well as biodegradation tests of the gels for analysing the controlled release are currently in progress. Results: The resulting solution can be turned into a gel at will under physiological pH, in presence of oxygen. Rheometric assays of the hydrogels revealed similar properties than commercial, top-of-the-range viscosupplementation alternatives that do not have the chondroprotective counterpart. A preliminary biological characterization, with human chondrocytes, suggests that the CS grafting to the HA does not compromise its biocompatibility, as compared to the bare macromolecules. Conclusions: We developed a protein-free biomimetic proteoglycan with the ability to make the SOL-GEL transition on an osteoarthritic joint that will have a controlled and sustained release of chondroprotective biomolecules. Acknowledgements: Generalitat Valenciana (Spain) through Grant CIGE/2021/174 and Spanish Ministerio de Ciencia e Innovación through Grant PID2021-128213OB-I00.