Osteoarthritis (OA) is a degenerative disease characterised with pain, stiffness and loss of function in the weight-bearing joints, caused by the inflammatory biological molecules that disturb the balance between the tissue synthesis and degradation. Maintaining the composition of the physiological lubricant, named synovial fluid, by restoration of homeostasis is thus a necessary step to retard the OA progression and provide a suitable environment for tissue remodelling.<br/><br/>Thiolated hyaluronic acid (HA-SH) was enzymatically crosslinked with gallic acid (GA) by the action of laccase as a method to prepare multifunctional hydrogels, designed as delivery systems that enable long-term efficiency of biological entities in cell-based therapies. Owing to its characteristics and mild conditions employed, the encapsulation of very unstable and sensitive cargoes is possible, highlighting its potential as a platform for a variety of biomedical applications. A cytokine cocktail (ACC) and chondrocytes cells were encapsulated together as therapy to delay the disease progression and boost the anabolic pathways for recovery of the damaged cartilage. The morphology, swelling ratio, rheological properties and stability of the hydrogels were characterised and optimised in order to fit the requirements of the therapy. The efficiency of the developed platforms was evaluated <i>in vitro</i> against the major factors governing the OA disease, namely the anti-inflammatory effect, cellular ROS scavenging and the inhibitory capacity of the hydrogels towards deleterious enzymes as MMPs, MPO and hyalurodinase. Finally, experiments to determine the ability of the cells to survive, growth and differentiate in the multifunctional hydrogels were assessed in order to explore their potential in a cell-based therapies and regenerative medicine.

Enzymatically generated hyaluronic acid hydrogel for cytokine therapy of osteoarthritis

255th National Meeting (2018)

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