Injectable Hydrogels of Hyaluronic Acid and Doxycycline Synergistically Down-Regulate the Progression of the Cartilage Degeneration in Rabbit Oa Model

Treatment of OA has targeted modifiable reagent to be the connective tissue structure - modifying agents (CTSMAs) and disease-modifying osteoarthritis drugs (DMODs), such as hyaluronic acid (HA) and modified tetracycline (doxycycline). Doxycycline (DC) has showed significant inhibition of IL-1β and MMPs and improved the structure of subchondrobone. Hyaluronic acid has been put to use on the clinical OA treatment at the present day. HA can effectively remedy OA symptoms like alleviate pain and irritation. A three-year research project aim was to examine the treatment of injectable hyaluronic acid and Doxycycline (HA-DC) hydrogel via intra-articular injection to synergistically restore the matrix of arthritic knee joints in rabbit OA model is proposed. We will development HA and DC gel by divalent Zinc cation, furthermore we will determine release characterization by viscosity, turbidity and drug release tests in the first year period. We will demonstrate HA, DC and combined gels on human chondrocyte whether inhibits MMPs activity or regulate the matrix repair of cell’s ECM, eg: type II collagen and aggrecan in the second year period. It was administered into the partial meniscectomy and unilateral fibular ligament transected knee joints of 13-week old New Zealand White rabbits in comparison with that of DC, HA, and normal saline. OA progression was histopathologically evaluated by Alcian blue and eosin staining, by the modified grading method and microscopy in the third year period。