Osteoarthritis (OA) is a degenerative joint disease characterized by progressive breakdown of articular cartilage and surrounding extracellular matrix. It predominantly affects elderly individuals, leading to chronic pain, reduced mobility, and disability. Current treatments primarily focus on symptom relief rather than modifying the underlying disease process. Non-steroidal anti-inflammatory drugs, glucosamine, and calcitonin are commonly used but often limited by side effects or insufficient long-term efficacy. There is an urgent need for therapies that not only alleviate pain but also slow or halt structural joint deterioration. In this study, we investigated the therapeutic potential of an injectable hydrogel composed of hyaluronic acid (HA) and doxycycline (DOX) in a rabbit model of experimental osteoarthritis induced by partial meniscectomy and fibular ligament transection.
The HA-DOX hydrogel was formulated using electrostatic interactions between HA and DOX molecules, cross-linked via zinc-mediated chelation of phenolic moieties in DOX. Rheological analysis demonstrated that the hydrogel exhibited enhanced viscoelasticity compared to HA alone, with dynamic elastic modulus (G’) and viscous modulus (G”) increasing significantly with DOX concentration in the presence of Zn²⁺ ions. This improved mechanical property suggests better retention within the joint space and greater capacity to restore synovial fluid lubrication. In vitro cytotoxicity assays revealed that while high concentrations of free DOX (50 μg/mL) were toxic to human chondrosarcoma cells (SW1353), the HA-DOX hydrogel formulation showed markedly reduced toxicity, indicating a protective effect of the polymer matrix.
In vivo evaluation involved 32 male New Zealand White rabbits aged 13 weeks, divided into four groups: normal saline (NT), HA, DOX, and HA-DOX hydrogel. Injections were administered intra-articularly immediately after surgery and repeated on days 3, 6, 9, and 12. Pain assessment was conducted every three days using weight-bearing distribution measurements. By day 7 post-treatment, both HA and HA-DOX groups showed significant improvement in weight distribution, indicating effective analgesia.Benzanthrone supplier The HA-DOX group demonstrated superior outcomes, with more pronounced pain reduction and sustained benefits throughout the observation period.Sparfloxacin MedChemExpress
Macroscopic examination at 14 days post-surgery revealed that the HA-DOX group had smoother cartilage surfaces, minimal ulceration, smaller osteophytes, and fewer fissures compared to other groups.PMID:35126181 Histopathological analysis confirmed these findings: the HA-DOX group exhibited preserved chondrocyte organization, reduced proteoglycan loss, and decreased cartilage erosion at femoral condyles and tibial plateau. Cloning of chondrocytes—indicative of abnormal repair response—was least prominent in the HA-DOX group, suggesting a more stable and regenerative environment.
These results collectively demonstrate that the injectable HA-DOX hydrogel possesses dual functionality: it provides immediate symptomatic relief through enhanced viscoelasticity and prolonged therapeutic action via sustained release of DOX. The drug’s ability to inhibit matrix metalloproteinases, suppress inflammatory cytokines, and protect cartilage structure aligns with the ideal profile of a disease-modifying osteoarthritis drug (DMOAD) and connective tissue structure-modifying agent (CTSMA). Therefore, this novel hydrogel represents a promising, long-lasting pharmacotherapeutic option for the management of osteoarthritis.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com