In vivo impact on rabbit subchondral bone of viscosupplementation with a hyaluronic acid antioxidant conjugate
This study aimed to assess the effects of an antioxidant-conjugated Hyaluronic Acid (HA), specifically HA-4-aminoresorcinol (HA4AR), on articular cartilage and subchondral bone in osteoarthritis (OA). We conducted a comparative analysis between HA4AR and a commercially available high molecular weight HA formulation in a rabbit model of OA. Eighteen rabbits underwent unilateral anterior cruciate ligament transection (ACLT) and were divided into three groups of six based on the type of intra-articular injection received. Additionally, eight non-operated contralateral knees served as reference points (Contralateral-group). Six weeks post-surgery, iodine-enhanced micro-computed tomography imaging was used to evaluate articular cartilage volume and thickness, and to assess subchondral bone microarchitecture and mineral density. Cartilage thickness in both the HA and HA4AR groups was comparable to that of the Contralateral group. Notably, there was a significant reduction in subchondral bone plate tissue mineral density in the HA-group when compared to both the HA4AR and Saline groups (p<0.05). However, no significant differences in trabecular subchondral bone microarchitectural parameters and mineral densities were observed between the HA4AR-group and the Saline-group. When compared to the Contralateral, Saline, and HA4AR groups, the HA-group exhibited a marked decrease in subchondral bone plate tissue mineral density (p<0.05). Additionally, a significant reduction in trabecular bone volume fraction was noted in the HA-group compared to the Contralateral-group (p<0.05). The HA-4AR hydrogel demonstrated significant preservation of subchondral bone plate tissue mineral density compared to HA alone, while other bone microarchitectural parameters remained largely unchanged. These findings indicate that HA-4AR may provide enhanced osteoprotective benefits in the treatment of osteoarthritis.