  To assess the impact of an antioxidant-conjugated Hyaluronic Acid (HA) on
articular cartilage and subchondral bone in the context of osteoarthritis (OA),
we conducted a study using a hydrogel composed of HA-4-aminoresorcinol (HA4AR)
and compared it to 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 categorized into three
groups of six rabbits (Saline-group, HA-group and HA4AR-group) depending on the
intra-articular injection compound. Eight contralateral knees were used as
non-operated reference points (Contralateral-group). Iodine-enhanced
micro-computed tomography imaging was performed six weeks post-surgery to study
the articular cartilage volume and thickness as well as the subchondral bone
microarchitectural parameters and mineral density. In the HA and HA4AR groups,
the mean cartilage thickness was found to be similar to that of the
Contralateral-group. However, when we compared the HA-group to the HA4AR-group,
we observed a significant reduction in subchondral bone plate tissue mineral
density (p<0.05). In contrast, when we compared the HA4AR-group to the
Saline-group, no significant differences were noted in trabecular subchondral
bone microarchitectural parameters and subchondral bone plate and trabecular
bone mineral densities. Additionally, when the HA-group was compared to the
Saline-group, a notable decrease in subchondral bone plate tissue mineral
density was evident (p<0.01). Notably, the HA4AR hydrogel, comprising
HA-antioxidant conjugate, effectively preserved subchondral bone plate tissue
mineral density when compared to HA alone. Nevertheless, other aspects of bone
microarchitectural parameters remained unaltered, resulting in subchondral bone
mineral loss six weeks after surgery in the rabbit model.
