Yoshioka K, et al. - In the present study, researchers examined the biocompatibility of three multiple-injection intra-articular (IA) injection of hyaluronic acid (HA) (IA-HA) products accessible in the global market. IA injection of Avian-CL-HA into rabbit knee joints produced the aggregation of inflammatory cells, infiltration of eosinophils, and an escalation in the number of cells in the synovial fluid. Nevertheless, in the Avian-HA and Bio-HA groups, these impacts were not observed. In all HA products, the residual protein content and the contaminant levels of bacterial endotoxins were lesser than the limit of quantitation. Avian-CL-HA had comparatively a great amount of (1 → 3)-β-D-glucan, but in the other HA products, it was below the lower limit of quantification. Thus, the biocompatibility of Avian-HA is similar to that of Bio-HA, and they were both acknowledged to have an agreeable safety profile for the treatment of symptomatic OA of the knee. Nonetheless, immunostimulatory activity was seen following the injection of Avian-CL-HA, which might be a consequence of its unique cross-linking structure and/or the substantial amount of (1 → 3)-β-D-glucan impurity present in the formulation.