The present pilot study provides interesting and promising results for the use of AC beads in H hydrogel in animal. It indeed prevented the development of OA cartilage lesions without inflammatory signs. The potencies of this biomaterial to protect OA joint should be further documented. It could then represent a new alternative for viscosupplementation in human OA management.

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Background: Single-injection viscosupplementation is currently performed with cross-linked hyaluronan (e.g., Durolane®) for treating symptomatic knee osteoarthritis. Objective: This first-in-human study evaluated the safety and performance of single-injection treatment with non-crosslinked KiOmedine®CM-Chitosan. Methods: Patients with painful knee osteoarthritis were randomly assigned to the KiOmedine®CM-Chitosan (n=63) or Durolane® (n=32) group. Patients were blinded to treatment and followed up for 26 weeks. Durolane® was used as scientific control to ensure the validity of the study and reliability of results. No direct comparison was performed between the two groups. The primary objective was defined as an intra-group effect size of 0.8 at 13 weeks post-injection compared to baseline on WOMAC-A (pain). Secondary outcomes included self-reported knee stiffness and knee function, responder rate, quality-of-life questionnaires, and safety. Results: The primary objective for both the KiOmedine®CM-Chitosan and the Durolane® groups was met: mean pain reduction of 62.5% (effect size 2.08) for the KiOmedine®CM-Chitosan group and 62.4% (effect size 2.28) for the Durolane® group. Secondary performance outcomes showed all clinically relevant treatment effects over 26 weeks for both groups (p<0.05). Treatment-related adverse events were more often reported in the KiOmedine®CM-Chitosan than Durolane® group and were limited to local reactions. No serious treatment-related adverse events were reported. Conclusion: A single intra-articular injection of non-crosslinked KiOmedine®CM-Chitosan is safe and effective for treating symptomatic knee osteoarthritis with a high responder rate. Pain reduction is maintained for 6 months with a high responder rate. The clinical trial registration number: NCT03679208.

Objective Lubrication and free radical scavenging are key features of biomaterials used for viscosupplementation (VS) of joints affected by osteoarthritis (OA). The objective of this study was to describe the non-clinical performance characterization of KiOmedine® CM-Chitosan, a non-animal carboxymethyl chitosan, in order to assess its intended action in VS and to compare it to existing viscosupplements based on crosslinked hyaluronan (HA) formulations. Method The lubrication capacity of the tested viscosupplements (VS) was evaluated in-vitro and ex-vivo. In-vitro, the coefficient of friction (COF) was measured using a novel tribological system. Meanwhile, an ex-vivo biomechanical model in ovine hindlimbs was developed to assess the recovery of join mobility after an intra-articular (IA) injection. Free radical scavenging capacity of HA and KiOmedine® CM-Chitosan formulations was evaluated using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. Results In the in-vitro tribological model, KiOmedine® CM-Chitosan showed high lubrication capacity with a significant COF reduction than crosslinked HA formulations. In the ex-vivo model, the lubrication effect of KiOmedine® CM-Chitosan following an IA injection in the injured knee was proven again by a COF reduction. The recovery of joint motion was optimal with an IA injection of 3 ml of KiOmedine® CM-Chitosan, which was significantly better than the crosslinked HA formulation at the same volume. In the in-vitro TEAC assay, KiOmedine® CM-Chitosan showed a significantly higher free radical scavenging capacity than HA formulations. Conclusion Overall, the results provide a first insight into the mechanism of action in terms of lubrication and free radical scavenging for the use of KiOmedine® CM-Chitosan as a VS treatment of OA. KiOmedine® CM-Chitosan demonstrated a higher capacity to scavenge free radicals, and it showed a higher recovery of mobility after a knee lesion than crosslinked HA formulations. This difference could be explained by the difference in chemical structure between KiOmedine® CM-Chitosan and HA and their formulations.

When designing innovative biomaterials, biocompatibility is regarded as a prerequisite for safe clinical use in humans. In this study, the biological safety of KiOmedine® CM-chitosan, which is a non-animal carboxymethyl chitosan biomaterial, was evaluated using a large panel of both in vitro and in vivo biocompatibility tests in accordance with the ISO 10993 series. KiOmedine® CM-chitosan was non-cytotoxic and non-genotoxic in vitro. The biomaterial was neither found to be haemolytic nor was it able to potentiate the activation of the central complement component C5a or the inflammatory mediators IL-1β and IL-8 in the presence of human whole blood. Furthermore, no evidence of any significant irritation, sensitization, pyrogenicity, and organ toxicity was detected in specific animal studies conducted with KiOmedine® CM-chitosan, and only minimal local tissue effects were observed after the intra-articular or intra-dermal injection of KiOmedine® CM-chitosan in the rabbit model. KiOmedine® CM-chitosan had minimal potential to induce immunotoxic reactions in the mouse air pouch model. Its biodegradation process was appropriately characterized at the histological level. In summary, our study represents an unprecedented body of work supporting the biological safety evaluation of KiOmedine® CM-chitosan, allowing its use in injectable medical devices.