OASIS, Integrated Veterinary Research Unit, Namur Research Institute of Life Sciences (NARILIS), Namur University, Namur, Belgium.
BEAMS Department, Université Libre de Bruxelles, Brussels, Belgium.
PLoS One. 2021 Oct 11;16(10):e0256770. doi: 10.1371/journal.pone.0256770. eCollection 2021.
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.
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.
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.
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.
润滑和清除自由基是用于治疗骨关节炎（OA）关节的黏弹性补充（VS）的生物材料的关键特性。本研究的目的是描述 KiOmedine®CM-壳聚糖（一种非动物源性羧甲基壳聚糖）的非临床性能特征，以评估其在 VS 中的预期作用，并将其与基于交联透明质酸（HA）制剂的现有黏弹性补充剂进行比较。
在体外和体内评估了测试的黏弹性补充剂（VS）的润滑能力。在体外，使用新型摩擦学系统测量摩擦系数（COF）。同时，开发了一种绵羊后肢的体外生物力学模型，以评估关节内（IA）注射后关节活动度的恢复。使用 Trolox 等效抗氧化能力（TEAC）测定法评估 HA 和 KiOmedine®CM-壳聚糖制剂的清除自由基能力。
在体外摩擦学模型中，KiOmedine®CM-壳聚糖表现出高润滑能力，与交联 HA 制剂相比，COF 显著降低。在体内模型中，KiOmedine®CM-壳聚糖在受伤膝关节 IA 注射后的润滑效果再次得到证明，COF 降低。IA 注射 3ml KiOmedine®CM-壳聚糖时，关节运动的恢复最佳，明显优于相同体积的交联 HA 制剂。在体外 TEAC 测定中，KiOmedine®CM-壳聚糖表现出比 HA 制剂更高的清除自由基能力。
总的来说，这些结果首次提供了关于 KiOmedine®CM-壳聚糖作为 OA 黏弹性补充治疗的润滑和清除自由基作用机制的见解。KiOmedine®CM-壳聚糖表现出更高的清除自由基能力，并且在膝关节损伤后其运动恢复能力明显高于交联 HA 制剂。这种差异可以通过 KiOmedine®CM-壳聚糖和 HA 及其制剂之间的化学结构差异来解释。
