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通过关节腔内注射递送的多巴胺共轭透明质酸可提供关节软骨润滑和保护。

Dopamine-conjugated hyaluronic acid delivered via intra-articular injection provides articular cartilage lubrication and protection.

作者信息

Ren Ke, Wan Hongping, Kaper Hans J, Sharma Prashant K

机构信息

University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands.

University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands; College of Veterinary Medicine, Sichuan Agricultural University, Department of Animal and Plant Quarantine, Chengdu 611130, China.

出版信息

J Colloid Interface Sci. 2022 Aug;619:207-218. doi: 10.1016/j.jcis.2022.03.119. Epub 2022 Mar 28.

DOI:10.1016/j.jcis.2022.03.119
PMID:35397456
Abstract

Due to its high molecular weight and viscosity, hyaluronic acid (HA) is widely used for viscosupplementation to provide joint pain relief in osteoarthritis. However, this benefit is temporary due to poor adhesion of HA on articular surfaces. In this study, we therefore conjugated HA with dopamine to form HADN, which made the HA adhesive while retaining its viscosity enhancement capacity. We hypothesized that HADN could enhance cartilage lubrication through adsorption onto the exposed collagen type II network and repair the lamina splendens. HADN was synthesized by carbodiimide chemistry between hyaluronic acid and dopamine. Analysis of Magnetic Resonance (NMR) and Ultraviolet spectrophotometry (Uv-vis) showed that HADN was successfully synthesized. Adsorption of HADN on collagen was demonstrated using Quartz crystal microbalance with dissipation (QCM-D). Ex vivo tribological tests including measurement of coefficient of friction (COF), dynamic creep, in stance (40 N) and swing (4 N) phases of gait cycle indicated adequate protection of cartilage by HADN with higher lubrication compared to HA alone. HADN solution at the cartilage-glass sliding interface not only retains the same viscosity as HA and provides fluid film lubrication, but also ensures better boundary lubrication through adsorption. To confirm the cartilage surface protection of HADN, we visualized cartilage wear using optical coherence tomography (OCT) and atomic force microscopy (AFM).

摘要

由于其高分子量和粘度,透明质酸(HA)被广泛用于粘弹性补充,以缓解骨关节炎中的关节疼痛。然而,由于HA在关节表面的附着力较差,这种益处是暂时的。因此,在本研究中,我们将HA与多巴胺共轭形成HADN,使其具有粘性,同时保留其增粘能力。我们假设HADN可以通过吸附到暴露的II型胶原网络上增强软骨润滑,并修复光泽层。通过透明质酸和多巴胺之间的碳二亚胺化学合成了HADN。磁共振(NMR)分析和紫外分光光度法(Uv-vis)表明HADN已成功合成。使用带耗散的石英晶体微天平(QCM-D)证明了HADN对胶原蛋白的吸附。包括摩擦系数(COF)测量、动态蠕变、步态周期的站立(40 N)和摆动(4 N)阶段在内的体外摩擦学测试表明,与单独的HA相比,HADN对软骨有足够的保护作用,润滑效果更好。软骨-玻璃滑动界面处的HADN溶液不仅保持了与HA相同的粘度并提供液膜润滑,还通过吸附确保了更好的边界润滑。为了证实HADN对软骨表面的保护作用,我们使用光学相干断层扫描(OCT)和原子力显微镜(AFM)观察了软骨磨损情况。

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