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一种仿生型黏液附着剂通过重建板层样结构恢复退化软骨的润滑功能。

A bioinspired mucoadhesive restores lubrication of degraded cartilage through reestablishment of lamina splendens.

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.

出版信息

Colloids Surf B Biointerfaces. 2020 Sep;193:110977. doi: 10.1016/j.colsurfb.2020.110977. Epub 2020 Apr 30.

DOI:10.1016/j.colsurfb.2020.110977
PMID:32408255
Abstract

Adsorbed lubricious films composed of biomacromolecules are natively present at all articulating interfaces in the human body where they provide ultralow friction and maintain normal physiological function. Biolubrication gets impaired due to diseases such as osteoarthritis, in which cartilage damage results from alterations in synovial fluid and lamina splendens composition. Osteoarthritis is treated with hyaluronic acid (HA) orally or via intra-articular injection, but due to the poor adsorption of HA on the cartilage surface in the absence of adhesive molecules, pain relief is temporary. Here, we describe how natural lubrication on degraded cartilage surface can be restored with the help of a bioinspired mucoadhesive biopolymer chitosan catechol (Chi-C). Quartz crystal microbalance was used to mimic the formation of lamina splendens in vitro, known as synovial fluid conditioning films (SyCF), and colloidal probe atomic force microscopy was used to measure their nanoscale frictional properties. Clear evidence of glycoprotein (PRG4) recruitment by Chi-C increased the softness of SyCF, which also improved nanoscale lubrication in vitro, decreasing the friction coefficient from 0.06 to 0.03. At the macroscale, cartilage damage induced by Chondroitinase ABC increased the coefficient of friction (COF) from 0.07 ± 0.04 (healthy tissue) to 0.15 ± 0.03 (after tissue damage) in the presence of synovial fluid after sliding for 50 min. After Chi-C treatment of damaged cartilage, the COF fell to 0.06 ± 0.03, which is comparable to healthy cartilage. Chi-C did not adversely affect the metabolic activity of human chondrocytes. This study provides new key insight into the potential for restoring biolubrication through the use of muco-adhesive molecules.

摘要

吸附性生物大分子润滑膜存在于人体所有的关节界面中,它们提供超低摩擦力并维持正常的生理功能。由于骨关节炎等疾病,生物润滑作用会受到损害,在这些疾病中,软骨损伤是由于滑液和板层弹性蛋白组成的改变而导致的。骨关节炎的治疗方法是口服或关节内注射透明质酸(HA),但由于缺乏粘性分子,HA 在软骨表面的吸附不良,因此缓解疼痛是暂时的。在这里,我们描述了如何在没有粘性分子的情况下,借助生物仿生黏附性生物聚合物几丁质儿茶酚(Chi-C)来恢复降解软骨表面的天然润滑。我们使用石英晶体微天平模拟板层弹性蛋白在体外的形成,即滑液调理膜(SyCF),并使用胶体探针原子力显微镜测量它们的纳米级摩擦特性。Chi-C 对糖蛋白(PRG4)的明显募集增加了 SyCF 的柔软度,这也改善了体外纳米级润滑,使摩擦系数从 0.06 降低到 0.03。在宏观层面上,软骨损伤诱导的软骨素酶 ABC 增加了滑液中的摩擦系数(COF),从 0.07 ± 0.04(健康组织)增加到 0.15 ± 0.03(组织损伤后),在滑行了 50 分钟后。在 Chi-C 处理受损软骨后,COF 降至 0.06 ± 0.03,与健康软骨相当。Chi-C 不会对人软骨细胞的代谢活性产生不利影响。这项研究为通过使用黏附性分子恢复生物润滑提供了新的关键见解。

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