Bioengineered lubricin alters the lubrication modes of cartilage in a dose-dependent manner.

IF 2.1 3区 医学 Q2 ORTHOPEDICS Journal of Orthopaedic Research® Pub Date : 2024-11-09 DOI:10.1002/jor.26009
Karan Vishwanath, Jin Su, Marshall J Colville, Matthew Paszek, Heidi L Reesink, Lawrence J Bonassar
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Abstract

The low friction nature of articular cartilage has been attributed to the synergistic interaction between lubricin and hyaluronic acid in the synovial fluid (SF). Lubricin is a mucinous glycoprotein that lowers the boundary mode coefficient of friction of articular cartilage in a dose-dependent manner. While there have been multiple attempts to produce recombinant lubricin and lubricin mimetic cartilage lubricants over the last two decades, these materials have not found clinical use due to challenges associated with large scale production, manufacturing, and purification. Recently, a novel method using codon scrambling was developed to produce a stable, full-length bioengineered equine lubricin (eLub) in large reproducible quantities. While preliminary frictional analysis of eLub and other recombinantly produced forms revealed they can lubricate cartilage, a complete tribological characterization is lacking, with previous studies evaluating the friction coefficient only at a single dose or a single speed. The objective of this study was to analyze the dose-dependent tribological properties of eLub using the Stribeck framework of tribological analysis. Recombinantly produced eLub at doses greater than 1.5 mg/mL exhibits friction coefficients on par with healthy bovine SF, and a maximal 5 mg/mL dose exhibits a nearly 50% lower friction coefficient than healthy SF. eLub also modulates the shift in lubrication mode of the cartilage from the high friction boundary mode to the low friction minimum mode at high concentrations.

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生物工程润滑素以剂量依赖的方式改变软骨的润滑模式。
关节软骨的低摩擦性归因于滑液(SF)中的润滑蛋白和透明质酸之间的协同作用。润滑素是一种粘液糖蛋白,能以剂量依赖性方式降低关节软骨的边界摩擦系数。在过去的二十年里,人们曾多次尝试生产重组润滑蛋白和润滑蛋白模拟软骨润滑剂,但由于大规模生产、制造和纯化方面的挑战,这些材料一直未能应用于临床。最近,一种使用密码子扰乱的新方法被开发出来,用于大量生产稳定的全长生物工程马润滑蛋白(eLub)。虽然对 eLub 和其他重组生产的形式进行的初步摩擦分析表明它们可以润滑软骨,但缺乏完整的摩擦学特征描述,以往的研究仅评估了单一剂量或单一速度下的摩擦系数。本研究的目的是利用斯特里贝克摩擦学分析框架来分析 eLub 随剂量变化的摩擦学特性。重组生产的eLub在剂量大于1.5毫克/毫升时的摩擦系数与健康牛SF相当,最大剂量为5毫克/毫升时的摩擦系数比健康SF低近50%。
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来源期刊
Journal of Orthopaedic Research®
Journal of Orthopaedic Research® 医学-整形外科
CiteScore
6.10
自引率
3.60%
发文量
261
审稿时长
3-6 weeks
期刊介绍: The Journal of Orthopaedic Research is the forum for the rapid publication of high quality reports of new information on the full spectrum of orthopaedic research, including life sciences, engineering, translational, and clinical studies.
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