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使用机械刺激增强组织工程关节软骨性能的指南。

A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties.

机构信息

Biomedical Engineering Department, University of California , Irvine, California.

出版信息

Tissue Eng Part B Rev. 2018 Oct;24(5):345-358. doi: 10.1089/ten.TEB.2018.0006. Epub 2018 Apr 26.

Abstract

The use of tissue-engineered articular cartilage (TEAC) constructs has the potential to become a powerful treatment option for cartilage lesions resulting from trauma or early stages of pathology. Although fundamental tissue-engineering strategies based on the use of scaffolds, cells, and signals have been developed, techniques that lead to biomimetic AC constructs that can be translated to in vivo use are yet to be fully confirmed. Mechanical stimulation during tissue culture can be an effective strategy to enhance the mechanical, structural, and cellular properties of tissue-engineered constructs toward mimicking those of native AC. This review focuses on the use of mechanical stimulation to attain and enhance the properties of AC constructs needed to translate these implants to the clinic. In vivo, mechanical loading at maximal and supramaximal physiological levels has been shown to be detrimental to AC through the development of degenerative changes. In contrast, multiple studies have revealed that during culture, mechanical stimulation within narrow ranges of magnitude and duration can produce anisotropic, mechanically robust AC constructs with high cellular viability. Significant progress has been made in evaluating a variety of mechanical stimulation techniques on TEAC, either alone or in combination with other stimuli. These advancements include determining and optimizing efficacious loading parameters (e.g., duration and frequency) to yield improvements in construct design criteria, such as collagen II content, compressive stiffness, cell viability, and fiber organization. With the advancement of mechanical stimulation as a potent strategy in AC tissue engineering, a compendium detailing the results achievable by various stimulus regimens would be of great use for researchers in academia and industry. The objective is to list the qualitative and quantitative effects that can be attained when direct compression, hydrostatic pressure, shear, and tensile loading are used to tissue-engineer AC. Our goal is to provide a practical guide to their use and optimization of loading parameters. For each loading condition, we will also present and discuss benefits and limitations of bioreactor configurations that have been used. The intent is for this review to serve as a reference for including mechanical stimulation strategies as part of AC construct culture regimens.

摘要

组织工程化关节软骨(TEAC)构建物的应用具有成为治疗创伤或早期病理导致的软骨损伤的有效治疗选择的潜力。尽管已经开发出基于使用支架、细胞和信号的基本组织工程策略,但导致能够转化为体内使用的仿生 AC 构建物的技术尚未得到充分证实。组织培养过程中的机械刺激可以是一种有效的策略,可增强组织工程化构建物的机械、结构和细胞特性,以模拟天然 AC。本综述重点介绍了机械刺激在获得和增强 AC 构建物特性方面的应用,这些特性对于将这些植入物转化为临床应用至关重要。在体内,最大和超生理水平的机械负荷已被证明对 AC 有害,会导致退行性变化。相比之下,多项研究表明,在培养过程中,在幅度和持续时间的狭窄范围内进行机械刺激可以产生各向异性的、机械坚固的 AC 构建物,具有高细胞活力。在 TEAC 中,已经在评估各种机械刺激技术方面取得了重大进展,这些技术可以单独使用或与其他刺激物结合使用。这些进展包括确定和优化有效的加载参数(例如,持续时间和频率),以提高构建物设计标准,例如胶原 II 含量、压缩刚度、细胞活力和纤维组织。随着机械刺激作为 AC 组织工程中的有效策略的发展,详细列出各种刺激方案可以实现的结果的汇编将对学术界和工业界的研究人员非常有用。目的是列出直接压缩、静水压力、剪切和拉伸加载用于组织工程化 AC 时可以获得的定性和定量效果。我们的目标是提供有关使用和优化加载参数的实用指南。对于每种加载条件,我们还将介绍和讨论已经使用的生物反应器配置的优缺点。本综述旨在作为将机械刺激策略作为 AC 构建物培养方案的一部分的参考。

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