A High-Throughput Mechanical Activator for Cartilage Engineering Enables Rapid Screening of in vitro Response of Tissue Models to Physiological and Supra-Physiological Loads.
A High-Throughput Mechanical Activator for Cartilage Engineering Enables Rapid Screening of in vitro Response of Tissue Models to Physiological and Supra-Physiological Loads.
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DOI：
10.1159/000514985
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发表时间：
2022
影响因子：
2.7
通讯作者：
Gottardi, Riccardo
中科院分区：
文献类型：
--
作者：
Capuana, Elisa;Marino, Davide;Di Gesu, Roberto;La Carrubba, Vincenzo;Brucato, Valerio;Tuan, Rocky S.;Gottardi, Riccardo
关节软骨在发育、健康和疾病期间受到负荷的显着影响。然而，我们对促进工程软骨成熟或组织修复的机械条件的了解仍然不完整。目前允许精确控制局部机械环境的体外模型受到吞吐量非常低的极大限制，通常每个实验只有几个样本。为了克服这一限制，我们开发了一种用于组织结构高通量压缩加载的新设备：软骨工程高通量机械激活器 (HiT-MACE)，它可以机械激活比现有技术多 6 倍的样品。借助 HiT-MACE，我们能够在一次运行中对多达 24 个样本应用生理范围（例如，相当于步行和正常日常活动）和超生理范围（例如，有害冲击或广泛超载）的循环载荷。在本报告中，我们将软骨对生理和超生理机械负荷的早期反应与对 IL-1β 暴露的反应进行了比较，IL-1β 是一种常见但初级的软骨骨关节炎体外模型。生理负荷沿着 TGF-β1 途径快速上调合成代谢标志物的基因表达。值得注意的是，培养基中不包含TGF-β1或血清。超生理负荷引起轻微的分解代谢反应，而 IL-1β 暴露则导致快速的合成代谢转变。这与最近的研究结果非常吻合，表明超载是软骨退化的更现实和仿生模型。总而言之，这些发现表明，HiT-MACE 的应用允许使用更多的样本来生成更多的数据，以有效地探索软骨力学生物学，这将使设计更有效的退行性软骨病理修复和康复策略成为可能。
Articular cartilage is crucially influenced by loading during development, health, and disease. However, our knowledge of the mechanical conditions that promote engineered cartilage maturation or tissue repair is still incomplete. Current in vitro models that allow precise control of the local mechanical environment have been dramatically limited by very low throughput, usually just a few specimens per experiment. To overcome this constraint, we have developed a new device for the high throughput compressive loading of tissue constructs: the High Throughput Mechanical Activator for Cartilage Engineering (HiT-MACE), which allows the mechanoactivation of 6 times more samples than current technologies. With HiT-MACE we were able to apply cyclic loads in the physiological (e.g., equivalent to walking and normal daily activity) and supra-physiological range (e.g., injurious impacts or extensive overloading) to up to 24 samples in one single run. In this report, we compared the early response of cartilage to physiological and supra-physiological mechanical loading to the response to IL-1β exposure, a common but rudimentary in vitro model of cartilage osteoarthritis. Physiological loading rapidly upregulated gene expression of anabolic markers along the TGF-β1 pathway. Notably, TGF-β1 or serum was not included in the medium. Supra-physiological loading caused a mild catabolic response while IL-1β exposure drove a rapid anabolic shift. This aligns well with recent findings suggesting that overloading is a more realistic and biomimetic model of cartilage degeneration. Taken together, these findings showed that the application of HiT-MACE allowed the use of larger number of samples to generate higher volume of data to effectively explore cartilage mechanobiology, which will enable the design of more effective repair and rehabilitation strategies for degenerative cartilage pathologies.
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