Chang Minki, Takahashi Yosuke, Miyahira Kyosuke, Omuro Yuma, Montagne Kevin, Yamada Ryusei, Gondo Junki, Kambe Yu, Yasuno Masashi, Masumoto Noriyasu, Ushida Takashi, Furukawa Katsuko S
Department of Bioengineering, Graduate School of Engineering, University of Tokyo, Tokyo 113-8656, Japan.
Department of Mechanical Engineering, Graduate School of Engineering, University of Tokyo, Tokyo 113-8656, Japan.
Micromachines (Basel). 2023 Aug 18;14(8):1632. doi: 10.3390/mi14081632.
In vivo, articular cartilage tissue is surrounded by a cartilage membrane, and hydrostatic pressure (HP) and compressive strain increase simultaneously with the compressive stress. However, it has been impossible to investigate the effects of simultaneous loading in vitro. In this study, a bioreactor capable of applying compressive stress under HP was developed to reproduce ex vivo the same physical loading environment found in cartilage. First, a HP stimulation unit was constructed to apply a cyclic HP pressure-resistant chamber by controlling a pump and valve. A compression-loading mechanism that can apply compressive stress using an electromagnetic force was implemented in the chamber. The synchronization between the compression and HP units was evaluated, and the stimulation parameters were quantitatively evaluated. Physiological HP and compressive strain were applied to the chondrocytes encapsulated in alginate and gelatin gels after applying high HP at 25 MPa, which induced damage to the chondrocytes. It was found that compressive stimulation increased the expression of genes related to osteoarthritis. Furthermore, the simultaneous application of compressive strain and HP, which is similar to the physiological environment in cartilage, had an inhibitory effect on the expression of genes related to osteoarthritis. HP alone also suppressed the expression of osteoarthritis-related genes. Therefore, the simultaneous hydrostatic and compressive stress-loading device developed to simulate the mechanical environment in vivo may be an important tool for elucidating the mechanisms of disease onset and homeostasis in cartilage.
在体内，关节软骨组织被软骨膜包围，静水压力（HP）和压缩应变随压缩应力同时增加。然而，在体外研究同时加载的影响一直是不可能的。在本研究中，开发了一种能够在HP下施加压缩应力的生物反应器，以在体外再现软骨中发现的相同物理加载环境。首先，构建了一个HP刺激单元，通过控制泵和阀门来施加循环HP耐压腔。在腔室内实现了一种能够利用电磁力施加压缩应力的压缩加载机制。评估了压缩单元和HP单元之间的同步性，并对刺激参数进行了定量评估。在25MPa的高HP作用下对包裹在藻酸盐和明胶凝胶中的软骨细胞造成损伤后，对其施加生理HP和压缩应变。发现压缩刺激增加了与骨关节炎相关基因的表达。此外，与软骨中的生理环境相似的压缩应变和HP的同时施加对与骨关节炎相关基因的表达具有抑制作用。单独的HP也抑制了骨关节炎相关基因的表达。因此，为模拟体内机械环境而开发的同时施加静水压力和压缩应力的加载装置可能是阐明软骨疾病发病机制和稳态的重要工具。
