Auckland Bioengineering Institute, University of Auckland, Auckland 1010, New Zealand.
Department of Biomedical Science and Engineering, Inha University College of Medicine, Incheon 22212, South Korea.
J Biomech Eng. 2021 Aug 1;143(8). doi: 10.1115/1.4051116.
Physiological loading is essential for the maintenance of articular cartilage through the regulation of tissue remodeling. To correctly understand the behavior of chondrocytes in their native environment, cell stimulating devices and bioreactors have been developed to examine the effect of mechanical stimuli on chondrocytes. This study describes the design and validation of a novel system for analyzing chondrocyte deformation patterns. This involves an in vitro mechanical device for a controlled application of multi-axial-loading regimes to chondrocyte-seeded agarose constructs and in silico models for analyzing chondrocyte deformation patterns. The computer-controlled device precisely applies compressive, tensile, and shear strains to hydrogel constructs using a customizable macro-based program. The synchronization of the displacements is shown to be accurate with a 1.2% error and is highly reproducible. The device design allows housing for up to eight novel designed free-swelling three-dimensional hydrogel constructs. Constructs include mesh ends and are optimized to withstand the application of up to 7% mechanical tensile and 15% shear strains. Constructs were characterized through mapping the strain within as mechanical load was applied and was validated using light microscopy methods, chondrocyte viability using live/dead imaging, and cell deformation strains. Images were then analyzed to determine the complex deformation strain patterns of chondrocytes under a range of dynamic mechanical stimulations. This is one of the first systems that have characterized construct strains to cellular strains. The features in this device make the system ideally suited for a systematic approach for the investigation of the response of chondrocytes to a complex physiologically relevant deformation profile.
生理负荷对于通过调节组织重塑来维持关节软骨是必不可少的。为了正确了解软骨细胞在其自然环境中的行为，已经开发出细胞刺激装置和生物反应器来检查机械刺激对软骨细胞的影响。本研究描述了一种用于分析软骨细胞变形模式的新型系统的设计和验证。这涉及一种体外机械装置，用于对软骨细胞接种琼脂糖构建体进行多轴加载方案的受控应用，以及用于分析软骨细胞变形模式的计算模型。计算机控制的装置使用可定制的基于宏的程序精确地向水凝胶构建体施加压缩、拉伸和剪切应变。位移的同步性显示出具有 1.2%的误差的准确性，并且高度可重复。该装置设计允许容纳多达八个新设计的自由膨胀三维水凝胶构建体。构建体包括网格端，并经过优化，可承受高达 7%的机械拉伸和 15%的剪切应变。通过在施加机械载荷时映射构建体内的应变来对构建体进行特征描述，并使用荧光显微镜方法、活/死成像中的软骨细胞活力和细胞变形应变进行验证。然后分析图像以确定在一系列动态机械刺激下软骨细胞的复杂变形应变模式。这是第一个对构建体应变到细胞应变进行特征描述的系统之一。该装置的特点使其非常适合用于系统地研究软骨细胞对复杂生理相关变形谱的反应。
