Development of high-throughput perfusion-based microbioreactor platform capable of providing tunable dynamic tensile loading to cells and its application for the study of bovine articular chondrocytes |
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| Authors: | Min-Hsien Wu Hsin-Yao Wang Heng-Liang Liu Shih-Siou Wang Yen-Ting Liu Yan-Ming Chen Shiao-Wen Tsai Chun-Li Lin |
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| Institution: | (1) Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan;(2) School of Medicine, Chang Gung University, Taoyuan, Taiwan;(3) Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan;(4) Department of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan; |
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| Abstract: | Mammalian cells are sensitive to extracellular microenvironments. In order to precisely explore the physiological responses
of cells to tensile loading, a stable and well-defined culture condition is required. In this study, a high-throughput perfusion-based
microbioreactor platform capable of providing dynamic equibiaxial tensile loading to the cultured cells under a steady culture
condition was proposed. The mechanism of generating tensile stimulation to cells is based on the pneumatically-driven deformation
of an elastic polydimethylsiloxan (PDMS) membrane which exerts tensile loading to the attached cells. By modulating the magnitude
and frequency of the applied pneumatic pressure, various tensile loading can be generated in a controllable manner. In this
study, the microbioreactor platform was designed with the aid of the experimentally-validated finite element (FE) analysis
to ensure the loading of tensile strain to cells is uniform and definable. Based on this design, the quantitative relationship
between the applied pneumatic pressure and the generated tensile strain on the PDMS membrane was established via FE analysis.
Results demonstrated that the proposed device was able to generate the tensile strain range (0~0.12), which covers the physiological
condition that articular chondrocytes experience tensile strain under human walking condition. In this study, moreover, the
effect of tensile loading on the metabolic, biosynthetic and proliferation activities of articular chondrocytes was investigated.
Results disclosed that the dynamic tensile loading of 0.12 strain at 1 Hz might significantly up-regulate the synthesis of
glycosaminoglycans while such stimulation was found no significant influence on the metabolic activity, the synthesis of collagen,
and the proliferation of chondrocytes. Overall, this study has presented a high throughput perfusion micro cell culture device
that is suitable for precisely exploring the effect of tensile loading on cell physiology. |
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