JRM Vol.25 No.4 pp. 657-664
doi: 10.20965/jrm.2013.p0657


Design and Fabrication of Changeable Cell Culture Mold

Puwanan Chumtong*, Masaru Kojima*, Kenichi Ohara**,
Yasushi Mae*, Mitsuhiro Horade*, Yoshikatsu Akiyama***,
Masayuki Yamato***, and Tatsuo Arai*

*Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama-cho, Toyonaka, Osaka 560-8531, Japan

**Faculty of Science and Technology, Meijo University, 1-501 Shiogamaguchi, Tempaku, Nagoya, Aichi 468-8502, Japan

***Institute of Advanced Biomedical Engineering and Science (ABMES) at TWIns, Tokyo Women’s Medical University (TWMU), 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan

February 12, 2013
June 6, 2013
August 20, 2013
cell culture device, microactuator array, fabrication of micropatterned gel sheet

Although the fabrication of engineered organs as replacements for damaged organs has been widely studied over the past decade, practical fabrication is very difficult because the engineered organ usually has a very complex structure and cannot be fabricated simply by using a fixed scaffold. Special attention has therefore been paid to methods of making engineered organs by assembling composite parts. Since structures of these individual parts are very different, fabrication using fixed scaffolds requires a lot of effort and time. The concept of a changeable scaffold offered by “changeable cell culture (C3) mold” is proposed in this paper as a means to simplify the fabrication of these parts. Using a thin PDMS membrane as an actuator layer enables various scaffold structures to be formed and altered, in turn enabling the fabrication of many different tissue structures. C3 mold consists of a 3 × 3 microactuator array with a diameter of 500 µm and spacing of 650 µm. Plant oil is used as the working fluid enabling deformation of the actuator layer. Various micropatterned gel sheets are fabricated, in order to demonstrate the possibility of using C3 molds in future tissue fabrication.

Cite this article as:
Puwanan Chumtong, Masaru Kojima, Kenichi Ohara,
Yasushi Mae, Mitsuhiro Horade, Yoshikatsu Akiyama,
Masayuki Yamato, and Tatsuo Arai, “Design and Fabrication of Changeable Cell Culture Mold,” J. Robot. Mechatron., Vol.25, No.4, pp. 657-664, 2013.
Data files:
  1. [1] T. Shimizu, M. Yamato, A. Kikuchi, and T. Okano, “Cell sheet engineering for myocardial tissue reconstruction,” Biomaterials, Vol.24, No.13, pp. 2309-2316, 2003.
  2. [2] Y. Haraguchi, T. Shimizu, T. Sasagawa, H. Sekine, K. Sakaguchi, T. Kikuchi, W. Sekine, S. Sekiya, M. Yamato, M. Umezu, and T. Okano, “Fabrication of functional three-dimensional tissues by stacking cell sheets in vitro,” Nature Protocols, Vol.7, No.5, pp. 850-858, 2012.
  3. [3] K. Sugibayashi, Y. Kumashiro, T. Shimizu, J. Kobayashi, and T. Okano, “A molded hyaluronic acid gel as a micro-template for blood capillaries,” J. of Biomaterials Science, Polymer Edition, Vol.24, 2013.
  4. [4] N. N. Kachouie, Y. Du, H. Bae, M. Khabiry, A. F. Ahari, B. Zamanian, J. Fukuda, and A. Khademhosseini, “Directed assembly of cell-laden hydrogels for engineering functional tissues,” Organogenesis, Vol.6, No.4, pp. 234-244, 2011.
  5. [5] A. Nishiguchi, H. Yoshida, M. Matsusaki, and M. Akashi, “Rapid construction of three-dimensional multilayered tissues with endothelial tube networks by the cell-accumulation technique,” Advanced Materials, Vol.23, pp. 3506-3510, 2011.
  6. [6] V. L. Tsang and S. N. Bhatia, “Three-dimensional tissue fabrication,” Advanced Drug Delivery Reviews, pp. 1635-1647, 2004.
  7. [7] T. Masuda, N. Takei, T. Nakano, T. Anada, O. Suzuki, and F. Arai, “A microfabricated platform to form three-dimensional toroidal multicellular aggregate,” Biomedical Microdevices, Vol.14, Issue 6, pp. 1085-1093, 2012.
  8. [8] T. Anada, T. Masuda, Y. Honda, J. Fukuda, F. Arai, T. Fukuda, and O. Suzuki, “Three-dimensional cell culture device utilizing thin membrane deformation by decompression,” Sensors and Actuators B: Chemical, Vol.147, pp. 376-379, 2010.
  9. [9] T. A. Gwyther, J. Z. Hu, K. L. Billiar, and M. W. Rolle, “Directed Cellular Self-Assembly to Fabricate Cell-Derived Tissue Rings for Biomechanical Analysis and Tissue Engineering,” J. of Visualized Experiments, Issue 57, 2011.
  10. [10] B. Guillotin and F. Guillemot, “Cell patterning technologies for organotypic tissue fabrication,” Trends in Biotechnology, Vol.29, No.4, pp. 183-190, 2011.
  11. [11] M. de Volder and D. Reynaerts, “Pneumatic and hydraulic microactuators: a review,” J. of Micromechanics and Microengineering, Vol.20, No.4, 2010.
  12. [12] J. H. Ryoo, G. S. Jeong, E. Kang, and S. H. Lee, “Ultrathin, hyperelastic PDMS nano membrane: fabrication and characterization,” Int. Conf. on Miniaturized Systems for Chemistry and Life Sciences, Seattle, Washington, USA, pp. 686-688, 2011.
  13. [13] T. Anada, J. Fukuda, Y. Sai, and O. Suzuki, “An oxygen-permeable spheroid culture system for the prevention of central hypoxia and necrosis of spheroids,” Biomaterials, Vol.33, Issue 33, pp. 8430-8441, 2012.
  14. [14] T. C. Merkel, V. I. Bondar, K. Nagai, B. D. Freeman, and I. Pinnau, “Gas Sorption, Diffusion, and Permeation in Poly(dimethylsiloxane),” J. of Polymer Science: Part B, Vol.38, pp. 415-434, 2000.
  15. [15] M. Johnson, G. Liddiard, M. Eddings, and B. Gale, “Bubble inclusion and removal using PDMS membrane-based gas permeation for applications in pumping, valving and mixing in microfluidic devices,” J. of Micromechanics and Microengineering, Vol.19, No.9, 2009.
  16. [16] K. Khanafer, A. Duprey, M. Schlicht, and R. Berguer, “Effects of strain rate, mixing ratio, and stress-strain definition on the mechanical behavior of the polydimethylsiloxane (PDMS) material as related to its biological applications,” Biomedical Microdevices, Vol.11, Issue 2, pp. 503-508, 2009.
  17. [17] S. Sang and H. Witte, “Fabrication of a surface stress-based PDMS micro-membrane biosensor,” Microsystem Technologies, Vol.16, Issue 6, pp. 1001-1008, 2010.
  18. [18] A. L. Thangawng, R. S. Ruoff, M. A. Swartz, and M. R. Glucksberg, “An ultra-thin PDMS membrane as a bio/micro-nano interface: fabrication and characterization,” Biomedical Microdevices, Vol.9, Issue 4, pp. 587-595, 2007.
  19. [19] H. Wu, B. Huang, and R. N. Zare, “Construction of microfluidic chips using polydimethylsiloxane for adhesive bonding,” The Royal Society of Chemistry, Vol.5, pp. 1393-1398, 2005.
  20. [20] B.-H. Jo, L. M. van Lerberghe, K. M. Motsegood, and D. J. Beebe, “Three-Dimensional Micro-Channel Fabrication in Polydimethylsiloxane (PDMS) Elastomer,” J. of Microelectromechanical Systems, Vol.9, No.1, pp. 76-81, 2000.
  21. [21] Y. Zhang, M. Ishida, Y. Kazoe, Y. Sato, and N. Miki, “Water-Vapor Permeability Control of PDMS by the Dispersion of Collagen Powder,” Trans. on Electrical and Electronic Engineering, Vol.4, No.3, pp. 442-449, 2009.

  22. Supporting Online Materials:
  23. [a] “National data reports of the Organ Procurement and Transplantation Network (OPTN),” Health Resources and Services Administration, U.S. Department of Health and Human Services. [Accessed January 18, 2013]

*This site is desgined based on HTML5 and CSS3 for modern browsers, e.g. Chrome, Firefox, Safari, Edge, Opera.

Last updated on Feb. 25, 2021