Morphologic Reconstruction of 2D Cellular Micro-scaffold Based on Digital Holographic Feedback

  • Xin LiEmail author
  • Huaping Wang
  • Qing Shi
  • Juan Cui
  • Tao Sun
  • Hongpeng Qin
  • Qiang Huang
  • Toshio Fukuda
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 11740)


The artificial 2D cellular micro-scaffold is increasingly needed in tissue engineering and biomedical engineering. Yet, the study of the influence between the scaffold physical properties and the cell behaviors during cell cultures still remains lacking. In this paper, the micro-scaffold based on the PEGDA hydrogel was fabricated by combining digital holographic microscope technique and DMD-based manipulation system. The morphology and thickness coefficients of the micro-scaffold shaped under the UV exposure was sampled in real-time by the holographic microscopy as the feedback and utilized to control the DMD-based local solidification of the micro-scaffold, which can modify and reconstruct the morphology of the scaffold to improve the fidelity of the shape. With this technique, the system can fabricate micro-scaffold with any customized shape and thickness, which can be seeded or encapsulated with cells to study the influence of substrate mechanism to the cell behaviors under micro-nano scale. The RGDS-linked (Arg-Gly-Asp-Ser) PEGDA as a typical hydrogel was utilized to fabricate the micro-scaffold to verify the effectiveness of the system. Through encapsulating NIH/3T3 cells inside scaffold with different morphologies, we cultured the cells for 7 days and evaluate the cell behaviors. As a result, the NIH/3T3 cell can maintain different proliferation speed with very high cell viability. The proposed micro-scaffold fabrication method provide novel techniques for more accurate biofabrication of microtissues for the future regenerative medicine.


2D cellular micro-scaffold Cell behavior study PEGDA hydrogel Digital holographic microscope Tissue engineering 



This research was funded by National Key R&D Program of China under grant number 2017YFE0117000, and National Nature Science Foundation of China (NSFC) under grant number 61603044.


  1. 1.
    Chan, V., Zorlutuna, P., Jeong, J.H., et al.: Three-dimensional photopatterning of hydrogels using stereolithography for long-term cell encapsulation. Lab Chip 10(16), 2062–2070 (2010)CrossRefGoogle Scholar
  2. 2.
    Chiang, M.Y., Hsu, Y.W., Hsieh, H.Y., et al.: Constructing 3D heterogeneous hydrogels from electrically manipulated prepolymer droplets and crosslinked microgels. Sci. Adv. 2(10), e1600964–e1600964 (2016)CrossRefGoogle Scholar
  3. 3.
    Lauffenburger, D.A.: Cell migration: a physically integrated molecular process. Cell 84(3), 359–369 (1996)CrossRefGoogle Scholar
  4. 4.
    Klymkowsky, M.W., Parr, B.: The body language of cells: The intimate connection between cell adhesion and behavior. Cell 83(1), 5–8 (1995)CrossRefGoogle Scholar
  5. 5.
    Pathak, A., Kumar, S.: Independent regulation of tumor cell migration by matrix stiffness and confinement. Proc. National Acad. Sci. 109(26), 10334–10339 (2012)CrossRefGoogle Scholar
  6. 6.
    Aubin, H., Nichol, J.W., et al.: Directed 3D cell alignment and elongation in microengineered hydrogels. Biomaterials 31(27), 6941–6951 (2010)CrossRefGoogle Scholar
  7. 7.
    Kim, H.N., Kang, D.H., Kim, M.S., et al.: Patterning methods for polymers in cell and tissue engineering. Ann. Biomed. Eng. 40(6), 1339–1355 (2012)CrossRefGoogle Scholar
  8. 8.
    Pedde, R.D., Mirani, B., Navaei, A., et al.: Emerging biofabrication strategies for engineering complex tissue constructs. Adv. Mater. 29(19), 1–27 (2017)CrossRefGoogle Scholar
  9. 9.
    Bhise, N.S., Manoharan, V., Massa, S., et al.: A liver-on-a-chip platform with bioprinted hepatic spheroids. Biofabrication 8(1), 1–9 (2016)CrossRefGoogle Scholar
  10. 10.
    Qian, J., Lei, M., Dan, D., et al.: Full-color structured illumination optical sectioning microscopy. Sci. Rep. 5(1), 1–13 (2015)Google Scholar
  11. 11.
    Chung, S.E., Park, W., Park, H., et al.: Optofluidic maskless lithography system. In: Transducers International Actuators & Microsystems Conference. IEEE (2007)Google Scholar
  12. 12.
    Fedorovich, N.E., Oudshoorn, M.H., Geemen, D.V., et al.: The effect of photopolymerization on stem cells embedded in hydrogels. Biomaterials 30(3), 344–353 (2009)CrossRefGoogle Scholar
  13. 13.
    Mann, B.K., Gobin, A.S., Tsai, A.T., et al.: Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: synthetic ECM analogs for tissue engineering. Biomaterials 22(22), 3045–3051 (2001)CrossRefGoogle Scholar
  14. 14.
    Latychevskaia, T., Fink, H.W.: Simultaneous reconstruction of phase and amplitude contrast from a single holographic record. Opt. Express 17(13), 10697–10705 (2009)CrossRefGoogle Scholar
  15. 15.
    Dainty, J.C.: Optical holography: principles, techniques and applications. Opt. Acta Int. J. Opt. 32(1), 1 (1985)CrossRefGoogle Scholar
  16. 16.
    Kim, M.K.: Principles and techniques of digital holographic microscopy. J. Photonics Energy 1(1), 1–51 (2009)Google Scholar
  17. 17.
    Park, K.H., Na, K., Kim, S.W., et al.: Phenotype of hepatocyte spheroids behavior within thermo-sensitive poly (NiPAAm-co-PEG-g-GRGDS) hydrogel as a cell delivery vehicle. Biotechnol. Lett. 27(15), 1081–1086 (2005)CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Xin Li
    • 1
    Email author
  • Huaping Wang
    • 1
  • Qing Shi
    • 1
  • Juan Cui
    • 1
  • Tao Sun
    • 1
  • Hongpeng Qin
    • 2
  • Qiang Huang
    • 1
  • Toshio Fukuda
    • 1
  1. 1.The Intelligent Robotics Institute, School of Mechatronical EngineeringBeijing Institute of TechnologyBeijingChina
  2. 2.Beijing TaiGeekTechnology Co., Ltd.BeijingChina

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