Three-dimensional spheroid culture targeting versatile tissue bioassays using a PDMS-based hanging drop array

  • Sci Rep. 2017 Jun 29;7(1):4363. doi: 10.1038/s41598-017-04718-1.
Ching-Te Kuo  1  2 Jong-Yueh Wang  2 Yu-Fen Lin  1 Andrew M Wo  3 Benjamin P C Chen  4 Hsinyu Lee  5
Affiliations
  • 1. Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 2. Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
  • 3. Institute of Applied Mechanics, National Taiwan University, Taipei, Taiwan, ROC.
  • 4. Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA. [email protected].
  • 5. Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC. [email protected].
Abstract

Biomaterial-based tissue culture platforms have emerged as useful tools to mimic in vivo physiological microenvironments in experimental Cell Biology and clinical studies. We describe herein a three-dimensional (3D) tissue culture platform using a polydimethylsiloxane (PDMS)-based hanging drop array (PDMS-HDA) methodology. Multicellular spheroids can be achieved within 24 h and further boosted by incorporating Collagen fibrils in PDMS-HDA. In addition, the spheroids generated from different human tumor cells exhibited distinct sensitivities toward drug chemotherapeutic agents and radiation as compared with two-dimensional (2D) cultures that often lack in vivo-like biological insights. We also demonstrated that multicellular spheroids may enable key hallmarks of tissue-based bioassays, including drug screening, tumor dissemination, cell co-culture, and tumor invasion. Taken together, these results offer new opportunities not only to achieve the active control of 3D multicellular spheroids on demand, but also to establish a rapid and cost-effective platform to study anti-cancer therapeutics and tumor microenvironments.