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.
Highlights
Three-dimensional (3D) tissue cultures show distinct characteristics in terms of cellular heterogeneity/plasticity/ morphology, mass transport, and complex cell-matrix or cell-cell interactions as compared with conventional 2D cell cultures[1,2,3]
The improved methodology relied on the interaction between PDMS surfaces and collagen fibrils Fig. 1(a–c)
Our results indicate that supplementing the medium mixture with 500 μg/ml collagen is the optimal condition to induce the growth of a single and compact spheroid of MCF7 and MDA-MB-231 cells hung by the PDMS surface Fig. (1e)
Summary
Three-dimensional (3D) tissue cultures show distinct characteristics in terms of cellular heterogeneity/plasticity/ morphology, mass transport, and complex cell-matrix or cell-cell interactions as compared with conventional 2D cell cultures[1,2,3]. The malignant phenotypes and the mechanotransduction between extracellular matrix (ECM) and cells dramatically diminish in 2D4–7 Because of their ability to mimic human physiological conditions and integrating with high-throughput and high-content techniques, biomaterial-based tissue culture platforms are ideal tools to address these critical issues. Different techniques have been tested for 3D tissue culture platforms including organic[10, 11] or inorganic matrix[12, 13] coating on plastic substrates, paper-supported scaffolds[2, 14], magnetic levitation of cells[15], and hanging drops[16].
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