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A high-throughput three-dimensional cell culture platform for drug screening

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Abstract

Traditional two-dimensional (2D) cell cultures lack the extracellular matrix (ECM)-like structure or dynamic fluidic microenvironment for cells to maintain in vivo functionality. Three-dimensional (3D) tissue scaffolds, on the other hand, could provide the ECM-like microenvironment for cells to reformulate into tissue or organoids that are highly useful for in vitro drug screening. In this study, a high-throughput two-chamber 3D microscale tissue model platform is developed. Porous scaffolds are selectively foamed on a commercially available compact disk using laser. Perfusion of cell culture medium is achieved with centrifugal force-driven diffusion by disk rotation. Experimental studies were conducted on the fabrication process under various gas saturation and laser power conditions. Cell cultures were performed with two types of human cell lines: M059K and C3A-sub28. It is shown that the structure of microscale porous scaffolds can be controlled with laser foaming parameters and that coating with polydopamine these scaffolds are inducive for cell attachment and aggregation, forming a 3D network. With many such two-chamber models fabricated on a single CD and perfusion driven by the centrifugal force from rotation, the proposed platform provides a simple solution to the high-cost and lengthy drug development process with a high-throughput and physiologically more relevant tissue model system.

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References

  1. Abbott A (2003) Cell culture: biology’s new dimension. Nature 424(6951):870–872

    Article  Google Scholar 

  2. Venkatesh S, Lipper RA (2000) Role of the development scientist in compound lead selection and optimization. J Pharm Sci 89(2):145–154

    Article  Google Scholar 

  3. Ma L, Barker J, Zhou C, Li W, Zhang J, Lin B et al (2012) Towards personalized medicine with a three-dimensional micro-scale perfusion-based two-chamber tissue model system. Biomaterials 33(17):4353–4361

    Article  Google Scholar 

  4. Powers MJ, Janigian DM, Wack KE, Baker CS, Beer Stolz D, Griffith LG (2002) Functional behavior of primary rat liver cells in a three-dimensional perfused microarray bioreactor. Tissue Eng 8(3):499–513

    Article  Google Scholar 

  5. Domansky K, Inman W, Serdy J, Dash A, Lim MH, Griffith LG (2010) Perfused multiwell plate for 3D liver tissue engineering. Lab Chip 10(1):51–58

    Article  Google Scholar 

  6. Ock J, Li W (2014) Fabrication of a three-dimensional tissue model microarray using laser foaming of a gas-impregnated biodegradable polymer. Biofabrication 6(2):024110

    Article  Google Scholar 

  7. Ock J, Li W (eds) Selective laser foaming for three-dimensional cell culture on a compact disc. In: ASME 2015 international manufacturing science and engineering conference; 2015. V002T03A007

  8. Ock J, Li W (2017) Modeling and simulation of a selective laser foaming process for fabrication of microliter tissue engineering scaffolds. J Manuf Sci E-T ASME 139(11):111016

    Article  Google Scholar 

  9. Ock JG, Li W (2015) Selective laser foaming for three-dimensional cell culture on a compact disc. In: Proceedings of the ASME 10th international manufacturing science and engineering conference, vol 2

  10. Cho JH, Katsumata R, Zhou SX, Kim CB, Dulaney AR, Janes DW et al (2016) Ultrasmooth polydopamine modified surfaces for block copolymer nanopatterning on flexible substrates. ACS Appl Mater Interfaces 8(11):7456–7463

    Article  Google Scholar 

  11. Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9(7):671–675

    Article  Google Scholar 

  12. Wang H, Li W (2008) Selective ultrasonic foaming of polymer for biomedical applications. J Manuf Sci Eng 130(2):021004

    Article  Google Scholar 

  13. Wang X, Li W, Kumar V (2006) A method for solvent-free fabrication of porous polymer using solid-state foaming and ultrasound for tissue engineering applications. Biomaterials 27(9):1924–1929

    Article  Google Scholar 

  14. Oh SH, Park IK, Kim JM, Lee JH (2007) In vitro and in vivo characteristics of PCL scaffolds with pore size gradient fabricated by a centrifugation method. Biomaterials 28(9):1664–1671

    Article  Google Scholar 

  15. Yang S, Leong K-F, Du Z, Chua C-K (2001) The design of scaffolds for use in tissue engineering. Part I. Traditional factors. Tissue Eng 7(6):679–689

    Article  Google Scholar 

  16. Danielsson C, Ruault S, Simonet M, Neuenschwander P, Frey P (2006) Polyesterurethane foam scaffold for smooth muscle cell tissue engineering. Biomaterials 27(8):1410–1415

    Article  Google Scholar 

  17. Schwartz I, Robinson BP, Hollinger JO, Szachowicz EH, Brekke J (1995) Calvarial bone repair with porous D, L-polylactide. Otolaryngol Head Neck Surg 112(6):707–713

    Article  Google Scholar 

  18. Zardiackas LD, Parsell DE, Dillon LD, Mitchell DW, Nunnery LA, Poggie R (2001) Structure, metallurgy, and mechanical properties of a porous tantalum foam. J Biomed Mater Res 58(2):180–187

    Article  Google Scholar 

  19. Bobyn J, Stackpool G, Hacking S, Tanzer M, Krygier J (1999) Characteristics of bone ingrowth and interface mechanics of a new porous tantalum biomaterial. J Bone Joint Surg Br 81(5):907–914

    Article  Google Scholar 

  20. Krasteva N, Seifert B, Albrecht W, Weigel T, Schossig M, Altankov G et al (2004) Influence of polymer membrane porosity on C3A hepatoblastoma cell adhesive interaction and function. Biomaterials 25(13):2467–2476

    Article  Google Scholar 

  21. Lee J, Cuddihy MJ, Kotov NA (2008) Three-dimensional cell culture matrices: state of the art. Tissue Eng Part B Rev 14(1):61–86

    Article  Google Scholar 

  22. Ravi M, Paramesh V, Kaviya S, Anuradha E, Solomon F (2015) 3D cell culture systems: advantages and applications. J Cell Physiol 230(1):16–26

    Article  Google Scholar 

  23. Millerot-Serrurot E, Guilbert M, Fourré N, Witkowski W, Said G, Van Gulick L et al (2010) 3D collagen type I matrix inhibits the antimigratory effect of doxorubicin. Cancer Cell Int 10(1):26

    Article  Google Scholar 

  24. Loessner D, Stok KS, Lutolf MP, Hutmacher DW, Clements JA, Rizzi SC (2010) Bioengineered 3D platform to explore cell–ECM interactions and drug resistance of epithelial ovarian cancer cells. Biomaterials 31(32):8494–8506

    Article  Google Scholar 

  25. Lee S-W, Kang JY, Lee I-H, Ryu S-S, Kwak S-M, Shin K-S et al (2008) Single-cell assay on CD-like lab chip using centrifugal massive single-cell trap. Sens Actuators A Phys 143(1):64–69

    Article  Google Scholar 

  26. Eftekhari A (2003) Diffusion of electrolytes in solution under gravitational forces. Chem Phys Lett 381(3):427–433

    Article  Google Scholar 

  27. Archibald WJ (1938) The process of diffusion in a centrifugal field of force. Phys Rev 53(9):746

    Article  Google Scholar 

  28. Mashimo T (1988) Self-consistent approach to the diffusion induced by a centrifugal field in condensed matter: sedimentation. Phys Rev A 38(8):4149

    Article  Google Scholar 

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Acknowledgements

This material in this study is based upon work supported by the US National Science Foundation under Grant No. CMMI-1131710. We thank Dr. Liang Ma for taking images of 2D and 3D cell culture results.

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Correspondence to Wei Li.

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The authors declare that there is no conflict of interest.

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This study does not contain any studies with human or animal subjects performed by any of the authors.

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Ock, J., Li, W. A high-throughput three-dimensional cell culture platform for drug screening. Bio-des. Manuf. 3, 40–47 (2020). https://doi.org/10.1007/s42242-020-00061-z

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  • DOI: https://doi.org/10.1007/s42242-020-00061-z

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