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Fabrication of Microfluidic Chip for Investigation of Wound Healing Processes

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Abstract

This work describes a microfludic cell culture device embedded with microstructured posts fabricated by a photolithography technique and a replica-molding technique. BALB/3T3 fibroblast cells were cultured inside the PDMS microfludic chip to form a confluent state, and an external pressure was applied to the top part of the microfluidic chip to remove the cells from the contact areas of the posts. The applied pressure was removed after the formation of wound areas in the cell layer, and the wound healing processes were investigated by monitoring the migration and proliferation of BALB/3T3 fibroblast cells. The function of the microfluidic chip actuated by an applied pressure was investigated by a fluorescent material, and the formation of the wound areas by an applied pressure was investigated by optical microscopy. After the formation of the wound in the cell layer, optical microscopic images of the cells at the same positions were captured by an optical microscope at intervals of 12 h in order to monitor the wound healing processes by migration and proliferation of the cells. Finally, the wound healing was quantitatively assessed by plotting a growth curve. In conclusion, because the microfluidic device developed in this work is very simple and easy to use, the device might be applicable to assessing the wound healing processes and monitoring the migration and proliferation of other cells.

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References

  1. Lamalice, L., Le Boeuf, F. & Huot, J. Endothelial cell migration during angiogenesis. Circ. Res. 100, 782–794 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Chung, S., Sudo, R., Vickerman, V., Zervantonakis, I.K. & Kamm, R.D. Microfluidic platforms for studies of angiogenesis, cell migration, and cell-cell interactions. Ann. Biomed. Eng. 38, 1164–1177 (2010).

    Article  PubMed  Google Scholar 

  3. Reig, G., Pulgar, E. & Concha, M.L. Cell migration: from tissue culture to embryos. Development 141, 1999–2013 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. Broughton, G. II, Janis, J.E. & Attinger, C.E. Wound healing: an Overview. Plast. Reconstr. Surg. 117, 1e–S–32–eS (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Nauta, A., Gurtner, G.C. & Longaker, M.T. Wound healing and regenerative strategies. Oral Dis. 17, 541–549 (2011).

    Article  CAS  PubMed  Google Scholar 

  6. Martin, P. & Nunan, R. Catellular and molecular mechanisms of repair in acute and chronic wound healing. Br. J. Dermatol. 173, 370–378 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Friedl, P. & Wolf, K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat. Rev. Cancer 3, 362–374 (2003).

    Article  CAS  PubMed  Google Scholar 

  8. Valastyan, S. & Weinberg, R.A. Tumor metastasis: molecular insights and evolving paradigms. Cell 147, 275–292 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Boyden, S. The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. J. Exp. Med. 115, 453–466 (1962).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zigmond, S.H. Oatrientation chamber in chemotaxis. Methods Enzymol. 162, 65–72 (1988).

    Article  CAS  PubMed  Google Scholar 

  11. Zicha, D., Dunn, G.A. & Brown, A.F. A new directviewing chemotaxis chamber. J. Cell. Sci. 99, 769–775 (1991).

    PubMed  Google Scholar 

  12. Kramer, N. et al. In vitro cell migration and invasion assays. Mut. Res. 752, 10–24 (2013).

    Article  CAS  Google Scholar 

  13. Schwarz, J. et al. A microfluidic device for measuring cell migration towards substrate-bound and soluble chemokine gradients. Sci. Rep. 6, 36440 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jeon, N.L. et al. Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device. Nat. Biotech. 20, 826–830 (2002).

    Article  CAS  Google Scholar 

  15. Moraes, C., Mehta, G., Lesher-Perez, S.C. & Takayama, S. Oatrgans-on-a-chip: a focus on compartmentalized microdevices. Ann. Biomed. Eng. 40, 1211–1227 (2012).

    Article  PubMed  Google Scholar 

  16. Chen, Y.-C. et al. Single-cell migration chip for chemotaxis-based microfluidic selection of heterogeneous cell populations. Sci. Rep. 5, 9980 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Velve-Casquillas, G., Le Berre, M., Piel, M. & Tran, P.T. Microfluidic tools for cell biological research. Nano Today 5, 28–47 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Riahi, R., Yang, Y., Zhang, D.D. & Wong, P.K. Advances in wound-healing assays for probing collective cell migration. J. Lab. Autom. 17, 59–65 (2012).

    Article  CAS  PubMed  Google Scholar 

  19. Nie, F.-Q. et al. On-chip cell migration assay using microfluidic channels. Biomaterials 28, 4017–4022 (2007).

    Article  CAS  PubMed  Google Scholar 

  20. Zhang, M., Li, H., Ma, H. & Qin, J. A simple microfluidic strategy for cell migration assay in an in vitro wound-healing model. Wound Rep. Reg. 21, 897–903 (2013).

    Article  Google Scholar 

  21. Gao, A.X., Tian, T.L., Shi, Z.Z. & Yu, L. A Cost-effective microdevice bridges microfluidic and conventional in vitro scratch/wound-healing assay for personalized therapy validation. BioChip J. 10, 56–64 (2016).

    Article  CAS  Google Scholar 

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Correspondence to Seog Woo Rhee.

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Go, H., Tian, T. & Rhee, S.W. Fabrication of Microfluidic Chip for Investigation of Wound Healing Processes. BioChip J 12, 146–153 (2018). https://doi.org/10.1007/s13206-017-2207-7

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  • DOI: https://doi.org/10.1007/s13206-017-2207-7

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