Skip to main content
SpringerLink
Log in

Imaging oxygen microenvironment in hydrogel microwell array

  • Research Paper
  • Published:
Acta Mechanica Sinica Aims and scope Submit manuscript

Abstract

Hydrogel microwell arrays (HMAs) have been wildly used for engineering cell microenvironments by providing well-controlled biophysical and biochemical cues (e.g., three-dimensional (3-D) physical boundary, biomolecule coating) for cells. Among these cues, the oxygen microenvironment has shown great effect on the cellular physiological processes. However, it is currently technically challenging to characterize the local oxygen microenvironment within HMAs. Here, we prepared HMAs with different cross-linking concentrations to adjust the structural and physical properties of HMAs. Then we introduced a scanning electrochemical microscopy (SECM)-based electrochemical method to map the surface topography and oxygen microenvironment around HMAs. The SECM results show both the 3-D topography and the oxygen permeability of HMAs in aqueous solution. The obtained oxygen permeability of HMAs increases with increasing the cross-linking concentration, and the microwell boundaries show the highest oxygen permeability throughout HMAs. This work demonstrates that SECM offers a high spatial resolution and in situ method for characterization of the topography and the local oxygen permeability of HMAs, which can provide useful information for better engineering cell microenvironments through optimizing HMAs design.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Li, Y.H., Hong, Y., Xu, G.K., et al.: Non-contact tensile viscoelastic characterization of microscale biological materials. Acta Mech. Sin. 34, 589–599 (2018)

    Article  Google Scholar 

  2. Huang, G.Y., Li, F., Zhao, X., et al.: Functional and biomimetic materials for engineering of the three-dimensional cell microenvironment. Chem. Rev. 117, 12764–12850 (2017)

    Article  Google Scholar 

  3. Kise, K., Kinugasa-Katayama, Y., Takakura, N.: Tumor microenvironment for cancer stem cells. Adv. Drug Deliv. Rev. 99, 197–205 (2016)

    Article  Google Scholar 

  4. Loessner, D., Kobel, S., Clements, J., et al.: Hydrogel microwell arrays allow the assessment of protease-associated enhancement of cancer cell aggregation and survival. Microarrays 2, 208–227 (2013)

    Article  Google Scholar 

  5. Selimović, S., Piraino, F., Bae, H., et al.: Microfabricated polyester conical microwells for cell culture applications. Lab on a Chip 11, 2325–2332 (2011)

    Article  Google Scholar 

  6. Xu, F., Wu, J., Wang, S., et al.: Microengineering methods for cell-based microarrays and high-throughput drug-screening applications. Biofabrication 3, 034101 (2011)

    Article  Google Scholar 

  7. Wong, R.S.H., Ashton, M., Dodou, K.: Effect of crosslinking agent concentration on the properties of unmedicated hydrogels. Pharmaceutics 7, 305–319 (2015)

    Article  Google Scholar 

  8. Gobaa, S., Hoehnel, S., Roccio, M., et al.: Artificial niche microarrays for probing single stem cell fate in high throughput. Nat. Methods 8, 949–955 (2011)

    Article  Google Scholar 

  9. Cordey, M., Limacher, M., Kobel, S., et al.: Enhancing the reliability and throughput of neurosphere culture on hydrogel microwell arrays. Stem Cells 26, 2586–2594 (2008)

    Article  Google Scholar 

  10. Huang, G.Y., Wang, L., Wang, S.Q., et al.: Engineering three-dimensional cell mechanical microenvironment with hydrogels. Biofabrication 4, 042001 (2012)

    Article  Google Scholar 

  11. Tilghman, R.W., Cowan, C.R., Mih, J.D., et al.: Matrix rigidity regulates cancer cell growth and cellular phenotype. PLoS ONE 5, e12905 (2010)

    Article  Google Scholar 

  12. Marguerat, S., Bahler, J.: Coordinating genome expression with cell size. Trends Genet. 28, 560–565 (2012)

    Article  Google Scholar 

  13. Benjamin, W.J., Young, M.D.: The relationship between water content and oxygen permeability for conventional hydrogel materials. Invest. Ophthalmol. Vis. Sci. 44, 3708 (2003)

    Google Scholar 

  14. Lee, G., Jun, Y., Jang, H., et al.: Enhanced oxygen permeability in membrane-bottomed concave microwells for the formation of pancreatic islet spheroids. Acta Biomater. 65, 185–196 (2018)

    Article  Google Scholar 

  15. Compan, V., Andrio, A., Lopez-Alemany, A., et al.: Oxygen permeability of hydrogel contact lenses with organosilicon moieties. Biomaterials 23, 2767–2772 (2002)

    Article  Google Scholar 

  16. Obeidat, Y.M., Evans, A.J., Tedjo, W., et al.: Monitoring oocyte/embryo respiration using electrochemical-based oxygen sensors. Sens. Actuators B: Chem. 276, 72–81 (2018)

    Article  Google Scholar 

  17. Izquierdo, J., Knittel, P., Kranz, C.: Scanning electrochemical microscopy: an analytical perspective. Anal. Bioanal. Chem. 410, 307–324 (2018)

    Article  Google Scholar 

  18. Zoski, C.G.: Review-advances in scanning electrochemical microscopy (SECM). J. Electrochem. Soc. 163, H3088–H3100 (2016)

    Article  Google Scholar 

  19. Saito, T., Wu, C.C., Shiku, H., et al.: Oxygen consumption of cell suspension in a poly(dimethylsiloxane) (PDMS) microchannel estimated by scanning electrochemical microscopy. Analyst 131, 1006–1011 (2006)

    Article  Google Scholar 

  20. Shiku, H., Shiraishi, T., Aoyagi, S., et al.: Respiration activity of single bovine embryos entrapped in a cone-shaped microwell monitored by scanning electrochemical microscopy. Anal. Chim. Acta 522, 51–58 (2004)

    Article  Google Scholar 

  21. Jeerage, K.M., LaNasa, S.M., Hughes, H.A., et al.: Scanning electrochemical microscopy measurements of photopolymerized poly(ethylene glycol) hydrogels. Polymer 51, 5456–5461 (2010)

    Article  Google Scholar 

  22. Wei, Z., Yang, J.H., Du, X.J., et al.: Dextran-based self-healing hydrogels formed by reversible diels-alder reaction under physiological conditions. Macromol. Rapid Commun. 34, 1464–1470 (2013)

    Article  Google Scholar 

  23. Gonsalves, M., Barker, A.L., Macpherson, J.V., et al.: Scanning electrochemical microscopy as a local probe of oxygen permeability in cartilage. Biophys. J. 78, 1578–1588 (2000)

    Article  Google Scholar 

  24. Gonsalves, M., Macpherson, J.V., O’Hare, D., et al.: High resolution imaging of the distribution and permeability of methyl viologen dication in bovine articular cartilage using scanning electrochemical microscopy. Biochim. Biophys. Acta Gen. Subj. 1524, 66–74 (2000)

    Article  Google Scholar 

  25. Kang, L., Hancock, M.J., Brigham, M.D., et al.: Cell confinement in patterned nanoliter droplets in a microwell array by wiping. J. Biomed. Mater. Res. A 93, 547–557 (2010)

    Google Scholar 

  26. Yu, Y., Zhang, Y., Martin, J.A., et al.: Evaluation of cell viability and functionality in vessel-like bioprintable cell-laden tubular channels. J. Biomech. Eng. 135, 91011 (2013)

    Article  Google Scholar 

  27. Du, X., Xu, F., Li, F., et al.: New application of scanning electrochemical microscopy in characterization of hydrogel microwell arrays. Sci. Sin. Chim. 44, 1814–1822 (2014)

    Google Scholar 

  28. Polcari, D., Dauphin-Ducharme, P., Mauzeroll, J.: Scanning electrochemical microscopy: a comprehensive review of experimental parameters from 1989 to 2015. Chem. Rev. 116, 13234–13278 (2016)

    Article  Google Scholar 

  29. Revzin, A., Tompkins, R.G., Toner, M.: Surface engineering with poly(ethylene glycol) photolithography to create high-density cell arrays on glass. Langmuir 19, 9855–9862 (2003)

    Article  Google Scholar 

  30. Barker, A.L., Macpherson, J.V., Slevin, C.J., et al.: Scanning electrochemical microscopy (SECM) as a probe of transfer processes in two-phase systems: theory and experimental applications of SECM-induced transfer with arbitrary partition coefficients, diffusion coefficients, and interfacial kinetics. J. Phys. Chem. B 102, 1586–1598 (1998)

    Article  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grants 21775117, 11532009) and the General Financial Grant from the China Postdoctoral Science Foundation (Grant 2016M592773).

Author information

Authors and Affiliations

  1. The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, China

    Meng Wang, Shaobao Liu & Fei Li

  2. Bioinspired Engineering and Biomechanics Center (BEBC), Xi’an Jiaotong University, Xi’an, 710049, China

    Meng Wang, Shaobao Liu & Fei Li

  3. MOE Key Laboratory for Multifunctional Materials and Structures, Xi’an Jiaotong University, Xi’an, 710049, China

    Shaobao Liu

Authors
  1. Meng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shaobao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fei Li.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, M., Liu, S. & Li, F. Imaging oxygen microenvironment in hydrogel microwell array. Acta Mech. Sin. 35, 321–328 (2019). https://doi.org/10.1007/s10409-018-0832-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10409-018-0832-6

Keywords

Search

Navigation