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Engineered 3D tissue models for cell-laden microfluidic channels

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Abstract

Delivery of nutrients and oxygen within three-dimensional (3D) tissue constructs is important to maintain cell viability. We built 3D cell-laden hydrogels to validate a new tissue perfusion model that takes into account nutrition consumption. The model system was analyzed by simulating theoretical nutrient diffusion into cell-laden hydrogels. We carried out a parametric study considering different microchannel sizes and inter-channel separation in the hydrogel. We hypothesized that nutrient consumption needs to be taken into account when optimizing the perfusion channel size and separation. We validated the hypothesis by experiments. We fabricated circular microchannels (r = 400 μm) in 3D cell-laden hydrogel constructs (R = 7.5 mm, volume = 5 ml). These channels were positioned either individually or in parallel within hydrogels to increase nutrient and oxygen transport as a way to improve cell viability. We quantified the spatial distribution of viable cells within 3D hydrogel scaffolds without channels and with single- and dual-perfusion microfluidic channels. We investigated quantitatively the cell viability as a function of radial distance from the channels using experimental data and mathematical modeling of diffusion profiles. Our simulations show that a large-channel radius as well as a large channel to channel distance diffuse nutrients farther through a 3D hydrogel. This is important since our results reveal that there is a close correlation between nutrient profiles and cell viability across the hydrogel.

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Acknowledgment

We would like to thank the Randolph Hearst Foundation and Department of Medicine, Brigham and Women’s Hospital for the Young Investigators in Medicine Award. This research is performed at the Bio-Acoustic-MEMS in Medicine (BAMM) Labs, HST Center for Bioengineering, Brigham and Women’s Hospital, Harvard Medical School.

Author contributions

YSS, RLL, UD, and EH wrote the paper. YSS carried out the simulation. GM and GL performed the experiments and collected data. YSS created the model and the theoretical analysis. RLL, YSS, GM, EH, and UD conducted the data analyses. GD, SSY, EK, AK, and EH read and gave feedback on the paper.

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Authors and Affiliations

  1. Bio-Acoustic-MEMS in Medicine Lab, HST Center for Bioengineering, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne Street #252, Cambridge, MA, 02139, USA

    Young S. Song, Richard L. Lin, Grace Montesano, Grace Lee & Utkan Demirci

  2. Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA, 02215, USA

    Naside G. Durmus

  3. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Seung-Schik Yoo, Ali Khademhosseini & Utkan Demirci

  4. Yeditepe University Faculty of Medicine, 26 Agustos Yerlesimi, 34755, Kayisdagi, Istanbul, Turkey

    Emre Kayaalp

  5. Electronics Research Laboratory, Department of Physics, University of Helsinki, POB 64,, 00014, Finland

    Edward Hæggström

  6. Division of Health Sciences and Technology, Harvard-MIT, Cambridge, MA, 02139, USA

    Ali Khademhosseini & Utkan Demirci

Authors
  1. Young S. Song
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  2. Richard L. Lin
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  3. Grace Montesano
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  4. Naside G. Durmus
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  5. Grace Lee
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  6. Seung-Schik Yoo
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  7. Emre Kayaalp
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  8. Edward Hæggström
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  9. Ali Khademhosseini
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  10. Utkan Demirci
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Corresponding author

Correspondence to Utkan Demirci.

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Author contributions

RLL, YSS, GD, and EH wrote the paper. GM and GL performed the experiments and collected data. RLL, YSS, and EH worked on the theoretical analysis. RLL, YSS, GM, EH, and UD conducted the data analyses. GD, SSY, EK, AK, and EH read and gave feedback on the paper. UD oversaw the project, designed the experiments, and wrote the paper.

Young Seok Song and Richard L. Lin have contributed equally to this contribution

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Song, Y.S., Lin, R.L., Montesano, G. et al. Engineered 3D tissue models for cell-laden microfluidic channels. Anal Bioanal Chem 395, 185–193 (2009). https://doi.org/10.1007/s00216-009-2935-1

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  • DOI: https://doi.org/10.1007/s00216-009-2935-1

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