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3D printed transwell-integrated nose-on-chip model to evaluate effects of air flow-induced mechanical stresses on mucous secretion

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Abstract

While there are many chip models that simulate the air-tissue interface of the respiratory system, only a few represent the upper respiratory system. These chips are restricted to unidirectional flow patterns that are not comparable to the highly dynamic and variable flow patterns found in the native nasal cavity. Here we describe the development of a tunable nose-on-chip device that mimics the air-mucosa interface and is coupled to an air delivery system that simulates natural breathing patterns through the generation of bi-directional air flow. Additionally, we employ computational modeling to demonstrate how the device design can be tuned to replicate desired mechanical characteristics within specific regions of the human nasal cavity. We also demonstrate how to culture human nasal epithelial cell line RPMI 2650 within the lab-on-chip (LOC) device. Lastly, Alcian Blue histological staining was performed to label mucin proteins, which play important roles in mucous secretion. Our results revealed that dynamic flow conditions can increase mucous secretion for RPMI 2650 cells, when compared to no flow, or stationary, conditions.

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Acknowledgements

We appreciate David Mohl (WPAFB) for his advice on development of airflow generation systems. We are grateful to Joe Althaus, Tom Mitchell, and Logan Rowland, MakerHub staff (Wright Brothers Institute, Dayton, OH) for their guidance and assistance with 3D printing. Angela Dixon, Ph.D., was supported by a National Research Council Research Assistantship and Zachary Brooks, M.S., by a Defense Associated Graduate Student Innovators (DAGSI) Graduate Fellowship. This material is based on research sponsored by the Air Force Research Laboratory and the Southwestern Council for Higher Education under agreement FA8650-19-2-9300. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of Southwestern Ohio Council for Higher Education and the Air Force Research Laboratory (AFRL) or the U.S. Government.

Funding

This material is based on research sponsored by the Air Force Research Laboratory and the Southwestern Council for Higher Education under agreement FA8650-19–2-9300.

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Authors and Affiliations

  1. Air Force Research Laboratory, 711Th Human Performance Wing, Wright-Patterson AFB, Dayton, OH, USA

    Zachary Brooks, Saber Hussain & Angela R. Dixon

  2. Department of Biomedical, Industrial and Human Factors Engineering, College of Engineering and Computer Science, Wright State University, OH, Dayton, USA

    Zachary Brooks & Tarun Goswami

  3. UES, Inc, Beavercreek, OH, USA

    Zachary Brooks

  4. Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Ohio State University, Columbus, OH, USA

    Kanghyun Kim & Kai Zhao

  5. Department of Biology, College of Arts and Sciences, Case Western Reserve University, Cleveland, OH, USA

    Angela R. Dixon

  6. Department of Biomedical Engineering, School of Engineering, Case Western Reserve University, Cleveland, OH, USA

    Angela R. Dixon

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  1. Zachary Brooks
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  2. Kanghyun Kim
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  3. Kai Zhao
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  4. Tarun Goswami
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  5. Saber Hussain
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  6. Angela R. Dixon
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Correspondence to Saber Hussain or Angela R. Dixon.

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Brooks, Z., Kim, K., Zhao, K. et al. 3D printed transwell-integrated nose-on-chip model to evaluate effects of air flow-induced mechanical stresses on mucous secretion. Biomed Microdevices 24, 8 (2022). https://doi.org/10.1007/s10544-021-00602-y

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