AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.3895
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RESEARCH ARTICLE

3D-bioprinted respiratory disease model: Exploring the importance of culture conditions and controlled release in modeling infection

Amanda Zimmerling1,2* ,  Lauren Aubrey2 ,  Kathryn Avery1 ,  Xavier Tabil1 ,  Jim Boire1,3 ,  Xiongbiao Chen1* ,  Yan Zhou2*
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1 Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, Canada
2 Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Canada
3 RMD Engineering Inc., Saskatoon, Canada
IJB, 3895 https://doi.org/10.36922/ijb.3895
Submitted: 8 June 2024 | Accepted: 12 September 2024 | Published: 12 September 2024
(This article belongs to the Special Issue Bioprinting for Tissue Engineering and Modeling)
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The burden of respiratory illnesses is substantial, significantly impacting healthcare systems worldwide. As researchers work to better understand chronic diseases, as well as newly emerging respiratory viruses, the need for improved respiratory models has become evident. While 3D bioprinting has been illustrated as a feasible method to create complex cellularized constructs or respiratory models, it remains to be determined whether incorporating relevant biomechanical stimuli and/ or relevant growth factors significantly impacts the response of these models to infection. In this study, an alginate/gelatin/collagen solution was synthesized and characterized in terms of rheology, printability, degradation, mechanical properties, and biocompatibility. The bioink, which incorporated primary human pulmonary fibroblasts and THP-1 cells, was bioprinted to form hierarchical 3D constructs and subsequently seeded with primary human bronchial epithelial cells to form the respiratory tissue model. To explore the importance of growth factors and culture conditions in modeling infection, we strategically developed a hepatocyte-growth-factor-loaded nanoparticle system and incorporated them into the bioink for bioprinting the respiratory tissue model, followed by culturing under dynamic conditions in a breath-mimicking bioreactor. The effect of incorporating growth factors and dynamic culture conditions was examined over 28 days, followed by the infection of these constructs with the influenza A virus. It was determined that these constructs support infection, demonstrating a more clinically relevant infection pattern than 2D models. It was further determined that the inclusion of hepatocyte growth factor aids in epithelial cell growth, while the inclusion of biomechanical stimulus increases cellular metabolism and has a moderating effect on response to infection.

Keywords
Bioprinting
Respiratory tissue model
Influenza
Disease model
Funding
This study was supported by the University of Saskatchewan Dean’s Scholarship to Amanda Zimmerling; the Natural Science and Engineering Research Council of Canada (NSERC) Canada Graduate Scholarship-Doctoral (CGS-D) to Amanda Zimmerling; and the Discovery Grants from NSERC to Yan Zhou and Xiongbiao Chen. VIDO receives operational funding from the Government of Saskatchewan through Innovation Saskatchewan and the Ministry of Agriculture and from the Canada Foundation for Innovation through the Major Science Initiatives. This work is published with the permission of the director of VIDO as manuscript series #1049.
Conflict of interest
Authors declare they have no competing interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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