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International Journal of Bioprinting 3D-bioprinted respiratory disease model

5. Conclusion Conflict of interest
The development of more advanced respiratory models for Authors declare they have no competing interests. The
use in disease modeling is a promising avenue of research funders had no role in the design of the study; in the
to speed up and increase the efficiency of therapeutic collection, analyses, or interpretation of data; in the writing
development. This study aimed to characterize an alginate/ of the manuscript; or in the decision to publish the results.
gelatin/collagen solution, incorporate multiple cell types
(including HPFs, THP-1 cells, and HBEpCs), and use 3D Author contributions
bioprinting to form a complex hierarchical respiratory Conceptualization: Amanda Zimmerling
tissue model. The influence of culturing the printed Data curation: Amanda Zimmerling, Kathryn Avery,
constructs in a breath-mimicking bioreactor was evaluated Xavier Tabil
alongside the effect of incorporating a growth factor- Formal analysis: Amanda Zimmerling, Kathryn Avery,
loaded nanoparticle system, followed by testing the ability Xavier Tabil
of this model to function as an infection model for IAV. Funding acquisition: Amanda Zimmerling, Yan Zhou,
The results demonstrated that the synthesized solution Xiongbiao Chen
was highly printable and mechanically stable over a 28- Investigation: Amanda Zimmerling, Lauren Aubrey,
day culture period while demonstrating a high degree of Kathryn Avery, Xavier Tabil
biocompatibility. Further, the incorporated primary Methodology: Amanda Zimmerling, Lauren Aubrey,
cells were able to maintain high viability during long- Jim Boire
term culture, with the bioreactor and controlled release Resources: Jim Boire, Yan Zhou, Xiongbiao Chen
system enhancing cellular metabolism. These constructs Supervision: Yan Zhou, Xiongbiao Chen
supported IAV infection, demonstrating a similar Validation: Amanda Zimmerling, Jim Boire
cytokine release profile as that of a 2D in vitro model Writing - original draft: Amanda Zimmerling
while demonstrating a more clinically relevant clustered Writing - review & editing: Amanda Zimmerling, Lauren
infection pattern. Overall, this study demonstrated the Aubrey, Kathryn Avery, Xavier Tabil, Yan Zhou,
feasibility and benefits of using a 3D-bioprinted model Xiongbiao Chen
in infection studies, with the possibility of expanding its All authors have read and agreed to the published
application to therapeutic testing. version of the manuscript.

Acknowledgments Ethics approval and consent to participate
The authors would like the thank Nathalie Berube for her Not applicable.
assistance and training on RNA extraction and RT-qPCR
techniques. The authors would also like to thank the Consent for publication
Kurreck lab (TU Berlin) for sharing their knowledge and
“baby-pool” design, which was slightly modified for use in Not applicable.
this study.
Availability of data
Funding All data collected and analyzed in this manuscript
This study was supported by the University of are available upon reasonable request from the
Saskatchewan Dean’s Scholarship to Amanda Zimmerling; corresponding author.
the Natural Science and Engineering Research Council of References
Canada (NSERC) Canada Graduate Scholarship-Doctoral
(CGS-D) to Amanda Zimmerling; and the Discovery 1. Naghavi M, Antony C, Brauer M, et al. GBD 2019 Chronic Respiratory
Grants from NSERC to Yan Zhou and Xiongbiao Chen. Diseases Collaborators. Global burden of chronic respiratory diseases
VIDO receives operational funding from the Government and risk factors, 1990–2019: an update from the global burden of
of Saskatchewan through Innovation Saskatchewan and the disease study 2019. eClinicalMedicine. 2023;59:101936.
Ministry of Agriculture and from the Canada Foundation doi: 10.1016/j.eclinm.2023.101936
for Innovation through the Major Science Initiatives. This 2. Viegi G, Maoi S, Fasola S, Baldacci S. Global burden of chronic
work is published with the permission of the director of respiratory diseases. J Aerosol Med Pulm Drug Deliv. 2020;33(4):1-38.
VIDO as manuscript series #1049. doi: 10.1089/jamp.2019.1576

Volume 10 Issue 6 (2024) 427 doi: 10.36922/ijb.3895