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International
Journal of Bioprinting
RESEARCH ARTICLE
3D-bioprinted respiratory disease model:
Exploring the importance of culture conditions
and controlled release in modeling infection
Amanda Zimmerling * , Lauren Aubrey 2 id , Kathryn Avery 1 id , Xavier Tabil ,
1
1,2 id
Jim Boire , Xiongbiao Chen * , and Yan Zhou *
1,3
2 id
1 id
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
(This article belongs to the Special Issue: Bioprinting for Tissue Engineering and Modeling)
*Corresponding authors:
Amanda Zimmerling Abstract
(asz694@usask.ca)
Xiongbiao Chen The burden of respiratory illnesses is substantial, significantly impacting healthcare
(xbc719@usask.ca) systems worldwide. As researchers work to better understand chronic diseases,
Yan Zhou as well as newly emerging respiratory viruses, the need for improved respiratory
(yan.zhou@usask.ca) models has become evident. While 3D bioprinting has been illustrated as a feasible
Citation: Zimmerling A, Aubrey L, method to create complex cellularized constructs or respiratory models, it remains
Avery K, et al. 3D-bioprinted to be determined whether incorporating relevant biomechanical stimuli and/
respiratory disease model: or relevant growth factors significantly impacts the response of these models to
Exploring the importance of
culture conditions and controlled infection. In this study, an alginate/gelatin/collagen solution was synthesized and
release in modeling infection. characterized in terms of rheology, printability, degradation, mechanical properties,
Int J Bioprint. 2024;10(6):3895. and biocompatibility. The bioink, which incorporated primary human pulmonary
doi: 10.36922/ijb.3895
fibroblasts and THP-1 cells, was bioprinted to form hierarchical 3D constructs and
Received: June 8, 2024 subsequently seeded with primary human bronchial epithelial cells to form the
1st revised: August 28, 2024 respiratory tissue model. To explore the importance of growth factors and culture
2nd revised: September 10, 2024
Accepted: September 12, 2024 conditions in modeling infection, we strategically developed a hepatocyte-
Published Online: September 12, growth-factor-loaded nanoparticle system and incorporated them into the bioink
2024
for bioprinting the respiratory tissue model, followed by culturing under dynamic
Copyright: © 2024 Author(s). conditions in a breath-mimicking bioreactor. The effect of incorporating growth
This is an Open Access article factors and dynamic culture conditions was examined over 28 days, followed by the
distributed under the terms of the
Creative Commons Attribution infection of these constructs with the influenza A virus. It was determined that these
License, permitting distribution, constructs support infection, demonstrating a more clinically relevant infection
and reproduction in any medium, pattern than 2D models. It was further determined that the inclusion of hepatocyte
provided the original work is
properly cited. growth factor aids in epithelial cell growth, while the inclusion of biomechanical
stimulus increases cellular metabolism and has a moderating effect on response
Publisher’s Note: AccScience
Publishing remains neutral with to infection.
regard to jurisdictional claims in
published maps and institutional
affiliations. Keywords: Bioprinting; Respiratory tissue model; Influenza; Disease model
Volume 10 Issue 6 (2024) 407 doi: 10.36922/ijb.3895

