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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
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