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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Modeling inflammatory response using 3D

                                        bioprinting of polarized macrophages



                                        Nimal Raveendran, Kanchan Vaswani, Pingping Han, Saraswat Basu,
                                        Corey S. Moran, and Sašo Ivanovski*

                                        Centre for Orofacial Regeneration, Reconstruction and Rehabilitation, The School of Dentistry,
                                        The University of Queensland, Queensland, Australia



                                        Abstract

                                        The field of drug discovery has seen the rise of three-dimensional (3D) bioprinting as a
                                        promising tool for disease modeling. The focus to date has been on tissue engineering
                                        and cancer modeling, although the application of 3D-bioprinted models for the
                                        study of inflammation using macrophages is still in its infancy. This study explores the
                                        potential of bioprinting technology in the development of a 3D macrophage model
                                        and macrophage response to inflammatory stimuli using this platform. To this end,
                                        we established a 3D-bioprinted macrophage model and assessed the inflammatory
                                        and anti-inflammatory response to bacterial endotoxin (lipopolysaccharide, LPS)
                                        and  the drug  ibuprofen (Ibu), respectively. Optimal  conditions  for macrophage
                                        differentiation of the human monocytic cell line, THP-1, in the 3D environment were
                                        studied, as well as the effect of the 3D microenvironment on macrophage polarization.
                                        Viability of  THP-1 cells following the 3D bioprinting process was demonstrated
                                        and maintained, allowing successful macrophage differentiation of the cells. The
            *Corresponding author:      developed  3D-bioprinted  macrophage  model  exhibited  elevated  expression  of
            Saso Ivanovski
            (s.ivanovski@uq.edu.au)     selected  pro-inflammatory  gene  and  protein  markers  following  exposure  to  LPS,
                                        consistent with polarization from M0 to M1 phenotype. Additionally, the model was
            Citation: Raveendran N, Vaswani   responsive to the anti-inflammatory properties of Ibu, demonstrating its potential
            K, Han P, Basu S, Moran CS,
            Ivanovski S. Modeling inflammatory   in drug screening and discovery.  The current study highlights the potential of
            response using 3D bioprinting   bioprinting in the investigation of inflammatory cell response and behavior in a 3D
            of polarized macrophages. Int J   environment ex vivo, opening new avenues for research in modeling inflammatory
            Bioprint. 2024;10(2):2116.
            doi: 10.36922/ijb.2116      responses to various stimuli.
            Received: October 26, 2023
            Accepted: December 20, 2023  Keywords: Macrophages; 3D culture; 3D bioprinting; Drug discovery
            Published Online: February 21, 2024
            Copyright: © 2024 Author(s).
            This is an Open Access article
            distributed under the terms of the
            Creative Commons Attribution   1. Introduction
            License, permitting distribution,
            and reproduction in any medium,   The macrophage is an important immune cell that plays a key role in host defense. Elie
            provided the original work is   Metchnikoff, awarded the Nobel Prize in 1908 for his work on phagocytosis, proposed
            properly cited.             that the key to immunity was to “stimulate the phagocytes.”  Since then, immunologists
                                                                                      1,2
            Publisher’s Note: AccScience   have been studying macrophages and their role in the immune system. Inflammatory
            Publishing remains neutral with   and immune complications are an indicator of an impaired immune system. Researchers
            regard to jurisdictional claims in
            published maps and institutional   can use models of inflammatory response to study disease progression and the efficacy
            affiliations.               of anti-inflammatory drugs and other interventions.




            Volume 10 Issue 2 (2024)                       398                                doi: 10.36922/ijb.2116
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