Modeling inflammatory response using 3D bioprinting of polarized macrophages

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 developed 3D-bioprinted macrophage model exhibited elevated expression of selected pro-inflammatory gene and protein markers following exposure to LPS, consistent with polarization from M0 to M1 phenotype. Additionally, the model was responsive to the anti-inflammatory properties of Ibu, demonstrating its potential in drug screening and discovery. The current study highlights the potential of bioprinting in the investigation of inflammatory cell response and behavior in a 3D environment ex vivo, opening new avenues for research in modeling inflammatory responses to various stimuli.