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International Journal of Bioprinting 3D-bioprinted macrophage inflammation model

There are currently several techniques available for in integration of diverse cell types within a unified model.
vitro disease modeling, including three-dimensional (2D) The capability to generate patient-specific tissues enhances
and three-dimensional (3D) culture models. 2D culture is its applicability in comprehensively investigating disease
the most utilized model, although poor cell differentiation, mechanisms and devising personalized therapeutic
unrealistic cell proliferation, decreased drug resistance, strategies. Furthermore, 3D bioprinting plays a pivotal
and inaccurate response to stimuli remain the significant role in diminishing dependence on animal testing
challenges. 2D culture also limits the number of cell types and furnishes a realistic platform for drug evaluation,
3-5
that can be co-cultured and cannot accurately represent the thereby positioning itself as a forefront technology in
complex microenvironment of human tissues. 3D culture the progression of disease research and therapeutic
6
is a more complex model that facilitates better cell-to-cell advancement. Several human cell types are currently
9
contact and intercellular signaling. 3D culture provides a being researched using 3D-bioprinted models. 17,18
more native cell environment and is becoming increasingly Recent studies have established the feasibility of
important in drug development and preclinical testing. 3D-bioprinted constructs of anti-inflammatory (M2)
Protein expression patterns and intracellular junctions macrophages as a novel approach for disease modeling
19
more closely resemble in vivo conditions compared to 2D and tissue engineering applications. There is, however,
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monolayer cultures. Moreover, 3D models play a valuable a paucity of data related to modeling pro-inflammatory
role in the clinical development process, allowing for better (M1) macrophages. Recently, a bioprinted lung tissue
characterization of cells and their microenvironments, as model was developed to study inflammation and the
well as drug response, efficacy, and toxicity. Comparatively, use of viral inhibitors. At the time of writing, this
21
2D culture is a less complex and less expensive option, is the only study that incorporated M1 macrophage
but 3D models provide more robust and relevant polarization and investigated pathogenic biology while
results, gradually becoming essential for advancing our shedding light on the development of new therapeutic
understanding of cellular and molecular mechanisms in anti-inflammatory drugs. The objective of the present
health and disease. study was to establish a 3D-bioprinted inflammation
In the field of drug testing, there exist three distinct model using the macrophage cell line THP-1, and within
3D models: scaffold-based cultures, non-scaffold-based this model, evaluate the efficacy of ibuprofen (Ibu) as
cultures such as organoids and cellular spheroids, an anti-inflammatory agent. The outcomes of this study
and tissue-engineered models utilizing bioprinting will contribute to the advancement of knowledge in the
technology. Tissue-engineered models present several field of 3D-bioprinted macrophage models and their
7-9
benefits compared to their scaffold-based and non- application in the study of inflammation.
scaffold-based counterparts. First, tissue-engineered
models more accurately replicate the natural organization 2. Materials and methods
(cellular niche) and function of human tissues through 2.1. Cell culture
cell culture techniques, providing a more physiologically The human leukemia monocytic cell line THP-1
relevant representation of human anatomy. 10,11 Second, (courtesy of Prof. K. Schroder, Institute for Molecular
these models facilitate the formation of complex and Biosciences, University of Queensland, Australia) was
functional cell–cell interactions, which play a critical cultured in basal medium (BM) made of RPMI 1640
role in proper tissue function and may not be attainable Medium (Life Technologies, Australia) supplemented
in scaffold-based or non-scaffold-based cultures. with 10% (v/v) heat-inactivated fetal bovine serum (FBS;
11
Third, tissue-engineered models afford a more realistic Gibco , Australia) and 1% (v/v) antibiotic-antimycotic
®
representation of drug response in human tissues, leading (Gibco , Australia) at 37°C under 5% CO . The cells were
®
2
to improved predictions of drug efficacy and toxicity. 12,13 differentiated into macrophages (M0) using phorbol
Finally, tissue-engineered models can be tailored to 12-myristate 13-acetate (PMA; Sigma-Aldrich, USA). M0
specific disease states or therapeutic targets, enabling were polarized into classically activated macrophages (M1)
more targeted drug testing. Thus, tissue-engineered with lipopolysaccharides produced from Escherichia coli
14
models offer a more accurate representation of human (LPS; Sigma-Aldrich, USA).
tissues and are a valuable tool for drug discovery and
testing as they enable tissue-like structures to be created 2.2. Optimization of 3D bioprinting of THP-1 and
in vitro. 15,16 The pre-eminence of 3D bioprinting as a tissue evaluation of printability (Pr)
engineering method for disease modeling is underscored The optimal concentration of gelatin methacryloyl
by its aptitude for accurate reproduction of intricate (GelMA; Gelomics Pty Ltd., Australia) was determined
tissue structures, enabling precise customization and the with a 55 ± 3% degree of functionalization for 3D

Volume 10 Issue 2 (2024) 399 doi: 10.36922/ijb.2116