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Development of model tissues by 3D bioprinting to study macrophages in breast cancer
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- Cancer remains a major medical challenge, representing one of the most devastating categories of human pathologies, with an estimated 12.7 million new cases worldwide, a figure projected to double by 2030. Current treatment modalities have shown limited success in achieving complete eradication. This is largely due to the complexity of the tumor micro environment and the involvement of immune cells such as monocytes, especially in breast cancer, where they play an important role in patient survival. Although engineered animal models offer 3D spatial complexity for these cancer models, inherent species-specific differences often result in unreliable results and limited translational applicability to human disease. These limitations underscore the need for alternative model systems that integrate both 3D cellular organization and functional human-derived components. This work represents an initial step towards developing such innovative solutions, focusing on the use of 3D extrusion bioprinting to create a three-dimensional model based on monocytes embedded within a composite alginate-agarose hydrogel to create a bioink. Bioprintability assessments of varying alginate:agarose volume compositions revealed that 80:20, 75:25 and 70:30 had optimal bioprinting conditions and cell viability. Observations also included cell escape, structural fragmentation, and cellular alignment within the gels. Importantly, 3D bioprinted cultures promoted monocyte differentiation into M1-polarized macrophages (increased CD80, CD86 expression) without exogenous growth factors. Furthermore, stiffness of the composite gel increased after 5 days in culture medium, hinting at a re-organization of the macromolecular network in presence of the medium. These findings collectively highlight the potential of this bioprinting protocol for the in vitro study of monocyte behavior and function, offering a novel platform for complex biological models such as breast cancer tissue.