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International Journal of Bioprinting Bioprint micro breast cancer

genetic backgrounds. Notably, for breast cancer alone, primary cells and ensuring consistent and reproducible
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more than 90 distinct cell lines have been identified. research outcomes.
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These cell lines have proven invaluable in advancing basic Our bioprinting technologies bridge this divide, with
cancer research, developing therapeutics, and facilitating 3D bioprinting presenting a physiologically relevant
their transition into clinical applications. However, this platform that encapsulates the intricacies of in vivo tumor
traditional 2D culture approach cannot capture the environments. These 3D models, housing heterogeneous
complex 3D nature of in vivo cancer, prompting researchers cell populations like cancer cells, fibroblasts, and
to explore more representative models. 6 endothelial cells, simulate the dynamic tumor interactions
Recent research has shifted towards using primary more effectively. They prove instrumental for drug
cells to develop 3D structures, like organoids, which offer testing, enabling the evaluation of drug penetration and
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a closer representation of native tissues. However, while tumor invasion, as well as immune and drug responses.
these models demonstrate promise in emulating in vivo Specifically, we focused on breast cancer tissues, given
cancer tissues, they come with challenges. Predominantly that breast cancer remains the most frequently diagnosed
relying on primary cells introduces limitations such as cancer worldwide. Its incidence has surged in recent
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restricted availability, sourcing difficulties, patient consent years. Despite significant advancements in therapeutic
issues, and technical challenges in isolation. Moreover, interventions, over 2.3 million individuals were diagnosed
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the inherent genetic and phenotypic variability in primary with breast cancer in 2020 alone, leading to 685,000
cells from different patient tumors can result in inconsistent fatalities. This underscores the pressing need for more
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experimental outcomes. effective treatment strategies.
3D bioprinting is a transformative technology in tissue Nonetheless, we aim to address this gap by leveraging
engineering and regenerative medicine that enables the PMCaTs. These models, comprising 3D configurations
creation of complex, functional living tissues through various of multiple cell types, can mirror the actual physiological
methods, each with distinct mechanisms and applications. conditions, providing a platform that is both versatile and
Extrusion-based bioprinting methodically deposits bioink highly representative. By focusing on breast cancer, we
layerwise through a nozzle, offering the versatility to print not only address a significant public health concern but
a broad spectrum of materials with high cell densities. also offer an opportunity to study a variety of interactions
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Meanwhile, vat photopolymerization-based bioprinting that are pivotal for cancer progression and treatment
harnesses light to cure liquid resin into solid 3D structures responses. Given this critical context, exploring innovative
layerwise, achieving high resolution and smooth finishes. methodologies to better understand and treat breast
However, its utility is constrained by the requirement for cancer becomes paramount. In our study, we harnessed
bioinks that are compatible with the photopolymerization 3D bioprinting, utilizing various breast cancer cell lines,
process. The jetting-based or drop-on-demand (DOD) fibroblasts, and endothelial cells, to delve into diverse
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technique, known for its precision in ejecting bioink cancer behaviors. This encompasses typical breast cancer
droplets onto a substrate, is particularly adept at generating morphology, cancer invasion, metastasis, drug penetration,
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microtissues with the capability of controlling droplet sizes immune therapy, and drug responsiveness. Taken together,
and deposition rate. To address these challenges, we have our approach demonstrates promise in closely mimicking
developed a novel direct-volumetric DOD (DVDOD) in vivo conditions.
technology that distinguishes itself from other existing
DOD technologies by directly controlling droplet volume 2. Methods
via linear advancement and facilitating droplet release and The present study is proposed as a proof-of-concept study
deposition through pulsed air, enabling an almost seamless that utilizes the DVDOD method, following its successful
two-step process that allows for the precise dispensation of applications in tissue regeneration. The assays are divided
bioink droplets down to 10 nL with <5% variation.
into two categories, each with corresponding goals:
To address these challenges, we utilized the previously
developed DVDOD bioprinting method to generate (i) feasibility assays to evaluate morphology creation (an
important aspect of cancer biology), where the goal
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printed micro-cancer tissues (PMCaTs). To leverage is to analyze the morphology of PMCaTs in relation
bioink droplet scattering, we were able to precisely to the pathology studies of native cancer tissue.
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construct cancer tissue structures that closely resemble
native tissues. Furthermore, our approach leverages the (ii) A quantitative study aimed at assessing drug
stability, well-documented genetic profiles, and widespread responses and comparing them with the data from a
availability of cancer cell lines, bypassing the need for clinical trial.

Volume 10 Issue 3 (2024) 558 doi: 10.36922/ijb.2911