Speaker
Description
In this work, we present our latest advances in the biofabrication of monoculture and polyculture tumor niches using chaotic bioprinting as an enabling strategy for in vitro cancer research.
We first focus on the fabrication of monoculture breast cancer models designed to study tumor cell migration and invasion. Understanding these processes requires sophisticated models that accurately replicate structural and functional aspects of the tumor microenvironment. We employed a chaotic bioprinting approach to create prevascularized tumor niches integrating cancer spheroids and longitudinal vascular-like microchannels within a single construct. Using MDA-MB-231 breast cancer cells, we demonstrate that multichannel scaffolds fabricated via chaotic bioprinting significantly enhance cancer cell migration and directional alignment compared to traditional solid hydrogel constructs. By day 20, migratory fronts in multichannel filaments extended up to four times farther and achieved 88% alignment, indicating robust directional migration.
Gene expression analysis revealed accelerated epithelial-to-mesenchymal transition (EMT) in multichannel constructs, characterized by earlier and stronger upregulation of N-cadherin and vimentin. This enhanced migration was accompanied by increased proliferation, as evidenced by elevated Ki-67 expression. Importantly, the absence of hypoxia in the migratory fronts underscores the role of engineered microchannel architecture in supporting sustained, non-hypoxic migration.
We also report the fabrication of multicellular tumor niches incorporating breast cancer cells, human fibroblasts, and macrophages into chaotically printed hydrogel constructs. These prevascularized polycultures exhibited high viability, dynamic cellular activity, and rich intercellular interactions for over four weeks in culture. Furthermore, treatment with doxorubicin, a commonly used chemotherapeutic agent, revealed distinct responses in terms of viability, cell death, and gene expression profiles, highlighting the model’s potential for pharmacological testing.
Overall, this work establishes chaotic bioprinting as a powerful and flexible platform for engineering advanced tumor models with high structural complexity and biological relevance—offering new opportunities to study cancer progression and improve the evaluation of anti-cancer therapies.
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