Bioprinting native-like 3D micro breast cancer tissues utilizing existing cancer cell lines

Abstract

3D cancer cell models provide a more accurate representation of in vivo conditions than traditional 2D cultures. Many cancer cell lines, while stable and extensively characterized in 2D environments, often underperform compared to primary cells in 3D models due to the inherent resource constraints and variability of the latter. To bridge this gap and harness the full potential of established cancer cell lines, we adopted the innovative direct volumetric drop-on-demand (DVDOD) bioprinting methodology that we have developed previously, leading to the inception of printed micro-cancer tissues (PMCaTs). Our method, notable for its bioink droplet scattering technique, enables the generation of intricate features within a droplet, allowing for the creation of typical architectures of breast cancer tissue. We created PMCaTs that captured the essence of micro breast cancer tissues, from native-like ductal structures and cancer nests to the intricate cancer microenvironment. This encompasses elements like cancer-associated fibroblasts, detailed microvasculature, and regions marked by both intensive proliferation and hypoxia. These bioprinted models demonstrate long-term viability and are instrumental for diverse research areas—from exploring cancer growth dynamics and hypoxia-induced behaviors to investigating the nuances of microvasculature, drug penetration capabilities, immune responses, metastatic trends, and clinical drug response predictions. Ultimately, our groundbreaking DVDOD bioprinting technique holds the promise of reshaping the landscape of cancer research, introducing advanced in vitro models poised to transform therapeutic exploration.