Bioprinting Breast Cancer In Situ to Study Cell Communication in Disease Progression

Project Overview

The goal of this project was to engineer new models of breast ducts and their derangement in early cancer, determine the effect of malignant transformation on the surrounding extracellular matrix and advance bioengineering of epithelial barrier tissues. This project developed two new models of malignant transformation and advanced understanding of extracellular matrix. This work improves our understanding of early malignancy and contributes to Lawrence Livermore National Laboratory's (LLNL's) mission in bioscience and bioengineering.

Mission Impact

This project advanced the LLNL core competencies in Bioscience and Bioengineering and Advanced Materials and Manufacturing by developing improved models of epithelial barrier function and early malignancy. Specifically, this work has advanced the understanding of the biophysics and biochemistry of extracellular matrix hydrogels, developed new systems for understanding epithelial biology, and linked cell biophysics to tissue function.

Publications, Presentations, and Patents

Pepona M, Balough P, Puleri DF, Hynes WF, Robertson C, Moya ML, Randles A. "Investigating the interaction between circulating tumor cells and local hydrodynamics via experiment and simulations," accepted to Cell and Molecular Bioengineering, 2020. LLNL-JRNL-805606.

Hochman-Mendez C, Coelho-Sampaio T, Kent AJ, Inman JL, Bissell MJ, Robertson C. "Generating fractal microstructure of laminin-111 to signal to cells," accepted to Journal of Visualized Experiments, 2020. LLNL-JRNL-799443.

Hynes WF, Pepona M, Robertson C, Alvarado JA, Dubbin K, Triplett M, Adorno JJ, Randles A, Moya ML. "Examining metastatic behavior within 3D bioprinted vasculature for the validation of a 3D computational flow model," accepted to Science Advances, 2020 LLNL-JRNL-805139.

Dubbin K, Robertson C, Hinckley A, Alvarado JA, Gilmore SF, Hynes WF, Wheeler WK, Moya ML. "Macromolecular gelatin properties affect fibrin microarchitecture and tumor spheroid behavior in fibrin-gelatin gels," Biomaterials, Aug 2020, 250.

Kent AJ, Mayer N, Inman JL, Hochman-Mendez C, Bissell MJ, Robertson C. "The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins," Biomaterials. 218, October 2019, 119337 LLNL-JRNL-800043

Robertson, C., Bioprinting and tissue engineering for breast cancer model development. Invited talk presented at University of New Mexico, Dec 2019.

Hynes WF, Pepona M, Robertson C, Alvarado JA, Dubbin K, Triplett M, Adorno JJ, Randles A, Moya ML. "Examining metastatic behavior within 3D bioprinted vasculature for the validation of a 3D computational flow model." UCSF breast oncology program annual symposium, San Francisco, CA, Feb 20, 2020.

Robertson C, Triplett M, Moya ML, Hynes WF, Wheeler EK. "Growth pressure induces formation of premalignant papillae in engineered breast ducts." BMES cell and molecular bioengineering, Puerto Rico, Jan 2-5, 2020.