title: 3D hydrogel-based microwell arrays as a tumor microenvironment model to study breast cancer growth.
abstract: The tumor microenvironment (TME) is distinctly heterogeneous and is involved in tumor growth, metastasis, and drug resistance. Mimicking this diverse microenvironment is essential for understanding tumor growth and metastasis. Despite the substantial scientific progress made with traditional cell culture methods, microfabricated three-dimensional (3D) cell cultures that can be precisely controlled to mimic the changes occur in the TME over tumor progression are necessary for simulating organ-specific TME in vitro. In this research, to simulate the breast cancer TME, microwell arrays of defined geometry and dimensions were fabricated using photo-reactive hydrogels for a cancer cell line and primary explant tissue culture. Microwell arrays fabricated from 4-arm polyethylene glycol acrylate and methacrylated gelatin with different degrees of methacrylation for controlled cell-matrix interactions and tunable stiffness were used to create a platform for studying the effects of distinct hydrogel compositions and stiffness on tumor formation. Using these microwell arrays, size-controlled spheroids of human breast cancer cell line HCC1806 were formed and the cell attachment properties, viability, metabolic activity, and migration levels of these spheroids were examined. In addition, primary mammary organoid tissues explanted from mice were successfully cultured in these hydrogel-based microwell arrays and the organoid morphology and viability, as well as organoid branching were studied. The microwell array platform developed and characterized in this study could be useful for generating a tissue-specific TME for in vitro high throughput studies of breast cancer development and progression as well as in drug screening studies for breast cancer treatment.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Casey
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Yue
authors.forename: Trung Dung
authors.initials: TD
authors.lastname: Nguyen
authors.forename: Aylin
authors.initials: A
authors.lastname: Acun
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Zellmer
authors.forename: Siyuan
authors.initials: S
authors.lastname: Zhang
authors.forename: Pinar
authors.initials: P
authors.lastname: Zorlutuna
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D005780:Gelatin; D057166:High-Throughput Screening Assays; D006801:Humans; D020100:Hydrogels; D008321:Mammary Glands, Animal / Q000033:anatomy & histology; D008422:Materials Testing; D051379:Mice; D011092:Polyethylene Glycols; D018874:Spheroids, Cellular / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D011092:Polyethylene Glycols; D005780:Gelatin