1. Rapid 3D Extrusion of Synthetic Tumor Microenvironments
- Author
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Joshua M. Grolman, Andrew M. Smith, Jeffrey S. Moore, Kristopher A. Kilian, and Douglas Zhang
- Subjects
Spatial positioning ,Cell type ,Materials science ,Alginates ,Cell Survival ,Microfluidics ,Breast Neoplasms ,Nanotechnology ,Single step ,Adenocarcinoma ,Article ,Mice ,Glucuronic Acid ,Tissue engineering ,Biomimetic Materials ,Cell Movement ,Cell Line, Tumor ,Lab-On-A-Chip Devices ,Tumor Microenvironment ,Animals ,Humans ,General Materials Science ,Tumor microenvironment ,Tissue Scaffolds ,Hexuronic Acids ,Macrophages ,Mechanical Engineering ,Hydrogels ,Equipment Design ,Coculture Techniques ,Mechanics of Materials ,Self-healing hydrogels ,Biophysics ,Extrusion - Abstract
Solid tumors house an assortment of complex and dynamically changing microenvironments in which signaling events between multiple cell types are known to play a critical role in tumor progression, invasion, and metastasis. To deepen our understanding of this biology, it is desirable to accurately model these structures in vitro for basic studies and for drug screening; however, current systems fall short of mimicking the complex organization of cells and matrix in vivo. Here we demonstrate the generation of spatially-organized 3D hydrogels of cells and matrix produced from a simple concentric flow device in a single step. Multiple cell types are pre-seeded in different spatial domains such as concentric regions of vessel-like tubular structures to reproducibly establish heterotypic cellular environments in 3D. Using macrophages and breast adenocarcinoma cells as an example of a paracrine loop that regulates metastasis, we explored the effects of clinical drug treatments and observed a dose-dependent modulation of cellular migration. This versatile and tunable approach for tissue fabrication will enable a means to study a wide range of microenvironments and may provide a clinically-viable solution for personalized assessment of patient response to therapeutics.
- Published
- 2015
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