Generation of Biocompatible Scaffolds for Modeling Tumor Microenvironments

The National Cancer Institute estimates that approximately 40% of men and women will be diagnosed with cancer at some point in their lifetime. The importance and prevalence of this disease has spurred growing demands for novel methods for prevention, diagnosis, and treatment in recent decades. One facet of cancer research currently lacking is the availability of model systems which recapitulate vital aspects of cancer progression, such as cell migration. Traditionally, in vivo and in vitro studies have utilized animal or 2D cell culture models to predict the effect of certain treatments on the tumor environment and surrounding tissue. A developing avenue is 3D cell culture models, which more closely mimic biological phenomena. Specifically, microfluidic systems provide many benefits including low energy consumption, low material volumes, and the ability to run many analyses in parallel. Coupling microfluidic fabrication with 3D cell culture facilitates examination of tumor micro-environmental factors which are otherwise difficult to control, such as curvature. Here, we describe developments in translating direct write 3D printing of isomalt scaffolds into biologically compatible gels for cell culturing. First, the effect of several operational parameters on the print were characterized using optical microscopy. Next, a theoretical model for how these parameters affect print diameter was validated using our data. Ultimately, we will develop a protocol to use 3D sacrificial molds for the creation of microchannels in a biologically compatible gel. The gels can be seeded with different types of cells—from healthy to diseased—to study their phenotypes and behaviors. The unique application of 3D printing to cell culture provides access to culture devices which would be difficult with conventional manufacturing.National Science Foundation grant# EEC 14-61038Ope