(143g) Nanostructured Platforms to Evaluate Cell Migration-Microenvironment Interactions in Glioma

Research has established that two dimensional tissue culture models, such as tissue culture polystyrene, fail to adequately recapitulate conditions in the tumor microenvironment. Thus, there is substantial interest in developing new models to mimic unique chemical, mechanical, and topographical conditions in vivo. For example, hydrogels composed of collagen, hyaluronic acid, Matrigel, and peptide-modified synthetic materials, have all been employed to evaluate interactions of cancer cells with specific microenvironment cues. Similarly, electrospun fibers can mimic the topography of ordered anatomical structures, such as blood vessels and white matter tracts.

Here, we will discuss important caveats that we have uncovered in using and developing these models to evaluate cell response to mechanical cues in the microenvironment. First, we show that cells can sense the mechanical environment of the underlying support within an “edge effects” region close to the interface. Thus, in this region, cell responses may not reflect those corresponding to the intended hydrogel mechanical properties. Further, many tissues are viscoelastic; however, tissue characterization primarily focuses on the Young’s or Elastic modulus, rather than the viscoelastic response. We show that tissues can have similar moduli, but very different Maxwell elasticity and viscoelasticity, which may influence cell behaviors. Finally, we show that shearing forces may be better predictors of cell behavior than tensile forces or Young’s modulus. All of these factors should be considered in the design of biomaterials to mimic the cancer microenvironment.

As a model system, we will discuss hydrogels and electrospun fiber mats to mimic the brain microenvironment for gliomas, astrocytomas of the nervous system. Because the average patient survival is ~ 12-15 months with best of care, additional strategies for glioma are urgently needed. In addition, glioma is highly infiltrative, spreading to the contralateral hemisphere even with complete resection of the tumor-containing hemisphere. Gliomas typically travel along blood vessels and white matter tracts that provide ordered topographical features. These structures are well modeled by fibrous collagen hydrogels or electrospun nanofibers, whereas hyaluronic acid (HA) is the primary tissue component of brain. Thus, this presentation will describe collagen, HA, and collagen-HA hydrogels, as well as electrospun fiber mat models of glioma.