Glioblastoma Growth In Vitro 3D Modelling in an Adjustable Nanofiber-Hydrogel Hybrid Synthetic Scaffold
Nikita Grigoryev,
Adjunct Professor,
NYU Tandon School of Engineering
Glioblastoma multiforme (GBM), the most aggressive form of brain cancer that originates from glial type stem cells. Recent discoveries show that glioma growths show a mysterious property of mosaic tumor heterogeneity. Arising from the same common precursor, later stage tumors and individual migrating GBM cells exist in intermingled clonal subpopulations with mutually exclusive gene amplification contributing to an “epigenetic switch” that gives rise to malignant invasive subclones that escape the original tumor, heavily aggravating the disease progression and patient survival. Current in vitro models are typically far from physiological actuality and do not provide necessary 3D mechanobiological environment native to brain tissue. Our unique approach uses a marriage of patented electrospinning/nanofiber coating technique and dipping/cell trapping gelation method to create a layered scaffold construct for GBM in 3D. A hydrogel layer is built over a glass rod by dipping into either an acellular alginate solution (as a niche for cancerous invasion) or a cells-alginate suspension and is crosslinked by dipping into a cation solution. Subsequently, electrospun nanofibers are deposited directly onto each hydrogel layer for controllable nanotopography exterior similar that of native, while the hydrogel, as soft as brain, itself surrounds cells. We have confirmed successful growth, spread and invasion of originally seeded cells into acellular layers of our construct with an appearance of tumor-like structures resembling those found in-vivo. Our proposed adjustable 3D model is completely artificial and provides cells with mechanobiological nanoenvironment comparable to that of native tissue, while also allowing for easy cancerous growth tracking through transparent layers.
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