Fabrication of collagen-based microfluidic devices for in vitro study of tumor microenvironment
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Microfluidic technology has led to the development of advanced in vitro tumor platforms that overcome the challenges of in vivo animal and in vitro two dimensional models. This paper presents platform designs and methods used to develop in vitro models that replicate the tumor microenvironment. Features of these platforms include a continuous endothelium that allows for cell-cell interactions between vasculature and tumor cells. Additionally, we can recreate the abnormal shear stresses and the tortuous vasculature seen in patient tumors. Various methods such as subtractive, additive, and soft lithography techniques have been used by groups to manufacture complex microfluidic tumor models. A novel platform for fabrication of a single endothelialized microchannel encased within a collagen hydrogel hosting breast cancer cells was developed and utilized to study the influence of cellular interaction on transport phenomenon through vasculature in a hyperpermeable tumor microenvironment. We have confirmed the platforms ability to recapitulate physiological features of the tumor microenvironment and demonstrated the influence of tumor endothelial interactions on transport. Additionally, a second platform capable of combining lithographic techniques with additive tissue engineering methods was used to create endothelialized microfluidic networks that capture the more complex geometries of tumor microvasculature. By modeling microvascular networks after in vivo tumors we are able to create patient specific in vitro platforms that can be used to develop personalized patient treatments.