SUMMARY

The “Tumor microenvironment” TME is a complex, interacting system including the tumor itself, other noncancerous cell types such as immune, stromal and endothelial cells, and the extracellular matrix surrounding these cells. Developing in vitro assays that closely replicate the pathophysiology of 3D vascularized tumor microenvironments (TME) is critical to understand the formation and development of tumors and unravel the mechanisms by which tumor cells grow, metastasize, and resist against drugs. To this end, this thesis first describes the method to create in vivo like vascularize tumor spheroid Polydimethylsiloxane (PDMS)-based model. We developed vascularized tumor spheroid model that reproduces the pathological and morphological characteristics of in vivo vascularized solid TME. We observed that cancer-EC hybrid spheroids enhanced uniformity of spheroid, tumor aggressiveness, and tumor angiogenesis. Moreover, tumor vasculature showed a higher permeability coefficient and increased focal intercellular openings, demonstrating hallmarks of leaky tumor vasculature. We further visualized and quantitatively demonstrated the effects of cancer drug; Axitinib by monitoring blood vessel area and spheroid tumor size, highlighting the significance of tumor vascularization and revealing the importance of the dose and treatment timing. Secondly, this thesis describes Injection-molded based vascularized tumor microenvironment platform. PDMS-based platform has been widely adopted as in vitro platforms for mimicking tumor microenvironment. However, PDMS has not been welcomed as a standardized commercial application for preclinical screening due to inherent material limitations that make it difficult to scale-up production. Here, we present an injection-molded plastic array 3D spheroid culture platform (Sphero-IMPACT). The platform is made of polystyrene in a standardized 96-well plate format with a user-friendly interface. The platform that mediate open microfluidics allows implement spontaneous fluid patterning with high repeatability from the end user. To demonstrate versatile use of the platform, we established a tumor spheroid induced angiogenesis model that can be applicable for drug screening. at GT, given my joint Ph.D. status, the entirety of my proposal and defense is to be done through video conferencing Bluejeans link: https://bluejeans.com/5798096222