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Matrix Mimetic Hydrogels for High-Throughput Screening

Abstract

Cell-matrix interactions mediate complex physiological processes through biochemical, mechanical, and geometrical cues, influencing pathological changes and therapeutic responses. Accounting for matrix effects earlier in the drug development pipeline is expected to increase the likelihood of clinical success of novel therapeutics. Biomaterial-based strategies recapitulating specific tissue microenvironments in 3D cell culture exist but integrating these with the 2D culture methods primarily used for drug screening has been challenging. The development of methods which can incorporate the flexibility and utility of biomaterials will improve therapeutic development for diseases like Glioblastoma (GBM). Whose unique physiological characteristics have rendered traditional therapies ineffective for treatment. First, I adapt previous hydrogel-based technologies to be compatible with high-throughput (HT) drug screening platforms. Second, I further improve upon the underlying technique by developing a system capable of HT screening of 3-dimensional cultures and demonstrate a proof-of concept personalized medicine type application. Third, I developed techniques to quantify and characterize the diffusivity of solutes into hydrogels as a way to understand how physical pore size of hydrogels may affect penetration of therapeutics to encapsulated cells. Altogether, this work demonstrated the utility of including hydrogel based technologies in screening platforms for drug development and the establishment of fundamental techniques to characterize the effectiveness of future therapeutics for GBM.

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