Development of in vitro three dimensional tumor models
Abstract
The in vitro evaluation of chemotherapeutic delivery systems is essential as a prediction of in vivo chemotherapeutic efficacy. Conventional cellular monolayer models have provided poorly correlated outcomes of in vivo chemotherapeutic efficacy. Morphological differences of the tumor cells and lack of cell-cell and cell-extracellular matrix interactions in two-dimensional (2D) culture environment contribute to the discrepancies in cellular drug responses. Hence, there is a strong need for the development of in vitro tumor models closely mimicking the in vivo tumors. The main goal of this dissertation was to develop an in vitro 3D tumor model using hydrogels and to assess its application in evaluation of an anti-cancer drug. To achieve the goal, first, a surface engineering method was designed to develop a 3D tumor model by cross-linking a hydrogel. Secondly, applications of 3D tumor models were demonstrated to investigate effects of ECM-mimicking hydrogels and to evaluate the therapeutic efficacy of doxorubicin. Lastly, uniformly sized 3D tumor models were developed by the hydrogel template method and investigate the effect of dynamic culture condition. By understanding the characteristics of hydrogels, their mechanical properties were altered to create a microenvironment conducive for cancer cells to form 3D tumor models. Convenient and inexpensive methods developed in this study enabled culturing of 3D tumor models. These 3D tumor models showed great potential as valuable tools to investigate cellular drug responses.
Degree
Ph.D.
Advisors
Park, Purdue University.
Subject Area
Biomedical engineering|Pharmacy sciences
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