Adapting a gelatin hydrogel platform to investigate glioblastoma progression

According to the World of Health Organization, cancer is the leading cause of death worldwide, responsible for approximately 1 in 6 deaths globally. In the United States alone, there are approximately 80,000 new cases of primary brain tumors diagnosed annually, with a third of those being malignant brain cancer. Glioblastoma is the most common and lethal form of adult brain cancer, contribute to about 13,000 new cases annually in the U.S. Despite current clinical standard-of-care, which involves surgical tumor debulking followed by chemotherapy and radiotherapy, patient prognosis remains poor (median survival ~15 months; 5+ year survival <5-15%) and has not significantly improved for decades. Poor survival is linked to the rapid, diffuse infiltration of GBM throughout the brain and the inability to surgically resect or therapeutically target these diffusely spread cells. While significant insight has been gained to how structural or mechanical features of the tumor microenvironment may influence GBM invasion, it is unclear how cohorts of diverse cells that exist within the tumor microenvironment shape GBM invasion and drug resistance. This dissertation describes a bioengineering approach to develop biomaterial models of the GBM tumor microenvironment to study how structural (stiffness, hyaluronan content) and metabolic (e.g., hypoxia) gradients within the tumor margin, as well as the heterogenous cellular make-up of the GBM tumor shape its progression. We fabricated brain mimetic hydrogels matching biophysical features of the tumor and margins, designed culture conditions mimicking tumor hypoxia and activation of microglia immune cells from the GBM tumor microenvironment. Together, we showed that the combined influence of transitions in biophysical and biochemical composition as well as the immune cells greatly influence on GBM invasion, bringing new insight to potential therapeutic interventions to better target this disease.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2020

Author dc:creator

• Chen, Jee-Wei Emily

Contributors dc:contributor

• Harley, Brendan
• Kraft, Mary
• Gaskins, H Rex
• Kong, Hyun Joon

• glioblastoma
• biomaterials

Statement dc:rights

• Copyright 2020 Jee-Wei Chen

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/108080

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/108080