Date Approved

8-27-2020

Embargo Period

8-28-2020

Document Type

Thesis

Degree Name

M.S. Mechanical Engineering

Department

Mechanical Engineering

College

Henry M. Rowan College of Engineering

First Advisor

Miri, Amir K.

Second Advisor

Thompson, Gary L.

Third Advisor

Alpaugh, Mary

Keywords

Bioprinting, DLP Printing, glioblastoma, Microfluidics, organ-on-chip

Subject(s)

Additive manufacturing; Brain--Tumors

Disciplines

Biomedical Engineering and Bioengineering | Mechanical Engineering

Abstract

Glioblastoma multiform (GBM) is one of the most aggressive forms of primary brain tumors. GBM is fast progressing and resistant to treatment, resulting in a low survival rate. Conventional 2-dimensional tissue culture models cannot fully replicate the complexities of cancer lesions that contain multiple cell types and structures (e.g. vessels composed of endothelial cells, cancer cells, normal cells, etc.) as well as an intricate scaffold of proteins comprising the extracellular matrix (ECM). In addition, animal models cannot translate into the clinical disease in patients. Thus, this study has developed a bioprintable organ-on-a-chip (OOAC) model that mimics the important ECM factors of the GBM tumor microenvironment to study GBM invasive migration in vitro. Gelatin methacrylol (GelMA), endothelial cell (HUVEC) lined channels, human GBM cells (U87) and hyaluronic acid (HA) were selected to create bioinks to print the OOAC. 5-7% (w/v). GelMA with variable levels of HA was found to be mechanically comparable to native ECM of the brain. Different bioink combinations were explored to match the Young's modulus of common GBM tumors found in literature. Spreading of endothelial cells in a microfluidic channel were observed with a monoculture OOAC, and a viable bioink composition and culture method were developed to support co-culture in the OOAC. Our diseased tissue model can replicate the GBM ECM and can allow for multi-cell culture migration studies in the future.

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