Description
- Abstract:
- Abstract of 3D Neural Microtissues as a Platform to Study Neuropathology of Mechanical Injury and Glioblastoma, by Dominick J. Calvao, Ph.D., Brown University, May 2025. The central nervous system is composed of a diverse array of cells and specialized structures, making the study of neuropathology particularly difficult. In vitro models capable of capturing this complexity are essential for advancing both mechanistic understanding and therapeutic development. This dissertation leverages a primary cell-derived cortical microtissue model to study the neuropathology of two distinct yet biologically complex central nervous system conditions: traumatic brain injury and glioblastoma. In the first application, a compression-based injury system was developed to apply controlled mechanical impacts to cortical microtissues, simulating traumatic brain injury stimuli. Injury response was evaluated using immunohistochemistry, viability assays, and calcium imaging. A key finding was that embedding the microtissues in hydrogels as a force transfer medium induced significant cell death, highlighting the need for careful material selection in 3D models. Modified protocols allowed delivery of mechanical strain directly to the tissues, resulting in injury phenotypes consistent with known traumatic brain injury pathology, including cell death, neurite damage, and glial reactivity. In the second application, glioblastoma cells were introduced into cortical microtissues to generate brain-cancer microtissues, enabling the study of cancer infiltration and the tumor microenvironment. Two distinct glioblastoma cell lines were introduced, each retaining hallmark phenotypic behaviors within the model. Infiltration dynamics were found to depend on the maturation stage of the microtissue, and the model captured cell line-specific differences in tumor interactions. Furthermore, key features of tumor-neuron, tumor-astrocyte, and tumor-microglia interactions were captured, highlighting the model’s utility in probing complex, multicellular tumor-neural dynamics. Together, these studies demonstrate that cortical microtissues provide a versatile and high-throughput platform for modeling diverse central nervous system pathologies. The model faithfully recapitulates key cellular features of brain tissue, including the presence of microglia and complex intercellular interactions. This work establishes cortical microtissues as a robust platform for the study of both mechanical injury and cancer-driven disruption in the brain, offering a promising tool for translational neuroscience research.
- Notes:
- Thesis (Ph. D.)--Brown University, 2025
Citation
Calvao, Dominick,
"3D Neural Microtissues as a Platform to Study Neuropathology of Mechanical Injury and Glioblastoma"
(2025).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:tff7zz22/
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....