Graduation Semester and Year
Fall 2025
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Biomedical Engineering
Department
Bioengineering
First Advisor
Dr. Michael Cho
Second Advisor
Dr. Abdel Kareem Azab
Abstract
Vascular homeostasis is sustained by a delicate equilibrium between barrier integrity and controlled permeability. When this balance is disrupted, the consequences extend across every organ system – fueling inflammation, edema, and tissue injury. Two seemingly contrasting pathologies, brain trauma and cancer, share a common hallmark of vascular dysfunction characterized by leaky and poorly regulated endothelium. This loss of vascular integrity not only contributes to secondary injury in the brain but also creates a hostile, hypoxic microenvironment in tumors that limits drug delivery and promotes resistance. Restoring the endothelium’s ability to act as a selective, dynamic barrier therefore represents a unifying therapeutic goal across neurological and oncological disease.
This dissertation explores the potential of Poloxamer 188 (P188) – a non-ionic, amphiphilic triblock copolymer – to stabilize and repair compromised vasculature through direct biophysical interactions with endothelial membranes. Unlike traditional pharmacologic agents that modulate signaling pathways, P188 acts by integrating into damaged lipid bilayers to restore surface tension and reduce permeability without affecting intact cells. Its established clinical safety and unique mechanism of membrane sealing make it an appealing candidate for broad vascular repair.
Through three interconnected studies, this work investigates P188 at multiple biological scales. First, a fully automated image-analysis pipeline was developed to quantify P188 uptake dynamics in endothelial cells, revealing active endocytic internalization and sustained intracellular retention after injury. Next, an in-vitro model of blood–brain barrier disruption demonstrated that P188 restores tight-junction organization and significantly reduces paracellular leakage. Finally, extending these findings to the tumor microenvironment, P188 was shown to normalize blood flow, enhance macromolecular delivery, and potentiate the efficacy of chemotherapy in triple-negative breast cancer models. Together, these studies establish P188 as a biophysical therapeutic capable of restoring endothelial integrity across distinct pathological contexts – bridging the gap between vascular protection in neurotrauma and vascular normalization in cancer.
Keywords
Vascular repair, Blood-brain barrier, Tight junctions, Membrane stabilization, Poloxamer 188, Endothelial permeability, Tumor vasculature, Cancer immunotherapy, Drug delivery, Triple-negative breast cancer
Disciplines
Biomedical Engineering and Bioengineering
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Alsup, Anne M., "Therapeutic Strategies to Restore Vascular Function in Brain Injury and Cancer" (2025). Bioengineering Dissertations. 206.
https://mavmatrix.uta.edu/bioengineering_dissertations/206