MEMP PhD Thesis Defense: Katarzyna Grzelak

Engineering Perfusable Vascular Networks Using Exogenous Electrical Stimulation

Effective and lasting vascularization remains a major challenge in tissue engineering. Current approaches for generating vasculature in vitro require multistep fabrication methods or complex and costly media supplements, limiting their scalability. In this thesis, I demonstrate exogenous electrical stimulation (estim) as a promising strategy for achieving functional vascularization in engineered human tissues. First, I engineer a modular set of devices and leverage low-voltage and low-frequency estim to promote formation of dense and branched vascular networks in endothelial-fibroblast cocultures. Furthermore, in a microfluidic device model, I demonstrate that estim treatment significantly promotes vascular perfusability. This benefit translates into vasculature within implanted engineered human tissue, and I specifically present engineering vasculature in liver tissue cell therapy as a proof-of-concept application of estim. Moreover, I explore the electrophysiological mechanisms through which estim affects endothelium. I show that estim induces membrane hyperpolarization and identify that this effect is facilitated by voltage-gated potassium channels. This serves as a key mechanism by which estim promotes vascular assembly and function. Additionally, using a pharmacological approach, I explore membrane hyperpolarization as a stimulus driving vascular assembly, and directly link membrane potential dynamics to the vasculogenic responses. Collectively, this thesis work establishes estim as a novel and easily adaptable tool that enables control over important cell signaling machinery promoting formation of perfusable vasculature in engineered tissues.

Thesis Supervisor:
Sangeeta N. Bhatia, MD, PhD
John J. and Dorothy Wilson Professor of Engineering, Department of Electrical Engineering & Computer Science and Institute for Medical Engineering and Science, MIT

Thesis Committee Chair:
Ellen Roche, PhD
Abby Rockefeller Mauzé Professor, Department of Mechanical Engineering, and Institute for Medical Engineering and Science, MIT

Thesis Readers:
Christopher S. Chen, MD, PhD
William F. Warren Distinguished Professor of Biomedical Engineering, Department of Biological Engineering, Boston University

Alan J. Grodzinsky, ScD
Professor of Biological Engineering, Electrical Engineering, and Mechanical Engineering, Emeritus, MIT

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Katarzyna Grzelak is inviting you to a scheduled Zoom meeting

Topic: Katarzyna Grzelak MEMP PhD Thesis Defense
Time: Friday, July 25, 2025, 10:00 AM Eastern Time (US and Canada)

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