Date of Award

12-24-2025

Date Published

January 2026

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical and Chemical Engineering

Advisor(s)

Pranav Soman

Keywords

Biofabrication;Capillaries;Cavitation bubble;Cell Culture;Microfluidics

Abstract

Biological tissues exhibit complex three-dimensional (3D) architectures composed of diverse cell types embedded within extracellular matrices (ECM), where precise spatial organization governs critical cellular behaviors and tissue functions. Accurately replicating these native tissue microenvironments in vitro remains a major challenge, especially in controlling single-cell connectivity within natural ECMs and generating physiologically relevant microvascular networks. Current methods often lack reproducibility, spatial precision, and scalability, limiting their utility for fundamental biological studies and translational applications. This dissertation presents two microfabrication-based technologies to address these limitations. The first, Cellnet, uses femtosecond laser cavitation to create customizable 3D microchannel networks in collagen within microfluidic chips. Cells seeded into these networks self-organize into single-cell resolution circuits with defined connectivity and architecture, enabling real-time analysis of functional signaling responses, including calcium dynamics and perturbation effects. The second platform enables the generation of Artificial Capillaries, endothelial cell-lined microchannels with user-defined lumen sizes (10–40 µm) and architecture (straight, curved, branched). The system allows ECs to co-culture with stromal cells in adjacent silos and supports dynamic editing of capillary architecture. Together, these platforms offer accessible, reproducible, and scalable solutions to model complex tissue microenvironments, advancing the study of cellular communication and microvascular biology. By democratizing these tools for broader adoption, this work aims to accelerate research in tissue engineering, disease modeling, and drug discovery.

Access

Open Access

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