Topographic Control of Cell Migration: A Nanofabricated 3D Imaging Platform for Biomaterial and Device Interface Engineering

Abstract

Two-dimensional (2D) cell culture systems, while experimentally convenient, fail to replicate the geometric complexity of in vivo environments. Three-dimensional (3D) culture platforms are therefore essential for studying phenomena such as tumor progression, cell migration, and cell:material interfaces, yet existing 3D systems are limited by poor optical clarity, inconsistent fabrication, and low geometric fidelity. This thesis presents the design and fabrication of a Cellular Topographic Testing (CTT) Chip: a platform combining Euclidean and non-Euclidean (Gaussian curvature) surface geometries including high aspect ratios, extreme curvature gradients, sharp discontinuities, and singularities. These chips serve to probe how epithelial cells sense and respond to complex surface topography on its own similar length scale. Epithelial cells serve as the biological model given their role as the physical barrier between external and tissue environments in organs such as skin and organ lining, making them ideal candidates for curvature response studies. The CTT Chip was developed to address three unmet gaps in the literature: (1) establishing a reproducible fabrication pipeline combining nanofabrication with PDMS double molding to achieve high magnification resolution; (2) determining the geometric limits of epithelial tissue migration across convex, concave, and barrier geometries of varying height and aspect ratio; and (3) quantifying how local curvature governs epithelial layer thickness and nuclear positioning. The platform is designed to be biocompatible, imageable under confocal microscopy at 40×magnification and above, and reproducible without significant geometric degradation. Beyond fundamental research, the CTT Chip can be extrapolated in broader translational applications. As a high fidelity in vitro model, it offers a viable diagnostic to 2D cell cultures by capturing how malignant vs. benign cells approach and grown on different curvatures, or measuring other phenotypical/behavioral differences. This positions the platform as a tool for preclinical drug screening, where understanding interactions between therapeutics and geometrically complex epithelial barriers is critical. Furthermore, by recreating the curved and discontinuous surfaces encountered at cell material interfaces such as neural electrodes and implantable devices, the CTT Chip provides a standardized testbed that could inform FDA regulatory frameworks for evaluating biocompatibility and tissue response in next generation medical devices and drug delivery systems.