Modeling the Endothelial Glycocalyx Post-Pneumonectomy in a 3D Fluidic Chip - An Approach to Fabricating a Vascular-based Organ-on-Chip System.

Abstract

Endothelial glycocalyx (GCX), a carbohydrate-rich layer coating the luminal surface of endothelial cells, plays a pivotal role in regulating cellular responses to stimuli. It is comprised of transmembrane proteins serving as mechanotransducers for cellular responses. While it naturally maintains its structure and stability under homeostatic conditions, exposure to high-shear stress can induce damage with numerous consequences. General shear stress effects on endothelial cells have been explored, but the extent and impact of shear stress on vascular systems, specifically post-pneumonectomy, have not been well studied. To investigate this, a comprehensive approach was undertaken, involving the creation of a CAD model of pulmonary vasculature pre- and post-pneumonectomy. Utilizing computational fluid simulation, key regions of elevated shear stress and pressure were identified and replicated in an organ-on-chip (OOC) system. Human lung microvascular endothelial cells (HLMVECs) were seeded onto a mold in the shape of the selected sections to characterize the effects of elevated shear stress in vitro. Following experimentation, HLMVECs were immunostained to qualitatively evaluate GCX health under normal and increased stresses induced by pneumonectomy. The integration of computational modeling and experimental analysis enhances our understanding of how changes in shear stress affect GCX, clarifying their effects on vascular function and post-surgical complications.