Session: Research Posters

Paper Number: 171996

Vascular Bioreactor for Endothelial Mechanobiology and Cardiovascular Dynamics 

Abstract:

Background:
Cardiovascular disease is the leading cause of mortality worldwide, responsible for more than 17 million deaths annually. A central event in disease progression is endothelial dysfunction, which contributes to vascular inflammation, increased permeability, and the development of atherosclerosis and related pathologies. The vascular endothelium is highly sensitive to mechanical forces, including fluid shear stress, pressure, and cyclic stretch, all of which influence cell alignment, barrier function, and inflammatory signaling. However, most traditional in vitro systems rely on static cell culture or oversimplified flow chambers that fail to reproduce the dynamic mechanical cues present in the human circulation. This lack of physiologic relevance limits our ability to translate fundamental findings into clinically meaningful insights and therapeutic advances.

Objective:
The goal of this project is to design and validate a vascular bioreactor that replicates physiologically relevant flow conditions to study endothelial mechanobiology and cardiovascular dynamics. Unlike static or two-dimensional cultures, this platform will allow researchers to expose endothelial cells to controlled, sustained, and adjustable shear stress environments that mimic both protective laminar flow and pathological low or oscillatory flow conditions. The overarching aim is to establish a tool that enables mechanistic investigation of endothelial barrier integrity, inflammation, and remodeling, with long-term applications in disease modeling and drug screening.

Methods:
The vascular bioreactor is built around optically transparent and biocompatible channels engineered to support endothelial cell culture under controlled flow. Human Coronary Artery Endothelial Cells (HCAECs) will be seeded onto the channels following coating with extracellular matrix proteins such as collagen IV, fibronectin, and laminin to mimic the vascular basement membrane. Once confluent monolayers are established, endothelial cells will be exposed to a spectrum of shear stress environments ranging from physiological laminar flow (10–20 dyn/cm²) to pathological low or disturbed shear (<4 dyn/cm²). Real-time monitoring of flow and pressure within the channels will ensure reproducibility and allow precise calibration of mechanical conditions.

Planned Biological Testing:
Endothelial responses will be examined using a comprehensive suite of assays. Live-cell imaging will assess junctional proteins such as VE-cadherin to determine barrier continuity. Immunofluorescence will evaluate actin cytoskeletal remodeling in response to flow. Molecular analysis will include qPCR, ELISA, and Western blotting to quantify markers of inflammation (ICAM-1, VCAM-1, IL-6), oxidative stress (ROS, MDA), and autophagy-related proteins (LC3-II, Beclin-1). Impedance-based assays (ECIS) will provide quantitative assessment of barrier function and permeability changes over time. Collectively, these readouts will provide an integrated view of how distinct hemodynamic environments regulate endothelial physiology and dysfunction.

Preliminary Results:
Initial prototype testing confirms that the vascular channels maintain structural stability under continuous flow and deliver reproducible shear stress environments consistent with computational fluid dynamics predictions. Pilot cell seeding experiments demonstrate strong endothelial adhesion and early junction formation on extracellular matrix coatings, supporting the suitability of the system for extended culture periods. These preliminary findings establish feasibility and provide a foundation for longer-term biological validation.

Conclusion and Future Work:
This vascular bioreactor represents a next-generation experimental platform for studying endothelial mechanobiology under controlled flow conditions. By bridging the gap between static in vitro models and complex in vivo physiology, the system enables mechanistic studies with greater translational relevance. In future stages, the platform will be expanded to include co-culture with vascular smooth muscle and immune cells to more closely approximate the vessel wall environment. Applications include modeling inflammatory vascular diseases such as vasculitis and atherosclerosis, testing candidate therapeutics, and exploring the cellular basis of vascular remodeling. Ultimately, this system is expected to provide a powerful tool for advancing cardiovascular research and developing strategies for precision medicine.

Acknowledgements:
This work is supported by the Florida Heart Research Foundation and the Nova Southeastern University President’s Research Grant (PRG #334986).

Presenting Author: Manuel Salinas Manuel Salinas

Presenting Author Biography: Dr. Manuel Salinas is an Associate Professor of Biomedical Engineering at Nova Southeastern University’s College of Computing and Engineering. He serves as Director of the Center for Cardiovascular Mechanics and holds an affiliate appointment at the Farquhar Honors College. Dr. Salinas earned his Ph.D. in Biomedical Engineering from Florida International University and completed postdoctoral training at Harvard Medical School and Brigham and Women’s Hospital. His research focuses on cardiovascular biomechanics, soft robotics, and fluid-structure interaction, with applications in vascular disease modeling and medical device development. He has received multiple research grants, including two NSU President’s Research Grants, and actively mentors students in interdisciplinary STEM research.

Authors:

Manuel Salinas Manuel Salinas
Andrew Sourial Nova Southeastern University