Research Projects

Atherosclerosis is one of the most serious cardiovascular diseases (CVDs), causing an alarming global health concern and attributing to the highest number of mortalities among all CVDs [1]. The pathogenesis of atherosclerosis is very complex, involving dynamic interactions between various human cells, inflammatory factors, and disturbed hemodynamics of blood within the vessels [2]. As a result, there is the formation of fibrofatty plaque in the vessels, which can rupture and elevate thrombus formation and movement, causing heart attacks and strokes [11]. Traditionally, animal models (rats, pigs) and in vitro 2D cell culture models have been extensively used to understand the pathogenesis of atherosclerosis and drug development and testing. However, these models fail to mimic human physiology, require rigorous ethical clearance, and are expensive [1,2]. Therefore, there is an urgent need to develop a sophisticated, portable OOC model that can accurately mimic the human physiology. The proposed project aims to develop an organ-on-a-chip (OOC) model that integrates patient-specific physiology and micro-environment on a microfluidics platform. The specific objectives of the proposed projects include real-time monitoring of atherosclerosis progression, investigation of the effect of vascular remodeling, plaque instability, and efficacy and safety of targeted drugs. PI aims to accomplish the goals of the project with combined numerical and experimental approaches. She plans to design and develop an OOC model that will mimic the exact human physiology of blood vessels and disease progression. For that, the OOC model will be designed and fabricated using the lithography/bioprinting methods. Later, patient-specific endothelial cells, vascular smooth muscle cells, and extracellular matrix will be seeded in the microchannels to provide a micro-physiological environment. Extensive experiments will be performed by introducing blood by micropumps into the OOC model. Later, various concentrations of oxidized low-density lipoprotein will be introduced in the model to initiate and evolve lipid accumulation in the blood vessels to mimic various stages of the disease. Further, various concentrations of cytokines (TNF-α or IL-1β) will be introduced into the bloodstream to investigate the inflammatory response. Real-time imaging will be performed using a fluorescence microscope by fluorescently labeling the biomarkers for disease progression. In addition, PI plans to do numerical simulations to investigate the effect of vascular remodeling and plaque instability using COMSOL Multiphysics software. The model will also be used for the development of personalized drugs. The successful development of the OOC model will provide a powerful tool to the medical community for the real-time monitoring of cardiovascular diseases, providing predictive solutions for the early detection of disease and the development of personalized medicines.