Biofluid Mechanics Research Laboratory

Research

Hemodynamic Performance of Mechanical Heart Valves

One of the major disadvantages associated with the implantation of mechanical heart valves (MHVs) is the need for chronic anticoagulation therapy to prevent thrombosis and thromboembolic complications. Patients with MHVs implants are plagued by an increased risk of bleeding, infection, and/or autoimmune response. These bi-leaflet mechanical valves lack a central flow across the valve annulus, which lead to an increased resistance to blood flow. Blood flow through mechanical prostheses can lead to elevated turbulent (Reynolds) stresses that may damage and/or activate blood elements and initiate platelet aggregation. Platelet aggregation can lead to thrombus formation with disastrous consequences for the patient; thrombi can detach from the valve and become lodged in a downstream blood vessel, thus reducing or even cutting off the blood supply to vital tissues. In recent years, computational fluid dynamics has emerged to provide a potentially promising in vitro alternative to investigate the hemodynamics within the heart valves.



Novel Carotid Artery Stent

Carotid artery stenosis is caused by atherosclerosis, mainly over the bifurcation of carotid artery. Small fragments (emboli) detached from the atherosclerotic plaque follow the blood flow into the brain circulation and cause stroke. The current minimally invasive treatment is carotid artery stenting; however, a bare-metal stent fails to constrain all the small fragments and the consequent stroke. In addition, as the carotid bifurcation is involved, a covered stent will jeopardize the perfusion of external carotid artery (ECA). Hence, we have designed a novel covered stent that can prevent the friable fragments of the atherosclerotic plaque from getting into the circulation and yet preserves the flow of ECA, with a simple deployment procedure. We have examined the performance of this novel carotid stent both experimentally (in vitro) using particle image velocimetry (PIV) flow measurements of the in-house manufactured prototype, and computationally by fluid-structure interaction (FSI) simulations. Currently, animal trials of this novel stent are in process.



Prototype and delivery system optimization of a novel covered stent for treatment of athero-embolic arterial disease

The prototypes of the novel covered stent are made for further function evaluation and design modification. The delivery system is developed and optimized for the coming animal tests and clinical trials of the stent. Compared with brachial and carotid approach, femoral access offers improved catheter and guide wire maneuverability; it also avoids the extreme angulation and the risk of damaging the median nerve. A transfemoral delivery system is developed to increase the placement accuracy of the novel covered stent for the minimally invasive carotid stenting.



A high throughput in vitro platform for assessment of drug induced cardiotoxicity

Drug induced cardiotoxicity is a leading cause of drug withdrawal from the market, accounting for 19% of drugs withdrawn from the US market on the last 40 years. Early detection of candidate compounds that are cardiotoxic during the in vitro stage would help reduce the incidence of drug induced cardiotoxicty and also save costs for pharmaceutical companies. The heart tissue has complex macroscale to nanoscale structural organization important for cardiac function. The myocytes that make up the myocardium are aligned in parallel such that the force of contraction and impulse propagation velocity are higher along the long axis of the fiber. However, this organization is usually lost in conventional in vitro cell culture. Various topographical cues have been used to restore this alignment and thereby improve functions of the cardiomyocytes in vitro In addition, mechanical cues like substrate stiffness have been shown to also have effect on cell function, with cardiomyocytes performing better on stiffness similar to what is obtained in vitro.



3D coculture for HCV in vitro infection and replication

170 million people worldwide are infected by Hepatitis C Virus (HCV) and the only treatment available is inefficient for the most prevalent genotype 1. Although HCV is very contagious in vivo, its life cycle cannot be studied accurately in vitro due to the lack of good cellular models. Our aim is to build a new system which will support HCV genotype 1 in vitro infection and replication. We use hepatoma cell line spheroids in coculture with 3T3 mouse fibroblasts. Our spheroids present better polarization and viral receptors localization compared to monolayer culture, and maintain them over a week in our coculture model. We believe that the better polarity and viral receptors localization in our model will lead to enhanced infection and viral particle production. In collaboration with Hanry Yu's group at NUS Physiology department.



Abdominal Aortic Aneurysm

Aortic aneurysms are localised dilation in the descending aorta due to degeneration of wall. Experimental and computational studies for patient specific are conducted on the disease with collaboration with National University Health System and Singapore General Hospital.






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