BIO FLUIDS LAB
SKY
PROJECTS
1
CARDIOVASCULAR FLUID MECHANICS AND DEVICES
The significance of cardiovascular disease today, specifically heart disease, can be observed in the following statistics: an estimated 785,000 Americans had a new coronary attack and about 470,000 had a recurrent attack in 2009 alone. Interestingly, coronary artery disease which is caused by the narrowing of small vessels (ie, development of atherosclerosis) correlates to abnormal mechanical conditions (ie, shear stress, strain, pressure). Treatment methods generally include surgical (coronary artery bypass grafts) or percutaneous coronary interventions (balloon angioplasty and stents). Although both treatment options have shown great success, growth of new tissue (neointimal hyperplasia) at specific treatment sites has lead to re-blockage of blood flow. To overcome these limitations, the next generation of clinical devices incorporates drugs to minimize neointimal hyperplasia. Clinical results, however, have questioned the safety of these devices due to delayed healing and incomplete endothelialization. In fact, much remains to be understood regarding the cellular response to the current therapeutic devices and drugs and their interaction to local mechanical forces. Therefore, the main guiding objective for the BioFluids laboratory will be to use a multidimensional approach to understand and identify the limitations of current devices and to ultimately develop safer and more effective treatment options to treat cardiovascular disease. Specific efforts will be (1) to characterize the mechanical environment prone to neointimal hyperplasia, (2) to elucidate the relationship of shear stress and mechanical strain on endothelial cell proliferation and migration following injury, and (3) to optimize the delivery of therapeutic anti-proliferative drugs intended to suppress neointimal growth.
2
NON-STENT PLATFORM DRUG DELIVERY
Peripheral arterial disease (PAD) is a growing problem that affects more than 5 million adults in the US. PAD occlusions are treated by atherectomy (to open blockage) and then stented to prevent re-occlusion. Stents prevent re-occlusion by their physical barrier and by delivering anti-proliferative drugs to inhibit smooth muscle cell (SMC) proliferation, the main cause of new tissue growth that re-occludes arteries. However, the physical barrier of stents are compromised by high fracture rates. Furthermore, the presence of the metallic stent in the artery triggers a chronic injury response. This injury response leads to continued proliferation of SMC and results in re-occlusion following the depletion of the stents anti-proliferative drug coating. Therefore, a major goal of our lab is to develop new approaches to avoid the limitations of stents. We are currently developing novel drug coated balloons and determining the efficacy and safety of perfusion catheters to deliver locally anti-proliferative therapeutic agents.
3
MODEL DEVELOPMENT & DEVICE TESTING
Preclinical evaluation of devices such as drug coated balloons and vascular stents is vital to understanding the safety and efficacy of these devices. Currently, biological testing of these devices is mostly limited to in-vivo animal models, preformed to observe physiological and mechanistic responses post device delivery. While the pharmacokinetic data obtained from these procedures are effective, in-vivo animal testing is deficient in many areas. Surgical procedures are expensive, time consuming, and a large quantity of animals is needed to achieve statistically significant results. Our lab is focused on developing new modeling methods to bridge the gap between bench-top testing and pre-clinical modeling. Our work has been catalytic in enabling predictive testing of early stage research ideas and concepts to be accomplished quickly and at lower cost yielding enhanced understanding and faster forward progress to be made.