As the leading cause of death in industrialized nations and as an increasing problem in developing countries, the treatment for cardiovascular disease can impact a very large population. Interventions common to cardiovascular disease involve blood-contacting medical devices that are at-risk for thrombosis (blood clots). Since thrombosis on these devices can lead to ischemia in vital organs and possible death, it is critical to mitigate the risk. Therefore, patients are commonly placed on antiplatelet and anticoagulant drug regimens. Unfortunately, these therapies can create additional bleeding risks and do not completely prevent the risk for thrombosis. Therefore, many material scientists have been investigating alternative non-thrombogenic materials to those currently used in order to minimize the need for drug therapeutics. Superhydrophobic surfaces are one of the surface treatments that has exhibited excellent results in static conditions at mitigating processes involved in thrombus growth. However, the response of blood to superhydrophobic materials remains ill-defined in a flow environment more relevant to cardiovascular devices. This environment consists of spatially changing shear, which has been shown to have a very large impact on platelet aggregation. Therefore the ultimate goal of the proposed work is to assess superhydrophobic materials in this environment to determine if these materials should be investigated further for devices such as prosthetic heart valves or stents. For this investigation we have 2 aims:
Specific Aim 1) Prepare and characterize superhydrophobic surfaces in microfluidic channels involving large changes in shear rate. A series of surface treatments of varying texture and surface energy will be characterized by evaluating contact angles, surface structure, and flow over the surfaces. These treatments will be applied to microfluidic channels involving flow constrictions to assess material durability in a shear environment and to determine if air pockets exist along the superhydrophobic surface, which is common to surfaces with texture and low surface energy.
Specific Aim 2) Analyze the impact of spatially varying hemodynamic shear forces on blood cell dynamics and the role for chemical activators using a novel Lab-on-Chip approach. We will be testing the ability for superhydrophobic surfaces to prevent platelet aggregation in a shear gradient. To test this, a series of microfluidic devices wil be developed for high throughput evaluation of material thrombogencity in a flow environment pertinent to medical devices. These tools will be combined with imaging techniques to evaluate different shear environments to guide future cardiovascular device designs and to determine the role for soluble agonist platelet activation in the aggregation process for superhydrophobic surfaces.

Public Health Relevance

(Public Health Relevance) Medical devices used to treat cardiovascular disease, e.g. prosthetic heart valves and stents, create a thrombotic (blood clot) risk in patients that is clinically addressed with anticoagulation and antiplatelet therapies. Experimental evidence indicates that surfaces that strongly repel water, like a lotus leaf, may be effective at reducing the risk for blood clots. Therefore, we are evaluating these surfaces in a flow environment typical of medical devices to assess their efficacy for future use in medical devices.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL129730-03
Application #
9173415
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Meadows, Tawanna
Project Start
2015-09-10
Project End
2018-09-09
Budget Start
2016-09-10
Budget End
2017-09-09
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Bark Jr, David L; Vahabi, Hamed; Bui, Hieu et al. (2017) Hemodynamic Performance and Thrombogenic Properties of a Superhydrophobic Bileaflet Mechanical Heart Valve. Ann Biomed Eng 45:452-463
Bark Jr, David L; Yousefi, Atieh; Forleo, Marcio et al. (2016) Reynolds shear stress for textile prosthetic heart valves in relation to fabric design. J Mech Behav Biomed Mater 60:280-287