Thromboinflammation

Neutrophils tethering to a platelet monolayer.

It is increasingly recognized that platelets can stimulate an inflammatory response. We are investigating thromboinflammatory responses to various stimuli and how they can lead to complications in blood circulation. We are further quantifying biomechanical characteristics of these processes with an aim of identifying therapeutic targets that leverage mechanics.

Understanding the role of mechanics in heart development

The heart is the first organ that forms during embryogenesis. Pumping blood as an initial valveless “straight” tube, it undergoes a series of changes as chambers become more defined and valves form. To study embryonic heart development, we utilize zebrafish as a model, which exhibits similar heart development to humans during early stages. Our group is interested in identifying the role of mechanics in driving specific stages of heart development, relating functional, biomechanical, mechanobiological roles. Currently, we are investigating the mechanical properties of the embryonic heart and how they change as the heart transitions from a straight valveless tube to a multichambered adult heart.

Introducing a cannula to pressurize a zebrafish heart.
Wall shear stress and vorticity through the human fetal heart.

We are interested in understanding the role of mechanics in the formation of human congenital heart defects. For this effort, we are working with cardiologists at Children’s Hospital Colorado to collect ultrasound data. This data is processed, allowing us to perform computational simulations of flow through the fetal heart. Through this approach we can identify specific flow patterns in congenital heart defects, which may lead to a better understanding of cardiac function for specific cases, while also allowing us to identify if specific patterns actually drive the formation of a defect.

Developing blood-contacting medical devices

Mechanical heart valves are commonly used to replace failing heart valves but often suffer thromboembolic complications, particularly associated with the hinge region of these valves. As such, their use has been declining. Therefore, we are investigating the thrombotic and coagulant responses of blood in this region to better identify the specific features of the hinge that can otherwise lead to complications once implanted.

Left: Contour plot of shear rate through a microchannel involving a constriction. Right: Thrombus formation in the constriction region in DIC and fluorescence.

To improve blood-material interactions on mechanical heart valves, our collaborators are developing new surface treatments, such as the superhydrophobic treatment shown in the video to the left and the video below. Blood can be seen to bounce and roll or slide off of superhydrophobic surfaces. We are now investigating microscale responses of platelets and plasma proteins.

Bouncing blood droplet on pyrolytic carbon relative to a superhydrophobic surface. Reprinted by permission from: Springer Nature Annals of Biomedical Engineering Bark, David L., et al. “Hemodynamic performance and thrombogenic properties of a superhydrophobic bileaflet mechanical heart valve.” Annals of biomedical engineering 45.2 (2017): 452-463., Copyright 2017.

Blood sliding down glass, pyrolytic carbon, hydrophobic treatment, and superhydrophobic treatment. Reprinted by permission from: Springer Nature Annals of Biomedical Engineering Bark, David L., et al. “Hemodynamic performance and thrombogenic properties of a superhydrophobic bileaflet mechanical heart valve.” Annals of biomedical engineering 45.2 (2017): 452-463., Copyright 2017.