Single-Cell RNA Sequencing Reveals That Adaptation of Human Aortic Endothelial Cells to Antiproliferative Therapies Is Modulated by Flow-Induced Shear Stress.

Background: Endothelial cells (ECs) are capable of quickly responding in a coordinated manner to a wide array of stresses to maintain vascular homeostasis. Loss of EC cellular adaptation may be a potential marker for cardiovascular disease and a predictor of poor response to endovascular pharmacological interventions such as drug-eluting stents. Here, we report single-cell transcriptional profiling of ECs exposed to multiple stimulus classes to evaluate EC adaptation.

A Dynamic, In Vitro BBB Model to Study the Effects of Varying Levels of Shear Stress.

The blood-brain barrier (BBB) consists of a tight network of blood capillaries in the brain that separate the circulatory system from the central nervous system. Its particular properties are based on the dynamic interaction between cerebral endothelial cells and other surrounding cells, especially astrocytes. We have designed and synthesized a three-dimensional scaffold that recapitulates the main hallmarks of the BBB extracellular matrix and serves as a platform to co-culture human brain microvascular endothelial cells and human cortical astrocytes.

Balloon-based drug coating delivery to the artery wall is dictated by coating micro-morphology and angioplasty pressure gradients.

Paclitaxel coated balloon catheters (PCB) were developed as a polymer-free non-implantable alternative to drug eluting stents, delivering similar drug payloads in a matter of minutes. While PCB have shown efficacy in treating peripheral arterial disease in certain patient groups, restenosis rates remain high and there is no class effect. To help further optimize these devices, we developed a scanning electron microscopy (SEM) imaging technique and computational modeling approach that provide insights into the coating micromorphology dependence of in vivo drug transfer and retention.