Hemodynamic environments from opposing sides of human aortic valve leaflets evoke distinct endothelial phenotypes in vitro.

The regulation of valvular endothelial phenotypes by the hemodynamic environments of the human aortic valve is poorly understood. The nodular lesions of calcific aortic stenosis (CAS) develop predominantly beneath the aortic surface of the valve leaflets in the valvular fibrosa layer. However, the mechanisms of this regional localization remain poorly characterized.

Functional endothelialized microvascular networks with circular cross-sections in a tissue culture substrate.

Functional endothelialized networks constitute a critical building block for vascularized replacement tissues, organ assist devices, and laboratory tools for in vitro discovery and evaluation of new therapeutic compounds. Progress towards realization of these functional artificial vasculatures has been gated by limitations associated with the mechanical and surface chemical properties of commonly used microfluidic substrate materials and by the geometry of the microchannels produced using conventional fabrication techniques. Here we report on a method for constructing microvascular networks from polystyrene substrates commonly used for tissue culture, built with circular cross-sections and smooth transitions at bifurcations.

Biomechanical forces promote embryonic haematopoiesis.

Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3-5), a master regulator of haematopoiesis, and give rise to haematopoietic cells. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential.

Cell migration into scaffolds under co-culture conditions in a microfluidic platform.

Capillary morphogenesis is a complex cellular process that occurs in response to external stimuli. A number of assays have been used to study critical regulators of the process, but those assays are typically limited by the inability to control biochemical gradients and to obtain images on the single cell level. We have recently developed a new microfluidic platform that has the capability to control the biochemical and biomechanical forces within a three dimensional scaffold coupled with accessible image acquisition.

Biomechanical Regulation of Endothelium-dependent Events Critical for Adaptive Remodeling.

Alterations in hemodynamic shear stress acting on the vascular endothelium are critical for adaptive arterial remodeling. The molecular mechanisms regulating this process, however, remain largely uncharacterized. Here, we sought to define the responses evoked in endothelial cells exposed to shear stress waveforms characteristic of coronary collateral vessels and the subsequent paracrine effects on smooth muscle cells.