Abstract
Microengineering advances have enabled the development of perfusable, endothelialized models of the microvasculature that recapitulate the unique biological and biophysical conditions of the microcirculation in vivo. Indeed, at that size scale (<100 μm)—where blood no longer behaves as a simple continuum fluid; blood cells approximate the size of the vessels themselves; and complex interactions among blood cells, plasma molecules, and the endothelium constantly ensue—vascularized microfluidics are ideal tools to investigate these microvascular phenomena. Moreover, perfusable, endothelialized microfluidics offer unique opportunities for investigating microvascular diseases by enabling systematic dissection of both the blood and vascular components of the pathophysiology at hand. We review (a) the state of the art in microvascular devices and (b) the myriad of microvascular diseases and pressing challenges. The engineering community has unique opportunities to innovate with new microvascular devices and to partner with biomedical researchers to usher in a new era of understanding and discovery of microvascular diseases.
Highlights
Diseases of the microvasculature can be caused by changes to the endothelium, blood, or their ensuing pathological interactions. (a) The microvasculature is composed of arterioles, capillaries, and venules
Capillaries only have a layer of endothelial cells and an associated basement membrane, and in some cases they are smaller than red blood cells (RBCs)
Endothelial cell behavior is modulated by soluble mediators, mechanical forces, cell-to-cell interactions with pericyte and smooth muscle cells, cell-to-matrix interactions, pH, and pO2 [3, 7], which can all vary in the microvasculature
Summary
Diseases of the microvasculature can be caused by changes to the endothelium, blood, or their ensuing pathological interactions. (a) The microvasculature is composed of arterioles, capillaries, and venules. Diseases of the microvasculature can be caused by changes to the endothelium, blood, or their ensuing pathological interactions. (a) The microvasculature is composed of arterioles, capillaries, and venules. Blood cells must nominally deform to pass through the microvasculature, and changes to the adhesiveness or stiffness significantly influence transport. Soluble factors in blood can modulate endothelial cell, smooth muscle cell, and pericyte activity. (b) In sickle cell disease, sickled red blood cells (RBCs) are stiffer and occlude endothelium, white blood cells (WBCs) are more adhesive, and free heme damages the endothelium. (c) Acute respiratory distress syndrome involves an inflamed, leaky endothelium and activated leukocytes, which are stiff and more adhesive. Www.annualreviews.org Vascularized Microfluidics 409 a Arteriole Smooth muscle Capillaries Venule b
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