Recapitulating the Vasculature using organ-on-chip technology

\u3cp\u3eThe development of Vasculature-on-Chip has progressed rapidly over the last decade and recently, a wealth of fabrication possibilities has emerged that can be used for engineering vessels on a chip. All these fabrication methods have their own advantages and disadvantages but, more importantly, the capability of recapitulating the in vivo vasculature differs greatly between them. The first part of this review discusses the biological background of the in vivo vasculature and all the associated processes. We then evaluate the biological relevance of different fabrication methods proposed for Vasculature-on-Chip, we indicate their possibilities and limitations, and we assess which fabrication methods are capable of recapitulating the intrinsic complexity of the vasculature. This review illustrates the complexity involved in developing in vitro vasculature and provides an overview of fabrication methods for Vasculature-on-Chip in relation to the biological relevance of such methods.\u3c/p\u3

3D printing of round microfluidic channels to mimic the microvasculature

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3D sugar printing of networks mimicking the vasculature

\u3cp\u3eThe vasculature plays a central role as the highway of the body, through which nutrients and oxygen as well as biochemical factors and signals are distributed by blood flow. Therefore, understanding the flow and distribution of particles inside the vasculature is valuable both in healthy and disease-associated networks. By creating models that mimic the microvasculature fundamental knowledge can be obtained about these parameters. However, microfabrication of such models remains a challenging goal. In this paper we demonstrate a promising 3D sugar printing method that is capable of recapitulating the vascular network geometry with a vessel diameter range of 1 mm down to 150 µm. For this work a dedicated 3D printing setup was built that is capable of accurately printing the sugar glass material with control over fibre diameter and shape. By casting of printed sugar glass networks in PDMS and dissolving the sugar glass, perfusable networks with circular cross-sectional channels are obtained. Using particle image velocimetry, analysis of the flow behaviour was conducted showing a Poisseuille flow profile inside the network and validating the quality of the printing process.\u3c/p\u3

A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions

\u3cp\u3eCell signalling and mechanics influence vascular pathophysiology and there is an increasing demand for in vitro model systems that enable examination of signalling between vascular cells under hemodynamic conditions. Current 3D vessel wall constructs do not recapitulate the mechanical conditions of the native tissue nor do they allow examination of cell-cell interactions under relevant hemodynamic conditions. Here, we describe a 3D microfluidic chip model of arterial endothelial and smooth muscle cells where cellular organization, composition and interactions, as well as the mechanical environment of the arterial wall are mimicked. The hemodynamic EC-VSMC-signalling-on-a-chip consists of two parallel polydimethylsiloxane (PDMS) cell culture channels, separated by a flexible, porous PDMS membrane, mimicking the porosity of the internal elastic lamina. The hemodynamic EC-VSMC-signalling-on-a-chip allows co-culturing of human aortic endothelial cells (ECs) and human aortic vascular smooth muscle cells (VSMCs), separated by a porous membrane, which enables EC-VSMC interaction and signalling, crucial for the development and homeostasis of the vessel wall. The device allows real time cell imaging and control of hemodynamic conditions. The culture channels are surrounded on either side by vacuum channels to induce cyclic strain by applying cyclic suction, resulting in mechanical stretching and relaxation of the membrane in the cell culture channels. The blood flow is mimicked by creating a flow of medium at the EC side. Vascular cells remain viable during prolonged culturing, exhibit physiological morphology and organization and make cell-cell contact. During dynamic culturing of the device with a shear stress of 1-1.5 Pa and strain of 5-8%, VSMCs align perpendicular to the given strain in the direction of the flow and EC adopt a cobblestone morphology. To our knowledge, this is the first report on the development of a microfluidic device, which enables a co-culture of interacting ECs and VSMCs under hemodynamic conditions and presents a novel approach to systematically study the biological and mechanical components of the intimal-medial vascular unit.\u3c/p\u3

In-vitro investigation of the relationship between microvascular structure and ultrasound contrast agent dynamics

Prostate cancer (PCa) is the second leading cause of cancer mortality in men in western countries. Tumor-driven angiogenesis is a recognized hallmark of cancer. Typical features of angiogenic vasculature include increased microvascular density (MVD), smaller vessel diameter and higher tortuosity, resulting in complex blood-flow patterns. Dynamic contrast-enhanced ultrasound (DCE-US) widely provides a noninvasive diagnostic tool for PCa detection with the passage of ultrasound contrast agents (UCAs) through the prostate. Analysis of the UCA dispersion kinetics in the tumor vasculature has shown promise for PCa diagnostics, but a clear link between the estimated kinetics parameters and the underlying microvascular structure is still lacking. In this work, modeling the prostate microvasculature as a porous medium, we developed tissue-mimicking phantoms with variable pore size, representing different MVD and vessel diameter. The UCA flow through the phantoms was recorded by DCE-US, and UCA velocity and dispersion coefficient were estimated by model-based deconvolution. In general, phantoms reproducing increased MVD and smaller vessel diameter lead to increased velocity and decreased dispersion coefficient. This is line with our in-vivo findings in PCa patients. Further validation will be performed by insilico simulation and more complex in-vitro phantoms in the future