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Generating perfusable 3D microvessels in vitro is an important goal for tissue engineering, as well as for reliable modelling of blood vessel function. To date, in vitro blood vessel models have not been able to accurately reproduce the dynamics and responses of endothelial cells to grow perfusable and functional 3D vascular networks. Here we describe a microfluidic-based platform whereby we model natural cellular programs found during normal development and angiogenesis to form perfusable netwo

Modeling the in vivo microenvironment typically involves placing cells in a three-dimensional (3D) extracellular matrix (ECM) in physiologically relevant context with respect to other cells. The mechanical and chemical features of 3D microenvironments play important roles in tissue engineering, tumor growth and metastasis, and in defining stem cell niches, and it is increasingly recognized that cells behave much differently when surrounded by a 3D ECM than when anchored to a 2D substrate. To cre

A crucial yet ill-defined phenomenon involved in the remodeling of vascular networks, including angiogenic sprouting, is flow-mediated endothelial dynamics and phenotype changes. Despite interstitial flow (IF) being ubiquitously present in living tissues surrounding blood capillaries, it is rarely investigated and poorly understood how endothelial cells respond to this flow during morphogenesis. Here we develop a microfluidic 3D in vitro model to investigate the role of IF during vasculogenic fo

This paper describes the in vitro formation and characterization of perfusable capillary networks made of human umbilical vein endothelial cells (HUVECs) in microfluidic devices (MFDs). Using this platform, an array of three-dimensional (3D) tubular capillaries of various dimensions (50-150 μm in diameter and 100-1600 μm in length) can be formed reproducibly. To generate connected blood vessels, MFDs were completely filled with fibrin gel and subsequently processed to selectively leave behind ge

Current in vitro systems mimicking bone tissues fail to fully integrate the three-dimensional (3D) microvasculature and bone tissue microenvironments, decreasing their similarity to in vivo conditions. Here, we propose 3D microvascular networks in a hydroxyapatite (HA)-incorporated extracellular matrix (ECM) for designing and manipulating a vascularized bone tissue model in a microfluidic device. Incorporation of HA of various concentrations resulted in ECM with varying mechanical properties. Sp

The human central nervous system (CNS) vasculature expresses a distinctive barrier phenotype, the blood-brain barrier (BBB). As the BBB contributes to low efficiency in CNS pharmacotherapy by restricting drug transport, the development of an in vitro human BBB model has been in demand. Here, we present a microfluidic model of CNS angiogenesis having three-dimensional (3D) lumenized vasculature in concert with perivascular cells. We confirmed the necessity of the angiogenic tri-culture system (br

The "Tumor microenvironment" (TME) is a complex, interacting system of the tumor and its surrounding environment. The TME has drawn more attention recently in attempts to overcome current drug resistance and the recurrence of cancer by understanding the cancer and its microenvironment systematically, beyond past reductionist approaches. However, a lack of experimental tools to dissect the intricate interactions has hampered in-depth research into the TME. Here, a biomimetic TME model using a mic

Microphysiological systems have emerged in the last decade to provide an alternative to in vivo models in basic science and pharmaceutical research. In the field of vascular biology, in particular, there has been a lack of a suitable in vitro model exhibiting a three-dimensional structure and the physiological function of vasculature integrated with organ-on-a-chip models. The rapid development of organ-on-a-chip technology is well positioned to fulfill unmet needs. Recently, functional integrat

Bone is one of the most common sites of cancer metastasis, as its fertile microenvironment attracts tumor cells. The unique mechanical properties of bone extracellular matrix (ECM), mainly composed of hydroxyapatite (HA) affect a number of cellular responses in the tumor microenvironment (TME) such as proliferation, migration, viability, and morphology, as well as angiogenic activity, which is related to bone metastasis. In this study, we engineered a bone-mimetic microenvironment to investigate

The application of microfluidics to neuroscience applications has always appealed to neuroscientists because of the capability to control the cellular microenvironment in both a spatial and temporal manner. Recently, there has been rapid development of biological micro-electro-mechanical systems (BioMEMS) for both fundamental and applied neuroscience research. In this review, we will discuss the applications of BioMEMS to various topics in the field of neuroscience. The purpose of this review is

A global ban on animal experiments has been proposed. Hence, it is imperative to develop alternative models. Artificial skin models should reflect the responses of subcutaneous blood vessels and the immune system to elucidate disease and identify cosmetics' base materials. Notably, <i>in vivo</i> skin-irritation cascades involve disruption of the epidermal barrier and the release of proinflammatory mediators in response to chemical stimuli. Such proinflammatory factors promote angiogenesis and b