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The vasculature is an essential component of the circulatory system that plays a vital role in the development, homeostasis, and disease of various organs in the human body. The ability to emulate the architecture and transport function of blood vessels in the integrated context of their associated organs represents an important requirement for studying a wide range of physiological processes. Traditional in vitro models of the vasculature, however, largely fail to offer such capabilities. Here we combine microfluidic three-dimensional (3D) cell culture with the principle of vasculogenic self-assembly to engineer perfusable 3D microvascular beds in vitro. Our system is created in a micropatterned hydrogel construct housed in an elastomeric microdevice that enables co-culture of primary human vascular endothelial cells and fibroblasts to achieve de novo formation, anastomosis, and controlled perfusion of 3D vascular networks. An open-top chamber design adopted in this hybrid platform also makes it possible to integrate the microengineered 3D vasculature with other cell types to recapitulate organ-specific cellular heterogeneity and structural organization of vascularized human tissues. Using these capabilities, we developed stem cell-derived microphysiological models of vascularized human adipose tissue and the blood-retina barrier. Our approach was also leveraged to construct a 3D organotypic model of vascularized human lung adenocarcinoma as a high-content drug screening platform to simulate intravascular delivery, tumor-killing effects, and vascular toxicity of a clinical chemotherapeutic agent. Furthermore, we demonstrated the potential of our platform for applications in nanomedicine by creating microengineered models of vascular inflammation to evaluate a nanoengineered drug delivery system based on active targeting liposomal nanocarriers. These results represent a significant improvement in our ability to model the complexity of native human tissues and may provide a basis for developing predictive pre-clinical models for biopharmaceutical applications.
This article was published in the following journal.
Name: ACS nano
Diverse biological processes in the body rely on the ability of cells to exert contractile forces on their extracellular matrix (ECM). In three-dimensional (3D) cell culture, however, this intrinsic c...
Microphysiological systems replicate human organ function, and are promising technologies for discovery of translatable biomarkers, pharmaceuticals, and regenerative therapies. Because microphysiologi...
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Methods and techniques used to modify or select cells and develop conditions for growing cells for biosynthetic production of molecules (METABOLIC ENGINEERING), for generation of tissue structures and organs in vitro (TISSUE ENGINEERING), or for other BIOENGINEERING research objectives.
The reallocation of beds from one type of care service to another, as in converting acute care beds to long term care beds.
The number of beds which a hospital has been designed and constructed to contain. It may also refer to the number of beds set up and staffed for use.
Application of principles and practices of engineering science to the transformation, design, and manufacture of substances on an industrial scale.
A branch of engineering concerned with the design, construction, and maintenance of environmental facilities conducive to public health, such as water supply and waste disposal.
Types of Cell Culture Open https://www.youtube.com/watch?v=WGKoJRNKADY to view video on cell culture basics. Four catagories of cell culture techniques are listed below: Adherent cells Cells shown to require attachment for growth are sa...
Vascular relates to blood vessels (Oxford Medical Dictionary) and can be used to describe the supply of blood, a disease affecting the blood vessels or molecules associated with these structures. For example, <!--LGfEGNT2Lhm-->atherosclerosis ...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...