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The construction of well-controllable in vitro models of physiological and pathological vascular endothelium remains a fundamental challenge in tissue engineering and drug development. Here, we present an approach for forming a synthetic endothelial extracellular matrix (ECM) that closely resembles that of the native structure by locally depositing basement membrane materials onto type 1 collagen nanofibers only in a region adjacent to the endothelial cell (EC) monolayer. Culturing the EC monolayer on this synthetic endothelial ECM remarkably enhanced its physiological properties, reducing its vascular permeability, and promoting a stabilized, quiescent phenotype. We demonstrated that the EC monolayer on the synthetic endothelial ECM neither creates non-physiological barriers to cell-cell or cell-ECM interactions, nor hinders molecular diffusion of growth factors and other molecules. The synthetic endothelial ECM and vascular endothelium on it may help us enter in a new phase of research in which various models of the biological barrier behavior can be tested experimentally.

Deregulation of angiogenesis-the growth of blood capillaries--contributes to the development of many diseases, including cancer, arthritis and blindness (1,2). Most US Food and Drug Administration (FDA)-approved angiogenesis inhibitors target the [...], Angiogenesis is controlled by physical interactions between cells and extracellular matrix as well as soluble angiogenic factors, such as VEGF. However, the mechanism by which mechanical signals integrate with other microenvironmental cues to regulate neovascularization remains unknown. Here we show that the Rho inhibitor, p190RhoGAP (also known as GRLF1), controls capillary network formation in vitro in human microvascular endothelial cells and retinal angiogenesis in vivo by modulating the balance of activities between two antagonistic transcription factors, TFII-I (also known as GTF21) and GATA2, that govern gene expression of the VEGF receptor VEGFR2 (also known as KDR). Moreover, this new angiogenesis signalling pathway is sensitive to extracellular matrix elasticity as well as soluble VEGF. This is, to our knowledge, the first known functional cross-antagonism between transcription factors that controls tissue morphogenesis, and that responds to both mechanical and chemical cues.

The integration of semiporous membranes into poly(dimethylsiloxane) (PDMS) microfluidic devices is useful for mass transport control. Several methods such as plasma oxidation and manual application of PDMS prepolymer exist to sandwich such membranes into simple channel structures, but these methods are difficult to implement with reliable sealing and no leakage or clogging for devices with intricate channel features. This paper describes a simple but robust strategy to bond semiporous polyester and polycarbonate membranes between layers of PDMS microchannel structures effectively without channel clogging. A thin layer of PDMS prepolymer, spin-coated on a glass slide, is transferred to PDMS substrates with channel features as well as to the edges of the semiporous membrane by stamping. This thin PDMS prepolymer serves as 'mortar' to strongly bond the two PDMS layers and seal off the crevices generated from the thickness of the membranes. This bonding method enabled the fabrication of an 8 x 12 criss-crossing microfluidic channel array with 96 combinations of fluid interactions. The capability of this device for bioanalysis was demonstrated by measuring responses of cells to different color fluorescent reagents.

This paper describes a simple microfluidic sorting system that can perform size profiling and continuous mass-dependent separation of particles through combined use of gravity (1 g) and hydrodynamic flows capable of rapidly amplifying sedimentation-based separation between particles. Operation of the device relies on two microfluidic transport processes: (i) initial hydrodynamic focusing of particles in a microchannel oriented parallel to gravity and (ii) subsequent sample separation where positional difference between particles with different mass generated by sedimentation is further amplified by hydrodynamic flows whose streamlines gradually widen out due to the geometry of a widening microchannel oriented perpendicular to gravity. The microfluidic sorting device was fabricated in poly(dimethylsiloxane), and hydrodynamic flows in microchannels were driven by gravity without using external pumps. We conducted theoretical and experimental studies on fluid dynamic characteristics of laminar flows in widening microchannels and hydrodynamic amplification of particle separation. Direct trajectory monitoring, collection, and postanalysis of separated particles were performed using polystyrene microbeads with different sizes to demonstrate rapid (< 1 min) and high-purity (>99.9%) separation. Finally, we demonstrated biomedical applications of our system by isolating small-sized (diameter

Seed‐mediated growth of core–shell nanoparticles, which is conventionally performed in a batch reactor, is successfully reproduced in a microfluidic reactor for a facile production of uniform metal core–shell nanoparticles. The proposed microfluidic design is based on the microstructure inversion for achieving multi‐scale homogeneous mixing with uniform nanoparticle residence time. Simulations demonstrate that among the staggered herringbone microstructures investigated in this study, the upper herringbone (UH) structure can rapidly and homogeneously mix multiple‐sized reagents and can also prevent both the irreversible trapping and long residence time of the nanoparticles inside the microfluidic channel. A wide variety of metal core–shell nanoparticles, namely Au@Ag, Au@Pd, and Au@Au with an interior nanogap, are synthesized by using the microfluidic reactor with built‐in UH microstructures. The proposed microfluidic synthesis produces a more uniform shell size than the conventional batch synthesis. This work could significantly expand the practical utility of metal core–shell nanoparticles in a multitude of applications ranging from catalysis to nanomedicine. [ABSTRACT FROM AUTHOR]