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      Multivascular networks and functional intravascular topologies within biocompatible hydrogels

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          Abstract

          Solid organs transport fluids through distinct vascular networks that are biophysically and biochemically entangled, creating complex three-dimensional (3D) transport regimes that have remained difficult to produce and study. We establish intravascular and multivascular design freedoms with photopolymerizable hydrogels by using food dye additives as biocompatible yet potent photoabsorbers for projection stereolithography. We demonstrate monolithic transparent hydrogels, produced in minutes, comprising efficient intravascular 3D fluid mixers and functional bicuspid valves. We further elaborate entangled vascular networks from space-filling mathematical topologies and explore the oxygenation and flow of human red blood cells during tidal ventilation and distension of a proximate airway. In addition, we deploy structured biodegradable hydrogel carriers in a rodent model of chronic liver injury to highlight the potential translational utility of this materials innovation.

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          Most cited references43

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          It is difficult to mix solutions in microchannels. Under typical operating conditions, flows in these channels are laminar-the spontaneous fluctuations of velocity that tend to homogenize fluids in turbulent flows are absent, and molecular diffusion across the channels is slow. We present a passive method for mixing streams of steady pressure-driven flows in microchannels at low Reynolds number. Using this method, the length of the channel required for mixing grows only logarithmically with the Péclet number, and hydrodynamic dispersion along the channel is reduced relative to that in a simple, smooth channel. This method uses bas-relief structures on the floor of the channel that are easily fabricated with commonly used methods of planar lithography.
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            The advancement of tissue and, ultimately, organ engineering requires the ability to pattern human tissues composed of cells, extracellular matrix, and vasculature with controlled microenvironments that can be sustained over prolonged time periods. To date, bioprinting methods have yielded thin tissues that only survive for short durations. To improve their physiological relevance, we report a method for bioprinting 3D cell-laden, vascularized tissues that exceed 1 cm in thickness and can be perfused on chip for long time periods (>6 wk). Specifically, we integrate parenchyma, stroma, and endothelium into a single thick tissue by coprinting multiple inks composed of human mesenchymal stem cells (hMSCs) and human neonatal dermal fibroblasts (hNDFs) within a customized extracellular matrix alongside embedded vasculature, which is subsequently lined with human umbilical vein endothelial cells (HUVECs). These thick vascularized tissues are actively perfused with growth factors to differentiate hMSCs toward an osteogenic lineage in situ. This longitudinal study of emergent biological phenomena in complex microenvironments represents a foundational step in human tissue generation.
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              Volumetric additive manufacturing via tomographic reconstruction

              Additive manufacturing promises enormous geometrical freedom and the potential to combine materials for complex functions. The speed, geometry, and surface quality limitations of additive processes are linked to the reliance on material layering. We demonstrated concurrent printing of all points within a three-dimensional object by illuminating a rotating volume of photosensitive material with a dynamically evolving light pattern. We print features as small as 0.3 mm in engineering acrylate polymers, as well as printing soft structures with exceptionally smooth surfaces into a gelatin methacrylate hydrogel. Our process enables us to construct components that encase other pre-existing solid objects, allowing for multi-material fabrication. We developed models to describe speed and spatial resolution capabilities. We also demonstrated printing times of 30–120 s for diverse centimeter-scale objects.
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                Author and article information

                Journal
                Science
                Science
                American Association for the Advancement of Science (AAAS)
                0036-8075
                1095-9203
                May 02 2019
                May 03 2019
                May 02 2019
                May 03 2019
                : 364
                : 6439
                : 458-464
                Article
                10.1126/science.aav9750
                7769170
                31048486
                c26015b0-a3b4-4dda-9fc5-183022510180
                © 2019

                http://www.sciencemag.org/about/science-licenses-journal-article-reuse

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