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      Capillary‐Scale Hydrogel Microchannel Networks by Wire Templating

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          Abstract

          Microvascular networks are essential for the efficient transport of nutrients, waste products, and drugs throughout the body. Wire‐templating is an accessible method for generating laboratory models of these blood vessel networks, but it has difficulty fabricating microchannels with diameters of ten microns and narrower, a requirement for modeling human capillaries. This study describes a suite of surface modification techniques to  selectively control the interactions amongst wires, hydrogels, and world‐to‐chip interfaces. This wire templating method enables the fabrication of perfusable hydrogel‐based rounded cross‐section capillary‐scale networks whose diameters controllably narrow at bifurcations down to 6.1 ± 0.3 microns in diameter. Due to its low cost, accessibility, and compatibility with a wide range of common hydrogels of tunable stiffnesses such as collagen, this technique may increase the fidelity of experimental models of capillary networks for the study of human health and disease.

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          Most cited references51

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          Mussel-inspired surface chemistry for multifunctional coatings.

          We report a method to form multifunctional polymer coatings through simple dip-coating of objects in an aqueous solution of dopamine. Inspired by the composition of adhesive proteins in mussels, we used dopamine self-polymerization to form thin, surface-adherent polydopamine films onto a wide range of inorganic and organic materials, including noble metals, oxides, polymers, semiconductors, and ceramics. Secondary reactions can be used to create a variety of ad-layers, including self-assembled monolayers through deposition of long-chain molecular building blocks, metal films by electroless metallization, and bioinert and bioactive surfaces via grafting of macromolecules.
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            Rapid casting of patterned vascular networks for perfusable engineered 3D tissues

            In the absence of perfusable vascular networks, three-dimensional (3D) engineered tissues densely populated with cells quickly develop a necrotic core [1]. Yet the lack of a general approach to rapidly construct such networks remains a major challenge for 3D tissue culture [2–4]. Here, we 3D printed rigid filament networks of carbohydrate glass, and used them as a cytocompatible sacrificial template in engineered tissues containing living cells to generate cylindrical networks which could be lined with endothelial cells and perfused with blood under high-pressure pulsatile flow. Because this simple vascular casting approach allows independent control of network geometry, endothelialization, and extravascular tissue, it is compatible with a wide variety of cell types, synthetic and natural extracellular matrices (ECMs), and crosslinking strategies. We also demonstrated that the perfused vascular channels sustained the metabolic function of primary rat hepatocytes in engineered tissue constructs that otherwise exhibited suppressed function in their core.
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              Preparation of hydrogel substrates with tunable mechanical properties.

              The modulus of elasticity of the extracellular matrix (ECM), often referred to in a biological context as "stiffness," naturally varies within the body, e.g., hard bones and soft tissue. Moreover, it has been found to have a profound effect on the behavior of anchorage-dependent cells. The fabrication of matrix substrates with a defined modulus of elasticity can be a useful technique to study the interactions of cells with their biophysical microenvironment. Matrix substrates composed of polyacrylamide hydrogels have an easily quantifiable elasticity that can be changed by adjusting the relative concentrations of its monomer, acrylamide, and cross-linker, bis-acrylamide. In this unit, we detail a protocol for the fabrication of statically compliant and radial-gradient polyacrylamide hydrogels, as well as the functionalization of these hydrogels with ECM proteins for cell culture. Included as well are suggestions to optimize this protocol to the choice of cell type or stiffness with a table of relative bis-acrylamide and acrylamide concentrations and expected elasticity after polymerization.
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                Author and article information

                Contributors
                Journal
                Small
                Small
                Wiley
                1613-6810
                1613-6829
                October 2023
                June 02 2023
                October 2023
                : 19
                : 42
                Affiliations
                [1 ] Department of Bioengineering Imperial College London South Kensington London SW7 2AZ UK
                [2 ] Cancer Research UK Convergence Science Centre London SW7 2AZ UK
                Article
                10.1002/smll.202301163
                0995ba0d-661b-4479-be0e-0b15385e99aa
                © 2023

                http://creativecommons.org/licenses/by/4.0/

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