7/10/2023 0 Comments Jordan lattice patternDuring material optimization and screening of potential additives, we found that the addition of starch stiffened the base material, but it imparted inferior optical clarity and therefore limited potential use with matrices that are commonly crosslinked by photochemical reactions. This simple mixture was too hygroscopic and soft to handle. Our early experiments were based on a sucrose-glucose mixture developed by the food industry, which showed that while sucrose is unstable in supersaturated solutions, the addition of glucose prevents recrystallization and facilitates the formation of a stable and inexpensive glass. This carbohydrate glass formulation was developed specifically to accommodate two seemingly opposing design criteria that we identified for biocompatible 3D sacrificial materials: 1) sufficient mechanical stiffness to physically support its own weight in an open 3D lattice of filaments and 2) the ability to dissolve rapidly and biocompatibly in the presence of living cells.Ĭarbohydrate glass can be formed by dissolving one or more carbohydrates in water and then boiling of the solvent. Here, we describe a biocompatible sacrificial material-a simple glass made from mixtures of inexpensive and readily available carbohydrates-and a means to 3D print the material to facilitate the rapid casting of patterned vascular networks in engineered tissues. However, 3D sacrificial molding of perfusable channels has so far required the use of cytotoxic organic solvents or processing conditions for either removing the sacrificial filaments or casting the surrounding material, and thus could not be accomplished with aqueous-based ECMs or in the presence of living cells. Proof-of-concept studies have shown that a network of channels can be fabricated by creating a rigid 3D lattice of filaments, casting the lattice into a rubber or plastic material, and then sacrificing the lattice to reveal a microfluidic architecture in the bulk material. In contrast to these methods, 3D sacrificial molding provides an intriguing alternative. Bioprinting, in which cells and matrix are deposited dropwise, has been developed over the past decade but also is a slow, serial process with limitations on print resolution, materials, and cells. However, layer-by-layer assembly is slow and results in seams or other structural artifacts throughout the construct while simultaneously placing considerable design constraints on the materials, channels, and cells used during fabrication. In this approach, a trench is molded into one layer such that a second, separately fabricated layer can then be aligned and laminated to close the lid to form channels in an iterative fashion. To create perfusable channels in engineered tissues, layer-by-layer assembly has been explored. Although tremendous progress has been made in the past several decades to isolate and culture cells from native tissues, simple methods to generate tissue constructs populated at physiologic cell densities that are sustained by even the most basic vascular architectures have remained elusive. Such vessels deliver nutrients and oxygen to, and remove metabolic byproducts from, all of the organ systems in the body and were critical to the rise of large-scale multicellular organisms. Living tissues have complex mass transport requirements that are principally met by blood flow through multiscale vascular networks of the cardiovascular system. 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. 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. 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. Yet the lack of a general approach to rapidly construct such networks remains a major challenge for 3D tissue culture. In the absence of perfusable vascular networks, three-dimensional (3D) engineered tissues densely populated with cells quickly develop a necrotic core.
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