Rapid casting of patterned vascular networks for perfusable engineered 3D tissues

Rapid casting of patterned vascular networks for perfusable engineered 3D tissues

2012 September ; 11(9): 768–774. doi:10.1038/nmat3357 | Jordan S. Miller, Kelly R. Stevens, Michael T. Yang, Brendon M. Baker, Duc-Huy T. Nguyen, Daniel M. Cohen, Esteban Toro, Alice A. Chen, Peter A. Galie, Xiang Yu, Ritika Chaturvedi, Sangeeta N. Bhatia, Christopher S. Chen
This article introduces a novel method for rapidly casting patterned vascular networks in engineered 3D tissues using a biocompatible sacrificial material called carbohydrate glass. The approach involves 3D printing rigid carbohydrate glass filaments, which are then used as a template to create cylindrical vascular channels that can be lined with endothelial cells and perfused with blood under high-pressure pulsatile flow. The carbohydrate glass is designed to be both mechanically rigid and biocompatible, allowing for the independent control of network geometry, endothelialization, and extravascular tissue. The method is compatible with a wide variety of cell types, synthetic and natural extracellular matrices (ECMs), and crosslinking strategies. The vascular networks are created by encapsulating the carbohydrate glass lattice in an ECM and then dissolving the glass to form perfusable channels. This process allows for the sustained metabolic function of primary rat hepatocytes in engineered tissue constructs, which would otherwise exhibit suppressed function in their core. The method is flexible and can be applied to a wide range of natural and synthetic ECM materials, and it supports the survival, spread, and migration of encapsulated cells in channeled scaffolds. The approach enables the creation of complex vascular networks with various diameters and interconnections, and it supports the formation of smooth, fluidic connections between adjoining vascular channels. The method also allows for the patterning of cells or immobilized factors within the construct into step, linear, and exponential gradients, demonstrating the potential for creating highly functional 3D cell cultures. The vascular networks support the metabolic activity of cells in metabolically demanding settings, such as physiologically high cell densities, and enable the sustained function of primary hepatocytes in engineered tissues. The method is rapid, efficient, and compatible with a wide range of ECM materials, and it allows for the creation of perfusable vascular networks without the need for complex fabrication steps. The approach is also scalable and can be used to create tissue constructs of arbitrary size. The study demonstrates the potential of this method for creating functional 3D cell cultures that can be used as experimental models or therapeutic replacements for human tissues.This article introduces a novel method for rapidly casting patterned vascular networks in engineered 3D tissues using a biocompatible sacrificial material called carbohydrate glass. The approach involves 3D printing rigid carbohydrate glass filaments, which are then used as a template to create cylindrical vascular channels that can be lined with endothelial cells and perfused with blood under high-pressure pulsatile flow. The carbohydrate glass is designed to be both mechanically rigid and biocompatible, allowing for the independent control of network geometry, endothelialization, and extravascular tissue. The method is compatible with a wide variety of cell types, synthetic and natural extracellular matrices (ECMs), and crosslinking strategies. The vascular networks are created by encapsulating the carbohydrate glass lattice in an ECM and then dissolving the glass to form perfusable channels. This process allows for the sustained metabolic function of primary rat hepatocytes in engineered tissue constructs, which would otherwise exhibit suppressed function in their core. The method is flexible and can be applied to a wide range of natural and synthetic ECM materials, and it supports the survival, spread, and migration of encapsulated cells in channeled scaffolds. The approach enables the creation of complex vascular networks with various diameters and interconnections, and it supports the formation of smooth, fluidic connections between adjoining vascular channels. The method also allows for the patterning of cells or immobilized factors within the construct into step, linear, and exponential gradients, demonstrating the potential for creating highly functional 3D cell cultures. The vascular networks support the metabolic activity of cells in metabolically demanding settings, such as physiologically high cell densities, and enable the sustained function of primary hepatocytes in engineered tissues. The method is rapid, efficient, and compatible with a wide range of ECM materials, and it allows for the creation of perfusable vascular networks without the need for complex fabrication steps. The approach is also scalable and can be used to create tissue constructs of arbitrary size. The study demonstrates the potential of this method for creating functional 3D cell cultures that can be used as experimental models or therapeutic replacements for human tissues.
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