Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues

• Published in: Nature materials Vol. 11; no. 9; pp. 768 - 774
• Main Authors: Miller, Jordan S., Stevens, Kelly R., Yang, Michael T., Baker, Brendon M., Nguyen, Duc-Huy T., Cohen, Daniel M., Toro, Esteban, Chen, Alice A., Galie, Peter A., Yu, Xiang, Chaturvedi, Ritika, Bhatia, Sangeeta N., Chen, Christopher S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2012; Nature Publishing Group
• Subjects: 639/301/54/990; 639/301/54/994; Animals; Biocompatible Materials - chemistry; Biocompatible Materials - metabolism; Biocompatible Materials - pharmacology; Biomaterials; Blood; Blood vessels; Blood Vessels - cytology; Carbohydrates - chemistry; Channels; Chemistry and Materials Science; Condensed Matter Physics; Construction; Culture; Endothelial cells; Glass - chemistry; Hepatocytes - cytology; Hepatocytes - drug effects; Hepatocytes - metabolism; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - drug effects; Humans; letter; Materials Science; Mathematical analysis; Nanotechnology; Networks; Optical and Electronic Materials; Perfusion; Population density; Printing - methods; Rats; Strategy; Three dimensional; Time Factors; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds - chemistry; Tissues; Vascular endothelial growth factor
• ISSN: 1476-1122; 1476-4660
• DOI: 10.1038/nmat3357

Tissues with perfusable vascular networks can be fabricated through layer-by-layer assembly, bioprinting or sacrificial moulding, but current approaches are slow, have limited resolution, or place significant constraints on the materials or the processing conditions. A rapid and general vascular casting approach using carbohydrate glass as a sacrificial template to generate tissues containing cylindrical networks that can be lined with endothelial cells and perfused with blood under high-pressure pulsatile flow is now reported. 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 , 3 , 4 . Here, we printed rigid 3D filament networks of carbohydrate glass, and used them as a cytocompatible sacrificial template in engineered tissues containing living cells to generate cylindrical networks that 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, 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.