Generation of model tissues with dendritic vascular networks via sacrificial laser-sintered carbohydrate templates

• Published in: Nature biomedical engineering Vol. 4; no. 9; pp. 916 - 932
• Main Authors: Kinstlinger, Ian S., Saxton, Sarah H., Calderon, Gisele A., Ruiz, Karen Vasquez, Yalacki, David R., Deme, Palvasha R., Rosenkrantz, Jessica E., Louis-Rosenberg, Jesse D., Johansson, Fredrik, Janson, Kevin D., Sazer, Daniel W., Panchavati, Saarang S., Bissig, Karl-Dimiter, Stevens, Kelly R., Miller, Jordan S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2020; Nature Publishing Group
• Subjects: 631/61/2035; 631/61/490; 631/61/54; 639/166/985; 639/301/54; Algorithms; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Blood Vessels - cytology; Blood Vessels - physiology; Carbohydrates; Carbohydrates - chemistry; Cell culture; Cell Proliferation; Complexity; Convection; Dendritic powders; Dendritic structure; Equipment Design; Extrusion; Hepatocytes - cytology; Humans; Hydrogels; Hydrogels - chemistry; Laser sintering; Lasers; Mass transport; Metabolites; Networks; Oxygen Consumption; Perfusion; Printing, Three-Dimensional; Sintering (powder metallurgy); Three dimensional printing; Tissue Engineering - instrumentation; Tissue Engineering - methods; Tissue Scaffolds - chemistry; Volumetric analysis
• ISSN: 2157-846X; 2157-846X
• DOI: 10.1038/s41551-020-0566-1

Sacrificial templates for patterning perfusable vascular networks in engineered tissues have been constrained in architectural complexity, owing to the limitations of extrusion-based 3D printing techniques. Here, we show that cell-laden hydrogels can be patterned with algorithmically generated dendritic vessel networks and other complex hierarchical networks by using sacrificial templates made from laser-sintered carbohydrate powders. We quantified and modulated gradients of cell proliferation and cell metabolism emerging in response to fluid convection through these networks and to diffusion of oxygen and metabolites out of them. We also show scalable strategies for the fabrication, perfusion culture and volumetric analysis of large tissue-like constructs with complex and heterogeneous internal vascular architectures. Perfusable dendritic networks in cell-laden hydrogels may help sustain thick and densely cellularized engineered tissues, and assist interrogations of the interplay between mass transport and tissue function. Cell-laden hydrogels can be patterned with algorithmically generated sacrificial dendritic vessel networks made of laser-sintered carbohydrate powders.