Three-dimensional bioprinting of thick vascularized tissues

The advancement of tissue and, ultimately, organ engineering requires the ability to pattern human tissues composed of cells, extracellular matrix, and vasculature with controlled microenvironments that can be sustained over prolonged time periods. To date, bioprinting methods have yielded thin tiss...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2016-03, Vol.113 (12), p.3179-3184
Main Authors: Kolesky, David B., Homan, Kimberly A., Skylar-Scott, Mark A., Lewis, Jennifer A.
Format: Article
Language:English
Subjects:
Blood Vessels
Human Umbilical Vein Endothelial Cells
Humans
Physical Sciences
Printing, Three-Dimensional
Stem cells
Tissues
Veins & arteries
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Summary:The advancement of tissue and, ultimately, organ engineering requires the ability to pattern human tissues composed of cells, extracellular matrix, and vasculature with controlled microenvironments that can be sustained over prolonged time periods. To date, bioprinting methods have yielded thin tissues that only survive for short durations. To improve their physiological relevance, we report a method for bioprinting 3D cell-laden, vascularized tissues that exceed 1 cm in thickness and can be perfused on chip for long time periods (>6 wk). Specifically, we integrate parenchyma, stroma, and endothelium into a single thick tissue by coprinting multiple inks composed of human mesenchymal stem cells (hMSCs) and human neonatal dermal fibroblasts (hNDFs) within a customized extracellular matrix alongside embedded vasculature, which is subsequently lined with human umbilical vein endothelial cells (HUVECs). These thick vascularized tissues are actively perfused with growth factors to differentiate hMSCs toward an osteogenic lineage in situ. This longitudinal study of emergent biological phenomena in complex microenvironments represents a foundational step in human tissue generation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1521342113