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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Published inProceedings of the National Academy of Sciences - PNAS Vol. 113; no. 12; pp. 3179 - 3184
Main Authors Kolesky, David B., Homan, Kimberly A., Skylar-Scott, Mark A., Lewis, Jennifer A.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 22.03.2016
National Acad Sciences
Subjects
Blood Vessels
Human Umbilical Vein Endothelial Cells
Humans
Physical Sciences
Printing, Three-Dimensional
Stem cells
Tissues
Veins & arteries
stem cells
vasculature
biomaterials
tissues
bioprinting
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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.
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Edited by Kristi S. Anseth, Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO, and approved February 2, 2016 (received for review October 28, 2015)
1D.B.K., K.A.H., and M.A.S.-S. contributed equally to this work.
Author contributions: D.B.K., K.A.H., M.A.S.-S., and J.A.L. designed research; D.B.K., K.A.H., and M.A.S.-S. performed research; D.B.K., K.A.H., M.A.S.-S., and J.A.L. analyzed data; and D.B.K. and J.A.L. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1521342113