title: Three-dimensional bioprinting of thick vascularized tissues.
abstract: 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.
authors.affiliation: School of Engineering and Applied Sciences, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138.
authors.forename: David B
authors.initials: DB
authors.lastname: Kolesky
authors.affiliation: School of Engineering and Applied Sciences, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Homan
authors.affiliation: School of Engineering and Applied Sciences, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Skylar-Scott
authors.affiliation: School of Engineering and Applied Sciences, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138 jalewis@seas.harvard.edu.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Lewis
mesh_terms: D001808:Blood Vessels; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D066330:Printing, Three-Dimensional
keywords: biomaterials; bioprinting; stem cells; tissues; vasculature