title: Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips.
abstract: Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.
authors.affiliation: School of Engineering and Applied Sciences, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, United States of America.|Pharmaceutical Sciences, Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland.
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, Massachusetts, United States of America.
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, Massachusetts, United States of America.
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, Massachusetts, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Herrmann
authors.affiliation: School of Engineering and Applied Sciences, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Humphrey
authors.initials: H
authors.lastname: Obuobi
authors.affiliation: Pharmaceutical Sciences, Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland.
authors.forename: Annie
authors.initials: A
authors.lastname: Moisan
authors.affiliation: School of Engineering and Applied Sciences, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Lewis
mesh_terms: D062028:Bioprinting / Q000379:methods*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000166:cytology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D009924:Organ Culture Techniques; D010477:Perfusion; D066330:Printing, Three-Dimensional; D023822:Tissue Engineering
chemical_list: D016572:Cyclosporine