title: Elastomeric free-form blood vessels for interconnecting organs on chip systems.
abstract: Conventional blood vessel-on-a-chip models are typically based on microchannel-like structures enclosed within bulk elastomers such as polydimethylsiloxane (PDMS). However, these bulk vascular models largely function as individual platforms and exhibit limited flexibility particularly when used in conjunction with other organ modules. Oftentimes, lengthy connectors and/or tubes are still needed to interface multiple chips, resulting in a large waste volume counterintuitive to the miniaturized nature of organs-on-chips. In this work, we report the development of a novel form of a vascular module based on PDMS hollow tubes, which closely emulates the morphology and properties of human blood vessels to integrate multiple organs-on-chips. Specifically, we present two templating strategies to fabricate hollow PDMS tubes with adjustable diameters and wall thicknesses, where metal rods or airflow were employed as the inner templates, while plastic tubes were used as the outer template. The PDMS tubes could then be functionalized by human umbilical vein endothelial cells (HUVECs) in their interior surfaces to further construct elastomeric biomimetic blood vessels. The endothelium developed biofunctionality as demonstrated by the expression of an endothelial biomarker (CD31) as well as dose-dependent responses in the secretion of von Willebrand factor and nitric oxide upon treatment with pharmaceutical compounds. We believe that with their clear advantages including high optical transparency, gas permeability, and tunable elasticity matching those of native blood vessels, these free-form PDMS vascular modules can supplement bulk vascular organoids and likely replace inert plastic tubes in integrating multiple organoids into a single microfluidic circuitry.
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Shanghai Ocean University, Shanghai, 201306, PR China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02139, USA.
authors.forename: Yu Shrike
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and COMSATS Institute of Information and Technology, Islamabad 45550, Pakistan.
authors.forename: Syeda Mahwish
authors.initials: SM
authors.lastname: Bakht
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Julio
authors.initials: J
authors.lastname: Aleman
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02139, USA.
authors.forename: Su Ryon
authors.initials: SR
authors.lastname: Shin
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Kan
authors.initials: K
authors.lastname: Yue
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Department of Biomedical Engineering, Politecnico di Torino, Torino 10129, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sica
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Doctoral Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, Institute for Interdisciplinary Research, University of Coimbra, Coimbra 3030-789, Portugal and Biocant-Biotechnology Innovation Center, Cantanhede 3060-197, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Ribas
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Department of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
authors.forename: Margaux
authors.initials: M
authors.lastname: Duchamp
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Ju
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Ramin Banan
authors.initials: RB
authors.lastname: Sadeghian
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Duckjin
authors.initials: D
authors.lastname: Kim
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02139, USA.
authors.forename: Mehmet Remzi
authors.initials: MR
authors.lastname: Dokmeci
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC 27101, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA. alik@bwh.harvard.edu and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Department of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland and Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Seoul 143-701, Republic of Korea and Department of Physics, King Abdulaziz University, Jeddah 21569, Saudi Arabia.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004548:Elasticity; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D056656:Lab-On-A-Chip Devices; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D055616:Microtechnology / Q000379:methods; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013718:Tensile Strength; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004129:Dimethylpolysiloxanes; D007166:Immunosuppressive Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D059005:Topoisomerase II Inhibitors; D014665:Vasodilator Agents; D014841:von Willebrand Factor; D009569:Nitric Oxide