title: Bioprinted thrombosis-on-a-chip.
abstract: Pathologic thrombosis kills more people than cancer and trauma combined; it is associated with significant disability and morbidity, and represents a major healthcare burden. Despite advancements in medical therapies and imaging, there is often incomplete resolution of the thrombus. The residual thrombus can undergo fibrotic changes over time through infiltration of fibroblasts from the surrounding tissues and eventually transform into a permanent clot often associated with post-thrombotic syndrome. In order to understand the importance of cellular interactions and the impact of potential therapeutics to treat thrombosis, an in vitro platform using human cells and blood components would be beneficial. Towards achieving this aim, there have been studies utilizing the capabilities of microdevices to study the hemodynamics associated with thrombosis. In this work, we further exploited the utilization of 3D bioprinting technology, for the construction of a highly biomimetic thrombosis-on-a-chip model. The model consisted of microchannels coated with a layer of confluent human endothelium embedded in a gelatin methacryloyl (GelMA) hydrogel, where human whole blood was infused and induced to form thrombi. Continuous perfusion with tissue plasmin activator led to dissolution of non-fibrotic clots, revealing clinical relevance of the model. Further encapsulating fibroblasts in the GelMA matrix demonstrated the potential migration of these cells into the clot and subsequent deposition of collagen type I over time, facilitating fibrosis remodeling that resembled the in vivo scenario. Our study suggests that in vitro 3D bioprinted blood coagulation models can be used to study the pathology of fibrosis, and particularly, in thrombosis. This versatile platform may be conveniently extended to other vascularized fibrotic disease models.
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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, Boston, MA 02115, USA.
authors.forename: Yu Shrike
authors.identifier: 0000-0002-0045-0808
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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: Farideh
authors.initials: F
authors.lastname: Davoudi
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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 Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, D-69120, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Walch
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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: Amir
authors.initials: A
authors.lastname: Manbachi
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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 Sorbonne Universités, Université de Technologie de Compiègne, UMR CNRS 7338, BMBI, Compiègne, France.
authors.forename: Xuan
authors.initials: X
authors.lastname: Luo
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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, 10129 Torino, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Dell'Erba
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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: Amir K
authors.initials: AK
authors.lastname: Miri
authors.affiliation: Department of Surgery, Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Albadawi
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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: Andrea
authors.initials: A
authors.lastname: Arneri
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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 State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou, 510640, PR China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Li
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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 State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou, 510640, PR China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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, Boston, MA 02115, USA.
authors.forename: Mehmet Remzi
authors.initials: MR
authors.lastname: Dokmeci
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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, Boston, MA 02115, USA and Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Hwayang-dong, Gwangjin-gu, 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
authors.affiliation: Biomaterials Innovation Research Center, Division of Engineering in Medicine, 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 Division of Vascular & Interventional Radiology, Mayo Clinic, Scottsdale, AZ 85259, USA. oklu.rahmi@mayo.edu.
authors.forename: Rahmi
authors.initials: R
authors.lastname: Oklu
mesh_terms: D062028:Bioprinting / Q000295:instrumentation*; D024042:Collagen Type I / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D056656:Lab-On-A-Chip Devices; D013927:Thrombosis
chemical_list: D024042:Collagen Type I