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Alveolar-capillary microfluidic model for the analysis of lung injury, regeneration and repair

English title Alveolar-capillary microfluidic model for the analysis of lung injury, regeneration and repair
Applicant Guenat Olivier
Number 141127
Funding scheme Project funding (Div. I-III)
Research institution ARTORG Center Medizinische Fakultät Universität Bern
Institution of higher education University of Berne - BE
Main discipline Pathophysiology
Start/End 01.05.2012 - 30.04.2015
Approved amount 337'000.00
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All Disciplines (2)

Discipline
Pathophysiology
Other disciplines of Engineering Sciences

Keywords (11)

Microfluidics; Pulmonary fibrosis; Hypoxia; Lung on Chip; Hepatic growth factor; Alveolar-capillary model; In-vitro model; Wound-healing; Bioartificial membrane; Air-liquid interface; Epithelial microinjuries

Lay Summary (English)

Lead
Lay summary

Pulmonary fibrosis is a chronic and progressive lung disease, whose deadliest and most common form is called idiopathic pulmonary fibrosis (IPF). Although the pathogenesis of IPF is incompletely understood, it is suggested that it is primarily a disease of abnormal alveolar wound repair and remodeling after repeated epithelial microinjuries. Fundamental understanding of the reepithelialization requires advanced alveolar-capillary in vitro models that best reproduce the in vivo microenvironment.

The objective of this project is therefore to develop a microfluidic based lung-on-chip device that has the capability to mimic the in vivo conditions of the alveolar-capillary barrier, including the simulation of the respiratory movements of the lung. As research in this field is at an early stage, the proposed program lies at the forefront of research in this domain. In addition, to the best of our knowledge, the development of such a bioartificial lung-on-chip has never been proposed for therapeutic applications. This novel tool is particularly designed to investigate the pathophysiology of IPF. For this, the epithelial layer of the bioartificial alveolar membrane, ultimately made of human primary cells, will be chemically injured to imitate in vivo fibrosis. The restoration by the epithelial layer will be investigated by accurate delivery of hepatic growth factor (HGF) and/or by co-culturing bone marrow stromal cells, which are expected to contribute to alveolar repair in the injured lung. This advanced lung-on-chip model will thus serve to gain a better understanding of the cellular and molecular mechanisms that take place during fibrosis and during the restoration of the epithelial layer.

It is expected that at the end of the project, the pathophysiology of IPF will be better understood, and most of all, a novel model of a bioartificial alveolar-capillary barrier will be available for further study of fibrosis-like injury on chip.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium.
Felder Marcel, Sallin Pauline, Barbe Laurent, Haenni Beat, Gazdhar Amiq, Geiser Thomas, Guenat Olivier (2012), Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium., in Lab Chip, 12, 640.
A lung-on-a-chip array with an integrated bio-inspired respiration mechanism
Stucki AO1 Stucki JD Hall SR Felder M Mermoud Y Schmid RA Geiser T Guenat OT., A lung-on-a-chip array with an integrated bio-inspired respiration mechanism, in Lab Chip.
In vitro-ex vivo model systems for nanosafety assessment
Wick Peter, Chortarea Savvina, Guenat Olivier, Roesslein Matthias, Stucki Janick, Hirn Stephanie, Petri-Fink Alke, Rothe-Rutishauser Barbara, In vitro-ex vivo model systems for nanosafety assessment, in European Journal of Nanomedicine, 7(3), 169-179.
Potential of microfluidic lung epithelial wounding: towards in vivo-like alveolar microinjuries
Felder Marcel, Stucki Andreas, Stucki Janick, Geiser Thomas, Guenat Olivier, Potential of microfluidic lung epithelial wounding: towards in vivo-like alveolar microinjuries, in Integrative Biology.

Collaboration

Group / person Country
Types of collaboration
Core Facilities for Light Microscopies at the Department of Clinical Research, University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ICLAF 2014 (18th International Colloquium on Lung and Airway Fibrosis) Poster In vitro assay for microaspiration-induced alveolar epithelial wounding using hydrodynamic focusing in a microfluidic channel 20.09.2014 Mont-Tremblant (QC), Canada Felder Marcel;
MMB2013 Talk given at a conference TOWARDS IN-VIVO-LIKE ALVEOLAR EPITHELIAL MICROINJURIES 11.04.2013 Marina del Rey, United States of America Felder Marcel; Guenat Olivier;


Self-organised

Title Date Place
Organs-on-Chip Seminar 18.11.2014 Bern, Switzerland

Knowledge transfer events



Self-organised

Title Date Place
Visit of the ARTORG Center by two gymnasium classes: Focus: Lung-on-chip 15.05.2014 ARTORG Center, Bern, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: radio, television Emission Corpus (5.1.2015) RTS Western Switzerland 2015
Media relations: print media, online media FORSCHUNG bekommt mehr Luft Schweizer Familie German-speaking Switzerland 2015
Media relations: print media, online media Grosse Preise für miniature Tropfen und biokünstliche Mini-Lungen Der Bund German-speaking Switzerland 2015
Media relations: print media, online media Mini-Lunge aus dem Labor 20 Minuten German-speaking Switzerland 2015

Awards

Title Year
Ypsomed 2nd Prize (http://www.innovationsfonds.ch/Medienmit-Ypsomed-Innovationsfonds-2015-01-14.pdf) 2015
Venturekick I (http://www.venturekick.ch/index.cfm?page=119858&profil_id=6712) 2014
Venturekick II (http://www.venturekick.ch/index.cfm?page=119858&profil_id=6712) 2014

Use-inspired outputs


Start-ups

Name Year
AlveoliX 2015

Associated projects

Number Title Start Funding scheme
145003 A new Zeiss LSM 710 laser scanning microscope for the DCR LCI Core Facility 01.12.2012 R'EQUIP
157748 Microscopy Equipment for Organ-on-Chips and Perfused Microfluidic Systems with High Speed Camera 01.12.2014 R'EQUIP
185365 Bioartificial Microvascularized Lung Alveoli Array 01.04.2019 Project funding (Div. I-III)
150823 Serial block face SEM 01.12.2013 R'EQUIP

Abstract

Pulmonary fibrosis is a chronic and progressive lung disease, whose deadliest and most common form is called idiopathic pulmonary fibrosis (IPF). Although the pathogenesis of IPF is incompletely understood, it is suggested that it is primarily a disease of abnormal alveolar wound repair and remodeling after repeated epithelial microinjuries. Fundamental understanding of the reepithelialization requires advanced alveolar-capillary in vitro models that best reproduce the in vivo microenvironment. The objective of this project is therefore to develop a microfluidic based lung-on-chip device that has the capability to mimic the in vivo conditions of the alveolar-capillary barrier, including the simulation of the respiratory movements of the lung. This novel tool is particularly designed to analyze lung injury, regeneration and repair. For this, the epithelial layer of the bioartificial alveolar membrane, ultimately made of human primary cells, will be chemically injured to imitate in vivo fibrosis. The restoration by the epithelial layer will be investigated by accurate delivery of hepatic growth factor (HGF) and/or by co-culturing bone marrow stromal cells, which are expected to contribute to alveolar repair in the injured lung.
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