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dc.contributor.author
van der Valk, Dewy C.
dc.contributor.author
van der Ven, Casper F.T.
dc.contributor.author
Blaser, Mark C.
dc.contributor.author
Grolman, Joshua M.
dc.contributor.author
Wu, Pin-Jou
dc.contributor.author
Fenton, Owen S.
dc.contributor.author
Lang, Lee H.
dc.contributor.author
Tibbitt, Mark W.
dc.contributor.author
Andresen, Jason L.
dc.contributor.author
Wen, Jennifer R.
dc.contributor.author
Ha, Anna H.
dc.contributor.author
Buffolo, Fabrizio
dc.contributor.author
Buffolo, Fabrizio
dc.contributor.author
van Mil, Alain
dc.contributor.author
Bouten, Carlijn V.C.
dc.contributor.author
Body, Simon C.
dc.contributor.author
Mooney, David J.
dc.contributor.author
Sluijter, Joost P.G.
dc.contributor.author
Aikawa, Masanori
dc.contributor.author
Hjortnaes, Jesper
dc.contributor.author
Langer, Robert
dc.contributor.author
Aikawa, Elena
dc.date.accessioned
2018-06-13T13:17:21Z
dc.date.available
2018-05-18T14:54:28Z
dc.date.available
2018-06-13T13:17:21Z
dc.date.issued
2018-05-03
dc.identifier.other
10.3390/nano8050296
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/265090
dc.identifier.doi
10.3929/ethz-b-000265090
dc.description.abstract
In calcific aortic valve disease (CAVD), microcalcifications originating from nanoscale calcifying vesicles disrupt the aortic valve (AV) leaflets, which consist of three (biomechanically) distinct layers: the fibrosa, spongiosa, and ventricularis. CAVD has no pharmacotherapy and lacks in vitro models as a result of complex valvular biomechanical features surrounding resident mechanosensitive valvular interstitial cells (VICs). We measured layer-specific mechanical properties of the human AV and engineered a three-dimensional (3D)-bioprinted CAVD model that recapitulates leaflet layer biomechanics for the first time. Human AV leaflet layers were separated by microdissection, and nanoindentation determined layer-specific Young’s moduli. Methacrylated gelatin (GelMA)/methacrylated hyaluronic acid (HAMA) hydrogels were tuned to duplicate layer-specific mechanical characteristics, followed by 3D-printing with encapsulated human VICs. Hydrogels were exposed to osteogenic media (OM) to induce microcalcification, and VIC pathogenesis was assessed by near infrared or immunofluorescence microscopy. Median Young’s moduli of the AV layers were 37.1, 15.4, and 26.9 kPa (fibrosa/spongiosa/ventricularis, respectively). The fibrosa and spongiosa Young’s moduli matched the 3D 5% GelMa/1% HAMA UV-crosslinked hydrogels. OM stimulation of VIC-laden bioprinted hydrogels induced microcalcification without apoptosis. We report the first layer-specific measurements of human AV moduli and a novel 3D-bioprinted CAVD model that potentiates microcalcification by mimicking the native AV mechanical environment. This work sheds light on valvular mechanobiology and could facilitate high-throughput drug-screening in CAVD.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
MDPI
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Aortic valve
en_US
dc.subject
calcific aortic valve disease
en_US
dc.subject
calcification
en_US
dc.subject
mechanobiology
en_US
dc.subject
Bioprinting
en_US
dc.subject
3D printing
en_US
dc.subject
microdissection
en_US
dc.subject
nanoindentation
en_US
dc.title
Engineering a 3D-Bioprinted Model of Human Heart Valve Disease Using Nanoindentation-Based Biomechanics
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
Nanomaterials
ethz.journal.volume
8
en_US
ethz.journal.issue
5
en_US
ethz.pages.start
296
en_US
ethz.size
21 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Basel
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02130 - Dep. Maschinenbau und Verfahrenstechnik / Dep. of Mechanical and Process Eng.::02629 - Institut für Verfahrenstechnik / Institute of Process Engineering::09472 - Tibbitt, Mark / Tibbitt, Mark
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02130 - Dep. Maschinenbau und Verfahrenstechnik / Dep. of Mechanical and Process Eng.::02629 - Institut für Verfahrenstechnik / Institute of Process Engineering::09472 - Tibbitt, Mark / Tibbitt, Mark
en_US
ethz.date.deposited
2018-05-18T14:54:29Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-06-13T13:19:01Z
ethz.rosetta.lastUpdated
2019-02-03T02:13:49Z
ethz.rosetta.versionExported
true
ethz.COinS
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