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dc.contributor.author
Julier, Ziad
dc.contributor.author
Karami, Rezvan
dc.contributor.author
Nayer, Bhavana
dc.contributor.author
Lu, Yen-Zhen
dc.contributor.author
Park, Anthony J.
dc.contributor.author
Maruyama, Kenta
dc.contributor.author
Kuhn, Gisela A.
dc.contributor.author
Müller, Ralph
dc.contributor.author
Akira, Shizuo
dc.contributor.author
Martino, Mikaël M.
dc.date.accessioned
2020-06-22T08:14:50Z
dc.date.available
2020-06-21T02:59:24Z
dc.date.available
2020-06-22T08:14:50Z
dc.date.issued
2020-06-10
dc.identifier.issn
2375-2548
dc.identifier.other
10.1126/sciadv.aba7602
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/421479
dc.identifier.doi
10.3929/ethz-b-000421479
dc.description.abstract
Although growth factors (GFs) are key molecules for regenerative medicine, their use has been limited by issues associated with suboptimal delivery systems and incomplete understanding of their signaling dynamics. Here, we explored how proinflammatory signals affect GF regenerative potential. Using bone regeneration in mouse, we found that the regenerative capacity of two clinically relevant GFs (BMP-2 and PDGF-BB) is impaired by interleukin-1 receptor (IL-1R1). Mechanistically, IL-1R1 activation in bone-forming cells desensitizes them to GFs and accelerates senescence. Moreover, administration of the GFs triggers IL-1 release by macrophages. To provide localized and sustained IL-1R1 inhibition, we engineered IL-1R antagonist (IL-1Ra) to bind the extracellular matrix (ECM) very strongly and demonstrate that codelivering GFs with ECM-binding IL-1Ra induces superior regeneration. Thus, we highlight that GF regenerative activity is hindered by proinflammatory signals, and GF-based therapies should integrate immunomodulation. Particularly, ECM-binding IL-1Ra holds clinical translational potential by enhancing efficacy of GF therapies.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
American Association for the Advancement of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc/4.0/
dc.title
Enhancing the regenerative effectiveness of growth factors by local inhibition of interleukin-1 receptor signaling
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial 4.0 International
dc.date.published
2020-06-12
ethz.journal.title
Science Advances
ethz.journal.volume
6
en_US
ethz.journal.issue
24
en_US
ethz.journal.abbreviated
Sci Adv
ethz.pages.start
eaba7602
en_US
ethz.size
13 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Washington, DC
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2020-06-21T02:59:30Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-06-22T08:15:01Z
ethz.rosetta.lastUpdated
2020-06-22T08:15:01Z
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true
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