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Immune-Informed Mucin Hydrogels Evade Fibrotic Foreign Body Response In Vivo
AlbaNova Univ Ctr, KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Div Glycosci,Dept Chem, S-10691 Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.ORCID iD: 0000-0002-6381-2968
AlbaNova Univ Ctr, KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Div Glycosci,Dept Chem, S-10691 Stockholm, Sweden.
Tech Univ Munich, Dept Mech Engn, Boltzmannstr 11, D-85748 Garching, Germany;Tech Univ Munich, Munich Sch Bioengn, Boltzmannstr 11, D-85748 Garching, Germany.ORCID iD: 0000-0002-6334-6696
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2019 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 29, no 46, article id 1902581Article in journal (Refereed) Published
Abstract [en]

The immune-mediated foreign body response to biomaterial implants can trigger the formation of insulating fibrotic capsules that can compromise implant function. To address this challenge, the intrinsic bioactivity of the mucin biopolymer, a heavily glycosylated protein that forms the protective mucus gel covering mucosal epithelia, is leveraged. By using a bioorthogonal inverse electron demand Diels-Alder reaction, mucins are crosslinked into implantable hydrogels. It is shown that mucin hydrogels (Muc-gels) modulate the immune response driving biomaterial-induced fibrosis. Muc-gels do not elicit fibrosis 21 days after implantation in the peritoneal cavity of C57Bl/6 mice, whereas medical-grade alginate hydrogels are covered by fibrous tissues. Further, Muc-gels dampen the recruitment of innate and adaptive immune cells to the gel and trigger a pattern of very mild activation marked by a noticeably low expression of the fibrosis-stimulating transforming growth factor beta 1 cytokine. Macrophages recruited to Muc-gels upregulate the gene expression of the protein inhibitor of activated STAT 1 (PIAS1) and SH2-containing phosphatase 1 (SHP-1) cytokine regulatory proteins, which likely contributes to their low cytokine expression profiles. With this advance in mucin materials, an essential tool is provided to better understand mucin bioactivities and to initiate the development of new mucin-based and mucin-inspired "immune-informed" materials for implantable devices subject to fibrotic encapsulation.

Place, publisher, year, edition, pages
2019. Vol. 29, no 46, article id 1902581
Keywords [en]
B cells, bovine submaxillary mucin, fibrosis, foreign body response, hydrogels, macrophages, TGF-beta 1
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-399014DOI: 10.1002/adfm.201902581ISI: 000486591100001OAI: oai:DiVA.org:uu-399014DiVA, id: diva2:1379118
Funder
Swedish Foundation for Strategic Research , FFL15-0072Swedish Research Council Formas, 2015-1316Swedish Research Council, 2014-6203Swedish Research CouncilKnut and Alice Wallenberg FoundationGerman Research Foundation (DFG), SFB863Ragnar Söderbergs stiftelseAvailable from: 2019-12-16 Created: 2019-12-16 Last updated: 2019-12-16Bibliographically approved

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Seignez, Cedric

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Seignez, CedricWinkeljann, BenjaminBlakeley, MatthewLieleg, OliverCrouzier, Thomas
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