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Immune-Informed Mucin Hydrogels Evade Fibrotic Foreign Body Response In Vivo
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
Uppsala Univ, Dept Med Cell Biol, Div Integrat Physiol, S-75123 Uppsala, Sweden..
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
Tech Univ Munich, Dept Mech Engn, Boltzmannstr 11, D-85748 Garching, Germany.;Tech Univ Munich, Munich Sch Bioengn, Boltzmannstr 11, D-85748 Garching, Germany..
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2019 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, 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
WILEY-V C H VERLAG GMBH , 2019. article id 1902581
Keywords [en]
B cells, bovine submaxillary mucin, fibrosis, foreign body response, hydrogels, macrophages, TGF-beta 1
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-261313DOI: 10.1002/adfm.201902581ISI: 000486591100001Scopus ID: 2-s2.0-85073777460OAI: oai:DiVA.org:kth-261313DiVA, id: diva2:1358845
Note

QC 20191008

Available from: 2019-10-08 Created: 2019-10-08 Last updated: 2020-02-04Bibliographically approved

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Yan, HongjiCrouzier, Thomas

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