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Synthetic Mucin Gels with Self-Healing Properties Augment Lubricity and Inhibit HIV-1 and HSV-2 Transmission
KTH Royal Institute of Technology, Sweden.
Technical University of Munich, Germany.
Technical University of Munich, Germany.
Karolinska Institute, Sweden.
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2022 (English)In: Advanced Science, E-ISSN 2198-3844, Vol. 9, no 32, article id 2203898Article in journal (Refereed) Published
Abstract [en]

Mucus is a self-healing gel that lubricates the moist epithelium and provides protection against viruses by binding to viruses smaller than the gel's mesh size and removing them from the mucosal surface by active mucus turnover. As the primary nonaqueous components of mucus (≈0.2%–5%, wt/v), mucins are critical to this function because the dense arrangement of mucin glycans allows multivalence of binding. Following nature's example, bovine submaxillary mucins (BSMs) are assembled into “mucus-like” gels (5%, wt/v) by dynamic covalent crosslinking reactions. The gels exhibit transient liquefaction under high shear strain and immediate self-healing behavior. This study shows that these material properties are essential to provide lubricity. The gels efficiently reduce human immunodeficiency virus type 1 (HIV-1) and genital herpes virus type 2 (HSV-2) infectivity for various types of cells. In contrast, simple mucin solutions, which lack the structural makeup, inhibit HIV-1 significantly less and do not inhibit HSV-2. Mechanistically, the prophylaxis of HIV-1 infection by BSM gels is found to be that the gels trap HIV-1 by binding to the envelope glycoprotein gp120 and suppress cytokine production during viral exposure. Therefore, the authors believe the gels are promising for further development as personal lubricants that can limit viral transmission. © 2022 The Authors. 

Place, publisher, year, edition, pages
John Wiley and Sons Inc , 2022. Vol. 9, no 32, article id 2203898
Keywords [en]
HIV-1, HSV-2, immune suppression, lubricant, mucin hydrogels, self-healing, strain-weakening, Crosslinking, Diseases, Gels, Hydrogels, Mammals, Self-healing materials, Shear strain, Sols, Herpes virus type 2, Human immunodeficiency virus, Human immunodeficiency virus type 1, Mesh size, Mucin hydrogel, Mucosal surface, Self-healing properties, Viruses
National Category
Physical Sciences
Identifiers
URN: urn:nbn:se:ri:diva-60270DOI: 10.1002/advs.202203898Scopus ID: 2-s2.0-85137917305OAI: oai:DiVA.org:ri-60270DiVA, id: diva2:1702143
Note

Funding details: Deutsche Forschungsgemeinschaft, DFG, 111166240, 2017‐05848, 2020‐02129, SFB‐863; Funding details: Stiftelsen för Strategisk Forskning, SSF, FFL15‐0072; Funding details: Svenska Forskningsrådet Formas, 2015‐1316; Funding details: Kungliga Tekniska Högskolan, KTH; Funding details: Vetenskapsrådet, VR, 2014‐6203; Funding text 1: M.K. and R.C.‐D. contributed equally to this work. H.Y. and T.C. gratefully acknowledge financial support from the Swedish Foundation for Strategic Research (Grant No. FFL15‐0072), FORMAS (Grant No. 2015‐1316), the Swedish Research Council (Grant No. 2014‐6203), and the KTH Lifescience Platform Grant (2021). O.L. and M.K. gratefully acknowledge funding from the German Research Foundation (DFG) through SFB‐863 (Grant No. 111166240). A.S. and R.C. gratefully acknowledge grants from the Swedish Research Council (Grant Nos. 2017‐05848 and 2020‐02129). The authors thank Ms. Pacella F. for her help in preparing Figure 2C and Prof. E. Tyrode at KTH for discussion of the ATR‐FTIR data and analysis. The author thank Prof. Y. Hsieh for suggesting COMU/DIPEA coupling chemistry at KTH and Dr. P. Chives at KI for discussion during minor revision of the manuscript.

Available from: 2022-10-10 Created: 2022-10-10 Last updated: 2023-03-30Bibliographically approved

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