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Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions
Biomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo, or about how such responses influence biomaterial function. Here, we probed these factors in mice using a plat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718896/ https://www.ncbi.nlm.nih.gov/pubmed/33277474 http://dx.doi.org/10.1038/s41467-020-19906-3 |
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author | OʼShea, Timothy M. Wollenberg, Alexander L. Kim, Jae H. Ao, Yan Deming, Timothy J. Sofroniew, Michael V. |
author_facet | OʼShea, Timothy M. Wollenberg, Alexander L. Kim, Jae H. Ao, Yan Deming, Timothy J. Sofroniew, Michael V. |
author_sort | OʼShea, Timothy M. |
collection | PubMed |
description | Biomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo, or about how such responses influence biomaterial function. Here, we probed these factors in mice using a platform of injectable hydrogels readily modified to present interfaces with different physiochemical properties to host cells. We found that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. We show that the nature and intensity of CNS FBRs are determined by definable properties that significantly influence hydrogel functions, including resorption and molecular delivery when injected into healthy brain or stroke injuries. Cationic interfaces elicit stromal cell infiltration, peripherally derived inflammation, neural damage and amyloid production. Nonionic and anionic formulations show minimal levels of these responses, which contributes to superior bioactive molecular delivery. Our results identify specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications. |
format | Online Article Text |
id | pubmed-7718896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77188962020-12-07 Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions OʼShea, Timothy M. Wollenberg, Alexander L. Kim, Jae H. Ao, Yan Deming, Timothy J. Sofroniew, Michael V. Nat Commun Article Biomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo, or about how such responses influence biomaterial function. Here, we probed these factors in mice using a platform of injectable hydrogels readily modified to present interfaces with different physiochemical properties to host cells. We found that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. We show that the nature and intensity of CNS FBRs are determined by definable properties that significantly influence hydrogel functions, including resorption and molecular delivery when injected into healthy brain or stroke injuries. Cationic interfaces elicit stromal cell infiltration, peripherally derived inflammation, neural damage and amyloid production. Nonionic and anionic formulations show minimal levels of these responses, which contributes to superior bioactive molecular delivery. Our results identify specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications. Nature Publishing Group UK 2020-12-04 /pmc/articles/PMC7718896/ /pubmed/33277474 http://dx.doi.org/10.1038/s41467-020-19906-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article OʼShea, Timothy M. Wollenberg, Alexander L. Kim, Jae H. Ao, Yan Deming, Timothy J. Sofroniew, Michael V. Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions |
title | Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions |
title_full | Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions |
title_fullStr | Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions |
title_full_unstemmed | Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions |
title_short | Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions |
title_sort | foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718896/ https://www.ncbi.nlm.nih.gov/pubmed/33277474 http://dx.doi.org/10.1038/s41467-020-19906-3 |
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