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Cited by 70Hydrogels: synthesis, properties, applicationsTissue Engineering and Regenerative MedicineNeuroscience and Neural Engineering

Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions

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OʼShea, Timothy M., Wollenberg, Alexander L., Kim, Jae H., Ao, Yan, Deming, Timothy J., Sofroniew, Michael V.·2020·Nature Communications
DOI 10.1038/s41467-020-19906-3PMC PMC7718896

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Abstract

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.

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  • The leading protagonist involved in the foreign body reaction is classically activated M1 macrophages.

    “The leading protagonist involved in the foreign body reaction is classically activated M1 macrophages”

    From Nanosilver alleviates foreign body reaction and facilitates wound repair by regulating macrophage polarization (2023) · cites this paper as O 'Shea et al., 2020

    The Results section, “Hydrogel FBRs differ in inflammatory cell recruitment/persistence” (page not available), reports macrophage-lineage cells in some foreign body responses. It does not identify them as classically activated M1 macrophages or establish them as the leading cell type; other responses included substantial neutrophil infiltration. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
OʼShea, T. M., Wollenberg, A. L., Kim, J. H., Ao, Y., Deming, T. J., & Sofroniew, M. V.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Sofroniew, Michael V.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-12-04
Volume
11
Issue
1
Pages
6203-6203
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-19906-3
PMC
PMC7718896
OpenAlex
W3106992221
Cited by
70
References
9
Citations by year
2026: 9 · 2025: 14 · 2024: 16 · 2023: 8 · 2022: 8 · 2021: 15
FWCI
2.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • OpenBU (Boston University) (publishedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • Craig H. Neilsen Foundation (381357)
  • Paralyzed Veterans of America Research Foundation (RF3170)
  • American Australian Association
  • Wings for Life
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
Keywords
foreign body reaction, central nervous system, biomaterials, injectable hydrogel, biomaterial interfaces, cationic surfaces, stromal cell infiltration, neuroinflammation, amyloid fibril formation, biomolecule delivery, blood-brain barrier
MeSH terms
Animals, Biocompatible Materials, Brain, Central Nervous System, Female, Foreign-Body Reaction, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Hydrogels, Biomimetics

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