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...

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Published inNature communications Vol. 11; no. 1; p. 6203
Main Authors OʼShea, Timothy M., Wollenberg, Alexander L., Kim, Jae H., Ao, Yan, Deming, Timothy J., Sofroniew, Michael V.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 04.12.2020
Nature Publishing Group
Nature Portfolio
Subjects
13/1
13/51
631/378/87
639/301/54
64/60
Amyloid
Animals
Biocompatible Materials - chemistry
Biocompatible Materials - pharmacology
Biomaterials
Biomedical materials
Biomimetics
Brain - drug effects
Brain - physiology
Brain - physiopathology
Brain injury
Central nervous system
Central Nervous System - drug effects
Central Nervous System - pathology
Central Nervous System - physiopathology
Damage
Female
Foreign bodies
Foreign-Body Reaction - prevention & control
Humanities and Social Sciences
Humans
Hydrogels
Hydrogels - chemistry
Hydrogels - pharmacology
In vivo methods and tests
Interfaces
Male
Mice, Inbred C57BL
Mice, Transgenic
Molecular modelling
multidisciplinary
Nervous system
Physiochemistry
Science
Science (multidisciplinary)
Surgical implants
Therapeutic applications
Wounds
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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. Implantable biomaterials evoke foreign body responses in the central nervous system. The authors compare hydrogel-based biomaterials to identify cellular interactions and molecular mechanisms that drive different types of foreign body responses that have different effects on biomaterial function.
AbstractList Implantable biomaterials evoke foreign body responses in the central nervous system. The authors compare hydrogel-based biomaterials to identify cellular interactions and molecular mechanisms that drive different types of foreign body responses that have different effects on biomaterial function.
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.Implantable biomaterials evoke foreign body responses in the central nervous system. The authors compare hydrogel-based biomaterials to identify cellular interactions and molecular mechanisms that drive different types of foreign body responses that have different effects on biomaterial function.
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.
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. Implantable biomaterials evoke foreign body responses in the central nervous system. The authors compare hydrogel-based biomaterials to identify cellular interactions and molecular mechanisms that drive different types of foreign body responses that have different effects on biomaterial function.
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.
ArticleNumber 6203
Author OʼShea, Timothy M.
Kim, Jae H.
Sofroniew, Michael V.
Deming, Timothy J.
Wollenberg, Alexander L.
Ao, Yan
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  surname: Sofroniew
  fullname: Sofroniew, Michael V.
  email: sofroniew@mednet.ucla.edu
  organization: Department of Neurobiology, David Geffen School of Medicine, University of California
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SSID ssj0000391844
Score 2.541988
Snippet Biomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign...
Abstract Biomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS...
Implantable biomaterials evoke foreign body responses in the central nervous system. The authors compare hydrogel-based biomaterials to identify cellular...
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Open Access Repository
Aggregation Database
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Publisher
StartPage 6203
SubjectTerms 13/1
13/51
631/378/87
639/301/54
64/60
Amyloid
Animals
Biocompatible Materials - chemistry
Biocompatible Materials - pharmacology
Biomaterials
Biomedical materials
Biomimetics
Brain - drug effects
Brain - physiology
Brain - physiopathology
Brain injury
Central nervous system
Central Nervous System - drug effects
Central Nervous System - pathology
Central Nervous System - physiopathology
Damage
Female
Foreign bodies
Foreign-Body Reaction - prevention & control
Humanities and Social Sciences
Humans
Hydrogels
Hydrogels - chemistry
Hydrogels - pharmacology
In vivo methods and tests
Interfaces
Male
Mice, Inbred C57BL
Mice, Transgenic
Molecular modelling
multidisciplinary
Nervous system
Physiochemistry
Science
Science (multidisciplinary)
Surgical implants
Therapeutic applications
Wounds
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Title Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions
URI https://link.springer.com/article/10.1038/s41467-020-19906-3
https://www.ncbi.nlm.nih.gov/pubmed/33277474
https://www.proquest.com/docview/2473283875
https://search.proquest.com/docview/2467616363
https://pubmed.ncbi.nlm.nih.gov/PMC7718896
https://doaj.org/article/3f9ac0fa07be4aa38f0b487bb917087c
Volume 11
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