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

• Published in: Nature 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
• Language: English
• 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
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19906-3

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.