title: Development of a nanomaterial bio-screening platform for neurological applications.
abstract: Nanoparticle platforms are being intensively investigated for neurological applications. Current biological models used to identify clinically relevant materials have major limitations, e.g. technical/ethical issues with live animal experimentation, failure to replicate neural cell diversity, limited control over cellular stoichiometries and poor reproducibility. High-throughput neuro-mimetic screening systems are required to address these challenges. We describe an advanced multicellular neural model comprising the major non-neuronal/glial cells of the central nervous system (CNS), shown to account for ~99.5% of CNS nanoparticle uptake. This model offers critical advantages for neuro-nanomaterials testing while reducing animal use: one primary source and culture medium for all cell types, standardized biomolecular corona formation and defined/reproducible cellular stoichiometry. Using dynamic time-lapse imaging, we demonstrate in real-time that microglia (neural immune cells) dramatically limit particle uptake in other neural subtypes (paralleling post-mortem observations after nanoparticle injection in vivo), highlighting the utility of the system in predicting neural handling of biomaterials.
authors.affiliation: Cellular and Neural Engineering Group, Institute for Science and Technology in Medicine, Keele University, UK.
authors.forename: Stuart Iain
authors.initials: SI
authors.lastname: Jenkins
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Roach
authors.affiliation: Cellular and Neural Engineering Group, Institute for Science and Technology in Medicine, Keele University, UK. Electronic address: d.chari@keele.ac.uk.
authors.forename: Divya Maitreyi
authors.initials: DM
authors.lastname: Chari
mesh_terms: D023401:Animal Use Alternatives; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001672:Biocompatible Materials / Q000737:chemistry; D002490:Central Nervous System / Q000378:metabolism; D018920:Coculture Techniques; D003470:Culture Media / Q000737:chemistry; D017628:Microglia / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry*; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology; D015203:Reproducibility of Results; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001672:Biocompatible Materials; D003470:Culture Media
keywords: Biomaterials screening; Glia; Multicellular models; Neural cells; Protein corona