title: Brain biocompatibility and microglia response towards engineered self-assembling (RADA)4 nanoscaffolds.
abstract: (RADA)4-based nanoscaffolds have many inherent properties making them amenable to tissue engineering applications: ease of synthesis, ease of customization with bioactive moieties, and amenable for in situ nanoscaffold formation. There is a dearth in the literature on their biocompatibility in brain tissues; where the glia response is key to regulating the local host response. Herein, nanoscaffolds composed of (RADA)4 and (RADA)4-IKVAV mixtures were evaluated in terms of their effect on primary microglia in culture and general tissue (in vivo) biocompatibility (astrocyte and migroglia). Laminin-derived IKVAV peptide was chosen to promote beneficial cell interaction and attenuate deleterious glial responses. Microglia remained ramified when cultured with these nanoscaffolds, as observed using TNF-α and IL-1β, NO, and proliferation assays. Evidence suggests that cultured microglia phagocytise the matrix whilst remaining ramified and viable, as shown visually and metabolically (MTT). Nanoscaffold intracerebral injection did not lead to microglia migration or proliferation, nor were glial scarring and axonal injury observed over the course of this study. IKVAV had no affect on microglia activation and astrogliosis. (RADA)4 should be advantageous for localized injection as a tuneable-platform device, which may be readily cleared without deleterious effects on tissue-resident microglia.
  
  
  CONCLUSIONS
  Self-assembling nanoscaffolds have many inherent properties making them amenable to tissue engineering applications: ease of synthesis, ease of customization with bioactive moieties, and amenable for in situ nanoscaffold formation. A dearth of literature exists on their biocompatibility in brain tissues; where the glia response is key to regulating the local host response. Herein, nanoscaffolds composed of the peptides (RADA)4 and (RADA)4-IKVAV mixtures were evaluated in terms of their effect on microglia cells in culture and general tissue (in vivo) biocompatibility (astrocyte and migroglia). Laminin-derived IKVAV peptide was chosen to promote beneficial cell interaction and attenuate deleterious glial responses. (RADA)4 nanoscaffolds showed no adverse effect from these cell types and should be advantageous for localized injection as a tuneable-platform device.
authors: Department of Chemical and Materials Engineering, University of Alberta, 11487-89 Ave., Edmonton, AB, Canada, T6G 2M7; National Institute for Nanotechnology, NRC, 11421 Saskatchewan Dr NW, Edmonton, AB, Canada, T6G 2M9.
authors: K M
authors: KM
authors: Koss
authors: Neurochemical Research Unit, Department of Psychiatry, University of Alberta, 11487-89 Ave., Edmonton, AB, Canada, T6G 2M7.
authors: M A
authors: MA
authors: Churchward
authors: Department of Pediatrics and Neuroscience, University of Alberta, 11487-89 Ave., Edmonton, AB, Canada, T6G 2M7.
authors: A T
authors: AT
authors: Nguyen
authors: Department of Pediatrics and Neuroscience, University of Alberta, 11487-89 Ave., Edmonton, AB, Canada, T6G 2M7.
authors: J Y
authors: JY
authors: Yager
authors: Neurochemical Research Unit, Department of Psychiatry, University of Alberta, 11487-89 Ave., Edmonton, AB, Canada, T6G 2M7.
authors: K G
authors: KG
authors: Todd
authors: Department of Chemical and Materials Engineering, University of Alberta, 11487-89 Ave., Edmonton, AB, Canada, T6G 2M7; National Institute for Nanotechnology, NRC, 11421 Saskatchewan Dr NW, Edmonton, AB, Canada, T6G 2M9. Electronic address: lunswort@ualberta.ca.
authors: L D
authors: LD
authors: Unsworth
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001672:Biocompatible Materials / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D007276:Injections, Intraventricular; D053583:Interleukin-1beta / Q000378:metabolism; D017628:Microglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010455:Peptides / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D053583:Interleukin-1beta; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha
keywords: Biocompatibility; Brain tissue; Microglia; Nanoscaffold; Neural tissue engineering; Primary cell culture; Self-assembling peptides