title: Impact of degradable nanowires on long-term brain tissue responses.
abstract: BACKGROUND
  A promising approach to improve the performance of neural implants consists of adding nanomaterials, such as nanowires, to the surface of the implant. Nanostructured interfaces could improve the integration and communication stability, partly through the reduction of the cell-to-electrode distance. However, the safety issues of implanted nanowires in the brain need to be evaluated and understood before nanowires can be used on the surface of implants for long periods of time. To this end we here investigate whether implanted degradable nanowires offer any advantage over non-degradable nanowires in a long-term in vivo study (1 year) with respect to brain tissue responses.
  
  
  RESULTS
  The tissue response after injection of degradable silicon oxide (SiOx)-coated gallium phosphide nanowires and biostable hafnium oxide-coated GaP nanowires into the rat striatum was compared. One year after nanowire injection, no significant difference in microglial or astrocytic response, as measured by staining for ED1 and glial fibrillary acidic protein, respectively, or in neuronal density, as measured by staining for NeuN, was found between degradable and biostable nanowires. Of the cells investigated, only microglia cells had engulfed the nanowires. The SiOx-coated nanowire residues were primarily seen in aggregated hypertrophic ED1-positive cells, possibly microglial cells that have fused to create multinucleated giant cells. Occasionally, degradable nanowires with an apparently intact shape were found inside single, small ED1-positive cells. The biostable nanowires were found intact in microglia cells of both phenotypes described.
  
  
  CONCLUSIONS
  The present study shows that the degradable nanowires remain at least partly in the brain over long time periods, i.e. 1 year; however, no obvious bio-safety issues for this degradable nanomaterial could be detected.
authors: Department of Experimental Medical Science, Medical Faculty, Neuronano Research Center (NRC), Lund University, Scheelevägen 2, 223 81, Lund, Sweden. lina.gallentoft@med.lu.se.
authors: Lina
authors: L
authors: Gällentoft
authors: Department of Experimental Medical Science, Medical Faculty, Neuronano Research Center (NRC), Lund University, Scheelevägen 2, 223 81, Lund, Sweden.
authors: Lina M E
authors: LM
authors: Pettersson
authors: Department of Experimental Medical Science, Medical Faculty, Neuronano Research Center (NRC), Lund University, Scheelevägen 2, 223 81, Lund, Sweden.
authors: Nils
authors: N
authors: Danielsen
authors: Department of Experimental Medical Science, Medical Faculty, Neuronano Research Center (NRC), Lund University, Scheelevägen 2, 223 81, Lund, Sweden.
authors: Jens
authors: J
authors: Schouenborg
authors: Department of Experimental Medical Science, Medical Faculty, Neuronano Research Center (NRC), Lund University, Scheelevägen 2, 223 81, Lund, Sweden. christelle.prinz@ftf.lth.se.|Division of Solid State Physics/NanoLund, Lund University, P.O. Box 118, 221 00, Lund, Sweden. christelle.prinz@ftf.lth.se.
authors: Christelle N
authors: CN
authors: Prinz
authors: Department of Experimental Medical Science, Medical Faculty, Neuronano Research Center (NRC), Lund University, Scheelevägen 2, 223 81, Lund, Sweden. cecilia.eriksson_linsmeier@med.lu.se.
authors: Cecilia Eriksson
authors: CE
authors: Linsmeier
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002459:Cell Fusion; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053331:Ectodysplasins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005708:Gallium / Q000494:pharmacology; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006195:Hafnium / Q000494:pharmacology; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053770:Nanowires / Q000008:administration & dosage* / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology; D010720:Phosphines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000494:pharmacology
chemical_list: D034961:Antigens, Nuclear; D015415:Biomarkers; D020099:Coated Materials, Biocompatible; D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D010087:Oxides; D010720:Phosphines; C546339:Rbfox3 protein, rat; C545179:hafnium oxide; C485338:gallium phosphide; D012822:Silicon Dioxide; D005708:Gallium; D006195:Hafnium
keywords: Biocompatibility; Biomaterial; Brain; Foreign body reaction; Immunohistochemistry; Nanomedicine; Nanowires; Neural interfaces; Tissue responses