title: The role of neurotrophic factors conjugated to iron oxide nanoparticles in peripheral nerve regeneration: in vitro studies.
abstract: Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half-life of few minutes. In order to prolong their activity, we have conjugated to iron oxide nanoparticles three neurotrophic factors: nerve growth factor (βNGF), glial cell-derived neurotrophic factor (GDNF), and basic fibroblast growth factor (FGF-2). Comparative stability studies of free versus conjugated factors revealed that the conjugated neurotrophic factors were significantly more stable in tissue cultures and in medium at 37°C. The biological effects of free versus conjugated neurotrophic factors were examined on organotypic dorsal root ganglion (DRG) cultures performed in NVR-Gel, composed mainly of hyaluronic acid and laminin. Results revealed that the conjugated neurotrophic factors enhanced early nerve fiber sprouting compared to the corresponding free factors. The most meaningful result was that conjugated-GDNF, accelerated the onset and progression of myelin significantly earlier than the free GDNF and the other free and conjugated factors. This is probably due to the beneficial and long-acting effect that the stabilized conjugated-GDNF had on neurons and Schwann cells. These conclusive results make NVR-Gel enriched with conjugated-GDNF, a desirable scaffold for the reconstruction of severed peripheral nerve.
authors.affiliation: NVR Research Ltd., Heharash Street 11, 74031 Ness-Ziona, Israel.
authors.forename: Ofra
authors.initials: O
authors.lastname: Ziv-Polat
authors.affiliation: NVR Research Ltd., Heharash Street 11, 74031 Ness-Ziona, Israel.
authors.forename: Abraham
authors.identifier: 0000-0003-4894-2593
authors.initials: A
authors.lastname: Shahar
authors.affiliation: Institute of Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, 52900 Ramat-Gan, Israel.
authors.forename: Itay
authors.identifier: 0000-0002-1689-4032
authors.initials: I
authors.lastname: Levy
authors.affiliation: Institute of Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, 52900 Ramat-Gan, Israel.
authors.forename: Hadas
authors.identifier: 0000-0002-2431-8078
authors.initials: H
authors.lastname: Skaat
authors.affiliation: NVR Research Ltd., Heharash Street 11, 74031 Ness-Ziona, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Neuman
authors.affiliation: Department of Clinical and Biological Sciences, Università degli studi di Torino, Regione Gonzole 10, 10043 Orbassano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Fregnan
authors.affiliation: Department of Clinical and Biological Sciences, Università degli studi di Torino, Regione Gonzole 10, 10043 Orbassano, Italy.
authors.forename: Stefano
authors.identifier: 0000-0002-6962-831X
authors.initials: S
authors.lastname: Geuna
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Street 1, 30623 Hannover, Germany ; Center for Systems Neuroscience (ZSN) Hannover, 30559 Hannover, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Grothe
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Street 1, 30623 Hannover, Germany ; Center for Systems Neuroscience (ZSN) Hannover, 30559 Hannover, Germany.
authors.forename: Kirsten
authors.identifier: 0000-0003-2502-8969
authors.initials: K
authors.lastname: Haastert-Talini
authors.affiliation: Institute of Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, 52900 Ramat-Gan, Israel.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Margel
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005290:Ferric Compounds / Q000737:chemistry*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D009186:Myelin Sheath / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013997:Time Factors
chemical_list: D005290:Ferric Compounds; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; C000499:ferric oxide