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BioMed Research International
Volume 2014, Article ID 267808, 10 pages
Research Article

The Role of Neurotrophic Factors Conjugated to Iron Oxide Nanoparticles in Peripheral Nerve Regeneration: In Vitro Studies

1NVR Research Ltd., Heharash Street 11, 74031 Ness-Ziona, Israel
2Institute of Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, 52900 Ramat-Gan, Israel
3Department of Clinical and Biological Sciences, Università degli studi di Torino, Regione Gonzole 10, 10043 Orbassano, Italy
4Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Street 1, 30623 Hannover, Germany
5Center for Systems Neuroscience (ZSN) Hannover, 30559 Hannover, Germany

Received 9 February 2014; Accepted 17 June 2014; Published 16 July 2014

Academic Editor: Fausto Viterbo

Copyright © 2014 Ofra Ziv-Polat et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.