Among the progressive strategies to promote peripheral nerve repair artificial conduits are the most promising and studied. Despite the good results achieved in patients with empty conduits, the search for new strategies to accelerate and enhance axonal regeneration led to focus on materials capable of releasing the right neurotrophic factor. In fact conduits, tubes that alone are able to lead nerve regeneration in the right direction, can be filled with a biomaterial carrying neurotrophic factors or engineered cells in order to stimulate and accelerate the regenerative process. The main disadvantage with neurotrophic factors is their short life time and fast degradation in the body, for that reason it was proposed to use in tissue-engineering factors conjugated to metallic nanoparticles that can increase the stability without compromising the activity (Skaat et al., 2011). Iron oxide nanoparticles are already used in various biomedical applications, like cell labelling and sorting, magnetic resonance imaging, X-ray contrast agents (Ziv-Polat et al., 2012) and for their suitable property (biocompatibility, relative non-toxicity, biodegradability and high surface area to volume ratio) are a good candidate to produce conjugated factors for clinical use. In the present study we focused on three neuronal growth factors: nerve growth factor (NGF) (Tucker, 2002), glial cell line derived growth factor (GDNF) (Paveliev et al., 2004) and basic fibroblast growth factor (FGF-2 also known as bFGF ) (Klimaschewski et al., 2004), all factors well known for their ability to promote neuronal survival and growth, and their critical role in nerve injury repair (Grothe et al., 2006; Gordon, 2009). Objective: The aim of this study was to analyse the biological activity of factors conjugated to iron oxide nanoparticles, with the future prospective to use them in artificial conduits for nerve regeneration. For this analysis a neurite growth assay was performed using the in vitro model of dorsal root ganglion (DRG). Three factors were tested: NGF, GDNF and FGF2. Similar experiments had been done to evaluate neurite growth inside a Neural and Vascular Reconstruction (NVR) gel, a possible biomaterial for filling artificial conduit.
In vitro Evaluation of NVR-gel Enriched with Neurotrophic Factors Conjugated to Iron Oxide Nanoparticles for Peripheral Nerve Repair
MORANO, MICHELA;FREGNAN, Federica;GEUNA, Stefano
2014-01-01
Abstract
Among the progressive strategies to promote peripheral nerve repair artificial conduits are the most promising and studied. Despite the good results achieved in patients with empty conduits, the search for new strategies to accelerate and enhance axonal regeneration led to focus on materials capable of releasing the right neurotrophic factor. In fact conduits, tubes that alone are able to lead nerve regeneration in the right direction, can be filled with a biomaterial carrying neurotrophic factors or engineered cells in order to stimulate and accelerate the regenerative process. The main disadvantage with neurotrophic factors is their short life time and fast degradation in the body, for that reason it was proposed to use in tissue-engineering factors conjugated to metallic nanoparticles that can increase the stability without compromising the activity (Skaat et al., 2011). Iron oxide nanoparticles are already used in various biomedical applications, like cell labelling and sorting, magnetic resonance imaging, X-ray contrast agents (Ziv-Polat et al., 2012) and for their suitable property (biocompatibility, relative non-toxicity, biodegradability and high surface area to volume ratio) are a good candidate to produce conjugated factors for clinical use. In the present study we focused on three neuronal growth factors: nerve growth factor (NGF) (Tucker, 2002), glial cell line derived growth factor (GDNF) (Paveliev et al., 2004) and basic fibroblast growth factor (FGF-2 also known as bFGF ) (Klimaschewski et al., 2004), all factors well known for their ability to promote neuronal survival and growth, and their critical role in nerve injury repair (Grothe et al., 2006; Gordon, 2009). Objective: The aim of this study was to analyse the biological activity of factors conjugated to iron oxide nanoparticles, with the future prospective to use them in artificial conduits for nerve regeneration. For this analysis a neurite growth assay was performed using the in vitro model of dorsal root ganglion (DRG). Three factors were tested: NGF, GDNF and FGF2. Similar experiments had been done to evaluate neurite growth inside a Neural and Vascular Reconstruction (NVR) gel, a possible biomaterial for filling artificial conduit.
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