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Affinity-based release of glial-derived neurotrophic factor from fibrin matrices enhances sciatic nerve regeneration

Department of Biomedical Engineering, Washington University, Campus Box 1097, One Brookings Drive, St. Louis, MO 63130, USA.
Acta biomaterialia (Impact Factor: 5.68). 05/2009; 5(4):959-68. DOI: 10.1016/j.actbio.2008.11.008
Source: PubMed

ABSTRACT Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron survival. The delivery of GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study, we evaluated the effect of affinity-based delivery of GDNF from a fibrin matrix in a nerve guidance conduit on nerve regeneration in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated which received GDNF or nerve growth factor (NGF) with the delivery system within the conduit, control groups excluding one or more components of the delivery system, and nerve isografts. Nerves were harvested 6 weeks after treatment for analysis by histomorphometry and electron microscopy. The use of the delivery system (DS) with either GDNF or NGF resulted in a higher frequency of nerve regeneration vs. control groups, as evidenced by a neural structure spanning the 13 mm gap. The GDNF DS and NGF DS groups were also similar to the nerve isograft group in measures of nerve fiber density, percent neural tissue and myelinated area measurements, but not in terms of total fiber counts. In addition, both groups contained a significantly greater percentage of larger diameter fibers, with GDNF DS having the largest in comparison to all groups, suggesting more mature neural content. The delivery of GDNF via the affinity-based delivery system can enhance peripheral nerve regeneration through a silicone conduit across a critical nerve gap and offers insight into potential future alternatives to the treatment of peripheral nerve injuries.

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Available from: Matthew D Wood, Jul 28, 2015
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    • "In addition, RT-PCR analysis has indicated that some AF cells express a number of neurotrophic factors, such as BDNF, GDNF, CNTF, NGF, and NT-3 (Pan et al. 2007). Since neurotrophic factors have frequently been shown to be neuroprotective in ischemic stroke models (Beck et al. 1994; Duarte et al. 2012; Ferrer et al. 1998; Kiprianova et al. 1999; Kitagawa et al. 1998a, 1998b; Miyazaki et al. 1999; Schabitz et al. 1997; Wang et al. 1997; Yamashita et al. 1997), traumatic brain injury (Minnich et al. 2010), and peripheral nerve injury (Fine et al. 2002; Kokai et al. 2011; Wood et al. 2009), it is possible that some of the beneficial effects of AF cells may be explained by the release of trophic factors. AF cells have also been shown to secrete a number of immune-modulating cytokines such as Il-6, and growth related oncogene (GRO) and monocyte chemotactic protein (MCP) family members (Moorefield et al. 2011), which might serve to limit the damage after nervous system injury. "
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    • "In subsequent studies, the system has been used to deliver lower affinity heparin-binding growth factors, such as NGF (Sakiyama-Elbert & Hubbell, 2000b; Wood et al., 2007, 2009), NT-3 (Taylor et al., 2004; Willerth et al., 2008), glial-derived neurotrophic growth factor (Wood et al., 2008, 2009), platelet-derived growth factor (Willerth et al., 2008) and sonic hedgehog (Willerth et al., 2008). Wood et al. (2009) investigated the repair of a 13 mm gap in a rat sciatic nerve using a silicone nerve guidance conduit containing the delivery system loaded with GDNF; see Fig. 2. It was found that systems that contained the delivery system resulted in a higher frequency of nerve regeneration compared with control groups without the delivery system. "
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