Collagen nerve conduits releasing the neurotrophic factors GDNF and NGF

Madduri, Srinivas; Feldman, Kirill; Tervoort, Theo A.; Papaloïzos, Michaël; Gander, Bruno

doi:10.1016/j.jconrel.2009.12.017

Cited by 110 publications

(83 citation statements)

References 34 publications

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“…GDNF can improve motor and sensory nerve survival, influence SCs migration, improve the survival of dopamine neurons, and promote peripheral nerve regeneration. 25,26 To this end, we fabricated GDNF-loaded gelatin microspheres, and the microspheres were formed via complexation procedures between positively charged GDNF (isoelectric point [pI] =9.23) and negatively charged Type B gelatin (pI =4.7-5.2) in a neutral condition. We then studied the releasing property of GDNF-loaded gelatin microspheres in vitro via enzyme-linked immunosorbent assay.…”

Section: Zhuang Et Almentioning

confidence: 99%

Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

Zhuang¹,

Bu²,

Liu³

et al. 2016

IJN

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In this study, we fabricated glial cell-line derived neurotrophic factor (GDNF)-loaded microspheres, then seeded the microspheres in gelatin-methacrylamide hydrogel, which was finally integrated with the commercial bilayer collagen membrane (Bio-Gide ® ). The novel composite of nerve conduit was employed to bridge a 10 mm long sciatic nerve defect in a rat. GDNF-loaded gelatin microspheres had a smooth surface with an average diameter of 3.9±1.8 μm. Scanning electron microscopy showed that microspheres were uniformly distributed in both the GelMA gel and the layered structure. Using enzyme-linked immunosorbent assay, in vitro release studies (pH 7.4) of GDNF from microspheres exhibited an initial burst release during the first 3 days (18.0%±1.3%), and then, a prolonged-release profile extended to 32 days. However, in an acidic condition (pH 2.5), the initial release percentage of GDNF was up to 91.2%±0.9% within 4 hours and the cumulative release percentage of GDNF was 99.2%±0.2% at 48 hours. Then the composite conduct was implanted in a 10 mm critical defect gap of sciatic nerve in a rat. We found that the nerve was regenerated in both conduit and autograft (AG) groups. A combination of electrophysiological assessment and histomorphometry analysis of regenerated nerves showed that axonal regeneration and functional recovery in collagen tube filled with GDNF-loaded microspheres (GM + CT) group were similar to AG group ( P >0.05). Most myelinated nerves were matured and arranged densely with a uniform structure of myelin in a neat pattern along the long axis in the AG and GM + CT groups, however, regenerated nerve was absent in the BLANK group, left the 10 mm gap empty after resection, and the nerve fiber exhibited a disordered arrangement in the collagen tube group. These results indicated that the hybrid system of bilayer collagen conduit and GDNF-loaded gelatin microspheres combined with gelatin-methacrylamide hydrogels could serve as a new biodegradable artificial nerve guide for nerve tissue engineering.

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Section: Zhuang Et Almentioning

confidence: 99%

Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

Zhuang¹,

Bu²,

Liu³

et al. 2016

IJN

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“…Hence, a better way to apply NTFs and prolong their presence in close contact with regenerating axons and Schwann cells is still needed to optimize the effects of NTFs on regeneration. In attempts to increase the NTF availability at the site of injury over time, different approaches have been utilized by using repeated injections through catheters (Mcdonald et al, 2003), osmotic minipumps (Hontanilla et al, 2007), binding to extracellular matrix molecules (Sternel et al, 1997;Sakiyama-Elbert et al, 2000;Lee et al, 2003) or to the wall of nerve conduits (Madduri et al, 2010;Piquilloud et al, 2007) and gene therapy (Allodi et al, 2014;Eggers et al, 2013;Haastert et al, 2006). However, these strategies still present some difficulties to reach optimal nerve regeneration.…”

Section: Introductionmentioning

confidence: 99%

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

et al. 2016

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Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spinal cord slices were used to characterize MP properties and the bioactivity of the released NTFs. Results of organotypic cultures showed that encapsulated NTFs maintain longer bioactivity and enhance neurite regeneration of both sensory and motor neurons compared with free NTFs. For in vivo assays, the rat sciatic nerve was transected and repaired with a silicone tube filled with collagen gel or collagen mixed with PBS encapsulated MPs (control groups) and with free or encapsulated NGF, BDNF, GDNF or FGF-2. After 20 days, a retrotracer was applied to the regenerated nerve to quantify motor and sensory axonal regeneration. NTF encapsulation in MPs improved regeneration of both motor and sensory axons, as evidenced by increased numbers of retrolabeled neurons. Hence, our results show that slow release of NTFs with PLGA MP enhance nerve regeneration.

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“…NCs were coated with several layers of PLGA after fabrication. The release of the neurotrophic factors was sustained for over 30 days and remained biologically active, as confirmed by an in vitro bioassay using chicken embryonic dorsal root ganglion (DRG) explants [53] .This method protected the bioactivity of NTFs by trapping NTF proteins in collagen and preventing fast release of NTFs by coating a PLGA layer outside.…”

Section: Bio-interface Of Traditional Biopolymers In Neuroregenerationmentioning

confidence: 78%

Bio‐Interface of Conducting Polymer‐Based Materials for Neuroregeneration

Weng

Diao

et al. 2015

Adv Materials Inter

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Nerve system diseases like Parkinson's disease, Huntington's disease, Alzheimer's disease, etc. seriously affect thousands of patients' lives every year, making them suffer from pains and inconvenience. Recently, biointerfaces between neural cells/tissues and polymer based biomaterials attracted worldwide attention due to the ability of polymer based biomaterials to serve as nerve conduits, drug carriers and neurites guidance platform in neuroregeneration. The role that bio-interface played and the way it interacted with neural tissues and cells have been thoroughly investigated by the researchers. In this paper we mainly focus on reviewing the bio-interface between nerve tissues/cells and advanced functional biocompatible polymers, such as conducting polymers and advanced carbon composite materials. These advanced polymers can provide combined interfacial stimulations including interfacial external neurotrophic factors (NTFs) delivery, electrical stimulation, surface guidance and molecules decoration to lesion cells and tissues to promote neuroregeneration in vitro and in vivo, and have contributed greatly to nerve diseases therapy. At the end of this review, the criteria of polymer based biomaterials utilized in neuroregeneration are summarized and the perspectives for future development of bio-interfaces are also discussed. Nerve system diseases like Parkinson's disease, Huntington's disease and Alzheimer's disease etc. seriously affect thousands of patients' lives every year, making the patients suffer from pains and inconvenience brought about by these diseases. Recently, bio-interface between neural cells/tissues and polymer based biomaterials attracted worldwide attention due to the ability of polymer based biomaterials to serve as nerve conduits, drug carrier and neurites guidance platform in neuroregeneration. The role that bio-interface played and the way it interacted with neural tissues and cells have been thoroughly investigated by the researchers.In this paper we mainly focus on reviewing bio-interface between nerve tissues/cells and advanced functional biocompatible polymers, such as conducting polymers and advanced carbon composites materials.. These advanced polymers can provide combined interfacial stimulations including interfacial NTFs delivery, electrical stimulation, surface guidance and molecules decoration to lesion cells and tissues to promote neuroregeneration in vitro and in vivo, and have contributed greatly to nerve diseases therapy. At the end of this review, the criteria of polymer based biomaterials utilized in neuroregeneration are summarized and the perspectives for future development of bio-interfaces are also discussed.

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Collagen nerve conduits releasing the neurotrophic factors GDNF and NGF

Cited by 110 publications

References 34 publications

Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

Bio‐Interface of Conducting Polymer‐Based Materials for Neuroregeneration

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