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

Hai Zhuang,1–3 Shoushan Bu,1 Lei Hua,1 Mohammad A Darabi,2,3 Xiaojian Cao,4 Malcolm Xing2,3 1Department of Stomatology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Mechanical Engineering, Bi...

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Autores principales:	Zhuang H, Bu SS, Hua L, Darabi MA, Cao XJ, Xing M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	controlled release of GDNF gelatin microspheres biodegradable nerve conduit gelatin-methacrylamide hydrogel sciatic nerve regeneration Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7ed77ed475f54f23b56b26608ec3b9f2
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spelling	oai:doaj.org-article:7ed77ed475f54f23b56b26608ec3b9f22021-12-02T00:53:28ZGelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth1178-2013https://doaj.org/article/7ed77ed475f54f23b56b26608ec3b9f22016-04-01T00:00:00Zhttps://www.dovepress.com/gelatin-methacrylamide-gel-loaded-with-microspheres-to-deliver-gdnf-in-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hai Zhuang,1–3 Shoushan Bu,1 Lei Hua,1 Mohammad A Darabi,2,3 Xiaojian Cao,4 Malcolm Xing2,3 1Department of Stomatology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Mechanical Engineering, Biochemistry & Medical Genetics, 3Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada; 4Department of Orthopedics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China Abstract: 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. Keywords: controlled release of GDNF, gelatin microspheres, biodegradable nerve conduit, gelatin-methacrylamide hydrogel, sciatic nerve regenerationZhuang HBu SSHua LDarabi MACao XJXing MDove Medical Pressarticlecontrolled release of GDNFgelatin microspheresbiodegradable nerve conduitgelatin-methacrylamide hydrogelsciatic nerve regenerationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1383-1394 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	controlled release of GDNF gelatin microspheres biodegradable nerve conduit gelatin-methacrylamide hydrogel sciatic nerve regeneration Medicine (General) R5-920
spellingShingle	controlled release of GDNF gelatin microspheres biodegradable nerve conduit gelatin-methacrylamide hydrogel sciatic nerve regeneration Medicine (General) R5-920 Zhuang H Bu SS Hua L Darabi MA Cao XJ Xing M Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth
description	Hai Zhuang,1–3 Shoushan Bu,1 Lei Hua,1 Mohammad A Darabi,2,3 Xiaojian Cao,4 Malcolm Xing2,3 1Department of Stomatology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Mechanical Engineering, Biochemistry & Medical Genetics, 3Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada; 4Department of Orthopedics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China Abstract: 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. Keywords: controlled release of GDNF, gelatin microspheres, biodegradable nerve conduit, gelatin-methacrylamide hydrogel, sciatic nerve regeneration
format	article
author	Zhuang H Bu SS Hua L Darabi MA Cao XJ Xing M
author_facet	Zhuang H Bu SS Hua L Darabi MA Cao XJ Xing M
author_sort	Zhuang H
title	Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth
title_short	Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth
title_full	Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth
title_fullStr	Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth
title_full_unstemmed	Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth
title_sort	gelatin-methacrylamide gel loaded with microspheres to deliver gdnf in bilayer collagen conduit promoting sciatic nerve growth
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/7ed77ed475f54f23b56b26608ec3b9f2
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Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

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