Thermosensitive heparin-poloxamer hydrogels enhance the effects of GDNF on neuronal circuit remodeling and neuroprotection after spinal cord injury

doi:10.1002/jbm.a.36134

科研成果详情

题名	Thermosensitive heparin-poloxamer hydrogels enhance the effects of GDNF on neuronal circuit remodeling and neuroprotection after spinal cord injury
作者	Zhao, Ying-Zheng1,2,3; Jiang, Xi 1,4; Lin, Qian 2,5; Xu, He-Lin2; Huang, Ya-Dong 6; Lu, Cui-Tao1,2; Cai, Jun 1,5
发表日期	2017-10
发表期刊	JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 影响因子和分区
语种	英语
原始文献类型	Article
关键词	thermosensitive hydrogels GDNF nerve regeneration neuronal circuit remodeling spinal cord injury
其他关键词	NEUROTROPHIC FACTOR ; FUNCTIONAL RECOVERY ; CORTICOSPINAL TRACT ; CONTROLLED-RELEASE ; REGENERATION ; GROWTH ; CELLS ; DELIVERY ; TRANSPLANTATION ; ACCUMULATION
摘要	Traumatic spinal cord injury (SCI) results in paraplegia or quadriplegia, and currently, therapeutic interventions for axonal regeneration after SCI are not clinically available. Animal studies have revealed that glial cell-derived neurotrophic factor (GDNF) plays multiple beneficial roles in neuroprotection, glial scarring remodeling, axon regeneration and remyelination in SCI. However, the poor physicochemical stability of GDNF, as well as its limited ability to cross the blood-spinal cord barrier, hampers the development of GDNF as an effective therapeutic intervention in clinical practice. In this study, a novel temperature-sensitive heparin-poloxamer (HP) hydrogel with high GDNF-binding affinity was developed. HP hydrogels showed a supporting scaffold for GDNF when it was injected into the lesion epicenter after SCI. GDNF-HP by orthotopic injection on lesioned spinal cord promoted the beneficial effects of GDNF on neural stem cell proliferation, reactive astrogliosis inhibition, axonal regeneration or plasticity, neuroprotection against cell apoptosis, and body functional recovery. Most interestingly, GDNF demonstrated a bidirectional regulation of autophagy, which inhibited cell apoptosis at different stages of SCI. Furthermore, the HP hydrogel promoted the inhibition of autophagy-induced apoptosis by GDNF in SCI. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2816-2829, 2017.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81360195, 81571392, 81603036]; Zhejiang provincial program for the cultivation of high-level innovative health talents; 151 talent project of Zhejiang province; 551 talent project of Wenzhou; key support of high level talent innovation and technology project of Wenzhou; Zhejiang Provincial Foundation for Health Department [2015ZDA023, 2016KYA136]; Medicine Grant from Wenzhou Bureau of Science and Technology [Y20160086]; School Talent Start Fund of Wenzhou Medical University [QTJ15020]; Major Scientific Project of Guangdong Province [2012A080201010]; Science and Technology Program of Guangzhou, China [201508020001]
出版者	WILEY
出版地	HOBOKEN
ISSN	1549-3296
EISSN	1552-4965
卷号	105 期号:10 页码:2816-2829
DOI	10.1002/jbm.a.36134
页数	61
WOS类目	Engineering, Biomedical ; Materials Science, Biomaterials
WOS研究方向	Engineering ; Materials Science
WOS记录号	WOS:000408493200018
收录类别	SCIE ; PUBMED ; EI ; SCOPUS
EI入藏号	20173003980733
EI主题词	Hydrogels
URL	查看原文
PubMed ID	28593744
SCOPUSEID	2-s2.0-85025476200
通讯作者地址	[Lu, Cui-Tao]The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
Scopus学科分类	Ceramics and Composites;Biomaterials;Biomedical Engineering;Metals and Alloys
引用统计	被引频次：13[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/11231
专题	第二临床医学院，附属第二医院、育英儿童医院附属第二医院药学院（分析测试中心）_药学系
通讯作者	Lu, Cui-Tao
作者单位	1.The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.College of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 3.Hainan Medical College,Haikou,570102,China; 4.Zhejiang University Mingzhou Hospital,Zhejiang,315104,China; 5.Kosair Children's Hospital Research Institute at the Department of Pediatrics,University of Louisville School of Medicine,Louisville,40202,United States; 6.Biopharmaceutical R&D Center of Jinan University,Guangzhou,510000,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院; 药学院（分析测试中心）_药学系
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
推荐引用方式 GB/T 7714	Zhao, Ying-Zheng,Jiang, Xi,Lin, Qian,et al. Thermosensitive heparin-poloxamer hydrogels enhance the effects of GDNF on neuronal circuit remodeling and neuroprotection after spinal cord injury[J]. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A,2017,105(10):2816-2829.
APA	Zhao, Ying-Zheng., Jiang, Xi., Lin, Qian., Xu, He-Lin., Huang, Ya-Dong., ... & Cai, Jun. (2017). Thermosensitive heparin-poloxamer hydrogels enhance the effects of GDNF on neuronal circuit remodeling and neuroprotection after spinal cord injury. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 105(10), 2816-2829.
MLA	Zhao, Ying-Zheng,et al."Thermosensitive heparin-poloxamer hydrogels enhance the effects of GDNF on neuronal circuit remodeling and neuroprotection after spinal cord injury".JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 105.10(2017):2816-2829.