{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T02:35:04Z","timestamp":1789958104898,"version":"4.0.1"},"reference-count":61,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,7,14]],"date-time":"2017-07-14T00:00:00Z","timestamp":1499990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81360195"],"award-info":[{"award-number":["81360195"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571392"],"award-info":[{"award-number":["81571392"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81603036"],"award-info":[{"award-number":["81603036"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010derived 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\u2013spinal cord barrier, hampers the development of GDNF as an effective therapeutic intervention in clinical practice. In this study, a novel temperature\u2010sensitive heparin\u2013poloxamer (HP) hydrogel with high GDNF\u2010binding affinity was developed. HP hydrogels showed a supporting scaffold for GDNF when it was injected into the lesion epicenter after SCI. GDNF\u2010HP 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\u2010induced apoptosis by GDNF in SCI. \u00a9 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2816\u20132829, 2017.<\/jats:p>","DOI":"10.1002\/jbm.a.36134","type":"journal-article","created":{"date-parts":[[2017,6,8]],"date-time":"2017-06-08T02:52:41Z","timestamp":1496890361000},"page":"2816-2829","source":"Crossref","is-referenced-by-count":27,"title":["Thermosensitive heparin\u2010poloxamer hydrogels enhance the effects of GDNF on neuronal circuit remodeling and neuroprotection after spinal cord injury"],"prefix":"10.1002","volume":"105","author":[{"given":"Ying\u2010Zheng","family":"Zhao","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang 325000 People's Republic of China"},{"name":"College of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 People's Republic of China"},{"name":"Hainan Medical College Haikou Hainan 570102 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang 325000 People's Republic of China"},{"name":"Zhejiang University Mingzhou Hospital Zhejiang 315104 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 People's Republic of China"},{"name":"Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville School of Medicine Louisville Kentucky 40202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He\u2010Lin","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Dong","family":"Huang","sequence":"additional","affiliation":[{"name":"Biopharmaceutical R&amp;D Center of Jinan University Guangzhou Guangdong 510000 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui\u2010Tao","family":"Lu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang 325000 People's Republic of China"},{"name":"College of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Cai","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang 325000 People's Republic of China"},{"name":"Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville School of Medicine Louisville Kentucky 40202"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2004.21.1355"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.2340\/16501977-0812"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-200109000-00002"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2013.07.004"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/ip.8.suppl_4.iv33"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4890-04.2005"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1999.16.817"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2004.01.004"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1991.75.1.0015"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-10-03457.2001"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200502080-00004"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.2220\/biomedres.26.223"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(99)00072-6"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19980201)51:3<316::AID-JNR5>3.0.CO;2-J"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/367170a0"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-14-05560.1997"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1998.00071.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9536-1"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00809.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm901235g"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1163\/156856201744461"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013038716373"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1039\/B814584A"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/03639040500214688"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5173(01)00809-2"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2003.09.013"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2009.01.040"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.08.058"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00040-2"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2010.01.029"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.11.083"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-013-8432-8"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1995.12.1"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/micr.20685"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1977.47.4.0577"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7200"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.05.006"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.10.014"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073178"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00323-8"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(02)00165-1"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(97)00043-9"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1717"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(04)00099-1"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401777"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1956"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-013-8460-4"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/132172"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.R115.053751"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/10915810802244595"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm0701189"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20903"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2007.06.011"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.02.001"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms131013484"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20061747"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.1963"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/62.9.943"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001967"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb05594.x"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2973-12.2013"}],"container-title":["Journal of Biomedical Materials Research Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbm.a.36134","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.36134","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T02:29:59Z","timestamp":1696386599000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbm.a.36134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,14]]},"references-count":61,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1002\/jbm.a.36134"],"URL":"https:\/\/doi.org\/10.1002\/jbm.a.36134","archive":["Portico"],"relation":{},"ISSN":["1549-3296","1552-4965"],"issn-type":[{"value":"1549-3296","type":"print"},{"value":"1552-4965","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,14]]}}}