PMID- 25522968 OWN - NLM STAT- MEDLINE DCOM- 20150818 LR - 20220317 IS - 1878-5905 (Electronic) IS - 0142-9612 (Linking) VI - 41 DP - 2015 Feb TI - The linear-ordered collagen scaffold-BDNF complex significantly promotes functional recovery after completely transected spinal cord injury in canine. PG - 89-96 LID - S0142-9612(14)01191-0 [pii] LID - 10.1016/j.biomaterials.2014.11.031 [doi] AB - Spinal cord injury (SCI) is still a worldwide clinical challenge for which there is no viable therapeutic method. We focused on developing combinatorial methods targeting the complex pathological process of SCI. In this study, we implanted linear-ordered collagen scaffold (LOCS) fibers with collagen binding brain-derived neurotrophic factor (BDNF) by tagging a collagen-binding domain (CBD) (LOCS + CBD-BDNF) in completely transected canine SCI with multisystem rehabilitation to validate its potential therapeutic effect through a long-term (38 weeks) observation. We found that LOCS + CBD-BDNF implants strikingly promoted locomotion and functional sensory recovery, with some dogs standing unassisted and transiently moving. Further histological analysis showed that administration of LOCS + CBD-BDNF reduced lesion volume, decreased collagen deposits, promoted axon regeneration and improved myelination, leading to functional recovery. Collectively, LOCS + CBD-BDNF showed striking therapeutic effect on completely transected canine SCI model and it is the first time to report such breakthrough in the war with SCI. Undoubtedly, it is a potentially promising therapeutic method for SCI paralysis or other movement disorders caused by neurological diseases in the future. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Han, Sufang AU - Han S AD - State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China. FAU - Wang, Bin AU - Wang B AD - State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China; Department of Pharmacology & Cancer Biology, Duke University, Durham, NC 27708, USA. FAU - Jin, Wei AU - Jin W AD - Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China. FAU - Xiao, Zhifeng AU - Xiao Z AD - State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China; Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. FAU - Li, Xing AU - Li X AD - State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China. FAU - Ding, Wenyong AU - Ding W AD - State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China. FAU - Kapur, Meghan AU - Kapur M AD - Department of Pharmacology & Cancer Biology, Duke University, Durham, NC 27708, USA. FAU - Chen, Bing AU - Chen B AD - State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China; Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. FAU - Yuan, Baoyu AU - Yuan B AD - Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China. FAU - Zhu, Tiansheng AU - Zhu T AD - Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China. FAU - Wang, Handong AU - Wang H AD - Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China. FAU - Wang, Jing AU - Wang J AD - Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China. FAU - Dong, Qun AU - Dong Q AD - Department of Pathology, St. Joseph's Hospital, Syracuse, NY 13203, USA. FAU - Liang, Weibang AU - Liang W AD - Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China. FAU - Dai, Jianwu AU - Dai J AD - State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China; Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. Electronic address: jwdai@genetics.ac.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141205 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Axons/drug effects/pathology MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cattle MH - Collagen/*pharmacology MH - Dogs MH - Humans MH - Myelin Sheath/metabolism MH - Nerve Regeneration/drug effects MH - Recovery of Function/*drug effects MH - Spinal Cord/drug effects/pathology/ultrastructure MH - Spinal Cord Injuries/pathology/*physiopathology/*therapy MH - Tissue Scaffolds/*chemistry OTO - NOTNLM OT - CBD-BDNF OT - Canine OT - Linear ordered collagen scaffold (LOCS) OT - Regeneration OT - Spinal cord injury (SCI) EDAT- 2014/12/20 06:00 MHDA- 2015/08/19 06:00 CRDT- 2014/12/20 06:00 PHST- 2014/08/28 00:00 [received] PHST- 2014/10/30 00:00 [revised] PHST- 2014/11/08 00:00 [accepted] PHST- 2014/12/20 06:00 [entrez] PHST- 2014/12/20 06:00 [pubmed] PHST- 2015/08/19 06:00 [medline] AID - S0142-9612(14)01191-0 [pii] AID - 10.1016/j.biomaterials.2014.11.031 [doi] PST - ppublish SO - Biomaterials. 2015 Feb;41:89-96. doi: 10.1016/j.biomaterials.2014.11.031. Epub 2014 Dec 5.