title: The linear-ordered collagen scaffold-BDNF complex significantly promotes functional recovery after completely transected spinal cord injury in canine.
abstract: 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.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Wenyong
authors.initials: W
authors.lastname: Ding
authors.affiliation: Department of Pharmacology & Cancer Biology, Duke University, Durham, NC 27708, USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Kapur
authors.affiliation: 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.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
authors.forename: Baoyu
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, St. Joseph's Hospital, Syracuse, NY 13203, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
authors.forename: Weibang
authors.initials: W
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002417:Cattle; D003094:Collagen / Q000494:pharmacology*; D004285:Dogs; D006801:Humans; D009186:Myelin Sheath / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003094:Collagen
keywords: CBD-BDNF; Canine; Linear ordered collagen scaffold (LOCS); Regeneration; Spinal cord injury (SCI)