title: Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury.
abstract: Persistent neurotrophic factor delivery is crucial to create a microenvironment for cell survival and nerve regeneration in spinal cord injury (SCI). This study aimed to develop a NT-3/fibroin coated gelatin sponge scaffold (NF-GS) as a novel controlled artificial release therapy for SCI. In vitro, bone marrow-derived mesenchymal stem cells (MSCs) were planted into the NF-GS and release test showed that NF-GS was capable to generate a sustainable NT-3 release up to 28 days. MSCs in NF-GS had high cell activity with excellent cell distribution and phenotype. Then, the NF-GS was transplanted into the injury site of spinal cord of rat and canine in vivo, which exhibited strong biocompatibility during post-transplantation period. Four weeks following transplantation, the concentration of NT-3 was much higher than that in control groups. Cavity areas in the injury/graft site were significantly reduced due to tissue regeneration and axonal extensions associated with myelin sheath through the glial scar into the NF-GS. Additionally, the NF-GS decreased the inflammation by reducing the CD68 positive cells and TNF-α. A striking feature was the occurrence of some cells and myelin-like structure that appeared to traverse the NF-GS. The present results demonstrate that the NF-GS has the property to control the release of NT-3 from the NT-3/fibroin complex thus facilitating regeneration of injured spinal cord.
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Ming-Tian
authors.initials: MT
authors.lastname: Che
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Qin
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Third Affiliate Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Rui-Qiang
authors.initials: RQ
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Third Affiliate Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Rong
authors.affiliation: Department of Human Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, 510120, China; Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Hui-Yong
authors.initials: HY
authors.lastname: Shen
authors.affiliation: Department of Neurology, First Affiliate Hospiyal, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Si-Mei
authors.initials: SM
authors.lastname: Long
authors.affiliation: Department of Electron Microscope, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jin-Lang
authors.initials: JL
authors.lastname: Wu
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China; Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, 510120, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: zengysh@mail.sysu.edu.cn.
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zeng
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001369:Axons / Q000187:drug effects / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003198:Computer Simulation; D004285:Dogs; D005260:Female; D005349:Fibroins / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects*; D009457:Neuroglia / Q000378:metabolism; D020933:Neurotrophin 3 / Q000494:pharmacology / Q000627:therapeutic use*; D011161:Porifera / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D054457:Tissue Scaffolds / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D011508:Chondroitin Sulfate Proteoglycans; D005349:Fibroins; D005780:Gelatin; D020933:Neurotrophin 3; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Controlled artificial release system; Fibroin; Gelatin sponge scaffold; Neurotrophin-3; Spinal cord injury; Transplantation