PMID- 33391504 OWN - NLM STAT- MEDLINE DCOM- 20210804 LR - 20210804 IS - 1838-7640 (Electronic) IS - 1838-7640 (Linking) VI - 11 IP - 2 DP - 2021 TI - Implantation of regenerative complexes in traumatic brain injury canine models enhances the reconstruction of neural networks and motor function recovery. PG - 768-788 LID - 10.7150/thno.50540 [doi] AB - Rationale: The combination of medical and tissue engineering in neural regeneration studies is a promising field. Collagen, silk fibroin and seed cells are suitable options and have been widely used in the repair of spinal cord injury. In this study, we aimed to determine whether the implantation of a complex fabricated with collagen/silk fibroin (SF) and the human umbilical cord mesenchymal stem cells (hUCMSCs) can promote cerebral cortex repair and motor functional recovery in a canine model of traumatic brain injury (TBI). Methods: A porous scaffold was fabricated with cross-linked collagen and SF. Its physical properties and degeneration rate were measured. The scaffolds were co-cultured with hUCMSCs after which an implantable complex was formed. After complex implantation to a canine model of TBI, the motor evoked potential (MEP) and magnetic resonance imaging (MRI) were used to evaluate the integrity of the cerebral cortex. The neurologic score, motion capture, surface electromyography (sEMG), and vertical ground reaction force (vGRF) were measured in the analysis of motor functions. In vitro analysis of inflammation levels was performed by Elisa while immunohistochemistry was used in track the fate of hUCMSCs. In situ hybridization, transmission electron microscope, and immunofluorescence were used to assess neural and vascular regeneration. Results: Favorable physical properties, suitable degradation rate, and biocompatibility were observed in the collagen/SF scaffolds. The group with complex implantation exhibited the best cerebral cortex integrity and motor functions. The implantation also led to the regeneration of more blood vessels and nerve fibers, less glial fibers, and inflammatory factors. Conclusion: Implantation of this complex enhanced therapy in traumatic brain injury (TBI) through structural repair and functional recovery. These effects exhibit the translational prospects for the clinical application of this complex. CI - (c) The author(s). FAU - Jiang, Jipeng AU - Jiang J AD - Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience, Center for Neurology and Neurosurgery of Characteristic Medical Center of Chinese People's Armed Police Force (PAP), Chenglin Road No.220, Tianjin 300162, China. AD - Postgraduate school, Medical school of Chinese People's Liberation Army (PLA), General Hospital of PLA, Fuxing Road No. 28, Beijing 100853, China. FAU - Dai, Chen AU - Dai C AD - Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience, Center for Neurology and Neurosurgery of Characteristic Medical Center of Chinese People's Armed Police Force (PAP), Chenglin Road No.220, Tianjin 300162, China. FAU - Liu, Xiaoyin AU - Liu X AD - Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, China. FAU - Dai, Lujia AU - Dai L AD - Department of Neurology, the Armed Police Corps Hospital of Zhejiang Province, Hangzhou 310000, China. FAU - Li, Ruixin AU - Li R AD - Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin Stomatological Hospital, Tianjin 300041, China. FAU - Ma, Ke AU - Ma K AD - Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience, Center for Neurology and Neurosurgery of Characteristic Medical Center of Chinese People's Armed Police Force (PAP), Chenglin Road No.220, Tianjin 300162, China. FAU - Xu, Huiyou AU - Xu H AD - Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience, Center for Neurology and Neurosurgery of Characteristic Medical Center of Chinese People's Armed Police Force (PAP), Chenglin Road No.220, Tianjin 300162, China. FAU - Zhao, Fei AU - Zhao F AD - Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience, Center for Neurology and Neurosurgery of Characteristic Medical Center of Chinese People's Armed Police Force (PAP), Chenglin Road No.220, Tianjin 300162, China. FAU - Zhang, Zhiwen AU - Zhang Z AD - SUSTech-UTokyo Joint Research Center on Super Smart City, Southern University of Science and Technology, Center for Spatial Information Science, The University of Tokyo, Tokyo 277-8568, Japan. FAU - He, Tao AU - He T AD - Department of pathology, Characteristic Medical Center of Chinese People's Armed Police Force (PAP), Chenglin Road No.220, Tianjin 300162, China. FAU - Niu, Xuegang AU - Niu X AD - Department of Neurosurgery of Tianjin Fourth Central Hospital, Zhongshan Road No.1, Tianjin 300143, China. FAU - Chen, Xuyi AU - Chen X AD - Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience, Center for Neurology and Neurosurgery of Characteristic Medical Center of Chinese People's Armed Police Force (PAP), Chenglin Road No.220, Tianjin 300162, China. FAU - Zhang, Sai AU - Zhang S AD - Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience, Center for Neurology and Neurosurgery of Characteristic Medical Center of Chinese People's Armed Police Force (PAP), Chenglin Road No.220, Tianjin 300162, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210101 PL - Australia TA - Theranostics JT - Theranostics JID - 101552395 RN - 9007-34-5 (Collagen) RN - 9007-76-5 (Fibroins) SB - IM MH - Animals MH - Brain Injuries, Traumatic/pathology/*therapy MH - Collagen/chemistry MH - Dogs MH - Fibroins/chemistry MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/*cytology MH - *Motor Activity MH - *Nerve Regeneration MH - *Neural Pathways MH - *Recovery of Function MH - Tissue Engineering MH - Tissue Scaffolds/chemistry PMC - PMC7738861 OTO - NOTNLM OT - Collagen OT - Hemiplegic limb OT - Mesenchymal stem cell OT - Silk fibroin OT - Traumatic brain injury COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2021/01/05 06:00 MHDA- 2021/08/05 06:00 PMCR- 2021/01/01 CRDT- 2021/01/04 05:28 PHST- 2020/07/10 00:00 [received] PHST- 2020/10/13 00:00 [accepted] PHST- 2021/01/04 05:28 [entrez] PHST- 2021/01/05 06:00 [pubmed] PHST- 2021/08/05 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - thnov11p0768 [pii] AID - 10.7150/thno.50540 [doi] PST - epublish SO - Theranostics. 2021 Jan 1;11(2):768-788. doi: 10.7150/thno.50540. eCollection 2021.