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Peripheral Nerve‐Derived Matrix Hydrogel Promotes Remyelination and Inhibits Synapse Formation
Authors:Jian‐Long Zou  Sheng Liu  Jia‐Hui Sun  Wei‐Hong Yang  Yi‐Wei Xu  Zi‐Long Rao  Bin Jiang  Qing‐Tang Zhu  Xiao‐Lin Liu  Jin‐Lang Wu  Calvin Chang  Hai‐Quan Mao  Eng‐Ang Ling  Da‐Ping Quan  Yuan‐Shan Zeng
Affiliation:1. Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat‐sen University, Ministry of Education, Guangzhou, Guangdong, China;2. PCFM Lab, School of Chemistry, Sun Yat‐sen University, Guangzhou, Guangdong, China;3. Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat‐sen University, Guangzhou, Guangdong, China;4. Department of Orthopedic and Microsurgery, The First Affiliated Hospital of SunYat‐sen University, Guangzhou, China;5. Department of Electron Microscope, Zhongshan School of Medicine, Sun Yat‐sen University, Guangzhou, Guangdong, China;6. Translational Tissue Engineering Center, and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA;7. Institute for NanoBioTechnology, and Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA;8. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;9. Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat‐sen University, Guangzhou, Guangdong, China;10. Joint Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China;11. Institute of Spinal Cord Injury, Sun Yat‐sen University, Guangzhou, Guangdong, China
Abstract:Regeneration of injured nerve tissues requires intricate interplay of complex processes like axon elongation, remyelination, and synaptic formation in a tissue‐specific manner. A decellularized nerve matrix‐gel (DNM‐G) and a decellularized spinal cord matrix‐gel (DSCM‐G) are prepared from porcine sciatic nerves and spinal cord tissue, respectively, to recapitulate the microenvironment cues unique to the native tissue functions. Using an in vitro dorsal root ganglion–Schwann cells coculture model and proteomics analysis, it is confirmed that DNM‐G promotes far stronger remyelination activity and reduces synapse formation of the regenerating axons in contrast to DSCM‐G, Matrigel, and collagen I, consistent with its tissue‐specific function. Bioinformatics analysis indicates that the lack of neurotrophic factors and presence of some axon inhibitory molecules may contribute to moderate axonal elongation activity, while laminin β2, Laminin γ1, collagens, and fibronectin in DNM‐G promote remyelination. These results confirm that DNM‐G is a promising matrix material for peripheral nerve repair. This study provides more insights into tissue‐specific extracellular matrix components correlating to biological functions supporting functional regeneration.
Keywords:decellularized matrix  hydrogels  myelination  peripheral nerve  spinal cord
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