Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth
Abstract Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its re...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-05-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202105586 |
| _version_ | 1828385743310946304 |
|---|---|
| author | Lei Fan Can Liu Xiuxing Chen Lei Zheng Yan Zou Huiquan Wen Pengfei Guan Fang Lu Yian Luo Guoxin Tan Peng Yu Dafu Chen Chunlin Deng Yongjian Sun Lei Zhou Chengyun Ning |
| author_facet | Lei Fan Can Liu Xiuxing Chen Lei Zheng Yan Zou Huiquan Wen Pengfei Guan Fang Lu Yian Luo Guoxin Tan Peng Yu Dafu Chen Chunlin Deng Yongjian Sun Lei Zhou Chengyun Ning |
| author_sort | Lei Fan |
| collection | DOAJ |
| description | Abstract Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell‐derived exosomes (BMSC‐exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue‐like electroconductive hydrogels loaded with BMSC‐exosomes are developed for the synergistic treatment of SCI. These exosomes‐loaded electroconductive hydrogels modulate microglial M2 polarization via the NF‐κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68‐positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC‐exosomes is a promising therapeutic strategy for SCI repair. |
| first_indexed | 2024-12-10T05:25:10Z |
| format | Article |
| id | doaj.art-354c5cdc47034ae3ab44d35afc410186 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-10T05:25:10Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-354c5cdc47034ae3ab44d35afc4101862022-12-22T02:00:42ZengWileyAdvanced Science2198-38442022-05-01913n/an/a10.1002/advs.202105586Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon GrowthLei Fan0Can Liu1Xiuxing Chen2Lei Zheng3Yan Zou4Huiquan Wen5Pengfei Guan6Fang Lu7Yian Luo8Guoxin Tan9Peng Yu10Dafu Chen11Chunlin Deng12Yongjian Sun13Lei Zhou14Chengyun Ning15School of Materials Science and Engineering and National Engineering Research Center for Tissue Restoration and Reconstruction South China University of Technology No. 381, Wushan Road, Tianhe District Guangzhou 510641 ChinaDepartment of Orthopedic Surgery The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Department of Medical Oncology Sun Yat‐sen Memorial Hospital Sun Yat‐sen University No. 107, Yanjiang West Road, Yuexiu District, Guangzhou Guangzhou 510120 ChinaLaboratory Medicine Center Nanfang Hospital Southern Medical University No. 1838, Guangzhou Avenue North, Baiyun District Guangzhou Guangdong 510515 ChinaDepartment of Radiology the Third Affiliated Hospital of Sun Yat‐sen University No. 600, Tianhe Road, Tianhe District Guangzhou 510630 ChinaDepartment of Radiology the Third Affiliated Hospital of Sun Yat‐sen University No. 600, Tianhe Road, Tianhe District Guangzhou 510630 ChinaDepartment of Pediatric Orthopedic Center for Orthopedic Surgery The Third Affiliated Hospital of Southern Medical University No.183, Zhongshan Avenue West Guangzhou 510515 ChinaSchool of Preclinical Medicine Beijing University of Chinese Medicine No.11, North Third Ring East Road, Chaoyang District Beijing 100029 ChinaSchool of Chemical Engineering and Light Industry Guangdong University of Technology No.100, Waihuan West Road, Panyu District Guangzhou 510006 ChinaSchool of Chemical Engineering and Light Industry Guangdong University of Technology No.100, Waihuan West Road, Panyu District Guangzhou 510006 ChinaSchool of Materials Science and Engineering and National Engineering Research Center for Tissue Restoration and Reconstruction South China University of Technology No. 381, Wushan Road, Tianhe District Guangzhou 510641 ChinaLaboratory of Bone Tissue Engineering Beijing Research Institute of Orthopaedics and Traumatology Beijing JiShuiTan Hospital No.31, Xinjiekou East Street, Xicheng District Beijing 100035 ChinaSchool of Materials Science and Engineering and National Engineering Research Center for Tissue Restoration and Reconstruction South China University of Technology No. 381, Wushan Road, Tianhe District Guangzhou 510641 ChinaDepartment of Pediatric Orthopedic Center for Orthopedic Surgery The Third Affiliated Hospital of Southern Medical University No.183, Zhongshan Avenue West Guangzhou 510515 ChinaGuangzhou Key Laboratory of Spine Disease Prevention and Treatment Department of Spine Surgery The Third Affiliated Hospital Guangzhou Medical University No. 63, Duobao Road, Liwan District Guangzhou 510150 ChinaSchool of Materials Science and Engineering and National Engineering Research Center for Tissue Restoration and Reconstruction South China University of Technology No. 381, Wushan Road, Tianhe District Guangzhou 510641 ChinaAbstract Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell‐derived exosomes (BMSC‐exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue‐like electroconductive hydrogels loaded with BMSC‐exosomes are developed for the synergistic treatment of SCI. These exosomes‐loaded electroconductive hydrogels modulate microglial M2 polarization via the NF‐κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68‐positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC‐exosomes is a promising therapeutic strategy for SCI repair.https://doi.org/10.1002/advs.202105586anti‐inflammationaxonal regenerationBMSC‐derived exosomeselectroconductive hydrogelsspinal cord injury |
| spellingShingle | Lei Fan Can Liu Xiuxing Chen Lei Zheng Yan Zou Huiquan Wen Pengfei Guan Fang Lu Yian Luo Guoxin Tan Peng Yu Dafu Chen Chunlin Deng Yongjian Sun Lei Zhou Chengyun Ning Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth Advanced Science anti‐inflammation axonal regeneration BMSC‐derived exosomes electroconductive hydrogels spinal cord injury |
| title | Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth |
| title_full | Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth |
| title_fullStr | Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth |
| title_full_unstemmed | Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth |
| title_short | Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth |
| title_sort | exosomes loaded electroconductive hydrogel synergistically promotes tissue repair after spinal cord injury via immunoregulation and enhancement of myelinated axon growth |
| topic | anti‐inflammation axonal regeneration BMSC‐derived exosomes electroconductive hydrogels spinal cord injury |
| url | https://doi.org/10.1002/advs.202105586 |
| work_keys_str_mv | AT leifan exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT canliu exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT xiuxingchen exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT leizheng exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT yanzou exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT huiquanwen exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT pengfeiguan exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT fanglu exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT yianluo exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT guoxintan exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT pengyu exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT dafuchen exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT chunlindeng exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT yongjiansun exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT leizhou exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth AT chengyunning exosomesloadedelectroconductivehydrogelsynergisticallypromotestissuerepairafterspinalcordinjuryviaimmunoregulationandenhancementofmyelinatedaxongrowth |