A reactive oxygen species-responsive hydrogel loaded with Apelin-13 promotes the repair of spinal cord injury by regulating macrophage M1/M2 polarization and neuroinflammation
Abstract Spinal cord injury (SCI) is a chronic condition whereby persistent aberrant macrophage activation hinders the repair process. During acute trauma, dominant M1 macrophages produce high levels of reactive oxygen species (ROS), leading to increased apoptosis in neurons, glial cells, and oligod...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-024-02978-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544289474052096 |
|---|---|
| author | Zhiyue Li Qun Zhao Jiahui Zhou Yuyan Li Yifan Zheng Linxi Chen |
| author_facet | Zhiyue Li Qun Zhao Jiahui Zhou Yuyan Li Yifan Zheng Linxi Chen |
| author_sort | Zhiyue Li |
| collection | DOAJ |
| description | Abstract Spinal cord injury (SCI) is a chronic condition whereby persistent aberrant macrophage activation hinders the repair process. During acute trauma, dominant M1 macrophages produce high levels of reactive oxygen species (ROS), leading to increased apoptosis in neurons, glial cells, and oligodendrocytes. This study investigated the specific effects of a ROS-responsive hydrogel loaded with Apelin-13 (Apelin-13@ROS-hydrogel) on macrophage polarization and neuroinflammation, thereby exploring its role in boosting SCI repair. Apelin-13@ROS-hydrogel was prepared, and its ROS-scavenging capacities were evaluated using DPPH, H2O2, and ·O2- assays. The effects of Apelin-13@ROS-hydrogel on macrophage polarization, inflammatory mediators and oxidative stress were assessed in LPS-pre-treated microglia BV2 cells and an SCI rat model. Apelin-13 was downregulated in SCI rats. Treatment with Apelin-13 improved functional recovery and reduced inflammatory factors and M1 markers but increased the M2 marker Arg-1. Apelin-13@ROS-hydrogel showed significantly higher ROS-scavenging capacities compared to the control hydrogel. Apelin-13@ROS-hydrogel decreased pro-inflammatory mediators and increased anti-inflammatory mediators in BV2 cells. Apelin-13@ROS-hydrogel enhanced the healing process and neurological functions, reducing inflammatory factors and M1 markers while increasing Arg-1 levels by day 28 in SCI rats. Collectively, Apelin-13 enhances SCI repair through macrophage regulation, M1/M2 polarization, and neuroinflammation. The ROS-responsive hydrogel further amplifies these effects, offering a promising therapeutic strategy for SCI. |
| format | Article |
| id | doaj-art-76f0fac96f9c487f8321f226967c8b30 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-76f0fac96f9c487f8321f226967c8b302025-01-12T12:38:17ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123111810.1186/s12951-024-02978-4A reactive oxygen species-responsive hydrogel loaded with Apelin-13 promotes the repair of spinal cord injury by regulating macrophage M1/M2 polarization and neuroinflammationZhiyue Li0Qun Zhao1Jiahui Zhou2Yuyan Li3Yifan Zheng4Linxi Chen5Department of Spine Surgery, The Third Xiangya Hospital, Central South UniversityHealth Management Medicine Center, The Third Xiangya Hospital, Central South UniversityDepartment of Spine Surgery, The Third Xiangya Hospital, Central South UniversityNanChang University Queen Mary SchoolDepartment of Spine Surgery, The Third Xiangya Hospital, Central South UniversitySchool of Pharmaceutical Science, University of South ChinaAbstract Spinal cord injury (SCI) is a chronic condition whereby persistent aberrant macrophage activation hinders the repair process. During acute trauma, dominant M1 macrophages produce high levels of reactive oxygen species (ROS), leading to increased apoptosis in neurons, glial cells, and oligodendrocytes. This study investigated the specific effects of a ROS-responsive hydrogel loaded with Apelin-13 (Apelin-13@ROS-hydrogel) on macrophage polarization and neuroinflammation, thereby exploring its role in boosting SCI repair. Apelin-13@ROS-hydrogel was prepared, and its ROS-scavenging capacities were evaluated using DPPH, H2O2, and ·O2- assays. The effects of Apelin-13@ROS-hydrogel on macrophage polarization, inflammatory mediators and oxidative stress were assessed in LPS-pre-treated microglia BV2 cells and an SCI rat model. Apelin-13 was downregulated in SCI rats. Treatment with Apelin-13 improved functional recovery and reduced inflammatory factors and M1 markers but increased the M2 marker Arg-1. Apelin-13@ROS-hydrogel showed significantly higher ROS-scavenging capacities compared to the control hydrogel. Apelin-13@ROS-hydrogel decreased pro-inflammatory mediators and increased anti-inflammatory mediators in BV2 cells. Apelin-13@ROS-hydrogel enhanced the healing process and neurological functions, reducing inflammatory factors and M1 markers while increasing Arg-1 levels by day 28 in SCI rats. Collectively, Apelin-13 enhances SCI repair through macrophage regulation, M1/M2 polarization, and neuroinflammation. The ROS-responsive hydrogel further amplifies these effects, offering a promising therapeutic strategy for SCI.https://doi.org/10.1186/s12951-024-02978-4Spinal cord injury (SCI)Apelin-13ROS-responsive hydrogelMacrophage M1/M2 polarizationImmune microenvironment |
| spellingShingle | Zhiyue Li Qun Zhao Jiahui Zhou Yuyan Li Yifan Zheng Linxi Chen A reactive oxygen species-responsive hydrogel loaded with Apelin-13 promotes the repair of spinal cord injury by regulating macrophage M1/M2 polarization and neuroinflammation Journal of Nanobiotechnology Spinal cord injury (SCI) Apelin-13 ROS-responsive hydrogel Macrophage M1/M2 polarization Immune microenvironment |
| title | A reactive oxygen species-responsive hydrogel loaded with Apelin-13 promotes the repair of spinal cord injury by regulating macrophage M1/M2 polarization and neuroinflammation |
| title_full | A reactive oxygen species-responsive hydrogel loaded with Apelin-13 promotes the repair of spinal cord injury by regulating macrophage M1/M2 polarization and neuroinflammation |
| title_fullStr | A reactive oxygen species-responsive hydrogel loaded with Apelin-13 promotes the repair of spinal cord injury by regulating macrophage M1/M2 polarization and neuroinflammation |
| title_full_unstemmed | A reactive oxygen species-responsive hydrogel loaded with Apelin-13 promotes the repair of spinal cord injury by regulating macrophage M1/M2 polarization and neuroinflammation |
| title_short | A reactive oxygen species-responsive hydrogel loaded with Apelin-13 promotes the repair of spinal cord injury by regulating macrophage M1/M2 polarization and neuroinflammation |
| title_sort | reactive oxygen species responsive hydrogel loaded with apelin 13 promotes the repair of spinal cord injury by regulating macrophage m1 m2 polarization and neuroinflammation |
| topic | Spinal cord injury (SCI) Apelin-13 ROS-responsive hydrogel Macrophage M1/M2 polarization Immune microenvironment |
| url | https://doi.org/10.1186/s12951-024-02978-4 |
| work_keys_str_mv | AT zhiyueli areactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation AT qunzhao areactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation AT jiahuizhou areactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation AT yuyanli areactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation AT yifanzheng areactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation AT linxichen areactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation AT zhiyueli reactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation AT qunzhao reactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation AT jiahuizhou reactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation AT yuyanli reactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation AT yifanzheng reactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation AT linxichen reactiveoxygenspeciesresponsivehydrogelloadedwithapelin13promotestherepairofspinalcordinjurybyregulatingmacrophagem1m2polarizationandneuroinflammation |