Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair
The crosstalk between immune cells and the neurovascular unit plays a pivotal role in neural regeneration following central nervous system (CNS) injury. Maintaining brain immune homeostasis is crucial for restoring neurovascular function. In this study, an interactive bridge was developed via an imm...
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KeAi Communications Co., Ltd.
2025-02-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24004845 |
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| author | Tongtong Xu Lin Gan Wei Chen Dandan Zheng Hanlai Li Shiyu Deng Dongliang Qian Tingting Gu Qianyuan Lian Gracie Shen Qingzhu An Wanlu Li Zhijun Zhang Guo-Yuan Yang Huitong Ruan Wenguo Cui Yaohui Tang |
| author_facet | Tongtong Xu Lin Gan Wei Chen Dandan Zheng Hanlai Li Shiyu Deng Dongliang Qian Tingting Gu Qianyuan Lian Gracie Shen Qingzhu An Wanlu Li Zhijun Zhang Guo-Yuan Yang Huitong Ruan Wenguo Cui Yaohui Tang |
| author_sort | Tongtong Xu |
| collection | DOAJ |
| description | The crosstalk between immune cells and the neurovascular unit plays a pivotal role in neural regeneration following central nervous system (CNS) injury. Maintaining brain immune homeostasis is crucial for restoring neurovascular function. In this study, an interactive bridge was developed via an immunomodulatory hydrogel microsphere to link the interaction network between microglia and the neurovascular unit, thereby precisely regulating immune-neurovascular crosstalk and achieving neural function recovery. This immunomodulatory crosstalk microsphere (MP/RIL4) was composed of microglia-targeted RAP12 peptide-modified interleukin-4 (IL-4) nanoparticles and boronic ester-functionalized hydrogel using biotin-avidin reaction and air-microfluidic techniques. We confirmed that the immunomodulatory microspheres reduced the expression of pro-inflammatory factors including IL-1β, iNOS, and CD86, while upregulating levels of anti-inflammatory factors such as IL-10, Arg-1, and CD206 in microglia. In addition, injection of the MP/RIL4 significantly mitigated brain atrophy volume in a mouse model of ischemic stroke, promoted neurobehavioral recovery, and enhanced the crosstalk between immune cells and the neurovascular unit, thus increasing angiogenesis and neurogenesis of stroke mice. In summary, the immunomodulatory microspheres, capable of orchestrating the interaction between immune cells and neurovascular unit, hold considerable therapeutic potential for ischemic stroke and other CNS diseases. |
| format | Article |
| id | doaj-art-4ac3ce2b50214e27b5eecff21a6fe43c |
| institution | DOAJ |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-4ac3ce2b50214e27b5eecff21a6fe43c2025-08-20T02:39:29ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-02-014455857110.1016/j.bioactmat.2024.10.031Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repairTongtong Xu0Lin Gan1Wei Chen2Dandan Zheng3Hanlai Li4Shiyu Deng5Dongliang Qian6Tingting Gu7Qianyuan Lian8Gracie Shen9Qingzhu An10Wanlu Li11Zhijun Zhang12Guo-Yuan Yang13Huitong Ruan14Wenguo Cui15Yaohui Tang16Department of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, ChinaDepartment of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, ChinaDepartment of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, ChinaDepartment of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, ChinaDepartment of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, ChinaDepartment of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, ChinaDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical School, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, ChinaDepartment of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, ChinaDepartment of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, ChinaLoomis Chaffee School, 4 Batchelder Road, Windsor, CT, 06095, USADepartment of Neurosurgery, Huashan Hospital, Shanghai Medical School, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, ChinaDepartment of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, ChinaDepartment of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, ChinaDepartment of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, ChinaDepartment of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, China; Corresponding author. Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.Department of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, China; Corresponding author. Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.Department of Orthopaedics and School of Biomedical Engineering, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, Shanghai, 200025, China; Corresponding author. School of Biomedical Engineering 1954 Hua Shan Road, Shanghai Jiao Tong University, Shanghai, 200030, China.The crosstalk between immune cells and the neurovascular unit plays a pivotal role in neural regeneration following central nervous system (CNS) injury. Maintaining brain immune homeostasis is crucial for restoring neurovascular function. In this study, an interactive bridge was developed via an immunomodulatory hydrogel microsphere to link the interaction network between microglia and the neurovascular unit, thereby precisely regulating immune-neurovascular crosstalk and achieving neural function recovery. This immunomodulatory crosstalk microsphere (MP/RIL4) was composed of microglia-targeted RAP12 peptide-modified interleukin-4 (IL-4) nanoparticles and boronic ester-functionalized hydrogel using biotin-avidin reaction and air-microfluidic techniques. We confirmed that the immunomodulatory microspheres reduced the expression of pro-inflammatory factors including IL-1β, iNOS, and CD86, while upregulating levels of anti-inflammatory factors such as IL-10, Arg-1, and CD206 in microglia. In addition, injection of the MP/RIL4 significantly mitigated brain atrophy volume in a mouse model of ischemic stroke, promoted neurobehavioral recovery, and enhanced the crosstalk between immune cells and the neurovascular unit, thus increasing angiogenesis and neurogenesis of stroke mice. In summary, the immunomodulatory microspheres, capable of orchestrating the interaction between immune cells and neurovascular unit, hold considerable therapeutic potential for ischemic stroke and other CNS diseases.http://www.sciencedirect.com/science/article/pii/S2452199X24004845Immune modulating microsphereIschemic strokeCrosstalkAngiogenesisNeurogenesis |
| spellingShingle | Tongtong Xu Lin Gan Wei Chen Dandan Zheng Hanlai Li Shiyu Deng Dongliang Qian Tingting Gu Qianyuan Lian Gracie Shen Qingzhu An Wanlu Li Zhijun Zhang Guo-Yuan Yang Huitong Ruan Wenguo Cui Yaohui Tang Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair Bioactive Materials Immune modulating microsphere Ischemic stroke Crosstalk Angiogenesis Neurogenesis |
| title | Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair |
| title_full | Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair |
| title_fullStr | Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair |
| title_full_unstemmed | Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair |
| title_short | Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair |
| title_sort | bridging immune neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair |
| topic | Immune modulating microsphere Ischemic stroke Crosstalk Angiogenesis Neurogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24004845 |
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