Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair

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

Bioactive Materials (Feb 2025)

Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair

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

Affiliations

Tongtong Xu: 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
Lin Gan: 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
Wei Chen: 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
Dandan Zheng: 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
Hanlai Li: 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
Shiyu Deng: 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
Dongliang Qian: Department of Neurosurgery, Huashan Hospital, Shanghai Medical School, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China
Tingting Gu: 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
Qianyuan Lian: 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
Gracie Shen: Loomis Chaffee School, 4 Batchelder Road, Windsor, CT, 06095, USA
Qingzhu An: Department of Neurosurgery, Huashan Hospital, Shanghai Medical School, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China
Wanlu Li: 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
Zhijun Zhang: 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
Guo-Yuan Yang: 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
Huitong Ruan: 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.
Wenguo Cui: 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.
Yaohui Tang: 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.

Journal volume & issue: Vol. 44
pp. 558 – 571

Abstract

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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.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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