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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| creator | Xu, Tongtong Gan, Lin Chen, Wei Zheng, Dandan Li, Hanlai Deng, Shiyu Qian, Dongliang Gu, Tingting Lian, Qianyuan Shen, Gracie An, Qingzhu Li, Wanlu Zhang, Zhijun Yang, Guo-Yuan Ruan, Huitong Cui, Wenguo Tang, Yaohui |
| 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.
The immune-neurovascular crosstalk bridge via the immunomodulatory microsphere (MP/RIL4) was constructed, which could induce the transformation of microglia into an anti-inflammatory phenotype, and link their interaction with neurovascular unit, ultimately succeeding to promote angiogenesis and neurogenesis in ischemic stroke model mice. [Display omitted]
•Immunomodulatory microspheres (MP/RIL4) held great anti-inflammatory effects in vitro and in vivo.•MP/RIL4 mitigated brain atrophy volume and promoted neurobehavioral recovery for a long-time of ischemic stroke mice.•MP/RIL4 increased angiogenesis and neurogenesis via enhancing immune-neurovascular crosstalk of ischemic stroke mice. |
| doi_str_mv | 10.1016/j.bioactmat.2024.10.031 |
| format | Article |
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The immune-neurovascular crosstalk bridge via the immunomodulatory microsphere (MP/RIL4) was constructed, which could induce the transformation of microglia into an anti-inflammatory phenotype, and link their interaction with neurovascular unit, ultimately succeeding to promote angiogenesis and neurogenesis in ischemic stroke model mice. [Display omitted]
•Immunomodulatory microspheres (MP/RIL4) held great anti-inflammatory effects in vitro and in vivo.•MP/RIL4 mitigated brain atrophy volume and promoted neurobehavioral recovery for a long-time of ischemic stroke mice.•MP/RIL4 increased angiogenesis and neurogenesis via enhancing immune-neurovascular crosstalk of ischemic stroke mice.</description><identifier>ISSN: 2452-199X</identifier><identifier>ISSN: 2097-1192</identifier><identifier>EISSN: 2452-199X</identifier><identifier>DOI: 10.1016/j.bioactmat.2024.10.031</identifier><identifier>PMID: 39584066</identifier><language>eng</language><publisher>China: Elsevier B.V</publisher><subject>Angiogenesis ; Atrophy ; Avidin ; Biomedical materials ; Biotin ; Brain ; Brain injury ; Bridge maintenance ; CD86 antigen ; Central nervous system ; Crosstalk ; Cytokines ; Genotype & phenotype ; Growth factors ; Homeostasis ; Hydrogels ; Immune modulating microsphere ; Immune system ; Immunomodulation ; Immunomodulators ; Interleukin 4 ; Ischemia ; Ischemic stroke ; Microfluidics ; Microglia ; Microspheres ; Nanoparticles ; Nervous system ; Neurogenesis ; Nitric-oxide synthase ; Peptides ; Polyvinyl alcohol ; Recovery ; Regeneration ; Scanning electron microscopy ; Signal transduction ; Solvents ; Stroke ; Traumatic brain injury</subject><ispartof>Bioactive materials, 2025-02, Vol.44, p.558-571</ispartof><rights>2024 The Authors</rights><rights>2024 The Authors.</rights><rights>2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c275t-bb4ac7d522e3715a7a36b257603c3ef619ee356b62f5fad6c02eef2e15a2c0753</cites><orcidid>0000-0002-5200-8149</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/3140512603?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,864,21388,27924,27925,33744,33745,43805,64385,64387,64389,72469,73123,73128,73129,73131</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39584066$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Tongtong</creatorcontrib><creatorcontrib>Gan, Lin</creatorcontrib><creatorcontrib>Chen, Wei</creatorcontrib><creatorcontrib>Zheng, Dandan</creatorcontrib><creatorcontrib>Li, Hanlai</creatorcontrib><creatorcontrib>Deng, Shiyu</creatorcontrib><creatorcontrib>Qian, Dongliang</creatorcontrib><creatorcontrib>Gu, Tingting</creatorcontrib><creatorcontrib>Lian, Qianyuan</creatorcontrib><creatorcontrib>Shen, Gracie</creatorcontrib><creatorcontrib>An, Qingzhu</creatorcontrib><creatorcontrib>Li, Wanlu</creatorcontrib><creatorcontrib>Zhang, Zhijun</creatorcontrib><creatorcontrib>Yang, Guo-Yuan</creatorcontrib><creatorcontrib>Ruan, Huitong</creatorcontrib><creatorcontrib>Cui, Wenguo</creatorcontrib><creatorcontrib>Tang, Yaohui</creatorcontrib><title>Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair</title><title>Bioactive materials</title><addtitle>Bioact Mater</addtitle><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.
The immune-neurovascular crosstalk bridge via the immunomodulatory microsphere (MP/RIL4) was constructed, which could induce the transformation of microglia into an anti-inflammatory phenotype, and link their interaction with neurovascular unit, ultimately succeeding to promote angiogenesis and neurogenesis in ischemic stroke model mice. [Display omitted]
•Immunomodulatory microspheres (MP/RIL4) held great anti-inflammatory effects in vitro and in vivo.•MP/RIL4 mitigated brain atrophy volume and promoted neurobehavioral recovery for a long-time of ischemic stroke mice.•MP/RIL4 increased angiogenesis and neurogenesis via enhancing immune-neurovascular crosstalk of ischemic stroke mice.</description><subject>Angiogenesis</subject><subject>Atrophy</subject><subject>Avidin</subject><subject>Biomedical materials</subject><subject>Biotin</subject><subject>Brain</subject><subject>Brain injury</subject><subject>Bridge maintenance</subject><subject>CD86 antigen</subject><subject>Central nervous system</subject><subject>Crosstalk</subject><subject>Cytokines</subject><subject>Genotype & phenotype</subject><subject>Growth factors</subject><subject>Homeostasis</subject><subject>Hydrogels</subject><subject>Immune modulating microsphere</subject><subject>Immune 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Mater</addtitle><date>2025-02-01</date><risdate>2025</risdate><volume>44</volume><spage>558</spage><epage>571</epage><pages>558-571</pages><issn>2452-199X</issn><issn>2097-1192</issn><eissn>2452-199X</eissn><abstract>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.
The immune-neurovascular crosstalk bridge via the immunomodulatory microsphere (MP/RIL4) was constructed, which could induce the transformation of microglia into an anti-inflammatory phenotype, and link their interaction with neurovascular unit, ultimately succeeding to promote angiogenesis and neurogenesis in ischemic stroke model mice. [Display omitted]
•Immunomodulatory microspheres (MP/RIL4) held great anti-inflammatory effects in vitro and in vivo.•MP/RIL4 mitigated brain atrophy volume and promoted neurobehavioral recovery for a long-time of ischemic stroke mice.•MP/RIL4 increased angiogenesis and neurogenesis via enhancing immune-neurovascular crosstalk of ischemic stroke mice.</abstract><cop>China</cop><pub>Elsevier B.V</pub><pmid>39584066</pmid><doi>10.1016/j.bioactmat.2024.10.031</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-5200-8149</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Atrophy Avidin Biomedical materials Biotin Brain Brain injury Bridge maintenance CD86 antigen Central nervous system Crosstalk Cytokines Genotype & phenotype Growth factors Homeostasis Hydrogels Immune modulating microsphere Immune system Immunomodulation Immunomodulators Interleukin 4 Ischemia Ischemic stroke Microfluidics Microglia Microspheres Nanoparticles Nervous system Neurogenesis Nitric-oxide synthase Peptides Polyvinyl alcohol Recovery Regeneration Scanning electron microscopy Signal transduction Solvents Stroke Traumatic brain injury |
| title | Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair |
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