Engineering spatially-confined conduits to tune nerve self-organization and allodynic responses via YAP-mediated mechanotransduction
Abstract Chronic allodynia stemming from peripheral stump neuromas can persist for extended periods, significantly compromising patients’ quality of life. Conventional managements for nerve stumps have demonstrated limited effectiveness in ensuring their orderly termination. In this study, we presen...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55118-9 |
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| author | Xiaobin Luo Jia Yang Yonggang Zhao Toshitatsu Nagayasu Junlin Chen Peilun Hu Zhi He Zifan Li Jun Wu Zhe Zhao Guman Duan Xiaodan Sun Lingyun Zhao Yongwei Pan Xiumei Wang |
| author_facet | Xiaobin Luo Jia Yang Yonggang Zhao Toshitatsu Nagayasu Junlin Chen Peilun Hu Zhi He Zifan Li Jun Wu Zhe Zhao Guman Duan Xiaodan Sun Lingyun Zhao Yongwei Pan Xiumei Wang |
| author_sort | Xiaobin Luo |
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| description | Abstract Chronic allodynia stemming from peripheral stump neuromas can persist for extended periods, significantly compromising patients’ quality of life. Conventional managements for nerve stumps have demonstrated limited effectiveness in ensuring their orderly termination. In this study, we present a spatially confined conduit strategy, designed to enhance the self-organization of regenerating nerves after truncation. This innovative approach elegantly enables the autonomous slowing of axonal outgrowth in response to the gradually constricting space, concurrently suppressing neuroinflammation through YAP-mediated mechanotransduction activation. Meanwhile, the decelerating axons exhibit excellent alignment and remyelination, thereby helping to prevent failure modes in nerve self-organization, such as axonal twisting in congested regions and overgrowth beyond the conduit’s capacity. Additionally, proteins associated with mechanical allodynia, including TRPA1 and CGRP, exhibit a gradual reduction in expression as spatial constraints tighten, a trend inversely validated by the administration of the YAP-targeted inhibitor Verteporfin. This spatially confined conduit strategy significantly alleviates allodynia, thus preventing autotomy behavior and reducing pain-induced gait alterations. |
| format | Article |
| id | doaj-art-fb6436b4b9194f289022040b86695863 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-fb6436b4b9194f289022040b866958632025-01-05T12:40:12ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-024-55118-9Engineering spatially-confined conduits to tune nerve self-organization and allodynic responses via YAP-mediated mechanotransductionXiaobin Luo0Jia Yang1Yonggang Zhao2Toshitatsu Nagayasu3Junlin Chen4Peilun Hu5Zhi He6Zifan Li7Jun Wu8Zhe Zhao9Guman Duan10Xiaodan Sun11Lingyun Zhao12Yongwei Pan13Xiumei Wang14State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua UniversityState Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua UniversityState Key Laboratory for Performance and Structure Safety of Petroleum Tubular Goods and Equipment Materials, Tubular Goods Research Institute of CNPCState Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua UniversityState Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua UniversityState Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua UniversityState Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua UniversityState Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua UniversityAerospace Information Research Institute, Chinese Academy of SciencesDepartment of Orthopedics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua UniversityDepartment of Orthopedics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua UniversityState Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua UniversityState Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua UniversityDepartment of Orthopedics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua UniversityState Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua UniversityAbstract Chronic allodynia stemming from peripheral stump neuromas can persist for extended periods, significantly compromising patients’ quality of life. Conventional managements for nerve stumps have demonstrated limited effectiveness in ensuring their orderly termination. In this study, we present a spatially confined conduit strategy, designed to enhance the self-organization of regenerating nerves after truncation. This innovative approach elegantly enables the autonomous slowing of axonal outgrowth in response to the gradually constricting space, concurrently suppressing neuroinflammation through YAP-mediated mechanotransduction activation. Meanwhile, the decelerating axons exhibit excellent alignment and remyelination, thereby helping to prevent failure modes in nerve self-organization, such as axonal twisting in congested regions and overgrowth beyond the conduit’s capacity. Additionally, proteins associated with mechanical allodynia, including TRPA1 and CGRP, exhibit a gradual reduction in expression as spatial constraints tighten, a trend inversely validated by the administration of the YAP-targeted inhibitor Verteporfin. This spatially confined conduit strategy significantly alleviates allodynia, thus preventing autotomy behavior and reducing pain-induced gait alterations.https://doi.org/10.1038/s41467-024-55118-9 |
| spellingShingle | Xiaobin Luo Jia Yang Yonggang Zhao Toshitatsu Nagayasu Junlin Chen Peilun Hu Zhi He Zifan Li Jun Wu Zhe Zhao Guman Duan Xiaodan Sun Lingyun Zhao Yongwei Pan Xiumei Wang Engineering spatially-confined conduits to tune nerve self-organization and allodynic responses via YAP-mediated mechanotransduction Nature Communications |
| title | Engineering spatially-confined conduits to tune nerve self-organization and allodynic responses via YAP-mediated mechanotransduction |
| title_full | Engineering spatially-confined conduits to tune nerve self-organization and allodynic responses via YAP-mediated mechanotransduction |
| title_fullStr | Engineering spatially-confined conduits to tune nerve self-organization and allodynic responses via YAP-mediated mechanotransduction |
| title_full_unstemmed | Engineering spatially-confined conduits to tune nerve self-organization and allodynic responses via YAP-mediated mechanotransduction |
| title_short | Engineering spatially-confined conduits to tune nerve self-organization and allodynic responses via YAP-mediated mechanotransduction |
| title_sort | engineering spatially confined conduits to tune nerve self organization and allodynic responses via yap mediated mechanotransduction |
| url | https://doi.org/10.1038/s41467-024-55118-9 |
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