A dynamically phase-adaptive regulating hydrogel promotes ultrafast anti-fibrotic wound healing
Abstract Achieving rapid and scar-free wound repair is a key goal in the field of regenerative medicine. Herein, a dynamically Schiff base-crosslinked hydrogel (F/R gel) with phase-adaptive regulating functions is constructed to integratedly promote rapid re-epithelization with suppressed scars on c...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58987-w |
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| author | Fan Zhang Haijuan Zhang Shengfu Wang Mingying Gao Kaiyi Du Xinyuan Chen Yang Lu Qianqian Hu Anyu Du Shenghu Du Jian Wang Keqing Shi Zimiao Chen Zhuo Li Zhenglin Li Jian Xiao |
| author_facet | Fan Zhang Haijuan Zhang Shengfu Wang Mingying Gao Kaiyi Du Xinyuan Chen Yang Lu Qianqian Hu Anyu Du Shenghu Du Jian Wang Keqing Shi Zimiao Chen Zhuo Li Zhenglin Li Jian Xiao |
| author_sort | Fan Zhang |
| collection | DOAJ |
| description | Abstract Achieving rapid and scar-free wound repair is a key goal in the field of regenerative medicine. Herein, a dynamically Schiff base-crosslinked hydrogel (F/R gel) with phase-adaptive regulating functions is constructed to integratedly promote rapid re-epithelization with suppressed scars on chronic infected wounds. Specifically, the gel effectively eliminates multidrug-resistant bacterial biofilm at infection stage via antimicrobial activity of ε-polylysine firstly dissociated from hydrogel matrix in infectious microenvironment, and interrupts the severe oxidative stress-inflammation cycle at wound site by the released ceria nanozyme, thus stimulating a pro-regenerative environment to ensure tissue repair. Subsequently, fibroblast growth factor/c-Jun siRNA co-loaded microcapsules gradually disintegrate to release drugs, facilitating neoangiogenesis and cell proliferation but simultaneously blocking c-Jun overexpression for fibrotic scar suppression. Notably, the F/R gel facilitates normal-like skin regeneration with no perceptible scars formed on infected male mouse wound and female rabbit ear wound models. Our work offers a promising regenerative strategy emphasizing immunomodulatory and fibroblast subtype modulation for scarless wound repair. |
| format | Article |
| id | doaj-art-b424a49cd5d8431bb177e6334b7c0e48 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b424a49cd5d8431bb177e6334b7c0e482025-08-20T02:17:58ZengNature PortfolioNature Communications2041-17232025-04-0116112010.1038/s41467-025-58987-wA dynamically phase-adaptive regulating hydrogel promotes ultrafast anti-fibrotic wound healingFan Zhang0Haijuan Zhang1Shengfu Wang2Mingying Gao3Kaiyi Du4Xinyuan Chen5Yang Lu6Qianqian Hu7Anyu Du8Shenghu Du9Jian Wang10Keqing Shi11Zimiao Chen12Zhuo Li13Zhenglin Li14Jian Xiao15Department of Wound healing, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Wound healing, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Wound healing, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Wound healing, The First Affiliated Hospital of Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical UniversityDepartment of Wound healing, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Wound healing, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Wound healing, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Wound healing, The First Affiliated Hospital of Wenzhou Medical UniversityKey Laboratory of Functional Inorganic Materials Chemistry (Ministry of Education), School of Chemistry and Materials Science, Heilongjiang UniversityDepartment of Wound healing, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Wound healing, The First Affiliated Hospital of Wenzhou Medical UniversityAbstract Achieving rapid and scar-free wound repair is a key goal in the field of regenerative medicine. Herein, a dynamically Schiff base-crosslinked hydrogel (F/R gel) with phase-adaptive regulating functions is constructed to integratedly promote rapid re-epithelization with suppressed scars on chronic infected wounds. Specifically, the gel effectively eliminates multidrug-resistant bacterial biofilm at infection stage via antimicrobial activity of ε-polylysine firstly dissociated from hydrogel matrix in infectious microenvironment, and interrupts the severe oxidative stress-inflammation cycle at wound site by the released ceria nanozyme, thus stimulating a pro-regenerative environment to ensure tissue repair. Subsequently, fibroblast growth factor/c-Jun siRNA co-loaded microcapsules gradually disintegrate to release drugs, facilitating neoangiogenesis and cell proliferation but simultaneously blocking c-Jun overexpression for fibrotic scar suppression. Notably, the F/R gel facilitates normal-like skin regeneration with no perceptible scars formed on infected male mouse wound and female rabbit ear wound models. Our work offers a promising regenerative strategy emphasizing immunomodulatory and fibroblast subtype modulation for scarless wound repair.https://doi.org/10.1038/s41467-025-58987-w |
| spellingShingle | Fan Zhang Haijuan Zhang Shengfu Wang Mingying Gao Kaiyi Du Xinyuan Chen Yang Lu Qianqian Hu Anyu Du Shenghu Du Jian Wang Keqing Shi Zimiao Chen Zhuo Li Zhenglin Li Jian Xiao A dynamically phase-adaptive regulating hydrogel promotes ultrafast anti-fibrotic wound healing Nature Communications |
| title | A dynamically phase-adaptive regulating hydrogel promotes ultrafast anti-fibrotic wound healing |
| title_full | A dynamically phase-adaptive regulating hydrogel promotes ultrafast anti-fibrotic wound healing |
| title_fullStr | A dynamically phase-adaptive regulating hydrogel promotes ultrafast anti-fibrotic wound healing |
| title_full_unstemmed | A dynamically phase-adaptive regulating hydrogel promotes ultrafast anti-fibrotic wound healing |
| title_short | A dynamically phase-adaptive regulating hydrogel promotes ultrafast anti-fibrotic wound healing |
| title_sort | dynamically phase adaptive regulating hydrogel promotes ultrafast anti fibrotic wound healing |
| url | https://doi.org/10.1038/s41467-025-58987-w |
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