Dynamically urethra-adapted and obligations-oriented trilayer hydrogels integrate scarless urethral repair
Abstract In urethral damage/stricture prevention, open and harsh urethral microenvironments and isotropic compression and swelling properties of exogenous implants render urethral repair intractable. Here a dynamically urethra-adapted and obligations-oriented trilayer hydrogel was engineered to inte...
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| Format: | Article |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62851-2 |
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| author | Ming Yang Maocheng Zuo Ranxing Yang Kaile Zhang Ruonan Jia Binxu Yin Ying Wang Meng Liu Wenzhuo Fang Huaijuan Guo Yangwang Jin Qiang Fu Kun Zhang |
| author_facet | Ming Yang Maocheng Zuo Ranxing Yang Kaile Zhang Ruonan Jia Binxu Yin Ying Wang Meng Liu Wenzhuo Fang Huaijuan Guo Yangwang Jin Qiang Fu Kun Zhang |
| author_sort | Ming Yang |
| collection | DOAJ |
| description | Abstract In urethral damage/stricture prevention, open and harsh urethral microenvironments and isotropic compression and swelling properties of exogenous implants render urethral repair intractable. Here a dynamically urethra-adapted and obligations-oriented trilayer hydrogel was engineered to integrate scarless urethral repair. Therein, the diethylacrylamide-hydroxyethylacrylamide (HEAm) (D-H) hydrogel layer featuring high anti-fouling performance prevent adhesions of bacterial and blood cells, and its poor swelling avoids urethra occlusion. The upper swellable and verteporfin (VP)-loaded N,N’-methylenebisacrylamide-poly (N-isopropylacrylamide) (BP) layer encourages urethra regeneration through expediting cell migration and proliferation. The rigid and water-resistant Zein middle layer opposes urine voiding-arised BP shedding, urethral diastole/contraction, inward BP swelling-arised urethra occlusion and urine permeation. Importantly, systematic proteomic and genomic analysis reveals that such hydrogel scaffolds expedite epithelial & vascular regenerations, attenuate tight cell junction, oppose inflammation microenvironment and regulate extracellular matrix secretion and metabolism to realize integrated urethral repair. The microenvironment-adaptable design concepts provide reliable rationales to engineer urethral regeneration scaffolds. |
| format | Article |
| id | doaj-art-23b4964bb8a84be1950cc01770266dcc |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-23b4964bb8a84be1950cc01770266dcc2025-08-20T04:02:56ZengNature PortfolioNature Communications2041-17232025-08-0116111710.1038/s41467-025-62851-2Dynamically urethra-adapted and obligations-oriented trilayer hydrogels integrate scarless urethral repairMing Yang0Maocheng Zuo1Ranxing Yang2Kaile Zhang3Ruonan Jia4Binxu Yin5Ying Wang6Meng Liu7Wenzhuo Fang8Huaijuan Guo9Yangwang Jin10Qiang Fu11Kun Zhang12Department of Urology, affiliated Sixth People’s Hospital, Shanghai Jiaotong UniversityDepartment of Orthopedics and Central Laboratory, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaDepartment of Urology, affiliated Sixth People’s Hospital, Shanghai Jiaotong UniversityDepartment of Urology, affiliated Sixth People’s Hospital, Shanghai Jiaotong UniversityDepartment of Orthopedics and Central Laboratory, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaDepartment of Orthopedics and Central Laboratory, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaDepartment of Urology, affiliated Sixth People’s Hospital, Shanghai Jiaotong UniversityDepartment of Urology, affiliated Sixth People’s Hospital, Shanghai Jiaotong UniversityDepartment of Urology, affiliated Sixth People’s Hospital, Shanghai Jiaotong UniversityDepartment of Orthopedics and Central Laboratory, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaDepartment of Urology, affiliated Sixth People’s Hospital, Shanghai Jiaotong UniversityDepartment of Urology, affiliated Sixth People’s Hospital, Shanghai Jiaotong UniversityDepartment of Orthopedics and Central Laboratory, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaAbstract In urethral damage/stricture prevention, open and harsh urethral microenvironments and isotropic compression and swelling properties of exogenous implants render urethral repair intractable. Here a dynamically urethra-adapted and obligations-oriented trilayer hydrogel was engineered to integrate scarless urethral repair. Therein, the diethylacrylamide-hydroxyethylacrylamide (HEAm) (D-H) hydrogel layer featuring high anti-fouling performance prevent adhesions of bacterial and blood cells, and its poor swelling avoids urethra occlusion. The upper swellable and verteporfin (VP)-loaded N,N’-methylenebisacrylamide-poly (N-isopropylacrylamide) (BP) layer encourages urethra regeneration through expediting cell migration and proliferation. The rigid and water-resistant Zein middle layer opposes urine voiding-arised BP shedding, urethral diastole/contraction, inward BP swelling-arised urethra occlusion and urine permeation. Importantly, systematic proteomic and genomic analysis reveals that such hydrogel scaffolds expedite epithelial & vascular regenerations, attenuate tight cell junction, oppose inflammation microenvironment and regulate extracellular matrix secretion and metabolism to realize integrated urethral repair. The microenvironment-adaptable design concepts provide reliable rationales to engineer urethral regeneration scaffolds.https://doi.org/10.1038/s41467-025-62851-2 |
| spellingShingle | Ming Yang Maocheng Zuo Ranxing Yang Kaile Zhang Ruonan Jia Binxu Yin Ying Wang Meng Liu Wenzhuo Fang Huaijuan Guo Yangwang Jin Qiang Fu Kun Zhang Dynamically urethra-adapted and obligations-oriented trilayer hydrogels integrate scarless urethral repair Nature Communications |
| title | Dynamically urethra-adapted and obligations-oriented trilayer hydrogels integrate scarless urethral repair |
| title_full | Dynamically urethra-adapted and obligations-oriented trilayer hydrogels integrate scarless urethral repair |
| title_fullStr | Dynamically urethra-adapted and obligations-oriented trilayer hydrogels integrate scarless urethral repair |
| title_full_unstemmed | Dynamically urethra-adapted and obligations-oriented trilayer hydrogels integrate scarless urethral repair |
| title_short | Dynamically urethra-adapted and obligations-oriented trilayer hydrogels integrate scarless urethral repair |
| title_sort | dynamically urethra adapted and obligations oriented trilayer hydrogels integrate scarless urethral repair |
| url | https://doi.org/10.1038/s41467-025-62851-2 |
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