Dynamically urethra-adapted and obligations-oriented trilayer hydrogels integrate scarless urethral repair

Ming Yang, Maocheng Zuo, Ranxing Yang, Kaile Zhang, Ruonan Jia, Binxu Yin, Ying Wang, Meng Liu, Wenzhuo Fang, Huaijuan Guo, Yangwang Jin, Qiang Fu () and Kun Zhang ()
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Ming Yang: Shanghai Jiaotong University
Maocheng Zuo: University of Electronic Science and Technology of China
Ranxing Yang: Shanghai Jiaotong University
Kaile Zhang: Shanghai Jiaotong University
Ruonan Jia: University of Electronic Science and Technology of China
Binxu Yin: University of Electronic Science and Technology of China
Ying Wang: Shanghai Jiaotong University
Meng Liu: Shanghai Jiaotong University
Wenzhuo Fang: Shanghai Jiaotong University
Huaijuan Guo: University of Electronic Science and Technology of China
Yangwang Jin: Shanghai Jiaotong University
Qiang Fu: Shanghai Jiaotong University
Kun Zhang: University of Electronic Science and Technology of China

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-62851-2

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