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, Kun Zhang, Kun Zhang, Kun Zhang
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. In urethral damage, exogenous implants designed for urethral repair are hindered by the open and harsh urethral microenvironments and the isotropic compression and swelling properties of the material. Here, Yang et al. develop a tri-layer hydrogel with anti-fouling and low-swelling properties for scarless urethral repair.