Dynamically Urethra-Adapted and Obligations-Oriented Trilayer Hydrogels Integrate Scarless Urethral Repair

In urethral damage/stricture prevention, open and harsh urethral microenvironments as well as the isotropic compression and swelling properties of exogenous implants render urethral repair intractable. Here, a dynamically urethra-adapted and obligation-oriented trilayer hydrogel was constructed for integrated scarless urethral repair. The bottom diethylacrylamide -hydroxyethylacrylamide (D-H) hydrogel featuring high anti-fouling performance, the upper swellable verteporfin (VP)-loaded N,N'-methylenebisacrylamide-poly (N-isopropylacrylamide) (BP) with a hydrophilic Janus surface promote urethral regeneration through expediting cell migration and proliferation and the rigid and water-resistant Zein middle layer opposes urine voiding-arised BP shedding and resists inward BP swelling-driven urethral occlusion and urine permeation. Importantly, systematic proteomic and genomic analyses revealed that such hydrogel scaffolds expedite regeneration, alleviate inflammation and regulate extracellular matrix secretion, where BP swelling-induced outgrowth for fibrosis and scar formation is significantly inhibited by VP through the blockade of the scar-associated YAP signaling pathway. These microenvironment-adaptable design concepts provide a rationale for engineering urethral regeneration scaffolds. We used a newly designed urethral repair stent for in vivo repair and reconstruction, and analyzed the mechanism by which the new urethral stent promotes urethral repair through sequencing