Abstract

Urethral stricture, a fibrotic condition causing lumen narrowing, lacks effective pharmacological treatments, with autologous grafts facing donor-site limitations. Tissue engineering strategies, particularly anisotropic hydrogels, offer promising alternatives but remain unexplored in urethral repair. Here, we developed a multifunctional anisotropic polyvinyl alcohol/tannic acid (APVA/TA) hydrogel via mechanical training and hydrogen-bond crosslinking for urethral reconstruction. The APVA/TA hydrogel exhibited enhanced crystallinity, mechanical strength, and anti-swelling properties, with TA conferring potent antioxidant and broad-spectrum antibacterial activity. In vitro, TA suppressed LPS-induced inflammatory responses, while the anisotropic structure synergistically promoted endothelial cell migration and angiogenesis. In a rabbit urethral stricture model, the APVA/TA2.5 hydrogel significantly reduced stricture recurrence (12.6% obstruction rate) and facilitated improved repair through enhanced epithelial regeneration (pan-CK), vascularization (CD31), and smooth muscle regeneration (α-SMA). This study demonstrates the dual role of anisotropic structure and TA in enabling functional urethral reconstruction, providing a novel tissue-engineered solution for stricture management.