Silk fibroin based in situ antibacterial hydrogel for urethral defect repair

Due to urethral strictures post hypospadias and bacterial infection, desirable urethral repair remains a great challenge in clinic. In situ formed hydrogels have shown great capacity on promoting tissue regeneration and can be delivered to fill irregularities in injury sites. In this study, we developed an in situ antibacterial hydrogel system (SFPLMA) by combining methacrylated silk fibroin (SFMA) and methacrylated polylysine (PLMA). The rapid photo-crosslinking of the methacryloyl moieties in SFMA and PLMA enabled the SFPLMA hydrogel to effectively fill the congenital irregularities associated with hypospadias, while exhibiting excellent biocompatibility and appropriate mechanical properties. Notably, the introduction of PLMA into the hydrogel system not only conferred promising antimicrobial efficacy against pathogens such as Escherichia coli and Staphylococcus aureus, thereby reducing the risk of post-surgical infections, but also enhanced the capacity for promoting axonal regrowth. Furthermore, treatment with the SFPLMA hydrogel resulted in a significant reduction in strictures and fistulas, alongside improved regeneration of urethral epithelium and smooth muscle in a rabbit model. Overall, we present a multifunctional hydrogel system that holds promise as a valuable tool in urethral reconstructive therapy.