Development of a Janus nanofibrous patch with antibacterial and anti-oxidative properties for urethral regeneration

Background: Urethral injury is the primary cause of urinary tract stenosis and hydronephrosis. Limited by the common drawbacks of autografts, the clinical treatment of urethral injury remains challenging. In recent years, biocompatible and biodegradable biomaterials (BBBs) are emerging as a potential substitute for autografts to upgrade the research paradigms of regenerative medicine. However, ideal BBBs for urethral regeneration have rarely been reported. Methods: A Janus nanofibrous PC/SMC patch composed of the outer layer of PLLA/CRRI-3 nanofibers and the inner layer of SF/MCe heterojunction nanofibers were first fabricated. Its antibacterial and antioxidant properties were assessed. After passing biosafety evaluation, the patch's efficacy in repairing urethral defects was evaluated using a rabbit model, with repair outcomes analyzed via histological staining. Results: PC/SMC patch not only inhibits bacterial proliferation and survival via the release of the antibacterial peptide CRRI-3, but it also relieves oxidation stress and promotes tissue regeneration by the nanozyme-like activities of the MCe heterojunction. The biocompatibility of PC/SMC patch has met the general requirements for Class-III medical devices. The application in vivo was evaluated using a urethral injury model of rabbits. The results showed that PC/SMC patch could improve urethral regeneration and prevent urethral stricture via multiple mechanisms, including promoting re-epithelialization, cell proliferation and M2 macrophage polarization, and inhibiting of fibrosis and scar formation. Conclusion: The PC/SMC nanofibrous patch has good biocompatibility and antibacterial properties, and can effectively promote the regeneration and repair of urethral tissue.