Sustained drug-releasing hydrogel coatings for ureteral stents to prevent iatrogenic injury-induced ureteral stricture

Iatrogenic injury-induced ureteral stricture often occurs during the treatment of ureteral disorders, and can lead to serious consequences requiring further medical care. The stricture prevention requires effective strategies to inhibit fibrosis, reduce oxidative stress and inflammatory responses during the insertion of ureteral stents. Here, we explore the anti-stricture effects of commercial ureteral stents modified with hydrogel coatings, which contain functionalized poly (lactic-co-glycolic acid) (fPLGA) nanoparticles (NPs) loaded with the drug of pirfenidone (PFD). The polyacrylamide (PAM) hydrogel coatings are robustly grafted onto the polyurethane (PU) stent using the surface initiated radical polymerization, while PFD-fPLGA NPs decorated with acryloyl functional groups were securely anchored in PAM networks during the reaction. This NPs-hydrogel coating possesses multiple advantages, such as high hydrophilicity and low elastic modulus, which can reduce frictional force and alleviate irritation during stent insertion. The hydrogel coating exhibits excellent stability, with only 45 % mass loss after being immersed in an artificial urine environment for 3 months, and also demonstrates good biocompatibility and antifouling performance. More importantly, the slow degradation of fPLGA leads to sustained delivery of antifibrotic PFD, with a cumulative drug release rate of approximately 82 % within 12 weeks. These combined benefits contribute to the prevention of ureteral strictures after iatrogenic injury, as evidenced by inhibited fibrosis, alleviated oxidative stress, and suppressed inflammatory response in both vitro and in vivo studies.