Rectifying disorder of extracellular matrix to suppress urethral stricture by protein nanofilm-controlled drug delivery from urinary catheter

Abstract Urethral stricture, which afflicts both patients and urologists, involves excessive deposition of extracellular matrix in the submucosal and periurethral tissues. Although various anti-fibrotic drugs have been applied to urethral stricture by irrigation or submucosal injection, their clinical feasibility and effectiveness are limited. To prevent stricture after endoscopic therapy, urethroplasty, and traumatic catheterization, we designed a protein-based nanofilm-controlled drug delivery system and assembled it on the catheter to target inordinate extracellular matrix deposition. This approach is simple to manufacture and simultaneously integrates excellent anti-biofilm property into a urinary catheter in one step. Stable and controlled drug delivery over tens of days ensures optimal efficacy and negligible side effects. Anti-fibrotic catheters maintain extracellular matrix homeostasis by reducing fibroblast-derived collagen production and enhancing metalloproteinase 1-induced collagen degradation in a rabbit model of urethral injury, resulting in the greatest improvement in lumen stenosis than other topical therapies for urethral stricture prevention. Such biocompatible coating with antibacterial contamination and sustained-drug-release functionality could also be an advanced paradigm for a range of biomedical applications.