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

Juanhua Tian, Delai Fu, Yongchun Liu, Yibing Guan, Shuting Miao, Yuquan Xue, Ke Chen, Shanlong Huang, Yanfeng Zhang, Li Xue, Tie Chong () and Peng Yang ()
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Juanhua Tian: The Second Affiliated Hospital of Xi’an Jiaotong University
Delai Fu: The Second Affiliated Hospital of Xi’an Jiaotong University
Yongchun Liu: Shaanxi Normal University
Yibing Guan: The First Affiliated Hospital of Zhengzhou University
Shuting Miao: Shaanxi Normal University
Yuquan Xue: The Second Affiliated Hospital of Xi’an Jiaotong University
Ke Chen: Beihang University (BUAA)
Shanlong Huang: The Second Affiliated Hospital of Xi’an Jiaotong University
Yanfeng Zhang: Xi’an Jiaotong University
Li Xue: The Second Affiliated Hospital of Xi’an Jiaotong University
Tie Chong: The Second Affiliated Hospital of Xi’an Jiaotong University
Peng Yang: Shaanxi Normal University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Urethral stricture secondary to urethral injury, afflicting both patients and urologists, is initiated by 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. Here, to target the pathological state of the extracellular matrix, we design a protein-based nanofilm-controlled drug delivery system and assemble it on the catheter. This approach, which integrates excellent anti-biofilm properties with stable and controlled drug delivery for tens of days in one step, ensures optimal efficacy and negligible side effects while preventing biofilm-related infections. In a rabbit model of urethral injury, the anti-fibrotic catheter maintains extracellular matrix homeostasis by reducing fibroblast-derived collagen production and enhancing metalloproteinase 1-induced collagen degradation, resulting in a greater improvement in lumen stenosis than other topical therapies for urethral stricture prevention. Such facilely fabricated biocompatible coating with antibacterial contamination and sustained-drug-release functionality could not only benefit populations at high risk of urethral stricture but also serve as an advanced paradigm for a range of biomedical applications.

Date: 2023
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DOI: 10.1038/s41467-023-38282-2

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