Rectifying disorder of extracellular matrix to suppress urethral stricture by protein nanofilm-controlled drug delivery from urinary catheter.
Juanhua TianDelai FuYongchun LiuYibing GuanShuting MiaoYuquan XueKe ChenShanlong HuangYanfeng ZhangLi XueTie ChongPeng YangPublished in: Nature communications (2023)
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.
Keyphrases
- extracellular matrix
- urinary incontinence
- drug delivery
- drug release
- endoscopic submucosal dissection
- ultrasound guided
- pseudomonas aeruginosa
- staphylococcus aureus
- wound healing
- systemic sclerosis
- systematic review
- ejection fraction
- cancer therapy
- idiopathic pulmonary fibrosis
- small molecule
- risk assessment
- peritoneal dialysis
- protein protein
- climate change
- prognostic factors
- escherichia coli
- physical activity
- patient reported outcomes
- biofilm formation
- human health
- endothelial cells
- amino acid
- binding protein
- anti inflammatory