Urethral stricture is a common and challenging urological disorder marked by fibrotic narrowing of the urethral lumen, which leads to urinary obstruction and diminished quality of life. Current surgical options are associated with high recurrence rates and limited tissue regeneration.
To address these limitations, we developed a multifunctional therapeutic platform integrating a nanostructured graphene oxide scaffold functionalized with polyethylene glycol and poly(ε-caprolactone) (GO/PEG-NH₂/PCL), seeded with human adipose-derived mesenchymal stem cells (ADMSCs) and combined with oral sildenafil. In vitro analyses confirmed scaffold biocompatibility and sustained ADMSC viability, as assessed by fluorescence microscopy, with preservation of spindle-shaped morphology at low GO concentrations. In vivo, we employed a rabbit model of surgically induced urethral stricture and compared four groups: Control, Stricture, Scaffold+ADMSCs, and Scaffold+ADMSCs+Sildenafil. Ten weeks post-treatment, histological and immunohistochemical evaluations revealed that the combinatorial approach significantly restored urethral architecture and lumen patency. This was accompanied by reduced collagen deposition, enhanced smooth muscle organization, and upregulated expression of epithelial differentiation markers (Uroplakin, Desmocollin) and progenitor markers (CD117), alongside downregulation of the fibrotic mediator MMP2. Quantitative scoring indicated that fibrosis and inflammation levels in the treated group approached those of normal tissue. The GO/PEG-NH₂/PCL nanoscaffold supported ADMSC adhesion and differentiation, while sildenafil provided complementary antifibrotic and angiogenic modulation. Together, these findings support this composite system as a promising regenerative strategy for functional urethral repair, offering translational relevance for the management of complex urethral strictures.
Tissue & cell. 2025 Oct 02 [Epub ahead of print]
Marcela Durán, Gabriela Cardoso de Arruda Camargo, Gabriela Oliveira, João Carlos Cardoso Alonso, Paulo César Martins Alves, Bruno Bosh Volpe, José Ronaldo de Castro Roston, Sergio San Juan Dertkigil, Angela Cristina Malheiros Luzo, Nelson Durán, Wagner José Fávaro
Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), Universidade Estadual de Campinas (UNICAMP), Campinas City, São Paulo State, Brazil., Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), Universidade Estadual de Campinas (UNICAMP), Campinas City, São Paulo State, Brazil; Paulínia Municipal Hospital, Paulínia City, São Paulo State, Brazil., Center for Investigation in Pediatrics, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas City, São Paulo State, Brazil., Department of Radiology and Oncology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas City, São Paulo State, Brazil., Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), Universidade Estadual de Campinas (UNICAMP), Campinas City, São Paulo State, Brazil; Nanomedicine Research Unit (Nanomed), Federal University of ABC (UFABC), Santo André City, São Paulo State, Brazil., Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), Universidade Estadual de Campinas (UNICAMP), Campinas City, São Paulo State, Brazil. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41043313