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Duran, Marcela
;
Camargo, Gabriela Cardoso de Arruda
;
Oliveira, Gabriela
;
Alonso, Joao Carlos Cardoso
;
Alves, Paulo Cesar Martins
;
Volpe, Bruno Bosh
;
Roston, Jose Ronaldo de Castro
;
Dertkigil, Sergio San Juan
;
Luzo, Angela Cristina Malheiros
;
Duran, Nelson
;
Favaro, Wagner Jose
Número total de Autores: 11
|
| Tipo de documento: | Artigo Científico |
| Fonte: | TISSUE & CELL; v. 98, p. 14-pg., 2026-02-26. |
| Resumo | |
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(epsilon-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. (AU) | |
| Processo FAPESP: | 18/10052-1 - Novas Abordagens Terapêuticas para o Câncer de Bexiga Não-Músculo Invasivo (CBNMI): Uso Intravesical do Modificador de Resposta Biológica OncoTherad e Sua Associação com o Plasma Rico em Plaquetas (PRP) |
| Beneficiário: | Wagner José Fávaro |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/18053-0 - Estudo comparativo de tratamentos imunoterápicos para câncer de ovário quimicamente induzido em ratas |
| Beneficiário: | Gabriela de Oliveira |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 14/12047-4 - Mecanismos e efeitos do imunomodulador P-MAPA no tratamento dos cânceres de próstata e não-músculo invasivo da bexiga urinária: interfaces entre metabolismo energético, balanço oxidativo, angiogênese e via de sinalização dos receptores toll-like |
| Beneficiário: | Wagner José Fávaro |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 14/50906-9 - INCT 2014: em Materiais Complexos Funcionais (INOMAT) |
| Beneficiário: | Fernando Galembeck |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 17/19186-8 - Avaliação da diferenciação celular das células mesenquimais estromais adiposas após a utilização de scaffold de óxido de grafeno em reparo de lesões urológicas |
| Beneficiário: | Leandro das Neves Bernardi |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 14/08349-5 - Células-tronco e óxido de grafeno: desafio de desenvolvimento de um material biocompatível no reparo de lesões urológicas |
| Beneficiário: | Marcela Andrea Durán Haun Senatore |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |