Fabrication and Characterization of Bioengineered Sandwich Model Scaffold for Urethral Stricture Reconstruction.

Urethral stricture remains a challenging clinical condition, particularly in patients with long or complex defects where suitable donor tissue is limited. Tissue engineering offers a promising alternative through the development of biomimetic scaffolds capable of restoring urethral structure and function. In this study, we fabricated a sandwich nanofibrous scaffold based on polyglycolic acid (PGA) and decellularized urethral extracellular matrix (uECM) using a sandwich design (uECM/PGA/uECM) and compared it with PGA and mix (PGA-uECM) scaffolds. Successful decellularization was confirmed by histological and molecular analyses, demonstrating effective removal of cellular components while preserving ECM architecture. Structural characterization revealed high porosity, enhanced hydrophilicity, favorable swelling behavior, and controlled degradation in ECM-containing scaffolds. The uECM/PGA/uECM construct exhibited superior mechanical strength while maintaining suitable elasticity for urethral applications. Biological evaluation showed significantly improved endothelial cell adhesion, cell viability, and migration in ECM-integrated scaffolds compared with PGA alone. In vivo implantation demonstrated excellent biocompatibility, absence of adverse inflammatory responses, and evident neovascularization. Overall, the sandwich uECM/PGA/uECM scaffold combines mechanical stability with bioactive functionality, highlighting its potential as a promising candidate for urethral tissue regeneration.