Biomimetic multilayered hydrogel scaffold with dual cell types and mesh support for urethral reconstruction.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Urethral strictures and hypospadias remain major challenges in urology, with current treatments limited by donorsite morbidity, graft shrinkage, and poor long-term outcomes. To address these limitations, we developed a biomimetic multilayered hydrogel scaffold with dual cell types and mesh reinforcement for urethral reconstruction. The construct combined predifferentiated buccal mucosa cells and adipose-derived mesenchymal stem cells within a gelatin methacrylate-silk fibroin (GelMA-SF) hydrogel supported by electrowritten and electrospun polymeric meshes, designed to reproduce both epithelial and smooth muscle layers of the native urethra. Implanted into the rabbit urethra and followed for 12 weeks, the scaffold showed favorable integration with early but transient immune activation, preservation of systemic stability, and maintenance of urethral lumen architecture. Histological evaluation revealed the formation of a stratified urothelium and organized smooth muscle bundles with limited fibrosis, highlighting the scaffold's potential to support functional urethral regeneration and serve as an alternative to graft-based urethroplasty.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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