Constructing a biomimetic ECM protective barrier: a strategic interface design for urethral repair to mitigate foreign body reaction.

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 reconstruction often fails due to the foreign body reaction (FBR) triggered by the graft, leading to chronic inflammation, fibrosis, and lumen obstruction. To address this challenge, we developed an innovative strategy: a 3D-printed polylactic acid (PLA) scaffold was pre-implanted subcutaneously for 14 days to recruit host-derived fibroblasts, monocytes, and adipose-derived stem cells. These cells secreted a biomimetic extracellular matrix (ECM) rich in collagen, elastin, and glycosaminoglycans (GAGs), resulting in a proteoglycan (PG)-enriched, bioactive tissue-engineered urethral graft (TEUG). This PG-rich matrix interface, characterized by a high density of proteoglycans and glycosaminoglycans that mimic the native urethral microenvironment, closely mimicked native urethral tissue in terms of hydrophilicity, surface topography, roughness, and mechanical compliance. More importantly, compared with commercially available small intestinal submucosa (SIS)-based grafts, it significantly enhanced urothelial cell adhesion, spreading, and oriented spatial organization, effectively recapitulating the functional role of the native PG matrix. In a rabbit anterior urethral replacement model, TEUG not only provided essential structural support and elasticity but also maintained the tubular architecture and physiological distensibility of the urethra to accommodate pressure change

Evidence level

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

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