Work

In vivo evaluation of a chitosan/PLGA/chitosan composite versus monolayer PLGA electrospun scaffold for dorsal onlay urethroplasty: a controlled study in rabbits

Year: 2026

Type: article

Abstract: Background Autologous buccal mucosa grafts remain the surgical standard for complex urethral stricture repair but are limited by donor-site morbidity, restricted tissue availability, and inadequate graft vascularization. Acellular scaffolds, whether synthetic or natural, can offer either mechanical or biological signals but not both. Hybrid composite scaffolds combining synthetic structural support with natural bioactive polymers have been proposed to address this limitation. In this work, a trilayer scaffold consisting of a poly(lactide-co-glycolide) (PLGA) core with chitosan on either side was assessed in vivo in a controlled rabbit dorsal onlay urethroplasty model. Methods Twenty-four male New Zealand White rabbits were allocated 1:1:1 to dorsal onlay urethroplasty with the trilayer scaffold, a monolayer PLGA scaffold, or sham control, using weight-stratified allocation. The primary endpoint was vessel density on CD31-stained sections at 12 weeks; secondary endpoints included tissue thickness, fibrosis, smooth muscle content, re-epithelialization, inflammatory cell scores, and urethrography, assessed by blinded observers. Results Vessel density in the trilayer was intermediate between sham (highest) and the monolayer (lowest), with significant overall between-group variation ( p = 0.008); the trilayer did not significantly differ from the monolayer ( p = 0.248). Macrophage scores showed a non-significant trend toward lower values in the trilayer than in the monolayer ( p = 0.062), and multinucleated giant-cell scores were significantly higher in both scaffold groups than in sham ( p = 0.026), consistent with a foreign-body response. Vessel density was inversely correlated with tissue thickness and fibrosis, defining a coherent host-response signature. Re-epithelialization was complete across groups without ulceration features on histological review. Retrograde urethrography demonstrated preserved patency in all 23 animals completing follow-up, with no ≥50% stricture observed. Conclusion The trilayer scaffold was feasible to implant and well tolerated in a rabbit dorsal onlay urethroplasty model, supporting tissue regeneration with preserved urethral patency. The trilayer did not significantly increase vessel density over the monolayer at 12 weeks, although a non-significant trend toward lower macrophage scores was observed in the trilayer group. These findings refine rather than confirm the development hypothesis and motivate future studies with earlier endpoints, mechanical-modulus tuning, and alternative polymer ratios.

Source: Frontiers in Bioengineering and Biotechnology

DOI: 10.3389/fbioe.2026.1891449