In vivo evaluation of a chitosan/PLGA/chitosan composite versus monolayer PLGA electrospun scaffold for dorsal onlay urethroplasty: a controlled study in rabbits
7 affiliations
- 1Department of Renal Surgery and Urology, Aalborg University Hospital , ,
- 2Materials Science and Engineering Group, Department of Materials and Production, Aalborg University , ,
- 3Department of Pathology, Aalborg University Hospital , ,
- 4Department of Clinical Medicine, Aalborg University , ,
- 5Global Andrology Forum, Global Andrology Foundation , , ,
- 6Department of Pediatric Urology, Sidra Medicine and Weill Cornell Medical College , ,
- 7Regenerative Medicine, Department of Health Science and Technology, Faculty of Medicine, Aalborg University , ,
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.
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BibTeX
@article{mahdi2026vivo,
title = {{In vivo evaluation of a chitosan/PLGA/chitosan composite versus monolayer PLGA electrospun scaffold for dorsal onlay urethroplasty: a controlled study in rabbits}},
author = {Marco Bassam Mahdi and Fatemeh Mohtaram and Rikke Nørresø Haase and Grazvydas Tuckus and Peter Fojan and Joar Bergman and Christian Thomsen and Benedict Kjærgaard and Sanne Ross Sørensen and Hiva Alipour and Tariq O. Abbas and Cristian Pablo Pennisi and Tommy Kjærgaard Nielsen},
journal = {Frontiers in bioengineering and biotechnology},
year = {2026},
month = oct,
doi = {10.3389/fbioe.2026.1891449},
url = {https://europepmc.org/article/PMC/PMC13724350},
note = {CC BY},
}
RIS
TY - JOUR
TI - In vivo evaluation of a chitosan/PLGA/chitosan composite versus monolayer PLGA electrospun scaffold for dorsal onlay urethroplasty: a controlled study in rabbits
AU - Marco Bassam Mahdi
AU - Fatemeh Mohtaram
AU - Rikke Nørresø Haase
AU - Grazvydas Tuckus
AU - Peter Fojan
AU - Joar Bergman
AU - Christian Thomsen
AU - Benedict Kjærgaard
AU - Sanne Ross Sørensen
AU - Hiva Alipour
AU - Tariq O. Abbas
AU - Cristian Pablo Pennisi
AU - Tommy Kjærgaard Nielsen
PY - 2026
DA - 2026/10/19
JO - Frontiers in bioengineering and biotechnology
DO - 10.3389/fbioe.2026.1891449
UR - https://europepmc.org/article/PMC/PMC13724350
AB - 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.
SN - 2296-4185
ER -