Introduction: Treatment of patients with VSD (Variation of Sex Development), in particular severe hypospadias, is associated with high rate of post-operative complications using current surgical procedures. This leads to a high rate of re-operation in an already emotionally complicated situation. We improved the tissue engineered acellular tubular collagen scaffolds that showed promising results in the rabbit model to implant it to a dog model. This FDA approved new version accomplishes the ethical criteria to establish human clinical trial.
Methods: The two layered collagen based tube used initially in the rabbit model was replaced by a single layered FDA approved bovine collagen tube with better mechanical properties and enhanced functional outcome. This was achieved, by varying the collagen density and fibre distribution. Our previous study in rabbits showed regeneration in a 2 cm long acellular graft. In the present study, 4 cm tubular urethral grafts were implanted in 9 weight matched stray dogs. An endoscopic examination of the urethra and a contrast voiding cysto-urethrography was done at time of euthanasia. The constructs were all acellular, potentially off-the-shelf.
Results: The initial two dogs from the pilot study had no macroscopic nor functional complications on the contrast voiding cysto-urethrography, were euthanized at 2 months post-surgery and the cystoscopic evaluation showed endoluminal regeneration in the total lenght of the graft. Histology and immuno-histochemistry analysis showed regeneration of the implanted site. Seven dogs are currently doing well after operation. No signs of stenosis nor fistula observed after one-year post implantation. They are kept for long term analysis to evaluate the occurrence of late complications as observed after human surgery with current procedures.
Conclusion: This off the shelf graft easy to handle for the surgeons, with high regenerative capacity, safe and cost effective is ideal for urethroplasty. We have shown success using an acellular platform for urethroplasties of 4 cm. The data generated from this study was used for submission for human clinical trial application. These procedures are planned to start at the end of 2018. Further studies, using the same general concept, are necessary to show similar results in vaginal reconstruction.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology