{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:33:13Z","timestamp":1792427593371,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Tissue engineering is a potential source of urethral substitutes to treat severe urethral defects. Our aim was to create tissue-engineered urethras by harvesting autologous cells obtained by bladder washes and then using these cells to create a neourethra in a chronic large urethral defect in a rabbit model.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A large urethral defect was first created in male New Zealand rabbits by resecting an elliptic defect (70 mm<jats:sup>2<\/jats:sup>) in the ventral penile urethra and then letting it settle down as a chronic defect for 5\u20136 weeks. Urothelial cells were harvested noninvasively by washing the bladder with saline and isolating urothelial cells. Neourethras were created by seeding urothelial cells on a commercially available decellularized intestinal submucosa matrix (Biodesign\u00ae Cook-Biotech\u00ae). Twenty-two rabbits were divided into three groups. Group-A (<jats:italic>n<\/jats:italic> = 2) is a control group (urethral defect unrepaired). Group-B (<jats:italic>n<\/jats:italic> = 10) and group-C (<jats:italic>n<\/jats:italic> = 10) underwent on-lay urethroplasty, with unseeded matrix (group-B) and urothelial cell-seeded matrix (group-C). Macroscopic appearance, radiology, and histology were assessed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The chronic large urethral defect model was successfully created. Stratified urothelial cultures attached to the matrix were obtained. All group-A rabbits kept the urethral defect size unchanged (70 \u00b1 2.5 mm<jats:sup>2<\/jats:sup>). All group-B rabbits presented urethroplasty dehiscence, with a median defect of 61 mm<jats:sup>2<\/jats:sup> (range 34\u201370). In group-C, five presented complete correction and five almost total correction with fistula, with a median defect of 0.3 mm<jats:sup>2<\/jats:sup> (range 0\u201312.5), demonstrating a significant better result (<jats:italic>p<\/jats:italic> = 7.85 \u00d7 10<jats:sup>\u22125<\/jats:sup>). Urethrography showed more fistulas in group-B (10\/10, versus 5\/10 in group-C) (<jats:italic>p<\/jats:italic> = 0.04). No strictures were found in any of the groups. Group-B histology identified the absence of ventral urethra in unrepaired areas, with squamous cell metaplasia in the edges toward the defect. In group-C repaired areas, ventral multilayer urothelium was identified with cells staining for urothelial cell marker cytokeratin-7.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> The importance of this study is that we used a chronic large urethral defect animal model and clearly found that cell-seeded transplants were superior to nonseeded. In addition, bladder washing was a feasible method for harvesting viable autologous cells in a noninvasive way. There is a place for considering tissue-engineered transplants in the surgical armamentarium for treating complex urethral defects and hypospadias cases.<\/jats:p>","DOI":"10.3389\/fped.2021.691131","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T04:50:47Z","timestamp":1624337447000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Creation of Tissue-Engineered Urethras for Large Urethral Defect Repair in a Rabbit Experimental Model"],"prefix":"10.3389","volume":"9","author":[{"given":"Maria Virginia","family":"Amesty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara 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