{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:34:09Z","timestamp":1788402849861,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["258229"],"award-info":[{"award-number":["258229"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Urethral reconstruction remains a challenge. Indeed, the use of oral mucosa, the reference biomaterial for urethroplasty, is associated with two main drawbacks: the limited availability of autologous tissues and potential short- and long-term complications, especially for patients with recurrences or severe anomalies. Therefore, the development of alternative approaches, such as urethral tissue engineering, is necessary. A new type of human urethral substitute devoid of exogenous biomaterials has been reconstructed in vitro. It presented sufficient mechanical strength and had histological and functional properties comparable to native tissues. These reconstructed tissues were implanted in vivo to repair hypospadias induced in tacrolimus-immunosuppressed rabbits via a two-stage urethroplasty. In the first stage, the distal part of the native urethra was removed, and a flat graft was implanted, leaving the urethra open proximally. Twelve weeks later, the graft was tubularized to create a neourethra, reproducing the usual clinical scenario. The results obtained for the experimental group were less effective than for the control group, with a success rate of 50% after excluding the animal affected by unwanted events unrelated to urethroplasty, and it is possible that the animal model or surgical technique used was not suitable and should be modified. Nevertheless, half of the urethral substitutes grafted on rabbits showed successful integration. These self-assembled artificial tissues represent promising substitutes for urethroplasty.<\/jats:p>","DOI":"10.3390\/ijms26051825","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T11:03:37Z","timestamp":1740049417000},"page":"1825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Correction of Significant Urethral Anomalies Using a Tissue-Engineered Human Urethral Substitute: Proof of Concept"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0811-0688","authenticated-orcid":false,"given":"Christophe","family":"Caneparo","sequence":"first","affiliation":[{"name":"Centre de Recherche en Organogen\u00e8se Exp\u00e9rimentale de l\u2019Universit\u00e9 Laval\/LOEX, Centre de Recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Axe M\u00e9decine R\u00e9g\u00e9n\u00e9ratrice, Qu\u00e9bec, QC G1J 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elissa","family":"Elia","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Organogen\u00e8se Exp\u00e9rimentale de l\u2019Universit\u00e9 Laval\/LOEX, Centre de Recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Axe M\u00e9decine R\u00e9g\u00e9n\u00e9ratrice, Qu\u00e9bec, QC G1J 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0389-667X","authenticated-orcid":false,"given":"St\u00e9phane","family":"Chabaud","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Organogen\u00e8se Exp\u00e9rimentale de l\u2019Universit\u00e9 Laval\/LOEX, Centre de Recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Axe M\u00e9decine R\u00e9g\u00e9n\u00e9ratrice, Qu\u00e9bec, QC G1J 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3580-0297","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Berthod","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Organogen\u00e8se Exp\u00e9rimentale de l\u2019Universit\u00e9 Laval\/LOEX, Centre de Recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Axe M\u00e9decine R\u00e9g\u00e9n\u00e9ratrice, Qu\u00e9bec, QC G1J 1Z4, Canada"},{"name":"Department of Surgery, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1851-5112","authenticated-orcid":false,"given":"Julie","family":"Fradette","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Organogen\u00e8se Exp\u00e9rimentale de l\u2019Universit\u00e9 Laval\/LOEX, Centre de Recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Axe M\u00e9decine R\u00e9g\u00e9n\u00e9ratrice, Qu\u00e9bec, QC G1J 1Z4, Canada"},{"name":"Department of Surgery, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6680-5563","authenticated-orcid":false,"given":"St\u00e9phane","family":"Bolduc","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Organogen\u00e8se Exp\u00e9rimentale de l\u2019Universit\u00e9 Laval\/LOEX, Centre de Recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Axe M\u00e9decine R\u00e9g\u00e9n\u00e9ratrice, Qu\u00e9bec, QC G1J 1Z4, Canada"},{"name":"Department of Surgery, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.4103\/0970-0358.118623","article-title":"Unfavourable results in hypospadias","volume":"46","author":"Agrawal","year":"2013","journal-title":"Indian J. Plast. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.urology.2011.11.085","article-title":"Surgical outcome of different types of primary hypospadias repair during three decades in a single center","volume":"79","author":"Prat","year":"2012","journal-title":"Urology"},{"key":"ref_3","first-page":"127","article-title":"Challenges and Perspectives in Male Anterior Urethra Reconstruction Using Tissue Engineering","volume":"2","author":"Caneparo","year":"2019","journal-title":"Urol. Res. Ther. J."},{"key":"ref_4","unstructured":"Caneparo, C., Pellerin, E., Grammond, E., Jakubowska, W., Chabaud, S., and Bolduc, S. (2019). Surgical Correction of Genitourinary Disorders Using the Self-Assembly Tissue Engineering. Int. J. Regen. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.5489\/cuaj.4386","article-title":"Current hypospadias management: Diagnosis, surgical management, and long-term patient-centred outcomes","volume":"11","author":"Keays","year":"2017","journal-title":"Can. Urol. Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0090-4295(98)00088-0","article-title":"Buccal mucosal grafts for urethral reconstruction","volume":"51","author":"Caldamone","year":"1998","journal-title":"Urology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/j.urology.2005.12.048","article-title":"Ten-year experience with composite bladder mucosa-skin grafts in hypospadias repair","volume":"67","author":"Fu","year":"2006","journal-title":"Urology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.eururo.2008.01.061","article-title":"Tissue-engineered buccal mucosa urethroplasty-clinical outcomes","volume":"53","author":"Bhargava","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0022-5347(01)66568-6","article-title":"Split-thickness skin graft urethroplasty and tunica vaginalis flaps for failed hypospadias repairs","volume":"155","author":"Ehrlich","year":"1996","journal-title":"J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/j.1464-410X.2007.07230.x","article-title":"Urethral substitution using autologous lingual mucosal grafts: An experimental study","volume":"101","author":"Song","year":"2008","journal-title":"BJU Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0022-5347(01)66566-2","article-title":"Dorsal free graft urethroplasty","volume":"155","author":"Barbagli","year":"1996","journal-title":"J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/01.ju.0000148540.57463.22","article-title":"Urethral reconstruction: A continuing challenge","volume":"173","author":"McAninch","year":"2005","journal-title":"J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/j.1464-410X.2004.05048.x","article-title":"Oral complications after buccal mucosal graft harvest for urethroplasty","volume":"94","author":"Dublin","year":"2004","journal-title":"BJU Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1007\/s11934-014-0424-3","article-title":"Graft surgery in extensive urethral stricture disease","volume":"15","author":"Djordjevic","year":"2014","journal-title":"Curr. Urol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.eururo.2012.06.035","article-title":"The first oral mucosal graft urethroplasty was carried out in the 19th century: The pioneering experience of Kirill Sapezhko (1857\u20131928)","volume":"62","author":"Korneyev","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1097\/01.ju.0000169421.27043.f2","article-title":"Long-term patient reported outcome and satisfaction after oral mucosa graft urethroplasty for hypospadias","volume":"174","author":"Nelson","year":"2005","journal-title":"J. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.joms.2007.11.023","article-title":"Morbidity associated with oral mucosa harvest for urological reconstruction: An overview","volume":"66","author":"Markiewicz","year":"2008","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/term.2112","article-title":"The potential role of tissue-engineered urethral substitution: Clinical and pre-clinical studies","volume":"11","author":"Atala","year":"2017","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1016\/j.juro.2012.02.057","article-title":"15 TISSUE\u2014ENGINEERED BUCCAL MUCOSA URETHROPLASTY. OUTCOME OF OUR FIRST 10 PATIENTS","volume":"187","author":"Engel","year":"2012","journal-title":"J. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.juro.2018.02.3102","article-title":"Anterior Urethroplasty Using a New Tissue Engineered Oral Mucosa Graft: Surgical Techniques and Outcomes","volume":"200","author":"Barbagli","year":"2018","journal-title":"J. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1111\/j.1651-2227.2012.02659.x","article-title":"Prepubertal follow-up after hypospadias repair with autologous in vitro cultured urothelial cells","volume":"101","author":"Fossum","year":"2012","journal-title":"Acta Paediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.eururo.2014.07.007","article-title":"Long-term follow-up after tissue-engineered buccal mucosa urethroplasty","volume":"66","author":"Osman","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Abbas, T.O., Yalcin, H.C., and Pennisi, C.P. (2019). From Acellular Matrices to Smart Polymers: Degradable Scaffolds that are Transforming the Shape of Urethral Tissue Engineering. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071763"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/S0140-6736(10)62354-9","article-title":"Tissue-engineered autologous urethras for patients who need reconstruction: An observational study","volume":"377","author":"Esquiliano","year":"2011","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ebiom.2017.08.014","article-title":"Results of Use of Tissue-Engineered Autologous Oral Mucosa Graft for Urethral Reconstruction: A Multicenter, Prospective, Observational Trial","volume":"23","author":"Barbagli","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/S0022-5347(01)68105-9","article-title":"A novel inert collagen matrix for hypospadias repair","volume":"162","author":"Atala","year":"1999","journal-title":"J. Urol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S0022-5347(05)64060-8","article-title":"Urethral stricture repair with an off-the-shelf collagen matrix","volume":"169","author":"Retik","year":"2003","journal-title":"J. Urol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1016\/j.eururo.2007.01.099","article-title":"Porcine small intestinal submucosa graft for repair of anterior urethral strictures","volume":"51","author":"Fiala","year":"2007","journal-title":"Eur. Urol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.juro.2007.11.101","article-title":"Randomized comparative study between buccal mucosal and acellular bladder matrix grafts in complex anterior urethral strictures","volume":"179","author":"AbouShwareb","year":"2008","journal-title":"J. Urol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Caneparo, C., Chabaud, S., Fradette, J., and Bolduc, S. (2022). Engineered human organ-specific urethra as a functional substitute. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-25311-1"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.eururo.2017.03.026","article-title":"Tissue Engineering of the Urethra: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies","volume":"72","author":"Versteegden","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"154564","DOI":"10.1155\/2013\/154564","article-title":"Tissue engineering of urinary bladder and urethra: Advances from bench to patients","volume":"2013","author":"Orabi","year":"2013","journal-title":"Sci. World J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/S0022-5347(17)34917-0","article-title":"The in vitro cytotoxicity of urine from patients with interstitial cystitis","volume":"151","author":"Hermann","year":"1994","journal-title":"J. Urol."},{"key":"ref_34","first-page":"716071","article-title":"Primary gallbladder small lymphocytic lymphoma as a rare postcholecystectomy finding","volume":"2014","author":"Psarras","year":"2014","journal-title":"Case Rep. Hematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.stemcr.2021.01.010","article-title":"Development of the Nude Rabbit Model","volume":"16","author":"Song","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2017.02.005","article-title":"Tubular collagen scaffolds with radial elasticity for hollow organ regeneration","volume":"52","author":"Versteegden","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1111\/wrr.12338","article-title":"The murine excisional wound model: Contraction revisited","volume":"23","author":"Chen","year":"2015","journal-title":"Wound Repair. Regen."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.actbio.2016.07.033","article-title":"Engineered acellular collagen scaffold for endogenous cell guidance, a novel approach in urethral regeneration","volume":"43","author":"Pinnagoda","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1089\/ten.tea.2013.0185","article-title":"Is there a need for smooth muscle cell transplantation in urethral reconstruction?","volume":"20","author":"Micol","year":"2014","journal-title":"Tissue Eng. Part A"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.juro.2011.10.132","article-title":"Introducing a large animal model to create urethral stricture similar to human stricture disease: A comparative experimental microscopic study","volume":"187","author":"Sievert","year":"2012","journal-title":"J. Urol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E4","DOI":"10.5489\/cuaj.187","article-title":"An endothelialized urothelial cell-seeded tubular graft for urethral replacement","volume":"7","author":"Imbeault","year":"2013","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1158\/1541-7786.MCR-17-0784","article-title":"Exosomes Induce Fibroblast Differentiation into Cancer-Associated Fibroblasts through TGFbeta Signaling","volume":"16","author":"Bernard","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.biomaterials.2017.08.041","article-title":"Tissue-engineered human 3D model of bladder cancer for invasion study and drug discovery","volume":"145","author":"Bernard","year":"2017","journal-title":"Biomaterials"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0305-4179(93)90028-7","article-title":"Improvement of human keratinocyte isolation and culture using thermolysin","volume":"19","author":"Germain","year":"1993","journal-title":"Burns"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1089\/ten.tea.2009.0473","article-title":"In vitro reconstruction of an autologous, watertight, and resistant vesical equivalent","volume":"16","author":"Bouhout","year":"2010","journal-title":"Tissue Eng. Part A"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1002\/term.2036","article-title":"Inexpensive production of near-native engineered stromas","volume":"11","author":"Chabaud","year":"2017","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kawecki, F., Mayrand, D., Ayoub, A., Attiogbe, \u00c9., Germain, L., Auger, F.A., and Moulin, V.J. (2021). Biofabrication and preclinical evaluation of a large-sized human self-assembled skin substitute. Biomed. Mater., 16.","DOI":"10.1088\/1748-605X\/abbdbe"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.eururo.2011.05.051","article-title":"Mechanical stimuli-induced urothelial differentiation in a human tissue-engineered tubular genitourinary graft","volume":"60","author":"Cattan","year":"2011","journal-title":"Eur. Urol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"128","DOI":"10.22203\/eCM.v036a10","article-title":"Autologous bilayered self-assembled skin substitutes (SASSs) as permanent grafts: A case series of 14 severely burned patients indicating clinical effectiveness","volume":"36","author":"Germain","year":"2018","journal-title":"Eur. Cell. Mater."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gu\u00e9rin, L.P., Larouche, D., Morcos, M.W., Faucher, A., Auger, F.A., Knoppers, B.M., Kyrillos, R., Bazin, R., and Germain, L. (2022). Cultured Autologous Corneal Epithelia for the Treatment of Unilateral Limbal Stem Cell Deficiency: A Case Series of 15 Patients. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081958"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Caneparo, C., Chabaud, S., Fradette, J., and Bolduc, S. (2022). Evaluation of a Serum-Free Medium for Human Epithelial and Stromal Cell Culture. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231710035"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/1825\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:39:02Z","timestamp":1760027942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/1825"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,20]]},"references-count":51,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26051825"],"URL":"https:\/\/doi.org\/10.3390\/ijms26051825","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,20]]}}}