BACKGROUND: Complex urethral problems can occur as a result of injury, disease, or congenital defects and treatment options are often limited. Urethras, similar to other long tubularised tissues, can stricture after reconstruction. We aimed to assess the effectiveness of tissue-engineered urethras using patients' own cells in patients who needed urethral reconstruction. METHODS: Five boys who had urethral defects were included in the study. A tissue biopsy was taken from each patient, and the muscle and epithelial cells were expanded and seeded onto tubularised polyglycolic acid:poly(lactide-co-glycolide acid) scaffolds. Patients then underwent urethral reconstruction with the tissue-engineered tubularised urethras. We took patient history, asked patients to complete questionnaires from the International Continence Society (ICS), and did urine analyses, cystourethroscopy, cystourethrography, and flow measurements at 3, 6, 12, 24, 36, 48, 60, and 72 months after surgery. We did serial endoscopic cup biopsies at 3, 12, and 36 months, each time in a different area of the engineered urethras. FINDINGS: Patients had surgery between March 19, 2004, and July 20, 2007. Follow-up was completed by July 31, 2010. Median age was 11 years (range 10-14) at time of surgery and median follow-up was 71 months (range 36-76 months). AE1/AE3, α actin, desmin, and myosin antibodies confirmed the presence of cells of epithelial and muscle lineages on all cultures. The median end maximum urinary flow rate was 27·1 mL/s (range 16-28), and serial radiographic and endoscopic studies showed the maintenance of wide urethral calibres without strictures. Urethral biopsies showed that the engineered grafts had developed a normal appearing architecture by 3 months after implantation. INTERPRETATION: Tubularised urethras can be engineered and remain functional in a clinical setting for up to 6 years. These engineered urethras can be used in patients who need complex urethral reconstruction. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.
BACKGROUND: Complex urethral problems can occur as a result of injury, disease, or congenital defects and treatment options are often limited. Urethras, similar to other long tubularised tissues, can stricture after reconstruction. We aimed to assess the effectiveness of tissue-engineered urethras using patients' own cells in patients who needed urethral reconstruction. METHODS: Five boys who had urethral defects were included in the study. A tissue biopsy was taken from each patient, and the muscle and epithelial cells were expanded and seeded onto tubularised polyglycolic acid:poly(lactide-co-glycolide acid) scaffolds. Patients then underwent urethral reconstruction with the tissue-engineered tubularised urethras. We took patient history, asked patients to complete questionnaires from the International Continence Society (ICS), and did urine analyses, cystourethroscopy, cystourethrography, and flow measurements at 3, 6, 12, 24, 36, 48, 60, and 72 months after surgery. We did serial endoscopic cup biopsies at 3, 12, and 36 months, each time in a different area of the engineered urethras. FINDINGS:Patients had surgery between March 19, 2004, and July 20, 2007. Follow-up was completed by July 31, 2010. Median age was 11 years (range 10-14) at time of surgery and median follow-up was 71 months (range 36-76 months). AE1/AE3, α actin, desmin, and myosin antibodies confirmed the presence of cells of epithelial and muscle lineages on all cultures. The median end maximum urinary flow rate was 27·1 mL/s (range 16-28), and serial radiographic and endoscopic studies showed the maintenance of wide urethral calibres without strictures. Urethral biopsies showed that the engineered grafts had developed a normal appearing architecture by 3 months after implantation. INTERPRETATION: Tubularised urethras can be engineered and remain functional in a clinical setting for up to 6 years. These engineered urethras can be used in patients who need complex urethral reconstruction. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.
Authors: Matthias C Hofmann; Bryce M Whited; Tracy Criswell; Marissa Nichole Rylander; Christopher G Rylander; Shay Soker; Ge Wang; Yong Xu Journal: Tissue Eng Part C Methods Date: 2012-05-10 Impact factor: 3.056
Authors: Hyun-Wook Kang; Sang Jin Lee; In Kap Ko; Carlos Kengla; James J Yoo; Anthony Atala Journal: Nat Biotechnol Date: 2016-02-15 Impact factor: 54.908
Authors: S Cem Millik; Ashley M Dostie; Dylan G Karis; Patrick T Smith; Michael McKenna; Nathan Chan; Chad D Curtis; Elizabeth Nance; Ashleigh B Theberge; Alshakim Nelson Journal: Biofabrication Date: 2019-07-12 Impact factor: 9.954