Anterior Urethroplasty Using a New Tissue Engineered Oral Mucosa Graft: Surgical Techniques and Outcomes.

PURPOSE: We investigated whether tissue engineered material may be adopted using standard techniques for anterior urethroplasty. MATERIALS AND METHODS: We performed a retrospective multicenter study in patients with recurrent strictures, excluding those with failed hypospadias, lichen sclerosus, traumatic and posterior strictures. A 0.5 cm2 oral mucosa biopsy was taken from the patient cheek and sent to the laboratory to manufacture the graft. After 3 weeks the tissue engineered oral mucosal MukoCell® graft was sent to the hospital for urethroplasty. Four techniques were used, including ventral onlay, dorsal onlay, dorsal inlay and a combined technique. Cystourethrography was performed 1 month postoperatively. Patients underwent clinical evaluation, uroflowmetry and post-void residual urine measurement every 6 months. When the patient showed obstructive symptoms, defined as maximum urine flow less than 12 ml per second, the urethrography was repeated. Patients who underwent further treatment for recurrent stricture were classified as having treatment failure. RESULTS: Of the 38 patients with a median age of 57 years who were included in study the strictures were penile in 3 (7.9%), bulbar in 29 (76.3%) and penobulbar in 6 (15.8%). Median stricture length was 5 cm and median followup was 55 months. Treatment succeeded in 32 of the 38 patients (84.2%) and failed in 15.8%. Success was achieved in 85.7% of ventral onlay, 83.3% of dorsal onlay, 80% of dorsal inlay and 100% of combined technique cases. No local or systemic adverse reactions due to the engineered material were noted. CONCLUSIONS: Our findings show that a tissue engineered oral mucosa graft can be implanted using the same techniques suggested for anterior urethroplasty and native oral mucosa, and guaranteeing a similar success rate.

Results of Use of Tissue-Engineered Autologous Oral Mucosa Graft for Urethral Reconstruction: A Multicenter, Prospective, Observational Trial.

BACKGROUND: Harvest of oral mucosa for urethroplasty due to urethral stricture is associated with donor-site-morbidity. We assessed functionality and safety of an authorized tissue-engineered oral mucosa graft (TEOMG) under routine practice in stricture recurrences of any etiology, location, length and severity (real-world data). METHODS: 99 patients from eight centers with heterogenous urethroplasty experience levels were included in this prospective, non-interventional observational study. Primary and secondary outcomes were success rate (SR) and safety at 12 and 24months. FINDINGS: All but one patient had ≥1, 77.1% (64 of 83)≥2 and 31.3% (26 of 83)≥4 previous surgical treatments. Pre- and postoperative mean±SD peak flow rate (Qmax) were 8.3±4.7mL/s (n=57) and 25.4±14.7mL/s (n=51). SR was 67.3% (95% CI 57.6-77.0) at 12 and 58.2% (95% CI 47.7-68.7) at 24months (conservative Kaplan Meier assessment). SR ranged between 85.7% and 0% in case of high and low surgical experience. Simple proportions of 12-month and 24-month SR for evaluable patients in all centers were 70.8% (46 of 65) and 76.9% (30 of 39). Except for one patient, no oral adverse event was reported. INTERPRETATIONS: TEOMG is safe and efficient in urethroplasty.

Regulatory challenges for autologous tissue engineered products on their way from bench to bedside in Europe.

Since the late eighties of last century the high potential of tissue engineered products (TEP)s has been shown for the treatment of various diseases and many scientific publications appeared in this field. However, only few products reached the market since. Development of TEPs is a promising but owing to its novelty a very challenging task that requires experts in this still developing field as well as ample financial resources. This paper summarises relevant regulatory challenges during quality, preclinical and clinical development of autologous TEPs in Europe. Selected strategies on how to manage major issues are presented, together with some examples from the development of an autologous TEP for urethroplasty. Considering these aspects may help other investigators with potential strategies during the development of novel TEPs.