Autores / Authors

OBJECTIVES OBJECTIVES METHODS METHODS

CRITICAL CONCLUSIONS CRITICAL CONCLUSIONS

Barbagli Guid, Arezzo, Italy; Ram-Liebig Gouya, Dresden, Germany; Romano Giuseppe, Arezzo, Italy; Fahlenkamp Dirk and Balsmeyer Ulf,

Chemnitz, Germany; Lazzeri Massimo, Milan, Italy

New bulbar urethroplasty using tissue-engineered oral mucosal graft: a preliminary clinical report New bulbar urethroplasty using tissue-engineered oral mucosal graft: a preliminary clinical report

RESULTSRESULTS

Repair of the anterior urethra is one of the most demanding surgical problems in

urology. In recent years, regenerative medicine and tissue engineering studies have

led to the development of novel biomaterials for urethral repair Here we describe the

first clinical report of a homogeneous series of patients who underwent tissue-

engineered oral mucosal graft urethroplasty for bulbar urethral stricture.

Study design. A German registered observational study, following guidelines of Good Clinical Practice.

Population and settings. Patients with idiopathic uncomplicated bulbar urethral stricture. Tertiary high volume centres.

Intervention. Inlay bulbar urethroplasty

Substitute material. Autologus engineered oral graft (MukoCell®). A tiny oral mucosa biopsy was taken form the cheek of patient under local

anaesthesia (Panel 1). The biopsy was sent to an advanced pharmaceutical clean room facility for manufacturing of cell-based medicinal

products according to "Good Manufacturing Practice" (GMP). Cells were expanded and cultured on the surface of a biocompatible scaffold

(Panel 2). MukoCell® was implanted in the bulbar urethra as an inlay graft on the urethral plate (Panel 3).

Primary outcome. Feasibility (technique) , safety (no adverse event) and efficacy (efficacy (patent urethra defined as Qmax > 14 ml/sec or

urethra passable for 14-16F catheter or urethroscope and no further interventions required).

Follow-up. Three weeks after surgery, all patients underwent a voiding urethrography. Uroflowmetry and clinical assessment were

performed every 3 months.

The current study population consists of 12 men who underwent tissue engineering bulbar inlay urethroplasty from December 2010 to May 2012. The median age was 53.5 year (28-75 years), with a median stricture length of 4 cm (range 2-6 cm). The mean follow-up was 18 months (range 12-28 months). All the procedures were completed without any intraoperative complications. Two patients (16,8%) developed a stricture recurrence requiring further urethral manipulation; no recurrence was reported for 10 patients (83,2%). The graft intake was observed in all patients and it was well tolerated. The mean maximum flow rate increased from 3 ml/sec preoperatively to 20 ml/sec postoperatively. No QoL questionnaire was recorded.

1. Study strength: i) First multicenter observational study in a wide patients series, with a mid-term follow-up using an nationally registered market-available

substitute materialii) Homogeneous patients series (the same stricture site, technique, and high volume surgeons for urethral reconstruction)iii)Sterility, validity and traceability of the autologous, degradable product.iv)Manufacture of the construct according to GMP (Good Manufacture Practice) guidelines.v) Efficiency at urethral site comparable to native oral mucosa.vi)Feasibility of operative implantation of an autologous product, while the manufacture site is different as implantation sites2. Critical points to be address:i) Non tubularized reconstruction vs. tubularized reconstruction; ii) Reconstruction in patients with critical aetiologies (LS and failed

hypospadias); iii) What the best urethroplasty technique? iv) Is MukoCell appropriate for reconstruction of bulbar as well as penile strictures?

 3. ConclusionAccording to our findings we concluded for satisfactory preliminary results at mid-term follow-up. We suggest larger study (stage 2a-b) with

longer follow-up.

Panel 3:surgical thechnique

Panel1

harvestIng

Panel 2:Factory