War Injured Urethral Stricture Repaired With Biodegradable Polymer Stents

Background: Various factors, such as congenital malformation, trauma, war wound, infection, carcinoma, may lead to urethral defect, stricture, and dysfunction. The reconstruction of functional urethral is still a clinical challenge due to have no appropriate materials. Although several innovative materials have been proposed for possible use as free grafts for urethral reconstruction, it is evident that all have specific advantages and disadvantages. The use of autologous tissue, such as genital and extragenital skin flaps, mucosal prafts from bladder or buccal regions, and tunica vaginalis, may be associated with additional procedures for grafts retrieval, prolonged hospitalization, and donor-site morbidity. Complications such as hair growth, grafts shrinkage, stricture, stone formation, diverticuli, mucosal glandular protrusion, meatal stenosis have been associated with these tissues. For these reasons, alternate materials have been sought for urethral repair. Then, the use of a variety of synthetic nondegradable materials composed of silicone, Teflon has been proposed for urethral reconstruction. Due to the problems such as erosion, dislodgement, fistula, stenosis, extravasation, and calcification associated with the use of these nondegradable meterials, the use of biodegradable substitutes has been pursued, such as polyglactin-fiber mesh, nonwoven meshs of polyglycolic acid. Although the results of experimental studies in animals appear promising, clinical studies have not been reported to date. Recently, naturally acellular matrix has been used for urethral reconstruction, and several advantages have been showed, but the source of the material is not plentiful. The use of the grafts to repair a long-tubular urethral defect may not suitable. In other hand, most of the previous models of urethral stricture were based on extraurethral injuries such as crush, transection, and external urethrotomy, or internal injuries such as endoscopic electrocoagulation of urethralwall. To our knowledge, no experimental models of urethral stricture based on war injuries have been reported to date.Objectives: Firstly, to develop an experimental model of war injured urethral stricture. Secondly, to design and fabricate tow types biodegradable stents : one is biodegradable spiral stents, the other one is biodegradable nonwoven mesh stents which seeded autologous urethral epithelial cells. Finally, use tow types stents for urethral repair in this experimental model, respectively, to evaluate the effect of the stents in reconstruction of urethra. Methods:Developing experimental model: Animal's (New Zealand male rabbit) bulbar urethra were bombed with a special instrument. The animals were assessed for urethral stricture by videourethroscopy and retrograde urethrography, and for histomorphological examination at the special time points.Designing and fabricating stents: The biodegradable spiral stents were designed and fabricated by dry-cast process. The characteristics of stents, such as degradation, self-expand rate, evaluated by scanning electron microscope (SEM) in vitro. The spiral interior layer of nonwoven mesh stent was fabricated based on dry-cast process while the outer layer based on electro-woven process and the mesh-fibers coated with chitosan. The biocompatiblity and cytotoxicity evaluated by MTT test, degradation characteristics evaluated by SEM. The animal urethral epithelial cells got by biopsy and cultured in vitro, and the cytologic characteristics evaluated by immunohistochemistry, fluorescein stain before the cells seeded to the outer layer of the nonwoven mesh biodegradable stents.Both of the stents were auto-replanted to the animals' urethra, respectively. Effect evaluated by immunohistochemistry, histologic examination, videourethroscopy and retrograde urethrography, urodynamic determination. Results: Animals developed a significant bulbar stricture (the length of stricture 5-10 mm, reducing the lumen by more than 50%). Histologic examination confirmed the presence of hyaline fibrosis mutilating the urethral wall, and theepithelial defected. Slight self-expand was found in both of the two types stents, degradation-time about 12 weeks. The factor of porosity of nonwoven mesh biodegradable stents is over 90%. The cultured cells adhere to fibers and growing very well. The polymer's biocompatibility is acceptable, and PLLA is not cytotoxic to the cells. After surgery, there was no evidence of voiding difficulty or other complication. Videourethroscopy and retrograde urethrography showed no evidence of stricture recurrence. Histologic examination of the neourethras demonstrated complete reepithelialization. Urodynamic determination showed that there was no difference between study and control group. Conclusion: First, the means (bombing) provides a reproducible model of war wound urethral stricture. Second, biologic and mechanical characteristics of the two types biodegradable stents are suitable for urethral reconstruction. Third, our studies suggest that both of the tow types stents can be used for the repair of war injured urethral stricture, the nonwoven mesh stents seems to have more advantages. The tow types stents , it is hoped, will allow clinic application in reconstruction of urethral stricture, caused by war injured, truma, infection and so on.