Biodegradable Drug-eluting Urethral Stent For Traumatic Urethral Injuries

Background:Traumatic urethral injuries are commom either in military setting or in daily life.1%-10% of the war injury was related to the genitourinary, and 7% of which involved the urethra. Like other war injury, blast injuries, such as gunshot injury, was the main factor lead to urethral injury. The optimal management strategy for urethral injuries remains controversial. Traditionally, initial management consisted of anastomotic urethroplasty, endoscopic realignment and the placement of a suprapubic cystostomy tube and delayed repair. However, every modality may result in high incidence of urethral stricture, especially by the treatment of the placement of a suprapubic cystostomy tube and delayed repair, all patients will suffer of strictures. Formation of stricture is the most commom complication to urethral injuries. Dialation, internal urethrotomy, laser, stent and open surgery are the available treatment for urethral stricture, the success rate of these modalities are 60%,50%,56%,40% and 90%. Open urethroplasty is most effective, but also most complicated, cost, and expensive. Although internal urethrotomy is simple, but 50% of the patients would occur restenosis in the first year. Restraining from materials, the treatmen for post-traumatic urethral stricture is more hard. Traumatic urethral stricture has been a challenge for urologist because no ideal substitute can be used. The emerge of biodegradable stent material brings new hope to the treatment of urethral stricutre. Our previos animal study has demonstrated that the biodegradable urethral stent is feasible and efective in the treatment of urethral stricture, but still has some deficiencies, such as acute inflammatory reaction, edema and stent-related tisuue reaction. We need to find a more simple but effective material for the treatment of traumatic urethral stricture.Objective:To develop a biodegradable paclitaxel-eluting urethral stent using polylactic acid as material, and evaluate the feasibility and effectiveness of the stent in the treatment of acute urethral injuries and traumatic urethral stricute.Materials and Methods:Fibroblast was primary cultured by enzyme digestion, and then we detect the effect of paclitaxel on the proliferation of fibroblat, thus to screen the optimal concentration of paclitaxel. After that, we develop a polylactic acid urethral stent, then soak the stent in the solution of paclitaxel to make a biodegradable paclitaxel-eluting stent. The animal model was made by a self-control explosion device, which had been proved reproducible and effective in our previous study. Stents were surgically implanted into the stenotic urethras of the rabbits under direct vision. Reparative effect, including biocompatibility assessment, was evaluated by urethroscopy, retrograde urethrography and histological findings at different time points.Results:We successfully cultured fibroblast in vitro, and confirmed paclitaxel can effectively inhibit the proliferation of fibroblast depend on concentration. We also developed a biodegradable drug-eluting stent, which contains 2050ug of paclitaxel. The animal model was successfully made, and all the stent was inserted uncomplicatedly. Animal study demonstrated that the stent can be used to treat acute urethral injuries effectively and significantly reduce the occurrence of urethral stricture, also it can be applied to the repair of urethral stricute with good biocompatibility.Conclusions:The polylactic acid paclitaxel urethral stent possess good mechanical and biological characters. It is effective for treating acute urethral injuries and traumatic urethral stricture in rabbit model.