Photodynamic therapy for male genital lichen sclerosus with urethral stricture-Case report.

Male genital lichen sclerosus (MGLSc) typically impacts the external genitalia, resulting in balanitis, erectile pain, urination symptoms, and/or urinary retention. Urethral stricture develops in up to 20 % of these patients, which is usually found in the distal part of the urethra but can, in severe instances, impact the entire urethra and cause structural changes. Patients with skin lesions limited to the foreskin and partially extending to the glans can typically be cured by circumcision, but the recurrence rate of stricture is high when the glans or urethra is extensively involved. In the following case report, we describe a 45-year-old man with a history of MGLSc for 3 years and urethral stricture for 2 years, and these conditions remained untreated after circumcision. We emphasize that treatment with 5-aminolevulinic acid-induced photodynamic therapy (ALA-PDT) may further improve outcomes in such severe cases.

Rectifying disorder of extracellular matrix to suppress urethral stricture by protein nanofilm-controlled drug delivery from urinary catheter.

Urethral stricture secondary to urethral injury, afflicting both patients and urologists, is initiated by excessive deposition of extracellular matrix in the submucosal and periurethral tissues. Although various anti-fibrotic drugs have been applied to urethral stricture by irrigation or submucosal injection, their clinical feasibility and effectiveness are limited. Here, to target the pathological state of the extracellular matrix, we design a protein-based nanofilm-controlled drug delivery system and assemble it on the catheter. This approach, which integrates excellent anti-biofilm properties with stable and controlled drug delivery for tens of days in one step, ensures optimal efficacy and negligible side effects while preventing biofilm-related infections. In a rabbit model of urethral injury, the anti-fibrotic catheter maintains extracellular matrix homeostasis by reducing fibroblast-derived collagen production and enhancing metalloproteinase 1-induced collagen degradation, resulting in a greater improvement in lumen stenosis than other topical therapies for urethral stricture prevention. Such facilely fabricated biocompatible coating with antibacterial contamination and sustained-drug-release functionality could not only benefit populations at high risk of urethral stricture but also serve as an advanced paradigm for a range of biomedical applications.

Efficacy of Mitomycin C Combined with Direct Vision Internal Urethrotomy for Urethral Strictures: A Systematic Review and Meta-Analysis.

BACKGROUND: The high recurrence of a urethral stricture after direct vision internal urethrotomy (DVIU) has been a problem for years. Mitomycin C (MMC) is an excellent antifibrosis antigen that has been used in many fields, but its effect on a urethral stricture remains controversial. The purpose of this review was to investigate the effectiveness of MMC in reducing the recurrence rate of a urethral stricture after the first urethrotomy. METHODS: Common databases were searched for publications prior to November 30, 2020. Randomized controlled and cohort trials were all included. Recurrence and success rates after the first urethrotomy of the posterior urethra were the main outcomes. Revman 5.3 was used for statistical analysis. Two evaluation systems, the Cochrane risk of bias tool and the Newcastle Ottawa Scale, were used to examine the risk of bias for RCTs and all studies. The quality of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation standard. RESULTS: Sixteen trials were included, the reporting quality of which was generally poor, and the evidence level was very low to moderate. The addition of MMC could significantly reduce the recurrence rate of urethral strictures (risk ratio [RR] = 0.42; 95% confidence interval [CI]: 0.26, 0.67; p = 0.0002; 9 trials; 550 participants). The results of the subgroup analysis suggested that the effect of MMC combined with DVIU was significant in short (≤2 cm) anterior urethral strictures (RR = 0.39; 95% CI: 0.20, 0.78; p = 0.008), >12-month follow-up (RR = 0.45; 95% CI: 0.26, 0.76; p = 0.003). It also increased the success rate of the first urethrotomy procedure for posterior urethral contracture (RR = 0.74; 95% CI: 0.65, 0.84; p < 0.00001; 7 trials; 342 participants). Low-dose local injection of MMC was the most commonly used method. CONCLUSION: MMC combined with DVIU is a promising way to reduce the long-term recurrence rate of a short-segment anterior urethral stricture. It also increases the success rate of the first urethrotomy of the posterior urethra. However, more high-quality randomized controlled trials are needed.

CARI Guidelines: urate-lowering treatment in early CKD

The scope of the guideline is urate-lowering therapy in patients with chronic kidney disease (not on dialysis) without symptomatic hyperuricemia (such as gout and/or uric acid stone formation). The guideline does not make recommendations about the management of uric-acid kidney stones or gout in people with chronic kidney disease.

Prospects and Challenges of Electrospun Cell and Drug Delivery Vehicles to Correct Urethral Stricture.

Current therapeutic modalities to treat urethral strictures are associated with several challenges and shortcomings. Therefore, significant strides have been made to develop strategies with minimal side effects and the highest therapeutic potential. In this framework, electrospun scaffolds incorporated with various cells or bioactive agents have provided promising vistas to repair urethral defects. Due to the biomimetic nature of these constructs, they can efficiently mimic the native cells' niches and provide essential microenvironmental cues for the safe transplantation of multiple cell types. Furthermore, these scaffolds are versatile platforms for delivering various drug molecules, growth factors, and nucleic acids. This review discusses the recent progress, applications, and challenges of electrospun scaffolds to deliver cells or bioactive agents during the urethral defect repair process. First, the current status of electrospinning in urethral tissue engineering is presented. Then, the principles of electrospinning in drug and cell delivery applications are reviewed. Finally, the recent preclinical studies are summarized and the current challenges are discussed.

Effect of local steroids on urethral strictures: A systematic review and meta-analysis.

PURPOSE: Urethral stricture disease is common and has high associated morbidity and impact on quality-of-life. This systematic review and meta-analysis aims to summarise current evidence on the efficacy of local urethral steroids post-direct vision internal urethrotomy (DVIU) for the treatment of urethral strictures in males. MATERIALS AND METHODS: A comprehensive search was performed using reputable databases and registries, up to 22 February 2022. Only randomised control trials in which participants were randomised to DVIU plus local urethral steroids versus DVIU only were included. Statistical analyses were performed using a random-effects model. Quality of evidence was rated according to the GRADE approach. RESULTS: The search identified seven studies in which 365 participants were randomised to DVIU plus local urethral steroids versus DVIU only. The application of local steroids appeared to reduce recurrence rates (risk ratio, 0.67; 95% confidence interval [CI], 0.49-0.90) and time-to-recurrence (hazard ratio, 0.58; 95% CI, 0.39-0.85). Qmax also improved following steroid application (mean difference, 0.82; 95% CI, -1.02-2.66); however, this was not statistically significant. No heterogeneity was identified between included studies for all outcomes. The certainty of evidence was downgraded due to study limitations with a small sample size and unclear risk-of-bias related to insufficient trial information. CONCLUSIONS: Compared to DVIU alone, adjuvant steroids applied to the urethra may reduce risk of recurrence and time-to-recurrence. These findings were statistically significant and likely also clinically significant given low associated costs and risk. However, more robust randomised trials are necessary to enhance the validity of these outcomes.

[Pirfenidone alleviates urethral stricture following urethral injury in rats by suppressing TGF-ß1 signaling and inflammatory response].

OBJECTIVE: To investigate the effect of pirfenidone for reducing urethral stricture following urethral injury in rats and explore the possible mechanism. METHODS: Thirty male SD rats were randomly assigned into negative control group, positive control group and pirfenidone group (n=10). In pirfenidone and positive control groups, the rats were subjected to incision of the posterior urethral cavernous body followed by daily intraperitoneal injection of pirfenidone (100 mg/kg) and an equivalent volume of solvent, respectively. The rats in the negative control group were given intraperitoneal injections of solvent without urethral injury. At two weeks after modeling, retrograde urethrography was performed for observing urethral stricture, and the injured urethral tissues were harvested for HE staining, Masson staining, immunohistochemical staining and Western blotting for detecting the protein expressions of α-SMA and TGF-ß1. The mRNA expressions of the inflammatory factors TNF-α, IL-6, and IL-1ß were detected using qRT-PCR. RESULTS: The body weight of the rats in pirfenidone group was significantly decreased compared with that in the other two groups (P < 0.05). Retrograde urethrography showed significant narrowing of the urethra in the positive control group but not in the pirfenidone group. HE staining of the injured urethral tissues showed obvious proliferation of urethral epithelial cells with narrow urethral cavity and increased inflammatory cells in positive control group. The pathological findings of the urethra were similar between pirfenidone group and the negative control group. Masson staining revealed obviously reduced collagen fibers and regular arrangement of the fibers in pirfenidone group as compared to the positive control group. Compared with those in the negative control group, the expressions of α-SMA and TGF-ß1 were significantly increased in the positive control group, and pirfenidone treatment significantly inhibited their expressions (P < 0.05 or 0.01). Pirfenidone also significantly inhibited the mRNA expressions of TNF-α, IL-6, and IL-1ß in the injured urethral tissue (P < 0.05 or 0.01). CONCLUSION: Pirfenidone can prevent urethral fibrosis and stricture after urethral injury possibly by inhibiting the TGF-ß1 pathway and inflammatory response.

The Effect of Radiation Therapy on the Efficacy of Internal Urethrotomy With Intralesional Mitomycin C for Recurrent Vesicourethral Anastomotic Stenoses and Bladder Neck Contractures: A Multi-Institutional Experience.

OBJECTIVE: To assess the efficacy, effect of radiotherapy, and complications of direct visual internal urethrotomy (DVIU) and intralesional mitomycin C (MMC) for recurrent bladder neck contracture/vesicourethral anastomotic stenosis (BNC/VUAS). METHODS: Patients who underwent DVIU with intralesional MMC for recurrent BNC/VUAS between 2007 and 2019 at 2 institutions were included. Cold knife incisions were performed in a reproducible fashion followed by injection of 0.3-0.4 mg/mL MMC at each incision site. Those with evidence of complete urethral obliteration, stenosis of the entire posterior urethra, or <3 months follow-up were excluded. Success was defined as the ability to pass a 17-French cystoscope postoperatively without the need for catheterization or additional procedures. RESULTS: Eighty-six patients were analyzed over a median follow-up of 21.1 months. Around 91% had at least 1 prior DVIU, 56% had at least 1 prior dilation, and 44% presented with an indwelling catheter or performed intermittent catheterization. Success was achieved in 65% after 1 procedure, an additional 18% after 2 procedures, and another 7% after 3 or more procedures (90% overall success rate). Nonradiated patients showed a higher overall success rate compared to radiated patients (94% vs 76%, P = 0.04). Of the 9 cystoscopic failures, 5 were asymptomatic and pursued observation. Only 2 (5%) patients with a history of catheterization required this postoperatively. Two patients underwent subsequent urinary diversion surgery. No long-term complications were seen. CONCLUSION: DVIU with low-dose MMC remains a safe and effective BNC/VUAS treatment. A patent bladder neck was achieved in >90% of nonradiated patients and >75% of radiated patients.

How I Do It: The Optilume drug-coated balloon for urethral strictures.

Urethral stricture disease can be difficult to treat and stricture recurrence is common. The management of stricture disease has evolved and urethroplasty can achieve a high rate of lasting urethral patency. Nevertheless, endoscopic treatments still seem to have sub-optimal outcomes with high stricture recurrence rates. The Optilume drug-coated balloon represents a step forward in the endoscopic management of urethral strictures. The drug-coated balloon may offer an intermediate step prior to repeated dilations, urethrostomies, or urethroplasty. This treatment modality is a promising alternative to current endoscopic management and an option for patients that are poor surgical candidates or decline urethroplasty.

Medical Management of Penile and Urethral Lichen Sclerosus with Topical Clobetasol Improves Long-Term Voiding Symptoms and Quality of Life.

PURPOSE: We evaluated the success of minimally invasive management of lichen sclerosus with topical and intraurethral clobetasol, as defined by improvement in patient reported outcome measures and nonprogression to surgery. MATERIALS AND METHODS: We conducted a review of our prospective ongoing quality improvement study to determine outcomes of our current standard practice for males with penile and urethral biopsy proven lichen sclerosus. Data were collected between 2011 and 2019, and included patient demographic information, medical and surgical histories, and location and extent of lichen sclerosus related pathology. The primary outcomes for this study were voiding function and voiding related quality of life, and were assessed using the AUASS (American Urological Association Symptom Score) and quality of life bother index, respectively. RESULTS: We identified 42 patients with biopsy proven lichen sclerosus related urethral stricture disease. Of these patients 85.7% were treated with intraurethral steroids alone and did not require surgical intervention. Median AUASS significantly improved from 12 to 8, and median quality of life bother index improved from 4 ("mostly dissatisfied") to 2 ("mostly satisfied"). Average stricture length of those with penile urethral disease and bulbar urethral disease was 4.8 cm (SD 3.0) and 16.2 cm (SD 6.5), respectively. Median followup was 8.4 months (IQR 2.6-26.4). CONCLUSIONS: Lichen sclerosus related urethral stricture disease can be effectively managed with intraurethral steroids. This minimally invasive management strategy improves patient reported voiding symptoms and voiding quality of life.

[The perspectives of adjuvant chemotherapy of urethral stricture].

A review of preclinical, clinical and postclinical (comparative) studies dedicated to adjuvant therapy for urethral strictures in the form of injections and instillations is presented in the article. The focus is on studies, carried out over the past decade. An information on new antifibrotic drugs used in other areas of medicine that could potentially be used in urology is also provided.

Efficacy of Use of Triamcinolone Ointment for Clean Intermittent Self Catheterization following Internal Urethrotomy.

INTRODUCTION: Internal urethrotomy is recommended for the treatment of urethral strictures shorter than 1.5 cm but has been associated with high recurrence rates. The aim of this study was to evaluate the efficacy of use of triamcinolone ointment for clean intermittent self catheterization in the prevention of urethral stricture recurrence after internal urethrotomy. METHODS: Total of 60 male patients undergoing internal urethrotomy were assigned into two groups and clean intermittent self catheterization was performed using either triamcinolone ointment or a water-based gel for lubrication of the catheter in this randomized clinical trial. Clean intermittent self catheterization regimen was continued for 6 months and patients were followed for 12 months. Urethrocystoscopic evaluation was done 6 and 12 months postoperatively. RESULTS: The recurrence rates were compared between the two groups. There were no significant differences in patient characteristics and etiology of the stricture between the two groups. There was a 6 (22.22%) recurrence rate in the patients of the triamcinolone group against 13 (46.42%) in those of the control group after the first internal urethrotomy (P=0.04). After second internal urethrotomy, the urethra was stabilized in 5 (83.3%) of the patients in the triamcinolone group and 8 (61.5%) those in the control group (P=0.05). We also found a significant correlation between recurrence and stricture length (P=0.02) but the time to recurrence was not statistically significant (P=0.16). CONCLUSIONS: The use of triamcinolone ointment in patients on CISC regimen after internal urethrotomy significantly decreased the stricture recurrence rate.

The Effectiveness of Tamoxifen in the Prevention of Recurrent Urethral Strictures Following Internal Urethrotomy.

OBJECTIVE: Tamoxifen was not used earlier in clinical practice to decrease the urethral re-stricture rate after visual internal urethrotomy (VIU). In this study, we are the first to report the use of Tamoxifen as an adjuvant therapy to decrease the re-fibrosis and stricture recurrence post-VIU. PATIENTS AND METHODS: Between 2015 and 2017, 60 patients underwent VIU for post-traumatic bulbar urethral stricture ≤1 cm. They were randomly divided into 2 groups (30 patients each). The Tamoxifen group cases received Tamoxifen 10 mg twice daily for 6 months post-VIU. The control group did not receive any medications. All patients were evaluated using the IPSS score, uroflowmetry, and perineal ultrasonography preoperatively at 3 and 6 months. RESULTS: At presentation, there was no significant difference between patients of both groups in terms of IPSS score, Qmax, stricture width, and length. At 6 months follow-up, the mean IPSS score for the Tamoxifen group was 12.3 (8-19) in comparison with 20 (12-26) in the control group (p < 0.001). The Tamoxifen group had mean Qmax 11.1 mL/s (9-14), while those of the control group had mean Qmax 8.2 mL/s (6-10; p < 0.001). Using perineal ultrasound, only stricture width showed to be significantly smaller in the Tamoxifen group (p = 0.001). CONCLUSION: Tamoxifen seemed to be effective in reducing the recurrence of urethral stricture post-VIU. There was a significant improvement of the clinical outcome regarding Qmax and IPSS score after Tamoxifen adjuvant therapy.

Evaluation of the Distribution of Paclitaxel After Application of a Paclitaxel-Coated Balloon in the Rabbit Urethra.

INTRODUCTION: Urethral strictures are a common urologic problem that could require complex reconstructive procedures. Urethral dilatation represents a frequent practiced intervention associated with high recurrence rates. Drug-coated percutaneous angioplasty balloons (DCBs) with cytostatic drugs have been effectively used for the prevention of vascular restenosis after balloon dilatation. To reduce restenosis rates of urethral dilatation, these balloons could be used in the urethra. Nevertheless, the urothelium is different than the endothelium and these drugs may not be distributed to the outer layers of the urethra. Thus, an experiment was performed to evaluate the distribution of paclitaxel (PTX) in the rabbit urethra after the inflation of a PTX-coated balloon (PCB). MATERIALS AND METHODS: Eleven rabbits underwent dilatation of the posterior urethra with common endoscopic balloons after urethrography. Nine of these rabbits were additionally treated with PCB. The urethras of the two control animals were removed along with three more dilated with PCB urethras immediately after the dilatation. The remaining of the urethras were removed after 24 (n = 3) and 48 hours (n = 3). The posterior segments of the urethras were evaluated with hematoxylin and eosin staining as well as with immunohistochemistry with polyclonal anti-PTX antibody. RESULTS: The two control specimens showed denudation of the urothelium after balloon dilatations and no PTX was observed. All specimens from dilated PCB urethras showed distribution of PTX to all layers of the urethra. The specimens that were immediately removed exhibited denudation of the urothelium without any inflammation. The specimens removed at 24 and 48 hours showed mild acute inflammation. CONCLUSION: PTX was distributed to the urothelial, submucosal, and smooth muscle layers of the normal rabbit urethra immediately after dilatation with a DCB. PTX and mild inflammation were present at the site 24 and 48 hours after the dilatation.

Collagenase Clostridium Histolyticum in the Treatment of Urologic Disease: Current and Future Impact.

INTRODUCTION: Peyronie's disease (PD) is a connective tissue disorder resulting in the abnormal accumulation of type I to III collagen, fibrin, and disorganized elastic fibers in the tunica albuginea of the penis. Many medical and non-pharmacologic modalities have been used in the treatment of PD; however, these approaches have proved largely ineffective, with surgery being the only definitive treatment. Intralesional injection of collagenase Clostridium histolyticum (CCH) has recently become the gold standard for minimally invasive treatment of PD, and studies have suggested the role of CCH could expand to the treatment of other urologic conditions such as urethral stricture disease. AIM: To provide an update on available data on the use of CCH in the treatment of PD and other urologic conditions. METHODS: Comprehensive review of recent clinical trials and in vivo studies that examined the safety and efficacy of CCH in urologic disease. MAIN OUTCOME MEASURES: Assessing the efficacy of CCH in the management of PD as determined by improvement in the severity of penile fibrosis, curvature deformity, and pain. RESULTS: Several well-designed clinical trials have demonstrated the efficacy and tolerability of CCH in the treatment of PD. CCH has demonstrated significant decreases in penile curvature and plaque consistency and improvements in patient satisfaction. Treatment durability and long-term adverse effects are still being assessed; however, outcomes of PD management with CCH continue to replicate the results obtained during the IMPRESS clinical trials. Preliminary studies support the premise that CCH can modify disease progression in patients with acute-phase PD. Furthermore, one in vivo study showed that CCH also could be applied to urethral stricture disease without serious adverse complications. CONCLUSION: CCH continues to be the mainstay for non-surgical management of stable-phase PD. However, its role in the treatment of acute-phase PD, PD with ventral plaques, and urethral stricture disease could expand in the coming years. Gabrielson AT, Spitz JT, Hellstrom WJG. Collagenase Clostridium Histolyticum in the Treatment of Urologic Disease: Current and Future Impact. Sex Med Rev 2018;6:143-156.

Internal Urethrotomy With Intralesional Mitomycin C: An Effective Option for Endoscopic Management of Recurrent Bulbar and Bulbomembranous Urethral Strictures.

OBJECTIVE: To describe our experience with direct visual internal urethrotomy (DVIU) and mitomycin C (MMC) for recurrent bulbar and bulbomembranous urethral strictures of radiation and non-radiation-induced etiologies. METHODS: We reviewed our database of consecutive patients presenting to our tertiary care institution with recurrent bulbar and bulbomembranous urethral strictures who underwent DVIU with MMC from 2011 to 2016. Patients were stratified by radiation-induced strictures (RIS) vs non-RIS. Cold-knife incisions were made at 12-, 3-, and 9-o'clock positions followed by intralesional injection of 10 mL MMC (0.4 mg/mL) in 0.2-0.4 mL aliquots and 1 month of postoperative daily clean intermittent catheterization (CIC). RESULTS: All 44 patients (RIS n = 18, non-RIS n = 26) failed prior endoscopic management or urethroplasty. Median stricture length was 2.0 cm (interquartile range [IQR] 1.0-2.5). Over a median follow-up of 25.8 months (IQR 12.9-47.2), 75.0% of patients (33/44) required no additional surgical intervention (RIS 12/18, 66.7%; non-RIS 21/26, 80.8%). Median time to stricture recurrence among those who recurred was 10.7 months (IQR 3.9-17.6; RIS 9.4 months, IQR 3.5-17.6; non-RIS 11.2 months, IQR 8.0-25.6). Four patients (RIS n = 2, non-RIS n = 2) elected to undergo urethroplasty for recurrence. A second DVIU with MMC was performed in the remaining recurrences (n = 7) with no further surgical intervention required in 37 of 40 of patients (92.5%) overall (RIS 14/16, 87.5%; non-RIS 23/24, 95.8%). No long-term complications were attributable to MMC. CONCLUSION: DVIU with MMC and short-term CIC for recurrent, short, bulbar and bulbomembranous urethral strictures is a safe endoscopic modality with promising early results. This approach may be useful for patients who are suboptimal candidates for open reconstruction.

Intraurethral Steroids are a Safe and Effective Treatment for Stricture Disease in Patients with Biopsy Proven Lichen Sclerosus.

PURPOSE: We investigated outcomes of the contemporary practice of administering intraurethral steroids to treat stricture disease in patients with biopsy proven lichen sclerosus. MATERIALS AND METHODS: We performed an institutional review board approved review of the records of patients with biopsy proven lichen sclerosus stricture disease from October 2010 to September 2015. Study inclusion criteria were age 18 years or greater and male gender. Extracted data included patient demographics, comorbidities, location of lichen sclerosus, previous therapies and need for further interventions. Management was considered successful when there was no need for subsequent escalation of therapy. The intraurethral steroid regimen consisted of applying clobetasol cream to the affected urethra to lubricate a calibration device such as a urinary catheter or meatal dilator. The initial phase of therapy included twice daily application for 2 to 3 months, at which point the frequency was decreased by the clinician, enabling the patient to titrate medication use as needed. RESULTS: We identified 40 patients with biopsy proven lichen sclerosus who had urethral stricture as part of the disease state. Of these patients 28 received the intraurethral steroid regimen and success was achieved in 25 (89%). Mean followup was 24.8 months. No patient who was started on the intraurethral steroid regimen proceeded to urethroplasty. CONCLUSIONS: Based on our outcomes we have developed a stepwise treatment algorithm for patients with biopsy proven lichen sclerosus stricture disease that uses intraurethral steroids before initiating plans for invasive surgery.

Application of Wnt Pathway Inhibitor Delivering Scaffold for Inhibiting Fibrosis in Urethra Strictures: In Vitro and in Vivo Study.

OBJECTIVE: To evaluate the mechanical property and biocompatibility of the Wnt pathway inhibitor (ICG-001) delivering collagen/poly(L-lactide-co-caprolactone) (P(LLA-CL)) scaffold for urethroplasty, and also the feasibility of inhibiting the extracellular matrix (ECM) expression in vitro and in vivo. METHODS: ICG-001 (1 mg (2 mM)) was loaded into a (P(LLA-CL)) scaffold with the co-axial electrospinning technique. The characteristics of the mechanical property and drug release fashion of scaffolds were tested with a mechanical testing machine (Instron) and high-performance liquid chromatography (HPLC). Rabbit bladder epithelial cells and the dermal fibroblasts were isolated by enzymatic digestion method. (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay) and scanning electron microscopy (SEM) were used to evaluate the viability and proliferation of the cells on the scaffolds. Fibrolasts treated with TGF-ß1 and ICG-001 released medium from scaffolds were used to evaluate the anti-fibrosis effect through immunofluorescence, real time PCR and western blot. Urethrography and histology were used to evaluate the efficacy of urethral implantation. RESULTS: The scaffold delivering ICG-001 was fabricated, the fiber diameter and mechanical strength of scaffolds with inhibitor were comparable with the non-drug scaffold. The SEM and MTT assay showed no toxic effect of ICG-001 to the proliferation of epithelial cells on the collagen/P(LLA-CL) scaffold with ICG-001. After treatment with culture medium released from the drug-delivering scaffold, the expression of Collagen type 1, 3 and fibronectin of fibroblasts could be inhibited significantly at the mRNA and protein levels. In the results of urethrography, urethral strictures and fistulas were found in the rabbits treated with non-ICG-001 delivering scaffolds, but all the rabbits treated with ICG-001-delivering scaffolds showed wide caliber in urethras. Histology results showed less collagen but more smooth muscle and thicker epithelium in urethras repaired with ICG-001 delivering scaffolds. CONCLUSION: After loading with the Wnt signal pathway inhibitor ICG-001, the Collagen/P(LLA-CL) scaffold could facilitate a decrease in the ECM deposition of fibroblasts. The ICG-001 delivering Collagen/P(LLA-CL) nanofibrous scaffold seeded with epithelial cells has the potential to be a promising substitute material for urethroplasty. Longer follow-up study in larger animals is needed in the future.