Overview of Urethral Reconstruction by Tissue Engineering: Current Strategies, Clinical Status and Future Direction

BACKGROUND: Urinary tract is subjected to a variety of disorders such as urethral stricture, which often develops as a result of scarring process. Urethral stricture can be treated by urethral dilation and urethrotomy; but in cases of long urethral strictures, substitution urethroplasty with genital skin and buccal mucosa grafts is the only option. However a number of complications such as infection as a result of hair growth in neo-urethra, and stone formation restrict the application of those grafts. Therefore, tissue engineering techniques recently emerged as an alternative approach, aiming to overcome those restrictions. The aim of this review is to provide a comprehensive coverage on the strategies employed and the translational status of urethral tissue engineering over the past years and to propose a combinatory strategy for the future of urethral tissue engineering. METHODS: Data collection was based on the key articles published in English language in years between 2006 and 2018 using the searching terms of urethral stricture and tissue engineering on PubMed database. RESULTS: Differentiation of mesenchymal stem cells into urothelial and smooth muscle cells to be used for urologic application does not offer any advantage over autologous urothelial and smooth muscle cells. Among studied scaffolds, synthetic scaffolds with proper porosity and mechanical strength is the best option to be used for urethral tissue engineering. CONCLUSION: Hypoxia-preconditioned mesenchymal stem cells in combination with autologous cells seeded on a prevascularized synthetic and biodegradable scaffold can be said to be the best combinatory strategy in engineering of human urethra.

Clinical study of transverse island fasciocutaneous fascia flap for treatment of meatus and navicular fossa stricture / 中华泌尿外科杂志

Objective To investigate the clinical effect of transverse island fasciocutaneous penile flap in the treatment of meatus and navicular fossa stricture.Methods Fifteen patients with urethral reconstruction with transverse island fasciocutaneous penile flap from October 2014 to December 2018 were enrolled.Six patients had a history of urethroscopic surgery,three had a history of lichensclerosus,three had a history of urethral dilation,and three had no obvious causes.All patients underwent transverse incision under the coronal sulcus,and after fully dissecting the urethra,the urethra was opened longitudinally ventrally.After measuring the actual length of stenosis,the irradiance fascia flap with the corresponding length of the incision was reconstructed.The patients were reviewed at 1 and 3 months after operation,and any complications such as recurrence or urinary fistula were recorded.The urine flow rate was tested 3 months after surgery.Results All 15 patients in this group underwent a successfully operation.The actual measurement of urethral stricture length was 0.5-4.0 cm during operation,with the average of 2.82 cm.Three months after the operation,the urine flow rate ranged from 13.5 ml/s to 23.7 ml/s,with an average of 18.5 ml/s.The overall successful rate was 93.3％ (14/15).The rate of post-operative fistula was 20.0％ (3/15).Two cases complained of needle-like fistula at the incision.One case healed after 3 months,and the other gave up further treatment.One patient developed urethral stricture and urethral skin spasm again 1 month later and was surgically repaired again.Conclusions The initial experience of pedicled island fascia flap for the treatment of urethral stenosis and scaphoid stenosis is safe,feasible and effective for the treatment of urethral stricture.

Selection of procedures in one stage urethroplasty for treatment of the coexistence of urethral stricture in the anterior and posterior urethra / 中华泌尿外科杂志

Objective To explore selection of the procedures in one stage urethroplasty for treatment of the coexistence of urethral strictures in anterior and posterior urethra.Methods Between January 2008 and December 2014, a total of 27 patients with coexist strictures simultaneously in anterior urethra and posterior urethra were treated in our hospital.The mean age was 38 years old (ranging 13-83 years old.Stricture etiology was secondary to lichen sclerosus in 2 patients, iatrogenic in 3 and posttraumatic in 22.The mean length of urethral stricture was 11cm (ranging 6-14cm).Two procedures for treatment of anterior urethral stricture, including augmentation of urethroplasty using penile skin flap was performed in 20 patients and augmentation of urethroplasty using lingual mucosa in 7.Three procedures for treatment of posterior urethral stricture, including non-transecting spongiosum end to end anastomosis of the two urethral ends was performed in 3 patients, end to end anastomosis of the two urethral ends was performed in 17 and substitution urethroplasty using different tissues was performed in reminder 7 patients.Of them, pedicle scrotal skin urethroplasty was performed in 2 patients and lingual mucosal graft urethroplasty in 5 patients.Results The patients were mean followed up 2.6 years (ranging 0.545.0 years) with an overall success rate of 88.9％ (24 of 27 cases).Complications developed in 3 patients (11.1％).Of the 17 patients with end to end anastomosis, urethral stricture developed respectively 4 and 6 months in 2 patients and voiding well after pedicle scrotal skin urethroplasty.Urethral pseudodiverticulum developed 9 months after pedicle penile flap urethroplasty in another patient and voiding well after urethroplasty.Urethrography showed patent urethra with adequate lumen in the remaining patients and mean urinary peak flows was 21.3 ml/s (ranging 14.2-37.9 ml/s).Conclusions Substitution urethroplasty using penile skin or oral mucosa was more good procedure for anterior urethral stricture during the treatment of the coexistence of urethral stricture in the anterior and posterior urethra.The treatment of posterior urethral stricture was based on the length of the stricture, local condition to make a choice between anastomotic urethral reconstruction and substitution urethroplasty using other tissue.

The efficacy of non-transecting spongiosum end to end anastomosis of urethra for treatment of posterior urethral stricture / 中华泌尿外科杂志

Objective To report preliminary experiences with a novel procedure of end-to-end anastomotic repairment of posterior urethral strictures.Methods From January 2011 to December 2014,a total of 26 patients with posterior urethral strictures(2 patients with exist simultaneously anterior urethral stricture)were treated.The mean age was 43 years (rang 13-83 years).The etiology of urethral strictures were trauma in 23 patients and iatrogenic causes in 3 patients.The mean length of urethral stricture was 2 cm (rang 1-3 cm).Suprapubic cystostomies were performed in all 26 patients.All patients accepted the non-transecting spongiosum bulbar-membranous end to end anastomosis.During the operation,the perineal incision was made.The dorsal stricture urethra was incised,extending to the 1.5 cm normal urethra at each side.Then,the interrupted end to end suture was performed with 3-0 absorbable suture.Results The mean surgical time was 55 minutes in 24 patients(45-65 minutes).There was no evidence of wound infection or urethrocutaneous fistula during perioperation period.The mean follow-up time for 26 patients were 16 months (4 mouths-3 years).There was no recurrent stricture on symptomatic assessment or uroflowmetry.The patients voided well with mean peak flows rate 25.4 ml/s (16.8-59.1 ml/s).Urethrography showed that each patient had a patent urethra with adequate lumen.Conclusions Non-transecting spongiosum end to end anastomosis of urethra technique could retain spongiosal blood support.In present preliminary study,it appears to give similar results as those of traditional anastomotic urethroplasty.

The selection of procedures for the treatment of panurethral stricture secondary to lichen sclerosus and the histological evidence of urethral involvement / 中华泌尿外科杂志

Objective To explore the procedure selection and outcomes of treatment for the patients with severe panurethral strictures secondary to lichen sclerosus ( LS ) and evaluated the bulbar urethral specimens histologically . Methods Seventy-eight patients with severe panurethral strictures of LS underwent one-stage urethroplasty using different mucosal grafts between January 2003 and December 2014. The mean age was 48 years (range 38-72).The mean stricture length was 14.3 ±2.6 cm (range 11.0-22.0).Midline perineal incisions or circumcoronal and midline perineal incisions were used and two procedures were chosen as follow:①the strictured urethras were dissected from the corpora cavernosa only along the left side and the stricture urethras were opened by a dorsal longitudinal incision which extended about 1.5 cm into the proximal healthy urethras .The strictured urethras were augmented using oral mucosal grafts(1.5 to 2.0 cm in width and an appropriate in length ) ( n=50); ② for the patients whose urethras were very narrow or obliterated , the urethras were reconstructed using colonic mucosal graft ( 3 cm in width and an appropriate in length)after the severe strictured urethras were excised (n=28).Biopsies were taken separately from the urethral meatus and bulbar urethral specimens .Results All of the 78 patients were followed up for 6-110 months (mean of 48.3 months).Sixty-nine patients (88.5%) urinated well, with the mean urinary peak flow rate of 23.4 ml/s ( range 15.2-47.0 ml/s ) , and urethrography showed that each had a patent urethra with adequate lumen .Complications associated with urethra occurred in 9 patients (11.5%) . Three patients developed urinary fistula secondary to infection , which required surgical correction;6 patients developed meatal stenosis 3 -11 months postoperatively , and all voided well after meatoplasty.The incidence of LS-positive biopsies was 100.0%in the glans and 88.5%in the meatus.In the bulbar urethral mucosa , the histological alteration in all biopsies was squamous metaplasia of the hyperplasia , and no histological evidence of typical LS was documented .However , homogenization of the collagen with diffuse lymphocyte infiltration was observed in the bulbar urethral specimens of 2 patients, and squamous metaplasia of the hyperplasia with serious orthokeratosis that was similar to its cutaneous counterpart was found in another 2 patients.Conclusions Our study suggests that urethroplasty with oral mucosal grafts is effective to treat panurethral stricture associated with LS .Urethroplasty with a colonic mucosal graft is suitable for repairing very severe strictured or obliterated urethra .No histological evidence of typical LS is observed in the bulbar urethral specimens .

Evaluation of erectile function after the reconstruction of long urethral stricture / 中华泌尿外科杂志

Objective To investigate the effect of substitutive reconstruction of long urethral stricture on male erectile function. Methods From January 2007 to January 2009, 23 patients with anterior or posterior long urethral stricture were accepted for a variety of onlay substitutive procedures, including lingual mucosa, perputial skin, and mid-scrotal skin. During the follow-up, data from the International Index of Erectile Function-5 (ⅡEF-5) questionnaire and the Quality of Life (QOL) questionnaire as well as maximal flow rate were recorded. All data were compared with those obtained before surgery. Results Significant improvement in QOL (1.22 ± 1.40, 1.82 ± 1. 17,2.07± 0.46) and maximal flow rate (22.46± 4.65, 23.81 ± 6.22, 21.52 ±7.44 ) could be observed 3, 6 and 12 months after surgery compared with those before surgery (5. 22 ± 0. 75, 3. 93 ± 3. 62)(P＜0.01). No significant differences in the responses to the ⅡEF-5 questionnaire were observed among all patients during the follow-up (P＞0. 05). At the 3, 6 and 12 months after procedure,scores of ⅡEF-5 in patients with anterior urethral stricture ( 17.79 ± 6.42, 16. 57 ± 4. 78, 16.01 ±3.85) were significantly higher than those with posterior urethral stricture (11.67 ± 2.59, 12.35 ±1.83,13. 19±1.67, P＜0.05). In patients with posterior urethral stricture, the multiple linear regression showed that age, time interval of injury and length of stricture were related to the ⅡEF-5score (P＜0.05). Conclusions Substitutive reconstruction for treating the long urethral stricture has little effect on male erectile function. But the location of stricture, especially extended to posterior urethra, may have impact on the erectile function.

Urethroplasty of Urethral Defect with Longitudinal Tubed Flap of Scrotal Skin after Fournier's Gangrene (Necrotizing Fascitis)

PURPOSE: The management of urethral defect represents one of the most challenging clinical problems in uroplastic surgery. Especially for defect after Fournier's Gangrene, optimal management is still a hard problem. During extensive urethral reconstruction, to overcome the poor vascularity due to periurethral scarred tissue and limitation of the choice of local flap, we report our experience with one-stage reconstruction of urethral defect using a longitudinal tubed flap of scrotal skin. METHODS: A 72-year-old man with several years of diabetes mellitus history visited for swelling and pain of scrotal area. After diagnosis of Fournier's Gangrene, radical debridement was performed and 6 cm of urethral defect on border of penile-scrotal ventral area was made. Rectangular scrotal skin flap (6 x 2.5 cm) based on external spermatic fascia was elevated and tubed longitudinally. After transfer the flap to the defect area, end-to-end anastomosis was performed bilaterally. RESULTS: 4 weeks after the operation, the patient started voiding him-self and urethrography showed good fluence of contrast agent. Long term evaluation reveals stable performance characteristics without any complications. CONCLUSION: We suggest a one-stage reconstruction of extensive urethral defect using a longitudinal tubed flap of scrotal skin. Advantages of this procedures are simple, one-stage reconstruction with the reliable scrotal skin flap based on external spermatic fascial vasculature, and no donor morbidity.

Advances in the research of urethral tissue engineering and scaffold materials / 国际生物医学工程杂志

Urethral reconstruction is required in congenital abnormalities such as hypospadia and urethral stricture caused by trauma or infection. The development of tissue engineering has brought new hope to the field of urethral reconstruction. Much progress has been made in the experimental and clinical research of using tissue engineering for urethral reconstruction as well as the research of the scaffold materials. This review focuses on the recent progress in this field.

Uso de mucosa bucal para reconstrucción uretral / Oral mucosa for uretral reconstruction

La reconstrucción de la estrechez uretral requiere la eliminación del tejido fibroso patológico y el aporte de tejido sano que reemplace la pared uretral dañada. En las últimas décadas, el uso de injertos de mucosa oral se ha consolidado como la técnica de primera elección en la mayoría de los casos. La mucosa oral está fácilmente disponible y es de sencillo procuramiento. Su textura es muy apropiada y los injertos “toman” con facilidad, prácticamente sin retracción. En este artículo se describe en detalle la técnica que usamos en nuestro hospital para el procuramiento de mucosa oral.

Urethral stricture reconstruction requires replacement of the pathologic fibrous urethral tissue with healthy, normal tissue. In the last decades, oral mucosa graft has become the preferred alternative inmost cases. Oral mucosa is readily available, simple to use and has a high success rate. In this communication we describe in detail the technique we use in our hospital for oral mucosa procurement.