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Purpose: To establish a psychometric validated pelvic fracture-urethral injury postoperative erectile function patient reported outcome measure (PFUI pEF PROM). We also aim to explore PFUI patients' potential classification and suitable postoperative erectile function assessment pattern., Methods: A total of 93 PFUI patients who treated by excision and primary anastomotic (EPA) urethroplasty from January 2020 to August 2022 were enrolled to this study. Patients who had intercourse completed the IIEF-5, those who had sexual stimulation other than intercourse finished PFUI pEF PROM, and those who performed both completed the IIEF-5, and PFUI pEF PROM. Erection Hardness Score (EHS) was completed by all patients. This PROM was performed psychometric validation and used to find PFUI patients potential classification through latent class analysis. Then, we determined the cut-off value though receiver-operating characteristic (ROC) curve and performed univariate analysis subgroups feature., Results: The PFUI pEF PROM demonstrated high reliability and validity with a Cronbach's alpha of 0.928. It correlated significantly with IIEF-5 (r = 0.550, p < 0.001) and EHS (r = 0.909, p < 0.001). The latent class analysis identified three patient subgroups, with 14.5 as the subgroup cut-off value. Urethral stricture length, IIEF-5, and EHS score were identified as influence factors for maximal erection potential. An assessment pattern combining IIEF-5, EHS, and the PFUI pEF PROM covered 92.5% of patients., Conclusion: This PROM effectively addresses the current limitation in assessing erectile function in PFUI patients. This study provides a promising tool for stratified assessment, prediction erection recovery, and treatment guidance in the PFUI Erectile dysfunction field., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To evaluate the efficacy of urethral-sparing laparoscopic simple prostatectomy (US-LSP) for the treatment of large-volume (>80 ml) benign prostatic hyperplasia (BPH) with asymptomatic urethral stricture (urethral lumen > 16 Fr) after urethral stricture surgery., Methods: We retrospectively analyzed clinical data of 39 large-volume BPH patients with asymptomatic urethral stricture after urethral stricture surgery who underwent US-LSP from January 2016 to October 2021. Postoperative follow-ups were scheduled at 1, 3, and 6 months., Results: All patients affected by significant BPH-related lower urinary tract symptoms (LUTS) including 22 cases with asymptomatic anterior urethral stricture and 17 cases with asymptomatic posterior urethral stricture. Median operative time was 118 min (interquartile range [IQR]100-145). Median estimated blood loss was 224 ml (IQR: 190-255). 33 patients(84.6%) avoided continuous bladder irrigation. Postoperative complications occurred in 5 patients (12.8%), including 4 cases with Clavien-Dindo grade 1 and grade 2 and 1 case with grade 3a. During follow-up, US-LSP presented statistically significant improvements in LUTS compared to baseline (P < 0.05). A total of 25 patients had normal ejaculation preoperatively and 3 patients (12%) complained retrograde ejaculation postoperatively. Two patients (5.1%) reported stress urinary incontinence (SUI) and no patient reported aggravated urethral stricture during follow-up., Conclusions: US-LSP was safe and effective in treating large-volume BPH with asymptomatic urethral stricture after urethral stricture surgery. Meanwhile, US-LSP could reduce the risk of SUI in patients with asymptomatic posterior urethral stricture and maintain ejaculatory function in a high percentage of patients., (© 2024. The Author(s).)

Previous studies have postulated that the urethral vasculature (UV) might play an important role in urinary continence for women. The goal of this research was to compare the UV in pre- and post-menopausal women using a super-resolution ultrasound imaging method called Super Ultrasound for Greater Accuracy and Resolution (SUGAR). We found that post-menopausal women exhibited decreased UV parameters such as fractal dimension, vessel proportion, and mean blood vessel diameter than pre-menopausal women. We also discriminated the vascular pattern in several layers of the urethra and its surrounding in vivo , including the urethral mucosa and submucosa, urethral muscle, and anterior vaginal wall. Besides, the statistical analysis of the vasculature pattern showed that most of the UV parameters peaked at mid-urethra. Ultimately, the UV parameters exhibited a tendency of first increasing, then reducing, and finally decreasing with age., Competing Interests: The authors have no disclosures to declare., (© 2024 The Author(s).)

Purpose: To compare the diagnostic ability of traditional radiographic urethrography and magnetic resonance urethrography (MRU) for iatrogenic bladder outlet obliteration (BOO), and explore the efficacy and complications of laparoscopic modified Y-V plasty for patients selected based on MRU evaluation., Methods: 31 patients with obliteration segments ≤ 2 cm and no false passages or diverticula based on MRU evaluation from eight centers in China were included. Obliteration segments were measured preoperatively by MRU and conventional RUG/VCUG and compared with intra-operative measurements. Surgical effects were evaluated by uroflow rates, urethrography, or cystoscopy at 1, 3, 6, and 12 months post-operation and then every 12 months. Postoperative urinary continence was assessed by 24-h urine leakage (g/day)., Results: The results showed that MRU measured the length of obliteration more accurately than RUG/VCUG (MRU 0.91 ± 0.23 cm, RUG/VCUG 1.72 ± 1.08 cm, Actual length 0.96 ± 0.36 cm, p < 0.001), and clearly detected false passages and diverticula. Laparoscopic Y-V plasty was modified by incisions at 5 and 7 o'clock positions and double-layer suture with barbed sutures. All operations were successfully completed within a median time of 75 (62-192) minutes and without any complications. Urethral patency and urinary continence rates were 90.3% (28/31) and 87.1% (27/31), respectively. Three recurrences were cured by direct visual internal urethrotomy. Four patients had stress urinary incontinence after catheter removal 14 days post-operation, with urine leakage of 80-120 g/day, not relieved during follow-up., Conclusions: Laparoscopic modified Y-V plasty based on MRU evaluation is a promising approach for iatrogenic BOO, with a high patency rate and a low incontinence rate., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Stem cell (SC) therapy has been shown high prospects in erectile dysfunction (ED) treatment. Without ethical issues and risks of immune rejection and tumorigenesis of exogenous SC therapy, endogenous stem/progenitor cells (S/PCs) have a better potential for ED management, and their homing and redistribution are controlled by SDF1-α/CXCR4 axis. Considering black phosphorus nanosheet (BPNS) has emerged as an efficient and safe drug vehicle due to its large surface area, biodegradability, and the ability to retain and slowly release its loaded drugs, BPNS is utilized to load SDF1-α, a chemokine for S/PCs, to construct the BP@SDF1-α complex to efficiently recruit stem cells (SCs) by injury-site injection and thus ameliorate ED within the bilateral cavernous nerve injury (BCNI) rat models. We find that BP@SDF1-α can efficiently recruit exogenous SCs and endogenous S/PCs to corpus cavernosum and main pelvic ganglion (MPG) by local administration. Of note, ascribing to endogenous S/PCs recruitment, it also successfully alleviates ED in BCNI rat models by enhancing the protein expression levels of α-SMA, CD31, and nNOs, and eliciting less collagen deposition in the penis after its combined injection at corpus cavernosum and MPG. Thus, this study provides a new insight into the treatment of ED with endogenous S/PCs. BIODEGRADABLE NANO BLACK PHOSPHORUS BASED SDF1-α DELIVERY SYSTEM AMELIORATES ERECTILE DYSFUNCTION IN A CAVERNOUS NERVE INJURY RAT MODEL BY RECRUITING ENDOGENOUS STEM/PROGENITOR CELLS., (© 2023. The Author(s).)

The urothelium covers the inner surface of the urinary tract, forming a urinary tract barrier. Impairment of the integrity and dysfunction of the urinary tract barrier is associated with the occurrence and development of various diseases. The development of a three-dimensional model of the urothelium is critical for pathophysiological studies of this site, especially under physiological fluid shear stress stimulated by the urinary flow. In this study, a urothelium on-chip is fabricated with micromilling and replica molding techniques, which contains a microfluidic chip for cell culture and a pump-based fluid perfusion system. The mechanical properties of the human urinary tract are simulated by adjusting the concentration and degree of amino substitution of the gelatin methacrylate hydrogel. The matrix stiffness is similar to the natural urinary tract. Pulsatile flow and periodic flow are provided to simulate the fluid environment of the upper and lower urinary tracts, respectively. The results show that the physiological fluid shear stress could promote the differentiation and maturation of urothelial cells. The model could simulate the three-dimensional structure of urothelium and urinary flow microenvironment, showing morphological structure close to the natural urothelium, specific differentiation and maturation markers (uroplakin 2, cytokeratin 20), and urothelial barrier function., (Creative Commons Attribution license.)

Objective: To explored the curative effects of various surgical methods used to treat complicated posterior urethral strictures in boys and the long-term complication., Methods: We retrospectively studied 28 boys under 14 years of age with complicated posterior urethral strictures treated at our hospital from January 2015 to December 2020. Urethral angiography revealed posterior urethral strictures. Twelve had previously failed urethral surgery; four had urethral fistulae. All underwent end-to-end urethral anastomoses via a transperineal, inferior pubic approach. We freed the distal end of the urethra, split the penile cavernous septum, partially resected the lower edge of the pubic symphysis, and rerouted the urethra under a corpus cavernosum to reduce the tension of the urethral anastomosis., Results: All boys were 2-14 years of age at the time of surgery (mean 6.3 years). The urethral strictures were 3-5.5 cm in length (mean 4.2 cm). Catheters were removed 4 weeks postoperatively. The postoperative follow-up time was 4-72 months (mean 36.8 months). Twenty-four patients exhibited unobstructed urination after a single operation. The maximum urinary flow rate was 15-22 ml/s (average 17.8 ml/s); the success rate was 85.7%. Two patients required second urethral end-to-end anastomoses; urination became normal postoperatively. Two continued to exhibit cystostomies, and two evidenced mild incontinence. Of the six children who have attained puberty, two report erectile dysfunction., Conclusion: End-to-end urethral anastomosis via a transperineal inferior pubic approach is an ideal treatment for posterior urethral strictures in boys. The complications include incontinence and erectile dysfunction, and require long-term follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhu, Song, Sa, Xu and Fu.)

Context: Oral mucosa graft (OMG) and penile skin flap (PSF) are common substitutions in urethroplasty; however, the recommended substitution for anterior urethral strictures remains uncertain., Objective: To compare the efficacy of OMG and PSF in anterior urethral strictures in terms of success rate and prevalence of postvoid dribbling based on current studies., Evidence Acquisition: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and registered at PROSPERO (ID: CRD42022313879). All publications until March 1, 2022, were searched in the PubMed, EMBASE, and Cochrane Library databases without any restriction. Studies that focused on patients with anterior urethral strictures undergoing single-stage augmentation urethroplasty with OMG and PSF, and reported comparable success rates between the two substitutions were included., Evidence Synthesis: Thirteen studies involving a total of 1216 patients were included in the screening procedures, and 12 studies were eventually included in the meta-analysis. No significant difference in success rates was identified between OMG and PSF (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 0.96-2.07, p  = 0.08). No significant difference was observed in the comparison of success rates in penile urethral strictures (OR: 0.95, 95% CI: 0.53-1.70, p  = 0.86) and in the comparison of postvoid dribbling (OR: 0.59, 95% CI: 0.31-1.11, p  = 0.10). However, a subgroup analysis suggested that OMG had a higher success rate than PSF in studies with the top 50% sample size (six studies, OR: 1.678, 95% CI: 1.055-2.668, p  = 0.029) and the top 50% follow-up period (five studies, OR: 2.279, 95% CI: 1.193-4.352, p  = 0.013)., Conclusions: OMG provides the same success rate and postvoid dribbling as PSF. However, based on the existing evidence, OMG is more likely to perform better in a cohort with long-term follow-up and a relatively large sample size. More studies on the two substitutions are necessary to evaluate the factors of urethroplasty success rate, performance of substitutions in penile urethral strictures, and indicators of quality of life., Patient Summary: In this research, we compared the outcomes of oral mucosa graft (OMG) and penile skin flap for urethroplasty in anterior urethral stricture patients in 13 studies. We found that these were similar in terms of success rate and postvoid dribbling. However, OMG could probably provide a higher success rate when the studies had more patients or a longer follow-up period., (© 2023 The Author(s).)

Chiral and circularly polarized luminescence (CPL) materials with multiple stimuli responses have become a focus of attention. Meanwhile, elastomers have found substantial applications in a wide variety of fields. However, how to design and construct chiral elastomers, in particular CPL-active elastomers, still remains an academic challenge. In the present study, chiral helical substituted polyacetylene is chemically bonded with polydimethylsiloxane (PDMS) by hydrosilylation to form a chiroptically active elastomer. A CPL-active film was further fabricated by adding achiral fluorophores. Compared with the corresponding chiral helical polymer, the chiral films show much enhanced thermal stability in terms of chiroptical properties. The films also demonstrate reversible tunability in optical activity and CPL property when being subjected to a stretching-restoring process and exposed to a solvent like toluene. Further, noticeable chiral amplification is observed when the chiral PDMS film is superimposed with a pure PDMS film. This interesting finding is proposed to be due to the photoreflectivity of PDMS. This study provides an alternative strategy to exploit novel CPL-active elastomer materials with multiple stimuli responsivity and tunability, which may open up new opportunities for developing novel chiroptical devices.

The urinary system, comprising the kidneys, ureters, bladder, and urethra, has a unique mechanical and fluid microenvironment, which is essential to the urinary system growth and development. Microfluidic models, based on micromachining and tissue engineering technology, can integrate pathophysiological characteristics, maintain cell-cell and cell-extracellular matrix interactions, and accurately simulate the vital characteristics of human tissue microenvironments. Additionally, these models facilitate improved visualization and integration and meet the requirements of the laminar flow environment of the urinary system. However, several challenges continue to impede the development of a tissue microenvironment with controllable conditions closely resemble physiological conditions. In this review, we describe the biochemical and physical microenvironment of the urinary system and explore the feasibility of microfluidic technology in simulating the urinary microenvironment and pathophysiological characteristics in vitro . Moreover, we summarize the current research progress on adapting microfluidic chips for constructing the urinary microenvironment. Finally, we discuss the current challenges and suggest directions for future development and application of microfluidic technology in constructing the urinary microenvironment in vitro ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Objective: To investigate the treatment concept of Chinese urologists for anterior urethral strictures based on actual cases., Methods: A self-designed case-based questionnaire was distributed to the members of Official WeChat account of Learning Union from March 19, 2020, to April 10, 2020. Questionnaires requested respondents' demographic information and responses to five cases of anterior urethral stricture: short obliterative bulbar urethral stricture caused by straddle injury (Case 1), idiopathic bulbar urethral stricture after failure of multiple endoscopic therapy (Case 2), iatrogenic long penile urethral stricture (Case 3), lichen sclerosis-related urethral stricture (Case 4), and anterior urethral stricture in indwelling catheter after multiple failure of endoscopic surgery (Case 5). Data was described by frequency and percentage., Results: A total of 1,267 valid anonymous questionnaires were received. Urethroplasty was recommended more frequently than endoscopic surgery (Case 1: 47.8% vs. 32.8%,Case 2: 42.5% vs. 33.8%, Case 3: 36.1% vs. 26.7%). Referrals patients to other urologists engaged in urethral repair and reconstruction account for a high portion of the treatment (Case 1:18.4%, Case 2:23.1%, Case 3:36.5%, Case 4:27.7%,Case 5:9.3%). Excision and primary anastomosis urethroplasty (EPA) was preferred for treatment of Case 1 (42.5%). For Case 2, the most popular choice was EPA (30.6%). Although the patient has a history of failure in endoscopic surgery, 33.8% of urologists continue to choose endoscopic surgery. For Case 3, 20.0% of urologists would perform oral mucosal urethroplasty. Surprisingly, 5.9% chose EPA. For Case 4, 37.3% of urologists selected meatotomy, 30.4% suggested that glans and urethral biopsies should be performed. 21.0% chose to use steroid ointment after surgery. For Case 5, 26.3% of the respondents believed that urethrography should be performed after removing catheter more than one week, if the urine is obstructed during the period, performing cystostomy firstly., Conclusions: In China, the concept of urethroplasty is more widely accepted than endoscopic surgery for the treatment of anterior urethral strictures. The concept of referral has been widely formed among Chinese urologists. Better understanding of the comprehensive treatment of lichen sclerosis related anterior urethral stricture and the principle of urethral rest should be strengthened., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer WZ declared a past collaboration with the authors to the handling editor., (© 2022 Hou, Lin, Gu, Yuan, Wang, Xiu, Fu and Song.)

The aim of this study is to investigate the feasibility and efficacy of a novel biomimetic poly-l-lactide (PLLA) nanofiber membrane in repairing anterior urethral strictures from both preclinic and clinic. Biomimetic PLLA membrane was fabricated layer by layer according to the structure of human extracellular matrix. Microstructure, tensile strength, and suture retention strength were fully assessed. Before the clinical application, the safety and toxicology test of the biomimetic PLLA membrane was performed in vitro and in experimental animals. The patients underwent urethroplasty used dorsal onlay or lateral onlay technique. Then, they were followed up for 1 month, 3 months, 6 months, and then annually after the surgery. The mechanical experiments showed well property for application. Biomimetic PLLA membrane was safe according to the in vitro and animal studies. Then, a total of 25 patients (mean age 48.96 years) were included in the study from September 2016 to December 2018. After a mean follow-up of 33.56 months, 20 patients successfully treated with biomimetic PLLA membrane. Five patients (2 bulbar and 3 penile) suffered postoperational urethral stricture recurrence. None of infection or urinary fistula or any other adverse events related to the use of biomimetic PLLA membrane were observed during the follow-up period for all patients. The preliminary result confirmed the feasibility and efficacy of the biomimetic PLLA membrane as a novel material for anterior urethral repair. The long-term effects with more patients should be investigated in further studies., Competing Interests: Kunxue Deng, Jing Zhang, and Haitao Zhang are the employees of Medprin Regenerative Medical Technologies Co. Ltd. (Guangzhou, China), which is provider of the biomimetic poly‐l‐lactide (PLLA) nanofiber membrane. The other authors declare no competing interests., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Introduction and Hypothesis: Studies on the imaging of female periurethral masses are sparse, and most are focused on cystic lesions. In this article, we studied female periurethral solid masses and reported their ultrasonographic features., Methods: Fifteen women with periurethral solid masses pathologically diagnosed between January 2008 and April 2021 were assessed., Results: Each patient had only one mass. The pathological types included urethral caruncle (5 patients), urethral leiomyoma (3 patients), urethral malignant tumor (MT) (3 patients), periurethral spindle tumor (3 patients) and cartilage necrosis of pubic symphysis (PS) (1 patient). On ultrasound, all urethral caruncles were located at the urethral meatus. They were hypoechoic/isoechoic and rich in blood flow signal. Each leiomyoma presented as a well-defined hypoechoic mass with an oval shape. The urethral MT had inhomogeneous/isoechoic echoes, with medium to abundant blood flow signal. The spindle cell tumors had regular/irregular shapes, moderate/high density echogenicity and little/rich blood flow signals. The articular cartilage necrosis of PS was regular in shape, with mixed echogenicity and no blood flow., Conclusions: Ultrasound imaging is a convenient and useful method to evaluate the morphological characteristics of female periurethral solid masses., (© 2022. The International Urogynecological Association.)

Background: To provide direct evidence of whether primary realignment (PR) or suprapubic cystostomy (SPC) had different effects on the prostatic displacement and prognosis in patients with pelvic fracture urethral injury who needed delay anastomotic urethroplasty based on Magnetic Resonance (MR) urethrography., Methods: We screened the urethral stenosis database of our single institution from January 2016 to June 2020. Patients who underwent delayed anastomotic urethroplasty with a preoperative MR urethrography and no treatment history of urethra were included. We compared the urethral gap length and prostatic displacement between the PR and SPC group based on MR urethrography. The terminal outcomes such as stenosis-free rate, urinary continence and erectile function were also analyzed between two groups., Results: 66 patients were included in this retrospective study in which 36 were in PR group and 30 in SPC group. Mean follow-up time was 15.1 months (3-38 months). One and two patients experienced recurrence of stenosis after urethroplasty in two groups (p = 1.000). No difference of erectile dysfunction and urinary incontinence was found between two groups. Based on MR urethrography, the urethral gap length was 17.4 mm and 23.3 mm (p = 0.008) which presented a significant decrease in PR group. The superior prostatic displacement was similar in two groups (9.8 mm vs. 13.8 mm, p = 0.081). The numbers and distance of displacement on lateral aspect showed no difference, either. However, PR group had less anterior-posterior prostatic displacement (p = 0.005). Besides, the erectile function was significantly related to the lateral prostatic displacement (p = 0.030/0.047)., Conclusions: Based on MR urethrography, patients in PR group showed shorter urethral gap distance and slighter anterior-posterior prostatic displacement without extra erectile dysfunction or incontinence. Besides, patients' erectile function might be significantly related to the lateral prostatic displacement., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier Ltd.)

Background: To investigate the current diagnostic and therapeutic approaches to anterior urethral strictures of Chinese urologists and to compare with developed countries and the American Urologic Association guidelines., Methods: Anonymous questionnaires were distributed to members of Official Wechat Account of urology from March 19, 2020 to April 10, 2020. Descriptive and multiple correspondence analysis were used to analyze the data., Results: A total of 1276 online questionnaires were received. The response rate was 21.7% (1276/5878). The most common diagnostic methods for anterior urethral stricture were urethrography (90.7%) and urethrocystoscopy (85.4%), while urethral dilation (92.3%) and internal urethrotomy (60.1%) were the main therapeutic procedures. End-to-end urethroplasty (45.2%) was the most common open surgery, followed by skin flap urethroplasty (14.9%) and free graft urethroplasty (12.4%). 76.2% of urologists used urethroplasty only after the failure of minimally invasive surgery (reconstructive ladder treatment strategy). Furthermore, middle-aged or elderly urologists who had attended trainings, had senior practice roles, and who utilized a reconstructive ladder treatment approach were most likely to perform urethroplasties., Conclusions: Anterior urethral stricture treatment in China is still dominated by minimally invasive surgery, with most urologists using the reconstructive ladder treatment strategy. In general, the overall diagnostic and therapeutic strategies were similar between China and developed countries, with some deviations from the American Urologic Association guidelines., (© 2021. The Author(s).)

Objectives: To investigate the risk factors for postoperative infection, including systemic inflammatory response syndrome, sepsis and surgical site infection, after posterior urethral anastomosis for the treatment of male posterior urethral stenosis with pelvic fractures., Methods: We retrospectively analyzed data from patients who underwent transperineal end-to-end anastomotic urethroplasty between January 2016 and December 2018. Descriptive statistics were used to analyze patient characteristics and perioperative features. Univariate analysis was performed to identify prognostic factors associated with postoperative infection. Multivariate analysis was used to identify independent risk factors for postoperative infection., Results: Among 261 patients included in the analysis, 16.48% had SIRS, 3.83% had sepsis, and 8.05% had SSI. The primary results suggested that penile septum separation, inferior pubic resection, operating duration, preoperative urine culture result, preoperative waiting time, urethral stenosis length, and draining method were significant predictors of postoperative infections. Multivariate analysis revealed that more complex surgical procedures, operating duration and positive urine culture results were independent risk factors for SIRS and preoperative positive urine culture result was an independent risk factor for sepsis and SSI., Conclusions: Positive preoperative urine culture was the main risk factor for postoperative infections. More complex surgical procedures, such as penile septum separation and inferior pubic resection, and longer operating duration were more likely to be associated with postoperative SIRS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate the risk factors that pertain to stricture recurrence and oral complications., Methods: Patients with long segmented anterior urethral stricture who visited our hospital from 2009 to 2016 were treated with lingual mucosa graft (LMG) urethroplasty. The incidence of complications in all of 128 patients were evaluated. The data were analyzed using the chi-squared test and Fisher's exact test. A multi-factorial regression analysis was performed to identify the risk factors responsible for the recurrence and complications., Results: For patients having LMG urethroplasty, there were no significant difference in recurrence of urethral stricture according to the studied variables. Binary logistic regression analysis reveals that previous surgery involving the urethra was a significant predictor of urethral stricture recurrence (odds ratio [OR]=5.07; 95% confidence interval [95% CI], 1.06-24.40; P = .043). The length of the substitute was significantly related to oral morbidity (P = .020), even after controlling for the studied variables. Patients with a harvested oral mucosa longer than 7 cm had a higher risk of oral morbidity than those with a harvested oral mucosa shorter than 7 cm (OR=4.35; 95% CI, 1.35-14.06; P = .014)., Conclusion: Our study shows that LMG urethroplasty is effective for patients with long segmented anterior urethral stricture. Previous urethral surgery was identified as a risk factor to cause recurrence and injury to the tip of the tongue for the oral complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Bioelectronics based on biomaterial substrates are advancing toward biomedical applications. As excellent conductors, poly(3,4-ethylenedioxythiophene) (PEDOT) and its derivatives have been widely developed in this field. However, it is still a big challenge to obtain a functional layer with a good electroconductive property, transparency, and strong adhesion on the biosubstrate. In this work, poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-OH) was chemically polymerized and deposited on the surface of a regenerated silk fibroin (RSF) film in an aqueous system. Sodium dodecyl sulfate (SDS) was used as the surfactant to form micelles which are beneficial to the polymer structure. To overcome the trade-off between transparency and the electroconductive property of the PEDOT-OH coating, a composite oxidant recipe of FeCl 3 and ammonium persulfate (APS) was developed. Through electrostatic interaction of oppositely charged doping ions, a well-organized conductive nanoscale coating formed and a transparent conductive RSF/PEDOT-OH film was produced, which can hardly be achieved in a traditional single oxidant system. The produced film had a sheet resistance ( R s ) of 5.12 × 10 4 Ω/square corresponding to a conductivity of 8.9 × 10 -2 S/cm and a maximum transmittance above 73% in the visible range. In addition, strong adhesion between PEDOT-OH and RSF and favorable electrochemical stability of the film were demonstrated. Desirable transparency of the film allowed real-time observation of live cells. Furthermore, the PEDOT-OH layer provided an improved environment for adhesion and differentiation of PC12 cells compared to the RSF surface alone. Finally, the feasibility of using the RSF/PEDOT-OH film to electrically stimulate PC12 cells was demonstrated.

Background: Autologous tissue transplantation for urethral repair is often limited and causes donor site complications. Here, a cryopreserved rabbit skin epithelial cell sheet (SEC) combined with an acellular amniotic membrane (AM) was used to repair rabbit urethral defects., Methods: Abdominal skin was collected from 4-week-old New Zealand rabbits, and primary epithelial cells were extracted and cultured to form a cell sheet. Fresh SEC-AMs were constructed and cryopreserved. A cryopreservation system including optimized medium, two-pump perfusion, a programmed freezer and liquid nitrogen storage was established. Cell viability, mechanical strength, electron microscopy, and histological staining were performed in vitro after 1 month. Next, the sheets were transplanted subcutaneously for 2 weeks, and the graft was used to repair the rabbit urethral defect. Urinary function was measured and samples were collected for histological staining after 1 month., Results: We confirmed that cryopreservation damage of SECs was reduced by composition with acellular AMs in terms of high cell activity. The SEC mechanical strength was also enhanced by AMs, which was convenient for the operation. In in vivo experiments, we transplanted sheets into the groin area for two weeks and found that cryopreservation reduced inflammatory cell infiltration and significantly improved vascular density. In the urethral repair experiment, the near-normal passive urine flow rate, smooth mucosa of the gross specimen, intact epithelialization and abundant neovascularization were confirmed in the cryopreserved-SEC-AM group compared with the other groups., Conclusions: Cryopreserved SEC-AMs demonstrated similar outcomes of rabbit urethral defect repair as fresh SEC-AMs, showing good clinical application prospects., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A novel biomaterial ink consisting of regenerated silk fibroin (SF) and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized bacterial cellulose (OBC) nanofibrils was developed for 3D printing lung tissue scaffold. Silk fibroin backbones were cross-linked using horseradish peroxide/H 2 O 2 to form printed hydrogel scaffolds. OBC with a concentration of 7wt% increased the viscosity of inks during the printing process and further improved the shape fidelity of the scaffolds. Rheological measurements and image analyses were performed to evaluate inks printability and print shape fidelity. Three-dimensional construct with ten layers could be printed with ink of 1SF-2OBC (SF/OBC = 1/2, w/w). The composite hydrogel of 1SF-1OBC (SF/OBC = 1/1, w/w) printed at 25 °C exhibited a significantly improved compressive strength of 267 ± 13 kPa and a compressive stiffness of 325 ± 14 kPa at 30% strain, respectively. The optimized printing parameters for 1SF-1OBC were 0.3 bar of printing pressure, 45 mm/s of printing speed and 410 μm of nozzle diameter. Furthermore, OBC nanofibrils could be induced to align along the print lines over 60% degree of orientation, which were analyzed by SEM and X-ray diffraction. The orientation of OBC nanofibrils along print lines provided physical cues for guiding the orientation of lung epithelial stem cells, which maintained the ability to proliferate and kept epithelial phenotype after 7 days' culture. The 3D printed SF-OBC scaffolds are promising for applications in lung tissue engineering., Competing Interests: Conflict of interestThe authors state no conflict of interest., (© Springer Nature B.V. 2020.)

Background: To investigate the correlation between the magnetic resonance urethrography and the surgical approach and complexity for the patients with pelvic fracture urethral injury (PFUI) by combining the geometry with magnetic resonance imaging (MRI)., Methods: Forty-three male patients with PFUI (part of the patients complicated with rectal injury) from January 2016 to December 2018 were analyzed in this retrospective research. All the patients underwent a delayed anastomotic urethroplasty and were divided into 2 groups according to the approaches (simple perineal approach or inferior pubectomy). For magnetic resonance urethrography, we measured and calculated the geometric parameters such as the gap distance between two urethral ends, the pubourethral vertical distance (PUVD), and the rectourethral median distance (RUMD)., Results: Of the 43 patients, 16 underwent inferior pubectomy and 27 underwent simple perineal approach. The numbers of patients with and without rectal injury history were 17 and 26, respectively. The operation time and intraoperative blood loss was significantly higher in the inferior pubectomy group. Multivariate logistic analysis revealed that gap distance and PUVD were independent factors of the surgical approaches. The accuracies were 83.7% and 67.4% respectively in the ROC curve analysis. In addition, the RUMD was significantly shorter in the patients with rectal injury history (1.4, 1.8 cm)., Conclusions: Longer gap distance and shorter PUVD were the two independent factors of the inferior pubectomy approach. Furthermore, among the patients with rectal injury history, the tissue posterior to the urethra was often weaker and should be carefully handled during the surgery., Trial Registration: This research has been registered on the Chinese Clinical Trial Registry. The registration number is ChiCTR2000030573., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-1064). The authors have no conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)

Objective: To investigate the histomorphological changes of the divergent corpus spongiosum surrounding the urethral plate in hypospadias., Methods: Seventy boys with hypospadias were divided into the distal (n = 44) and proximal (n = 26) groups by the location of the ectopic meatus. The morphology of the divergent corpus spongiosum was evaluated and the histopathological studies were carried out by HE staining, Masson staining, and immunohistochemical analyses of α-SMA, CD34, TGF-β1 and androgen receptor. Western blotting was performed to measure the expression of TGF-β1 and androgen receptor., Results: The divergent corpus spongiosum was significantly thicker in the distal group than the proximal group (distal 3.14 ± 1.12 mm, proximal 1.74 ± 0.87 mm, P <.0001). Histological evaluation suggested the cavernous sinus in the hypospadias group had an abnormal structure, which was characterized by an increase in the width of the vascular lumen (control 7.20 ± 1.12 μm, hypospadias 13.75 ± 8.08 μm, P = .0068), an increased vascular wall thickness (control 5.40 ± 1.28 μm, hypospadias 14.11 ± 7.59 μm, P = .0006), a decreased vascular density (control 15.66 ± 1.17, hypospadias 7.24 ± 4.19, P <.0001) and a decreased trabecular density (control 9.80 ± 1.92, hypospadias 3.68 ± 2.87, P <.0001). The severity of the structural abnormalities was greater in the proximal group than the distal group. Immunohistochemical analysis and Western blotting showed decreased TGF-β1 and androgen receptor expression in the hypospadias group (P <.0001)., Conclusions: Histomorphological analysis showed that the divergent corpus spongiosum in hypospadias is abnormal. The structural variation is positively correlated with the severity of hypospadias., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Development of chiral drugs has become one of the most important subjects for academic research and pharmaceutical industry. Even though it has been well known that a pair of enantiomers of a chiral drug frequently have different biological and physiological effects, a certain number of chiral drugs are currently still commercialized and used in the form of racemate. In the above context, investigation of enantio-differentiating release and enantioselective effects may lead to alternative use approaches for chiral drugs. In spite of the noticeable advancements, there has been no review paper yet focused on enantioselective release, except the earlier one published by us (Ind. Eng. Chem. Res. 2016, 55, 6037). The present paper reviews the latest advancements made in enantioselective release, with emphasis on the construction of chiral releasing materials. The currently existing difficulty in performing enantioselective release and the emerging issues associated with chiral drugs (and chiral agrochemicals, etc.) are summarized. The issues include: enantioselective effects in chiral carrier-chiral guest compound and chiral carrier-achiral guest compound releasing systems; chiral inversion in release process; chiral pollutants in environment, etc. The review paper might provide new insights into the development and use of chiral drugs., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We developed a stromal cell-derived factor-1 alpha (SDF-1α)-aligned silk fibroin (SF)/three-dimensional porous bladder acellular matrix graft (3D-BAMG) composite scaffold for long-section ventral urethral regeneration and repair in vivo. SDF-1α-aligned SF microfiber/3D-BAMG, aligned SF microfiber/3D-BAMG, and nonaligned SF microfiber/3D-BAMG scaffolds were prepared using electrostatic spinning and wet processing. Adipose-derived stem cell (ADSC) and bone marrow stromal cell (BMSC) migration was assessed in the SDF-1α-loaded scaffolds. Sustained SDF-1α release in vitro and vivo was analyzed using enzyme-linked immunosorbent assay (ELISA) and western blotting, respectively. The scaffolds were used to repair a 1.5 × 1 cm 2 ventral urethral defect in male rabbits in vivo. General observation and retrograde urinary tract contrast assessment were used to examine urethral lumen patency and continuity at 1 and 3 months post-surgery. Postoperative rehabilitation was evaluated using histological detection. The composite scaffolds sustained SDF-1α release for over 16 days in vitro. SDF-1α-aligned SF nanofiber promoted regeneration of urethral mucosa, submucosal smooth muscles, and microvasculature, increased cellular proliferation, and reduced collagen deposition. SDF-1α expression was increased in reconstructed urethra at 3 months post-surgery in SDF-1α-aligned SF group. SDF-1α-aligned SF microfiber/3D-BAMG scaffolds may be used to repair and reconstruct long urethral defects because they accelerate urethral regeneration., (© 2020 Wiley Periodicals, Inc.)

Antibacterial scaffolds are highly desirable for the repair and reconstruction of injured soft tissues. However, the direct fabrication of scaffolds with excellent biocompatibility, flexibility, and antibacterial capacity remains a challenge, especially those based on biomaterials. In this study, we report the biomaterial-based antibacterial scaffolds based on regenerated silk fibroin, 2-hydroxypropyltrimethyl ammonium chloride chitosan, and bladder acellular matrix graft by blend and coaxial electrospinning. This approach eliminated the use of organic solvents and inorganic nanoparticles, ensuring greater clinical safety, mimicking physiological extracellular matrix structures, and the required softness for a suture material. Thus, the scaffold obtained in this study exhibited excellent biocompatibility, the required mechanical characteristics, and excellent antibacterial capacity. The rate of bacterial elimination of Staphylococcus aureus and Escherichia coli reached up to 99.5 and 98.3%, respectively. The scaffold design favored cell growth and proliferation and resulted in the significant promotion of repair and reconstruction of the urethra, indicating that it can be an ideal antibacterial suture material for soft tissue restoration.

Rapid vascularization is very important in tissue engineering. Bladder acellular matrix (BAM) with inherent bioactive factors, a natural extracellular matrix (ECM) derived biomaterial, has been widely used as a scaffold to facilitate the repair and reconstruction of urinary tissues. However, the application of the traditional BAM scaffold has been limited due to the dense structure. To investigate the angiogenic potential of BAM, BAM hydrogels with tailored porous structures were prepared in this study by tuning BAM concentrations (4, 6, and 8 mg/mL). The 6 mg/mL BAM hydrogel was loaded with porcine iliac endothelial cells (PIECs), and their angiogenic potential was analyzed in vitro and in vivo . The mechanical strength and gelation speed of the BAM hydrogels increased, while their pore size decreased as concentration increased. Commercially available collagen hydrogel (2.5 mg/mL) showed weaker mechanical properties than BAM hydrogels but similar gelation speed and pore size as 6 mg/mL BAM hydrogel. To ensure a similar three-dimensional microenvironment for the PIECs, 6 mg/mL BAM and collagen hydrogels were selected for the in vitro and in vivo experiments. A significantly higher density of viable, fusiform PIECs of average length ∼50 μm was observed in the BAM hydrogel, while those inside the collagen hydrogel were spherical and ∼30 μm long. In addition, the PIECs/BAM hydrogel resulted in significantly higher revascularization compared with the PIECs/collagen and unloaded BAM hydrogels. The higher angiogenic potential of the PIECs/BAM hydrogel is due to the growth factors that promote PIEC proliferation and therefore vascularization.

Electrospun scaffold with three-dimensional (3D) geometry and appropriate pore structure is an important challenge to mimic natural tissues such as skin, cartilage, etc. In this work, 3D silk fibroin (SF) electrospun scaffolds with gradient pore size were prepared by combining multi-step electrospinning with low temperature (LTE) collecting. The LTE electrospun scaffolds achieved 3D macro-structure with large pore size. The effects of relative humidity (RH), collecting temperature on the morphology of the scaffolds were investigated by scanning electron microscopy and computed tomography. The pore size of the scaffolds was tailored by adjusting SF concentration, electric field, flow rate, needle gauge and collector temperature during electrospinning at 50% RH. L929 cell infiltration results of the scaffolds showed that conventional electrospun scaffolds with small pore size (average diameter 5.9 ± 1.4 μm) restrained cell proliferation and infiltration. On the contrary, LTE electrospun scaffolds with medium pore size (average diameter 11.6 ± 1.4 μm) improved cell proliferation obviously. Large pore size scaffolds (average diameter 37.2 ± 12.9 μm) was beneficial to cell infiltration depth in the thickness direction of the scaffolds. The scaffolds, which were integrated with layers of small, medium and large pores, are promising in the repair of tissue with gradient pore structures., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To explore the value of transurethral contrast-enhanced ultrasonography (CEUS) in the diagnosis and evaluation of female urethral diverticula., Methods: This study prospectively enrolled 35 women with periurethral cystic lesions, who underwent preoperative transurethral CEUS at our single center between April 2015 and May 2017. The diagnosis of a urethral diverticulum was made by the detection of microbubbles inside the lesion. Data regarding the structure and ostia of the diverticula were collected and then compared with intraoperative findings., Results: The median (interquartile range) age of the 35 patients was 43 (34-48) years. The most common manifestations were dysuria (43%) and palpable masses (40%). On transurethral CEUS, 20 patients were found to have urethral diverticula. The diverticula involved the proximal, mid, and distal urethra with different sizes. The shapes of the diverticula were simple in 4 patients (20%), U shaped in 8 patients (40%), and circumferential in 8 patients (40%). A total of 23 ostia were identified. Seventeen women (85%) had 1 ostium, and 3 women (15%) had 2 ostia. Twenty-one diverticular ostia (91%) were located from the 3- to 9-o'clock positions. The median (interquartile range) distance from the diverticular ostia to the bladder neck was 20 (9-31) mm. During surgery, all US presentations correlated well with surgical findings, and 21 patients were confirmed to have urethral diverticula. The transurethral CEUS had sensitivity of 95% and specificity of 100%., Conclusions: Transurethral CEUS is an effective method for identifying the structure and ostium of female urethral diverticula. It may have a potential role in preoperative planning and surgical management., (© 2018 by the American Institute of Ultrasound in Medicine.)

Objective: To evaluate the effects of urethral regeneration with prevascularized bladder acellular matrix hydrogel (BAMH)/silk fibroin (SF) composite scaffolds in a rabbit model., Materials and Methods: BAMH/SF and collagen Type I hydrogel/SF (CH/SF) scaffolds were prepared and the structure of the scaffolds was assessed using scanning electron microscopy. BAMH/SF, CH/SF and SF scaffolds were incubated in the omentum of male rabbits for two weeks and then harvested for repairing autologous urethral defects. Histological analysis of the incubated scaffolds was performed to evaluate the neovascularization capacity, and the outcomes of urethroplasty were evaluated at one and three months post-operatively., Results: The composited scaffolds were composed of a highly porous BAMH or CH buttressed by compact SF outer layer. The histological analysis of the incubated BAMH/SF revealed a signifcant increase of the neovascularization among three groups after a two-week incubation. At three months, the urethra maintained wide caliber in the BAMH/SF group. Strictures were found in the CH/SF and SF groups. Histologically, at one month, intact and multilayer epithelium occurred in the BAMH/SF group, and one layer epithelium was found in the CH/SF and SF groups. However, there was similar epithelial regeneration in BAMH/SF and CH/SF groups at three months (p > 0.05). Comparisons of smooth muscle content and vessel density among the SF, CH/SF and BAMH/SF revealed a significant increase at each time point (p < 0.05)., Conclusion: Our results demonstrate that incubated BAMH/SF promote neovascularization, and prevascularized BAMH/SF promote the regeneration of the urethral epithelium and smooth muscle, which indicates its potential for urethral reconstruction.

The aim of the present study was to determine whether it was possible to repair urethral defects with a material of adipose mesenchymal stem cells (ADMSCs)‑porous silk fibroin (SF). A total of 39 male New Zealand white rabbits were randomly divided into a control group, an SF group and a bromodeoxyuridine (BrdU)‑labeled ADMSCs‑SF group (SSF group; n=13/group). Defects were made by resecting the posterior urethral wall. The defects in the SF and SSF groups were repaired using SF and BrdU‑labeled ADMSCs‑SF materials respectively. Then the anterior wall was sutured, and the urethral catheter was retained for 3 weeks following surgery. The catheter was rinsed with nitrofurazone once a day. The cells with positive expressions of factor VIII related antigen (FVIII‑RAg), α‑smooth muscle actin (α‑SMA) and pan‑cytokeratin (AE1/AE3) were detected by immunohistochemical assay, and the distributions of BrdU positive cells and macrophages were observed. Urethrography was performed prior to and following surgery. All rabbits had normal urethral morphologies prior to surgery. The incidence rates of postoperative complications in the control, SF and SSF groups were 76.92 (7/13), 23.07 (3/13) and 15.38% (2/13), respectively (P<0.05). The number of positive macrophages in the SSF group was significantly lower than that of the SF group 4 weeks following surgery (P<0.05). In the SSF group, BrdU positive cells were scattered within the SF material following surgery, primarily at the intersection between the SF material and the urethra. The number of FVIII‑RAg positive cells in the SSF and SF groups were significantly different (P<0.05), which were also significantly higher than that of control group (P<0.01). The number of α‑SMA positive cells in the SSF and SF groups were significantly different (P<0.05), and these values also significantly exceeded those exhibited by the control group (P<0.01). In addition, the SSF and SF groups had positive staining of AE1/AE3. Similar to normal urethral mucosa, the cytoplasm was stained brownish yellow (P<0.05). It is thus feasible to repair urethral defects using ADMSCs‑SF material.

The early and effective treatment of wounds is vital to ensure proper wound closure and healing with appropriate functional and cosmetic outcomes. The use of human amnion membranes for wound care has been shown to be safe and effective. However, the difficulty in handling and placing thin sheets of membrane, and the high costs associated with the use of living cellularized tissue has limited the clinical application of amniotic membrane wound healing products. Here, we describe a novel amnion membrane-derived product, processed to result in a cell-free solution, while maintaining high concentrations of cell-derived cytokines and growth factors. The solubilized amnion membrane (SAM) combined with the carrier hyaluronic acid (HA) hydrogel (HA-SAM) is easy to produce, store, and apply to wounds. We demonstrated the efficacy of HA-SAM as a wound treatment using a full-thickness murine wound model. HA-SAM significantly accelerated wound closure through re-epithelialization and prevented wound contraction. HA-SAM-treated wounds had thicker regenerated skin, increased total number of blood vessels, and greater numbers of proliferating keratinocytes within the epidermis. Overall, this study confirms the efficacy of the amnion membrane as a wound treatment/dressing, and overcomes many of the limitations associated with using fresh, cryopreserved, or dehydrated tissue by providing a hydrogel delivery system for SAM. Stem Cells Translational Medicine 2017;6:2020-2032., (© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Bladder acellular matrix (BAM) hydrogel may have great potential in tissue engineering due to outstanding biocompatibility and the presence of inherent bioactive factors in BAM. In this study, we prepared the BAM hydrogel by the method of enzymatic solubilization with pepsin and characterize the microrheological properties of the BAM precursor solution. The structures of the BAM hydrogel were characterized by scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Furthermore, the growth factors including vascular endothelial growth factor (VEGF), platelet-derived growth factor B (PDGF-BB), keratinocyte growth factor (KGF) were quantified by ELISA. The biological performances of the hydrogels were evaluated by cultivating porcine iliac endothelial cells (PIECs) in vitro. Lyophilized BAM showed porous structure with pore diameter ranging from 50 to 100μm. BAM 4-G hydrogel (4mg/mL) with a short gelation time of 3.95±0.07min presents better thermal stability than BAM 6-G hydrogel (6mg/mL). Growth factors in the BAM hydrogel maintain valuable biological activity even after digestion process. The BAM hydrogel supported the adhesion and growth of PIECs well and has great potential for further tissue engineering., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Urethral stricture is a common condition seen after urethral injury. The currently available treatments are inadequate and there is a scarcity of substitute materials used for treatment of urethral stricture. The traditional tissue engineering of urethra involves scaffold design, fabrication and processing of multiple cell types., Methods: In this study, we have used 3D bioprinting technology to fabricate cell-laden urethra in vitro with different polymer types and structural characteristics. We hypothesized that use of PCL and PLCL polymers with a spiral scaffold design could mimic the structure and mechanical properties of natural urethra of rabbits, and cell-laden fibrin hydrogel could give a better microenvironment for cell growth. With using an integrated bioprinting system, tubular scaffold was formed with the biomaterials; meanwhile, urothelial cells (UCs) and smooth muscle cells (SMCs) were delivered evenly into inner and outer layers of the scaffold separately within the cell-laden hydrogel., Results: The PCL/PLCL (50:50) spiral scaffold demonstrated mechanical properties equivalent to the native urethra in rabbit. Evaluation of the cell bioactivity in the bioprinted urethra revealed that UCs and SMCs maintained more than 80% viability even at 7days after printing. Both cell types also showed active proliferation and maintained the specific biomarkers in the cell-laden hydrogel., Conclusion: These results provided a foundation for further studies in 3D bioprinting of urethral constructs that mimic the natural urethral tissue in mechanical properties and cell bioactivity, as well a possibility of using the bioprinted construct for in vivo study of urethral implantation in animal model., Significance of Statements: The 3D bioprinting is a new technique to replace traditional tissue engineering. The present study is the first demonstration that it is feasible to create a urethral construct. Two kinds of biomaterials were used and achieved mechanical properties equivalent to that of native rabbit urethra. Bladder epithelial cells and smooth muscle cells were loaded in hydrogel and maintained sufficient viability and proliferation in the hydrogel. The highly porous scaffold could mimic a natural urethral base-membrane, and facilitate contacts between the printed epithelial cells and smooth muscle cells on both sides of the scaffold. These results provided a strong foundation for future studies on 3D bioprinted urethra., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Stem cells are regarded as possible cell therapy candidates for skeletal muscle regeneration. However, invasive harvesting of those cells can cause potential harvest-site morbidity. The goal of this study was to assess whether human urine-derived stem cells (USCs), obtained through non-invasive procedures, can differentiate into skeletal muscle linage cells (Sk-MCs) and potentially be used for skeletal muscle regeneration. In this study, USCs were harvested from six healthy individuals aged 25-55. Expression profiles of cell-surface markers were assessed by flow cytometry. To optimize the myogenic differentiation medium, we selected two from four different types of myogenic differentiation media to induce the USCs. Differentiated USCs were identified with myogenic markers by gene and protein expression. USCs were implanted into the tibialis anterior muscles of nude mice for 1 month. The results showed that USCs displayed surface markers with positive staining for CD24, CD29, CD44, CD73, CD90, CD105, CD117, CD133, CD146, SSEA-4 and STRO-1, and negative staining for CD14, CD31, CD34 and CD45. After myogenic differentiation, a change in morphology was observed from 'rice-grain'-like cells to spindle-shaped cells. The USCs expressed specific Sk-MC transcripts and protein markers (myf5, myoD, myosin, and desmin) after being induced with different myogenic culture media. Implanted cells expressed Sk-MC markers stably in vivo. Our findings suggest that USCs are able to differentiate into the Sk-MC lineage in vitro and after being implanted in vivo. Thus, they might be a potential source for cell injection therapy in the use of skeletal muscle regeneration. Copyright © 2014 John Wiley & Sons, Ltd., (Copyright © 2014 John Wiley & Sons, Ltd.)

To investigate the synergistic effect of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) on cavernous nerve regeneration, two different aligned scaffolds consisting of coaxial electrospun silk fibers were prepared by switching the position of the two factors in either core or shell domain. The order and release rate of the dual factors delivery were relatively different because of the distinct location of two factors in coaxial fibers. An in vitro assay showed that the inner-VEGF/outer-BDNF scaffolds could more obviously accelerate Schwann cells growth, proliferation and spreading owing to the rapid release of BDNF. However, in vivo scaffold implantation demonstrated that the inner-BDNF/outer-VEGF scaffolds significantly facilitated more angiogenesis, and promoted more nerve regeneration based on great benefit of angiogenesis. Results showed that the reasonable dual-delivery order of VEGF and BDNF from scaffolds could enhance synergistic effect of the factors and promote cavernous nerve regeneration.

Purpose: Erectile dysfunction (ED) continues to be a significant problem for men following radical prostatectomy. We hypothesize that intracavernous injection of BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) can ameliorate ED in a rat model of cavernous nerve electrocautery injury (CNEI)., Methods: Forty-two male Sprague-Dawley rats were randomly divided into four groups: sham + PBS (n = 6), CNEI + PBS (n = 12), CNEI + hUCB-MSCs (n = 12) and CNEI + BDNF-hUCB-MSCs (n = 12). At day 28 post-surgery, erectile function was examined and specimens were harvested for histology. Immunofluorescence staining, Masson's trichrome staining and transmission electron microscopy were performed to determine the structural changes in corpus cavernosum. Cells that are injected into penis were labeled by BrdU and tracked by immunofluorescence staining. Three days post-surgery, the concentration of BDNF protein in penile tissues was measured by Western blotting., Results: Rats intracavernosally injected with BDNF-hUCB-MSCs showed the most significant improvement in the ratio of maximal ICP to MAP (ICP/MAP). Histological examinations showed moderate recovery of nNOS-positive nerve fibers, ratio of smooth muscle to collagen and smooth muscle content in the CNEI + hUCB-MSCs group and remarkable recovery in the CNEI + BDNF-hUCB-MSCs group compared to the CNEI + PBS group. By TEM examination, atrophy of myelinated and non-myelinated nerve fibers was noted in CNEI + PBS group and significant recovery was observed in two treated groups. There were more BrdU-positive cells in the BDNF-hUCB-MSCs group than in the hUCB-MSCs group both in the penis and in the MPG. Three days post-surgery, the concentration of BDNF protein in penile tissues in BDNF-hUCB-MSCs group was much higher than in other groups., Conclusions: Intracavernous injection of BDNF-hypersecreting hUCB-MSCs can enhance the recovery of erectile function, promote the CNs regeneration and inhibit corpus cavernosum fibrosis after CNEI in a rat model.

Bombyx mori silk is of great interest to people for its outstanding mechanical and biological properties. However, the traditional electrospun regenerated silk fibroin (RSF) scaffolds from aqueous solution were weak and had limited applications. This study was to fabricate reinforced scaffolds with well-aligned RSF fibers electrospun on a layer of native extracellular matrix, bladder acellular matrix graft (BAMG). The silk fibroin fibers were well-aligned as a grill in multiple layers. Both the BAMG and the grill structure significantly improved the tensile properties and suture retention of the composite scaffolds, which can be sutured well with tissue during implantation. In vitro assay indicates that the scaffolds had a good biocompatibility. Porcine iliac endothelial cells (PIECs) attached and proliferated well on the vascular endothelial growth factor (VEGF) loaded scaffolds compared with those without VEGF. Moreover, the grill-like structure guides PIECs well along the aligned fiber.

Background: To investigate the feasibility of urethral reconstruction using tissue-engineered buccal mucosa (TEBM) with silk fibroin (SF) matrices in a canine model., Materials and Methods: Autologous oral keratinocytes and autologous fibroblasts were isolated, expanded, and seeded onto SF matrices to obtain TEBM. The TEBM was assessed using hematoxylin and eosin staining and scanning electron microscopy. A 5-cm urethral mucosal defect was created in 10 female canines. Urethroplasty was performed using TEBM in five canines in the experimental group and with SF matrices without cells in the five canines in the comparison group. Retrograde urethrography was performed after 6 mo of grafting. The urethral grafts were analyzed grossly and histologically., Results: The oral keratinocytes and fibroblasts exhibited good biocompatibility with the SF matrices. TEBM could be constructed using SF matrices. The canines implanted with the tissue-engineered mucosa voided without difficulty. The retrograde urethrography revealed no sign of stricture. The histologic staining showed that epithelial cells developed gradually and exhibited stratified epithelial layers at 6 mo. In the comparison group, the canines had difficulty voiding, and the retrograde urethrography showed urethra stricture. The histologic staining showed that one to two layers of epithelial cells developed., Conclusions: The TEBM using SF matrices could be a potential material for urethra reconstruction., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Over the last few decades, both synthetic and natural materials have been utilized to develop bladder substitutes. Most attempts have not been successful because of mechanical, structural, functional, or biocompatibility problems. Bladder acellular matrix (BAM) is obtained by removing cellular components from donor bladders, leaving a tissue matrix consisting of collagen, elastin, fibronectin, glycosaminoglycans, proteoglycans, and growth factors. Multiple BAM-based studies now suggest that tissue engineering techniques may provide efficacious alternatives to current methods of bladder augmentation. Efforts to optimize BAM-based scaffolds are ongoing and would be greatly assisted by feasible means of improving scaffold properties and interaction with cells and tissues. Future applications of BAM will likely include cell-seeded grafts with the eventual hope of producing "off the shelf" replacement materials for bladder augmentation.

The limited amount of available epithelial tissue is considered a main cause of the high rate of urethral reconstruction failures. The aim of this study was to investigate whether epithelial-differentiated rabbit adipose-derived stem cells (Epith-rASCs) could play a role of epithelium in vivo functionally and be a potential substitute of urothelium. Substitution urethroplasty was performed to repair an anterior urethral defect in male New Zealand rabbits using Epith-rASCs seeded bladder acellular matrix grafts (BAMGs) after 5-bromo-2'-deoxyuridine (BrdU) labeling, based on the in vitro epithelial induction system we previously described. Urethroplasty with cell-free BAMGs and with undifferentiated rASCs (Und-rASCs) seeded BAMGs were performed as controls. After surgery, a notable amelioration of graft contracture and recovery of urethral continuity were observed in the Epith-rASCs/BAMG group by retrograde urethrograms and macroscopic inspection. Immunofluorescence revealed that the BrdU-labeled Epith-rASCs/Und-rASCs colocalized with cytokeratin 13 or myosin. Consistent with the results of western blotting, at early postimplantation stage, the continuous epithelial layer with local multilayered structure was observed in the Epith-rASCs/BAMG group, whereas no significant growth and local monolayer growth profile of epithelial cells were observed in the BAMG and Und-rASCs/BAMG group, respectively. The results showed that Epith-rASCs could serve as a potential substitute of urothelium for urethral tissue engineering and be available to prevent lumen contracture and subsequent complications including recurrent stricture.

Background: We investigated the feasibility of urethral reconstruction using stretched electrospun silk fibroin matrices., Materials and Methods: A novel electrospun silk fibroin matrix was prepared. The structure of the material was assessed by scanning electron microscopy and a porosity test. Canine urothelial cells were isolated, expanded, and seeded onto the material for 1 wk to obtain a tissue-engineered graft. The tissue-engineered graft was assessed using hematoxylin and eosin staining and scanning electron microscopy. A dorsal urethral mucosal defect was created in nine female beagle dogs. In the experimental group, tissue-engineered mucosa was used to repair urethra mucosa defects in six dogs. No substitute was used in the three dogs of the control group. Retrograde urethrography was performed at 1, 2, and 6 mo after grafting. The urethral grafts were analyzed grossly and histologically., Results: Scanning electron microscope and a porosity test revealed that the material had a three-dimensional porous structure. Urothelial cells grew on the material and showed good biocompatibility with the stretched silk fibroin matrices. Canines implanted with tissue-engineered mucosa voided without difficulty. Retrograde urethrography revealed no signs of stricture. Histologic staining showed gradual epithelial cell development and stratified epithelial layers at 1, 2, and 6 mo. The canines in the control group showed difficulty in voiding. Retrograde urethrography showed urethra stricture. Histologic staining showed that no or only one layer of epithelial cells developed. A severe inflammatory reaction was also observed in the control group., Conclusions: Stretched electrospun silk fibroin matrices have good biocompatibility with urothelial cells, which could prove to be a potential material for use in urethra reconstruction., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Urethral injures, pelvic trauma, and certain congential abnormalities in male can often cause urethral strictures and scarring. Adequate and accurate imaging diagnosis of urethral strictures is critial to select a surgical approach. Although urethrography is commonly used in evaluating male urethral injury and strictures, its limitation is that the contrast offers images only at the urethral lumen but not of the periurethral structures. Sonourethrography (SUG) has the ability to define the periurethral tissues and without the radiation exposure, the degree of periurethral fibrosis can be shown with a view to guiding surgery especially in bulbar urethra. Computed tomography (CT) urethrography has the advantage of examining patients only in one position, and by generating three-dimensional images; it can accurately measure the stricture length. Magnetic resonance imaging (MRI) provide useful information in certain clinical situations, particularly posterior urethral trauma and in the evaluation of the periurethral soft tissues. However, both CT and MRI are relative high cost. The selection of imaging methods should depend on the etiology, sites, patient's general condition and the type of urethral injury, using a rational combination of different imaging methods can improve the accuracy of diagnosis for traumatic urethral strictures.

Background: To evaluate combined buccal mucosa and lingual mucosa grafts for urethroplasty in a dog model., Materials and Methods: Seven female mongrel dogs were randomly selected. After a segment of proximal urethra mucosa (4 cm × 1cm) was excised and onlayed urethroplasty was performed using the combined free buccal mucosa (2 cm × 1cm) graft harvested from the inferior cheek and free lingual mucosa graft (2 cm × 1cm) harvested from the inferior lateral surface of the tongue. A 12F urethral catheter was kept inside the urethra for a mean of 7 d. Retrograde urethrography was done and urethra diameter was calibrated with a 10Fr catheter before animals were sacrificed at wk 12. After sacrifice of all dogs, the grafted areas excised and evaluated by gross and histopathological examination., Results: All dogs survived the procedure and there were no tongue and oral complications. One of the seven dogs developed a severe urethral stricture near the proximal anastomosis. The remaining six dogs voided spontaneously with no difficulty. Retrograde urethrography showed that no strictures or fistulas had formed. The combined buccal mucosa graft and lingual mucosa graft shortened by 10.2% after surgery, from a mean (SD) of 4 (0.15) to 3.59 (0.23) cm (statistical significance, P < 0.05). No stricture was found in the connection of the buccal mucosa and lingual mucosa grafts. Histologic examination showed that the combined buccal mucosa and lingual mucosa grafts were well-incorporated into the urethral walls and covered by a keratinized squamous epithelium., Conclusions: We successfully developed a dog model for combined buccal mucosa graft and lingual mucosa graft and showed the feasibility of this approach for urethral substitution., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To investigate the feasibility of replacing urinary epithelial cells with oral mucosa cell to reconstruct tissue engineered urethra by being seeded on bladder acellular matrix graft (BAMG)., Methods: Eighteen male New Zealand rabbits, aged 10 weeks, weighing 0.3-0.5 kg, were used in this study. Oral mucosa cell of 12 rabbits were isolated and seeded onto a culture dish with a feeder layer of 3T3 and a culture dish without 3T3, respectively. The morphologic change and growth condition of oral mucosa cells were observed by inverted phase contrast microscope after 2 days of seeding. The quantity of oral mucosa cells was counted using cell counting meter; the cell growth curve was drawn and the immunofluorescence staining with broad-spectrum keratin antibody was carried out. The bladders taken from the rest 6 rabbits were decelluled to make BAMG and the tissue of 1 cm x 1 cm was randomly selected to observe the effect of acellularization. The second passage oral mucosa cells cultured with 3T3 were applied to sterilized BAMG to obtain a tissue-engineered mucosa. The tissue-engineered mucosa was assessed using HE staining and scanning electron microscope after being cultured for 1 week., Results: Oral mucosa cells seeded onto a feeder layer of 3T3 could be passaged for 7 or 8 generations with homogeneous forms and full function. Oral mucosa cells cultured without 3T3 could only be subcultured for 2 generations before aging and had multiple shapes and different sizes. Oral mucosa cells cultured by the two methods both started logarithmic growth on the 8th day and reached the peak value on the 14th day, which was indicated by the cell growth curve. However, more cells could be obtained through oral mucosa cells cultured with 3T3 than those cultured without 3T3. Oral mucosa cells manifestated green colour fluorescence cultured with or without 3T3. After the cells were removed, the BAMG presented as a porous membrane. The HE staining showed that the effect of acellularization was good and there were no cells at BAMG. The second passage oral mucosa cells cultured with 3T3 were expanded and seeded onto sterilized BAMG to obtain a tissue-engineered mucosa. Good compatibility of the compound graft was assessed using HE staining and scanning electron microscope. HE staining and scanning electron microscope showed that oral mucosa cells had good biocompatibility with BAMG after the tissue engineered mucosa was cultured for 1 week., Conclusion: Oral mucosa cells of rabbit can be cultured in vitro and attain magnitude quantities. Oral mucosa cell also have good biocompatibility with BAMG and the compound graft could be a new material for urethral reconstruction.

Introduction: This study investigates the feasibility of replacing urinary epithelial cells with oral keratinocytes seeded on a bladder acellular matrix graft (BAMG) to reconstruct a tissue-engineered urethra., Materials and Methods: After enzymatic treatment of a small segment of rabbit buccal mucosa (1.0 x 0.4 cm), the epidermis and dermis were separated mechanically. Oral keratinocytes were isolated from the epidermis and seeded onto a culture dish with a feeder layer of 3T3 mouse fibroblasts inhibited by mitomycin (i3T3) or on a culture dish without i3T3, respectively. These cells were expanded and applied to sterilized BAMG to obtain a tissue-engineered mucosa. Oral keratinocytes were assessed by growth curve, morphology and immunofluorescence staining. The tissue-engineered mucosa was assessed using morphology, immunohistochemistry staining and scanning electron microscopy., Results: Oral keratinocytes seeded onto a feeder layer of i3T3 had finer morphous and better amplification capability, and could be passaged for 8 generations. Oral keratinocytes that were cultured without i3T3 could only be subcultured 2 generations before ageing. Passage 2 oral keratinocytes cultured with i3T3 were expanded and seeded onto sterilized BAMG to obtain a tissue-engineered mucosa for urethral reconstruction. The compound graft was assessed using HE staining and scanning electron microscopy. Oral keratinocytes had good compatibility with BAMG., Conclusions: Rabbit oral keratinocytes of can be cultured in vitro and attain magnitude in quantity. Oral keratinocytes also had good compatibility with BAMG and the compound graft achieved could become a new choice in urethral reconstruction., (2008 S. Karger AG, Basel)