Efficacy of simultaneous bilateral surgery using the oblique overriding position in the treatment of bilateral kidney stones.

To compare the safety and the efficacy of simultaneous bilateral surgery in the oblique overriding position versus staging surgery in the treatment of bilateral renal calculi. A total of 46 patients with bilateral renal stones from May 2019 to January 2022 in our center were retrospectively analyzed, including 29 males and 17 females, with a mean age of 48 ± 13.6 years, body mass index of 24.6 ± 2.3 kg/m2, and uneven size of bilateral renal stones, with a mean diameter of 29.5 ± 9.1 mm on the side with the larger kidney stones (PCNL) and a mean diameter of 13.1 ± 3.2 mm on the side with the smaller kidney stones. The patients were divided into two groups for simultaneous and stepwise bilateral endoscopic surgery, and the operative time, anesthesia time, postoperative hemoglobin, blood creatinine, postoperative VAS pain score, Clavien complication rating, average hospital stay, and stone removal rate at one month after surgery were evaluated in both groups. The simultaneous group outperformed the other group in anesthesia time, operative time, VAS score, and mean number of days in the hospital, and there were no significant differences between the two groups in postoperative hemoglobin drop values, hematocrit elevation values, Clavien complication ratings, and stone clearance rate at one month. Both simultaneous surgery and staging surgery were safe and effective. Simultaneous surgery can effectively shorten the operation and anesthesia time, and reduce the postoperative pain and hospital days of patients while ensuring similar stone clearance rates.

Injectable Decellularized Extracellular Matrix-Based Bio-Ink with Excellent Biocompatibility for Scarless Urethra Repair.

In recent years, decellularized extracellular matrices (dECM) derived from organs have attracted much attention from researchers due to their excellent biocompatibility, capacity to promote cell proliferation and migration, as well as pro-vascularization. However, their inferior mechanical properties, slow cross-linking, weak strengths, and poor supporting properties remain their inevitable challenges. In our study, we fabricated a novel dECM hydrogel with better crosslinking strength and speed, stronger support properties, and better mechanical properties. The hydrogel, which we named gelatin-based dECM powder hydrogel (gelatin-dECM hydrogel), was prepared by mixing dECM microparticles in gelatin solution and adding certain amount of 1-Ethyl-3-(3-dimethyl-aminopropyl-1-carbodiimide) (EDC) and N-hydroxysuccinimide (NHS). We evaluated the utility of this hydrogel by assessing the degradation rate, mechanical properties, and biocompatibility. The results showed that the gelatin-dECM hydrogel has high mechanical properties and biocompatibility and also has the ability to promote cell proliferation and migration. After injection of this hydrogel around the surgical sites of urethras in rabbits, the incorporation of dECM powder was demonstrated to promote angiogenesis as well as scarless repair by histological sections after surgery. The application of this novel hydrogel provides a new perspective for the treatment of post-traumatic urethral stricture.

Hydrogels for 3D bioprinting in tissue engineering and regenerative medicine: Current progress and challenges.

Three-dimensional (3D) bioprinting is a promising and innovative biomanufacturing technology, which can achieve precise position controlling of cells and extracellular matrix components, and further create complex and functional multi-cellular tissues or organs in a 3D environment. Bioink in the form of the cell-loaded hydrogel is most commonly used in bioprinting, and it is vital to the process of bioprinting. The bionic scaffold should possess suitable mechanical strength, biocompatibility, cell proliferation, survival, and other biological characteristics. The disadvantages of natural polymer hydrogel materials include poor mechanical properties as well as low printing performance and shape fidelity. Over the past years, a series of synthetic, modified, and nanocomposite hydrogels have been developed, which can interact through physical interactions, chemical covalent bond crosslinking, and bioconjugation reactions to change the characteristics to satisfy the requirements. In this review, a comprehensive summary is provided on recent research regarding the unique properties of hydrogel bioinks for bioprinting, with optimized methods and technologies highlighted, which have both high-value research significance and potential clinical applications. A critical analysis of the strengths and weaknesses of each hydrogel-based biomaterial ink is presented at the beginning or end of each section, alongside the latest improvement strategies employed by current researchers to address their respective shortcomings. Furthermore, we propose potential repair sites for each hydrogel-based ink based on their distinctive repair features, while reflecting on current research limitations. Finally, we synthesize and analyze expert opinions on the future of these hydrogel-based bioinks in the broader context of tissue engineering and regenerative medicine, offering valuable insights for future investigations.

Review on Additives in Hydrogels for 3D Bioprinting of Regenerative Medicine: From Mechanism to Methodology.

The regeneration of biological tissues in medicine is challenging, and 3D bioprinting offers an innovative way to create functional multicellular tissues. One common way in bioprinting is bioink, which is one type of the cell-loaded hydrogel. For clinical application, however, the bioprinting still suffers from satisfactory performance, e.g., in vascularization, effective antibacterial, immunomodulation, and regulation of collagen deposition. Many studies incorporated different bioactive materials into the 3D-printed scaffolds to optimize the bioprinting. Here, we reviewed a variety of additives added to the 3D bioprinting hydrogel. The underlying mechanisms and methodology for biological regeneration are important and will provide a useful basis for future research.

Efficacy and safety of mirabegron in the treatment of overactive bladder syndrome after radical prostatectomy: a prospective randomized controlled study.

Objectives: To evaluate the effects of mirabegron in the treatment of overactive bladder syndrome (OAB) after radical prostatectomy (RP). Patients and methods: A total of 108 post-operative RP patients were randomly assigned to either the mirabegron (study) or the placebo (control) group. The Overactive Bladder Syndrome Self-Assessment Scale (OABSS) was selected as the primary endpoint, and the International Prostate Symptom Score (IPSS) and Quality of Life (QOL) score were selected as secondary endpoints. Statistical analysis was performed using IBM SPSS Statistics 26, and the treatment effects were compared between the two groups using independent samples t-test. Results: In total, 55 patients were included in the study group and 53 patients in the control group. The mean age was(70.08 ± 7.54)years. There was no statistical difference in the baseline data between the two groups. OABSS scores decreased significantly in the study group compared to the control group during drug treatment (6.67 ± 1.06 vs. 9.14 ± 1.83, p < 0.01) and were better than the control group during the follow-up at week 8 and week 12. In addition, the decrease in IPSS scores (11.29 ± 3.89 and 15.34 ± 3.54, p<0.01) and the increase in QOL scores (2.40 ± 0.81 vs. 3.20 ± 1.00) were statistically significant in the study group. And the patients in the study group had better improvement in voiding symptoms and quality of life than the control group during the follow-up period. Conclusion: Daily administration of 50 mg mirabegron after RP surgery significantly improved the symptoms of OAB after surgery with fewer side effects. Additional randomized controlled trials should be conducted in the future to further evaluate the efficacy and safety of mirabegron.

Novel strategy using a spiral embedded flap for meatal stenosis after post-penile cancer amputation surgery: a single-center experience.

This study aimed to investigate the curative effect of spiral embedded flap urethroplasty for the treatment of meatal stenosis after penile carcinoma surgery. From January 2015 to January 2021, we used our technique to treat strictures of the external urethral orifice in seven patients, including four cases of meatal stenosis after partial penile resection and three cases of meatal stenosis after perineal stoma. All patients had previously undergone repeat urethral dilatation. The patients underwent spiral embedded flap urethroplasty to enlarge the outer urethral opening. The patients' mean age at the time of surgery was 60 (range: 42-71) years, the mean operative time was 43 min, and the median follow-up period was 18 months. The patients voided well post-operatively, and urinary peak flow rates ranged from 18.3 ml s-1 to 30.4 ml s-1. All patients were successful with absence of urethral meatus stricture. The present study showed that using spiral embedded flap urethroplasty to treat meatal stenosis after penile carcinoma surgery is an effective surgical technique with good long-term outcomes.

Urine-Microenvironment-Initiated Composite Hydrogel Patch Reconfiguration Propels Scarless Memory Repair and Reinvigoration of the Urethra.

The harsh urine microenvironment (UME), as an inherent hurdle, endangers and renders urethral repair unreachable. Innovatively, the unfavorable UME is utilized as the design source to construct a UME-responsive 3D-printed hydrogel patch for realizing scarless memory repair, wherein laser-excited reactive oxygen species (ROS) production and mechanical strength elevation using chemically crosslinked silicon quantum dots are accessible. Intriguingly, the proposed composite scaffolds can respond to Ca2+ in urine, cause structure reconfiguration, and repress swelling to further enhance scaffold stiffness. Systematic experiments validate that ROS birth and unexpected stiffness elevation in such UME-responsive scaffolds can realize scarless memory repair of the urethra in vivo. Comprehensive mechanism explorations uncover that the activations of cell proliferation and collagen-related genes (e.g., MMP-1 and COL3A1) and the dampening of fibrosis-related (e.g., TGF-ß/Smad) and mechanosensitive genes (e.g., YAP/TAZ) are responsible for the scarless memory repair of such UME-responsive scaffolds via enhancing collagen deposition, recalling mechanical memory, decreasing fibrosis and inflammation, and accelerating angiogenesis. The design rationales (e.g., UME-initiated structure reconfiguration and antiswelling) can serve as an instructive and general approach for urethra repair.

Effective Reconstruction of Functional Urethra Promoted With ICG-001 Delivery Using Core-Shell Collagen/Poly(Llactide-co-caprolactone) [P(LLA-CL)] Nanoyarn-Based Scaffold: A Study in Dog Model.

Hypospadias and urethral stricture are common urological diseases which seriously affect voiding function and life quality of the patients, yet current clinical treatments often result in unsatisfactory clinical outcome with frequent complications. In vitro experiments confirmed that ICG-001 (a well-established Wnt signaling inhibitor) could effectively suppress fibroblast proliferation and fibrotic protein expression. In this study, we applied a novel drug-delivering nanoyarn scaffold in urethroplasty in dog model, which continuously delivers ICG-001 during tissue reconstruction, and could effectively promote urethral recovery and resume fully functional urethra within 12 weeks. Such attempts are essential to the development of regenerative medicine for urological disorders and for broader clinical applications in human patients.

Magnetic targeting of super-paramagnetic iron oxide nanoparticle labeled myogenic-induced adipose-derived stem cells in a rat model of stress urinary incontinence.

Cell-based injectable therapy utilizing stem cells is a promising approach for the treatment of stress urinary incontinence (SUI). Applying a magnetically controlled cell delivery approach has enormous potential to enhance cell retention capability within the specified site. To assess the therapeutic efficacy of cellular magnetic targeting, we applied an external magnetic force to target an adipose-derived stem cell based therapy in a rat model of SUI. The results revealed that magnetic attraction of transplanted cells under the magnetic field was generated by cell uptake of superparamagnetic iron oxide nanoparticles in vitro. More importantly, magnetic targeting improved the retention rate of transplanted cells and facilitated the restoration of sphincter structure and function in a rat SUI model according to the results of histological examination and urodynamic testing. Therefore, magnetically guided targeting strategy might be a potential therapy method for treatment of SUI.

The Fabrication and Evaluation of a Potential Biomaterial Produced with Stem Cell Sheet Technology for Future Regenerative Medicine.

To date, the decellularized scaffold has been widely explored as a source of biological scaffolds for regenerative medicine. However, the acellular matrix derived from natural tissues and organs has a lot of defects, including the limited amount of autogenous tissue and surgical complication such as risk of blood loss, wound infection, pain, shock, and functional damage in the donor part of the body. In this study, we prepared acellular matrix using adipose-derived stem cell (ADSC) sheets and evaluate the cellular compatibility and immunoreactivity. The ADSC sheets were fabricated and subsequently decellularized using repeated freeze-thaw, Triton X-100 and SDS decellularization. Oral mucosal epithelial cells were seeded onto the decellularized ADSC sheets to evaluate the cell replantation ability, and silk fibroin was used as the control. Then, acellular matrix was transplanted onto subcutaneous tissue for 1 week or 3 weeks; H&E staining and immunohistochemical analysis of CD68 expression and quantitative real-time PCR (qPCR) were performed to evaluate the immunogenicity and biocompatibility. The ADSC sheet-derived ECM scaffolds preserved the three-dimensional architecture of ECM and retained the cytokines by Triton X-100 decellularization protocols. Compared with silk fibroin in vitro, the oral mucosal epithelial cells survived better on the decellularized ADSC sheets with an intact and consecutive epidermal cellular layer. Compared with porcine small intestinal submucosa (SIS) in vivo, the homogeneous decellularized ADSC sheets had less monocyte-macrophage infiltrating in vivo implantation. During 3 weeks after transplantation, the mRNA expression of cytokines, such as IL-4/IL-10, was obviously higher in decellularized ADSC sheets than that of porcine SIS. A Triton X-100 method can achieve effective cell removal, retain major ECM components, and preserve the ultrastructure of ADSC sheets. The decellularized ADSC sheets possess good recellularization capacity and excellent biocompatibility. This study demonstrated the potential suitability of utilizing acellular matrix from ADSC sheets for soft tissue regeneration and repair.

Bioengineered bladder patches constructed from multilayered adipose-derived stem cell sheets for bladder regeneration.

Cell-seeded scaffolds are a common route of cell transplantation for bladder repair and reconstruction. However, when cell suspensions are harvested, proteolytic enzymes often cause extracellular matrix damage and loss of intercellular junctions. To overcome this problem, we developed a bioengineered three-dimensional bladder patch comprising porous scaffolds and multilayered adipose-derived stem cell (ASC) sheets, and evaluated its feasibility for bladder regeneration in a rat model. Adipose-derived stem cells (ASCs) were labeled with ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticles. ASC patches were constructed using multilayered USPIO-labeled ASC sheets and porous polyglycolic acid scaffolds. To monitor the distribution and localization of bioengineered bladder patches in live animals, magnetic resonance imaging (MRI) was performed 2 weeks, 4 weeks and 8 weeks after transplantation. The bladder regenerative potential of ASC patches was further evaluated by urodynamic and histological analysis. Scanning electron microscopy indicated that cell sheets adhered tightly to the scaffold. MRI showed hypointense signals that lasted up to 8 weeks at the site of USPIO-labeled ASC sheet transplants. Immunofluorescence demonstrated that these tissue-engineered bladder patches promoted regeneration of urothelium, smooth muscle, neural cells and blood vessels. Urodynamic testing revealed that the ASC patch restored bladder function with augmented capacity. The USPIO-labeled ASC patch provides a promising perspective on image-guided tissue engineering and holds great promise as a safe and effective therapeutic strategy for bladder regeneration. STATEMENT OF SIGNIFICANCE: Adipose-derived stem cell (ASC) sheets avoid enzymatic dissociation and preserve the cell-to-cell interactions and extracellular matrix (ECM) proteins, which exhibit great potential for tissue regeneration. In this study, we developed a bioengineered three-dimensional bladder patch comprising porous scaffolds and multilayered ASC sheets, and evaluated its feasibility for bladder regeneration in a rat model. Tissue-engineered bladder patches restored bladder function and promoted regeneration of urothelium, smooth muscle, neural cells and blood vessels. Moreover, ultrasmall super-paramagnetic iron oxide (USPIO)-labeled bladder patches can be dynamically monitored in vivo by noninvasive MRI for long periods of time. Therefore, The USPIO-labeled bladder patch provides a promising image-guided therapeutic strategy for bladder regeneration.

The fabrication of 3D surface scaffold of collagen/poly (L-lactide-co-caprolactone) with dynamic liquid system and its application in urinary incontinence treatment as a tissue engineered sub-urethral sling: In vitro and in vivo study.

AIMS: To fabricate a novel nanoyarn biomaterial via a dynamic liquid electrospinning system, and to simultaneously evaluate whether nanoyarn is capable of being applied as a urinary sling for future clinical transfer. METHODS: Nanoyarn was cultured with adipose-derived stem cells (ADSCs). Cell morphology and function were observed on nanoyarn. Female rats that underwent vagina dilatation (VD) and bilateral ovarian resection (BOR) were used as the urinary incontinence model. After 2 weeks, the cells-sling was fixed to the suburethra. A commercial sling that tension-free vaginal tape-obturator (TVT-O) was used as a control. The urodynamic test for leak point pressure (LPP) and histological tests were used to evaluate the sling's performance in vivo. RESULTS: The nanoyarn possessed beneficial properties and the actin filament from ADSCs, which is very similar to muscle. Rats that underwent VD and BOR maintained a low LPP, whereas the LPP in rats with VD alone recovered to normal levels within 2 weeks. LPP in the nanoyarn group gradually decreased on the three urodynamic tests post-suburethral surgery, however, the cell-laden nanoyarn maintained LPP at normal levels for 8 weeks; the TVT-O group showed a significant increase in LPP at 8 weeks. Cell-laden nanoyarn was infiltrated with more cells, collagen, and vessels than the controls. CONCLUSIONS: The nanoyarn showed sufficient efficacy to maintain LPP in urinary incontinence rat model. In addition, it improved cell infiltration, collagen and muscle development compared to TVT-O. Thus, the combination of ADSCs and a nanoyarn scaffold could be a promising tissue-engineered sling for the treatment of urinary incontinence.

Efficacy of solifenacin in the prevention of short-term complications after laparoscopic radical prostatectomy.

Objective To evaluate the efficacy of solifenacin in the prevention of short-term complications after laparoscopic radical prostatectomy (LRP). Methods This randomized placebo-controlled study enrolled patients with histologically proven prostate cancer who underwent LRP. The patients were randomized to receive either solifenacin (5 mg once daily; study group) or placebo (control group) for the 15-day period beginning on the first day after surgery. The mean duration of detrusor overactivity (DO), the frequency of DO, the duration of macroscopic haematuria, and the days before catheter removal were recorded. The International Continence Society Short Form Male questionnaire, bladder neck stenosis episodes, and maximum urinary flow rate were evaluated at 1 month after surgery. The side-effects after using solifenacin were also recorded. Results A total of 120 patients were randomly assigned to the study group ( n = 62) or the control group ( n = 58). There were significantly lower rates of DO episodes during the daytime and night-time, haematuria and transient incontinence in the study group compared with the control group. Conclusion Solifenacin was a well-tolerated and effective treatment for the prevention of complications after LRP, with the main advantage compared with placebo being the decreased frequency of DO episodes during the daytime and night-time.

The Immediate Management of Pelvic Fracture Urethral Injury-Endoscopic Realignment or Cystostomy?

PURPOSE: We determined whether endoscopic realignment or cystostomy would provide the best immediate management of pelvic fracture urethral injury. MATERIALS AND METHODS: We retrospectively reviewed the records of 590 patients with pelvic fracture urethral injury. Of the patients 522 were included in analysis due to strict criteria, including 129 in the endoscopic realignment group and 393 in the cystostomy group. Data on stricture formation and length, intervention technique and long-term functional outcomes were analyzed. RESULTS: In the endoscopic realignment group stricture developed in 111 patients (83%) at a mean of 23.5 months, which is longer than the 7.6 months reported in the cystostomy group (p <0.05). Mean stricture length was 3.2 cm in the realignment group and 3.7 cm in the cystostomy group (p <0.05). Internal urethrotomy was performed in 21 patients (19%) treated with realignment vs 18 (5%) treated with cystostomy (p <0.05). Further repair was accomplished via simple perineal anastomosis in 57 patients (51%) with realignment and 138 (35%) with cystostomy (p <0.05). Ancillary procedures such as corporeal splitting, inferior pubectomy and crural rerouting were necessary in 14 (13%), 14 (13%) and 5 patients (4%) in the endoscopic realignment group, and in 94 (24%), 100 (25%) and 43 (11%), respectively, in the cystostomy group (all p <0.05). The rates of impotence and incontinence did not statistically differ between the endoscopy and cystostomy groups (14.3% vs 16.2% and 1.6% vs 2.1%, respectively, p >0.05). CONCLUSIONS: Endoscopic realignment may reduce stricture formation and length, and facilitate urethroplasty. However, endoscopic realignment is also associated with a prolonged clinical course for recurrence.

Structural and functional evaluation of oxygenating keratin/silk fibroin scaffold and initial assessment of their potential for urethral tissue engineering.

In this study, we report a new type of oxygen-generating scaffold, composed of human keratin, silk, gelatin and calcium peroxide (CPO). After mixing the silk/keratin (60:40) with 2% gelatin and 20% CPO, the film demonstrated excellent mechanical properties, non-cytotoxicity and oxygen-generative ability. The detailed structure of scaffold was revealed by confocal laser and electronic scanning microscopy. The gelatin formed the network structure, which mixed with silk fibroin and keratin. The CPOs were embedded into scaffold. A shell-core structure was formed in the CPO particles, in which the CPO was located in the core and the gelatin was mainly wrapped around the CPO. Furthermore, the oxygen-release test showed that scaffold was able to steadily release high level of oxygen over two weeks in vitro. In addition, the anti-bacterial function was also proved in the scaffold. Films with CPO enhanced the repair in dog urethral defect models, resulting in patent urethra. Improved organized muscle bundles and epithelial layer were observed in animals treated with CPO films compared with those treated with non-CPO films. This study suggests that this biomaterial could be suitable for tissue engineered urinary tract reconstruction.

Minimally invasive management with holmium laser in total urinary tract calculi.

OBJECTIVE: The purpose of this article was to study the management of total urinary tract calculi using holmium laser minimally invasive techniques. BACKGROUND DATA: It is rare for patients to present kidney stones, ureteral stones, and bladder stones simultaneously, and their treatment is considered to be complicated and difficult, specifically by minimally invasive techniques. METHODS: We collected seven cases of total urinary tract calculi from May 2007 to September 2012. Three cases were unilateral, and the others were bilateral. All of the cases presented calculus in the bladder, ureter, and kidney, which were secondary to the long-term indwelling double J stent or lower urinary obstruction. RESULTS: Extracorporeal shock-wave lithotripsy (SWL) was administered first, followed by the operation. For patients with bilateral calculi, at one stage, ureteroscopic lithotripsy (URL) with holmium laser was performed in all four cases to remove the bladder and bilateral ureter stones. Then, all patients underwent percutaneous nephrolithotomy (PCNL) with holmium procedures to address the bilateral kidney and upper ureter stones at the second stage. The indwelling double J stents were removed at the same time. For the patients with unilateral calculi, we performed a single operation, but it was conducted using the same treatment sequence as the bilateral procedure. The related symptoms in all cases disappeared after the operation. Re-examination showed that the stones were nearly dissolved and that renal function was recovered. CONCLUSIONS: URL with holmium laser for the bladder and ureters combined with PCNL to dissolve kidney and upper ureteral stones could be the ideal choice for the treatment of total urinary tract calculi.