Application of the ERAS guidelines in pediatric urological surgery: a systematic review.

INTRODUCTION: Consensus for Enhanced Recovery After Surgery (ERAS) in pediatrics has been achieved in neonatal intestinal surgery, yet it is not widely utilized in pediatric urology. We investigated the application of ERAS guidelines in pediatric urology, and determined its effects given the available level of evidence supporting the ERAS protocol in children. EVIDENCE ACQUISITION: A systematic literature review including series providing adoption of fast-track recovery protocols for pediatric urology procedures was carried out. Main outcome measures were study characteristics, adherence to the 19 ERAS items, complication rates and length of hospital stay. Sub-group analysis by surgery type (hypospadias versus major surgery) was performed. EVIDENCE SYNTHESIS: Nine series with data from 1272 surgical pediatric cases were included. An enhanced recovery pathway was applied in 67.3% of the reports. Two series included patients undergoing hypospadias repair and ERAS items were insufficiently reported. Studies including children undergoing major procedures mentioned a median of 15 ERAS items, yet applied a median of 11 items. Median compliance rate was 88.9% (range 50-100). More ERAS guideline items were reported (applied or mentioned) in the most recently published studies. CONCLUSIONS: There is limited reporting and use of the ERAS guidelines in urologic surgery particularly in hypospadias repair; whilst in major surgery in children, adherence and compliance rates vary widely. In more recent series there was an increase in ERAS items that have been mentioned and applied. Future research is needed to identify barriers and to overcome them in order to fully adopt and benefit from the ERAS pathway.

Challenging the Urologist of the Future: Time for a Change?

Physicians need both medical expertise and diverse skills for effective patient care. Adaptability is also key in embracing advances in technology and new techniques. We outline six thought-provoking points to guide the new generation of urologists.

What should be next in lifelong posterior hypospadias: Conclusions from the 2023 ERN eUROGEN and EJP-RD networking meeting.

BACKGROUND: A congenital disease is for life. Posterior hypospadias, the severe form of hypospadias with a penoscrotal, scrotal, or perineal meatus, is a challenging condition with a major impact on lifelong quality of life. AIM: Our network meeting is aimed to identify what is currently missing in the lifelong treatment of posterior hypospadias, to improve care, quality of life, and awareness for these patients. METHODS: The network meeting "Lifelong Posterior Hypospadias" in Utrecht, The Netherlands was granted by the European Joint Programme on Rare Diseases-Networking Support Scheme. There was a combination of interactive sessions (hackathons) and lectures. This paper can be regarded as the last phase of the hackathon. RESULTS: Surgery for hypospadias remains challenging and complications may occur until adulthood. Posterior hypospadias affects sexual function, fertility, and hormonal status. Transitional care from childhood into adulthood is currently insufficiently established. Patients should be more involved in defining desired treatment approach and outcome measures. For optimal outcome evaluation standardization of data collection and registration at European level is necessary. Tissue engineering may provide a solution to the shortage of healthy tissue in posterior hypospadias. For optimal results, cooperation between basic researchers from different centers, as well as involving clinicians and patients is necessary. CONCLUSIONS: To improve outcomes for patients with posterior hypospadias, patient voices should be included and lifelong care by dedicated healthcare professionals guaranteed. Other requirements are joining forces at European level in uniform registration of outcome data and cooperation in basic research.

Mobility and Sporting Activity After Renal Trauma: A Survey Regarding Best Clinical Practice During the Recovery Stage.

OBJECTIVE: To evaluate strategies that are followed after pediatric renal trauma during the recovery stage, with an emphasis on mobility and involvement in subsequent sporting activities. Renal trauma is the most common urogenital trauma in children. The American Association for the Surgery of Trauma (AAST) scale is most commonly used to stratify the severity of injury. There is no consensus in the existing literature with respect to the recovery stage following renal trauma. METHODS: A survey was constructed by the European Association of Urology (EAU) - Young Academic Urologists (YAU) Pediatric Urology Working Group and then made digitally available on SurveyMonkey. The survey consists of 15 questions exploring relevant factors and timing to start again with mobility and activity. RESULTS: In total 153 people responded, of whom 107 completed the entire survey. The presence of pain and severity of trauma were acknowledged as most important factors to commence mobilization, whereas presence of hematuria was identified as an additional factor for sporting activity. Regardless of severity of trauma a minimum of 90% of respondents recommend return to noncontact sports within 12weeks. For contact sports, a minimum of 33% of respondents advised >12weeks minimum before starting again. A small number of respondents would never allow sporting activities again. CONCLUSION: The time to allow sporting activity shows high variation among the respondents, some even restricting sporting activities completely. This survey highlights the need for a standardized protocol based on multicenter follow-up data.

A multi-institutional European comparative study of open versus robotic-assisted laparoscopic ureteral reimplantation in children with high grade (IV-V) vesicoureteral reflux.

INTRODUCTION: Traditionally, open ureteral reimplantation (OUR) has been the standard treatment for primary vesicoureteral reflux (VUR) requiring reimplantation. Robotic-assisted laparoscopic ureteral reimplantation (RALUR) is gaining popularity and high success rates have been reported. OBJECTIVE: In this multi-institutional study, we aimed to compare the perioperative and postoperative outcomes of OUR and RALUR for high-grade (IV + V) VUR in children. STUDY DESIGN: A retrospective evaluation was performed collecting data from 135 children (0-18 years) who underwent high grade VUR surgical correction at nine European institutions between 01/01/2009 and 01/12/2020, involving either open or robotic approaches. Institutional review board approval was obtained. Patients with lower grades of VUR (≤III), previous history of open or endoscopic ureteral surgery, neurogenic bladder, or refluxing megaureter in need of ureteral tapering were excluded. Pre-, peri- and post-operative data were statistically compared. RESULTS: Overall, 135 children who underwent either OUR (n = 68), or RALUR (n = 67) were included, and their clinic and demographic features were collected. The mean age of the open group was 11 months (interquartile range [IQR] 9.9-16.6 months), in the RALUR group it was 59 months (IQR 29-78mo) (p < 0.01); the open cohort had a weight of 11 kg (IQR 9.9-16.6 kg) while the RALUR group had 19 kg (IQR 13-25 kg) (p < 0.01). No significant differences were found for intraoperative (1.5 % vs 7.5 %, p = 0.09) or for postoperative complication rates (7.4 % vs 9 %, p = 0.15). Favorable outcomes were reported in the RALUR group: shorter time to stooling (1 vs 2 days), fewer indwelling urethral catheter days (1 vs 5 days), perioperative drain insertion time (1 vs 5 days) and a shorter length of hospital stay (2 vs 5 days) (p < 0.01). The success rate was 94.0 % and 98.5 % in the open and RALUR groups, respectively. The long-term clinical success rates from both groups was comparable:42 vs 23 months for open and RALUR, respectively. DISCUSSION: This study reported a large multicentric experience focusing on high grade VUR. Furthermore, this study compares favorably to OUR in a safety analysis. There was also a trend towards higher success rates with RALUR utilizing an extravesical approach which has not been previously reported. CONCLUSION: RALUR is an efficacious and safe platform to use during ureteral reimplantation for high grade VUR. The overall peri-operative and post-operative complication rates are at least equivalent to OUR, but it is associated with a faster functional recovery and time to discharge. Medium to long term success rates are also equivalent to OUR.

Undescended testis: A roundtable discussion based on clinical scenarios - Part 1.

Undescended testis (UDT, cryptorchidism) is the most common congenital anomaly of the genital tract. Despite its high incidence, the management of UDT varies between specialties (urology, pediatric surgery, pediatric urology, pediatric endocrinology). Therefore, as the European Association of Urology - Young Academic Urologists Pediatric Urology Working Group, we requested experts around the world to express their own personal approaches against various case scenarios of UDT in order to explore their individual reasoning. We intended to broaden the perspectives of our colleagues who deal with the treatment of this frequent genital malformation.

Primum Non Discernere: Glass Ceilings and Female Representation at the European Association of Urology and European Society for Paediatric Urology Annual Meetings, 2012-2022.

Background: The term glass ceiling coined by Loden in 1978 is commonly used to describe difficulties faced by minorities and women when trying to move into senior roles. Objective: To analyse trends and patterns for female representation at the European Association of Urology (EAU) and European Society for Paediatric Urology (ESPU) annual general meetings over the past decade. Design setting and participants: We used objective data on female representation in the roles of chairs, moderators, and lecture speakers at the EAU and ESPU meetings from 2012 to 2022. Outcome measurements and statistical analysis: We evaluated gender based representation in paediatric urology sessions at the EAU and ESPU meetings, collecting data on the overall number of sessions, lectures, symposiums, abstract/poster sessions, and courses, and analysed the male/female ratio. Data were derived from printed and digital programmes for the relevant meetings. Results and limitations: During the period from 2012 to 2022, the percentage female representation varied from 0% (2012) to a maximum of 35% (2022) at EUA paediatric urology sessions, and from 13.5% (2014) to a maximum of 32% (2022) at ESPU meetings. Both associations show clear progression towards equality. Conclusions: Female representation at EAU and ESPU meetings has risen over the years, reaching 35% and 32%, respectively, in 2022, which is in line with the number of female members. We hope that this motivates a move towards the equality objectives for 2030. A clear and fundamental societal change is needed, with fair and more consistent institutional policies and framework commitments in the areas of science, medicine, and global health. Gender equality and diversity taskforces are essential to achieve these goals. Patient summary: We analysed the male/female ratio for participants in annual meetings held by the European Association of Urology and the European Society for Paediatric Urology. From a low level in 2012, the ratio increased to over 30% in 2022, in line with the female membership of the societies. Focus on fair and consistent policies is needed to ensure that women are well represented in medicine.

Guideline Adherence of Paediatric Urolithiasis: An EAU Members' Survey and Expert Panel Roundtable Discussion.

Background: Paediatric nephrolithiasis has increased globally, requiring standardized recommendations. This study aims to assess the paediatric urolithiasis care between EAU members along with the statements of three experts in this field. Methods: The results of an electronic survey among EAU members comparing the guideline recommendations to their current practice managing paediatric nephrolithiasis in 74 centres are contrasted with insights from an expert-panel. The survey consisted of 20 questions in four main sections: demographics, instrument availability, surgical preferences and follow-up preferences. Experts were asked to give insights on the same topics. Results: A total of 74 responses were received. Computerised Tomography was predominantly used as the main imaging modality over ultrasound. Lack of gonadal protection during operations was identified as an issue. Adult instruments were used frequently instead of paediatric instruments. Stone and metabolic analysis were performed by 83% and 63% of the respondents respectively. Conclusions: Percutaneous Nephrolithotomy is the recommended standard treatment for stones > 20 mm, 12% of respondents were still performing shockwave lithotripsy despite PNL, mini and micro-PNL being available. Children have a high risk for recurrence yet stone and metabolic analysis was not performed in all patients. Expert recommendations may guide clinicians towards best practice.

What we learned from the Covid-19 first wave: a survey from Young Pediatric Urology Committee (YPUC) from ESPU.

BACKGROUND: The Corona virus still has a big impact on medical work. All medical specialties have been called to confront this unexpected event, even pediatric surgery. The objective of this study is to highlight the effect of pandemic on daily work of young pediatric surgeons during the Covid-19 first wave. METHODS: An online survey was sent via email by the Scientific Committee of YPUC in April 2020. The impact of Covid-19 was invested, by analyzing the results of answers received. The difference between young consultants and trainees (C and T) were examined to assess the effect of pandemic in 2 different categories. RESULTS: A total of 88 participants filled out the questionnaire. Guidelines around surgeries were well arranged: clear for 98% concerning triage with no difference between T and C; clear for 84% concerning pre-operative screening and for 81% concerning surgical dressing with a significance difference between T and C in understanding (p=0.07 and p=0.06). Forty-two respondents (48%) tested all surgical patients and the 20% operated patients positive for COVID-19. Thirteen (15%) were relocated to work in other divisions on different tasks, 12 were C. 86% of T did not participate in surgeries as much as before. CONCLUSIONS: The impact of the pandemic has been very significant for pediatric urologists and the difference between C and T confirm that the training could be impacted. After the first wave we should be careful on PPE, on pre-operative screening of surgical patients and we should protect the trainee learning curve.

Intravesical radiofrequency induced hyperthermia enhances mitomycin C accumulation in tumour tissue.

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is a highly recurrent disease with potential progression to muscle invasive disease despite the standard bladder instillations with mitomycin C (MMC) or Bacille Calmette-Guérin immunotherapy. Therefore, alternatives such as radiofrequency-induced chemohyperthermia (RF-CHT) with MMC are being investigated. The mechanism explaining the efficacy of RF-CHT is only partly understood. We examined whether RF-CHT results in higher MMC tissue concentrations as compared to cold MMC instillation. PATIENTS AND METHODS: Prior to a planned transurethral resection of bladder tumour (TURBT), patients with stage Ta NMIBC were allocated to either (1) cold MMC instillation or (2) RF-CHT. After MMC instillation, three biopsies were taken of both normal and tumour tissue. Biopsies were snap-frozen and MMC tissue concentrations were analysed using ultra-performance liquid chromatography. RESULTS: Eleven patients were included of which six received RF-CHT. Ten patients had TaG2-LG/HG papillary tumours at pathology. One patient in the RF-CHT group appeared to be free of malignancy and was excluded from the analysis as no tumour biopsies were available. The median MMC concentration in tumour tissue was higher in the RF-CHT group (median 665.00 ng/g vs. 63.75 ng/g, U = 51.0, p = 0.018). Moreover, in both techniques the MMC concentration was lower in normal tissue compared to tumour tissue. Tissue MMC concentration measurements varied substantially within, and between, different patients from the same group. CONCLUSION: Intravesical RF-CHT results in higher tumour MMC concentrations vs. cold MMC instillation which contributes to its superior efficacy.

Prediction model for recurrence probabilities after intravesical chemotherapy in patients with intermediate-risk non-muscle-invasive bladder cancer, including external validation.

PURPOSE: To develop a model to predict recurrence for patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) treated with intravesical chemotherapy which can be challenging because of the heterogeneous characteristics of these patients. METHODS: Data from three Dutch trials were combined. Patients treated with intravesical chemotherapy with characteristics according to the IR definition of the EAU guideline 2013 were included. Uni- and multivariable Cox regression with selection methods were used to identify predictors of recurrence at 1, 2, and 5 years. An easy-readable table for recurrence probabilities was developed. An external validation was done using data from Spanish patients. RESULTS: A total of 724 patients were available for analyses, of which 305 were primary patients. Recurrences occurred in 413 patients (57%). History of recurrences, history of intravesical treatment, grade 2, multiple tumors, and adjuvant treatment with epirubicin were relevant predictors for recurrence-free survival with hazard ratios of 1.48, 1.38, 1.22, 1.56, and 1.27, respectively. A table for recurrence probabilities was developed using these five predictors. Based on the probability of recurrence, three risk groups were identified. Patients in each of the separate risk groups should be scheduled for less or more aggressive treatment. The model showed sufficient discrimination and good predictive accuracy. External validation showed good validity. CONCLUSION: In our model, we identified five relevant predictors for recurrence-free survival in IR-NMIBC patients treated with intravesical chemotherapy. These recurrence predictors allow the urologists to stratify patients in risk groups for recurrence that could help in deciding for an individualized treatment approach.

Pharmacokinetic, Pharmacodynamic, and Activity Evaluation of TMX-101 in a Multicenter Phase 1 Study in Patients With Papillary Non-Muscle-Invasive Bladder Cancer.

INTRODUCTION/BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) has a strong tendency to recur despite adjuvant instillations. TMX-101 is a new liquid form of imiquimod for intravesical instillation and has activity in vitro against urothelial carcinoma. The purpose was to analyze the activity of TMX-101 in low-grade NMIBC. Furthermore, pharmacokinetic and pharmacodynamic characteristics and adverse events were evaluated. PATIENTS AND METHODS: A multicenter, prospective phase 1 trial in 7 patients with low-grade NMIBC was conducted. All patients underwent a marker lesion transurethral resection of the bladder tumor and 6 weekly instillations with TMX-101 0.2% or 0.4%. Cystoscopy 2 to 4 weeks after the last instillation evaluated the effect of TMX-101. RESULTS: The effective biologic dose (EBD = complete response [CR] in > 2 patients) could not be defined because none of the patients experienced CR. Maximum plasma concentration was 75.1 ng/mL in the 0.4% dose group. No drug accumulation was observed. In the pharmacodynamic analysis, urinary interleukin 1 receptor agonist (IL-1ra) represents the most sensitive and uniform response after TMX-101 instillation. A total of 87.0% reported at least 1 adverse event. All events were of grade 2 severity or less (Common Terminology Criteria of Adverse Events version 4.02). No clinically significant changes in laboratory parameters or vital signs were observed during or after treatment. CONCLUSION: Toll-like receptor 7 (TLR-7) agonists are effective in urothelial carcinoma in preclinical research. The EBD in this phase 1 study could not be determined because no patient experienced CR. IL-1ra could be valuable as a urinary biomarker in future developments. The safety of TMX-101 has been reconfirmed. New doses, other schedules, and NMIBC subgroups should be tested to define the EBD. A pilot study in carcinoma-in-situ patients is currently ongoing and results are expected shortly.

Urinary cytokines in patients treated with intravesical mitomycin-C with and without hyperthermia.

OBJECTIVES: To explore whether urinary cytokine and chemokine (CK) levels differed between cold mitomycin-C (cold-MMC)-treated patients and chemohyperthermia (C-HT)-treated patients, to shed light on the possible molecular mechanisms that might explain the superior outcome of C-HT. Furthermore, CK-differences were explored between C-HT responders and C-HT non-responders. METHODS: Twelve NMIBC patients were included. Nine received six-weekly C-HT, and three received four-weekly cold-MMC instillations. Urine was collected on 8-12 time points before and after every treatment. MDC, IL-2, IL-6, IL-8, IP-10, MCP-1 and RANTES were determined by Luminex(®)-analysis. RESULTS: Elevated urinary CK levels were observed in both groups after treatment. In general, CK-peaks were lower in the cold-MMC group in comparison with levels in the C-HT group. Significant higher MCP-1 and IL-6 levels were observed in C-HT-treated patients. Additionally, significant cumulative effects were observed for IP-10 and IL-2. However, IP-10 and IL-2 levels did not significantly differ between treatments. MDC levels after the first week of treatment were significantly higher in the C-HT responders compared with the non-responders. CONCLUSION: MMC treatment leads to elevated urinary CK levels with significantly higher MCP-1 and IL-6 levels in C-HT-treated patients. Increased MDC levels after the first C-HT instillation appear to be related to good clinical outcome and might be of additional value to personalize treatment. Studies involving more patients and longer follow-up are needed to substantiate this observation.

Comparison of expected treatment outcomes, obtained using risk models and international guidelines, with observed treatment outcomes in a Dutch cohort of patients with non-muscle-invasive bladder cancer treated with intravesical chemotherapy.

OBJECTIVE: To compare the risks according to the American Urological Association (AUA), EAU, European Organization for Research and Treatment of Cancer (EORTC) and Club Urológico Español de Tratamiento Oncologico (CUETO) classifications with real outcomes in a cohort of patients in the Netherlands, and to confirm that patients who were undertreated according to these risk models have worse outcomes than adequately treated patients. PATIENTS AND METHODS: Patients treated with complete transurethral resection of bladder tumour and intravesical chemotherapy were included. Not all patients would have received intravesical chemotherapy had they been treated to current standards, and thus comparison of the observed outcomes in our Dutch cohort vs expected outcomes based on the EORTC risk tables and CUETO scoring model was possible. The cohort was reclassified according to the definitions of five index patients (IPs), as defined by the AUA guidelines, and three risk groups, defined according to the EAU guidelines, to compare the outcomes of undertreated patients with those of adequately treated patients. RESULTS: A total of 1001 patients were available for comparison with the AUA definitions and 728 patients were available for comparison with the EORTC and CUETO models. There was a large overlap between the observed outcomes and expected recurrence and progression probabilities when comparison was made using the EORTC risk tables. The observed recurrence outcomes were in general higher than the expected probabilities according to the CUETO risk classification, especially in the long term. No differences in progression were found when comparing these two models to the Dutch cohort. Patients who were undertreated according to the guidelines showed, in general, a higher risk of developing recurrence and progression. Limitations are i.a. its retrospective nature and the differences in grading system. CONCLUSION: Comparisons between the observed outcomes in our Dutch cohort and the expected outcomes based on EAU and CUETO risk models and the EORTC and AUA guidelines showed that lack of adherence to existing guidelines translates into worse outcomes.

NMIBC risk calculators: how useful are they for the practicing urologist and how can their clinical utility be improved?

The natural history of non-muscle invasive bladder cancer (NMIBC) in individual patients can be unpredictable. Although there are known clinical and molecular factors associated with tumor recurrence and progression, it is challenging to reconcile these data during a typical patient encounter within a busy clinic. The authors discuss the European Organization for Research and Treatment of Cancer's risk tables along with other models for predicting prognosis in patients with NMIBC. The authors also describe their advantages and disadvantages and the barriers to using these risk models in daily clinical practice and provide a future perspective on prognostic models.

Results of a phase 1 dose escalation study of intravesical TMX-101 in patients with nonmuscle invasive bladder cancer.

PURPOSE: Imiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: We conducted a multicenter phase 1 dose escalation study in patients with nonmuscle invasive bladder cancer. Patients were included in 1 of 4 dose groups (0.05%, 0.1%, 0.2% or 0.4%) and treated with 6 weekly instillations of TMX-101, starting 2 weeks after transurethral resection of bladder tumor. Patients were evaluated weekly, and pharmacokinetic and pharmacodynamic parameters were measured. RESULTS: A total of 16 patients were included in the study with 4 per dose group. Two patients dropped out after instillation 2 in dose groups 1 and 2. Overall, 88 instillations were administered without serious adverse events. There were 118 adverse events, of which 84 were related to the study drug. All adverse events were mild or moderate and number or severity was not correlated with dose group. Of the related adverse events 70% were confined to the genitourinary tract and resolved without intervention. There was a dose dependent systemic uptake with low plasma levels up to dose group 3 (0.2%, 100 mg). Maximum plasma concentration in dose group 4 (0.4%, 200 mg) was 71.7 ng/ml. This is below plasma concentrations of 123 and 128 ng/ml without significant side effects measured in healthy volunteers after subcutaneous (30 mg) or oral intake (100 mg) of imiquimod, respectively. CONCLUSIONS: Intravesical treatment with TMX-101 is safe. The side effects are common but mild and mostly limited to the genitourinary tract. There is a low systemic uptake.

Intracutaneous and intravesical immunotherapy with keyhole limpet hemocyanin compared with intravesical mitomycin in patients with non-muscle-invasive bladder cancer: results from a prospective randomized phase III trial.

PURPOSE: Despite current treatment after transurethral resection of a bladder tumor, recurrences and progression remain a problem. Keyhole limpet hemocyanin (KLH) was beneficial in earlier studies. In this study, safety and efficacy of KLH were compared with that of mitomycin (MM). PATIENTS AND METHODS: Patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) without carcinoma in situ were enrolled in a randomized phase III trial. In all, 283 patients were randomly assigned for 16 adjuvant intravesical instillations with KLH after preimmunization, and 270 patients were randomly assigned for 11 adjuvant intravesical instillations with MM. Primary outcome measurement was recurrence-free survival (RFS). Secondary outcome measurements were progression-free survival, adverse events (AEs), and the effect of delayed-type hypersensitivity (DTH) response on clinical outcome. RESULTS: There were significantly more pT1 tumors in the MM group (P = .01). In a log-rank test, univariate and multivariate Cox regression analysis, KLH was less effective than MM regarding RFS (all P < .001). Progression was uncommon (n = 20). In univariate Cox regression analyses, KLH tended to prevent progression more effectively than MM, but in multivariate Cox regression analyses, this could not be shown. AEs were common but mild. Fever, flu-like symptoms, and fatigue occurred significantly more after KLH treatment. Allergic reactions and other skin disorders occurred significantly more after MM treatment. Significantly more DTH-positive patients developed a recurrence than DTH-negative patients. CONCLUSION: KLH had a different safety profile and was inferior to MM in preventing NMIBC recurrences. KLH tended to be more effective than MM in preventing progression. More research is needed to clarify the immunologic effects of KLH and the effects of KLH on progression.

Improving the cell distribution in collagen-coated poly-caprolactone knittings.

Adequate cellular in-growth into biomaterials is one of the fundamental requirements of scaffolds used in regenerative medicine. Type I collagen is the most commonly used material for soft tissue engineering, because it is nonimmunogenic and a highly porous network for cellular support can be produced. However, in general, adequate cell in-growth and cell seeding has been suboptimal. In this study we prepared collagen scaffolds of different collagen densities and investigated the cellular distribution. We also prepared a hybrid polymer-collagen scaffold to achieve an optimal cellular distribution as well as sufficient mechanical strength. Collagen scaffolds [ranging from 0.3% to 0.8% (w/v)] with and without a mechanically stable polymer knitting [poly-caprolactone (PCL)] were prepared. The porous structure of collagen scaffolds was characterized using scanning electron microscopy and hematoxylin-eosin staining. The mechanical strength of hybrid scaffolds (collagen with or without PCL) was determined using tensile strength analysis. Cellular in-growth and interconnectivity were evaluated using fluorescent bead distribution and human bladder smooth muscle cells and human urothelium seeding. The lower density collagen scaffolds showed remarkably deeper cellular penetration and by combining it with PCL knitting the tensile strength was enhanced. This study indicated that a hybrid scaffold prepared from 0.4% collagen strengthened with knitting achieved the best cellular distribution.