Developing biocompatible materials with improved angiogenic potential for surgical treatment of stress urinary incontinence and pelvic organ prolapse

Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are two related conditions that significantly impair the quality of life. One in ten women will require primary surgery for SUI and POP. Surgical treatment of both conditions often necessitates the use of a surgical mesh material which is now known to be associated with serious complications in up to 40% of women in long term follow- up. Recently, the use of vaginal mesh products in urogyneacological procedures have been suspended in NHS hospitals in England. There appears to be an unmet and urgent need for better biomaterials to support the pelvic floor which are able to better integrate into tissues at the sites of implantation. The aim of this thesis was to develop a synthetic, degradable material for use in the female pelvic floor that can promote angiogenesis and that can integrate well into tissues. As a first step, an in vivo assay has been developed and optimized to allow effective screening of constructed biomaterials. Biomaterials were processed with electrospinning of polylactic acid (PLA) which is a commonly used, degradable polymer for soft tissue applications. Electrospun PLA scaffolds were functionalized by incorporation of Vitamin C and Estradiol and were tested for their effects on stimulating new blood vessel formation and extracellular matrix production. As a final step, mesenchymal stem cells (MSCs) were also tested for their ability to promote angiogenesis. The final biomaterials were always tested for suitability of their biomechanical properties for applications in the pelvic floor. Both Vitamin C and Estradiol could effectively be incorporated into the electrospun PLA scaffolds with desirable ultrastructural and mechanical properties. Vitamin C was released from the scaffolds over several weeks whereas Estradiol was released over months. Both drugs increased the angiogenic potential of scaffolds and extracellular matrix production. Estradiol releasing electrospun PLA scaffolds resulted in the most dramatic increase in new blood vessel formation. Also MSCs had a mild stimulatory effect on angiogenesis. Future work is underway to test the Estradiol releasing scaffolds in relevant animal models

Parameatal Urethral Cyst: A Case Report

WOS: 000411191800010A 17-year-old boy presented with 15 mm swelling on the left side of his urethral meatus. He did not report any voiding symptoms. He was seeking medical treatment due to cosmetic concerns. Parameatal urethral cysts are benign conditions that are rarely reported in the literature. We performed complete excision of the cyst as previously suggested by some authors. On postoperative follow-up, there were no findings of voiding difficulty and cosmetic problem

Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering

WOS: 000399256500014PubMed ID: 28343005The aim of this study was to design a dermal substitute containing adipose derived stem cells (ADSC) that can be used to improve the regeneration of skin on difficult wound beds by stimulating rapid neovascularization. This was achieved by first synthesizing methacrylated gelatin (GeIMA) and methacrylated hyaluronic acid (HAMA) precursors which could be stored at -80 degrees C after lyophilisation. Polymer precursors were then dissolved in media (in 15:1 ratio), ADSCs added together with the photoinitiator and crosslinked with 40 s of W. Hydrogels degraded by 50% over 3 weeks in an in vitro environment. ADSC loaded hydrogels could be easily handled with forceps (compressive modulus was 6 kPa). Transparency of the gel would allow a full field-of-view of a wound site. The hydrogels provided a suitable microenvironment for ADSC proliferation as shown by the filopodia observed in confocal micrographs. In vivo studies demonstrated that stem cell loaded hydrogels increased vascularization by up to 3 fold compared to their cell free counterparts. In conclusion, GelMA/HAMA hydrogels loaded with ADSC showed the desired proliferative and angiogenic properties essential to promote angiogenesis for wound healing and improving survival of tissue engineered skin. (C) 2017 Elsevier Ltd. All rights reserved.Middle East Technical University Center of Excellence in Biomaterials and Tissue Engineering (BIOMATEN); TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [2211-C, 2214-A]; European Association of Urology Scholarship Programme (EUSP); Rosetrees TrustRosetrees Trust; Urology Foundation; Rosetrees TrustRosetrees Trust [M537]The authors acknowledge Middle East Technical University Center of Excellence in Biomaterials and Tissue Engineering (BIOMATEN) for the use of the facilities and for the financial support, and METU Central Laboratory for SEM analysis. The authors also acknowledge TUBITAK 2211-C and 2214-A scholarships and Menekse Ermis Sen, MD, PhD, for statistical analysis. Naside Mangir was funded by the European Association of Urology Scholarship Programme (EUSP), The Rosetrees Trust and The Urology Foundation. We thank Dr. Sabiniano Roman for providing the cultured ADSC used in this study

Use of a simple in vitro fatigue test to assess materials used in the surgical treatment of stress urinary incontinence and pelvic organ prolapse

AIMS: Stress urinary incontinence and pelvic organ prolapse are very common conditions with a proportion of patients requiring implantation of synthetic materials for a durable repair. However increasing numbers of post-surgical complications have been reported related to the use of polypropylene meshes. One hypothesis for the adverse response is poor mechanical matching of the relatively stiff polypropylene mesh particularly as materials in the pelvic floor will need to cope with decades of distension as occurs with increase of intraabdominal pressure on coughing, laughing, or sneezing. METHODS: In this study we have undertaken a very simple fatigue testing regime to compare the mechanical abilities of six materials. Four commercial meshes in clinical use and two novel electrospun materials not yet evaluated in the clinic were assessed using a uniaxial tensile test. This was performed on six samples of each dry material and on another six samples of each material after just 3 days of fatigue conditions using a dynamic bioreactor. RESULTS: The four commercial materials showed permanent mechanical deformation after just 3 days of stretching these materials by 25% elongation on a regular dynamic cycle, whereas the two new materials presented more elastic properties without deformation. CONCLUSIONS: We suggest that a test as simple as this 3-day fatigue testing is sufficient to distinguish between materials which have already been found to cause complications clinically and newer materials yet to be tested clinically which will hopefully prove more mechanically appropriate for implantation in the pelvic floor.status: publishe

What are the Predictive Factors of the Cure and Complication Rates for Midurethral Slings in the Treatment of Stress Urinary Incontinence in Women: A Multicenter and Multivariate Analysis Study

WOS: 000419241300002Objective: Predictive factors that could affect the cure and complication rates of midurethral slings (MUS) in the treatment of stress urinary incontinence (SUI) were investigated. Materials and Methods: A total of 594 women (outside-in transobturator in 285, inside-out transobturator in 91, and retropubic in 218) with SUI and who had undergone MUS were evaluated. The median age was 53.9 (27-82) years. Univariate analyses were done using chi-square test, Student's t-test and the Mann-Whitney U test. Multivariate analyses were done using logistic regression analysis to determine predictive factors affecting cure and complication rates. Results: The mean follow-up time was 48 months. The subjective cure rate was 84% and complication rate was 11.2%. On univariate and multivariate analyses, the cure rate was found to be increased in younger patients [odds ratio (OR): 0.97, 95% confidence interval (CI): 0.95-0.99, p=0.038] and in patients with pure SUI (OR: 2.17, 95% CI: 1.31-3.60, p=0.002). The type of surgery was the only statistically significant parameter affecting the complication rate, which was significantly higher in retropubic MUS procedure (OR: 6.28, 95% CI: 3.51-11.22, p<0.001). Conclusion: MUS is an effective and safe surgical procedure in the treatment of SUI. In this study, age and type of incontinence were the only significant predictive factors affecting the cure rate. Our study suggests that retropubic approach could be considered a risk factor for complication after MUS