Morphogenetic Aspects of the Response of Vaginal Tissues to Polypropylene Implants as the Basis of Mesh-Associated Complications.

Morphometric and immunohistochemical examination of the vaginal mucosa before and 12 months after installation of polypropylene implants for the correction of stress urinary incontinence was performed in 20 patients with genital prolapse. The research results confirmed good biocompatibility of polypropylene and the formation of full-fledged connective tissue in the vaginal mucosa, but revealed the presence of a weak lymphocytic reaction to polypropylene 12 months after surgery. According to immunohistochemical study, increased contents of B lymphocytes and plasma cells responsible for the inductive and productive stages of the immune response were revealed in the vaginal mucosa around the implants 12 months after surgery. This reaction in the presences of provoking factors can lead to the development of inflammation and erosion, a type of mesh-associated complications.

Experimental use of a cellulosic biopolymer as a new material for suburethral sling in the treatment of stress urinary incontinence.

PURPOSE: To analyze the interaction between the cellulose exopolysaccharide (CEC) and urethral tissue when used as a pubovaginal sling. MATERIALS AND METHODS: Forty Wistar rats were divided into four groups. In groups A and B the cellulose exopolysaccharide (CEC) was implanted around the urethral tissue (bladder neck below the upper margin) and the rats were sacrificed at 30 and 90 days. Similar procedure was used in groups C and D using a polypropylene mesh. After sacrifice bladder and urethra were sent for histological analysis. The histological parameters (inflammatory reaction) by evaluated by quantitative analysis. For collagen deposition analysis it was used stereological method. RESULTS: The cellulose exopolysaccharide (CEC) was inert and well preserved at the implanted region at the time of examination. Morphologic alterations were not found at the CEC implant but some reactions of foreign body type were observed at the adjacent structures. In some areas a process of neovascular formation was observed. Stereological analysis at the suburethral area showed a significant difference in collagen presence in favor of CEC. CONCLUSIONS: The CEC implant showed adequate results when used as a suburethral sling with good integration to the host tissue, preserving its architecture.

Long-term follow-up after urethral injection with polyacrylamide hydrogel for female stress incontinence.

Urethral injection therapy for treatment of stress urinary incontinence has been in use for years, but only a few long-term follow-up studies have been published. Twenty-five women, injected with polyacrylamide hydrogel 8 years earlier, were invited for follow-up. Twenty-four could be contacted; 15 had had no further treatment, seven had been re-operated with placement of mid-urethral slings, and two had been re-injected with polyacrylamide hydrogel. Eleven women attended for objective examination; all non-attenders were interviewed by telephone. Subjectively, in 44% the stress incontinence was cured or much improved, with a positive outcome according to the King's Health Questionnaire. Objectively, all patients had visible polyacrylamide hydrogel deposits on vaginal ultrasonography. No local adverse reactions were seen in the vaginal mucosa. The results of a later mid-urethral sling were unaffected by previous polyacrylamide hydrogel injection.

Reliability of a new method for assessing urethral compression following midurethral tape procedures using four-dimensional ultrasound.

OBJECTIVES: To evaluate the intra- and interobserver reliability of a new method of assessing resting and dynamic urethral compression after midurethral tape procedures using three- and four-dimensional (3D and 4D) ultrasound. METHODS: Thirty-one women who had undergone transobturator midurethral tape procedures at Cathay General Hospital were enrolled in the study and 4D ultrasound was performed pre- and postoperatively. Preoperative ultrasound assessment included measurement of the urethral central echolucent area (UCEA) in the axial plane. Postoperative ultrasound assessment included measurement of the tape-urethral distance (TUD) in the sagittal plane as well as UCEA and tape angle in the axial plane (ATA). The TUD was measured at the upper end (TUDu), central point (TUDc) and lower end (TUDl) of the tape. All pre- and postoperative ultrasound assessments were performed in women at rest, on maximum straining and during strong coughing. 4D ultrasound volume datasets were stored digitally and analyzed offline by two independent investigators blinded to clinical data and to each others' measurements. Intra- and interobserver reliability were evaluated using the intraclass correlation coefficient (ICC). RESULTS: There were significant reductions in TUDc, TUDl and UCEA during increased intra-abdominal pressure. ICC values for the measurement of TUD at rest, on straining and during coughing demonstrated very good reliability. ICC values for the pre- and postoperative measurement of UCEA at rest, on straining and during coughing demonstrated good to very good reliability. ICC values for the measurement of ATA at rest, on straining and during coughing demonstrated fair to good reliability. CONCLUSIONS: 4D ultrasound can be used to obtain measurements with good reliability in the assessment of urethral compression.

A biomimetic mesh for treating female stress urinary incontinence.

For patients with medium to severe incontinence, sub-urethral support surgery has a high cure rate, but using synthetic meshes leads to some complications such as mesh erosion/exposure and thigh pain. Autologous or acellular extracellular matrix grafts present few complications but have a high recurrence rate. Regensling™ is a new sling product made of a synthetic material with a biomimetic structure, aiming to provide long-term mechanical support with a lower complication rate. To assess the safety and effectiveness of Regensling™, both in vitro and in vivo experiments were performed. The mesh was implanted in the subcutaneous, intramuscular and sub-urethral regions of rabbits. At 4, 12, and 26 weeks post-implantation, the animals were executed and the implants were studied for their mechanical and biocompatible properties. Compared to the control material, the Regensling™ was covered by a thin layer of fibrous tissue with good compliance, and had a milder inflammatory response. During the period of the experiment, Regensling™ showed stable strength with an increasing trend over time.

Collagen deposition around polypropylene tapes implanted in the rectus fascia of female rats.

OBJECTIVE: Implantation of the mesh induces a foreign-body reaction followed by the development of connective tissue that may alter tape property. The aim of our study was to evaluate the deposition of collagen in the vicinity of monofilament tension-free vaginal tape (TVT; Ethicon Inc., Johnson & Johnson) and multifilament intravaginal slingplasty (IVS; Tyco Healthcare) polypropylene tapes implanted in female rats. METHODS: The samples of the meshes (10 mg each) were implanted in the rectus fascia of 14 Wistar female rats and removed after 42 days. Collagen was extracted with 0.5 M acetic acid and subsequently with pepsin (1 mg/ml in 0.5 M acetic acid). Collagen concentration was measured using Sircol Collagen Assay (Biocolor Ltd.) and normalised for milligrams of tape weight. For histological examination, tape samples were stained with haematoxylin and eosin or with silver for type III collagen. RESULTS: The total amount of collagen extracted did not differ significantly between TVT and IVS samples. For both tapes, extraction with acetic acid yielded a higher amount of collagen (about 70%) than extraction with pepsin. On histological examination, less densely packed bundles of collagen fibres and a slightly more intense inflammatory reaction were observed with TVT compared with IVS mesh. CONCLUSION: The total amount of collagen deposited around the polypropylene mesh implanted in female rats was similar for TVT and IVS meshes, but differences were noted in the arrangement of the collagen fibres and the intensity of the inflammatory reaction.

Local release from affinity-based polymers increases urethral concentration of the stem cell chemokine CCL7 in rats.

The protein chemokine (C-C motif) ligand 7 (CCL7) is significantly over-expressed in urethral and vaginal tissues immediately following vaginal distention in a rat model of stress urinary incontinence. Further evidence, in this scenario and other clinical scenarios, indicates CCL7 stimulates stem cell homing for regenerative repair. This CCL7 gradient is likely absent or compromised in the natural repair process of women who continue to suffer from SUI into advanced age. We evaluated the feasibility of locally providing this missing CCL7 gradient by means of an affinity-based implantable polymer. To engineer these polymers we screened the affinity of different proteoglycans, to use them as CCL7-binding hosts. We found heparin to be the strongest binding host for CCL7 with a 0.323 nM dissociation constant. Our experimental approach indicates conjugation of heparin to a polymer backbone (using either bovine serum albumin or poly (ethylene glycol) as the base polymer) can be used as a delivery system capable of providing sustained concentrations of CCL7 in a therapeutically useful range up to a month in vitro. With this approach we are able to detect, after polymer implantation, significant increase in CCL7 in the urethral tissue directly surrounding the polymer implants with only trace amounts of human CCL7 present in the blood of the animals. Whole animal serial sectioning shows evidence of retention of locally injected human mesenchymal stem cells (hMSCs) only in animals with sustained CCL7 delivery, 2 weeks after affinity-polymers were implanted.

Biomaterials for pelvic floor reconstructive surgery: how can we do better?

Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are major health issues that detrimentally impact the quality of life of millions of women worldwide. Surgical repair is an effective and durable treatment for both conditions. Over the past two decades there has been a trend to enforce or reinforce repairs with synthetic and biological materials. The determinants of surgical outcome are many, encompassing the physical and mechanical properties of the material used, and individual immune responses, as well surgical and constitutional factors. Of the current biomaterials in use none represents an ideal. Biomaterials that induce limited inflammatory response followed by constructive remodelling appear to have more long term success than biomaterials that induce chronic inflammation, fibrosis and encapsulation. In this review we draw upon published animal and human studies to characterize the changes biomaterials undergo after implantation and the typical host responses, placing these in the context of clinical outcomes.

[Tissue reaction to polypropylene mono-or multi-filament tapes used in surgical techniques of stress urinary incontinence treatment]. / Reakcja tkankowa wokól wszczepionych fragmentów tasmy polipropylenowej: mono-i multifilamentowej stosowanych w leczeniu wysilkowego nietrzymania moczu u kobiet.

OBJECTIVES: The "gold standard" in surgical treatment of stress urinary incontinence (SUI) is sling operation with polypropylene tape appliance under the mid urethra. There are two types of polypropylene tape which are the most popular nowadays. These two tapes are differently knitted so they have different biomechanical features. The TVT tape is monofilament, rarely knitted and highly elastic but the IVS mesh is multifilament, densly knitted and has only little possibility to stretch. The aim of our study was to assess the tissue reaction to the mono-(TVT) and multifilament (IVS) tapes. MATERIAL AND METHODS: The 10 mm x 10 mm pieces of TVT and IVS tapes were implanted inlay the fascia of musculus abdominis rectus of 14 rat females (2 groups of 7 animals). The tapes with the margin of surrounding fascia were taken off after 6 weeks of healing. All samples were fixed in 10% Formaldehyde in phosphate buffered saline and embedded in paraffin. Four micron tissue sections were stained with hematoxylin and eosin, the reticulin silver impregnation stain according to Gomori (for collagen type III) and periodic acid Schiff and alcian blue (for proteoglycan). RESULTS: In all sections filaments visible as elipsoids were surrounded by resorptive granulation with large multinucleated giant cells like around "foreign body". The diameter of monofilaments was about 150 microns. The connective tissue in the vicinity of mesh was rich of inflammatory cells like histiocytes, lymphocytes, a few polymorphonuclear leucocytes as well as adipocytes and fibroblasts. The large multinucleated giant cells adjacent to monofilaments were relatively bigger than these cells around multifilaments. Moreover, this granulation tissue has a lot of new blood vessels and collagenous fibrous tissue. The multifilaments were about 40 microns in diameter. The inflammatory granulation infiltrated aggregates of multifilaments. This tissue had only few inflammatory cells in comparison to tissue around monofilaments. The large multinucleated giant cells apposed to the mesh were small and collagen created thicker, more compacted bundles. CONCLUSION: The multifilament polypropylene tape induces weaker inflammatory tissue reaction than monofilament mesh. The thicker and more compacted collagen bundles are created around multifilaments so the natural tensile strength of the surrounding tissue is probably higher.

Visualization of polypropylene and polyvinylidene fluoride slings in perineal ultrasound and correlation with clinical outcome.

INTRODUCTION AND HYPOTHESIS: Complications and malfunctioning after TOT can occur due to several factors, such as the material of the sling. The aim of the present study is to evaluate morphology and functionality of two types of slings (PVDF; polypropylene) in vivo using perineal ultrasound (PUS). MATERIALS: In n = 47 women with TOT four criteria for PUS were taken and checked for possible differences: vertical stability of the sling position during Valsalva manoeuvre and contraction; distance "sling to urethra"; width of the sling and condition of the selvedges. RESULTS: We observed an increased vertical displacement of the PP-slings, a significantly smaller variance to the extent of the displacement in PVDF-slings (P < 0.01), a significantly larger distance between sling and urethra (P < 0.001) in PVDF-slings, and a significantly smaller width of the PP-slings (P < 0.0001). CONCLUSION: Significant differences were found between the slings according to the four criteria. There was no difference established between the slings in the improvement of continence and no significant influence of the parameters was found for the resulting state of continence. In future studies, PUS may help to link differences in the morphology and functionality of in vivo slings to their material properties.

Acute in vivo response to an alternative implant for urogynecology.

PURPOSE: To investigate in vivo the acute host response to an alternative implant designed for the treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP). METHODS: A biodegradable scaffold was produced from poly-L-lactic acid (PLA) using the electrospinning technique. Human and rat adipose-derived stem cells (ADSCs) were isolated and characterized by fluorescence-activated cell sorting and differentiation assays. PLA scaffolds were seeded and cultured for 2 weeks with human or rat ADSCs. Scaffolds with and without human or rat ADSCs were implanted subcutaneously on the abdominal wall of rats. After 3 and 7 days, 6 animals from each group were sacrificed. Sections from each sample were analyzed by Haematoxylin and Eosin staining, Sirius red staining, and immunohistochemistry for CD68, PECAM-1, and collagen I and III. RESULTS: Animals responded to the scaffolds with an acute macrophage response. After 7 days of implantation, there was extensive host cell penetration, new blood vessel formation, and new collagen deposition throughout the full thickness of the samples without obvious differences between cell-containing and cell-free scaffolds. CONCLUSIONS: The acute in vivo response to an alternative implant (both with and without cells) for the treatment of SUI and POP showed good acute integration into the host tissues.

Periurethral injection of autologous adipose-derived stem cells with controlled-release nerve growth factor for the treatment of stress urinary incontinence in a rat model.

BACKGROUND: Stem cell therapy is a promising therapeutic strategy for stress urinary incontinence (SUI). However, its current efficacy is insufficient. OBJECTIVE: We designed a stem cell transplantation system that contains autologous adipose-derived stem cells (ADSC) and controlled-release nerve growth factor (NGF). We evaluated whether this system could enhance the therapeutic efficacy of ADSCs by periurethral coinjection in SUI rats. DESIGN, SETTING, AND PARTICIPANTS: We first tested for the presence of NGF receptors in rat ADSCs and observed the effect of NGF on ADSCs in vitro and in vivo. NGF was encapsulated within poly(lactic-co-glycolic acid-PLGA) microspheres (PLGA/NGF) to control its release. SUI was created in rats, and ADSCs were harvested, cultured from fat tissue, and retained for later transplantation. SUI rats then received different forms of periurethral injection therapy. Their urodynamic index was monitored. Eight weeks after injection, the SUI rats were sacrificed and their urethra removed for histologic evaluation. INTERVENTION: Forty SUI rats were allocated to five groups for receiving periurethral injection with phosphate-buffered saline (PBS), ADSC, ADSC+PLGA, ADSC+NGF, or ADSC+PLGA/NGF. Bladder capacities, abdominal leak point pressure (ALPP), and retrograde urethral perfusion pressure (RUPP) were reassessed at 2, 6, and 8 wk after injection. MEASUREMENTS: The rat SUI model was generated by bilateral pudendal nerve transection (PNT). Real-time polymerase chain reaction (RT-PCR) and western blotting detected the NGF receptor Ark-A. The regeneration of muscles and peripheral nerves was evaluated by Masson's trichrome and immunohistochemical staining. RESULTS AND LIMITATIONS: Results revealed the presence of the NGF receptor Trk-A on rat ADSCs. Short-term observations showed that NGF could improve ADSCs' viability in vitro and in vivo. ADSCs delivered intramuscularly into the urethra in combination with PLGA/NGF resulted in significant improvements in ALPP and RUPP as well as the amount of muscle and ganglia. There was a significant difference between the ADSC+PLGA/NGF group and other groups. CONCLUSIONS: Periurethral coinjection of autologous ADSCs with controlled-release NGF may be a potential strategy for SUI treatment.

Experimental use of a cellulosic biopolymer as a new material for suburethral sling in the treatment of stress urinary incontinence

Purpose: To analyze the interaction between the cellulose exopolysaccharide (CEC) and urethral tissue when used as a pubovaginal sling. Materials and Methods: Forty Wistar rats were divided into four groups. In groups A and B the cellulose exopolysaccharide (CEC) was implanted around the urethral tissue (bladder neck below the upper margin) and the rats were sacrificed at 30 and 90 days. Similar procedure was used in groups C and D using a polypropylene mesh. After sacrifice bladder and urethra were sent for histological analysis. The histological parameters (inflammatory reaction) by evaluated by quantitative analysis. For collagen deposition analysis it was used stereological method. Results: The cellulose exopolysaccharide (CEC) was inert and well preserved at the implanted region at the time of examination. Morphologic alterations were not found at the CEC implant but some reactions of foreign body type were observed at the adjacent structures. In some areas a process of neovascular formation was observed. Stereological analysis at the suburethral area showed a significant difference in collagen presence in favor of CEC. Conclusions: The CEC implant showed adequate results when used as a suburethral sling with good integration to the host tissue, preserving its architecture.

A new technique combining both polypropylene and vaginal wall sling procedures: can it minimize the risk of urethral and vaginal erosion occurring with synthetic materials?

We describe a new technique combining in situ vaginal wall and polypropylene mesh slings that may decrease potential erosive complications caused by synthetic materials. A folded mucosal patch harboring the polypropylene mesh was placed between mid-urethra and bladder neck. Using this technique, 12 consecutive women (age range 44-66 years) were operated. Preoperative evaluation included a detailed history, pelvic examination, stress test, cystourethroscopy, basic urodynamic evaluation (cystometry, Valsalva leak point pressure measurement), and urine culture. Based on these evaluations, three, seven, and two patients had type I, II, and III stress urinary incontinence, respectively. A paraurethral cyst excision was carried out in one patient and anterior colporrhaphy in four patients during the same operation. No ischemia or sloughing at the operation site occurred in any case. Pelvic examination was repeated in all patients after 3 and 6 months of follow-up and symptoms were determined after 12 months of follow-up in eight patients by telephone interview. Average follow-up was 10 months (range: 6-14 months). None of the patients were incontinent, or complained of sexual dysfunction or erosive complications after 1 year. Since there are two distinct barriers between the sling and both urethra and vagina, our technique covers all advantages of a sling procedure with synthetic materials and avoids the risk of urethral and vaginal erosion. The other advantage of this technique is the concomitant utilization of the vaginal wall as sling material.

Influence of different sling materials on connective tissue metabolism in stress urinary incontinent women.

The aim of this study was to investigate the influence on the paraurethral connective tissue of different sling materials used in incontinence surgery. Biopsies from the paraurethral connective tissue were obtained intraoperatively from 16 women with stress urinary incontinence; all were operated on with the TVT procedure, 6 with Mersilene as the sling material and 10 with Prolene. Biopsies from 4 continent women with uterine bleeding irregularities, matched for age and parity, served as controls. New biopsies were obtained from all women after 2 years. The biopsies were examined histologically and analyzed for collagen concentration and solubility. An obvious inflammatory reaction with a significant increase in collagen extractability by pepsin was identified in patients where Mersilene was used as the sling material. A minimal inflammatory reaction without a significant change in collagen solubility was found in the Prolene group. In the control group no inflammatory reaction was seen. Mersilene gave rise to a significant foreign-body reaction in the paraurethral connective tissue after surgery. Such a reaction was not found with Prolene.

Transvaginal bone anchors in female stress urinary incontinence: poor results.

OBJECTIVE: This study evaluates the results of a minimally invasive technique for correcting female stress urinary incontinence by transvaginal implantation of pubic bone anchors. PATIENTS AND METHODS: Female stress urinary incontinence was treated by fixing a gelatin-coated Dacron sling between two miniature titanium anchors with Prolene sutures. RESULTS: A total of 26 patients (median age 57.2 years) underwent the sling procedure. The follow-up examination was performed after 11.4 months on average. Stress incontinence showed a median improvement from grade 2 to grade 0.5 (p = 0.01), although only 16 of the 26 patients were completely continent. Urethral pressure and functional length were not significantly influenced. Impaired vaginal wound healing was seen in 14 of the 26 patients (53.8%), and 13 of them underwent revision. All patients affected (15/26, 57.7%) as well as 1 with uneventful healing showed sensory urge symptoms or detrusor instability (7/26, 26.9%). The correlation between impaired wound healing and detrusor instability was highly significant (p < 0.003). 17 of the 26 patients (65.3%) were dissatisfied or very dissatisfied with the intervention. The unfavorable results did not significantly correlate with the patients' age, the number of previous operations, or the surgeon's skill. CONCLUSION: In view of the poor vaginal wound healing and the resultant irritative symptoms, transvaginal bone anchoring with fixation of a Dacron sling must be regarded as an unsuitable technique.

Transurethral implantation of silicone polymer for stress incontinence: evaluation of a porcine model and mechanism of action in vivo.

OBJECTIVE: To evaluate the anatomical location, histological appearances and mechanism of action of sili-cone polymer (Macroplastique(R)) after transurethral implantation. MATERIALS AND METHODS: An in vivo pig model was developed to investigate the organization of Macroplastique 6 weeks after injection. The results were compared with the immediate appearance of injected Macroplastique in a surgical training device (using isolated pig urethrae) and with the histological appearances of Macroplastique in an explanted human specimen. RESULTS: Macroplastique was subserosal in all specimens; it provoked a marked foreign-body inflammatory reaction, producing firm nodules 6 weeks after implantation. The histological appearances in the in vivo pig model and the human specimen were indistinguishable. CONCLUSIONS: These findings indicate that the mechanism of action of Macroplastique is to augment pressure transmission to the proximal urethra by producing focal but firm expansion of periurethral tissues.

TVT (cinta vaginal libre de tensión) nuevo tratamiento para la incontinencia urinaria de esfuerzo: experiencia en el Hospital Patrocinio Peñuela Ruíz / TVT (vaginal type free of tension) new treatment for the incontinence urinaria of effort: experience in the Hospital Patrocinio Peñuela Ruíz

Descripción de la técnica quirúrgica y evaluación en nuestra casuística del tratamiento de la incontinencia urinaria de esfuerzo con cinta vaginal libre de tensión (TVT). Se realizo una revisión de la literatura acerca de este nuevo método. Se revisaron las historias de las pacientes sometidas a este procedimiento en el Hospital Patrocinio Peñuela Ruíz, recolectando datos en tablas para la evaluación y análisis de la misma. Se encontraron un total de 14 casos, con un promedio de edad de 50 años. Se presentaron (2) casos de perforación de vejiga (14,2 por ciento), dos (2) casos presentaron retención urinaria en el postoperatorio inmediato (14,2 por ciento). La tasa de curación subjetiva fue de 81,8 por ciento. La mayoría de los casos fueron intervenidos en forma ambulatoria. Los resultados obtenidos son equiparables con los publicados en otras series. Concluimos se trata de una técnica sencilla, de fácil aprendizaje, con tiempo quirúrgico corto y corta estancia postoperatoria, siendo así una buena elección en el tratamiento de la incontinencia urinaria de esfuerzo.