Synthetic mesh slings have been shown to be an effective and durable option for treatment of stress urinary incontinence (SUI). Macroporous polypropylene (PP) is the most commonly used synthetic mesh material on the market. While PP slings are considered the gold standard, they can lead to mesh erosion and extrusion, persistent infections, pelvic pain, and dyspareunia. Postoperative complications with PP mesh requiring removal can be difficult due to substantial tissue infiltration into the large mesh pores. This can necessitate extensive surgical dissection for complete mesh removal, which can lead to increased patient morbidity. Additionally, PP is not inert post-implantation, with unpredictable shrinkage of up to 20%. 

The ideal synthetic mesh material for SUI would be functional, durable, chemically and physically inert, induce minimal foreign-body reaction, have minimal risk of infection, rejection, and erosion, and be easily removed should it be necessary [1]. This material has yet to be developed. New synthetic mesh sling alternatives are therefore needed. 

A newly engineered mesh implant was developed using expanded polytetrafluoroethylene (PTFE) with similar tensile strength as PP, but with a minimally microporous structure that remains completely inert post-implantation, with increased compliance, and negligible foreign body reaction. This material has an innovative and distinct microstructure compared to previous PTFE implants studied in the literature which showed high erosion rates [2].  

The aims of this study were to compare the novel PTFE implant to PP in a rat SUI model in (1) the treatment of SUI acutely and at 6 weeks after implantation and (2) the ease of implant extraction, adhesion formation, and induced histological changes at 1 and 6 weeks.  

We hypothesized that the newly developed sling would not only improve leak point pressure (LPP) in our rat SUI model, but also form less adhesions and thus be easier and faster to remove with decreased foreign body response compared to PP.

Cystometry with LPP were conducted acutely on 12 female Sprague-Dawley rats. Measurements were taken first at baseline, then following bilateral pudendal nerve transection (PNT) to induce SUI, and lastly after surgical implantation of either a PTFE or PP implant. Cystometry was performed via a suprapubic bladder catheter connected to a pressure transducer and flow pump. Each implant was placed under the mid-urethra and anchored to the rectus muscle and fascia via laparotomy. We calculated that a cohort of 6 animals per group would be needed to achieve significant results based on a sample size analysis using a paired t-test of the primary outcome, LPP, using each animal as its own control, with mean LPP of 30 cmH20, an anticipated change of LPP of 10 cmH20, a standard deviation of 7 cmH20, a power of 0.8 and an alpha of 0.05.

Subsequently, 14 rats underwent PNT followed by placement of either PTFE, PP, or sham implant. Sham implantation included all surgical steps performed in the mesh implant groups, except that the implant was removed immediately after placement under the mid-urethra. After 1 week, implant removal was timed, adhesions were scored on a 3-point grading scale (0=no adhesions, 1=thin adhesions, 2=focal dense adhesions, 3=dense widespread adhesions), and the urethra and anterior vagina were harvested for histological analysis. There are no quantitative outcomes for this study available for a sample size analysis. Animal number was based on our prior experience with placement of slings in female rats.

Lastly, 48 rats underwent PNT with implant placement (PTFE, PP, or sham), or underwent sham PNT with sham implant. After 6 weeks, we conducted cystometry with LPP, implant removal was timed, adhesions were scored, and tissue was harvested for histological analysis. We calculated that a cohort of 12 animals per group would be needed based on a sample size analysis of our prior data using an ANOVA, for statistically significant results of the primary outcome, LPP, with mean LPP of 30 cmH20, an anticipated change of LPP of 10 cmH20, a standard deviation of 7 cmH20, a power of 0.8 and an alpha of 0.05.

At both 1- and 6-weeks post-implantation, histological analysis included assessment of inflammatory response assessed using a 3-point scoring system on H&E stained tissue sections. Additionally, fibrotic reaction was quantified by collagen infiltration area using ImageJ on Masson's Trichrome stained sections.

LPP and histological analysis were blinded. Cytometry and LPP results were compared via one-way ANOVA, implant removal times were compared via two-tail T-test, adhesion scores were compared via Chi-square test, H&E results were compared via Chi-square test followed by a Bonferroni correction, and Masson’s trichrome results were compared via one-way ANOVA followed by Tukey’s multiple comparisons test.

Bilateral PNT decreased LPP both acutely and at 6 weeks (p<0.0001, p<0.0001). This decreased LPP was restored after implantation of either PTFE or PP implants acutely (p=0.03, p<0.01) and at 6 weeks (p<0.001, p<0.001). There were no differences in LPP between implants both acutely and at 6 weeks (Figure). 

PTFE implants created significantly less adhesions than PP implants at 1 week (0±0 vs 2±0; p=0.001) and 6 weeks (1±0.75 vs 3±0; p<0.0001). PTFE implants took significantly less time to remove compared to PP implants at 1 week (3±1 vs 428±134 sec; p=0.002) and 6 weeks (42±23 vs 683±133 sec; p<0.0001).

At 1 week, both PP and PTFE implants induced a comparable inflammatory response compared to sham (p=0.0001, p=0.0001). PTFE had increased collagen infiltration compared to sham and PP implant (p<0.05). At 6 weeks, PP and PTFE implants had increased inflammatory response compared to both sham controls, with PTFE exhibiting the highest inflammation level (p<0.0001). PP implant, PTFE implant, and sham implant with PNT had comparable increased collagen infiltration compared to pure sham (p<0.0001, p=0.0008, p<0.0001).

PNT successfully modeled SUI in this pre-clinical rat model. PTFE and PP implants comparably restored the PNT-induced SUI both acutely and after 6 weeks. PTFE implants created significantly less adhesions than PP after 1 and 6 weeks, enabling significantly faster removal times. Overall, PP and PTFE induced similar histologic changes with increased collagen infiltration and inflammatory response compared to sham. PTFE did have the highest inflammatory scoring histologically at 6 weeks; however, these findings  did not translate into appreciable clinical differences.

This novel PTFE implant has the potential to improve SUI, while also offering the advantage of easy and complete mesh removal when needed. Our next study will test the sling implant in a larger animal model that is more comparable to human anatomy and use a minimally invasive vaginal approach.

Karlovsky ME, Kushner L, Badlani GH. Synthetic biomaterials for pelvic floor reconstruction. Curr Urol Rep. 2005 Sep;6(5):376-84. doi: 10.1007/s11934-005-0057-7. PMID: 16120241.
Weinberger MW, Ostergard DR. Long-term clinical and urodynamic evaluation of the polytetrafluoroethylene suburethral sling for treatment of genuine stress incontinence. Obstet Gynecol. 1995 Jul;86(1):92-6. doi: 10.1016/0029-7844(95)00098-C. PMID: 7784030.