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. Author manuscript; available in PMC: 2023 Feb 1.
Published in final edited form as: Int Urogynecol J. 2021 Apr 16;33(2):327–335. doi: 10.1007/s00192-021-04792-0

A soft elastomer alternative to polypropylene for pelvic organ prolapse repair: a preliminary study

Katrina M Knight 1, Gabrielle E King 2, Stacy L Palcsey 2, Amanda M Artsen 1,3, Steven D Abramowitch 1,4, Pamela A Moalli 1,3,4
PMCID: PMC8521573  NIHMSID: NIHMS1701901  PMID: 33860812

Abstract

Introduction and Hypothesis:

We compared the impact of a mesh manufactured from the soft elastomer, polydimethylsiloxane (PDMS) to that of a widely used lightweight polypropylene (PP) mesh. To achieve a similar overall device stiffness between meshes, the PDMS mesh was made with more material and therefore, was heavier and less porous. We hypothesized that the soft polymer PDMS mesh, despite having more material, would have a similar impact on the vagina as the PP mesh.

Methods:

PDMS and PP meshes were implanted onto the vagina of 20 rabbits via colpopexy. Ten rabbits served as Sham. At 12 weeks, mesh-vagina complexes were explanted and assessed for contractile function, histomorphology, total collagen, and glycosaminoglycan content. Outcome measures were compared using one-way ANOVA and Kruskal-Wallis testing with appropriate post-hoc testing.

Results:

Relative to Sham, vaginal contractility was reduced following the implantation of PP (p=0.035) but not the softer PDMS (p=0.495). PP had an overall greater negative impact on total collagen and glycosaminoglycan content, decreasing by 53% (p<0.001) and 54% (p<0.001) compared to reductions of 35% (p=0.004 and p<0.001) with PDMS. However, there were no significant differences in the contractility, collagen fiber thickness, total collagen and glycosaminoglycan content between the two meshes.

Conclusions:

In spite of having a substantially higher weight, PDMS had a similar impact on the vagina as compared to a low weight PP mesh, implicating soft polymers as potential alternatives to PP. The notion that heavyweight meshes are associated with a worse host response is not applicable when comparing across materials.

Keywords: Elastomeric mesh, polypropylene mesh, rabbit, pelvic organ prolapse, smooth muscle morphology, vaginal contractile function

Brief Summary:

Heavyweight elastomeric and lightweight polypropylene meshes had a similar impact on the vagina; therefore, heavier weight does not result in worse outcomes for all materials.

Introduction

Pelvic organ prolapse (POP) is a life-altering condition in women characterized by the unnatural descent of the pelvic organs into the vagina. To overcome the high failure rates (up to 70%) associated with native tissue repairs [1,2], polypropylene meshes have been used in transvaginal and transabdominal prolapse surgeries. Though successful, mesh usage is hampered by complications. Mesh exposure through the vaginal epithelium and pain are the two most commonly reported [3], occurring in 8-20% of women undergoing transvaginal mesh procedures and 10.5% of sacrocolpopexies [4]. With 12.6% of women undergoing a repair of POP by age 80 [5], the number experiencing failure after a native tissue repair versus a mesh complication is not trivial. Thus, there is an urgent need for a product that affords long-term treatment of prolapse symptoms and minimal complications.

Since their introduction, the primary polymer used to manufacture prolapse mesh is polypropylene. However, manufacturers have moved from producing heavyweight, low porosity meshes to lightweight (<45 g/m2), large pore (>1 mm), high porosity (>55%) devices. This is consistent with studies demonstrating that lightweight, high porosity meshes are associated with more favorable host responses relative to heavyweight, low porosity meshes [6-12]. It is therefore assumed that lightweight and high porosity are “better”. However, this concept is specific for polypropylene meshes and has not been explored for meshes manufactured from other polymers.

The material stiffness of polypropylene (1000-3000 MPa) is two orders of magnitude stiffer than the vagina (6-34 MPa) [13-15]. Stiffness is a critical factor in the host response to mesh as stiffer meshes are associated with a maladaptive remodeling response characterized by deterioration in vaginal structure and function [16-18]. We therefore hypothesize that a mesh manufactured from a soft polymer, which has a material stiffness that is similar to vaginal tissue, will have a more favorable host response. To initially explore this hypothesis, we performed a preliminary study in which a mesh manufactured from a non-degradable, soft elastomer, polydimethylsiloxane (PDMS), with a material stiffness (10 MPa) that matches the vagina, was implanted onto the vagina of rabbits via a lumbar colpopexy. Given that PDMS is a soft polymer, more material (PDMS) was utilized to construct the mesh in order to approximate the overall device stiffness of the widely used polypropylene mesh, Restorelle (Coloplast, Minneapolis, MN, USA). This ultimately resulted in a PDMS mesh that was heavier and less porous – two properties typically associated with worse outcomes. We chose Restorelle, as it has been shown to be associated with a more favorable host response and to have the least negative impact on the vagina of all polypropylene meshes studied to date [16-18]. Despite being heavier and less porous, we hypothesized that the PDMS mesh would have a similar impact on vaginal function (i.e. the ability of the vagina to contract) and structure (i.e. vaginal morphology and key structural components within the vagina, e.g. collagen) relative to the PP mesh. In other words, we proposed that the negative impact of increased weight and lower porosity, would be less impactful in the context of a soft polymer. Here we present the results from this preliminary study in which we compared the structure and function of the vagina following implantation of the heavyweight, lower porosity soft polymer PDMS mesh vs the lightweight, higher porosity stiff polymer PP mesh. It is important to keep in mind that the purpose of this study was not to identify the impact of a specific textile property on the host response, but rather to explore the response of the vagina (i.e. how the structure and the function of the vagina are impacted in result of mesh implantation) to a mesh manufactured from a soft polymer and how this response compares to that of polypropylene.

Materials and Methods

Meshes

The heavier, less porous, soft elastomeric mesh was manufactured from polydimethylsiloxane (PDMS). The material stiffness of PDMS is similar to vaginal tissue, 10 MPa (PDMS material stiffness) vs 6-34 MPa (vaginal tissue material stiffness [13,15,14]). Briefly, the PDMS mesh was manufactured from Sylgard 184 Silicone Elastomer (Dow Corning, Midland, MI, USA) using a 3D printed, mold-fill process, which ultimately resulted in the mesh consisting of intersecting fibers and no knots (Figure 1). Prior to implantation, PDMS meshes were sterilized with EtO. In order to meet the loading demands roughly equivalent to that of a low stiffness PP mesh, the amount of material in the PDMS mesh had to be substantially increased. Consequently, the PDMS mesh had a relatively high mesh weight at 554.4 g/m2 and a lower mesh porosity (34%) but a low structural stiffness (0.06 N/mm – obtained by uniaxially loading to failure PDMS meshes that were 95 mm x 15 mm). For comparison, the PP mesh, Restorelle (Coloplast, Minneapolis, MN, USA) was chosen as it is one of the highest porosity (78%), lowest weight (19 g/m2), and least stiff meshes (0.18 N/mm – low stiffness) available on the market. Furthermore, it was previously shown to have the least negative impact on the functional and structural properties of the vagina in nonhuman primate studies [16-18].

Figure 1: Mesh-vagina explants.

Figure 1:

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Examples of the mesh-vagina complexes explanted 12-weeks after implantation with the corresponding meshes, PP (left bottom) and PDMS (right bottom). As demonstrated in the images, tissue was well incorporated within the pores of both meshes and the majority of the meshes implanted remained in a flat configuration as pictured.

Animals

Thirty New Zealand White rabbits were utilized in this study according to the University of Pittsburgh Institutional Animal Care and Use Committee (IACUC #16035431). All rabbits were retired breeders aged 2 to 3 years old and were housed in standard cages on a 12-hour alternating light/dark cycle. A standard rabbit diet supplemented with hay, greens, and water was provided to all rabbits ad libitum.

Surgical Procedures

Sterile samples of PP (n=10) and PDMS (n=10) meshes were implanted onto the internal vagina following an abdominal hysterectomy with preservation of the ovaries via a lumbar colpopexy as previously described [19]. Ten rabbits served as Sham (no mesh implanted). Following intubation and laparotomy, the bladder and rectum were dissected off of the vagina and a hysterectomy was performed preserving the ovaries. Next, two 12 cm long x 3 cm wide strips of mesh were attached to the anterior and posterior vagina respectively using continuous 3-0 PDS II sutures along each lateral edge. The muscles overlying the lumbar spine were then divided and the two strips of mesh were anchored to the ligamentous portion of the vertebral body via two 2-0 PDS II sutures. In the case of Sham animals, the vagina without mesh attached was anchored directly to the lumbar spine. Finally, the abdominal muscle layer and skin were closed with continuous 2-0 PDS II and 2-0 Vicryl sutures, respectively. After 12-weeks of implantation, the vagina alone (Sham) and mesh-vagina complexes were excised en bloc and harvested for histological, biochemical, and biomechanical analyses.

Masson’s Trichrome Staining

Full-thickness cross-sections of Sham and mesh implanted vaginas were fixed in formalin, embedded in paraffin, and sectioned at 7 μm. Sections were then stained with hematoxylin Gill no. 2 and trichrome stain AB solutions (Sigma-Aldrich, St. Louis, MO, USA) and imaged with a Nikon Eclipse 90i imaging microscope (Melville, NY, USA). The thickness of the vaginal smooth muscle was quantified using methods previously described [19].

Picrosirius Red Staining

The thickness of collagen fibers deposited within the pores of the meshes following implantation was characterized using picrosirius red staining. Briefly, tissue sections (7 μm) were stained with picrosirius red and 20X images of the tissue within the pores (approximately 3-5 pores per section) were imaged using polarized light with a Nikon Eclipse 90i imaging microscope (Melville, NY, USA). A custom Matlab script (The Mathworks, Natick, MA, USA), was used to define the thickness of the collagen fibers based on hue (green, yellow, orange, and red). The thinnest fibers are green, and the remaining fibers in order of increasing thickness are yellow, orange, and red. Given that the area of the tissue within the pores can vary for each mesh implanted, ImageJ (1.52a) was utilized to quantify the area of the tissue. From this analysis, the percentage of red, orange, yellow, and green fibers was normalized to the area of the tissue within the pores and the ratio of red to green fibers were quantified.

Hydroxyproline Assay

Two samples of vaginal tissue were obtained from each animal. Tissues were lyophilized, weighed, and papain digested (final concentration - 125 μg/ml). Purified collagen type I (4.2 mg/ml; Sigma) and hydroxyproline solution (1 mg/ml) were serially diluted and used as an internal control and standard, respectively. Total collagen content was measured using the hydroxyproline assay as previously described [18]. Briefly, aliquots of the samples and standards were first hydrolyzed in 6 M HCl at 110°C overnight, the acid was evaporated, and Chloramine-T reagent was added. Following oxidation for 30 minutes, Ehrlich’s aldehyde reagent was added to the samples and standards and incubated for 20 minutes at 65°C to develop the chromophore. The absorbance was then read using a spectrophotometer at 550 nm. The experiment was repeated at least three times for each animal. To estimate the total collagen content, it was assumed that hydroxyproline comprises 14% of the amino acid composition of collagen [18,20]. Finally, total collagen content was normalized to tissue dry weight.

1,9-Dimethylmethylene Blue Assay

The 1,9-Dimethylmethylene blue assay was used to determine the amount of sulphated glycosaminoglycan (sGAG) in the papain digested vaginal tissues as previously described [18]. Briefly, serial dilutions of the sGAG reference standard (100 μg/ml) from the Blyscan Glycosaminoglycan Assay Kit (Biocolor Ltd, Carrickfergus, UK) and tissue samples were aliquoted and prepared with papain digestion solution (final concentration - 125 μg/ml). The 1,9-dimethylmethylene blue solution was added to the standards and samples, vortexed, and allowed to stand at room temperature for 30 minutes. Next, samples and standards were centrifuged at 13,000 rpm for 15 minutes at room temperature and the absorbance of the supernatant was measured at 595 nm. The experiment was repeated at least three times per animal and the amount of sGAG was normalized to tissue dry weight.

Vaginal Contractile Function

The ability of the vagina to contract in the presence of mesh (i.e. with the mesh attached to the vagina in order to simulate in vivo conditions) was evaluated using a vaginal contractility assay as previously described [19]. Briefly, strips (approximately 7 mm x 2 mm) with and without mesh attached were excised from the anterior and posterior proximal vagina. All strips (2 per side) were oriented along the circumferential axis of the vagina and placed in an organ bath system containing oxygenated Krebs solution at 37°C. The maximum contractile force of the vagina in response to 120 mM KCl – muscle mediated contraction, was recorded. To account for differences in the amount of tissue between strips, the contractile force in response to 120 mM KCl was normalized to tissue volume.

Statistics

Sample sizes were calculated using previously published data in which the contractile function of the nonhuman primate vagina following the implantation of Restorelle and UltraPro (Ethicon, Somerville, NJ, USA) was compared to Sham [17]. Based on that data, eight animals per group would be needed to detect differences between Sham, PP, and PDMS in the contractile function (primary endpoint) with a power of 85% using a one-way ANOVA with a two-sided significance level of 0.05. Kolmogorov-Smirnov tests were utilized to assess the normality of the data. Normally distributed data is represented as mean ± standard deviation and non-normally distributed data is represented as median (interquartile range). One-way ANOVA with Gabriel’s post-hoc testing was utilized to compare the contractile response to 120 mM KCl, total collagen content, and sGAG between groups while smooth muscle thickness was compared between groups using Kruskal-Wallis tests followed by Mann-Whitney tests with a Bonferroni correction when appropriate. Mann-Whitney tests were used to compare the percent of red, orange, yellow, and green fibers and the red to green ratio. All statistical analyses were performed using SPSS 26.0 statistical software (IBM, Armonk, NY, USA).

Results

After a hysterectomy with preservation of the ovaries, New Zealand white rabbits (N=30) were implanted with PP or PDMS mesh vs Sham (no mesh) for 12 weeks via a lumbar colpopexy. At the time of euthanasia, all rabbits had similar weights (Sham – 4.4 (4.3, 4.9), PDMS – (4.2 (4.0, 4.7), PP – (4.4 (4.1, 4.7), p=0.314). Of the ten rabbits implanted with PP, one sustained a bowel obstruction and was excluded from the study. In the PDMS implanted group, one rabbit was euthanized early, as per protocol, due to anorexia resulting in more than a 20% weight loss. Thus, the final sample size for this study was Sham (n=10), PP (n=9), and PDMS (n=9).

Gross and Vaginal Histomorphology

Vaginal tissue was well incorporated within the pores of PP and PDMS meshes after 12-weeks of implantation (Figure 1). The majority of the meshes remained in a flat configuration as implanted with the exception of three PP meshes which wrinkled with one leading to an exposure of the mesh through the vaginal epithelium. Additionally, an exposure was observed in one PDMS mesh in a small area where the mesh had wrinkled. Of note, the material stiffness of the rabbit vagina is approximately 6 MPa and it is exceedingly thin as compared to the human vagina. It was interesting to note that wrinkles were most commonly associated with a mesh exposure in both groups.

Assessing vaginal histomorphology, the four characteristic layers of the vagina (epithelium, subepithelium, muscularis, and adventitia) were observed (Figure 2). Implanting both meshes onto the vagina resulted in thinning of the muscularis layer. Relative to Sham, the muscularis was 18% thinner in the presence of PP (Sham – 1577 (1403,1723) vs PP – 1287 (1272,1397), p=0.118) and 20% thinner with the implantation of PDMS (Sham – 1577 (1403,1723) vs PDMS – 1254 (1209,1462), p=0.109). The muscularis thickness was also not different between PP and PDMS, p=1.000. Despite the observed thinning, which may be the result of stress shielding, the overall architecture of the muscle fibers within the muscularis was maintained for both PP and PDMS meshes (Figure 2).

Figure 2: Smooth muscle morphology.

Figure 2:

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Representative cross-sectional images of Sham (a), PP (b), and PDMS (c) after Masson’s trichrome staining. Compared to Sham, the muscularis thinned following the implantation of PP and PDMS; however, the overall architecture of the muscularis was maintained. (♣) Mesh knot and (*) mesh fiber.

Picrosirius red staining was utilized to assess collagen fiber thickness. Qualitatively, there appeared to be more thick collagen fibers (red and orange) deposited in the area of the pores of PP and more thin collagen fibers (green) deposited in the area of pores of PDMS (Figure 3). Quantifying fiber thickness, the amount of thick (red) and the ratio of thick to thin (red to green) fibers was 2.6 and 6.8 times higher for PP compared to PDMS, respectively, although these differences were not significant (p=0.050 for both). Similarly, there were no significant differences in the percentage of orange, yellow, and green between the two meshes (Table 1).

Figure 3:

Figure 3:

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Representative picrosirius red staining images of the collagen fibers within the mesh pores (*) following the implantation of PDMS and PP. For the majority of the meshes, there appeared to be more red fibers within the pores of PP and more green fibers within the pores of PDMS; however, these qualitative differences did not reach statistical significance (see Table 1). Collagen fiber thickness from thick to thin, red->orange->yellow->green. Note: The scale bar for PDMS is larger than PP.

Table 1.

Collagen fiber thickness (thick to thin, red→orange→yellow→green) following implantation with PDMS and PP

Red (%) Orange (%) Yellow (%) Green (%) Red:Green
PDMS (n=8) 2.4(1.7, 2.8) 34.8 ± 7.7 3.2 ± 1.3 2.1 ± 1.1 0.9 (0.8,2.2)
PP (n=8) 6.2(3.1,10.0) 37.8 ± 8.4 3.1 ± 2.0 1.4 ± 0.9 6.1 (1.4,12.5)
p-value 0.050a 0.382a 0.505a 0.195a 0.050a
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Data represented as mean ± standard deviation or median (interquartile range).

a

P-value obtained using Mann-Whitney tests with a Bonferroni correction, p<0.01 for significance.

Vaginal Contractility Analysis

In response to 120 mM KCl, the ability of the muscle myofibers to produce a contraction was significantly decreased by 34% (p=0.035) with the implantation of PP relative to Sham (Table 2). In contrast, with PDMS, there was no significant difference in the contractile response compared to Sham (p=0.495). The contractile function of the vagina was also not different between the two meshes (p=0.438).

Table 2.

Maximum contractile force in response to stimuli

Mesh 120 mM Potassium
Chloride (mN/mm3)
Sham (n=10) 1.71 ± 0.52
PP (n=9) 1.13 ± 0.50
PDMS (n=9) 1.44 ± 0.38
Overall p-value 0.040a
Sham vs PP 0.035
Sham vs PDMS 0.495
PP vs PDMS 0.438
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Data represented as mean ± standard deviation.

a

P-value obtained using One-way ANOVA followed by a Gabriel’s post-hoc test.

Biochemical Analysis

Total collagen content was significantly decreased with the implantation of both meshes. However, the greatest decreases were observed with the implantation of PP (Table 3). Specifically, in the presence of PP, the total collagen content decreased by 53% relative to Sham (p<0.001) whereas only a 35% reduction was observed with the implantation of PDMS (p=0.004). Similar results were observed with the amount of sGAG. The implantation of PP and PDMS meshes resulted in a 54% and 35% reduction in the sGAG content, respectively (both meshes p<0.001), compared to Sham. There was no difference in the decreases observed between the two meshes.

Table 3.

Total collagen and sulphated glycosaminoglycan content

Mesh Total Collagen Content (%
tissue dry weight)		 Sulphated Glycosaminoglycan Content (%
tissue dry weight)
Sham (n=10) 36.5 ± 7.8 1.47 ± 0.2
PP (n=7) 17.1 ± 6.1 0.68 ± 0.2
PDMS (n=9) 23.8 ± 8.4 0.96 ± 0.3
Overall p-value <0.001a < 0.001a
Sham vs PP <0.001b <0.001b
Sham vs PDMS 0.004b <0.001b
PP vs PDMS 0.244b 0.090b
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Data represented as mean ± standard deviation.

a

P-value obtained using one-way ANOVAa followed by Gabriel’s post-hoc testb.

Discussion

To date, current prolapse meshes are manufactured primarily from polypropylene, a stiff polymer with a material stiffness that is orders of magnitude stiffer than the vagina. This stiffness mismatch likely contributes to a negative host response as stiffer meshes are associated with a maladaptive remodeling response [16-18]. One way to overcome this stiffness mismatch is to extrude the mesh into thin fibers and knit the mesh so that it is ultra-light weight, has very large pores and less material, as in the case of Restorelle. However, even though these modifications decrease the stiffness of the device, the stiffness of the polymer does not change. An alternative is to manufacture the mesh from a softer polymer with a material stiffness that is similar to vaginal tissue. However, when using a softer device, more material may be needed to achieve sufficient structural properties to meet the loads placed on the vagina. As a first step to exploring this concept, we manufactured a mesh from PDMS (material stiffness similar to vaginal tissue) and implanted this mesh onto the rabbit vagina. Substantially more material was used to manufacture the PDMS prototype in order to have an overall device stiffness that is roughly equivalent to Restorelle. Therefore, it was heavyweight and had a low porosity. The most important finding of this study was that a heavyweight, low porosity mesh manufactured from the soft polymer PDMS did no worse in terms of structural and functional outcomes than an ultra-light weight mesh manufactured from the very stiff polymer, polypropylene. These results are very promising as it is likely that future soft polymer devices can be made with less material and therefore, will likely be associated with improved outcomes over the lightest weight, highest porosity PP mesh (Restorelle).

Material (polymer) stiffness is an intrinsic property that describes the ability of a material (e.g. a single strand of polypropylene) to resist elongation. In vitro studies in the cardiovascular literature have identified material stiffness as a significant contributor to cell fate and function. Specifically, cardiomyocytes grown on substrates that mimic the stiffness of the native environment demonstrate optimal heart cell morphology and contractile function relative to cardiomyocytes grown on substrates that are too stiff or too soft [21,22]. Blakney et al 2011 also demonstrated the importance of stiffness on the host response using poly(ethylene glycol) hydrogels. After 28 days of subcutaneous implantation in mice, soft hydrogels were associated with reduced macrophage activation and accumulation at the implant surface surrounded by a thin fibrous capsule relative to stiff hydrogels [23]. A similar mechanism may be occurring with the current study in which the soft PDMS mesh had a favorable host response, despite being heavyweight with a low porosity, while there may be other contributing factors (e.g., the impact of surface chemistry on the host response). Thus, additional studies are needed to understand the mechanism by which the soft PDMS is driving the host response in the vagina.

Pore size/porosity and mesh weight are critical factors in determining the host response to polypropylene meshes. Specifically, large pore, high porosity meshes yield better tissue integration with decreased inflammation and fibrosis, increased collagen deposition between pores, and have a reduced risk of bridging fibrosis (the merging of the cellular response around adjacent fibers potentially leading to contraction, encapsulation, and pain) relative to small pore, low porosity meshes [6-9]. Furthermore, lightweight meshes are associated with increased tissue incorporation, reduced fibrosis and inflammation, and a more favorable M2 macrophage response compared to heavyweight meshes [8,10-12,24]. However, the concept that large pore, high porosity, and lightweight meshes are better is specific to meshes manufactured from polypropylene. The results of this study challenge this concept as the heavyweight, lower porosity PDMS had a similar impact on the vagina as compared to the lightweight, higher porosity PP mesh. This finding is significant and highlights the importance of material (polymer) in the response to mesh in addition to pore size and weight.

The use of a large animal model, the rabbit, that lacks lateral and apical support comparable to women with pelvic organ prolapse is a major strength of this study, as the vagina can be loaded by anchoring it to the spine similarly to a woman with advanced prolapse undergoing sacrocolpopexy. This ultimately allowed us to evaluate the impact of mesh textile properties with the vagina loaded in a standardized configuration. In addition to the benefit of tuning the material stiffness of the polymer to match that of the vagina, manufacturing a device from a soft elastomeric polymer would also provide the device with shape memory – the ability of a device to return to its original configuration in response to sudden and repetitive changes in forces (e.g., with coughing). This behavior is in contrast to current polypropylene meshes which permanently deform with repetitive loading which could lead to recurrent prolapse due to mesh lengthening [25]. The goal of this study was to compare meshes made from a stiff vs soft polymer with overall similar low structural stiffness. We appreciate that a soft polymer device would have to be made with more material. We therefore manufactured a device at the upper limits of weight in order to test our hypothesis. This led to the primary limitation of this study which is that the manufacturing technique (PP – knitted vs PDMS – molded) and textile properties of the PP and PDMS meshes differed. Knitting meshes creates knots and interstices (spaces between fibers that can be <10 μm) that would allow the passage of small bacteria (<1 μm) but prevent the passage of larger immune cells such as macrophages and leukocytes. This could ultimately make knitted meshes more susceptible to infections and bridging fibrosis. Molded meshes however do not have knots and interstices, which may afford an advantage over knitted meshes. Further differences between the two devices included: increased high structural stiffness, higher porosity, and lower weight of the PP mesh as compared to PDMS. Collectively these differences ultimately limit our ability to definitively isolate a single property, e.g. porosity or stiffness, as the major contributing factor to the host response. However, this limitation is to be expected as weight, material stiffness, porosity, overall device stiffness, etc. are highly interdependent. To overcome this limitation, this study focused broadly on comparing a soft vs stiff mesh rather than a specific textile property. Future studies will focus on studying the impact of a single textile property e.g. material stiffness. Although PDMS is easily manufacturable and is a soft elastomer with a material stiffness that is similar to vaginal tissue, we do not believe it is strong enough to withstand in vivo loads. Future studies will explore alternative materials with the strength and toughness to resist fracture – a property unlike silicone and other soft elastomers.

In summary, this study assessed the contractile function, histomorphology, and structure of the vagina following implantation with a heavyweight, lower porosity soft elastomeric mesh versus a lightweight, higher porosity stiff polypropylene mesh. The soft elastomeric mesh had a similar impact on vaginal structure and function as the polypropylene mesh, with the PDMS mesh having slightly less of a negative impact, suggesting that the host response to mesh is sensitive to the material. Moreover, the soft elastomeric mesh is a heavyweight, low porosity mesh, yet the host response was similar to a stiff, lightweight, high porosity mesh. Collectively, these results demonstrate that the concept of a lightweight, high porosity mesh is not “one size fits all” for meshes and that the material from which a mesh is produced is just as important as the weight and porosity. Furthermore, these results demonstrate a critical point in the design of future prolapse meshes. Manufacturing a mesh from a lower stiffness polymer may require more material in order to meet the loading demands. While typically more material (i.e., heavier weight mesh) is associated with negative outcomes, the results from this study, however, suggest that the host response to weight and textile properties is polymer specific. Thus, in the exploration of polymers for future prolapse meshes soft polymers should be considered, and likely will be made from less material than explored in this study. In future studies we will investigate stronger elastomers and determine the combination of stiffness and textile properties that will minimize the impact on the vagina for soft elastomeric meshes.

Acknowledgements:

The authors are grateful for the financial support provided the Department of Defense (DOD) (grant no. W81XWH-16-1-0133). The DOD did not provide any assistance with the study design, the collection, analysis and interpretation of data or in the writing of this report or in the decision to submit the article for publication. Research efforts for this publication was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award no. TL1TR001858. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors would also like to thank Dr. Naoki Yoshimura, MD PhD (Professor of Urology, Pharmacology, and Cell Biology, University of Pittsburgh) for allowing us to use the organ bath system to collect the contractility data reported, Dr. Leslie Meyn (Magee-Womens Research Institute) for statistical assistance and Jannah Mujaahid for her assistance with animal care and imaging. The code used to image the picrosirius red images was written by Christopher A. Carruthers (PhD graduate of the University of Pittsburgh, Bioengineering Department).

Funding:

Financial support was provided by the Department of Defense (DOD) W81XWH-16-1-0133 and the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) TL1 TR001858.

Footnotes

Financial Disclaimers/Conflict of Interest: None

Conference Presentation: American Urogynecology Society/International Urogynecological Association Joint Scientific Meeting, Nashville, Tennessee, September 24 – 28, 2019

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