Vaginal Smooth Muscle Response to Novel Elastomeric Membrane Implantation

Objectives: Polypropylene mesh, when used in sacrocolpopexy procedures to treat pelvic organ prolapse, is associated with complications such as pain and vaginal mesh exposure. The objective of this research was to define the impact of a novel elastomeric PCU membrane (EM) on the vaginal smooth muscle structure and function in a rabbit colpopexy model, compared to polypropylene mesh. The membranes were designed to have similar mechanical properties as Restorelle, and therefore, were manufactured with more material (18g/m2 vs 130-169g/m2). We hypothesized that the EMs, while substantially heavier, would result in a more favorable host response, characterized by the preservation of smooth muscle structure and function.

Methods: PCU EMs were 3D printed by fusion deposition modeling in two different stiffnesses, both within range of vaginal stiffness: EM low (N=24, 65MPa) and EM high (N=24, 149Mpa). Two commercially available polypropylene meshes were used for comparison: Restorelle (N=12, Coloplast, USA) and Gynemesh PS (N=12, Ethicon, USA). 1cmx2cm constructs of the devices were implanted onto six vaginal sites per animal in New Zealand White Rabbits (N=22). The control group was Sham (no implantation, N=10). Membrane and mesh-vagina complexes were explanted after 12 weeks. Explants were fresh-frozen in OCT, cryosectioned at 7um thickness, stained with Masson’s Trichrome, and imaged at 4X using a Nikon-Ni-E microscope. A custom python script was utilized to determine thickness of the smooth muscle layer from digitally outlined images. Explants were cut into 2mmx7mm strips, clamped circumferentially, attached to force transducers, placed in oxygenated Krebs solution at 37 ºC, and stimulated with 120 mM KCl, electrical field stimulation (EFS), and receptor-stimulating drugs. The magnitude of each contractile response was normalized by tissue volume. ANOVAs, Kruskal-Wallis tests, and post hoc tests were performed as appropriate. Statistical significance was p< 0.05.

Results: Qualitatively, the implantation of PCU EM high and both polypropylene meshes reduced the compactness of the smooth muscle bundles, but the smooth muscle bundle density in the EM low group most closely resembled Sham (Figure 1). Both EM low and EM high had similar preservation of smooth muscle thickness compared to Sham and Restorelle, and increased thickness compared to Gynemesh PS (Table 1). While all devices negatively impacted the contractile response compared to Sham, Gynemesh had the most negative impact (Table 1).

Conclusions: Overall, the data support the use of PCU EMs as an alternative to polypropylene for prolapse repair. Studies are underway to evaluate full-length EMs with greater overall size. Considerations of a membrane with less material are underway. As the weight of devices may impact contractility results, we will evaluate smooth muscle bundle size as an indicator of muscle function. Studies are needed to determine if differences exist between PCU EMs and polypropylene mesh with more robust vaginal tissue (non-human primates).