Pelvic organ prolapse (POP) is a common urogynecological disorder, with up to  19% of women having a lifetime risk of undergoing reconstructive surgery for POP [1], and a 30% risk of reoperation due to recurrent anatomical failure or adverse events associated with primary surgery [2]. There is a critical need to discover novel transvaginal grafts for the treatment of POP that are safe, surgically efficacious, and congruent with host native tissue. In nature, cell behaviour and structural development is supported by the nanoscale arrangement of the extracellular matrix (ECM).   In order to overcome the impediment posed by the tissue microenvironment, it is desirable to design biomaterials that mimic some mechanical and biochemical properties of the ECM of native tissues. Nanostructured poly-L-lactide-co-ε-caprolactone (PLCL) mesh is made from a biocompatible, elastic and flexible polymer that is well matched to the nanoarchitecture of vaginal tissue [3]. Furthermore, surface modification of the biomaterial helps to tailor its physicochemical behaviour, structural properties, and tissue interaction to significantly aid its biocompatibility. Plasma-polymerization is a surface modification technique where various organic monomers are introduced into a plasma discharge zone and converted into reactive fragments such that polymer thin films (100Å–1 μm) are deposited. Previous studies assessing the effect of plasma polymerization with allyamine have demonstrated significant improvements in cell adhesion, proliferation, and overall biocompatibility of grafts. Thus, this novel and emerging technology has great potential for improving the biological and physicochemical properties of tissue engineered grafts for pelvic floor reconstruction. This study is the first to assess the effect of plasma allyamine polymerization on the biological compatibility and immune response to degradable nanostructured PLCL mesh for applications in Urogynaecology. 

Objective: This study aimed to assess the effect of plasma surface modification on the fate and effect of degradable nanofiber PLCL grafts in an ovine pre-clinical model of female pelvic floor reconstruction (n=9). We hypothesised that ultrathin plasma polymerization with allyamine would significantly improve the host inflammatory response to reduce rates of mesh erosion and exposure, whilst strengthening the vaginal wall after colporrhaphy.

PLCL polymer (10%w/w) was electrospun at 18kV to form uniform nanofibers and assessed for fiber diameter, pore size, hydrophilicity and biomechanical properties. PLCL meshes of diameter 3x2cm were sterilised  followed by the glow discharge deposition of an ultrathin layer of plasma polymerization with an allylamine monomer (Aldrich, 98% purity). Multiparous ewes with demonstrated vaginal wall weakness were selected on the basis of abnormal modified POP-Q measurements. Following this, trained urogynecologists performed posterior vaginal repair (colporrhaphy) on a total of 9 sheep divided across three groups;  freshly coated PLCL (n = 3), coating with delayed implantation of by 30 days PLCL (n = 3) and uncoated PLCL grafts. Post-operative POP-Q measurements were taken and vaginal tissue harvested at the post-mortem time points of 30 days. Histology, immunohistochemistry, immunofluorescent microscopy, and scanning electron microscopy were used to assess mesh integration, host foreign body response, angiogenesis and ECM formation.

We observed that uncoated mesh appeared to have poorer tissue integration with greater tissue loss, increased acute inflammation and increased number of foreign body giant cell formations (Figure 1). Contrastingly, coated nanomesh had improved tissue integration, limited tissue loss, less inflammatory infiltration and evidence of neovascularization. Scanning electron microscopy revealed that  there was swelling of individual fibers of coated mesh and new collagen fibrils were formed within. We are currently assessing macrophage polarization, inflammation, elastin metabolism as well as tensile properties of vaginal explants.

Plasma surface modification is an emerging technology that significantly improves graft response with improved host vaginal tissue integration, neovascularization and foreign body response, with the potential for clinical translation in Urogynaecological constructs.

Our study highlights that plasma surface modification can significantly  improve the  foreign body response and thus impact the fate of biomaterial implants used for POP treatment. From a tissue engineering perspective, this technology has huge potential in the generation of highly compatible novel bioengineered  surgical constructs for pelvic floor reconstruction.

Smith, F. J., Holman, C. D., Moorin, R. E., & Tsokos, N. (2010). Lifetime risk of undergoing surgery for pelvic organ prolapse. Obstetrics and gynecology, 116(5), 1096–1100. https://doi.org/10.1097/AOG.0b013e3181f73729
Olsen, A. L., Smith, V. J., Bergstrom, J. O., Colling, J. C., & Clark, A. L. (1997). Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstetrics and gynecology, 89(4), 501–506. https://doi.org/10.1016/S0029-7844(97)00058-6
Mukherjee, S., Darzi, S., Rosamilia, A., Kadam, V., Truong, Y., Werkmeister, J. A., & Gargett, C. E. (2019). Blended Nanostructured Degradable Mesh with Endometrial Mesenchymal Stem Cells Promotes Tissue Integration and Anti-Inflammatory Response in Vivo for Pelvic Floor Application. Biomacromolecules, 20(1), 454–46https://doi.org/10.1021/acs.biomac.8b01661