Plasma Allylamine Polymerization of Nanostructured Poly-LLactide- Co-?-Caprolactone Implants for Pelvic Organ Prolapse.

Abstract

Introduction: There is a critical need to generate novel surgical constructs for applications in pelvic reconstructive surgery that are safe, efficacious, and congruent with host native tissue. Nanostructured poly-L-lactide-co-?-caprolactone (PLCL) implants are made from a biocompatible, elastic, and flexible polymer that matches the native vaginal tissue architecture. 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 (100A-1 mum) are deposited. Previous studies assessing the effect of plasma polymerization with allylamine have demonstrated significant improvements in cell adhesion, proliferation, and overall biocompatibility of implants. Objective(s): The aim of this study was to assess the effect of plasma allylamine surface modification on the biological compatibility and foreign body response to degradable nanostructured PLCL vaginal implants in an ovine pre-clinical model of female pelvic floor reconstruction. Method(s): 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 screened for vaginal wall laxity underwent posterior colporrhaphy by trained surgeons in three groups; freshly coated PLCL (n = 5), coating with delayed implantation PLCL (n = 4) and uncoated PLCL grafts (n = 4). Post-operative POP-Q measurements were taken and vaginal tissue harvested at day 30 post-operatively. Histology, immunohistochemistry, immunofluorescent microscopy, and scanning electron microscopy were used to assess mesh integration, host foreign body response, angiogenesis and ECM formation. Data were analysed after confirmation of normality using one-way ANOVA with Tukeys multiple comparison tests. A P value of <= 0.05 was considered to be statistically significant. Result(s): Uncoated PLCL implants appeared to have an exaggerated acute inflammatory response with significantly more multinucleated foreign body giant cell formations when compared with the freshly coated PLCL implants (p=0.0069) (Figure 1). Uncoated PLCL implants exhibited poorer overall tissue integration with increased tissue loss surrounding implants, though there was no significant difference in the thickness of the lamina propria or muscularis between implant groups. Collagen content was significantly reduced in the uncoated PLCL implant group (p=0.0102), with a maintenance of collagen content in coated (delayed and fresh) implants. Collagen birefringence revealed increased immature (green) collagen deposition surrounding coated PLCL implants (delayed and fresh) when compared to uncoated implants, indicating neo-collagen formation. There was no significant difference in elastin content. Conclusion(s): Plasma surface modification improves graft response evidenced by superior integration, reduced foreign body giant cell formation and favourable collagen metabolism in the host vaginal microenvironment. This established surface engineering technology can modify tissue responses to polymers and has a huge potential in generating highly compatible bioengineered surgical constructs for pelvic floor reconstruction and other surgical applications.