(652g) Elucidating the Effects of an IL-4 Eluting Coated Polypropylene Mesh in a Novel Rabbit Surgical Model of Pelvic Reconstruction

Pelvic organ prolapse (POP), a disorder in which the muscles of the pelvic floor are weakened over time, affects over a million women each year in the United States. A quarter of these women undergo a reconstructive procedure, increasingly using polypropylene mesh as mechanical reinforcement to the pelvic floor¹. However, complications including chronic pain, bacterial infection, mesh erosion, or exposure have been observed at rates as high as 10-20%¹. Mesh properties, such as stiffness, porosity, and weight have been shown to correlate with the degree of mesh integration with vaginal tissue. Previous studies have determined that the early macrophage polarization profile following biomaterial implantation is a strong indicator of overall tissue integration downstream². Recent work from our laboratory in developing a cytokine delivery system has shown that actively controlling the immune response to implanted mesh resulted in enhanced integration³. Therefore, we present a rabbit surgical model to implant and investigate the host response to mesh into two different sites, including the vagina and the abdomen and scale up of a methodology to alter this response using a clinically relevant size mesh implant.

Commercially available polypropylene mesh was used to investigate the modulation of the immune response. An adapted radio frequency glow discharge method is used to create a stable negative charge on the surface of the mesh, followed by the sequential deposition of polycationic and polyanionic polymers to provide a stable, conformal, nanoscale coating. Chitosan served as the polycation, chosen because of its known antimicrobial and biocompatibility properties. Dermatan Sulfate served as the polyanion, chosen for its important role in regulating extracellular matrix components and enhancing the activity of cytokines³. It is well known macrophages are characterized on a spectrum ranging from a pro-inflammatory M1 phenotype to an M2 anti-inflammatory phenotype. Interleukin-4 (IL-4), an immunomodulatory cytokine known to promote the M2 phenotype, is incorporated into the coating to be released in a controlled manner upon implantation. In vitro assays confirm the bioactivity and the controlled local release allowing for shifts in the immune response to promote implant integration.

Utilizing a novel surgical technique in New Zealand white rabbits, we implant mesh analogously to human implantation and evaluate changes in the immunologic response at early (14 days) and tissue remodeling outcomes at late stages (90 days) of implantation. The mesh-tissue complex was removed from each rabbit and processed for histological analysis as well as immunolabeling of immune cells, such as macrophages.

We present a nanometer thickness, tunable, and uniform coating capable of releasing bioactive IL-4. We evaluated the biological functionality of the coated mesh via bioactivity studies and in vivo implantation. An ideal mesh would provide mechanical support to the pelvic floor while decreasing the inflammatory response and increasing integration with the surrounding native tissue.

References: 1. FDA, Reclassification of Urogynecologic Surgical Mesh Instrumentation. 2016. 2. Brown, B.N., et al. AJOG 2013. 5, 2014. 3. Hachim, D., et al., Biomaterials, 2016. 112: p. 95-107.