Hypothesis / aims of study
Pelvic organ prolapse (POP) is a debilitating gynaecological condition caused by the herniation of pelvic organs into the vaginal wall. POP is mainly caused by vaginal childbirth injury and affects about 1 in 4 women. Until recently, transvaginal polypropylene meshes were often used to augment pelvic reconstructive surgery. However, they have been associated with serious complications such as inflammation, pain and erosion. As a result, transvaginal meshes were banned in several countries in the world. With a high failure rate of native tissue repair surgery at present, there is no optimal therapy for treatment of chronic POP leaving millions of women in despair. In order to develop the next generation of surgical constructs, it is imperative to fully understand the foreign body response to implanted biomaterials in the vagina and apply design principles that can enhance mesh integration and tissue healing for a successful outcome. This study aims to understand the relationship between mesh design factors such as angular geometry and inter fiber distance on the foreign body response in pre-clinical models. Given the global debacle of non-degradable meshes, this study assessed a range of 3D printed degradable meshes with varying designs to understand, control and minimise undesirable foreign body responses. We hypothesized that variations in these design parameters will influence as well as modulate the fibrotic and foreign body response.
Study design, materials and methods
The 3D printed meshes were fabricated using the melt-electrowriting (MEW) feature in a GESIM bioscaffolder printer. Meshes of poly ε-caprolactone (PCL) with hierarchical geometries were fabricated with MEW by two-way stacking of the strands at a fiber spacing of 1 mm and 0.5 mm with 3 different interlayer angles of 90º, 45º or 22.5º. The mesh morphology study by electron microscopy reveals the fiber diameter to be 18.86 ± 2.16 μm. Meshes printed at 45º and 22.5º had higher tensile strength under dry conditions. The meshes were subcutaneously implanted in C57BL/6 mice to assess the angle and type of foreign body reaction and their impact on the mesh integration, fibrotic response and inflammation using electron microscopy, histological staining and immunofluorescence microscopy respectively at 1 and 6 weeks post- implantation. To further assess whether the subcutaneous mouse model would vaginal response, we implanted meshes with varying angular geometry in our ovine model of POP.
Interpretation of results
The integration of meshes after implantation is dictated by the cascade of foreign body response in the body. For successful long-term outcomes, it is thus critical to modulate these responses to a favourable anti-inflammatory direction. Usually, such immunomodulatory effects are sought from anti-fibrotic drugs or therapeutic cellular sources. The findings of this study suggest that immunomodulation of post-surgical implantation can also be achieved in a cell and drug free approach by modifying the design parameters which largely influence the surface area of the meshes.