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.

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.

The main finding of the study is that design parameters have a significant impact on the in vivo foreign body response to the implanted meshes. Our results showed that meshes that were printed at 45º and 22.5º showed better tissue integration indicated by the greater number of host cell penetration, leading to deposition of tissue healing collagen inside the mesh, particularly 6 weeks after implantation. The fibrotic capsule thickness around the implanted mesh was significantly thinner in meshes with 22.5º than 90º. Similarly, the number of pro-inflammatory CCR7+ M1 and anti-inflammatory CD206+ M2 macrophages around the implanted mesh revealed that the pattern and geometry of the layer-by-layer deposition of the MEW meshes mediated macrophage polarization and the extent of the foreign body reaction.

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.

This study reveals that the intrinsic design properties of the degradable 3P printed meshes directly influence the foreign body and fibrotic responses after implantation in the body. This provides valuable knowledge to guide the further development of optimal alternate treatments in urogynaecological surgery for POP.