Emerging Nano/Micro-Structured Degradable Polymeric Meshes for Pelvic Floor Reconstruction

Abstract

Pelvic organ prolapse (POP) is a hidden women's health disorder that impacts 1 in 4 women across all age groups. Surgical intervention has been the only treatment option, often involving non-degradable meshes, with variable results. However, recent reports have highlighted the adverse effects of meshes in the long term, which involve unacceptable rates of erosion, chronic infection and severe pain related to mesh shrinkage. Therefore, there is an urgent unmet need to fabricate of new class of biocompatible meshes for the treatment of POP. This review focuses on the causes for the downfall of commercial meshes, and discusses the use of emerging technologies such as electrospinning and 3D printing to design new meshes. Furthermore, we discuss the impact and advantage of nano-/microstructured alternative meshes over commercial meshes with respect to their tissue integration performance. Considering the key challenges of current meshes, we discuss the potential of cell-based tissue engineering strategies to augment the new class of meshes to improve biocompatibility and immunomodulation. Finally, this review highlights the future direction in designing the new class of mesh to overcome the hurdles of foreign body rejection faced by the traditional meshes, in order to have safe and effective treatment for women in the long term.

Keywords: 3D printing foreign body response; cell therapy; mesh complications; nanofiber mesh; pelvic organ prolapse; tissue engineering.

Figure 1

(A) The relationship between muscle stretch ratios in selected LAM, PC, IC and PR muscle bands and (B) foetal head descent in the birth canal. The shaded region denotes the values of stretch tolerated by non-pregnant appendicular striated muscle without injury. (C) Initial and final muscle length. (D) Maximum corresponding stretch ratio of each LAM muscle corresponding to foetal head descent. Reproduced with permission of [26]. Copyright NIH Public Access, 2005.

Figure 2

Mesh topography showing fabrication patterns of various types of weaves (A–C), types of knits (D–F) and commercially available meshes (G–L) in POP surgery. Reproduced with permission of [19]. Copyright Elsevier, 2016. Reproduced with permission of [34].

Figure 3

Mesh exposure and erosion of using non degradable meshes in POP surgery. Reproduced with permission of [39]. Copyright AAGL, 2017.

Figure 4

(A) Electrospinning setup and optimisation parameters. (B) Electrospun nanofiber. (C) Schematic showing the nano scale interaction with the cell. Reproduced with permission of [78]. Copyright AAAS, 2005.

Figure 4

(A) Electrospinning setup and optimisation parameters. (B) Electrospun nanofiber. (C) Schematic showing the nano scale interaction with the cell. Reproduced with permission of [78]. Copyright AAAS, 2005.

Figure 5

Different types of electrospinning fabrication setups (A,B). Forcespinning setup (C). Reproduced with permission of [74]. Copyright Elsevier, 2016. Reproduced with permission of [84]. Copyright Elsevier, 2010.

Figure 6

3D printing setups showing (A) 3D Melt electrospinning, and (B) 3D Bioprinting.

Figure 7

Different types of electrospinning fabrication setups (A,B). Forcespinning setup (C). Reproduced with permission of [93]. Copyright Wiley-VCH Verlag GmbH & Co. 2013.

Figure 8

Schematic showing the foreign body response to an implanted inert biomaterial in the host’s body. (A) Protein adsorption; (B) cellular infiltration and acute inflammation; (C) chronic inflammation, cytokine release and further cell recruitment; (D) fibroblast recruitment and collagen matrix deposition; (E) formation of fibrous capsule. Reproduced with permission of [101].

Figure 9

Schematic showing the process of FBGC formation by macrophages responding to foreign particles of different sizes. (A) Phagocytosis; (B) multinucleated FBGCs around the particle; (C) multiple FBGCs attempt to fuse around the larger particle causing extracellular degradation. Reproduced with permission of [101].

Figure 10

Schematic showing material design factors influencing the macrophage-mediated foreign body response to biomaterial implants including pelvic floor reconstruction. Reproduced with permission of [101].

Figure 11

Tissue engineering attributes of electrospun nanofiber mesh showing nanofiber mesh (A), cell seeding and interaction with nano scale feature (B), tissue integration without formation of fibrous capsule and host response toward tissue healing (C). Reproduced with permission of [77]. Reproduced with permission of [78]. Copyright AAAS, 2005.

Figure 12

Tissue engineering attributes of 3D printed surface showing 3D melt electrospinning (A), Endometrial stem cell (eMSC) isolation using unique marker SUSD2 and transduction of mCherry gene (B), the difference in cytoskeletal morphology of migrating cells (C), 3D printing and bioprinting combination toward tissue healing in NSG mice (D). Reproduced with permission of [53]. Copyright Elsevier, 2019.