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.

A novel tropoelastin-based resorbable surgical mesh for pelvic organ prolapse repair

“…Recently, several groups have shown that electrospun constructs fabricated with degradable polymers have significant potential in POP treatment using small and large animal models [ [12] , [13] , [14] , [15] , [16] ]. We have previously shown that choice of polymer and surface topography largely influences the triggered in vivo immune response [ 17 ]. These features, and physical and mechanical properties such as fibrous architecture and large pore size (one mm diam), determine cellular attachment and infiltration, cytokine release and ectopic recruitment of tissue forming cells.…”

“…Electrospinning is a versatile technique used to fabricate fibers that has recently gained attention in urogynecological applications [ 15 , 17 , 23 ]. Electrospinning provides an adaptable path for the construction of nanofibers and microfibers with defined fiber morphology, dimensions and orientation, which present the multiple benefits of a high surface-to-volume ratio and twisting to generate yarns, which is conducive to delivering reproducible textiles [ 24 ] as demonstrated here.…”

Endometrial SUSD2+ Mesenchymal Stem/Stromal Cells in Tissue Engineering: Advances in Novel Cellular Constructs for Pelvic Organ Prolapse

“…Vaginal birth results in stress to the vaginal wall and surrounding ligamentous, fascial, and muscular structures, beyond their critical stretch limit, resulting in tissue damage through non-elastic deformation [ 19 ]. During labour, pressure from strong uterine contractions and the transiting foetal head are directed to the LAM muscle, particularly the medial portion of the pubococcygeus.…”

“…These emerging biomimetic electrospun meshes produce an ECM-like topography that mimic the ECM of vaginal tissue of women with POP at the nanoscale [ 73 ]. Nanostructured meshes also provide a larger surface area for the delivery of eMSC and other adsorbing proteins and growth factors [ 19 , 73 ]. Poly-L-lactide-co-ε-caprolactone (PLCL) is a biocompatible, elastic, and flexible polymer investigated by several groups for novel tissue engineering applications, as its elastic modulus is well matched to the nanoarchitecture of vaginal tissue [ 81 ].…”

“…The ability to purify and characterise these cells through relatively non-invasive procedures has encouraged a separate investigation into their potential therapeutic applications in various clinical conditions with significant burden of disease [ 60 ]. As described, the restorative and regenerative capacity of autologous and heterologous perivascular eMSC is under investigation for applications in POP [ 8 , 11 , 19 , 39 , 44 , 72 , 73 , 74 , 76 , 79 , 80 , 81 ]. In particular, autologous ovine eMSC have persisted 30 days in a non-degradable PA mesh seeded with eMSC in situ in a transvaginal POP surgery model [ 72 ], xenogenic human eMSC for 1–2 weeks when implanted in a non-degradable PA+G composite mesh in immunocompromised rodent models of subcutaneous wound repair, and for 3 days in immunocompetent mice [ 70 ].…”