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

Abstract

Pelvic organ prolapse is a common condition that affects 1 in 4 women across all age groups. It is mainly caused by vaginal birth injury and can be exacerbated by obesity and increased age. Until recently, treatment strategies often used non-degradable synthetic meshes for reconstructive surgery. However, owing to their frequent, unacceptable rate of adverse events such as mesh erosion, transvaginal meshes have been banned in many countries. Recent reports have highlighted the urgent need for biocompatible design of meshes for a safe and effective treatment in the long term. This study reports the design and evaluation of a novel, elastin based degradable mesh using an ovine model of POP as a potential surgical treatment. Elastin is a protein component of the ECM and provides elasticity to tissues throughout the body. Tropoelastin, the monomer subunit of elastin, has been used with success in electrospun constructs as it is a naturally cell interactive polymer. Biomaterials that incorporate tropoelastin support cell attachment and proliferation, and have been proven to encourage elastogenesis and angiogenesis in vitro and in vivo . The biological properties of tropoelastin were combined with the physical properties of PCL, a degradable synthetic polymer, with the aim of producing, characterizing and assessing the performance of continuous tropoelastin:PCL electrospun yarns. Using a modified spinneret electrospinning system and adjusting settings based on relative humidity, four blends of tropoelastin:PCL yarns were fabricated with concentration ratios of 75:25, 50:50, 25:75 and 0:100. Yarns were assessed for ease of manufacture, fibrous architecture, protein/polymer content, yarn stability - including initial tropoelastin release, mechanical strength, and ability to support cell growth. Based on overall favorable properties, a mesh woven from the 50:50 tropoelastin:PCL yarn was implanted into the vagina of a parous ewe with vaginal wall weakness as a model of pelvic organ prolapse. This mesh showed excellent integration with new collagen deposition by SEM and a predominant M2 macrophage response with few pro-inflammatory M1 macrophages after 30 days. The woven tropoelastin:PCL electrospun mesh shows potential as an alternative to non-degradable, synthetic pelvic organ prolapse mesh products.

The impact of bacterial contamination on the host response towards fully absorbable poly-4-hydroxybutyrate and nonabsorbable polypropylene pelvic floor implants

“…To assess the possibilities, future studies should focus on the long-term host response to P4HB in larger animal models, e.g. sheep [ [56] , [57] , [58] ], including the effect of mesh degradation and mechanical properties. Finally, as bacterial contamination significantly affects the host response, we would recommend future studies to take into account the effect of the vaginal microflora on mesh acceptance and integration.…”

A New Cell Stem Concept for Pelvic Floor Disorders Prevention and Treatment – Endometrial Mesenchymal Stem Cells

“…The key to safe and efficacious TE in PFDs was the generation of some tissue substitute by materials with nano-architecture/nanofiber technology [163] or 3D printing, mimicking EMC pelvic floor topography, mainly vaginal EMC, or to induce favorable tissue mechanical responses, or to add some EMC constituents (as tropoelastin-the elastin core in EMC network, besides collagen, lost in POP) [164], for production of mesh/scaffold new generation, which allows entrapment, and persistence of seeded eMSCs/MenSCs up to 14 days after implant [41]. eMSCs are in vitro optimized in serum free conditions-fibronectine is the optimal substrate for human eMSCs attachment [91], and eMSCs transcriptome reveals improved potential for cell based therapy after adding TGF-β receptor inhibitor in culture medium (to prolong their undifferentiated status after implantation, by eMSCs apoptosis, and senescence prevention, and maintaining the percentage of SUSD2 + cells to more than 90% for all samples) [165].…”

Recent advances in electrospun nanofiber vaginal formulations for women's sexual and reproductive health

“…However, due to the degradation rate of the electrospun biodegradable ureidopyrimidinone-polycarbonate mesh, the authors concluded that the Restorelle® and electrospun non-degradable polyurethane meshes were most suitable for further investigation Aghei-Ghareh-Bolagh et al reported manufacture of multimeter electrospun fibrous yarns based on tropoelastin/PCL mixtures (Fig. 9E-H) (Aghaei-Ghareh-Bolagh et al, 2020).. Tropoelastin is the monomer subunit of elastin, a component of the extracellular matrix, which is known to support cellular growth. Yarns containing 1:1 ratio of tropoelastin and PCL were degradable and supported cellular growth.…”