Towards rebuilding vaginal support utilizing an extracellular matrix bioscaffold

Abstract

As an alternative to polypropylene mesh, we explored an extracellular matrix (ECM) bioscaffold derived from urinary bladder matrix (MatriStem™) in the repair of vaginal prolapse. We aimed to restore disrupted vaginal support simulating application via transvaginal and transabdominal approaches in a macaque model focusing on the impact on vaginal structure, function, and the host immune response. In 16 macaques, after laparotomy, the uterosacral ligaments and paravaginal attachments to pelvic side wall were completely transected (IACUC# 13081928). 6ply MatriStem was cut into posterior and anterior templates with a portion covering the vagina and arms simulating uterosacral ligaments and paravaginal attachments, respectively. After surgically exposing the correct anatomical sites, in 8 animals, a vaginal incision was made on the anterior and posterior vagina and the respective scaffolds were passed into the vagina via these incisions (transvaginal insertion) prior to placement. The remaining 8 animals underwent the same surgery without vaginal incisions (transabdominal insertion). Three months post implantation, firm tissue bands extending from vagina to pelvic side wall appeared in both MatriStem groups. Experimental endpoints examining impact of MatriStem on the vagina demonstrated that vaginal biochemical and biomechanical parameters, smooth muscle thickness and contractility, and immune responses were similar in the MatriStem no incision group and sham-operated controls. In the MatriStem incision group, a 41% decrease in vaginal stiffness (P=0.042), a 22% decrease in collagen content (P=0.008) and a 25% increase in collagen subtypes III/I was observed vs. Sham. Active MMP2 was increased in both Matristem groups vs. Sham (both P=0.002). This study presents a novel application of ECM bioscaffolds as a first step towards the rebuilding of vaginal support.

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

“…Based on the donor source, the biologic meshes are divided into three groups, namely, autologous graft, allograft and xenograft [ 9 , 31 ]. Various sources include autologous dermis, fascia lata or rectus fascia, allograft cadaveric tissue, porcine intestinal submucosa, bovine pericardium [ 35 , 36 ]. They involve rigorous decellularisation steps to leave an organised collagen microstructured scaffold with histological similarity to the host tissue.…”

“…Designing an implantable construct for POP application involves the selection of polymers, as well as an optimum fabrication process to attain desired outcomes for augmenting the native tissue repair process. The selection of polymer for mesh design considers whether the fabricated construct can offer optimum fibre alignment [ 64 ], pore size, filament/fibre/strand thickness, sufficient mechanical strength to perform the implant surgery, controlled biodegradation/bioresorption to support tissue in growth [ 65 , 66 ] for extended periods of time and stiffness [ 35 , 36 , 37 ] matching the native tissue stiffness at the implant site. The biocompatibility of degradable meshes can be modified using plant-based aloe vera/alginate complex [ 53 ] as a printed top layer encapsulating a cell-based therapeutic agent.…”

Landmarks in vaginal mesh development: polypropylene mesh for treatment of SUI and POP

“…Second, some clinical studies demonstrate that avoiding a vaginal incision suture line being in direct contact with the mesh material could decrease mesh exposure 128,129 . Additionally, avoiding a vaginal incision when implanting a natural scaffold derived from natural extracellular matrix on the vaginal wall of rhesus macaques, in these cases the material was implanted transabdominally rather than through a vaginal incision,was also shown to eliminate the negative effects on overall structure and function of the vagina with increased vaginal stiffness, collagen content and an increased collagen I/ III ratio at 3 months 130 . Finally, vaginal mesh extrusion described as vaginal mesh being visualized through the separated vaginal epithelium most commonly occurs in the midline where the surgical incision is made 131 .…”

Recent advances in pelvic floor repair

“…This was used by Liang et al . 41 in monkeys to repair transected uterosacral ligaments and paravaginal attachments to the pelvic side wall. Matristem™ was used to repair the transected ligaments through either a transvaginal or transabdominal incision.…”