107 - The Future of Pelvic Floor Repair: Comparative Genomic, Histological and Efficacy Analysis of Fascia Lata and Synthetic Polypropylene Mesh.

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Hypothesis / aims of study Following the withdrawal of synthetic polypropylene transvaginal mesh due to its safety concerns, there has been an increasing demand for durable autologous biological grafts such as human fascia lata (HFL) in anti-incontinence procedures such as retropubic slings and prolapse procedures such as sacrocolpopexy and sacrohysteropexy. While HFL has long been used for anti-incontinence procedures, its implementation in graft-augmented vaginal reconstruction and abdominal apical suspension is novel. This is the first pre-clinical translational study that aims to systematically evaluate the biomechanical properties, histological profile, and host immune response to HFL in direct comparison with synthetic polypropylene mesh, with a specific focus on its viability as a durable alternative surgical graft in pelvic reconstructive surgery. Study design, materials and methods Autologous fascial grafts were surgically harvested from female patients undergoing fascial pubovaginal sling or vault suspension, following a formal consent and recruitment process in accordance with local HREC guidelines (protocol# 01-01-09-22). Pre-implantation tensile strength was quantified via cyclic uniaxial tensiometer to simulate physiological stress (3 cycles, 100% stretch, dry conditions), followed by monotonic tensile loading to mechanical failure. An abdominal wall implantation model (n=8/group/time-point) assessed in vivo host responses at 7 and 90 days in a total of 32 C57BL/6 immunocompetent mice (Figure 1). Explants from both HFL and polypropylene mesh groups underwent histology review (Masson’s trichrome, elastin, H&E) for cellular infiltration analysis, scanning electron microscopy (SEM) for structural morphology, and polarized imaging for collagen alignment. Finally, qPCR and single cell proteomics was used to assess fold change in markers for immune activation, neovascularisation and extracellular matrix homeostasis. Data were analysed using Fluidigm Real-Time PCR analysis software (V4.1.1). Statistical analysis was performed using GraphPad Prism v9. Data were analysed using non-parametric Mann-Whitney U test (comparison between mesh and HFL). Results HFL grafts demonstrated rapid neovascularization and cellular migration by postoperative day 7, while polypropylene mesh exhibited an acute neutrophilic inflammation with foreign body giant cell formation. Biomechanically, HFL retained 50% tensile strength post-cyclic loading vs. 13% for polypropylene (p<0.01). Polarized imaging revealed fibrillar collagen bundles that had a less organised appearance in comparison with synthetic mesh explants, indicating increased immature collagen III deposition. SEM showed preserved HFL fibrous networks at 90 days, and there was no graft-related erosions. qPCR results revealed a more robust immune response in HFL explants elaborating both pro-inflammatory M1 and anti-inflammatory M2 macrophages, concomitant with enhanced expression of markers for neovascularisation (CD90, CD31, CD38) and ECM homeostasis (Tgfb1, Tgfbr1, Timp2, Mmp3, and Mmp9) (Figure 2). Interpretation of results HFL’s biomechanical adaptability and collagen-driven integration mitigate key complications of synthetic mesh, including chronic inflammation and mechanical failure. Its complex connective tissue structure promotes endogenous tissue remodelling and results in superior tensile properties, critical for long-term pelvic support, therefore warranting its application in pelvic reconstructive surgery. Genomic analysis revealed a fine balance in M1 and M2 macrophage elaboration that fostered enhanced neovascularization and ECM remodelling around the implant site, suggesting that immune crosstalk is essential for effective healing and tissue integration subsequent to fascial graft implantation. Concluding message HFL is a highly durable alternative surgical graft with superior host tissue integration, tensile strength and durability, when compared to polypropylene mesh. As a autologous biological graft, HFL addresses the unmet need for durable, low-risk grafts in prolapse repair. Its adoption could redefine standards for pelvic floor reconstruction, prioritizing patient safety without compromising anatomical outcomes. Further pre-clinical and clinical trials are warranted to validate long-term efficacy of this graft in augmentative pelvic reconstructive surgery. Download: Download high-res image (58KB) Download: Download full-size image Figure 1 . Graphical representation of experimental methodology; Human fascial lata (HFL) was harvested from consenting women undergoing autologous fascial grafting for sacrocolpopexy or pubovaginal sling insertion (n=26). HFL or synthetic polypropylene was Download: Download high-res image (107KB) Download: Download full-size image Figure 2 . Comparative Analysis of ECM synthesis and Fibroblast Markers in HFL versus Ti Mesh Implants. a and b Quantitative gene expression analysis shows the fold change in ECM-related and remodelling-associated genes in HFL graft and Ti-PP mesh 7 and 90 d Funding Cabrini Research Foundation ($30,000 AUD) Clinical Trial No Subjects Animal Species Mice Ethics Committee Monash Unviersity Animal Ethics Committee

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