The use of autologous human fascia lata (HFL) in pelvic reconstructive procedures such as sacrocolpopexy (SCP) has become increasingly desired by patients due to a greater awareness of potential complications of synthetic mesh, following the recent withdrawal of meshes. HFL has long been used for incontinence procedures in Urogynaecology and Urology, and more recently for sacrocolpopexy or graft augmented vaginal repair where synthetic meshes are contra-indicated or unavailable. However, very little is known about the durability of HFL grafts when compared with synthetic mesh for sacrocolpopexy, which has demonstrated a low recurrence rate with long-term follow-up. Furthermore, the biomechanical, morphological, cellular, matrix, and immunological properties of HFL and its regulation post-implantation remain largely elusive. Thus, this study will advance the knowledge and understanding of HFL as a potential surgical graft. 

This study aimed to evaluate the morphometric properties, biomechanical properties and in vivo foreign body response of HFL in a pre-clinical murine abdominal incision model.  In particular, a direct comparison with synthetic polypropylene mesh was made in order to better characterize its long-term implications and assess its durability as a surgical graft. Furthermore,  we investigated the key molecular mechanisms driving its integration in the body to inform its application in augmentative procedures for pelvic organ prolapse.

Human fascial lata (HFL) was harvested from consenting women undergoing autologous fascial grafting for sacrocolpopexy or pubovaginal sling insertion (n=26). HFL and polypropylene were characterised using uniaxial tensiometry using cyclical loading (3 cycles, 100% stretch). HFL or synthetic polypropylene was implanted in C57/BL6 immunocompetent mice via an abdominal skin incision (n=8 mice/gp/time-point). The tissues were explanted and assessed at 7 and 90-day time points using histological stains for cellular infiltration, elastin and collagen. Quantitative PCR was used to assess 80 genes associated with ECM homeostasis, cell adhesion, angiogenesis and inflammation in explanted tissues as fold changes to non-operative controls. The macrophage response was determined using immunofluorescence of CD206, F4/80 and CCR7 using multi-colour immunofluorescence.  Histology and electron microscopy were used to visualize the matrix elements, collagen content and blood vessels surrounding HFL and polypropylene grafts in tissue explants.

HFL tissue is primarily comprised of relatively acellular fibrous collagen. Both grafts remained sutured at experimental endpoints and were well tolerated by mice with no erosions observed. At 7 days, HFL exhibited good tissue integration with histological evidence of host cell infiltration within the graft. Polypropylene mesh demonstrated loose integration, increased acute inflammatory cell infiltration and foreign body giant cell formation surrounding explants. We are currently assessing the tissue response at 90 days. Our on-going in vivo analysis of gene expression highlights that the differential immune response and tissue integration between explants may be explained by differences in gene expression of ECM genes such as Col1a1 , Col3a1, Col6a1, Col6a2; ECM regulatory genes such as Mmp2, Mmp19, Timp2 and Timp3; Cell adhesion genes such as Itgb1, Vcam, Cdh1 and Cdh2 ; acute inflammatory genes such as Tnfa, Ccl2, Ccl7, Cxcl1 and Ccr7; anti-inflammatory genes such as Mrc, Arg1, and Il10 as well as key angiogenic genes such as Vegfa, Tgfb1, Tgfb3, Ctgf, Fgf1, Ang1 and Pdgfa. Furthermore, we are assessing the influx of endogenous F4/80 macrophages, polarisation to M1 and M2 and the collagen matrix deposition around the grafts.

Our results suggest that HFL is significantly different from the foreign body response seen with synthetic polypropylene mesh, with more controlled host-graft integration, cellular infiltration and over all tissue integration.

Our research delves deep into the mechanisms of tissue integration and foreign body response using novel techniques of electron microscopy, confocal microscopy and advanced medical genomics to advance the knowledge on the in vivo response to HFL. HFL is a highly durable alternative surgical graft with superior tissue integration when compared to polypropylene mesh Consisting of fibrous structural proteins such as collagen and elastin confers high mechanical adaptability and durability, making this an ideal surgical implant for augmentative pelvic reconstructive procedures.

Continence 7S1 (2023) 100845
DOI: 10.1016/j.cont.2023.100845