Effects of collagen prosthesis cross‐linking on long‐term tissue regeneration following the repair of an abdominal wall defect

Abstract

Collagen prostheses used to repair abdominal wall defects, depending on their pretreatment (noncross-linked vs. cross-linked), besides repair may also achieve tissue regeneration. We assessed the host tissue incorporation of different bioprostheses using a new tool that combines immunofluorescence confocal microscopy with differential interference contrast images, making it possible to distinguish newly formed collagen. Partial hernial defects in the abdominal wall of rabbits were repaired using cross-linked/noncross-linked bioprostheses. Expanded polytetrafluoroethylene (ePTFE) was used as control. After 14/30/90/180 days of implant, specimens were taken for microscopy, immunohistochemistry, and quantitative-reverse transcription-polymerase chain reaction to determine host tissue ingrowth and collagen I/III protein and 1a1/3a1 gene expression. Shrinkage and stress resistance were also examined. At 14 days, cross-linked prostheses had suffered significantly less shrinkage than ePTFE or noncross-linked prostheses. Significantly higher shrinkage was recorded for ePTFE in the longer term. Microscopy revealed encapsulation of ePTFE by neoformed tissue, while the bioprostheses became gradually infiltrated by host tissue. Noncross-linked prosthesis showed better tissue ingrowth, more intense inflammatory reaction and more rapid degradation than the cross-linked prostheses. At 14 days, cross-linked prostheses induced up-regulated collagen 1a1 and 3a1 gene expression, while noncross-linked only showed increased collagen III protein expression at 90 days postimplant. At 6 months, the tensile strengths of cross-linked prostheses were significantly greater compared with ePTFE. Our findings demonstrate that despite the cross-linked collagen prostheses promoting less tissue ingrowth than the noncross-linked meshes, they became gradually replaced by good quality host tissue and were less rapidly degraded, leading to improved stress resistance in the long term.

To Cross-Link or Not to Cross-Link? Cross-Linking Associated Foreign Body Response of Collagen-Based Devices

“…However, this early inflammatory cell population recruitment has been shown to be lower for Permacol™ than non-cross-linked SIS and porcine and human dermis (Surgisis™, Strattice™ and Alloderm ® , respectively). However, this response was normalised between all grafts over extended periods 153,165 . Regarding cell infiltration, mononuclear cells were detected around Permacol™ and only infiltrated through material pores; only 20% of implants were colonised at day 14 and the totality of graft was colonised after 1 month 152,165,166 .…”

Diaphragmatic crural augmentation utilising cross-linked porcine dermal collagen biologic mesh (Permacol™) in the repair of large and complex para-oesophageal herniation: a retrospective cohort study

“…This results in a prosthesis that exhibits limited contraction following implantation [7], better retention of tensile strength after repetitive loading [22] and higher tensile strength after a period of enzymatic degradation [6] compared with non-cross-linked implants. Supplemental cross-linking does not appear to adversely affect tissue integration in animal models [23] or in man [24] in the long term, and has been associated with up-regulation of collagen type 1A1 gene expression in animal models, leading to a more mature type 1: type 3 collagen ratio compared with non-cross-linked implants [25].…”

Remodeling of Noncrosslinked Acellular Dermal Matrices in a Rabbit Model of Ventral Hernia Repair

“…Deeken et al [21] claim that this limitation of crosslinked meshes may be insignificant in the long term, reporting that although crosslinking differentiated biological meshes early on, at 1 year, histological features such as cell penetration and neovascularization were no longer affected. In our experience [11,22], crosslinked prostheses show poor remodeling in the long term, at 180 days, though it could be that remodeling and tissue incorporation improve in the even longer term.…”

“…In the present study, we tried to differentiate, through immunofluorescence confocal microscopy combined with differential interference contrast imaging [11], between the collagen comprising the implanted mesh and the host collagen in the neoformed connective tissue that will gradually invade and, ideally, replace the mesh. We observed neovascularization in some areas of the outer part of the biomesh in the long term (90 days after implantation) and newly formed collagen infiltrating the mesh mainly in the St and Pr groups, though this was insufficient to support the idea of evident remodeling even in the long term.…”

“…Some authors have reported good animal and clinical data using these biological materials [10,11]. However, so far the literature lacks sufficient follow-up data to draw valid conclusions regarding the benefits of the use of a bioprosthesis.…”