Impact of gentamicin-supplemented polyvinylidenfluoride mesh materials on MMP-2 expression and tissue integration in a transgenic mice model

Binnebösel, Marcel; Ricken, Christina; Klink, Christian D.; Junge, K.; Jansen, Marc; Schumpelick, Volker; Jansen, Petra Lynen

doi:10.1007/s00423-010-0601-x

Cited by 17 publications

(17 citation statements)

References 54 publications

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“…The mice strain used as animal model has been described recently [9,11,17,18]. In brief, mouse strain F8 harbour a β-galactosidase reporter gene (LacZ) under control of MMP-2 regulatory sequences -1686/+423 that extend to the middle of the second exon.…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, all histological and immunohistochemical investigations including the cross polarization microscopy were performed in the same manner as previously described [17]. …”

Section: Methodsmentioning

confidence: 99%

“…In a previously published study gentamicin coated polyvinylidenfluoride (PVDF) mesh material was detected to improve tissue integration due to an increased type I/III collagen ratio and a reduced MMP-2 protein expression [17]. However, our model analysing MMP-2 gene expression in transgenic mice revealed distinct MMP-2 promoter activation dependent on the course of time and on the concentration of gentamicin [17].…”

Section: Introductionmentioning

confidence: 98%

“…However, our model analysing MMP-2 gene expression in transgenic mice revealed distinct MMP-2 promoter activation dependent on the course of time and on the concentration of gentamicin [17]. To further elucidate our proven beneficial effect of biomaterial supplementation on foreign body reaction and tissue integration an in-depth understanding of the gentamicin induced enhancement of MMP-2 is necessary.…”

Section: Introductionmentioning

confidence: 99%

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Gentamicin supplemented polyvinylidenfluoride mesh materials enhance tissue integration due to a transcriptionally reduced MMP-2 protein expression

et al. 2012

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BackgroundA beneficial effect of gentamicin supplemented mesh material on tissue integration is known. To further elucidate the interaction of collagen and MMP-2 in chronic foreign body reaction and to determine the significance of the MMP-2-specific regulatory element (RE-1) that is known to mediate 80% of the MMP-2 promoter activity, the spatial and temporal transcriptional regulation of the MMP-2 gene was analyzed at the cellular level.MethodsA PVDF mesh material was surface modified by plasma-induced graft polymerization of acrylic acid (PVDF+PAAc). Three different gentamicin concentrations were bound to the provided active sites of the grafted mesh surfaces (2, 5 and 8 μg/mg). 75 male transgenic MMP-2/LacZ mice harbouring the LacZ reporter gene under control of MMP-2 regulatory sequence -1241/+423, excluding the RE-1 were randomized to five groups. Bilateral of the abdominal midline one of the five different meshes was implanted subcutaneously in each animal. MMP-2 gene transcription (anti-ß-galactosidase staining) and MMP-2 protein expression (anti-MMP-2 staining) were analyzed semiquantitatively by immunohistochemistry 7, 21 and 90 days after mesh implantation. The collagen type I/III ratio was analyzed by cross polarization microscopy to determine the quality of mesh integration.ResultsThe perifilamentary ß-galactosidase expression as well as the collagen type I/III ratio increased up to the 90th day for all mesh modifications, whereas no significant changes could be observed for MMP-2 protein expression between days 21 and 90. Both the 5 and 8 μg/mg gentamicin group showed significantly reduced levels of ß-galactosidase expression and MMP-2 positive stained cells when compared to the PVDF group on day 7, 21 and 90 respectively (5 μg/mg: p < 0.05 each; 8 μg/mg: p < 0.05 each). Though the type I/III collagen ratio increased over time for all mesh modifications significant differences to the PVDF mesh were only detected for the 8 μg/mg group at all 3 time points (p < 0.05 each).ConclusionsOur current data indicate that lack of RE-1 is correlated with increased mesh induced MMP-2-gene expression for coated as well as for non-coated mesh materials. Gentamicin coating reduced MMP-2 transcription and protein expression. For the 8 μg/mg group this effect is associated with an increased type I/III collagen ratio. These findings suggest that gentamicin is beneficial for tissue integration after mesh implantation, which possibly is mediated via RE-1.

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Section: Methodsmentioning

confidence: 99%

“…Briefly, all histological and immunohistochemical investigations including the cross polarization microscopy were performed in the same manner as previously described [17]. …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Gentamicin supplemented polyvinylidenfluoride mesh materials enhance tissue integration due to a transcriptionally reduced MMP-2 protein expression

et al. 2012

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“…The gentamicin supplemented mesh group induced a higher expression of mRNA of alpha 1 type I collagen and consequently an increased collagen type I/III ratio at the interface mesh/host tissue with a lowered expression of collagenases. This beneficial effect of gentamicin supplemented PVDF mesh material on wound healing and tissue integration could be confirmed in further investigations [25,189]. Interestingly, apart from its antibacterial activity due to an inhibitory effect on ribosome function, gentamicin is already been reported to interfere with various RNA molecules and has several other collateral effects.…”

Section: Extracellular Matrix Modulationmentioning

confidence: 60%

Mesh biocompatibility: effects of cellular inflammation and tissue remodelling

Junge

Binnebösel

Trotha

et al. 2011

Langenbecks Arch Surg

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115

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Mesh biocompatibility is basically determined by the foreign body reaction (FBR). In contrast to physiological wound healing and scar formation, the FBR at the host-tissue/biomaterial interface is present for the lifetime of the medical device. The cellular interactions at the mesh/tissue interface proceed over time ending up in a chronic inflammatory process. The time course of the FBR has been studied extensively and consists of three crucial steps that are protein absorption, cell recruitment and, finally, fibrotic encapsulation and extracellular matrix formation. Each of these steps involves a complex cascade of immune modulators including soluble mediators and various cell types. Recent research has focused on the cellular and molecular interactions of the distinct phases of the FBR offering a new basis for therapeutical strategies. The highly dynamic process of the FBR is considerably influenced by the biomaterial composition. Modifications of the type of polymer, the material weight, the filament structure and the pore size are realized and have substantial effects on the in vivo biocompatibility. Moreover, modern mesh technology aims to utilize the available implants as carrier systems for bioactive drugs. Studies in animal models account for the efficiency of these drugs that aim to reduce mesh-related infections or to minimize FBR by influencing inflammation or extracellular matrix remodelling. A thorough understanding of the molecular mechanisms of FBR provides a sophisticated background for the development of new biomaterials at least as carrier systems for bioactive reagents to reduce inflammation and to improve clinical outcome.

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Emerging Trends in Abdominal Wall Reinforcement: Bringing Bio‐Functionality to Meshes

Guillaume

Teuschl

Gruber-Blum

et al. 2015

Adv Healthcare Materials

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Abdominal wall hernia is a recurrent issue world-wide and requires the implantation of over 1 million meshes per year. Because permanent meshes such as polypropylene and polyester are not free of complications after implantation, many mesh modifications and new functionalities have been investigated over the last decade. Indeed, mesh optimization is the focus of intense development and the biomaterials utilized are now envisioned as being bioactive substrates that trigger various physiological processes in order to prevent complications and to promote tissue integration. In this context, it is of paramount interest to review the most relevant bio-functionalities being brought to new meshes and to open new avenues for the innovative development of the next generation of meshes with enhanced properties for functional abdominal wall hernia repair.

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Impact of gentamicin-supplemented polyvinylidenfluoride mesh materials on MMP-2 expression and tissue integration in a transgenic mice model

Cited by 17 publications

References 54 publications

Gentamicin supplemented polyvinylidenfluoride mesh materials enhance tissue integration due to a transcriptionally reduced MMP-2 protein expression

Gentamicin supplemented polyvinylidenfluoride mesh materials enhance tissue integration due to a transcriptionally reduced MMP-2 protein expression

Mesh biocompatibility: effects of cellular inflammation and tissue remodelling

Emerging Trends in Abdominal Wall Reinforcement: Bringing Bio‐Functionality to Meshes

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