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

Abstract

Purpose: Reinforcement of the abdominal wall by alloplastic mesh material results in a chronic foreign body reaction which is characterized by a transcriptionally induced overexpression of the matrix metalloproteinases-2 (MMP-2). Mesh modification represents a new approach to normalize the MMP-2 expression and thereby to reduce the foreign body reaction. Because of its proven beneficial effect on tissue integration, the influence of gentamicin-supplemented polyvinylidenfluoride (PVDF) mesh materials on MMP-2 transcription and protein expression was investigated in transgenic reporter mice harboring MMP-2 regulatory sequence-1686/+423.

Methods: A 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 microg/mg). Seventy-five male transgenic MMP-2/LacZ CD1-tg mice harboring MMP-2 regulatory sequences -1686/+423 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 and protein expression were analyzed semiquantitatively 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.

Results: The perifilamentary MMP-2 protein expression as well as the MMP-2 promoter activity decreased over time, whereas the collagen type I/III ratio increased up to the 90th day for all mesh modifications. The 8-microg/mg mesh material showed significantly reduced levels of MMP-2-positive stained cells when compared with the PVDF group on days 7, 21, and 90 (p = 0.008; p = 0.016; p = 0.016). In accordance, the 8-microg/mg group revealed a significant reduction of beta-galactosidase-positive stained cells at each time point in comparison with the PVDF group (p = 0.008; p = 0.047; p = 0.016). Though the type I/III collagen ratio increased over time for all mesh modifications significant differences to the PVDF mesh could only detected for 8-microg/mg group (p = 0.008; p = 0.032; p = 0.016).

Conclusions: Our results show a dose-dependent effect of gentamicin. The reduced MMP-2 protein expression and transcription after mesh coating with 8 microg/mg gentamicin together with the improved collagen type I/III hint on an advanced tissue integration even in the long-term. Subsequent studies are needed to elucidate interaction of collagen and MMP-2 in chronic foreign body reaction.