Impact of gentamicin-supplemented polyvinylidenfluoride mesh materials on MMP-2 expression and tissue integration in a transgenic mice model.
OBJECTIVE
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.
Department of Surgery, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany. mbinneboesel@ukaachen.de
Marcel
M
Binnebösel
Christina
C
Ricken
Christian D
CD
Klink
Karsten
K
Junge
Marc
M
Jansen
Volker
V
Schumpelick
Petra
P
Lynen Jansen
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials; D004195:Disease Models, Animal; D005549:Foreign-Body Reaction / Q000517:prevention & control; D005839:Gentamicins / Q000008:administration & dosage*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D008567:Membranes, Artificial; D051379:Mice; D008822:Mice, Transgenic; D011145:Polyvinyls; D019919:Prosthesis Implantation; D013526:Surgical Mesh; D014945:Wound Healing / Q000187:drug effects; D005465:Fluorocarbon Polymers
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D005839:Gentamicins; D020778:Matrix Metalloproteinase 2; D008567:Membranes, Artificial; D011145:Polyvinyls; C024865:polyvinylidene fluoride; D005465:Fluorocarbon Polymers