Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

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 μg/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-μg/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-μg/mg group revealed a significant reduction of β-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-μg/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 μg/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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Macintyre IM (2003) Best practice in groin hernia repair. Br J Surg 90:131–132

    Article  CAS  PubMed  Google Scholar 

  2. Forbes SS, Eskicioglu C, McLeod RS, Okrainec A (2009) Meta-analysis of randomized controlled trials comparing open and laparoscopic ventral and incisional hernia repair with mesh. Br J Surg 96:851–858

    Article  CAS  PubMed  Google Scholar 

  3. Conze J, Klinge U, Schumpelick V (2005) Incisional hernia. Chirurg 76:897–909

    Article  CAS  PubMed  Google Scholar 

  4. Deysine M (1998) Pathophysiology, prevention, and management of prosthetic infections in hernia surgery. Surg Clin North Am 78:1105–1115, viii

    Article  CAS  PubMed  Google Scholar 

  5. Leber GE, Garb JL, Alexander AI, Reed WP (1998) Long-term complications associated with prosthetic repair of incisional hernias. Arch Surg 133:378–382

    Article  CAS  PubMed  Google Scholar 

  6. Kumar S, Wilson RG, Nixon SJ, Macintyre IM (2002) Chronic pain after laparoscopic and open mesh repair of groin hernia. Br J Surg 89:1476–1479

    Article  CAS  PubMed  Google Scholar 

  7. White TJ, Santos MC, Thompson JS (1998) Factors affecting wound complications in repair of ventral hernias. AmSurg 64:276–280

    CAS  PubMed  Google Scholar 

  8. Junge K, Rosch R, Bialasinski L, Klinge U, Klosterhalfen B, Schumpelick V (2003) Persistent extracellular matrix remodelling at the interface to polymers used for hernia repair. Eur Surg Res 35:497–504

    Article  CAS  PubMed  Google Scholar 

  9. Klinge U, Klosterhalfen B, Muller M, Schumpelick V (1999) Foreign body reaction to meshes used for the repair of abdominal wall hernias. Eur J Surg 165:665–673

    Article  CAS  PubMed  Google Scholar 

  10. Jansen PL, Mertens PP, Klinge U, Schumpelick V (2004) The biology of hernia formation. Surgery 136:1–4

    Article  PubMed  Google Scholar 

  11. Binnebosel, M., Klink, C. D., Otto, J., Conze, J., Jansen, P. L., Anurov, M., Schumpelick, V., Junge, K. (2009) Impact of mesh positioning on foreign body reaction and collagenous ingrowth in a rabbit model of open incisional hernia repair. Hernia; 1248–9204

  12. Klinge U, Schumpelick V, Klosterhalfen B (2001) Functional assessment and tissue response of short- and long-term absorbable surgical meshes. Biomaterials 22:1415–1424

    Article  CAS  PubMed  Google Scholar 

  13. Klinge U, Klosterhalfen B, Muller M, Anurov M, Ottinger A, Schumpelick V (1999) Influence of polyglactin-coating on functional and morphological parameters of polypropylene-mesh modifications for abdominal wall repair. Biomaterials 20:613–623

    Article  CAS  PubMed  Google Scholar 

  14. Junge K, Rosch R, Krones CJ, Klinge U, Mertens PR, Lynen P, Schumpelick V, Klosterhalfen B (2005) Influence of polyglecaprone 25 (Monocryl) supplementation on the biocompatibility of a polypropylene mesh for hernia repair. Hernia 9:212–217

    Article  CAS  PubMed  Google Scholar 

  15. Rosch R, Junge K, Quester R, Klinge U, Klosterhalfen B, Schumpelick V (2003) Vypro II mesh in hernia repair: impact of polyglactin on long-term incorporation in rats. Eur Surg Res 35:445–450

    Article  CAS  PubMed  Google Scholar 

  16. Conze J, Junge K, Weiss C, Anurov M, Oettinger A, Klinge U, Schumpelick V (2008) New polymer for intra-abdominal meshes–PVDF copolymer. J BiomedMaterResB Appl Biomater 87:321–328

    PubMed  Google Scholar 

  17. Klinge U, Klosterhalfen B, Ottinger AP, Junge K, Schumpelick V (2002) PVDF as a new polymer for the construction of surgical meshes. Biomaterials 23:3487–3493

    Article  CAS  PubMed  Google Scholar 

  18. Junge K, Binnebosel M, Rosch R, Jansen M, Kammer D, Otto J, Schumpelick V, Klinge U (2009) Adhesion formation of a polyvinylidenfluoride/polypropylene mesh for intra-abdominal placement in a rodent animal model. Surg Endosc 23:327–333

    Article  PubMed  Google Scholar 

  19. Lynen JP, Klinge U, Anurov M, Titkova S, Mertens PR, Jansen M (2004) Surgical mesh as a scaffold for tissue regeneration in the esophagus. Eur Surg Res 36:104–111

    Article  Google Scholar 

  20. Schroeder R, Waldsich C, Wank H (2000) Modulation of RNA function by aminoglycoside antibiotics. EMBO J 19:1–9

    Article  CAS  PubMed  Google Scholar 

  21. Binnebosel M, Junge K, Kaemmer DA, Krones CJ, Titkova S, Anurov M, Schumpelick V, Klinge U (2009) Intraperitoneally applied gentamicin increases collagen content and mechanical stability of colon anastomosis in rats. Int J Colorectal Dis 24:433–440

    Article  PubMed  Google Scholar 

  22. Tekos A, Prodromaki E, Papadimou E, Pavlidou D, Tsambaos D, Drainas D (2003) Aminoglycosides suppress tRNA processing in human epidermal keratinocytes in vitro. Skin Pharmacol Appl Skin Physiol 16:252–258

    CAS  PubMed  Google Scholar 

  23. Wrzesniok D, Buszman E, Karna E, Nawrat P, Palka J (2002) Melanin potentiates gentamicin-induced inhibition of collagen biosynthesis in human skin fibroblasts. Eur J Pharmacol 446:7–13

    Article  CAS  PubMed  Google Scholar 

  24. Junge K, Klinge U, Rosch R, Lynen P, Binnebosel M, Conze J, Mertens PR, Schwab R, Schumpelick V (2007) Improved collagen type I/III ratio at the interface of gentamicin-supplemented polyvinylidenfluoride mesh materials. Langenbecks Arch Surg 392:465–471

    Article  PubMed  Google Scholar 

  25. Junge K, Rosch R, Klinge U, Krones C, Klosterhalfen B, Mertens PR, Lynen P, Kunz D, Preiss A, Peltroche-Llacsahuanga H, Schumpelick V (2005) Gentamicin supplementation of polyvinylidenfluoride mesh materials for infection prophylaxis. Biomaterials 26:787–793

    Article  CAS  PubMed  Google Scholar 

  26. Rosch R, Lynen-Jansen P, Junge K, Knops M, Klosterhalfen B, Klinge U, Mertens PR, Schumpelick V (2006) Biomaterial-dependent MMP-2 expression in fibroblasts from patients with recurrent incisional hernias. Hernia 10:125–130

    Article  CAS  PubMed  Google Scholar 

  27. Jansen PL, Kever M, Rosch R, Krott E, Jansen M, Alfonso-Jaume A, Dooley S, Klinge U, Lovett DH, Mertens PR (2007) Polymeric meshes induce zonal regulation of matrix metalloproteinase-2 gene expression by macrophages and fibroblasts. FASEB J 21:1047–1057

    Article  CAS  PubMed  Google Scholar 

  28. Olaso E, Labrador JP, Wang L, Ikeda K, Eng FJ, Klein R, Lovett DH, Lin HC, Friedman SL (2002) Discoidin domain receptor 2 regulates fibroblast proliferation and migration through the extracellular matrix in association with transcriptional activation of matrix metalloproteinase-2. J Biol Chem 277:3606–3613

    Article  CAS  PubMed  Google Scholar 

  29. Lee JG, Dahi S, Mahimkar R, Tulloch NL, Alfonso-Jaume MA, Lovett DH, Sarkar R (2005) Intronic regulation of matrix metalloproteinase-2 revealed by in vivo transcriptional analysis in ischemia. Proc Natl Acad Sci USA 102:16345–16350

    Article  CAS  PubMed  Google Scholar 

  30. Jansen PL, Rosch R, Jansen M, Binnebosel M, Junge K, Alfonso-Jaume A, Klinge U, Lovett DH, Mertens PR (2007) Regulation of MMP-2 gene transcription in dermal wounds. J Invest Dermatol 127:1762–1767

    CAS  PubMed  Google Scholar 

  31. Gupta B, Plummer C, Bisson I, Frey P, Hilborn J (2002) Plasma-induced graft polymerization of acrylic acid onto poly(ethylene terephthalate) films: characterization and human smooth muscle cell growth on grafted films. Biomaterials 23:863–871

    Article  CAS  PubMed  Google Scholar 

  32. Junqueira LC, Cossermelli W, Brentani R (1978) Differential staining of collagens type I, II and III by Sirius Red and polarization microscopy. Arch Histol Jpn 41:267–274

    CAS  PubMed  Google Scholar 

  33. Kehlet H (2008) Chronic pain after groin hernia repair. Br J Surg 95:135–136

    Article  CAS  PubMed  Google Scholar 

  34. Canziani M, Frattini F, Cavalli M, Agrusti S, Somalvico F, Campanelli G (2009) Sutureless mesh fibrin glue incisional hernia repair. Hernia 13:625–629

    Article  CAS  PubMed  Google Scholar 

  35. Kehlet H, Bay-Nielsen M (2008) Nationwide quality improvement of groin hernia repair from the Danish Hernia Database of 87,840 patients from 1998 to 2005. Hernia 12:1–7

    Article  CAS  PubMed  Google Scholar 

  36. Aasvang EK, Hansen JB, Kehlet H (2008) Can preoperative electrical nociceptive stimulation predict acute pain after groin herniotomy? J Pain 9:940–944

    Article  PubMed  Google Scholar 

  37. Rosch R, Junge K, Schachtrupp A, Klinge U, Klosterhalfen B, Schumpelick V (2003) Mesh implants in hernia repair. Inflammatory cell response in a rat model. Eur Surg Res 35:161–166

    Article  CAS  PubMed  Google Scholar 

  38. Inkinen K, Turakainen H, Wolff H, Ravanti L, Kahari VM, Ahonen J (2000) Expression and activity of matrix metalloproteinase-2 and -9 in experimental granulation tissue. APMIS 108:318–328

    Article  CAS  PubMed  Google Scholar 

  39. Ravanti L, Kahari VM (2000) Matrix metalloproteinases in wound repair (review). Int J Mol Med 6:391–407

    CAS  PubMed  Google Scholar 

  40. Jackson CJ, Xue M, Thompson P, Davey RA, Whitmont K, Smith S, Buisson-Legendre N, Sztynda T, Furphy LJ, Cooper A, Sambrook P, March L (2005) Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing. Wound Repair Regen 13:284–294

    Article  PubMed  Google Scholar 

  41. Ishikawa T, Nishigaki F, Miyata S, Hirayama Y, Minoura K, Imanishi J, Neya M, Mizutani T, Imamura Y, Naritomi Y, Murai H, Ohkubo Y, Kagayama A, Mutoh S (2005) Prevention of progressive joint destruction in collagen-induced arthritis in rats by a novel matrix metalloproteinase inhibitor, FR255031. Br J Pharmacol 144:133–143

    Article  CAS  PubMed  Google Scholar 

  42. Wu M, Li YG (2006) The expression of CD40-CD40L and activities of matrix metalloproteinases in atherosclerotic rats. Mol Cell Biochem 282:141–146

    Article  CAS  PubMed  Google Scholar 

  43. Agren MS (1994) Gelatinase activity during wound healing. Br J Dermatol 131:634–640

    Article  CAS  PubMed  Google Scholar 

  44. Mandal M, Mandal A, Das S, Chakraborti T, Sajal C (2003) Clinical implications of matrix metalloproteinases. Mol Cell Biochem 252:305–329

    Article  CAS  PubMed  Google Scholar 

  45. Ziats NP, Miller KM, Anderson JM (1988) In vitro and in vivo interactions of cells with biomaterials. Biomaterials 9:5–13

    Article  CAS  PubMed  Google Scholar 

  46. Romero F, Perez M, Chavez M, Parra G, Durante P (2009) Effect of uric acid on gentamicin-induced nephrotoxicity in rats—role of matrix metalloproteinases 2 and 9. Basic Clin Pharmacol Toxicol 105:416–424

    Article  CAS  PubMed  Google Scholar 

  47. Asch HL, Farnham PJ (1978) Effects of gentamicin on trypsin, chymotrypsin, and collagenase. J Infect Dis 138:257–259

    CAS  PubMed  Google Scholar 

  48. Frisch SM, Morisaki JH (1990) Positive and negative transcriptional elements of the human type IV collagenase gene. Mol Cell Biol 10:6524–6532

    CAS  PubMed  Google Scholar 

  49. Harendza S, Pollock AS, Mertens PR, Lovett DH (1995) Tissue-specific enhancer-promoter interactions regulate high level constitutive expression of matrix metalloproteinase 2 by glomerular mesangial cells. J Biol Chem 270:18786–18796

    Article  CAS  PubMed  Google Scholar 

  50. Cheng S, Alfonso-Jaume MA, Mertens PR, Lovett DH (2002) Tumour metastasis suppressor, nm23-beta, inhibits gelatinase A transcription by interference with transactivator Y-box protein-1 (YB-1). Biochem J 366:807–816

    CAS  PubMed  Google Scholar 

  51. Mertens PR, Harendza S, Pollock AS, Lovett DH (1997) Glomerular mesangial cell-specific transactivation of matrix metalloproteinase 2 transcription is mediated by YB-1. J Biol Chem 272:22905–22912

    Article  CAS  PubMed  Google Scholar 

  52. Menashe O, Kaganskaya E, Baasov T, Yaron S (2008) Aminoglycosides affect intracellular Salmonella enterica serovars typhimurium and virchow. Antimicrob Agents Chemother 52:920–926

    Article  CAS  PubMed  Google Scholar 

  53. Subramanian S, Roberts CL, Hart CA, Martin HM, Edwards SW, Rhodes JM, Campbell BJ (2008) Replication of colonic Crohn’s disease mucosal Escherichia coli isolates within macrophages and their susceptibility to antibiotics. Antimicrob Agents Chemother 52:427–434

    Article  CAS  PubMed  Google Scholar 

  54. Lynen JP, Klinge U, Mertens PR (2006) Hernia disease and collagen gene regulation: are there clues for intervention? Hernia 10:486–491

    Article  Google Scholar 

  55. Hartmuth K, Urlaub H, Vornlocher HP, Will CL, Gentzel M, Wilm M, Luhrmann R (2002) Protein composition of human prespliceosomes isolated by a tobramycin affinity-selection method. Proc Natl Acad Sci USA 99:16719–16724

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported by the Deutsche Forschungsgemeinschaft DFG grant JA 1123/1-1 (M. J. and P. L. J.). We are grateful to Mrs. Ellen Krott for most excellent and careful assistance during this investigation.

Contributions

The contributions of each author in preparing the manuscript are as follows:

Study conception and design: M. B., P. L. J., K. J., and V. S

Acquisition of data: M. B., C. R., C. D. K., K. J., M. J., V. S., and P. L. J

Analysis and interpretation of data: M. B., C. R., C. D. K., K. J., M. J., V. S., and P. L. J.

Drafting of manuscript: M. B., C. R., C. D. K., K. J., M. J., V. S., and P. L. J.

Critical revision of manuscript: M. B., C. R., C. D. K., K. J., M. J., V. S., and P. L. J.

Author information

Authors and Affiliations

  1. Department of Surgery, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany

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

Authors
  1. Marcel Binnebösel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christina Ricken
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christian D. Klink
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karsten Junge
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marc Jansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Volker Schumpelick
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Petra Lynen Jansen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcel Binnebösel.

Additional information

Best of Abstracts—Chirurgisches Forum 2010, Deutsche Gesellschaft für Chirurgie

Rights and permissions

Reprints and permissions

About this article

Cite this article

Binnebösel, M., Ricken, C., Klink, C.D. et al. Impact of gentamicin-supplemented polyvinylidenfluoride mesh materials on MMP-2 expression and tissue integration in a transgenic mice model. Langenbecks Arch Surg 395, 413–420 (2010). https://doi.org/10.1007/s00423-010-0601-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-010-0601-x

Keywords

Search

Navigation