Skip to main content
SpringerLink
Log in

Doxycycline shows dose-dependent changes in hernia repair strength after mesh repair

  • Published:
Surgical Endoscopy Aims and scope Submit manuscript

Abstract

Background

Ventral hernia is a commonly occurring surgical problem. Our earlier studies have shown that a 30 mg/kg dose of doxycycline can significantly impact the strength of polypropylene (PP) mesh in a rat hernia repair model at 6 and 12 weeks. The objective of the present study was to investigate the dose dependence of doxycycline treatment on hernia repair strengths in rats.

Study design

Fifty-six Sprague-Dawley rats underwent hernia repair with either PP mesh (n = 28) or sutures only (primary; n = 28); both groups were further divided into four doxycycline groups of seven animals each: control (0 mg/kg), low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg). One day before hernia repair surgery, animals received doxycycline doses by gavage and continued receiving daily until euthanasia. After 8 weeks, rats were euthanized and tissue samples from hernia repaired area were collected and analyzed for tensile strength using a tensiometer (Instron, Canton, MA, USA), while MMPs 2, 3, and 9, and collagen type 1 and 3 were analyzed by western blotting.

Results

In mesh-repaired animals, medium and high doxycycline dose repaired mesh fascia interface (MFI) showed significant increase in tensile strength when compared to control. In the primary repaired animals, there was no significant difference in MFI tensile strength in any dose group. In medium-dose MFI, there was a significant reduction in MMPs 2, 3, and 9. In this animal group, MFI showed significant increase in collagen 1 and significant reduction in collagen type 3 when compared to control.

Conclusion

It is possible to improve the strength of mesh-repaired tissue by administering a significantly lower dose of the drug, which has implications for translation of the findings.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Rutkow IM, Robbins AW (1993) Demographic, classificatory, and socioeconomic aspects of hernia repair in the United States. Surg Clin N Am 73:413–426

    CAS  PubMed  Google Scholar 

  2. Kingsnorth A (2006) The management of incisional hernia. Ann R Coll Surg Engl 88:252–260

    Article  PubMed  PubMed Central  Google Scholar 

  3. Mudge M, Hughes LE (1985) Incisional hernia: a 10 year prospective study of incidence and attitudes. Br J Surg 72:70–71

    Article  CAS  PubMed  Google Scholar 

  4. George CD, Ellis H (1986) The results of incisional hernia repair: a twelve year review. Ann R Coll Surg Engl 68:185–187

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Langer S, Christiansen J (1985) Long-term results after incisional hernia repair. Acta Chir Scand 151:217–219

    CAS  PubMed  Google Scholar 

  6. Anthony T, Bergen PC, Kim LT (2000) Factors affecting recurrence following incisional herniorrhaphy. World J Surg 24:95–101

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Franz MG (2008) The biology of hernia formation. Surg Clin N Am 88:1–15

    Article  PubMed  PubMed Central  Google Scholar 

  9. Salameh JR, Talbott LM, May W, Gosheh B, Vig PJ, McDaniel DO (2007) Role of biomarkers in incisional hernias. Am Surg 73:561–567; discussion 567–568

  10. Antoniou SA, Antoniou GA, Granderath FA, Simopoulos C (2009) The role of matrixmetallo-proteinases in the pathogenesis of abdominal wall hernias. Eur J Clin Invest 39:953–959

    Article  CAS  PubMed  Google Scholar 

  11. Lee HM, Ciancio SG, Tüter G, Ryan ME, Komaroff E, Golub LM (2004) Subantimicrobial dose doxycycline efficacy as a matrix metalloproteinase inhibitor in chronic periodontitis patients is enhanced when combined with a non-steroidal antiinflammatory drug. J Periodontol 75:453–463

    Article  CAS  PubMed  Google Scholar 

  12. Tharappel JC, Bower CE, Whittington-Harris J, Ramineni SK, Puleo DA, Roth JS (2014) Doxycycline administration improves fascial interface in hernia repair. J Surg Res 190:692–698

    Article  CAS  PubMed  Google Scholar 

  13. Tharappel JC, Ramineni SK, Reynolds D, Puleo DA, Roth JS (2013) Doxycycline impacts hernia repair outcomes. J Surg Res 184:699–704

    Article  CAS  PubMed  Google Scholar 

  14. Rice RD, Ayubi FS, Shaub ZJ, Parker DM, Armstrong PJ, Tsai JW (2010) Comparison of Surgisis, AlloDerm, and Vicryl woven mesh grafts for abdominal wall defect repair in an animal model. Aesth Plast Surg 34:290–296

    Article  Google Scholar 

  15. White AC, Hayat CS, Kimball KT (1987) Effects of lipophilic tetracyclines against Giardia lamblia. J Infect Dis 28:781–787

    Google Scholar 

  16. Sezaki M, Inouye S, Kondo S (1992) A new tetracycline antibiotic with antitumor activity. I. Taxonomy and fermentation of the producing strain, isolation and characterization of SF-2575. J Antibiotics 45:320–324

    Article  Google Scholar 

  17. Flanigan TP, Soave R (1991) Plasmodium falciparum growth and the effects of chlortetracycline. Clin Infect Dis 63:388–392

    Google Scholar 

  18. Castro MM, Tanus-Santos JE (2013) Inhibition of matrix metalloproteinases (MMPs) as a potential strategy to amelioratehypertension-induced cardiovascular alterations. Curr Drug Targets 14:335–343

    CAS  PubMed  Google Scholar 

  19. Antonio RC, Ceron CS, Rizzi E, Coelho EB, Tanus-Santos JE, Gerlach RF (2014) Antioxidant effect of doxycycline decreases MMP activity and blood pressure in SHR. Mol Cell Biochem 386:99–105

    Article  CAS  PubMed  Google Scholar 

  20. Wysocki AB, Staiano-Coico L, Grinnell F (1993) Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol 101:64–68

    Article  CAS  PubMed  Google Scholar 

  21. Woessner JF (1994) The family of matrix metalloproteinases. Ann N Y Acad Sci 732:11–21

    Article  CAS  PubMed  Google Scholar 

  22. Mignatti P, Rifkin DB, Welgus HG, Parks WC (1996) Proteinases and tissue remodeling. In: Clark RAF (ed) The molecular and cellular biology of wound repair, 2nd edn. Plenum Press, New York, pp 427–474

    Google Scholar 

  23. Murphy G, Willenbrock F, Crabbe T, O’Shea M, Ward R, Atkinson S, O’Connell J, Docherty A (1994) Regulation of matrix metalloproteinase activity. Ann N Y Acad Sci 732:31–41

    Article  CAS  PubMed  Google Scholar 

  24. Smith APS (2003) The role of MMPs in chronic wound edema. Podiatry Today 16:22–26

    Google Scholar 

  25. Wilcox JR, Covington DS, Paez N (2012) Doxycycline as a modulator of inflammation in chronic wounds. Wounds 24:339–349

    PubMed  Google Scholar 

  26. Ryan ME, Ashley RA (1998) How do tetracyclines work? Adv Dent Res 12:149–151

    Article  CAS  PubMed  Google Scholar 

  27. Lorenzl S, Albers DS, Narr S, Chirichigno J, Beal MF (2002) Expression of MMP-2, MMP-9, and MMP-1 and their endogenous counterregulators TIMP-1 and TIMP-2 in postmortem brain tissue of Parkinson’s disease. Exp Neurol 178:13–20

    Article  CAS  PubMed  Google Scholar 

  28. Guedez L, Courtemanch L, Stetler-Stevenson M (1998) Tissue inhibitor of metalloproteinase (TIMP)-1 induces differentiation and an antiapoptotic phenotype in germinal center B cells. Blood 92:1342–1349

    CAS  PubMed  Google Scholar 

  29. Guimaraes DA, Rizzi E, Ceron CS, Oliveira AM, Oliveira DM, Castro MM, Tirapelli CR, Gerlach RF, Tanus-Santos JE (2011) Doxycycline dose dependently inhibits MMP-2-mediated vascular changes in 2K1C hypertension. Basic Clin Pharmacol Toxicol 108:318–325

    Article  CAS  PubMed  Google Scholar 

  30. Nagase N (2001) Substrate specificity of MMPs. In: Clendeninn NJ, Krzysztof A (eds) Cancer drug discovery and development: matrix metalloproteinase inhibitors in cancer therapy. Humana Press Inc., Totowa

    Google Scholar 

Download references

Acknowledgments

This research was supported by a grant from Davol, Inc., Warwick, Rhode Island. Timely help in the preparation and submission of the manuscript by Ms. Linda Combs is greatly appreciated.

Author information

Authors and Affiliations

  1. Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-222, Lexington, KY, 40536-0298, USA

    Job C. Tharappel, Jennifer W. Harris, Brittany A. Zwischenberger, Salomon M. Levy & J. Scott Roth

  2. Department of Biomedical Engineering, University of Kentucky College of Medicine, Lexington, KY, USA

    David A. Puleo

Authors
  1. Job C. Tharappel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer W. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brittany A. Zwischenberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Salomon M. Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David A. Puleo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Scott Roth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Scott Roth.

Ethics declarations

Disclosures

Drs. Tharappel, Harris, Zwischenberger, and Levy have no conflicts of interest or financial ties to disclose. Dr. Puleo receives Grant funding from the NIH (R01AR060964). Dr. Roth has received external grant funding from Davol, Inc. for the support of this study; he has also received external grant funding and consulting fees from CR Bard; he is on speaker bureaus for CR Bard and Ethicon; and he is a Board member of the Musculoskeletal Transplant Foundation.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tharappel, J.C., Harris, J.W., Zwischenberger, B.A. et al. Doxycycline shows dose-dependent changes in hernia repair strength after mesh repair. Surg Endosc 30, 2016–2021 (2016). https://doi.org/10.1007/s00464-015-4434-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00464-015-4434-0

Keywords

Search

Navigation