title: Doxycycline administration improves fascial interface in hernia repair.
abstract: BACKGROUND
  Despite improvements in ventral hernia repair techniques, their recurrence rates are unacceptably high. Increased levels of matrix metalloproteinases (MMPs) and reduced collagen-1 to -3 ratios are implicated in incisional hernia formation. We have recently shown doxycycline treatment for 4 wk after hernia repair reduced MMP levels, significantly increased collagen-1 to -3 ratios, and increased tensile strength of repaired interface fascia. However, this increase was not statistically significant. In this study, we extended treatment duration to determine whether this would impact the tensile strength of the repaired interface fascia.
  
  
  METHODS
  Thirty-two male Sprague-Dawley rats underwent incision hernia creation and subsequent repair with polypropylene mesh. The animals received either saline (n = 16) or doxycycline (n = 16) beginning from 1 day before hernia repair until the end of survival time of 6 wk (n = 16) or 12 wk (n = 16). Tissue samples were investigated for MMPs and collagen subtypes using Western blot procedures, and tensiometric analysis was performed.
  
  
  RESULTS
  At both 6 and 12 wk after hernia repair, the tensiometric strength of doxycycline-treated mesh to fascia interface (MFI) tissue showed a statistically significant increase when compared with untreated control MFI. In both groups, collagen-1, -2, and -3 ratios were remarkably increased in doxycycline-treated MFI. At 6 wk, the doxycycline-treated MFI group showed a significant decrease in MMP-2, an increase in MMP-3, and no change in MMP-9. At 12 wk, MMP-9 showed a remarkable reduction, whereas MMP-2 and -3 protein levels increased in the doxycycline-treated MFI group.
  
  
  CONCLUSIONS
  Doxycycline administration results in significantly improved strength of repaired fascial interface tissue along with a remarkable increase in collagen-1, -2, and -3 ratios.
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, Kentucky.
authors.forename: Job C
authors.initials: JC
authors.lastname: Tharappel
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, Kentucky.
authors.forename: Curtis E
authors.initials: CE
authors.lastname: Bower
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, Kentucky.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Whittington Harris
authors.affiliation: Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Ramineni
authors.affiliation: Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky.
authors.forename: David A
authors.initials: DA
authors.lastname: Puleo
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, Kentucky. Electronic address: s.roth@uky.edu.
authors.forename: J Scott
authors.initials: JS
authors.lastname: Roth
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D005205:Fascia / Q000187:drug effects* / Q000201:enzymology; D006555:Hernia, Ventral / Q000201:enzymology / Q000601:surgery*; D008297:Male; D045726:Metalloproteases / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055502:Secondary Prevention; D013718:Tensile Strength
chemical_list: D000900:Anti-Bacterial Agents; D024042:Collagen Type I; D024061:Collagen Type III; D045726:Metalloproteases; D004318:Doxycycline
keywords: Collagen; Doxycycline; Hernia; Matrix metalloproteinase