Doxycycline alters collagen composition following ventral hernia repair.

Job C Tharappel, Jennifer W Harris, Crystal Totten, Brittany A Zwischenberger, John S Roth
Author Information
  1. Job C Tharappel: Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-225, Lexington, KY, 40536-0298, USA.
  2. Jennifer W Harris: Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-225, Lexington, KY, 40536-0298, USA.
  3. Crystal Totten: Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-225, Lexington, KY, 40536-0298, USA.
  4. Brittany A Zwischenberger: Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-225, Lexington, KY, 40536-0298, USA.
  5. John S Roth: Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-225, Lexington, KY, 40536-0298, USA. s.roth@uky.edu.

Abstract

BACKGROUND: doxycycline, a nonspecific metalloproteinase (MMP) inhibitor, has been demonstrated to impact the strength of the polypropylene (PP) mesh-repaired hernia with an increase in the deposition of collagen type 1. The impact of doxycycline with porcine acellular dermal matrices (PADM) is unknown; therefore, we evaluated the impact of doxycycline administration upon hernia repair with PP and PADM mesh.
METHODS: Sprague-Dawley rats weighing ~400 g underwent laparotomy with creation of a midline ventral hernia. After a 27-day recovery, animals were randomly assigned to four groups of eight and underwent intraperitoneal underlay hernia repair with either PP or PADM. Groups were assigned to daily normal saline (S) or daily doxycycline in normal saline 10 mg/kg (D) via oral gavage for 8 weeks beginning 24 h preoperatively. Animals were euthanized at 8 weeks and underwent tensiometric testing of the abdominal wall and western blot analyses for collagen subtypes and MMPs.
RESULTS: Thirty-two animals underwent successful hernia creation and repair with either PADM or PP. At 8 weeks, 15 of 16 PP-implanted animals survived with only 12 of 16 PADM-implanted animals surviving. There were no differences in the mesh to fascial interface tensiometric strength between groups. Densitometric counts in the PADM-D group demonstrated increased collagen type 1 compared to PP-S (PADM-D [1286.5], PADM-S [906.9], PP-S [700.4], p = 0.037) and decreased collagen type 3 compared to PP-S (PADM-D [7446.9], PADM-S [8507.6], PP-S [11,297.1], p = 0.01). MMP-9 levels were increased in PADM-D (PP-S vs. PADM-D, p = 0.04), while MMP-2 levels were similar between PADM-D and PADM-S, respectively.
CONCLUSIONS: Collagen type 1 deposition at the mesh to fascial interface is enhanced following administration of doxycycline in ventral hernia repairs with porcine acellular dermal matrices. doxycycline administration may have implications for enhancing hernia repair outcomes using biologic mesh.

Keywords

References

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MeSH Term

Abdominal Wall
Acellular Dermis
Animals
Anti-Bacterial Agents
Collagen
Collagen Type I
Collagen Type III
Disease Models, Animal
Doxycycline
Hernia, Ventral
Herniorrhaphy
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Random Allocation
Rats
Rats, Sprague-Dawley
Surgical Mesh
Wound Healing

Chemicals

Anti-Bacterial Agents
Collagen Type I
Collagen Type III
Collagen
Matrix Metalloproteinase 2
Mmp2 protein, rat
Matrix Metalloproteinase 9
Mmp9 protein, rat
Doxycycline

Word Cloud

Created with Highcharts 10.0.0herniaPADM-DcollagenrepairPP-SDoxycyclinePPtypedoxycyclinePADMmeshunderwentanimalsimpact1administrationventral8 weeksPADM-Sp = 0metalloproteinasedemonstratedstrengthdepositionporcineacellulardermalmatricescreationassignedgroupseitherdailynormalsalinetensiometric16fascialinterfaceincreasedcompared9]levelsCollagenfollowingBACKGROUND:nonspecificMMPinhibitorpolypropylenemesh-repairedincreaseunknownthereforeevaluateduponMETHODS:Sprague-Dawleyratsweighing~400 glaparotomymidline27-dayrecoveryrandomlyfoureightintraperitonealunderlayGroupsS10 mg/kgDviaoralgavagebeginning24 hpreoperativelyAnimalseuthanizedtestingabdominalwallwesternblotanalysessubtypesMMPsRESULTS:Thirty-twosuccessful15PP-implantedsurvived12PADM-implantedsurvivingdifferencesDensitometriccountsgroup[12865][906[7004]037decreased3[7446[85076][112971]01MMP-9vs04MMP-2similarrespectivelyCONCLUSIONS:enhancedrepairsmayimplicationsenhancingoutcomesusingbiologicalterscompositionHerniaMatrixMesh

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