title: Doxycycline alters collagen composition following ventral hernia repair.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-225, Lexington, KY, 40536-0298, USA.
authors: Job C
authors: JC
authors: Tharappel
authors: Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-225, Lexington, KY, 40536-0298, USA.
authors: Jennifer W
authors: JW
authors: Harris
authors: Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-225, Lexington, KY, 40536-0298, USA.
authors: Crystal
authors: C
authors: Totten
authors: Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-225, Lexington, KY, 40536-0298, USA.
authors: Brittany A
authors: BA
authors: Zwischenberger
authors: 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.
authors: John S
authors: JS
authors: Roth
mesh_terms: D034861:Abdominal Wall / Q000601:surgery; D062088:Acellular Dermis / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology*; D006555:Hernia, Ventral / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D059685:Herniorrhaphy; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013526:Surgical Mesh; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D024042:Collagen Type I; D024061:Collagen Type III; D003094:Collagen; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D004318:Doxycycline
keywords: Collagen; Doxycycline; Hernia; Matrix metalloproteinase; Mesh