Doxycycline Alters Collagen Composition following Ventral Hernia Repair

Crystal Totten, Instructor, of, Surgery, Job C Tharappel, PhD, John S Roth, Professor, of, Surgery. University of Kentucky

Introduction: Doxycycline, a nonspecific metalloproteinase (MMP) inhibitor, has been previously demonstrated to impact the strength of the polypropylene (PP) mesh repaired hernia as well as increase deposition of Collagen 1 and 3 in the repair sites. The impact of doxycycline upon hernia repair with porcine acellular dermal matrices has not previously been studied. The current study evaluates the impact of doxycycline administration upon hernia repair with polypropylene mesh and a porcine acellular dermal matrix.

Methods: 400 gram Sprague Dawley rats were acclimated and subsequently underwent laparotomy with creation of a midline ventral hernia (VH). 27 days following hernia creation, animals were randomly assigned to four groups of 8 animals and underwent hernia repair with an intraperitoneal underlay with either PP or porcine acellular dermal matrix (PADM). Groups were assigned to administration of  daily normal saline (NS) or doxycycline 10mg/kg daily (D) via oral gavage for 8 weeks beginning 24 hours prior to hernia repair. The animals were euthanized at 8 weeks and underwent tensiometric testing of the abdominal wall, western blot analyses for collagen sub-types and matrix metalloproteinases.

Results: 32 animals underwent successful hernia creation and repair with either PADM or PP. All PP implanted animals survived 8 weeks and 13 PADM implanted animals survived 8 weeks (8 PADM-D, 5 PADM-S). There were no differences in the tensiometric strengths of the mesh to fascial interface between groups. Densitometric counts in PADM-D groups demonstrated increased Collagen 1 compared to PP-S (PADM-D [1286.5] PADM-S [906.9] ,PP-S [700.4] , P=0.037) and decreased Collagen 3 compared to PP-S (PADM-D [7446.9], PADM-S [8507.6], PP-S [11297.1], p=.01). Collagen 3 expression was reduced in PP-D compared to PADM-S (12177.6 vs. 14562.0, p =.04). There were no differences in Collagen 1 or Collagen 3 expression between PP-D and PP-S. 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.

Conclusion: Collagen 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 outcomes following hernia repair.

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