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



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.



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.



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.
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
JC
Tharappel
Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-222, Lexington, KY, 40536-0298, USA.
Jennifer W
JW
Harris
Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-222, Lexington, KY, 40536-0298, USA.
Brittany A
BA
Zwischenberger
Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-222, Lexington, KY, 40536-0298, USA.
Salomon M
SM
Levy
Department of Biomedical Engineering, University of Kentucky College of Medicine, Lexington, KY, USA.
David A
DA
Puleo
Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-222, Lexington, KY, 40536-0298, USA. jsroth2@uky.edu.
J Scott
JS
Roth
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015153:Blotting, Western; D024042:Collagen Type I / Q000187:drug effects / Q000378:metabolism; D024061:Collagen Type III / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology*; D005205:Fascia / Q000187:drug effects* / Q000378:metabolism; D006555:Hernia, Ventral / Q000601:surgery*; D059685:Herniorrhaphy / Q000379:methods*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D011126:Polypropylenes; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D013526:Surgical Mesh; D013537:Sutures; D013718:Tensile Strength / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D024042:Collagen Type I; D024061:Collagen Type III; D011126:Polypropylenes; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D004318:Doxycycline
Doxycycline; Extracellular matrix; Hernia repair; Matrix metalloproteinase