Preclinical bioassay of a novel antibacterial mesh for the repair of abdominal hernia defects.

Abstract

In hernia surgery, soaking of meshes in antibiotics before implantation is a prophylactic strategy for minimizing the risk of infection while providing minimal, local, drug doses. This study describes the development and application of an antibacterial mesh coating comprising a carboxymethylcellulose gel loaded with rifampicin in a preclinical model of Staphylococcus aureus and S. epidermidis infection in rabbits. Antibacterial activity and cytocompatibility (with fibroblasts) of unloaded carboxymethylcellulose gel and 0.13 mg/mL rifampicin-carboxymethylcellulose gel were assessed in vitro. Then, partial abdominal wall defects (5 × 2 cm) were created in New Zealand white rabbits (n = 34), the wound inoculated with 0.25 mL of 10⁶ CFU Staphylococcus aureus/ S. epidermidis (n = 17 each), and the defect then repaired with a lightweight, monofilament, large pore polypropylene mesh either uncoated (n = 3) or coated with carboxymethylcellulose gel (n = 7) or rifampicin-carboxymethylcellulose gel (n = 7). By postoperative day 14, coating performance was evaluated by determining bacterial adhesion (via sonication), host tissue incorporation (via histology), macrophage response via immunostaining), and bloodstream drug diffusion (via high-performance liquid chromatography). In vitro, rifampicin-carboxymethylcellulose gel demonstrated great activity against Staphylococcus aureus/S. epidermidis, while being innocuous for fibroblasts. In vivo, rifampicin-carboxymethylcellulose gel-coated implants displayed full bacterial clearance and optimal tissue integration, irrespective of the strain of Staphylococcus. In contrast, uncoated and carboxymethylcellulose gel-coated implants exhibited macro/microscopic signs of infection and impaired tissue integration. Macrophage responses were less in rifampicin-carboxymethylcellulose gel implants than in uncoated mesh (Staphylococcus aureus/S. epidermidis; P < .01) and carboxymethylcellulose gel (S. epidermidis; P < .05) implants. Bloodstream levels of rifampicin were undetectable. Soaking meshes in rifampicin-carboxymethylcellulose gel inhibited effectively the bacterial adhesion to the mesh without compromising the tissue repair. This antibiotic gel constitutes an easy-to-use and effective prophylactic strategy that potentially reduce the prevalence of postoperative mesh infection.