Thermo-Responsive Antimicrobial Hydrogel for the In-Situ Coating of Mesh Materials for Hernia Repair

Abstract

The prophylactic coating of prosthetic mesh materials for hernia repair with antimicrobial compounds is commonly performed before implantation of the mesh in the abdominal wall. We propose a novel alternative, which is a rifampicin-loaded thermo-responsive hydrogel formulation, to be applied on the mesh after its implantation. This formulation becomes a gel in-situ once reached body temperature, allowing an optimal coating of the mesh along with the surrounding tissues. In vitro, the hydrogel cytotoxicity was assessed using rabbit fibroblasts and antimicrobial efficacy was determined against Staphylococcus aureus. An in vivo rabbit model of hernia repair was performed; implanted polypropylene meshes (5 × 2 cm) were challenged with S. aureus (106 CFU), for two study groups—unloaded (n = 4) and 0.1 mg/cm2 rifampicin-loaded hydrogel (n = 8). In vitro, antibacterial activity of the hydrogel lasted for 5 days, without sign of cytotoxicity. Fourteen days after implantation, meshes coated with drug-free hydrogel developed a strong infection and resulted in poor tissue integration. Coating meshes with the rifampicin-loaded hydrogel fully prevented implant infection and permitted an optimal tissue integration. Due to its great performance, this, degradable, thermo-responsive antimicrobial hydrogel could potentially be a strong prophylactic armamentarium to be combined with prosthesis in the surgical field.

Drug Release from Thermo‐Responsive Polymer Brush Coatings to Control Bacterial Colonization and Biofilm Growth on Titanium Implants

“…Recently, Perez-Köhler et al developed a thermo-responsive rifampicin-loaded PNIPAM hyaluronan derivative (HApN) hydrogel to coat polypropylene mesh materials. [29] At 37°C, an effective drug release showed strong anti-staphylococcal activity both in vitro and in vivo. However, high fatigue strength implant materials such as titanium or stainless steel with covalently attached thermo-responsive polymer coating as an antimicrobial implant device have not yet studied to the best of our knowledge.…”

Functionalized Strategies and Mechanisms of the Emerging Mesh for Abdominal Wall Repair and Regeneration

“…Recently, the thermoresponsive rifampicin-loaded hydrogel has been applied for the in situ coating of mesh. This formulation becomes a gel in situ once it reached body temperature, allowing an optimal coating of the mesh along with the surrounding tissues to fully prevent mesh infection and permit improved tissue integration . Similarly, the smart mesh that integrating regulators with nature-derived matrices is promising for antiadhesive application.…”

“…This formulation becomes a gel in situ once it reached body temperature, allowing an optimal coating of the mesh along with the surrounding tissues to fully prevent mesh infection and permit improved tissue integration. 176 Similarly, the smart mesh that integrating regulators with nature-derived matrices is promising for antiadhesive application. It works by intervening in the fibrin deposited process at different phases by releasing chemokines, cytokines, antibiotics, or antibodies with matrix degradation or by activating the sensors to trigger the release (Figure 8C).…”

Latest Trends on the Attenuation of Systemic Foreign Body Response and Infectious Complications of Synthetic Hernia Meshes

“…Despite the great outcomes, the antimicrobial coating carries the hazard of altering the morphological and biomechanical properties of the mesh, generating its limited clinical application. Perez-Kohler et al 95 use a thermoresponsive hyaluronic acid-derived hydrogel (HApN) loaded with antimicrobial agent, which is applied to the mesh surface after implanting it. Such stimulus-responsive polymer compounds can be polymerized in situ to form a hydrogel coating once it reaches human body temperature, which not only fully prevented implant infection but also permitted an optimal coating along with the surrounding tissues without affecting the biomechanical characteristics of the mesh.…”