Low-density polypropylene meshes coated with resorbable and biocompatible hydrophilic polymers as controlled release agents of antibiotics Mar Fernandez-Gutierrez a,⇑ , Enrique Olivares b , Gemma Pascual b , Juan M. Bellon b , Julio San Román a a Research, ICTP-CSIC, Biomaterials, Juan de la Cierva 3, Madrid 28006, Spain b University of Alcala, Alcala de Henares-CIBER-BBN, Spain article info Article history: Received 20 June 2012 Received in revised form 3 December 2012 Accepted 7 December 2012 Available online 20 December 2012 Keywords: Antibacterial Copolymer Infection In vitro test In vivo test abstract The application of bioactive meshes in abdominal surgery for the repair of hernias is an increasing clinical activity in a wide sector of the population. The main secondary effect is the appearance of infections from bacteria, specifically Staphylococcus aureus and S. epidermidis. This paper describes the development and application of low-density polypropylene meshes coated with a biocompatible and resorbable polymer as a controlled release system of the antibiotic vancomycin. The polymeric coating (a non-cross-linked copolymer of 2-hydroxyethyl methacrylate and 2-acrylamido-2-methylpropanesulfonic acid) has a thick- ness of 14–15 lm and contains 0.32 mg cm 2 of the antibiotic vancomycin. The in vitro experiments demonstrate the excellent inhibitory character of the coated meshes loaded with the antibiotic, following the standard protocol of inhibition of halo in agar diffusion test. This inhibitory effect is maintained for a relatively long period (at least 14 days) with a low concentration of antibiotic. The acrylic polymer sys- tem regulates the release of the antibiotic with a rate of 24 lgh 1 , due to its slow dissolution in the med- ium. Experiments in vivo, based on the implantation of coated meshes, demonstrate that the system controls the infection in the animal (rabbits) for at least 30 days. The concentration of antibiotic in the blood stream of the rabbits was below the detection limit of the analytical technique (<1–2 lg ml 1 ), which demonstrates that the antibiotic is released in the local area of the implant and remains concen- trated at the implantation site, without diffusion to the blood stream. The systems can be applied to other medical devices and implants for the application of new-generation antibiotics in a controlled release and targeted applications. Ó 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. 1. Introduction Hernia repair is one of the most frequently performed surgical procedures—midline laparotomy produces incisional hernias at a rate of 2–9% [1]; the placement of a synthetic mesh is the standard technique of reinforcement. The application of a polypropylene mesh by Uscher [2] was considered one of the greatest advances in this field. Surgical techniques have progressed, through the application of advanced designs and materials such as synthetic meshes [3]. The function of meshes is to provide mechanical clo- sure to the defect and to induce strong scar tissue with good bio- compatibility and low cell adhesion [4]. There is a variety of meshes made of synthetic resorbable materials, and non-resorbable or organic material derived from human or pig tissues. Meshes of polypropylene (PP) with controlled net size have been applied extensively because of polypropylene’s high biocompatibility, inert character, morphology and other properties [5]. Clinical complica- tions as a result of the application of surgical meshes include inflammatory response, irregular or low formation of scar tissue and, most importantly, the appearance of infections; these have been estimated to occur in about 3–4% of inguinal hernias and 6–10% of incisional hernias [6]. This is relevant because of the con- siderable number of surgical procedures. In the USA alone, infec- tion affects more than 30,000 patients a year with inguinal hernias and more than 3000 patients a year with incisional hernias. The more common microorganisms involved in these bacterial infections are Staphylococcus aureus (Sa) and S. epidermidis (Se), to- gether with Gram-negative species including Escherichia coli and Pseudomonas aeruginosa [7]. The adhesion of bacteria to the surface of a biomaterial is a cru- cial step in the pathogenesis of infection. Some microorganisms are capable of forming a biofilm on the mesh that protects the immune system and the action of the antibiotics [8]. Once the mesh has been infected, no treatment is possible and it is necessary to 1742-7061/$ - see front matter Ó 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.actbio.2012.12.012 ⇑ Corresponding author. Tel.: +34 916518806x212; fax: +34 915644853. E-mail addresses: marf@ictp.csic.es, fermargu@gmail.com (M. Fernandez- Gutierrez). Acta Biomaterialia 9 (2013) 6006–6018 Contents lists available at SciVerse ScienceDirect Acta Biomaterialia journal homepage: www.elsevier.com/locate/actabiomat