Combination of low-temperature plasma processes in the design of a novel ampicillin-loaded surgical mesh for hernia repair

摘要

Introduction: One of the new trends in biomaterials research is to deliver active compounds locally in the surgical site from the medical device. One way to manage post-operatory infections associated with mesh implants in abdominal hernia repair surgery can be the loading of antibiotics to the surgical meshes. Plasma treatment of polymer fibers has been commonly employed to tailor surface adhesion and wetting properties by changing the surface chemical composition. Appropriate selection of the plasma source enables the introduction of diverse functional groups on the target surface to improve wettability, biocompatibility or to allow subsequent covalent immobilization or physical adsorption of various molecules such as dyestuffs, pharmaceutical or cosmetic active principles. Plasma can also be used for the deposition of polymer thin coatings by plasma polymerization process. By modifying the process parameters of the plasma and the precursor, different kinds of biocompatible coatings can be produced, from cell-adhesive to antifouling coatings. Materials and Methods: A polypropylene (PP) mesh was functionalized in air plasma at atmospheric pressure by corona plasma (380W. 1.9A, ＜7.0s), before its loading with ampicillin (AMP) from an aqueous solution. Plasma polymerization of the AMP-loaded mesh was performed (0.4mbar, 200W, 13.56MHz, 2h) with Ar carrier gas, using Tetraglyme as precursor to obtain a PEG-like thin coating of the mesh. Characterization techniques such as AFM, SEM, XPS, etc. were employed to determine the effect of plasma treatment on the surface topography and chemical composition. To evaluate the biological behavior of the modified meshes, in vitro assays regarding cell proliferation, morphology, viability, chemotaxis and cell adhesion were carried out on the materials using NIH-3T3 fibroblasts and THP1 monocytes. Antibacterial assays and in vitro release experiments of the AMP from the fiber to an isotonic liquid media were also carried out. Results and Discussion: Combination of plasma functionalization and polymerization in the design of this textile-based drug delivery system is fully justified by the distinct effects produced by these two plasma treatments. As a first-step in the design of the AMP-loaded mesh, plasma fundionalization of the polymer surface with polar O-groups was used to modify the PP fiber surface at nanometric level. Surface wettability was improved due to the increased availability of chemical bonds with the introduction of new C-O and COOH functional groups. This was employed for the subsequent attachment of AMP allowing an increase of its loading as function of the plasma treatment time. The chemical and morphological changes on the surface of PP fibers lead to a 3-fold improvement of the AMP loading in the meshes after only 3.5s of plasma treatment. However, this plasma treatment and the subsequent loading of AMP on the PP fibers were related with lower fibroblast adhesion, altered morphology and enhanced chemotaxis. Thus, plasma polymerization was used as dry method to create a thin coating of PEG with the aim of keeping the high antibiotic loadings obtained with plasma fundionalization and to maintain essentially unchanged fibroblast properties such as chemotaxis or adhesion with respect to untreated meshes, fulfilling the requirement of biocompatible device for the finished AMP-loaded mesh. Conclusions: Combination of plasma processes has been used to tailor the surface properties of PP meshes to obtain high loadings of AMP, maintaining the biological adhesion and the antibacterial activity of the current surgical meshes. Beyond the added value brought by the antibiotic loading of the mesh for its release directly to the surgical site, the use of plasma processes in the design of biomaterials brings an original approach to control simultaneously physical and chemical surface properties, but also regarding the treatment of the mesh without the use of any other chemicals for the binding of the active principle with the fiber.