Naturally Derived Anti-Inflammatory and Antibacterial Coatings for Surgical Implants

摘要

The evolution of surgical approaches and procedures over the past century is remarkable. The brutality and risks associated with operations has substantially decreased, whereas the procedures themselves became safe and efficient. Nevertheless, none of the surgical procedures is completely safe, reliable and painless, which often leads to the patients experiencing post-operative discomforts. These discomforts are usually resolved within several days after the operation, and do not require any additional prophylaxes or treatments. However, in some cases, surgeries are followed by post-operative complications that cannot be resolved without additional medical attention. Shock, hemorrhage, deep vein thrombosis, pulmonary complications, urinary retention, reaction to anesthesia are among the most devastating post-surgical complications. However, the most important ones are infections and chronic pain. The emergence of these complications becomes more acute when surgical implants are used during the operation. Implant-associated complications often require specific medical treatment; in some cases, additional surgery or implant removal is necessary to resolve the complication. All these negatively affect patients' quality of life and put an additional economic pressure on a healthcare system. Therefore, the development of approaches to decrease the burden of surgical implant-associated complications, in particular chronic pain and infections, is an important objective and was addressed in the present study.;The first part of the dissertation is focused on the post-surgical infections. We addressed this problem in the example of orthopaedic Kirchner wires, bearing in mind high incidence rate of the pin-site infections, which can reach up to 100% for longer implant residence times. Therefore, novel approaches to prevention of microbial infections after insertion of orthopedic external fixators are in great demand. Monolaurin is an antimicrobial agent with known safety record, broadly used in food and cosmetic industries; however, its use in antimicrobial coatings of medical devices has not been studied in much detail. Here, we report the use of monolaurin as an antibacterial coating on external fixators for the first time. The monolaurin-coated Kirschner wires (K-wires) showed excellent antibacterial properties against three different bacterial strains - Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis. Both planktonic and adherent bacteria were completely eliminated, when brought in contact with monolaurin-coated K-wires. At the same time, monolaurin-coated K-wires did not show any observable cytotoxicity with mouse osteoblast cell cultures. Overall, monolaurin-coated K-wires could be promising as potent antimicrobial materials for orthopaedic surgery.;In the second part of the dissertation we address post-operative chronic pain in the example of hernia repair meshes. First, we focused on studying the mechanism of the development of post-hernioplasty chronic pain. Despite the relative safety of the procedure, hernia repairs are often associated with chronic post-operative pain. While this complication has been linked among others to mesh deterioration, details of the processes that lead this deterioration are still unknown. Here, we aimed to bridge this gap by analyzing the chemical, physical and structural alterations in hernia repair meshes exposed to oxidative stress in vitro. We developed a methodology to characterize effect of oxidation stress on structure and properties of polymeric hernia repair meshes. It was shown that structural changes in polypropylene meshes exposed to oxidative stress may involve formation of cross-links between the polymer chains, chain scissions, and hydrogen bonds between the carboxyl groups, which are formed in the material during the oxidation. These effects result in mesh stiffening, ultimately leading to chronic post-operative pain. Moreover, we demonstrated that Composix(TM) meshes are more vulnerable to the oxidative stress when compared with UltraProRTM meshes.;Consequently, we focused on coating polymeric hernia meshes with anti-inflammatory agents in an attempt to mitigate the oxidative stress and improve long-term outcomes of the surgery. In particular, polypropylene hernia repair meshes coated with vitamin E (alpha-tocopherol), a known antioxidant, were prepared and characterized. The adsorption isotherm of vitamin E on the mesh was characterized and a release profile study yielded a promising results, showing sustained release of the drug over a 10-day period. An animal study was conducted, and histological analysis 5 weeks after implantation exhibited a reduced host tissue response for a modified mesh as compared to a plain mesh, as evidenced by a higher mature collagen to immature collagen ratio, as well as lower level of fatty infiltrates, neovascularization and fibrosis in the case of modified mesh. These results support the use of alpha-tocopherol as a potential coating in attempt to reduce the extent of post-operative inflammation, and thereby improve long-term outcomes of hernioplasty.