Flame nanoengineering of antibiofilm surfaces for medical implants

Abstract: Infection of bone implants is a major problem in the Healthcare sector today. Over the last years it has started to become more problematic due to biofilm formation and increasing antimicrobial resistance (AMR). A biofilm provides mechanical shielding to bacteria by ingulfing them leading to a less effective treatment with antibiotics. AMR of bacteria in general increased over the last decade due to ineffective overuse and complements the natural resistance given by the biofilm. Untreated infections can cause multiple revision surgeries and might introduce life threating diseases. Currently, nanostructured implant coatings raise a lot of attention mainly due to the superior antibacterial efficiency of metal nanomaterials. Nanosilver is by far the most investigated candidate of those because of its multi-effective antibacterial actions. Silver ions (Ag+) released from such nanocoatings (NCs) kill bacteria on contact and prevent biofilm formation. However, those ions and NPs released from coatings were reported to be toxic towards mammalian cells in high doses. Hence, it is crucial to increase the biocompatibility by the design of a multifunctional coating with bioactive support materials. This can help to induce bone growth and the successful integration of the implant. Many nano manufacture processes found in the literature excel in those attributes but lack a reproducible upscale potential. In this thesis flame spray pyrolysis (FSP) was exploited to synthesis a reproducible and scalable NC for implants with osseointegration potential and antibiofilm properties. In Paper Ⅰ the antibiofilm potential of nanosilver was investigated systemically and it was evident that smaller NPs within the coating structure, a thicker coating and higher Ag contents lead to improved antibiofilm properties. Furthermore, a co-incubation set-up indicated that Ag+ ions are the major driving force for bacterial inhibition. With the addition of nanostructured bioglass (BG) in Paper Ⅱ, a hydroxyapatite (HA) formation could be observed in vitro and osteogenic markers for early bone growth could be identified while maintaining an antibiofilm behavior. The upscaling ability of FSP was demonstrated by depositing a NC on a commercially available screw. In Paper Ⅲ a smart and responsive surface coating was designed by depositing an Ag/gold (Au) nanoalloy coating. During physiological conditions the potential toxic Ag+ ion release was significantly lower compared to a corresponding nanosilver sample. In the acid pH environment of an early biofilm structure, the alloy leached and inhibited the same amount colony forming units (CFU) compared to the nanosilver sample. This indicates indirectly an increased triggered Ag+ release as the result of a pH change in the biofilm microenvironment and could be important to avoid any uncontrolled ion release with the accumulation in the body. It was possible to synthesize this multifunctional nanostructured surface coating with a reproducible and scalable method and validation in vivo is the next logical step. If successful, sufficient amounts of coating could be produced and deposited on more complex structures for clinical studies. This is a crucial advantage over other nano synthesis methods.

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