Burst Release of Antibiotics Combined with Long-Term Release of Silver Targeting Implant-Associated Infections: Design, Characterization and in vitro Evaluation of Novel Implant Hybrid Surface

Implant-associated infections represent a serious risk in human medicine and can lead to complications, revisions and in worst cases, amputations. To target these risks, the objective was to design a hybrid implant surface that allows a local burst release of antibiotics combined with long-term antimicrobial activity based on silver. The efficacy should be generated with simultaneous in vitro cytocompatibility. The investigations were performed on titanium K-wires and plates and gentamicin was selected as an illustrative antibiotic. A gentamicin depot (max 553 µg/cm(2)) was created on the surface using laser structuring. The antibiotic was released within 15 min in phosphate buffered saline (PBS) or agar medium. Metallic silver particles (4 µg/cm(2)) in a titanium dioxide layer were deposited using plasma vapor deposition (PVD). About 16% of the silver was released within 28 days in the agar medium. The local efficacy of the incorporated silver was demonstrated in a direct contact assay with a reduction of more than 99.99% (Escherichia coli). The local efficacy of the hybrid surface was confirmed in a zone of inhibition (ZOI) assay using Staphylococcus cohnii. The biocompatibility of the hybrid surface was proven using fibroblasts and osteoblasts as cell systems. The hybrid surface design seems to be promising as treatment of implant-associated infections, considering the achieved amount and release behavior of the active ingredients (gentamicin, silver). The generated in vitro results (efficacy, biocompatibility) proofed the concept. Further in vivo studies will be necessary translate the hybrid surface towards clinical applied research.