The holy grail of orthopedic implant design is to ward off both aseptic and septic loosening for long enough that the implant outlives the patient. Questing this holy grail is feasible only if orthopedic biomaterials possess a long list of functionalities that enable them to discharge the onerous task of permanently replacing the native bone tissue. Here, we present a rationally designed and additive manufacturing (AM) topologically ordered porous metallic biomaterial that is made from Ti-6Al-4V using selective laser melting and packs most (if not all) of the required functionalities into a single implant. In addition to presenting a fully interconnected porous structure and form-freedom that enables realization of patient-specific implants, the biomaterials developed here were biofunctionalized using plasma electrolytic oxidation to locally release both osteogenic (i.e. strontium) and antibacterial (i.e. silver ions) agents. The same single-step biofunctionalization process also incorporated hydroxyapatite into the surface of the implants. Our measurements verified the continued release of both types of active agents up to 28 days. Assessment of the antibacterial activity in vitro and in an ex vivo murine model demonstrated extraordinarily high levels of bactericidal effects against a highly virulent and multidrug-resistant Staphylococcus aureus strain (i.e. USA300) with total eradication of both planktonic and adherent bacteria. This strong antibacterial behavior was combined with a significantly enhanced osteogenic behavior, as evidenced by significantly higher levels of alkaline phosphatase (ALP) activity compared with non-biofunctionalized implants. Finally, we discovered synergistic antibacterial behavior between strontium and silver ions, meaning that 4–32 folds lower concentrations of silver ions were required to achieve growth inhibition and total killing of bacteria. The functionality-packed biomaterial presented here demonstrates a unique combination of functionalities that make it an advanced prototype of future orthopedic biomaterials where implants will outlive patients.@en

Background. In the coming years, the use of orthopaedic implants is expected to increase and subsequently the need to encounter the problems of poor osseointegration and implant-associated infection (IAI) is augmented. The unsuccessful implantation of an orthopaedic or dental implant has a considerable economic impact on the healthcare system and at the same time downgrades the quality of the patient’s life. Thus, the development of multifunctional surfaces that promote osseointegration and, at the same time, prevent IAI is needed. In addition, the advances in additively manufacturing techniques such as selective laser melting (SLM) enables the fabrication of customised implants with mechanical properties matching those of native bone tissue. Therefore, this study aimed to investigate the synthesis of multifunctional surfaces on additively manufactured Ti6Al4V implants by the incorporation of strontium and silver nanoparticles (Ag NP). Methods. Porous Ti6Al4V implants were designed and synthesised by the additive manufacturing process SLM. Thereafter, a titanium oxide layer was formed on the surface of the implants by plasma electrolytic oxidation (PEO) with electrolytes loaded with different concentrations of strontium and Ag NP in order to assess the effect of strontium on the biological performance and biomaterial properties. The surface morphology was analysed by scanning electron and optical microscopy, the chemical composition by energy dispersive X-ray spectroscopy (EDS) and the phase composition by X‑ray diffraction (XRD). In addition, the strontium and silver ion release were studied up to 1 month by inductively coupled plasma optical emission spectrometry (ICP-OES). The response of human mesenchymal stem cells (hMSC) on the multifunctional surfaces was evaluated by the metabolic and alkaline phosphatase (ALP) activity. Furthermore, the leachable antibacterial properties were assessed against methicillin-resistant Staphylococcus aureus (MRSA). Results. The surface of additively manufactured titanium implants was modified by PEO resulting in a TiO2 layer with interconnected porosity in which strontium in different concentrations and Ag NP were incorporated. The presence of strontium and Ag NP was confirmed by EDS and the release of strontium and silver ions after 1 month by ICP-OES. Additionally, XRD analysis revealed the formation of hydroxyapatite and strontium calcium phosphate phases. Furthermore, the addition of strontium revealed a biphasic effect on the metabolic and ALP activity of hMSCs. At lower concentration, the metabolic and ALP activity were hindered, while at high concentration no beneficial effect was observed. The antibacterial leaching activity test showed that the inhibition area was enlarged after the incorporation of strontium. Conclusions. The surface of porous additively manufactured implants was successfully modified by PEO incorporating strontium and Ag NP. Furthermore, the weight percentage of strontium incorporated in the TiO2 layer was proportional to strontium concentration in the electrolyte while strontium phases formed at higher strontium concentrations. Moreover, the antibacterial properties were not hindered by the addition of strontium. Although the results did not show an enhancement of the biological performance in terms of biocompatibility and osteogenic activity, further research about the optimal concentration of strontium could improve the biological performance of additively manufactured implants.