Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the treatment of IAI. The focus has, therefore, shifted towards the development of implants with intrinsic antibacterial activity to prevent the occurrence of infection. The use of Ag, Cu, and Zn has gained momentum as these elements display strong antibacterial behavior and target a wide spectrum of bacteria. In order to incorporate these elements into the surface of titanium-based bone implants, plasma electrolytic oxidation (PEO) has been widely investigated as a single-step process that can biofunctionalize these (highly porous) implant surfaces. Here, we present a systematic review of the studies published between 2009 until 2020 on the biomaterial properties, antibacterial behavior, and biocompatibility of titanium implants biofunctionalized by PEO using Ag, Cu, and Zn. We observed that 100% of surfaces bearing Ag (Ag-surfaces), 93% of surfaces bearing Cu (Cu-surfaces), 73% of surfaces bearing Zn (Zn-surfaces), and 100% of surfaces combining Ag, Cu, and Zn resulted in a significant (i.e., >50%) reduction of bacterial load, while 13% of Ag-surfaces, 10% of Cu-surfaces, and none of Zn or combined Ag, Cu, and Zn surfaces reported cytotoxicity against osteoblasts, stem cells, and immune cells. A majority of the studies investigated the antibacterial activity against S. aureus. Important areas for future research include the biofunctionalization of additively manufactured porous implants and surfaces combining Ag, Cu, and Zn. Furthermore, the antibacterial activity of such implants should be determined in assays focused on prevention, rather than the treatment of IAIs. These implants should be tested using appropriate in vivo bone infection models capable of assessing whether titanium implants biofunctionalized by PEO with Ag, Cu, and Zn can contribute to protect patients against IAI.

The effects of substrate composition on oxide layer properties following plasma electrolytic oxidation under similar conditions have been evaluated for α-cpTi, α/β-Ti6Al7Nb, β-Ti35Zr10Nb and β-Ti45Nb alloys. All oxidised surfaces revealed enhanced wettability, surface free energy and roughness relative to the non-oxidised surfaces. Nevertheless, the resultant oxides differed with respect to average pore size, pores density, layer chemistry and phase composition. The β-titanium alloys developed oxides with a larger average pore size and lower pore density relative to the α-cpTi and α/β-Ti6Al7Nb substrates. Anatase dominated the oxide layer formed on α-cpTi and β-Ti45Nb alloys, a mixture of anatase and rutile was present on the oxidised α/β-Ti6Al7Nb surface, whereas Ti₂ZrO₆ was the only phase detected on the oxidised surface of the β-Ti35Zr10Nb alloy.

In this study, a porous oxide layer was formed on the surface of 316L stainless steel (SS) by combining Ti magnetron sputtering and plasma electrolytic oxidation (PEO) with the aim to produce a polymer-free drug carrier for drug eluting stent (DES) applications. The oxidation was performed galvanostatically in Na₃PO₄ electrolyte. The surface porosity, average pore size and roughness varied with PEO treatment duration, and under optimum conditions, the surface showed a porosity of 7.43%, an average pore size of 0.44 µm and a roughness (Ra) of 0.34 µm. The EDS analyses revealed that the porous layer consisted of Ti, O and P. The cross-sectional morphology evidenced a double-layer structure, with a porous titania surface and an un-oxidized dense Ti film towards the interface with 316L SS. After the PEO treatment, wettability and surface free energy increased significantly. The results of the present study confirm the feasibility of forming a porous TiO₂ layer on stainless steel by combining sputtering technology and PEO. Further, the resultant porous oxide layer has the potential to be used as a drug carrier for DES, thus avoiding the complications associated with the polymer based carriers.

Hearing loss is a highly prevalent multifactorial disorder affecting 20% of the global population. Current treatments using the systemic administration of drugs are therapeutically ineffective due to the anatomy of the cochlea and the existing blood–labyrinth barrier. Local drug delivery systems can ensure therapeutic drug concentrations locally while preventing adverse effects caused by high dosages of systemically administered drugs. Here, we aimed to design, fabricate, and characterize a local drug delivery system for the human cochlea. The design was relevant to the size of the human ear, included two different shapes, and incorporated two different microporous structures acting as reservoirs for drug loading and release. The four cochlear implant designs were printed using the two-photon polymerization (2PP) technique and the IP-Q photoresist. The optimized 2PP process enabled the fabrication of the cochlear implants with great reproducibility and shape fidelity. Rectangular and cylindrical implants featuring cylindrical and tapered tips, respectively, were successfully printed. Their outer dimensions were 0.6 × 0.6 × 2.4 mm³ (L × W × H). They incorporated internal porous networks that were printed with high accuracy, yielding pore sizes of 17.88 ± 0.95 μm and 58.15 ± 1.62 μm for the designed values of 20 μm and 60 μm, respectively. The average surface roughness was 1.67 ± 0.24 μm, and the water contact angle was 72.3 ± 3.0°. A high degree of polymerization (~90%) of the IP-Q was identified after printing, and the printed material was cytocompatible with murine macrophages. The cochlear implants designed and 3D printed in this study, featuring relevant sizes for the human ear and tunable internal microporosity, represent a novel approach for personalized treatment of hearing loss through local drug delivery.

Implant-associated infections are highly challenging to treat, particularly with the emergence of multidrug-resistant microbials. Effective preventive action is desired to be at the implant site. Surface biofunctionalization of implants through Ag-doping has demonstrated potent antibacterial results. However, it may adversely affect bone regeneration at high doses. Benefiting from the potential synergistic effects, combining Ag with other antibacterial agents can substantially decrease the required Ag concentration. To date, no study has been performed on immobilizing both Ag and Fe nanoparticles (NPs) on the surface of additively manufactured porous titanium. We additively manufactured porous titanium and biofunctionalized its surface with plasma electrolytic oxidation using a Ca/P-based electrolyte containing Fe NPs, Ag NPs, and the combinations. The specimen’s surface morphology featured porous TiO₂ bearing Ag and Fe NPs. During immersion, Ag and Fe ions were released for up to 28 days. Antibacterial assays against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa showed that the specimens containing Ag NPs and Ag/Fe NPs exhibit bactericidal activity. The Ag and Fe NPs worked synergistically, even when Ag was reduced by up to three times. The biofunctionalized scaffold reduced Ag and Fe NPs, improving preosteoblasts proliferation and Ca-sensing receptor activation. In conclusion, surface biofunctionalization of porous titanium with Ag and Fe NPs is a promising strategy to prevent implant-associated infections and allow bone regeneration and, therefore, should be developed for clinical application.