Design and preparation of Ti-xFe antibacterial titanium alloys based on micro-area potential difference.

Fe was selected as an alloying element for the first time to prepare a new antibacterial titanium alloy based on micro-area potential difference (MAPD) antibacterial mechanism. The microstructure, the corrosion resistance, the mechanical properties, the antibacterial properties and the cell biocompatibility have been investigated in detail by optical microscopy, scanning electron microscopy, electrochemical testing, mechanical property test, plate count method and cell toxicity measurement. It was demonstrated that heat treatment had a significant on the compressive mechanical properties and the antibacterial properties. Ti-xFe (x = 3,5 and 9) alloys after 850 °C/3 h + 550 °C/62 h heat treatment exhibited strong antimicrobial properties with an antibacterial rate of more than 90% due to the MAPD caused by the redistribution of Fe element during the aging process. In addition, the Fe content and the heat treatment process had a significant influence on the mechanical properties of Ti-xFe alloy but had nearly no effect on the corrosion resistance. All Ti-xFe alloys showed non-toxicity to the MC3T3 cell line in comparison with cp-Ti, indicating that the microzone potential difference had no adverse effect on the corrosion resistance, cell proliferation, adhesion, and spreading. Strong antibacterial properties, good cell compatibility and good corrosion resistance demonstrated that Ti-xFe alloy might be a candidate titanium alloy for medical applications.

Immunomodulatory effect of Ti-Cu alloy by surface nanostructure synergistic with Cu2+ release.

The inflammatory response induced by implant/macrophage interaction has been considered to be one of the vital factors in determining the success of implantation. In this study, TiCuNxOy coating with an immunomodulatory strategy was proposed for the first time, using nanostructured TiCuNxOy coating synthesized on Ti-Cu alloy by oxygen and nitrogen plasma-based surface modification. It was found that TiCuNxOy coating inhibited macrophage proliferation but stimulated macrophage preferential activation and presented an elongated morphology due to the surface nanostructure. The most encouraging discovery was that TiCuNxOy coating promoted the initial pro-inflammatory response of macrophages and then accelerated the M1-to-M2 transition of macrophages via a synergistic effect of fast-to-slow Cu2+ release and surface nanostructure, which was considered to contribute to initial infection elimination and tissue healing. As expected, TiCuNxOy coating released desirable Cu2+ and generated a favorable immune response that facilitated HUVEC recruitment to the coating, and accelerated proliferation, VEGF secretion and NO production of HUVECs. On the other hand, it is satisfying that TiCuNxOy coating maintained perfect long-term antibacterial activity (≥99.9%), mainly relying on Cu2O/CuO contact sterilization. These results indicated that TiCuNxOy coating might offer novel insights into the creation of a surface with immunomodulatory effects and long-term bactericidal potential for cardiovascular applications.

A high-hydrophilic Cu2O-TiO2/Ti2O3/TiO coating on Ti-5Cu alloy: Perfect antibacterial property and rapid endothelialization potential.

In order to make novel antibacterial Ti-Cu alloy more suitable for cardiovascular implant application, a Cu-containing oxide coating was manufactured on Ti-Cu alloy by plasma-enhanced oxidation deposition in plasma enhanced chemical vapor deposition (PECVD) equipment to further improve the antibacterial ability and the surface bioactivity. The results of X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and water contact angle indicated that a sustainably high-hydrophilic Cu2O-TiO2/Ti2O3/TiO coating with nano-morphology on Ti-5Cu was successfully constructed. The corrosion performance results showed that the coating enhanced the corrosion resistance while releasing more Cu2+, compared with Ti-5Cu. Antibacterial tests confirmed the perfect antibacterial property of the coating (R ≥ 99.9 %), superior to Ti-Cu alloy (R > 90 %). More delightfully, it was observed by phalloidin-FITC and DAPI staining that the coating improved the early adhesion of HUVEC cells mainly due to strong hydrophilicity and nano-morphology. It was demonstrated that the extract of the coated sample significantly promoted proliferation (RGR = 112 %-138 % after cultivation for 1 to 3 days) and migration of HUVEC cells due to the appropriate Cu2+ release concentration. Hemolysis assay and platelet adhesion results showed that the coating had excellent blood compatibility. All results suggested that the coating on Ti-Cu alloy might be a promising surface with the perfect antibacterial ability, blood compatibility and evident promoting endothelialization ability for the cardiovascular application.

Development of a low elastic modulus and antibacterial Ti-13Nb-13Zr-5Cu titanium alloy by microstructure controlling.

In order to prepare a titanium with a low elastic modulus and good antibacterial property to meet the requirements as a biomedical material, Ti-13Nb-13Zr-5Cu (TNZ-5Cu) alloy was prepared by high vacuum consume electric arc melting furnace and then subjected to a solution treatment at 950 °C followed by a short-term aging treatment at 600 °C, for 15 min, 30 min, 1 h and 2 h, respectively. The microstructure, mechanical property, antibacterial property and biocompatibility of TNZ-5Cu were investigated in detail. The research results have shown that the solid solution treated alloy was mainly composed of ß-phase and α″-phase, while the aged alloys of ß-phase, α″-phase, α-phase and Ti2Cu. Compared with Ti-13Nb-13Zr alloy (65 GPa) and Ti-6Al-4 V alloy (111 GPa), the elastic modulus of TNZ-5Cu alloy after solution treatment was about 72 GPa and increased with the aging treatment up to 85 GPa, and the hardness was maintained at a higher level than that of Ti-13Nb-13Zr alloys (288 HV). The bacteria plate count results showed that the antibacterial ability of TNZ-5Cu alloy increased with the extension of the aging duration from <60% at 15-30 min to >90% at 1-2 h. Cell experiments showed that all TNZ-5Cu alloy had good cell compatibility. The low modulus and the antibacterial property could provide potential to avoid stress shield and device-related inflection in the clinical application.

The osteoimmunomodulatory effect of nanostructured TiFx/TiOxcoating on osteogenesis induction.

Macrophages play a central role in the host response and the integration of implant materials. The nanostructured TiFx/TiOxcoating (FOTi) on titanium surfaces has shown multiple properties, including antibacterial properties and bioactivity. However, little is known about the effects of these coatings on the regulation of macrophage activity and the subsequent immunomodulatory effects on osteogenesis. In this study, the behavior of macrophages on the FOTi samples was evaluated, and conditioned medium was collected and used to stimulate MC3T3-E1 cellsin vitro. The results showed that the FOTi samples stimulated macrophage elongation and promoted the production of proinflammatory cytokines at 24 h, while induced macrophage polarization to the anti-inflammatory M2 phenotype at 72 h. Furthermore, the immune microenvironment generated by macrophage/ FOTi samples interactions effectively promoted the osteogenic differentiation of MC3T3-E1 cells, as evidenced by improved cell adhesion, enhanced alkaline phosphatase activity and extracellular matrix mineralization, and upregulated osteogenesis-related gene expression. In summary, the FOTi samples mediated macrophage phenotype behaviors and induced beneficial immunomodulatory effects on osteogenesis, which could be a potential strategy for the surface modification of bone biomaterials.

Effect of ultrasonic micro-arc oxidation on the antibacterial properties and cell biocompatibility of Ti-Cu alloy for biomedical application.

In order to improve antibacterial properties and cell biocompatibility of Ti-Cu alloy, an ultrasonic micro-arc oxidation (UMAO) has been applied to Ti-Cu alloy. The corrosion resistance, antibacterial activity and cell compatibility of Ti-Cu alloy before and after UMAO were studied in detail by means of electrochemical test, plate count method and CCK-8 test scanning electron microscopy (SEM) technology to evaluate the application possibilities of UMAO as a surface bio-modification method for Ti-Cu alloy. The surface microstructure characterisation showed that a typical porous coating with a pore diameter of 3-8 µm and a thickness of 5-15 µm was formed on the surface of the Ti-Cu alloy, which significantly improved the surface roughness and hydrophilicity. The plate count method demonstrated that UMAO coatings on Ti-Cu alloy showed strong antibacterial activity (≥99%) against Staphylococcus aureus (S. aureus) even after being immersed in a physiological saline for up to 20 days, indicating that UMAO-treated Ti-Cu alloy had very strong long-term antibacterial properties. It is believed that the strong long-term antimicrobial properties of Ti-Cu-UMAO samples were mainly due to the formation of Cu2O and CuO in UMAO coatings. The results of cell compatibility evaluation showed that UMAO treatment did not bring about cytotoxicity but improved the early adhesion of MC3T3 cell.