A high current anodization to fabricate a nano-porous structure on the surface of Ti-based implants.

In this study, an oxide layer on Ti-based implants is fabricated by using a high current anodization (HCA) technique in the nitrate electrolyte. This layer is composed of micro-pits and nano-porous arrays in the honeycomb structure. The results show that both the roughness and the layer thickness are related to the reaction time, whereas the size of nano-pores has little to do with the anodization duration. Compared to the nano-tubular arrays constructed by the conventional anodization, this nano-porous layer shows significantly improved mechanical stability. Furthermore, the in vitro assay of osteoblasts shows that cells behaviors on this surface can be modulated by the topology of this special layer. A suitable hierarchical structure composed of micro-pits and nano-porous structure can significantly stimulate osteoblasts attachment, activity, spreading and ALP function. Therefore, this hierarchical surface layer may provide a promising approach, which endows the Ti-based implants with better stability and osseointegration.

Preparation of Al-doped mesoporous silica spheres (Al-MSSs) for the improvement of mechanical properties and aging resistance of dental resin composites.

OBJECTIVE: The purpose of this study was to synthesize Al-doped mesoporous silica spheres (Al-MSSs) and evaluate the effect of them as functional fillers on the mechanical properties and aging resistance of dental resin composites. METHODS: Al-MSSs were prepared by a two-step method. The effect of Al-MSSs on the performance of the composites was evaluated using neat resin matrix, commercial composites 3M Z350XT and samples containing mesoporous silica spheres (MSSs) and nonporous silica spheres (NSSs) as control. The neat resin matrix consisted of resin monomer (Bisphenol A glycerolate dimethacrylate/triethylene glycol dimethacrylate, 49.5/49.5, wt%) and photoinitiator (camphor quinone/Ethyl-4-dimethylaminobenzoate, 0.2/0.8, wt%). The mechanical properties (flexural strength, flexural modulus, compressive strength and microhardness) of them were evaluated by a universal testing machine and microhardness tester. The mechanical stabilities of the prepared composites in wet environment were evaluated by immersing them in deionized water at 37 °C. In addition, we evaluated the effect of Al-MSSs on other properties of the dental resin composites such as polymerization shrinkage, degree of conversion, curing depth, contact angle, water sorption and solubility according to ISO 4049: 2019. RESULTS: The synthesized Al-MSSs possessed good dispersibility with an average particle size of about 505 ± 16 nm. The mechanical properties of resin composites gradually increased with the increase of the loading amounts of inorganic fillers. The reinforcing effect of Al-MSSs was similar to that of MSSs and better than that of the NSSs groups at the same filler loading. After aging in deionized water at 37 °C for 30 days, the mechanical properties of all resin composites decreased. However, the decrease percentage of the composites filled with Al-MSSs was significantly lower than the other groups, indicating that the stability of the dental composites in wet environments was significantly improved by the Al-MSSs fillers. Furthermore, Al-MSSs had no obvious influence on the biocompatibility and other properties of dental resins. SIGNIFICANCE: The prepared Al-MSSs could effectively improve the mechanical properties and aging resistance without sacrificing other physic-chemical properties of dental resin composites.

Impact of surface biofunctionalization strategies on key effector cells response in polyacrylamide hydrogels for bone regeneration.

Despite the clinical prevalence of various bone defect repair materials, a full understanding of their influence on bone repair and regeneration remains elusive. This study focuses on poly(acrylamide) (PAAm) hydrogels, popular 2D model substrates, which have regulable mechanical properties within physiological. However, their bio-inert nature requires surface biofunctionalization to enhance cell-material interactions and facilitate the study of bone repair mechanisms. We utilized PAAm hydrogels of varying stiffness (18, 76 and 295 kPa), employed sulfosuccinimidyl-6-(4'-azido-2'-nitropheny-lamino) hexanoate (sulfo-SANPAH) and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride/N-hydroxysuccinimidyl acrylate (EDC/NHS) as crosslinkers, and cultured macrophages, endothelial cells, and bone mesenchymal stem cells on these hydrogels. Our findings indicated that sulfo-SANPAH's crosslinking efficiency surpassed that of EDC/NHS, irrespective of pore size and stiffness. Importantly, we observed that the stiffness and surface biofunctionalization method of hydrogels significantly impacted cell adhesion and proliferation. The collagen-modified hydrogels by EDC/NHS strategy failed to support the normal biological behavior of bone mesenchymal stem cells and hindered endothelial cell spreading. In contrast, these modified hydrogels by the sulfo-SANPAH method showed good cytocompatibility with the three types of cells. This study underscores the critical role of appropriate conjugation strategies for PAAm hydrogels, providing valuable insights for hydrogel surface modification in bone repair and regeneration research.

In situ titanium phosphate formation on a titanium implant as ultrahigh bonding with nano-hydroxyapatite coating for rapid osseointegration.

Titanium (Ti) has been widely used as a dental implant material due to its excellent mechanical property and good biocompatibility. However, its poor biological activity severely limits its ability to bond with bony tissues. To ameliorate this situation, a preparation method of ultra-high bonding nano-hydroxyapatite (n-HA) coating on the Ti surface is urgently needed. Here, Ti phosphate/n-HA (TiP-Ca) composite coatings with ultra-high bonding were prepared by a two-step hydrothermal treatment. The TiP coating was first formed in situ on the pure Ti substrate and then n-HA crystals further grew on the TiP surface. The formation mechanism of composite coating and reasons for increased bonding strength were systematically investigated. The results show that the TiP-Ca coating remains stable and exhibits an ultra-high bonding strength with the Ti implant (up to 783.30 ± 207.46 N). An effective solution was designed to address the problems of easy peel off. Cell experiments showed that TiP-Ca could promote the adhesion of MC3T3-E1 and expression of OCN, Runx2, and ALP. In vivo evaluation further confirmed that the TiP-Ca composite coating significantly enhanced osseointegration. The designed coating shows great potential in clinical application of implants.

Exosomes derived from magnesium ion-stimulated macrophages inhibit angiogenesis.

Angiogenesis, an essential prerequisite to osteogenesis in bone repair and regeneration, can be mediated by immunoregulation of macrophages. Magnesium and its alloys are promising biodegradable bone implant materials and can affect immunoregulation of macrophages by the degradation products (magnesium ions). Nevertheless, the mechanism of macrophage-derived exosomes stimulated by Mg ions in immunoregulation is still not well understood. Herein, 10-50 mM magnesium ions are shown to inhibit the macrophage viability and proliferation in a dose-dependent manner, but a high concentration results in macrophage apoptosis. The exosomes secreted by macrophages from magnesium ion stimulation inhibit angiogenesis of endothelial cells, as manifested by the suppressed cell viability, proliferation, migration, and tube formation, which arise at least partially from exosome-mediated downregulation of endothelial nitric oxide and the vascular endothelial growth factor. The findings reported in this paper suggest that the bio-functionality of biodegradable magnesium alloys must be considered from the perspective of immunoregulation of macrophage-derived exosomes. Our results also suggest potential cancer therapy by inhibiting tumor-associated angiogenesis.

Facile preparation of nanostructured octacalcium phosphate coatings on micro-arc oxidized magnesium with different functionalities for bone repair application.

Magnesium (Mg) has been considered as the next-generation orthopedic implant material due to its biodegradability, but high degradation rate and severe cytotoxicity hinder its clinical application. Preparing micro-arc oxidation (MAO)/octacalcium phosphate (OCP) composite coating is considered as an ideal approach to solve the problems. In this work, nanostructured OCP coatings with variable structures were prepared facilely on MAO coated Mg by chemical deposition (CD) in a simple trace PO43- ion contained Ca(NO3)2 solution. The results show that nanostructured OCP grows and covers the MAO coating completely after CD. The morphology and thickness of OCP coating can be regulated by varying deposition time. The thinnest OCP coating with a fine structure is observed after 0.5 h of deposition, which shows the best cytocompatibility. Extending deposition time roughens the surface structure and thickens the coatings. The thickest OCP coating with a coarse structure can be obtained after 2 h of deposition, which shows the best corrosion resistance and mineralization. These results clearly indicate the functionality of the OCP coating can be easily tailored only by varying deposition time to meet different clinical requirements.

Enhancement of Antibacterial and Mechanical Properties of Photocurable ε-Poly-l-lysine Hydrogels by Tannic Acid Treatment.

In this study, a photocurable hydrogel based on an ε-poly-l-lysine (EPL) composite was fabricated by a grafting reaction using glycidyl methacrylate and then complexed with tannic acid (TA) to improve the mechanical stability and antibacterial performance of the EPL hydrogels. UV-visible spectrophotometry, nuclear magnetic resonance, and Fourier transform infrared spectroscopy were introduced to characterize the chemical construction. The obtained EPLMA hydrogel was immersed into TA solution to induce the forming of the H-bond between EPL and TA, resulting in double networks in the composite hydrogel (EPLMA-TA). Due to the additional hydrogen-bond interaction between TA and EPLMA, the mechanical properties of hydrogels were improved and supported cell growth and proliferation. In addition, the antibacterial properties and antioxidant activities of the EPLMA-TA hydrogels were greatly enhanced due to the addition of TA. All the findings indicate that the EPLMA-TA hydrogels with multiple properties show great potential for biomedicine applications.

Regulation of endothelial functionality through direct and immunomodulatory effects by Ni-Ti-O nanospindles on NiTi alloy.

Stent implantation has become one of the most widely used methods for the treatment of cardiovascular diseases. However, endothelial dysfunction and abnormal inflammatory response following implantation may lead to delayed re-endothelialization, resulting in vascular restenosis and stent thrombus. To address the concerns, we constructed nanospindles composed of TiO2 and Ti4Ni2O through hydrothermal treatment of amorphous Ni-Ti-O nanopores anodically grown on NiTi alloy. The results show the treatment can significantly improve hydrophilicity and reduce Ni ion release, essentially independent of hydrothermal duration. The nanospindle surfaces not only promote the expression of endothelial functionality but also activate macrophages to induce a favorable immune response, downregulate pro-inflammatory M1 markers and upregulate pro-healing M2 markers. Moreover, nitric oxide (NO) synthesis, VEGF secretion, and migration of endothelial cells are enhanced after cultured in macrophage conditioned medium. The nanospindles thus are promising as vascular stent coatings to promote re-endothelization.

Dual light-induced in situ antibacterial activities of biocompatibleTiO2/MoS2/PDA/RGD nanorod arrays on titanium.

Prevention of bacterial infection and promotion of osseointegration are two important issues for titanium (Ti) implants in medical research. In addition, after a biofilm is formed on the surface of implants, the immune system and antibiotic therapy may fail. In this work, bio-functionalized titanium dioxide (TiO2)/molybdenum disulfide (MoS2)/polydopamine (PDA)/arginine-glycine-aspartic acid (RGD) nanorod arrays (NAs) are prepared on Ti implants to not only kill bacteria noninvasively upon co-irradiation of 660 nm visible light (VL) and 808 nm near infrared (NIR) light, but also promote the osteogenic activity simultaneously. Dual light irradiation triggers the TiO2/MoS2 NA to generate hyperthermia and reactive oxygen species (ROS) in 10 min. The synergistic effects of the generated hyperthermia and ROS increase the bacterial membrane permeability and bacteria are killed rapidly and efficiently in vitro and in vivo. The biofilm is also eradicated and RGD on the nanorods improves cell adhesion, proliferation, and osteogenic differentiation. The strategy described here for the design of bio-functionalized coatings on Ti implants has great clinical potential in orthopedics, dentistry, and other medical fields.

Preparation, characterization, corrosion behavior and cytocompatibility of NiTiO3 nanosheets hydrothermally synthesized on biomedical NiTi alloy.

The present work reports on the hydrothermal synthesis of nanosheets on biomedical NiTi alloy in pure water. The results show rhombohedral NiTiO3 nanosheets with thickness of 6 nm can be grown at 200 °C. Hydrothermal treatment enhances the corrosion resistance of the NiTi alloy. 30 min of the treatment significantly reduces Ni ion release, while prolonged hydrothermal time results in increased Ni ion release because of the growth of the nanosheets with large specific surface area. Excitingly, the nanosheets can well support cell growth, which suggests the release amount can be well tolerated. Good corrosion resistance and cytocompatibility combined with large specific surface area render the nanosheets promising as safe and efficient drug carriers of the biomedical NiTi alloy.

Effect of a biomimetic titania mesoporous coating doped with Sr on the osteogenic activity.

Fabrication of titanium (Ti)-based biomedical implants with appropriate topography as well as capacity for drug delivery is highly pursued in the field of orthopedic and dental implants. In this study, a biomimetic mesoporous coating imbedded with strontium (MPs-Sr) is prepared by the high current anodization (HCA) and hydrothermal treatment (HT). This coating provides a more stable mechanical performance than the conventional nanotube arrays. The Sr loading is regulated by the HT reaction time and the Sr is released in a controllable manner from the MPs-Sr surface. The hydrophilic performance of MPs-Sr are significantly improved. Furthermore, it is showed that the attachment and spreading of preosteoblast MC3T3-E1 cells are significantly up-regulated by the nanoscale topology of MPs and the doped Sr. The improved collagen secretion and matrix mineralization levels of cells are closely related with the Sr release. The excellent osteogenic properties of MPs-Sr samples highlight their promising potential for use in clinical application.

Effects of copper nanoparticles in porous TiO2 coatings on bacterial resistance and cytocompatibility of osteoblasts and endothelial cells.

Copper (Cu) has garnered increasing interest due to its excellent antimicrobial activity and important roles in human metabolism. Although the biological effects of Cu have been studied, the effects of Cu nanoparticles (NPs) on cell behavior are not well understood. In this study, porous TiO2 coatings doped with different amounts of Cu NPs (designated as 0 Cu, 0.3 Cu, and 3.0 Cu) are deposited on titanium by micro-arc oxidation (MAO). The Cu NPs coated samples exhibit excellent antibacterial activity against Staphylococcus aureus (S. aureus). In vitro cytocompatibility evaluation discloses that 0 Cu and 0.3 Cu have no toxicity to osteoblasts but 3.0 Cu shows cytotoxicity. 0.3 Cu promotes proliferation and adhesion of osteoblasts and enhances extracellular matrix mineralization (ECM), but has little effects on the alkaline phosphatase activity (ALP) and collagen secretion. Surprisingly, the Cu NPs coated samples show a different behavior with endothelial cells. Both 0.3 Cu and 3.0 Cu show no cytotoxicity on endothelial cells and promote cell proliferation. Production of nitric oxide (NO) and secretion of vascular endothelial growth factor (VEGF) by the endothelial cells are observed from the Cu NPs doped TiO2 coatings.

Length-dependent corrosion behavior, Ni2+ release, cytocompatibility, and antibacterial ability of Ni-Ti-O nanopores anodically grown on biomedical NiTi alloy.

In the present work, nickel-titanium-oxygen nanopores with different length (0.55-114 µm) were anodically grown on nearly equiatomic nickel-titanium (NiTi) alloy. Length-dependent corrosion behavior, nickel ion (Ni2+) release, cytocompatibility, and antibacterial ability were investigated by electrochemical, analytical chemistry, and biological methods. The results show constructing nanoporous structure on the NiTi alloy improve its corrosion resistance. However, the anodized samples release more Ni2+ than that of the bare NiTi alloy, suggesting chemical dissolution of the nanopores rather than electrochemical corrosion governs the Ni2+ release. In addition, the Ni2+ release amount increases with nanopore length. The anodized samples show good cytocompatibility when the nanopore length is <11 µm. Encouragingly, the length scale covers the one (1-11 µm) that the nanopores showing favorable antibacterial ability. Consequently, the nanopores with length in the range of 1-11 µm are promising as coatings of biomedical NiTi alloy for anti-infection, drug delivery, and other desirable applications.

Cellular response to nano-structured Zr and ZrO2 alloyed layers on Ti-6Al-4V.

The surface topography of biomaterials is known to influence cellular response such as adhesion, spreading and differentiation. In this work, the behavior of osteoblasts and endothelial cells on nano-structured Zr and micro/nano-structured ZrO2 alloyed layers of Ti-6Al-4V (TC4) was investigated. Zr alloyed layer (Zr@TC4) decreases the hydrophilicity whereas ZrO2 alloyed layers (ZrO2@TC4) is more hydrophilic than TC4 and more proteins adsorb on ZrO2@TC4 followed by Zr@TC4. The cells proliferate steadily on the smooth TC4 and nano-structured Zr@TC4 surfaces and the osteoblast activity is more pronounced on Zr@TC4 than TC4. The micro/nano-structured surface on ZrO2@TC4 restricts cellular adhesion and spreading independent of the surface wettability and protein adsorption. The findings provide insights into the design of micro/nano-structured biomaterials and interfaces with controlled tissue response.

Electrochemical corrosion, wear and cell behavior of ZrO2/TiO2 alloyed layer on Ti-6Al-4V.

Ti-6Al-4V (TC4) has received increasing attention as biomaterial but also raised concerns about the long-term safety of releasing of metal ions and poor wear resistance. In this work, an ZrO2/TiO2 alloyed layer was prepared on TC4 by plasma surface alloying with Zr and subsequently annealed in the air for improved corrosion and wear resistant. To assess the corrosion performance of the alloyed layer, the specimens were measured by open circuit potential, electrochemical impedance spectroscopy and potentiodynamic polarization in simulated body fluid solution. The result shows that the ZrO2/TiO2 alloyed layer exhibits strikingly high polarization resistance, wide passive region and very low current density, indicating the excellent corrosion resistance. The layer also displays significant improvement of wear resistance. Furthermore, the alloyed layer restricts cell adhesion and spreading. We infer that the ZrO2/TiO2 alloyed layer might be potentially useful implanted devices such as biosensors, bioelectronics or drug delivery devices.

Differential effect of hydroxyapatite nano-particle versus nano-rod decorated titanium micro-surface on osseointegration.

Coating materials applied for intraosseous implants must be optimized to stimulate osseointegration. Osseointegration is a temporal and spatial physiological process that not only requires interactions between osteogenesis and angiogenesis but also necessitates a favorable immune microenvironment. It is now well-documented that hierarchical nano-micro surface structures promote the long-term stability of implants, the interactions between nano-micro structure and the immune response are largely unknown. Here, we report the effects of microporous titanium (Ti) surfaces coated with nano-hydroxyapatite (HA) produced by micro-arc oxidation and steam-hydrothermal treatment (SHT) on multiple cell behavior and osseointegration. By altering the processing time of SHT it was possible to shift HA structures from nano-particles to nano-rods on the microporous Ti surfaces. Ti surfaces coated with HA nano-particles were found to modulate the inflammatory response resulting in an osteoimmune microenvironment more favorable for osteo-/angio-genesis, most likely via the activation of certain key signaling pathways (TGF-ß, OPG/RANKL, and VEGF). By contrast, Ti surfaces coated with nano-rod shaped HA particles had a negative impact on osteo-/angio-genesis and osteoimmunomodulation. In vivo results further demonstrated that Ti implant surfaces decorated with HA nano-particles can stimulate new bone formation and osseointegration with enhanced interaction between osteocytes and implant surfaces. This study demonstrated that Ti implants with micro-surfaces coated with nano-particle shaped HA have a positive impact on osseointegration. STATEMENT OF SIGNIFICANCE: Osteo-/angio-genesis are of importance during osteointegration of the implants. Recent advances unravel that immune response of macrophages and its manipulated osteoimmunomodulation also exerts a pivotal role to determine the fate of the implant. Surface nano-micro modification has evidenced to be efficient to influence osteogenesis, however, little is known links nano-microstructured surface to immune response, as well the osteoimmunomodulation. This study demonstrates that the nano-particles decorated micro-surface, compared with the nano-rods decorated micro-surface enables osteogenesis and angiogenesis concurrently that has not been investigated previously. This study also unravels that the immune response of macrophages can be manipulated by the nano-micro surface, especially the nano-dimension matters, leading to a differential effect on osteointegration. The additional knowledge obtained from this study may provide foundation and reference for future design of the coating materials for implantable materials.

A multifaceted coating on titanium dictates osteoimmunomodulation and osteo/angio-genesis towards ameliorative osseointegration.

A multifaceted coating for hard tissue implants, with favorable osteogenesis, angiogenesis, and osteoimmunomodulation abilities, would be of great value since it could improve osseointegration and alleviate prosthesis loosening. However, to date there are few coatings that fully satisfy these criteria. Herein we describe a microporous TiO2 coating decorated with hydroxyapatite (HA) nanoparticles that is generated by micro-arc oxidation of pure titanium (Ti) and followed annealing. By altering the annealing temperature, it is possible to simultaneously tune the coating's physical (morphology and wettability) and chemical (composites and crystallinity) properties. A coating produced with micro-arc oxidization (MAO) with an annealing temperature of 650 °C (MAO-650) exhibits numerous favorable physicochemical properties, such as hybrid micro-nano morphology, superhydrophilicity, and highly crystalline HA nanoparticles. In vitro experiments reveal that the MAO-650 coating not only supports proliferation and differentiation of both osteoblasts and endothelial cells, but also inhibits the inflammatory response of macrophages and enables a favorable osteoimmunomodulation to facilitate osteo/angio-genesis. In vivo evaluation mirrors these results, and shows that the MAO-650 coating results in ameliorative osseointegration when compared with the pristine MAO coating. These data highlight the profound effect of surface physicochemical properties on the regulation of osteo/angio-genesis and osteoimmunomodulation in the enhancement of osseointegration.

Linker-free covalent immobilization of heparin, SDF-1α, and CD47 on PTFE surface for antithrombogenicity, endothelialization and anti-inflammation.

Small-diameter vascular grafts made of biomedical polytetrafluoroethylene (PTFE) suffer from the poor long-term patency rate originating from thrombosis and intimal hyperplasia, which can be ascribed to the insufficient endothelialization and chronic inflammation of the materials. Hence, bio-functionalization of PTFE grafts is highly desirable to circumvent these disadvantages. In this study, a versatile "implantation-incubation" approach in which the biomedical PTFE is initially modified by plasma immersion ion implantation (PIII) is described. After the N2 PIII treatment, the surface of biomedical PTFE is roughened with nanostructures and more importantly, the abundant free radicals generated underneath the surface continuously migrate to the surface and react with environmental molecules. Taking advantage of this mechanism, various biomolecules with different functions can be steadily immobilized on the surface of PTFE by simple solution immersion. As examples, three typical biomolecules, heparin, SDF-1α, and CD47, are covalently grafted onto the PTFE. In addition to retaining the bioactivity, the surface-functionalized PTFE exhibits reduced thrombogenicity, facilitates the recruitment of endothelial progenitor cells, and even alleviates the inflammatory immune responses of monocytes-macrophages and is thus promising to the development of small-diameter prosthetic vascular grafts with good long-term patency.

Antibacterial ability and osteogenic activity of porous Sr/Ag-containing TiO2 coatings.

Implant-associated infection and poor osseointegration remains a major clinical challenge in Ti-based implant materials. A versatile strategy to endow Ti-based implants with long-term antibacterial ability as well as better osteogenic activity is highly desirable for high quality implantation. Strontium (Sr) has been shown to be a significant element to favor bone growth by promoting new bone formation and inhibiting bone resorption. In this study, a novel duplex-treatment technique encompassing magnetron sputtering with micro-arc oxidation is utilized to fabricate porous Sr/Ag-containing TiO2 coatings loaded with different concentrations of Ag and Sr. All coatings are porous with pore size less than 5 µm. Ag is primarily distributed homogeneously inside the pores, and the concentrations of Ag in Sr/Ag-containing TiO2 coatings with low and high Ag contents are 0.40 at.% and 0.83 at.% respectively. We have demonstrated that this kind of coating displays long-lasting antibacterial ability even up to 28 d due to the incorporation of Ag. Further, Sr/Ag-containing TiO2 coatings with optimum Ag and Sr contents revealed good cytocompatibility, enhanced osteoblast spreading and osseointegration, which stemmed primarily from the synergistic effect exerted by the porous surface topography and the bioactive element Sr. However, this study has also identified, for the first time, that proper addition of Ag would further facilitate osteogenic effects. Besides, Sr may be able to alleviate the potential cytotoxic effect of excessive Ag. Thus, integration of optimum functional elements Ag and Sr into Ti-based implant materials would be expected to expedite osseointegration while simultaneously sustaining long-term antibacterial activity, which would provide new insights for relevant fundamental investigations and biomedical applications.

Antibacterial activity and cytocompatibility of Cu-Ti-O nanotubes.

TiO2 nanotubes (NTs) have favorable biological properties, but the poor antibacterial activity limits their application especially in orthopedics fields. In this article, Cu-Ti-O nanotubes with different Cu contents are fabricated on sputtered TiCu films. Scanning electron microscopy reveals the NTs can be formed on sputtered TiCu films when the Cu content is less than 14.6 at %. X-ray photoelectron spectroscopy results indicate the NTs are consist of CuO mixed with TiO2 and the Cu content in NTs decreases dramatically compared with that in TiCu films. Biological experiments show that although these NTs have poor release antibacterial activity, their contact antibacterial activity has proven to be excellent, indicating the NT surface can effectively inhibit biomaterial-associated infections. The cytocompatibility of the NTs is closely related to the Cu content and when its content is relatively low (1.01 at %), there is no appreciable cytotoxicity. So Cu-Ti-O NTs with 1 at % Cu may be suitable to achieve proper antibacterial activity and desired cytocompatibility. The Cu-Ti-O NTs integrate the favorable antibacterial activity of Cu and excellent biological properties of TiO2 NTs therefore have potential applications in orthopedics, dentistry, and other biomedical fields.