key: cord-0773062-l93phro4
authors: Sarraf, Masoud; Nasiri-Tabrizi, Bahman; Yeong, Chai Hong; Madaah Hosseini, Hamid Reza; Saber-Samandari, Saeed; Basirun, Wan Jefrey
title: Mixed oxide nanotubes in nanomedicine: A dead-end or a bridge to the future?
date: 2020-09-24
journal: Ceram Int
DOI: 10.1016/j.ceramint.2020.09.177
sha: 4adc726b9fa9db73806d219bec78a45e92059d96
doc_id: 773062
cord_uid: l93phro4

Nanomedicine has seen a significant rise in the development of new research tools and clinically functional devices. In this regard, significant advances and new commercial applications are expected in the pharmaceutical and orthopedic industries. For advanced orthopedic implant technologies, appropriate nanoscale surface modifications are highly effective strategies and are widely studied in the literature for improving implant performance. It is well-established that implants with nanotubular surfaces show a drastic improvement in new bone creation and gene expression compared to implants without nanotopography. Nevertheless, the scientific and clinical understanding of mixed oxide nanotubes (MONs) and their potential applications, especially in biomedical applications are still in the early stages of development. This review aims to establish a credible platform for the current and future roles of MONs in nanomedicine, particularly in advanced orthopedic implants. We first introduce the concept of MONs and then discuss the preparation strategies. This is followed by a review of the recent advancement of MONs in biomedical applications, including mineralization abilities, biocompatibility, antibacterial activity, cell culture, and animal testing, as well as clinical possibilities. To conclude, we propose that the combination of nanotubular surface modification with incorporating sensor allows clinicians to precisely record patient data as a critical contributor to evidence-based medicine.

In the recent decade, there has been a great increase in patients requiring artificial implants as replacements for damaged tissues such as hip joints and teeth due to the increase of the elderly population [1] . Thus, many efforts have been directed toward identifying appropriate biomaterials for the production of durable medical implants.

Among the different kinds of biomaterials, metallic-based materials are the most common replacement compounds for bone treating [1] . Pure titanium (Ti) and its biomedical-grade alloys have been extensively used as medical implants owing to their high biocompatibility, fatigue life, corrosion resistance, and lower Young's modulus, compared to other medical implants, e.g., cobalt alloys and stainless steel [2] [3] [4] .

Despite the inherent benefits of Ti alloys, supplementary exploration is necessitated to attain developed clinical achievements. As this category of alloys is employed in the manufacturing of medical implants, due to insufficient physiological adaptation, increases the risk of implant failure [5] [6] [7] . This also causes the detrimental accumulation of wear debris and ions discharge into the biological media [8] . To overwhelmed these weaknesses, different types of surface reformations are proposed. For instance, surface coating of implants is a useful method to develop the biological performance of the medical implants, in which the coating layers commonly perform as defensive armors to minimize wear and corrosion, whereby diminishes the risk of implant failure [9] [10] [11] [12] [13] .

Electrochemical anodization is a process that produces a durable and corrosionresistant anodic oxide layer on a metal surface that protects the inner bulk metal [14] .

Nanotube coatings by anodization have received increased attention recently, for the manufacturing of orthopedic and dental implants . Numerous researchers have found that the coating morphology has a great impact on the biocompatibility of J o u r n a l P r e -p r o o f metallic implants [15, [42] [43] [44] . In particular, the nanotube morphology enhances the physical interlocking of the osteoblast cells on the surface of the implant. Also, the formation of nanotubular arrays improves osseointegration through the development of a bone-like apatite layer [45, 46] . For instance, a substantial increase in the cell adhesion was detected on titanium dioxide nanotubes (TiO 2 NTs) possibly due to an improved interlocking of the hydroxyapatite (HA) layer with the nanotubes [47] .

Accordingly, it seems that the combination of physical vapor deposition (PVD) and anodization, could produce well-adherent coating layers with high mechanical and tribological performance, in addition to the presence of porosity to improve the implant biomechanical performance [47] . On the other hand, the implantable materials should possess adequate antibacterial behavior to inhibit the development of bacterial agglomeration [48] [49] [50] . One particular approach to boost the antibacterial activity of biomaterials is with the integration of antimicrobial agents such as copper (Cu), silver (Ag), and zinc (Zn) [51] . However, the fast release of metal ions into the human body is inevitable, causing temporary antibacterial behavior and amplified cytotoxicity. This concern thus obliges an antibacterial compound with greater cytocompatibility and the restrained release of ions.

Based on the descriptions above, much attention has been focused on the design and fabrication of advanced implants to improve patient well-being [52] . The main advantages of advanced implants compared to the traditional products are that the patients experience less discomfort and have a lower risk of infections. Following the vast popularity of this approach, deeper questions emerge, the most important of which is whether this strategy leads the blind into a pit or a horizon with a huge outlook?

There are still several challenges that need to be addressed, on the safety and J o u r n a l P r e -p r o o f performance of the nanostructured implants prior to commercial use [53] . The present review focuses on the recent fabrication approaches of the MONs and their parameters, which control the tubular geometry, self-ordering degree, and crystal configuration. The review also includes the scientific aspects and clinical perceptions on MONs, also on their potential applications in nanomedicine, especially in advanced orthopedic implants. The final part sums up the central points of the review and presents some viewpoints for future consideration. Fig. 1 shows a schematic side view of various configurations of MONs. In chemistry, a mixed oxide is an oxide with cations of a single element in different oxidation states (Type I) or cations of more than one element (Type II) [54] . These oxide structures are usually produced by the template method. The magnetite (Fe 3 O 4 ) that includes the Fe 2+ (ferrous ion) and Fe 3+ (ferric ion) cations in a 1:2 ratio, as well as perovskite compounds i.e. ABX 3 (A and B are two cations of very different sizes, and X is an anion that bonded to both), are well-known as typically mixed oxides [55] . During the last decades, the preparation of mixed oxides has been developed as they have several significant properties such as superconductivity, magnetism, ferroelectricity, catalytic activity, and ionic conductivity [55] [56] [57] . It must be noted the nanotechnology has led to more efficient mass production, and as expected has become an important industry [58] .

Accordingly, numerous attempts have been made to employ nanotechnology in various sectors, for instance in electronics, environmental protection, and biomedical applications [59] . The main reason why nanotechnology has received great attention is that the physiochemical behavior of nanostructured materials is different from those of the bulk materials [60] . Thus, by utilizing these nanostructures, solutions to the On the other hand, an additional definition of MONs can be given by a mixture of different oxides, rather than a mixed M1-M2 oxide (Type III). This type of MONs is commonly produced by electrochemical anodization, where nanotubes with electrochemically tunable morphologies can be produced. For instance, high-resolution X-ray photoelectron spectroscopy (XPS) revealed that the nanotubes developed on the β-Ti-45Nb alloy are composed of TiO 2 and Nb 2 O 5 , rather than a mixed Ti-Nb oxide [61] . For this purpose, anodization or electrochemical oxidation is a well-known method to prepare the protective layers and self-organized mono-and mixed oxide nanotubes.

In view of the fact that the self-organized mono-and mixed oxide nanotubes can be formed on Ti and other valve metals, these unique nanotubular surface modifications have attracted increasing interest for the fabrication of more effective implantable apparatus for biomedical applications [62] [63] [64] . In this review, the main focus is not only to provide a comprehensive comparison of the current preparation and characterization of Type III MONs and generate a list of potentially suitable platforms but also to discuss the disadvantages and possible improvements in the fabrication process. 

In the past decades, electrochemical anodization for the growth of thick and homogeneous oxide coatings, as well as the development of self-organized nanotubes on different valve metals have received much attention in the literature [65] [66] [67] [68] [69] [70] [71] . The J o u r n a l P r e -p r o o f electrochemical oxidation is initiated at the interface of metal-oxide followed by the outwards migration of metallic ions under the application of an external electric field.

Simultaneously, oxygen ions migrate to the metal-oxide junction and react with cations and materialize into a dense metal-oxide layer. The oxide layer propagates on the condition that the electric field is sufficient to allow ion transmission throughout the oxide, but the procedure eventually ceases, leading to a finite thickness of the oxide layer. In addition to the development of self-assembled nanoporous and nanotube coatings, porous oxide films could also occur under controlled experimental conditions [72] . So far numerous findings have reported the formation of mono-and MONs coatings, with some of their outstanding achievements, are summarized in the following section.

The first report on the preparation of a self-organized nanoporous oxide film by anodization was performed on Al in an C 2 H 2 O 4 electrolyte under specific circumstances [73] . The results of this work initiated a new pathway for the anodization of different types of valve metals and triggered thousands of papers for the preparation and application of nanoporous structures. The anodized nanoporous Al 2 O 3 was utilized as photonic crystals and template for the fabrication of various nanostructures, thus several models have been proposed to describe the growth mechanisms of the self-ordered nanoporous alumina [72] . The proposed mechanisms of the self-ordering nanoporous Al 2 O 3 could also be applied in the development of self-organizing nanostructured coatings on various valve metals, e.g. Ti, Zr, Hf, V, Nb, Fe, and Ta [72, [74] [75] [76] [77] [78] [79] [80] .

Nevertheless, contrary to Al, anodization in an acidic solution causes the formation of a compact oxide coating. Therefore these conditions are inadequate to produce self-J o u r n a l P r e -p r o o f organizing nanoporous oxide layers of these metals [72] . To overcome this issue, the presence of fluoride anions is required for the development of self-organizing nanostructured coatings. The main advantage of fluoride is its potential to produce water-soluble metal-fluoride compounds, which prevents the development of metaloxide layer at the tubular bottom, by a mild but steady chemical dissolution of the metal-oxide layer. The size of the anions is also a vital issue, where the smaller Fions have a higher migration rate through the oxide lattice compared to the O 2ions. This causes the development of a fluoride-rich film at the metal-oxide interface which is the basis of the nanostructured coating development. Some outstanding books and reviews have described the growth mechanism of mono-oxide nanotube arrays by the anodizing method. In the following section, a summary of the development of some mono-oxide nanotubes under different experimental circumstances has been described [72, [81] [82] [83] [84] [85] .

One specific tactic to decrease the depreciation in body fluids and to improve the wear and corrosion resistance is to generate a homogeneous TiO 2 layer on the surface of the Ti implants. In particular, the development of anodic TiO 2 NTs has recently received much interest in the modification of metal implants owing to their outstanding biocompatibility and resistance to bio-corrosion. Fig. 2a displays a schematic view of electrochemical anodization, as well as the different generations of TiO 2 NTs synthesized via the anodization technique. The rapid oxide dissolution was the chief restriction of the primary generation of nanotube synthesis, leading to nanotubes with less than 1 μm length. Hence, in the second generation, HF was exchanged with KF or NaF to achieve a higher pH and expand the nanotube length up to ~5 μm. Nanotubes with a length of 6 μm could be formed in 0.1M KF, 1.0M H 2 SO 4 , and 0.2M C 6 H 8 O 7 aqueous electrolyte (25 V and 20 h) as the pH was kept to 5 [86, 87] . The third J o u r n a l P r e -p r o o f generation of synthesis gave more amendments in the NTs length through non-aqueous electrolytes or organic polar solvents, for instance, ethylene glycol (EG), dimethyl sulfoxide (DMSO), formamide (FA), dimethylformamide (DMF), and Nmethylformamide (NMF) mixed with HF, NH 4 F or KF [88] [89] [90] [91] [92] . Finally, the fourth generation of nanotube synthesis involves the use of non-fluoride electrolytes [93] .

All self-ordering nanotubes produced by electrochemical anodization in various electrolytes on various valve metals and their alloys appear to pursue the same growth principles and the key factors for the generation of nanotubes as shown in Fig. 2b . It is well-known that the diameter of the nanotube is controlled through the anodization voltage; while the length of nanotubes is governed by the oxide resistance against electrolyte solutions, which also attributes to the voltage of anodization, anodization time, and the oxygen amount delivered by water for the growth of nanotube arrays. As mentioned above, dependent upon the anodizing circumstances, self-organized nanostructured coatings can also be formed on various valve metals and their alloys, where the examination and optimization of processing parameters are favorable for obtaining nanotubes with high-aspect-ratio. Thick and smooth zirconium dioxide nanotubes (ZrO 2 NTs) could be achieved using organic and mixed electrolytes at a potential of 40 and 20 V, respectively [94] [95] [96] [97] [98] . Irregular ZrO 2 NTs were produced using a one-pot anodization process without any pretreatment, even in the presence of contaminations as well as surface heterogeneity. To attain highly ordered nanotube arrays, pretreatments on Zr were also proposed to boost the self-organizing process.

Electropolishing, dip-etching, and two-step anodizing were carried out on Zr substrates to attain highly self-organized nanotubular arrays. In the same way, hafnium oxide nanotubes (HfO 2 NTs) with a high aspect ratio can be fabricated under a broad range of anodization circumstances [99] .

With regards to tantalum, certain conditions must be met to achieve the nanoporous and nanotube arrays which are extremely corrosion resistant in the acidic media [100] [101] [102] [103] [104] [105] [106] [107] [108] . Based on the literature, Ta 2 O 5 nanotube arrays were grown under an anodization voltage range of 10-20 V after 5 to 120 seconds in a mixed H 2 SO 4 and HF electrolyte with 1 wt% H 2 O. However, prolonged anodization causes the destruction of the nanotubes and the presence of dimples which is most likely due to the development of a thin fluoride-containing layer at the interface of metal-oxide. Similarly, well-aligned anodic nanotubes have been obtained on other valve metals such as niobium (Nb) and tungsten (W) [109, 110] .

Nanotubular coatings can be fabricated by controlling the anodization conditions, where they can generate not only mono-oxide nanostructures but also MONs. However, the preparation of MONs by electrochemical anodization is not entirely understood because the formation mechanisms are complex, where a wide range of MONs can be produced depending on the type of metal and anodization conditions [55] . The formation of MONs have been observed on binary, ternary, quaternary systems as well on more complex alloy systems such as Ti-Al [111, 112] , Ti-Mo [113, 114] , Ti-Nb [61, [115] [116] [117] , Ti-Ta [116, 118, 119] , Ti-Zr [75, 116, [120] [121] [122] , Ti-Mn [123] , Ti-6Al-7Nb [124] [125] [126] [127] [128] [129] [130] [131] [132] , Ti-6Al-4V [132] [133] [134] [135] [136] [137] [138] [139] [140] [141] [142] , Ti-35Nb-5Zr [143] , Ti-28Zr-8Nb [132, 144] , and Ti-29Nb-13Ta-4.6Zr [145] [146] [147] . The presence of various elements in Ti alloys significantly J o u r n a l P r e -p r o o f influences the electrochemical behavior and morphology, as well as the composition of the resultant oxide nanotube arrays. In the presence of different elements, the composition of the as-anodized layer is closely related to the metallic ratio of the alloy.

For example, the nanotubes formed on the Ti-Al alloy system consist mainly of titania and alumina, and it is closely related to the ratio of Ti and Al in the base alloy. In some cases, it is not possible to identify the MONs due to the low phase fraction of other oxides relative to the dominant phase (TiO 2 ) [131] . In such cases, it is necessary to perform XPS to distinguish a mixed oxide structure from a mono structure and to measure the elemental composition, and chemical state of the elements in the MONs [61] .

Resembling the development of titania nanotubes on pure Ti, the formation of MONs on Ti-based alloys relies on the processing factors, such as pH, anodization time, anodic potential, and fluoride ion concentration. Nonetheless, the morphological features of nanotubular coatings on the Ti alloys are somewhat dissimilar compared to the formation on pure Ti owing to the selective dissolution of the oxide layer in fluoride electrolytes and the solubility of metal fluorides during the anodization process. For ternary systems, both the α and β phases are present with the addition of the other element, where organized nanotube coatings are formed in the α phase, while a combination of nanotubes and nanopores is observed in the two-phase (α + β) component. In the following section, the development of MONs on different Ti alloys is presented [61, 85] .

J o u r n a l P r e -p r o o f

Because of the dissimilar oxide morphologies that could be formed on Al and Ti, it is very interesting to assess the electrochemical feature of different compositions of the Ti-Al alloys prepared in an F − -comprising electrolyte and to appraise the critical circumstances which control the evolution of one type of morphology to the other.

Besides that, the length scale of the self-organization procedure is important, where the well-organized oxide configurations on Al and Ti surface by anodization could be voltage regulated [148, 149] , but the total self-organizing length is dissimilar for the two substrates. In this regard, the self-organizing properties of anodic oxides on refractory metals are studied in detail [150, 151] , which has two dissimilar morphologies, the highly organized parallel aligned porous oxide configurations, and the organized arrays of nanotubes. The top-view SEM micrographs of oxide-layers grown on Al, TiAl 3 , TiAl, Ti 3 Al, and Ti in 1 M H 2 SO 4 comprising 0.15 wt% HF at potentials of 10, 20, and 40 V are shown in Fig. 3 , where the evolution from porous to tubular configuration is detected [150] .

As shown in the figure, the self-ordered oxides could be generated over an extensive potential range. The very regular porous configuration is formed on Al, comprising of some hexagonal nanopores with the mean interpore distance ranging from 30 nm at 10 V to 55 nm at 40 V. In contrast, the pores are partly enclosed by bundles of oxide needles owing to the non-uniform etching of the pore walls throughout prolonged anodization in F − -comprising electrolytes at lower potentials [152] . It is J o u r n a l P r e -p r o o f reported that the morphological features in the self-ordered configurations depend on the anodization voltage and the alloy's composition, where the tubular division is attributed to the augmented stress due to the rising volume expansion, as changing the composition from Al to Ti [150, 151] .

Previous results on emerging Ti-Mo alloys showed that these alloys are promising as medical implants due to the low elastic modulus, electrochemical constancy in biological media, and high corrosion resistance [153] [154] [155] . However, the formation of MONs on Ti-Mo alloy is not free from challenges. For instance, it was suggested that a multi-purpose optimization of the electrolyte solution, especially the F − concentration and water quantity, at 150 V for 20 h, could lead to the development of self-organized MONs on Ti-7Mo alloy. However, the results showed that only porous oxide layers with higher Mo concentration were formed using the proposed approach [156, 157] .

Given the possible nanotubes generation on binary Ti-Mo alloys and to overcome the challenges, Oliveira et al. [114] studied the formation of self-organized nanotubes on biomedical Ti-Mo alloys (Ti-6Mo and Ti-15Mo) using the electrolyte solution proposed by Ji et al. [158] for pure Ti, to ensure that the matrix configuration is attained at the nanotubes, where the α phase is only formed on the Ti-6Mo, while the β phase is only formed on the Ti-15Mo [159] .

From the SEM images as shown in Fig. 4a -e, the nanopores were formed after 2 h, which are transformed into nanotubes following 4 h, and eventually well-defined, homogeneously distributed MONs with a mean diameter of 90 nm are developed on the Ti-Mo alloy after 6 h. The electrochemical assessments revealed that the MONs formation on the Ti-Mo alloys gave better protective features than the oxide films instinctively developed on the respective alloys [114] (Fig. 4f) .

Based on previous studies, the titania layer developed on the Ti-14.6Nb alloy showed excellent photocatalytic activity [113] . Besides that, Nb is an alloying element for Ti alloys that are widely utilized for biomedical applications, for instance, the Ti-29Nb-13Ta-4.6Zr alloy [160] . Accordingly, the findings on MONs formed on Ti-Nb alloys provide some essential information for employing MONs coatings on the Ti-based implants for different orthopedic applications [117, 161, 162] . Also, it is reported that a TiO 2 -Nb 2 O 5 mixture possesses a higher photocatalytic activity compared to the pure TiO 2 [163] and also found that this MONs structure possesses metallic behavior [164] , making them potential conducting transparent materials.

In electrochemical anodization, it is vital to reach an equilibrium between the oxide growth and local oxide dissolution, where the equilibrium is sensitive to the F − concentration, as the chemical dissolution of oxide is accompanied by the release of the soluble [TiF 6 ] 2complexes [61] . The different valve-metal oxides undergo dissimilar dissolution kinetics in F − -comprising solutions [165] . From the electrochemical data, the dissolution rate of Nb 2 O 5 is only 1 nm min -1 , compared to the dissolution of TiO 2 which is 20 nm min -1 [166] . This shows that the formation of Nb 2 O 5 at the anode is more resistant to F − ions compared to TiO 2 in 1M NaH 2 PO 4 with 0.5 wt% HF (pH 4.5) [61] .

Thus the TiO 2 dissolution rate in an F − -comprising electrolyte is of crucial importance to the length of the developed nanotubes [167] , likely, the growth of the anodic oxides on J o u r n a l P r e -p r o o f Ti-Nb alloys differs drastically from the pure Ti. In this context, Ghicov et al. [61] explored the formation of MONs in a binary Ti-45Nb alloy. They reported that the shape and dimensions of TiO 2 NTs reinforced with Nb 2 O 5 could be controlled within a wide parameter range. The Nb 2 O 5 undergoes a much lower chemical dissolution rate compared to the TiO 2 in the F − solution, thus the nanotube corrosion is hindered upon the formation, which results in the development of longer MONs ( Fig. 5a-g) . This feature enables the tuning of the TiO 2 NTs for particular applications, such as photon absorption and insertion of microbiological species. Furthermore, the MONs possess higher thermal resistance compared to the pure TiO 2 NTs, which enables thermal treatment at much higher temperatures.

In this regard, ultrafast MONs development on the Ti-Nb alloy by quick breakdown anodization in NaCl-NaClO 4 mixed electrolyte, NaCl, and NaClO 4 solutions at pH 4 was also examined by Jha et al. [116] , as shown in Fig. 5h -j. They found that the intense evolution of hydrogen at the Pt cathode took place instantaneously upon anodization.

The surface of Ti-Nb alloy is covered with white spots that are distributed very quickly over the surface upon 30 s of anodization. These white spots are the oxide nanotube bundles that form densely around a pit.

The results show the formation of two types of morphologies, which are the net-like and free-tubular configurations, were formed using quick breakdown anodization. For the net-like configurations, the MONs show a relatively homogeneous size (30-40 nm in diameter and several tens of micrometers in length), while in the case of free-tubular configuration, the diameter of the nanotubes varies significantly from 20 nm to more J o u r n a l P r e -p r o o f than 100 nm (Fig. 5h ). In addition to the mixed electrolyte, Fig. 5i and j displays SEM micrographs of nanotubes anodized in NaCl and NaClO 4 solutions, respectively. In NaCl solution, the anodized surface was covered with loosely packed nanotube bundles with net-like morphology (Fig. 5i) . On the contrary, the NaClO 4 solution led to the more uniform coating but the nanotubes are segmented into packets of around 2 μm length ( Fig. 5j) . Contrary to the NaCl electrolyte, the nanotubes generated in NaClO 4 solution had smooth walls without ripples, thus it can be deduced that the net-like nanotubes are attributed to the presence of Cl − , while the stacks of smooth-walled nanotubes are ascribed to the presence of ClO 4 − . This suggests that the mixed electrolyte possesses the advantage of attaining a large surface coating with a high adhesion strength, which is very important in modern implantology [168, 169] .

Apart from the optimization in structural features of nanotubes (geometry and functionality), another noteworthy aspect of the β-type Ti-based alloys is the bimodal self-assembly. In this arrangement, the nanotubes consist of ordered tubes with different diameter sizes i.e. larger tubes that are surrounded by smaller tubes. In this regard, Tsuchiya et al. [118] explored the development of MONs on the Ti-Ta alloys such as

Ti-13Ta, Ti-25Ta, Ti-50Ta, and Ti-80Ta, and examined possible formation mechanism of the bimodal self-organization on these alloys. Fig. 6g and h). This shows that an appropriate level of alloying elements is requisite for the nanotube development on two-size scales. Besides that, the Ta concentration significantly affects the nanotube diameter in such assemblies, as shown in Fig. 6i [118]. Fig. 6j , a nanoporous layer is initially generated on the alloy surface, followed by the generation of a nanotubular layer developed underneath the nanoporous layer (Fig. 6k) .

In this step, the nanotube growth occurs at different rates, i.e. the faster tube growth occurs further in lateral directions and consequently, the growth of slower tubes will be stopped. The growth on two alloy phases (α or β) is different, thus the attainable bimodal tube diameters vary in the two phases. Moreover, the chemical compositions of the outermost nanoporous layers depend on the substrate phase that causes a disparity in J o u r n a l P r e -p r o o f the nanoporous dissolution rate in diverse zones, leading to an alteration evident in the top-view morphology. The underneath nanotube layers become apparent (Fig. 6l) owing to the dissolution of the nanoporous, which is followed by the drastic etching of the tubes which leads to the nanotube wall thinning and the nanotube surface roughening caused by the preferential etching of the tubes (Fig. 6m ) [118] . It is therefore suggested that homogenous MONs formation on a single-phase substrate can be attained if the specimen is timely detached from the electrolyte upon the nanoporous layer dissolution [118, 170] . Following this study, Jha et al. [116] investigated ultrafast MONs formation 

The development of nanotubes on the Ti-Zr alloys is widely studied due to the higher structural flexibility of zirconium titanate nanotubes compared to the pure TiO 2 NTs [120, 171] . In particular, an extended range of diameter and length of configurations can be formed by altering the anodization potential without loosening the highly ordered character of the substance. In this regard, comprehensive studies on the formation of multilayered oxide nanotubes on Ti-Zr alloys for modifying the configuration of a nanotubular valve metal system by electrochemical anodization are implemented by

Yasuda et al. [75, 120, 122] . For this purpose, the first anodization was executed at 20 V for 15 min followed by a potential sweep from the OCP to 20 V at 20 V s -1 , followed by a second anodization step at 20 V for 15 min after an opened circuit for 1 min.

J o u r n a l P r e -p r o o f Fig. 7a , a two-layer MONs structure is formed after a two-step anodization process,

where the upper and lower layers were formed in the first and second anodization processes, respectively. There is a non-uniformity in the nanotube diameter in the zones,

where the potential was switched off and on again. Besides that, the length of the nanotube for each layer is in harmony with the theoretical amount measured from the electric charge in each procedure [122] . The magnified SEM image in Fig. 7b shows Also, as schematically illustrated in Fig. 7g , the new tube growth begins in the gaps between the present tubes [75] . Given the development stages of the nanotubes at the underside, the possible choice for the rate-determining step of the tube expansion is either (i) diffusion of a metal cation or oxygen anion in the solid phase, (ii) charges for oxidation, (iii) chemical dissolution of oxide into the electrolyte, or (iv) diffusion of ions in the electrolyte [122] . Yasuda et al. [122] reported that the anodic current is progressively decreased with the generation of the nanotubes even at the end of the J o u r n a l P r e -p r o o f commencement phase. They assumed that the current decrease is due to the nanotube growth from the (iv) diffusion of ionic species, i.e. either F − , TiF 6 2− , or ZrF 6 2− , and accordingly they proposed a diffusion-based model, as provided in Fig. 7h . In this model, the ions are consumed (F − ) or formed (TiF 6 2− , ZrF 6 2− ) merely at the base of the nanotube, and the upper dissolution is insignificant, where it was hypothesized that the ions had a linear dispersion in the electrolyte along a concentration gradient between the tube bottom and the bulk electrolyte. It should be mentioned that the concentration of F − and ionic species in the bulk electrolyte and at the bottom, respectively, is c 0 , while the concentration of F − and the ionic species at the bottom and the bulk electrolyte is zero [122] .

The XPS peak positions were compared to the reference peaks [172, 173] J o u r n a l P r e -p r o o f

It was predicted that the chemical diversity and dimensions of the MONs of the Tibased alloys possess interesting electronic and physical characteristics, which can be modulated for a wide range of purposes [71, 180] . From this viewpoint, organized arrays of MONs on Ti-Mn alloy with α + β microstructure can be a prospective material as both TiO 2 and Mn 2 O 3 are extensively employed in energy applications [181, 182] . In addition to this type of approach, the microstructural properties, mechanical behavior, and biocompatibility of low-cost β-type Ti- 

Long-term experiences reveal that some of the Ti-based alloys suffer inadequate load transfer to the adjoining remodeling bone that may cause bone resorption and ultimate detachment of the prosthetic devices [188] . To solve these difficulties and to attain better performance in terms of mechanical behavior and biocompatibility, new Ti-based alloys comprising non-toxic and non-allergic secondary elements, e.g., Nb, Ta, Zr, Hf, Mo, and Sn have been developed [189] . With regards to Hf, this element is a member of the same group with Ti in the periodic table. This suggests that an alloy of Ti with Hf would be expected to show good physicochemical properties. Besides that, the Ti-xHf alloy system does form any intermetallic compounds (IMCs) that are significant for excellent corrosion resistance [190, 191] . On the other hand, electrochemical anodization is an effective approach for the surface amendment of bio-implants which can also be employed in this system. In this regard, Jeong et al. [192, 193] MONs on the Ti-Hf alloys can be modified via changing the Hf content [192, 193] .

Based on the literature, a composite of Co 3 O 4 and TiO 2 NTs shows excellent performance in lithium-ion batteries [194] , supercapacitor [195] , wastewater treatment [196] , and photoelectric conversion [197] . Furthermore, highly porous Ti-Co alloys are recently being developed for biomedical applications [198] . Two methods are proposed for the combination of cobalt (II, III) oxides with TiO 2 NTs; (i) the anodization of Ti foils to create TiO 2 NTs followed by the deposition of cobalt (II, III) oxides via different approaches, and (ii) melting the Co and Ti into alloys and the formation of the MONs by electrochemical anodization [199, 200] . In the first method, the cobalt (II, III) oxides were deposited onto the surface of TiO 2 , leading to agglomeration, shedding, and 

Vanadium (V) is a transition metal, ubiquitously scattered in the water, air, soil, crude oil and is present in biological organisms and is a natural constituent in most living beings. Moreover, there are groups of organisms that utilize V in their biological pathways. This element is a biological constituent, thus it is not surprising that V-based therapeutic drugs have been tested for the treatment of some diseases, especially for the J o u r n a l P r e -p r o o f treatment of diseases caused by parasites, diabetes, and cancer [203] . However, in biomedical implants, the presence of V may not give the same effect.

Allergy is an adverse effect on patients with an implanted orthopedic prosthesis.

Although Ti is thought to be inert, the allergy towards Ti-based implants is still unknown. Recently, Engelhart and Segal [204] highlighted the case of a patient who experienced systemic dermatitis and implant failure after the surgical placement of a Tibased alloy plate in the left foot. The prosthesis was detached and the eruption was cleared in the following weeks. Microstructural and electrochemical analyses reveal that the plate and screws suffered galvanic corrosion due to their dissimilar microstructures.

This contributes to the in vivo release of vanadium. The patient was patch checked with some metals containing elements of the implant which gave a positive patch test reaction towards vanadium (III) chloride. This confirms the allergy towards V, thus clinicians should be aware of including vanadium as patch testing for patients with a suspected allergic reaction towards implants containing vanadium [204] .

As mentioned earlier, self-organized nanotubes could be developed successfully on a wide range of valve metals via optimized anodization processes. In some cases such as V, this approach is unsuccessful due to the increased solubility of oxides developed in common electrolytes. Thus, efforts to fabricate nanotubular arrays on Ti-V alloys are undertaken because V 2 O 5 is one of the most favorable oxides for supercapacitor applications [205] . Yang et al. [206, 207] atmosphere was drastically higher than that of the bare substrate.

In addition to the above-mentioned systems, other binary alloys have also been studied to fabricate MONs structures for various applications. For instance, Liu et al. [210] studied the anodic formation of Ti-Ni-O nanotubes on shape memory alloys via pulse anodization in glycerol-based electrolytes. They examined the effects of anodization parameters and the annealing process on the microstructures and surface morphology of MONs and found that the type electrolyte significantly affected the development of nanotubes (Fig. 11a-c) . This result could initiate focused research on the development of shape memory alloys for medical and non-medical applications. Besides that, Basahel et al. [213] studied the fabrication of self-ordered MONs anodized from Ti-Pt alloy with a low Pt content of 0.2 at% for photocatalytic hydrogen production. The MONs structure possessed a mean thickness of 13 μm which were composed of individual tube units with ~120 nm outer diameter. They have shown that prolonged anodization not only leads to the elongation of the nanotubes but also the increased particle density on the walls up to 250 μm -2 ( Fig. 11m-q) . This unique J o u r n a l P r e -p r o o f configuration resulted in a highly active photocatalyst for the production of H 2 under UV or visible light radiation.

Ti possesses low density, great biocompatibility, and corrosion resistance owing to the inherent oxide film on the surface, which is a good choice for medical applications [214] . Nevertheless, the inertness of Ti, along with its suboptimal mechanical behavior restricts the life cycle of Ti implants [215] . To overcome these limitations, Ti-based alloys are designed as alternative implant materials that could be microstructurally classified as α, near-α, α + β, metastable β, and stable β [216] . Due to their non-heattreatable character to maintain the α phase microstructure, the α and near-α Ti-based alloys have little influence on the mechanical behavior. In contrast, the β-based alloys attributable to the BCC crystal structure can be shaped even at low temperatures, which make it a proper option for multifaceted geometries. Merging the advantages of both phases, the α + β Ti-based alloys provide superior fracture toughness, tensile strength, wear-resistance, and heat treatable features enables the preparation of complex geometries for orthopedic purposes [217] . However, several studies have confirmed that the elastic behavior and load transfer from the implant device to the neighboring bone of the α + β type alloys are unsuitable for orthopedic applications [218] and could degrade after implantation [219] . In addition to modifying the chemical composition of the alloys, surface modification techniques such as physical deposition methods, thermochemical surface treatments, and electrochemical anodization have been J o u r n a l P r e -p r o o f investigated to modify the surface features of the Ti-based alloys [12, 13, 220] . In this section, the formation of MONs on ternary Ti-6Al-4V alloy is reviewed.

One of the pioneering efforts to utilize electrochemical anodization as an innovative approach for the surface modification of Ti-based alloys was performed by Dunn et al. [221, 222] , where porous surface coatings are formed by anodization and incorporating antibiotics onto the oxide surface. Zwilling et al. [223] also reported that anodization on

Ti and Ti-6Al-4V alloys in the F − ion solution is an effective approach to attain tunable tubular oxide layers under different anodization conditions [16, 17, 65, 133, .

Since the Ti-6Al-4V alloy is a dual-phase alloy, the development kinetics of nanotubes are dissimilar for the α and β phases [69] . Macak NTs over Ti6Al4V in connection with hard tissue engineering application was presented by Poddar et al. [264] , in which the anodization was carried at room temperature at different applied potential, i.e., 20, 25, and 30 V, as well as at a constant potential of 20 V at bath temperatures 30, 45, and 55 °C. As shown in Fig. 12a -f, the nanotube diameter and length increase with increasing the anodization voltage from 20 to 30 V. This suggests that longer NTs can be developed at higher voltages. Besides, dense NTs were formed as anodization was conducted at bath temperatures 45 and 55 °C (Fig. 12g-j) .

However, they believe that to recognize an exact growth mechanism at higher electrolyte temperature further studies is necessary. 

As mentioned above, among the Ti-based alloys, Ti-6Al-4V orthopedic implants are widely been used to substitute hard tissues and in bone fixation strategies due to the great strength, ductility as well as low density. Nevertheless, the main concern of using Ti-6Al-4V alloy in medical implants is the V content which could probably enhance the expressions of pro-inflammatory factors, provoke osteolysis, and have toxic effects in the body [204] . Research on the biological behavior of alloying elements shows that the chemical composition of alloys utilized in medical implants should be improved to reduce the adverse effects. Accordingly, alternative Ti-based alloys containing diverse alloying elements and concentrations are employed to improve the biocompatibility of the orthopedic implants. One such alloy is the Ti-6Al-7Nb [69] which possesses both the α and β phases, in which Al become constant the α phase while Nb as a substitute for V in the Ti-6Al-4V alloy becomes the stable β phase. This alloy is more ductile than J o u r n a l P r e -p r o o f

Ti-6Al-4V, provides higher formability for making complex parts with excellent corrosion resistance compared to the Ti-6Al-4V alloy [265] . For this reason, this alloy has received significant attention as femoral components of hip prostheses. Even though the integration of alloying elements could improve the physicochemical properties of Ti-based alloys, the bioinert character and the incapability of Ti implants to bond with the bone is still a challenging task and is among the major failure of orthopedic implants. To improve osseointegration, surface modification of the orthopedic implants is vital because the surface-modified implants deliver an improved medium for bone cell purposes, leading to improved incorporation of the implant with the juxtaposed bone tissue [62, 82] . To achieve this objective, various surface amendments are proposed to modify the physicochemical features of Ti-based alloys, such as sandblasting, hydrothermal process, sol-gel, physical as well as chemical vapor deposition [266] . Among them, the electrochemical anodization technique has attracted significant consideration owing to the effortlessness, lower cost, and capability of adjusting the surface properties in the nano regime [267] . MONs prepared on Ti-6Al-7Nb was comprehensively researched for medical purposes [269] . Recently, Ulfah et al. [140] also reported the formation of silver doped MONs with a mean diameter of 120 nm on Ti-6Al-7Nb alloy. These studies contribute significantly to the development of MONs for different biomedical applications such as medical implants, thanks to the microstructural features, photocatalytic mechanism, and antibacterial activity.

Ti and Ti-based alloys are the main metallic materials in biomedical appliances [218] , and significant attempts are focused on the substitution of alloying elements (Al and V), presently with non-toxic elements such as Nb and Zr [270, 271] . These substituting elements improve the mechanical behavior of the alloys because Nb is a β-stabilizer were developed as the Zr content increased (Fig. 14d-o) . Similar research focused on the formation of MONs structures on different Ti-Nb-Zr alloys was also performed [143, [277] [278] [279] [280] . Accordingly, the Ti-Nb-Zr alloys appear as potential substitutes for the Ti-6Al-4V alloy in different biomedical devices and medical implants [281] . 

In 

Quaternary β Ti-based alloys are receiving significant consideration as medical implant materials due to their very low Young's modulus analogous to human bone and outstanding biocompatibility [290] . The main objective of emerging such alloys is to reduce Young's modulus disparity between the bone (10−30 GPa) and the medical implant, which enhances the load sharing between them [291] . In this regard, different quaternary alloys such as Ti-Nb-Ta-Zr alloys (including Ti-4Nb-4Ta-15Zr [292] , Ti-29Nb-13Ta-4.6Zr [293] , and Ti-35Nb-5Ta-7Zr [294] ) were investigated. Among them, the Ti-35Nb-5Ta-7Zr possesses a lower elastic modulus (55 GPa) and thus is considered as one of the best options for medical implants [290] . However, works on the physicochemical, mechanical, and biological features of the MONs on such quaternary alloys are restricted [295] . Anodic oxidation of the Ti-Nb-Ta-Zr alloys gives dissimilar formation rates owing to the dissimilar electrochemical oxidation rates of these elements in the alloy [146] . As a result, the dissolution was more selective, and homogenous self-ordered anodic nanotubes grow to different sizes, where tubes with a larger diameter are adjacent with eight tubes with a smaller diameter. The nanotube growth initiates from two films -an outer nanoporous layer and a nanotube layer -from the potential sweep using a potentiostat. The outer nanoporous J o u r n a l P r e -p r o o f film dissolves in the electrolyte, thus prolonged anodization time is necessary to expand the nanotubes when the applied potential is low [147] . Recently Chiu et al. [295] presented a delicate anodizing process for the fabrication of quaternary Ti-Nb-Ta-Zr-O MONs which gave high-performance PEC water splitting. The MONs showed a higher photoactivity compared to the pristine TiO 2 NTs. The higher photoactivity is because of the incorporation of alloying elements which improve the number of charge carriers, adjust the electronic configuration, and improve the hole injection kinetics for enhanced water splitting. They found that the anodization time could be tuned to attain the required nanotube length for different samples (Fig. 15a-d) , which eliminates the effect of nanotube length on the PEC performance. Based on these findings, the MONs structures could be utilized for effective PEC water splitting for solar hydrogen production. The non-toxic and biocompatible features of this nanoarchitecture could achieve a distinct yet practically viable application in biotechnologically important fields, such as PEC biosensing and PEC biofuel reforming [295] .

On the other hand, compared to the crystalline alloys, glass-forming amorphous Tibased alloys possess superior features, e.g. higher strength and wear resistance, as well as and in part a lower elastic modulus and comparable corrosion resistance. In this context, some glass-forming Ti-based alloys, such as the Ti60-Zr10-Si15-Nb15, are fabricated for implant purposes [296] . These alloys have very low corrosion rates in simulated body fluid (SBF) and sufficient apatite forming capability [297] . Also, an Nb comprising alloy possesses enhanced glass-forming capacity and mechanical behavior compared to the Ti75-Zr10-Si15 [298] . The anodization behavior of the glassy forms of Ti-based alloys is still in the preliminary stages of the investigation. For the first time, J o u r n a l P r e -p r o o f two glass-forming Ti-based alloys, the Ti75-Zr10-Si15 and Ti60-Zr10-Si15-Nb15 alloys were anodized in an EG-containing electrolyte to form nanotubes [299] .

As these alloys are amorphous, they have no grain arrangement that is particularly interesting for the anodization of crystalline Ti, where the grain organization plays an important role in the consistency of the nanotubes [300] . As illustrated in Fig. 16a- xZr [302] , Ti-24Nb-4Zr-8Sn [303] , and Ti-xNb-Ag-Pt [304] , were investigated of their ability to form the MONs layer on these alloys. In the first case, Zhang et al. [302] investigated the formation of MONs on the Ti-6Al-4V-xZr alloys (x = 0, 20, 30, 40, 51) via electrochemical anodization in the mixture of 98% EG + 2% deionized water + 0.2 mol.L -1 NH 4 F at 20 V from 5 to 300 min. They reported that the anodization was comparatively intense and the wear resistance was improved with the addition of Zr. In The microstructural assessments showed that the needle-like configuration on α and α″ steadily vanishes with the increase of Nb, while the β-phase equilibrium structure appears with decreased particle size. In addition, the morphology of nanotubes could be altered depending on the Nb content. Consequently, as the Nb content increases, the J o u r n a l P r e -p r o o f highly ordered MONs degrades into irregular nanotubes, wherein the disparity in dissolution region at the bottom of the nanotubes was dependent on the Nb content. 

In addition to direct anodization of Ti alloys to develop MONs on the alloy surface, there are some different combined approaches, such as the PVD-assisted electrochemical anodization [74, 127, 129, 136, 166, 253, [305] [306] [307] [308] [309] and hydrothermalassisted electrochemical anodization [310] . In an innovative approach, Rafieerad et al. followed by anodization at 60 V between 30 to 300 min [127] . More recently, they reported a novel approach for an optimized PVD deposition process, anodization, and spin coating, to improve the mechanical, tribocorrosion performance, anti-bacterial and osteoblast cytocompatibility behavior of the Ti-6Al-7Nb implant. In this regard, silver nanoparticles/graphene oxide (AgNPs/GO) decorations on combined nanotubular coating are also developed. This hybrid approach could be also utilized in the fabrication of various complex multifaceted nanotubes for a variety of orthopedic ailments [124] .

The anodic mono-oxide nanotubes with outstanding properties have attracted much attention for various potential applications as anti-corrosion, self-cleaning thin films, and paints to sensors [311] , electrocatalysis, and water photoelectrolysis [312] , dyesensitized and solid-state bulk heterojunction solar cells [313] , photocatalysis [314] .

These nanostructures are also used in biomedical applications as biocompatible materials to enhance osseointegration, drug delivery systems, and advanced tissue engineering [43, [315] [316] [317] [318] . On the other hand, electrochemically developing MONs on various Ti-based alloys has been increasing in popularity as a chemical way to augment the existing and endow new properties to them. However, it is ambiguous whether this tactic can elicit properties strong enough to make MONs competitive for commercial purposes in medicine and elsewhere. 

In were also developed on the anodic MONs in Ti-15Mo, Ti-13Nb-13Zr, and Ti-6Al-7Nb alloys after alkali treatment which can be considered for dental implants [322] . These observations show that there are still many challenges to estimating MONs' biomineralization ability, especially in the case of binary, ternary, and quaternary Tibased alloys.

The cell-implant interplay is a significant process for effective clinical implantation while the surface adaptation in the nano regime considerably alters the cellular response [43, 68] . proliferation [68] . The study shows that MC3T3 cells interact in a different way with

MONs of dissimilar Ti alloys, where the adverse response to the pre-osteoblast cells was not observed. These findings suggest that osteoblast cell activity can be drastically improved through MONs surface engineering, and thus provide a suitable platform for orthopedic implants.

Titania nanotubes have suitable biocompatibility seeing that they exhibit some antibacterial behavior, low cytotoxicity, appropriate firmness, and cytocompatibility [325, 326] . Nevertheless, Ti-based materials possess inadequate antibacterial properties and many attempts have been conducted to improve their antibacterial activities, e.g.

surface improvements of titania nanotubes using incorporation of AgNPs into the tubular structure for medical implants [51, 327] . diameter NTs. Also, rutile could present higher antibacterial efficiency relative to anatase [320, 328] .

The NTs could be used for the encapsulation and identified transport of antibacterial agents. Popat et al. [11] employed TiO 2 NTs for the identified transport of gentamicin off-implants at the implantation zone. The liberation kinetics of gentamicin from these nano configurations and its impact on the bacterial adhesion were explored.

The outputs of these assessments corroborated the superior capacity of the nano configurations for the antibiotic drug encapsulation, whereby the bacterial linkage on the NTs decreased drastically [11] .

The antibacterial efficiency of the medical alloys covered with TiO 2 NTs could be boosted through the integration of other antibacterial mediators, e.g., AgNPs. In this context, Lai et al. [329] decorated AgNPs onto the TiO 2 NTs to enhance the implant confrontation against Escherichia coli (E. Coli) as a Gram-negative bacteria. Mei et al. [51] prepared TiO 2 NTs by integrating nanosized silver to enhance the antibacterial efficiency of dental implants against post-surgical bacterial infections. The amount of silver reserved the nanotubular morphology and effectively sterilized the oral pathogens. The results showed that the operation of inferior plasma voltages could give rise to an amassing of a high level of Ag on the surface, which notably compromised the biocompatibility of the sample. On the contrary, a low level of silver decoration was detected at high plasma voltages. The specimens produced at a high voltage are stated to possess continued antibacterial behavior owing to the adequate silver decoration in the right depths of nanotubes [328] .

Sarraf et al. [74, 328] recently prepared highly-ordered MONs decorated with Ag 2 O nanoparticles for enhanced in vitro performance of Ti-6Al-4V ( Fig. 18a and b) . 

Several assessments have provided evidence that MSCs, osteoclasts as well as Ti-6Al-7Nb after the first day of cultivation due to the inherent bioactivity of the substrate. However, the mutual action of metallic substrates with osteoblast in extended culturing times and implantation phase is an important issue that should be considered in developing nanostructured implants [124] . It is verified that the Ti with nanoporous structure encourages the ripening of focal linkages and the development of filopodia with specific nanoscale protrusions through the osteogenic cells [124] . In agreement with the MTT-ALP analysis, the microscopy observations in Fig. 19 

In general, there is insufficient in vivo data to recognize the reasons for the improved osseointegration and osteoconductivity of the nanostructured implants. However, some investigations of in vivo behavior on titania nanotube arrays with diverse properties are performed [44, 316, [334] [335] [336] [337] [338] [339] . For instance, the electrochemical behavior, surface features and improved in vivo bone reaction of nanostructures titania on microstructured surfaces of blasted, screw-formed Ti-based implants has been studied by Sul et al. al. [344] also reported that the nanotubes coating (length up to 1 μm) was free from damages following the implantation step. These findings show the significant progress in terms of improving and controlling bone-forming functionality for advanced orthopedic implant applications [72] . Recently, in a comprehensive study, Bose et al. Nevertheless, there are two concerns required to be clarified before more advancing anodic nanotubes technology as a drug carrier: (i) uncontrolled liberation of drug and (ii) poor mechanical behavior [347] . To overcome these issues, efforts have focused on developing a drug carrier using a composite of biodegradable polymer/anodic nanotubes [347] [348] [349] [350] . Instances of primary medical purposes of titania nanotubes towards bone healing and medical implants, cardiovascular stents, dentistry and cancer treatment are accessible [333, [351] [352] [353] . These attitudes can be further developed by using various

MONs surface modifications, which can be promising strategies for improving boneimplant interaction and accelerating the healing time [124, 129] . However, anodic nanotube research in orthopedic directions is still in its infancy and there is a long distance to go in clinical use. The biological interactions between cells and anodic nanotubes, especially MONs are required to expand from the cellular stage to the molecular phase and from morphological alterations to molecular changes. It is wellestablished that the diameter of nanotubes has direct effects on adhesion, scattering, and growth of osteoblast and mesenchymal stem cells, thus the consistency and basis of this development as well as other factors stimulating cells' performance are obliged to be further discovered [82] .

Despite vast global advances in orthopedic implants [354] ; however, there are no standardized schemes for evaluating fracture healing, with physicians relying on X-rays that are merely helpful at later steps of healing [355] . The global orthopedic tools market is expected to drop from $52.7 billion in 2019 to $39.3 billion in 2020 at a J o u r n a l P r e -p r o o f compound annual growth rate (CAGR) of -25.6%. This decrement is predominantly due to the COVID-19 outbreak and the measures to contain it [356] . Numerous medical care services in affected countries have been entirely closed or have been merely presenting minimal treatment for emergency cases. Accordingly, orthopedic surgeries have been delayed or even canceled owing to the nation's lockdown [357] [358] [359] , whereby the production of orthopedic devices and implants has been sharply decreased thanks to prolonging factory closures. The global orthopedic tools market is then expected to resume and raise at a CAGR of 5% from 2021 and overtake $63.6 billion in 2023 [356] .

With the growth of the medical implants market, there is great potential for the smart implant systems, which can incorporate with current orthopedic hardware platforms to give physicians information about each patient's healing trajectory [355, 360] . In this regard, Parkes [361] [355, 362] .

The main applications of this smart design seem to be in orthopedic implants (such as knee and hip arthroplasty, spinal fusion as well as fracture fixation) and dental implants, where physical stimuli are obtained using special technology used in implants.

Osteoarthritis of the knee is one of the most widespread musculoskeletal pathologies worldwide. Smart knee implants take an important part in the properties of knee biomechanics. From the data of intelligent knee implants, the peak force such as walking after total knee arthroplasty is around 1.8-2.6 times of the body weight and occurs in the middle of the tibial tray. Wholly in vivo purposes for fixed intelligent knee implants are still part of applied research and not part of clinical practice. Due to the importance of bio-functionality of permanent intelligent knee implants, future applications of these implants must involve the protection of the knee from external forces which hasten the wear, implant loosening, or premature collapse of the implant J o u r n a l P r e -p r o o f [363] . Osteoarthritis is also a frequent problem found in the hip. The enthusiasm towards in vivo intelligent hip implants is presently associated with applied research, and not towards clinical applications for the specific care of the patient. Accordingly, records from intelligent hip implants could be used to describe the load circumstances for testing and authenticating the in vitro function of implants [364, 365] . Besides this, intelligent implants can present some vital information about the function of posture, motion, and muscle activation in spine biomechanics, which is very essential as the spine loading takes a crucial part in the disease process and the therapeutic process for patients with lower back pain. Scrutinizing the loads on an intelligent fracture fixation device during weight-bearing is proof of the strengthening and fracture healing [363] .

Despite the above description, the sensor concept may not very practical particularly at the outer surface as the cellular layer will cover that within few hours and beyond a few days, those sensors generally don't function [366] .

On the other hand, smart implants probably have a better future in the field of spinal and dental implants [367] [368] [369] [370] [371] [372] . In this context, a self-directed intelligent dental prosthesis has been introduced by Van Ham et al. [367] for rapid rehabilitation, wherein the device can connect wirelessly with an exterior transceiver, which enables a patienttailored approach. A monolithic human oral motion-powered smart dental implant with suitable mechanical strength has been proposed by Park et al. [368] as an ambulatory photo-biomodulation therapy modality, wherein the system could convert human oral movements into well-regulated in situ light irradiances. This feature is made possible through the energy collecting from dynamic human oral movements using the developed piezoelectric dental crown, a linked circuit, and micro light emitting diodes (LEDs), as illustrated in Fig. 22 . The findings of this comprehensive study not only lead J o u r n a l P r e -p r o o f to highly advanced multi-functional implants to avoid peri-implant complications and lessen the risk of implant failure, but also could be employed to other orthopedic implants prone to continuous exposure to bacterial burdens.

Regarding the smart spinal implants, many efforts have been made to set up various sensing tactics; nevertheless, they fail to provide mechanical sensing necessities or deficiency in vivo translatability [373] [374] [375] [376] . This also provides some important physical data from inside the body, such as pressure, force, strain, displacement, proximity, and temperature [377] . This could significantly decrease the number of patients admitted to the hospital. Apart from the above explanations, intelligent orthopedic implantation for clinical practice is a challenging task, because the integration of the current sensor technology requires some substantial modifications of the implants [378] . Also, the physicochemical properties of anodic nanotubes, in particular, MONs for various orthopedic applications should be assessed in detail [307] . Thus, nano surface modification and biosensors for next-generation intelligent orthopedic implants should be simple, tiny, robust, and reasonably priced [363] , wherein deeper insights into their biomechanical function is vital before choosing a proper sensing mode. Based on innovative medical approaches, it is conceivable that a new generation of smart orthopedic implants will eventually become available to surgeons and enable intensive medical care.

One-dimensional anodic nanotubes are promising biomaterials in a broad range of biomedical applications due to their large surface-to-volume ratio, low-cost, chemical stability, outstanding biocompatibility, and resistance to bio-corrosion. In the field of 

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Obtaining self-organized nanotubes on biomedical Ti-Mo alloys

Formation of Photocatalytically Active TiO2 Layers on Ti-Nb Alloys by Two-Step Thermal Oxidation

Ultrafast oxide nanotube formation on TiNb, TiZr and TiTa alloys by rapid breakdown anodization

Effect of microstructure on the nanotube growth by anodic oxidation on Ti-10Nb alloy

Anodic oxide nanotube layers on Ti-Ta alloys: Substrate composition, microstructure and self-organization on two-size scales

Nanotubular structure formation on Ti-6Al-4V and Ti-Ta alloy surfaces by electrochemical methods

Formation of Self-Organized Zirconium Titanate Nanotube Layers by Alloy Anodization

Metallurgical aspects on the formation of self-organized anodic oxide nanotube layers

Control of morphology and composition of selforganized zirconium titanate nanotubes formed in (NH4)2SO4/NH4F electrolytes

Synthesis of self-organized mixed oxide nanotubes by sonoelectrochemical anodization of Ti-8Mn alloy

Simultaneous enhanced antibacterial and osteoblast cytocompatibility performance of Ti6Al7Nb implant by nano-silver/graphene oxide decorated mixed oxide nanotube composite

Large-scale hybrid silver nanowall-reduced graphene oxide biofilm: A novel morphology by facile electrochemical deposition

Not-yet-designed multilayer Nb/HA/MWCNT-Au/Se/AuNPs and NbO2/HA/GO/Se biocomposites coated Ti6Al7Nb implant

Vertically oriented ZrO2TiO2Nb2O5Al2O3 mixed nanopatterned bioceramics on Ti6Al7Nb implant assessed by laser spallation technique

Graphene Oxide Modified Anodic Ternary Nanobioceramics on Ti6Al7Nb Alloy for Orthopedic and Dental Applications, Procedia Engineering

Toward improved mechanical, tribological, corrosion and in-vitro bioactivity properties of mixed oxide nanotubes on Ti-6Al-7Nb implant using multi-objective PSO

Microstructural development and corrosion behavior of self-organized TiO2 nanotubes coated on Ti-6Al-7Nb

Self-organized TiO2 nanotube layer on Ti-6Al-7Nb for biomedical application

Self-organized nanotubular oxide layers on Ti-6Al-7Nb and Ti-6Al-4V formed by anodization in NH4F solutions

Effect of microstructural evolution on wettability and tribological behavior of TiO2 nanotubular arrays coated on Ti-6Al-4V

Silver oxide nanoparticles-decorated tantala nanotubes for enhanced antibacterial activity and osseointegration of Ti6Al4V

Highly-ordered TiO2 nanotubes decorated with Ag2O nanoparticles for improved biofunctionality of Ti6Al4V

Nanomechanical properties, wear resistance and in-vitro characterization of Ta2O5 nanotubes coating on biomedical grade Ti-6Al-4V

Fabrication of anti-aging TiO2 nanotubes on biomedical Ti alloys

Nanotube Nucleation Phenomena of Titanium Dioxide on the Ti-6Al-4V Alloy Using Anodic Titanium Oxide Technique

Adhesion measurement of highly-ordered TiO2 nanotubes on Ti-6Al-4V alloy

Synthesis and characterization of Ag-doped TiO2 nanotubes on Ti-6Al-4V and Ti-6Al-7Nb alloy

Microstructure and electrochemical behavior of TiO2 nanotubes coated on titanium-based substrate before and after thermal treatment

Precalcification Treatment of TiO2 Nanotube on Ti-6Al-4V Alloy

Anodic growth of uniform nanotube arrays on biphase Ti35Nb5Zr alloy

Electrochemical formation of selforganized anodic nanotube coating on Ti-28Zr-8Nb biomedical alloy surface

Anodic oxide nanotubes on Ti alloys

Self-Organization of Anodic Nanotubes on Two Size Scales

Nanotube oxide coating on Ti-29Nb-13Ta-4.6Zr alloy prepared by self-organizing anodization

Evaluation of pore diameter of anodic porous films formed on aluminum

TiO2 nanotubes: Tailoring the geometry in H3PO4/HF electrolytes

Transition from Nanopores to Nanotubes: Self-Ordered Anodic Oxide Structures on Titanium−Aluminides

Self-organized porous and tubular oxide layers on TiAl alloys

A new route for the formation of self-organized anodic porous alumina in neutral electrolytes

Corrosion behaviour of Ti-15Mo alloy for dental implant applications

Laser surface treatment of Ti-10Mo alloy under Ar and N2 environment for biomedical application

Ti-15Mo Alloy Decreases the Stress Concentration in Mandibular Angle Fracture Internal Fixation Hardware

Self-organized nano-tubes of TiO2-MoO3 with enhanced electrochromic properties

MoO3 in Self-Organized TiO2 Nanotubes for Enhanced Photocatalytic Activity

Fabrication of double-walled TiO2 nanotubes with bamboo morphology via one-step alternating voltage anodization

Development of Ti-Mo alloys for biomedical applications: microstructure and electrochemical characterization

Mechanical Properties of Biomedical ß-Type Titanium Alloy with Rare-Earth Metal Oxide Particles Formed by Rare-Earth Metal Addition

Studies on Ti-29Nb-13Ta-4.6Zr alloy for use as a prospective biomaterial

Characterization of the morphology, structure and wettability of phase dependent lamellar and nanotube oxides on anodized Ti-10Nb alloy

Nb2O5/TiO2 heterojunctions: synthesis strategy and photocatalytic activity

A transparent metal: Nb-doped anatase Ti O 2

Corrosion of metallic biomaterials: A review

Optimized fabrication and characterization of TiO2-Nb2O5-Al2O3 mixed oxide nanotube arrays on Ti-6Al-7Nb

High-aspect-ratio TiO2 nanotubes by anodization of titanium

Techniques for Deposition of Coatings with Enhanced Adhesion to Bio-Implants, Adhesion in Pharmaceutical

Electrochemical characteristics of nanotubes formed on Ti-Nb alloys

Nanotube oxide coating on Ti-29Nb-13Ta-4.6 Zr alloy prepared by self-organizing anodization

Nanostructure and corrosion behaviors of nanotube formed Ti-Zr alloy

X-ray Photoelectron Spectroscopy Study of High-and Low-Temperature Forms of Zirconium Titanate

Self-organized porous titanium oxide prepared in H 2 SO 4/HF electrolytes

Enhanced interfacial adhesion and osseointegration of anodic TiO2 nanotube arrays on ultra-fine-grained titanium and underlying mechanisms

The role of TiO2 nanotube surface on osseointegration of titanium implants: Biomechanical and histological study in rats

Thick self-organized porous zirconium oxide formed in H2SO4/NH4F electrolytes

Fabrication and characterization of smooth high aspect ratio zirconia nanotubes

Influences of structure and composition on growth of anodic oxide films on Ti Zr alloys

Self-ordered nanotubes of titanium oxides and titanium alloy oxides for energy storage and battery applications

Water-oxidizing complex in Photosystem II: Its structure and relation to manganese-oxide based catalysts

Ordered Arrays of Ti-Mn Oxide Nanotubes for High Capacity Li-Ion Battery

Microstructures, mechanical properties and cytotoxicity of low cost beta Ti-Mn alloys for biomedical applications

Surface characteristics and in vitro biocompatibility of a manganese-containing titanium oxide surface

Outstanding supercapacitive properties of Mn-doped TiO2 micro/nanostructure porous film prepared by anodization method

Preparation and capacitance properties of Mn-doped TiO2 nanotube arrays by anodisation of Ti-Mn alloy

Self-organized TiO2-MnO2 nanotube arrays for efficient photocatalytic degradation of toluene

Biological aspects of metals and metal-related diseases

Recent metallic materials for biomedical applications, Metallurgical and materials transactions A

-40wt%)Hf alloys for metallic biomaterials use

Electrochemical characterization of cast Ti-Hf binary alloys

Nanotube formation and morphology change of Ti alloys containing Hf for dental materials use

Surface characteristics of HA coated Ti-Hf binary alloys after nanotube formation

Co3O4-coated TiO2 nanotube composites synthesized through photo-deposition strategy with enhanced performance for lithium-ion batteries

Supercapacitive performance of homogeneous Co 3 O 4/TiO 2 nanotube arrays enhanced by carbon layer and oxygen vacancies

Cobalt-doped black TiO2 nanotube array as a stable anode for oxygen evolution and electrochemical wastewater treatment

Co3O4-modified TiO2 nanotube arrays via atomic layer deposition for improved visible-light photoelectrochemical performance

Synthesis and characterization of Ti-Co alloy foam for biomedical applications

Preparation of Fe-doped ZrO2 nanotube arrays by anodization of Zr-Fe alloy and their magnetic properties

Preparation and photoluminescence properties of Eu3+-doped ZrO2 nanotube arrays

Preparation and properties of Co 3 O 4-doped TiO 2 nanotube array electrodes

TiO2CoxOy composite nanotube arrays via one step electrochemical anodization for visible light-induced photocatalytic reaction

Vanadium compounds in medicine

Allergic reaction to vanadium causes a diffuse eczematous eruption and titanium alloy orthopedic implant failure

Effects of annealing on electrochemical performance in graphene/V2O5 supercapacitor

Electrochromic properties of anodically grown mixed V2O5-TiO2 nanotubes

Vertically aligned mixed V 2 O 5-TiO 2 nanotube arrays for supercapacitor applications

Growth, structure, and photocatalytic properties of hierarchical V2O5-TiO2 nanotube arrays obtained from the one-step anodic oxidation of Ti-V alloys

Tribo-Mechanical Properties and Corrosion Behavior Investigation of Anodized Ti-V Alloy

Anodic fabrication of Ti-Ni-O nanotube arrays on shape memory alloy

Fabrication and enhanced visible-light photoelectrochemical performance of periodic hierarchical 3D Ti-Fe-O structure

Vertically oriented Ti-Pd mixed oxynitride nanotube arrays for enhanced photoelectrochemical water splitting

Self-decoration of Pt metal particles on TiO2 nanotubes used for highly efficient photocatalytic H2 production

Biomedical applications of titanium and its alloys

The effects on bone cells of metal ions released from orthopaedic implants. A review, Clinical cases in mineral and bone metabolism

Homogeneous Anodic TiO2 Nanotube Layers on Ti-6Al-4V Alloy with Improved Adhesion Strength and Corrosion Resistance

Titanium-Based Alloys for Biomedical Applications

Surface Engineered Surgical Tools and Medical Devices

Ti alloy design strategy for biomedical applications

Thermodynamic and microstructural analyses of photocatalytic TiO2 from the anodization of biomedical-grade Ti6Al4V in phosphoric acid or sulfuric acid

Gentamicin sulfate attachment and release from anodized Ti-6Al-4V orthopedic materials

Formation and characterization of anodized layers on CP Ti and Ti-6Al-4V biomaterials

Structure and physicochemistry of anodic oxide films on titanium and TA6V alloy

Synthesis and characterization of titania nanotubes by anodizing of titanium in fluoride containing electrolytes

Enhancing surface characteristics of Ti-6Al-4V for bio-implants using integrated anodization and thermal oxidation

Fabrication and characterization of self-organized mixed oxide nanotube arrays by electrochemical anodization of Ti-6Al-4V alloy

Adhesion of sol-gel derived hydroxyapatite nanocoatings on anodised pure titanium and titanium (Ti6Al4V) alloy substrates

Surface microstructures and epoxy bonded shear strength of Ti6Al4V alloy anodized at various temperatures

Morphologies of nanostructured TiO2 doped with F on Ti-6Al-4V alloy

Preparation of stable superamphiphobic surfaces on Ti-6Al-4V substrates by one-step anodization

Facile fabrication of superhydrophobic surfaces with low roughness on Ti-6Al-4V substrates via anodization

In vivo and in vitro response to electrochemically anodized Ti-6Al-4V alloy

Fabrication of highly ordered TiO2 nanotube arrays via anodization of Ti-6Al-4V alloy sheet

Electrochemical behaviour and bioactivity of self-organized TiO2 nanotube arrays on Ti-6Al-4V in Hanks' solution for biomedical applications

Enhanced compatibility and initial stability of Ti6Al4V alloy orthodontic miniscrews subjected to anodization, cyclic precalcification, and heat treatment

Improved osteoblast and chondrocyte adhesion and viability by surface-modified Ti6Al4V alloy with anodized TiO2 nanotubes using a super-oxidative solution

Surface nanotopography-induced favorable modulation of bioactivity and osteoconductive potential of anodized 3D printed Ti-6Al-4V alloy mesh structure

Surface modification and bioactivity of anodic Ti6Al4V alloy

Influence of oxidative nanopatterning and anodization on the fatigue resistance of commercially pure titanium and Ti-6Al-4V

Optical and Electrochemical Properties of Self-Organized TiO2 Nanotube Arrays From Anodized Ti-6Al-4V Alloy

The bioactivity and photocatalytic properties of titania nanotube coatings produced with the use of the low-potential anodization of Ti6Al4V alloy surface

Effect of electrolyte type on the morphology and crystallinity of TiO2nanotubes from Ti-6Al-4V anodization

Preparation of titanium oxide and hydroxyapatite on Ti-6Al-4V alloy surface and electrochemical behaviour in bio-simulated fluid solution

Improved in vitro angiogenic behavior on anodized titanium dioxide nanotubes

Bacterial adherence to anodized titanium alloy

Growth of TiO2-based nanotubes on Ti-6Al-4V alloy

Preparation and characterization of TiO2 nanotube arrays on Ti6Al4V surface for enhancement of cell treatment

Hydroxyapatite precipitation on nanotubular films formed on Ti-6Al-4V alloy for biomedical applications

Morphological and chemical relationships in nanotubes formed by anodizing of Ti6Al4V alloy

Anodization of highly ordered TiO2 nanotube arrays using orthogonal design and its wettability

Structural, morphological, and electrochemical corrosion properties of TiO2 formed on Ti6Al4V alloys by anodization

Mechanism of TiO2 nanotubes formation on the surface of pure Ti and Ti-6Al-4V alloy

Mechanical Property Enhancement of Ti-6Al-4V by Multilayer Thin Solid Film Ti/TiO2 Nanotubular Array Coating for Biomedical Application

Thermal stability andin vitrobioactivity of Ti-Al-V-O nanostructures fabricated on Ti6Al4V alloy

Titanium Alloys: Towards Achieving Enhanced Properties for Diversified Applications

Morphology of Nanostructured TiO2 Surfaces for Biomedical Implants Developed by Electrochemical Anodization

The diameter of nanotubes formed on Ti-6Al-4V alloy controls the adhesion and differentiation of Saos-2 cells

Fatigue strength of Ti-6Al-4V alloy with surface modified by TiO2 nanotubes formation

Anodic voltage dependence of Ti-6Al-4V substrates and hydroxyapatite coating

TiO2 nanostructured surfaces for biomedical applications developed by electrochemical anodization, IOP Conference Series: Materials Science and Engineering

Electrochemical response of TiO2 anodic layers fabricated on Ti6Al4V alloy with nanoporous, dual and nanotubular morphology

Anodised TiO2 nanotubes as a scaffold for antibacterial silver nanoparticles on titanium implants

Bioactivity and generation of anodized nanotubular TiO2 layer of Ti-6Al-4V alloy in glycerol solution

A study on influence of anodization on the morphology of titania nanotubes over Ti6Al4V alloy in correlation to hard tissue engineering application

In vitro human monocyte response to wear particles of titanium alloy containing vanadium or niobium

Surface Modification on Titanium Alloy for Biomedical Application

Fluoride concentration effect on the anodic growth of self-aligned oxide nanotube array on Ti6Al7Nb alloy

Changing bioperformance of TiO2 amorphous nanotubes as an effect of inducing crystallinity

Electrochemical behavior and effect of heat treatment on morphology, crystalline structure of self-organized TiO2 nanotube arrays on Ti-6Al-7Nb for biomedical applications

In vitro cytotoxicity and hemocompatibility studies of Ti-Nb, Ti-Nb-Zr and Ti-Nb-Hf biomedical shape memory alloys

The effect of Zr content on the microstructure, mechanical properties and cell attachment of Ti-35Nb-xZr alloys

Mechanical, physical, and chemical characterization of Ti-35Nb-5Zr and Ti-35Nb-10Zr casting alloys

Effects of alloying elements on the cytotoxic response of titanium alloys

Enhanced photoassisted water electrolysis using vertically oriented anodically fabricated Ti− Nb− Zr− O mixed oxide nanotube arrays

Fabrication and hydrogen sensing properties of doped titania nanotubes

Electrochemical and surface behavior of hydyroxyapatite/Ti film on nanotubular Ti-35Nb-xZr alloys

Anodic Fabrication of Ti-Nb-Zr-O Nanotube Arrays

Surface Phenomena of Hydroxyapatite Film on the Nanopore Formed Ti-29Nb-xZr Alloy by Anodization for Bioimplants

Correlation of the nanostructure of the anodic layers fabricated on Ti13Nb13Zr with the electrochemical impedance response

Nanotubular oxide layers and hydroxyapatite coatings on 'Ti-13Zr-13Nb'alloy

Are new TiNbZr alloys potential substitutes of the Ti6Al4V alloy for dental applications? An electrochemical corrosion study

Morphology of hydroxyapatite coated nanotube surface of Ti-35Nb-xHf alloys for implant materials

Variations of nanotubes on the Ti-Nb-Hf alloys with applied voltages

Effects of Hf content on nanotubular structure of Ti-29Nb-xHf ternary alloys

Formation of titanium dioxide nanotubes on Ti-30Nb-xTa alloys by anodizing

Anodic formation of self-organized Ti(Nb,Sn) oxide nanotube arrays with tuneable aspect ratio and size distribution

Control of nanotube shape and morphology on Ti-Nb (Ta)-Zr alloys by varying anodizing potential

Fabrication of Ti-Al-Zr alloy oxide nanotube arrays in organic electrolytes by anodization

Fabrication and Photoelectrochemical Properties of Self-Organized Mixed Oxide Nanotubes by Anodization of Ti-2Al-1.5 Mn Alloy

Mechanical properties and corrosion resistance of low rigidity quaternary titanium alloy for biomedical applications

Titanium alloys in total joint replacement-a materials science perspective

A New Ti-15Zr-4Nb-4Ta alloy for medical applications

Fatigue performance and cyto-toxicity of low rigidity titanium alloy

High-strength metastable beta-titanium alloys for biomedical applications

Fully Depleted Ti-Nb-Ta-Zr-O Nanotubes: Interfacial Charge Dynamics and Solar Hydrogen Production

Designing biocompatible Ti-based metallic glasses for implant applications

Designing new biocompatible glass-forming Ti75-xZr10NbxSi15 (x = 0, 15) alloys: corrosion, passivity, and apatite formation

Effect of Nb addition on microstructure evolution and nanomechanical properties of a glass-forming Ti-Zr-Si alloy

Self-organized double-wall oxide nanotube layers on glass-forming Ti-Zr-Si(-Nb) alloys

Influence of the Ti microstructure on anodic self-organized TiO2 nanotube layers produced in ethylene glycol electrolytes

Production and characterization of TiO2 nanotubes on Ti-Nb-Mo-Sn system for biomedical applications

Effect of Zr addition on the microstructure and tribological property of the anodization of Ti-6Al-4V alloy

Nanotubular oxide layers formation on Ti-24Nb-4Zr-8Sn and Ti-13Zr-13Nb alloys in the ethylene glycol-based electrolyte: The role of alloying elements and phase composition

Nanotube Morphology Changes on the Ti-xNb-Ag-Pt Alloy with Nb Contents

Alias, Statistical optimization and fretting fatigue study of Zr/ZrO2 nanotubular array coating on Ti-6Al-4V

Anodic pine cone-like WO 3/MoO 3/TiO 2 film with well-defined nanoflakes on Ti-6Al-7Nb implant

GEP-based method to formulate adhesion strength and hardness of Nb PVD coated on Ti-6Al-7Nb aimed at developing mixed oxide nanotubular arrays

Optimizing PVD conditions for electrochemical anodization growth of welladherent Ta 2 O 5 nanotubes on Ti-6Al-4V alloy

Silver/silver oxide nanorod arrays from physical vapor deposition and subsequent anodization processes

Characterization and osteogenic activity of SrTiO3/TiO2 nanotube heterostructures on microporous titanium

Formation mechanism of TiO2 nanotubes and their applications in photoelectrochemical water splitting and supercapacitors

TiO 2 nanotubes with ultrathin walls for enhanced water splitting

Solid state dye-sensitized solar cell-encyclopedia of applied electrochemistry

TiO2 photocatalysis: Design and applications

Anodization parameters influencing the morphology and electrical properties of TiO2 nanotubes for living cell interfacing and investigations

Electrochemical growth behavior, surface properties, and enhanced in vivo bone response of TiO2 nanotubes on microstructured surfaces of blasted, screwshaped titanium implants

A functionalized Sm/Sr doped TiO2 nanotube array on titanium implant enables exceptional bone-implant integration and also self-antibacterial activity

Synergistic effects of lanthanum and strontium to enhance the osteogenic activity of TiO2 nanotube biological interface

Hydroxyapatite growth on anodic TiO2 nanotubes

In vitro bioactivity and corrosion resistance enhancement of Ti-6Al-4V by highly ordered TiO 2 nanotube arrays

Preparation of hydroxyapatite-titanium dioxide coating on Ti6Al4V substrates using hydrothermal-electrochemical method

Alkali treatment of anodized titanium alloys affects cytocompatibility

Whole Genome Expression Analysis Reveals Differential Effects of TiO2 Nanotubes on Vascular Cells

The effect of TiO2 nanotubes on endothelial function and smooth muscle proliferation

TiO2 nanotube surfaces: 15 nm-an optimal length scale of surface topography for cell adhesion and differentiation

Tailoring the surface functionalities of titania nanotube arrays

Antibacterial nano-structured titania coating incorporated with silver nanoparticles

Highlyordered TiO2 nanotubes decorated with Ag2O nanoparticles for improved biofunctionality of Ti6Al4V

Bioinspired patterning with extreme wettability contrast on TiO2 nanotube array surface: a versatile platform for biomedical applications

Dermal fibroblast and epidermal keratinocyte functionality on titania nanotube arrays

Nanosize and vitality: TiO2 nanotube diameter directs cell fate

Improved bone-forming functionality on diameter-controlled TiO2 nanotube surface

Nanotubular oxide layers formed on the Ti-based implants surfaces-application and possible damages: a review

The evaluation of osseointegration of dental implant surface with different size of TiO 2 nanotube in rats

Enhanced osteointegration of medical titanium implant with surface modifications in micro/nanoscale structures

Strontium (Sr) and silver (Ag) loaded nanotubular structures with combined osteoinductive and antimicrobial activities

Nanoengineered stent surface to reduce instent restenosis in vivo

Effect of TiO 2 nanotubes arrays on osseointegration of orthodontic miniscrew

Cellular behavior on TiO2 nanonodular structures in a micro-to-nanoscale hierarchy model

In vivo evaluation of anodic TiO2 nanotubes: an experimental study in the pig

The nanoscale geometry of TiO2 nanotubes influences the osteogenic differentiation of human adipose-derived stem cells by modulating H3K4 trimethylation

Bioactivity of Ti-6Al-4V alloy implants treated with ibandronate after the formation of the nanotube TiO2 layer

On the mechanical integrity of retrieved dental implants

Mechanical degradation of TiO2 nanotubes with and without nanoparticulate silver coating

Effect of calcium phosphate coating and rhBMP-2 on bone regeneration in rabbit calvaria using poly (propylene fumarate) scaffolds

Titania nanotube arrays for local drug delivery: recent advances and perspectives

Anodized TiO 2 Nanotube Film For Controllable Drug Delivery

Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications

Synthesis and applications of titania nanotubes: Drug delivery and ionomer composites

Titanium Dioxide Nanotube Arrays for Cardiovascular Stent Applications

Metal TiO2 Nanotube Layers for the Treatment of Dental Implant Infections

TiO2 nanotubes as a therapeutic agent for cancer thermotherapy

Biomaterials in orthopaedics: the past and future with immune modulation

Smart bone plates can monitor fracture healing

Orthopedic Devices Global Market Report 2020-30: Covid 19 Impact and Recovery

Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans

Post-COVID-19 return to elective orthopaedic surgery-is rescheduling just a reboot process? Which timing for tests? Is chest CT scan still useful? Safety of the first hundred elective cases? How to explain the "new normality health organization" to patients?

COVID-19 and orthopaedic surgeons: the Indian scenario

Monitoring of postoperative bone healing using smart trauma-fixation device with integrated self-powered piezofloating-gate sensors

Improving patient outcomes with smart implants

Application of Electrochemical Aptasensors toward Clinical Diagnostics, Food, and Environmental Monitoring

Smart implants in orthopedic surgery, improving patient outcomes: a review, Innovation and entrepreneurship in health

Hip joint contact forces during stumbling, Langenbeck's Archives of Surgery

Hip joint loading during walking and running, measured in two patients

Sensing Cellular Metabolic Activity via a Molecular-Controlled Semiconductor Resistor

An autonomous smart dental prosthesis for fast rehabilitation

Human Oral Motion-Powered Smart Dental Implant (SDI) for In Situ Ambulatory Photo-biomodulation Therapy

Advanced smart biomaterials and constructs for hard tissue engineering and regeneration

Laser printing of silver-based micro-wires in ZrO2 substrate for smart implant applications

Smart orthopaedic implants: A targeted approach for continuous postoperative evaluation in the spine

Spinal implant, Google Patents

The use of fiber Bragg grating sensors in biomechanics and rehabilitation applications: the state-of-the-art and ongoing research topics

Biodegradable and flexible arterial-pulse sensor for the wireless monitoring of blood flow

Structural health monitoring in composite structures by fiber-optic sensors

Intelligent Control of a Spinal Prosthesis to Restore Walking After Neural Injury: Recent Work and Future Possibilities

Titanium Dioxide Nanotube Arrays for Biomedical Implant Materials and Nanomedicine Applications, Titanium Dioxide-Material for a Sustainable Environment

Healthy aims: Developing new medical implants and diagnostic equipment