Biological Safety Evaluation and Surface Modification of Biocompatible Ti–15Zr–4Nb Alloy

We performed biological safety evaluation tests of three Ti–Zr alloys under accelerated extraction condition. We also conducted histopathological analysis of long-term implantation of pure V, Al, Ni, Zr, Nb, and Ta metals as well as Ni–Ti and high-V-containing Ti–15V–3Al–3Sn alloys in rats. The effect of the dental implant (screw) shape on morphometrical parameters was investigated using rabbits. Moreover, we examined the maximum pullout properties of grit-blasted Ti–Zr alloys after their implantation in rabbits. The biological safety evaluation tests of three Ti–Zr alloys (Ti–15Zr–4Nb, Ti–15Zr–4Nb–1Ta, and Ti–15Zr–4Nb–4Ta) showed no adverse (negative) effects of either normal or accelerated extraction. No bone was formed around the pure V and Ni implants. The Al, Zr, Nb, and Ni–Ti implants were surrounded by new bone. The new bone formed around Ti–Ni and high-V-containing Ti alloys tended to be thinner than that formed around Ti–Zr and Ti–6Al–4V alloys. The rate of bone formation on the threaded portion in the Ti–15Zr–4Nb–4Ta dental implant was the same as that on a smooth surface. The maximum pullout loads of the grit- and shot-blasted Ti–Zr alloys increased linearly with implantation period in rabbits. The pullout load of grit-blasted Ti–Zr alloy rods was higher than that of shot-blasted ones. The surface roughness (Ra) and area ratio of residual Al₂O₃ particles of the Ti–15Zr–4Nb alloy surface grit-blasted with Al₂O₃ particles were the same as those of the grit-blasted Alloclassic stem surface. It was clarified that the grit-blasted Ti–15Zr–4Nb alloy could be used for artificial hip joint stems.     

Zirconia versus Titanium Implants: 8-Year Follow-Up in a Patient Cohort Contrasted with Histological Evidence from a Preclinical Animal Model

Zirconia ceramic (ZC) implants are becoming more common, but comparisons between preclinical histology and long-term clinical trials are rare. This investigation comprised (1) 8-year clinical follow-up of one-piece ZC or titanium (Ti) implants supporting full overdentures and (2) histomorphometric analysis of the same implants in an animal model, comparing implants with various surface treatments. Methods: (1) Clinical trial: 24 completely edentulous participants (2 groups of N = 12) received 7 implants (one-piece ball-abutment ZC or Ti; maxilla N = 4, mandible N = 3) restored with implant overdentures. Outcomes after 8-years included survival, peri-implant bone levels, soft-tissue responses, and prosthodontic issues. (2) Preclinical trial: 10 New Zealand sheep received 4 implants bilaterally in the femoral condyle: Southern Implants ZC or Ti one-piece implants, identical to the clinical trial, and controls: Southern ITC^® two-piece implants with the same surface or Nobel (NBC) anodised (TiUnite™) surface. %Bone-implant contact (%BIC) was measured after 12 weeks of unloaded healing. Results: 8 of 24 participants (33%) of an average age of 75 ± 8 years were recalled; 21% of original participants had died, and 46% could not be contacted. 80.4% of implants survived; excluding palatal sites, 87.5% of Ti and 79% of ZC implants survived. All failed implants were in the maxilla. Three ZC implants had fractured. Bone loss was similar for Ti vs. ZC; pocket depths (p = 0.04) and attachment levels (p = 0.02) were greater for Ti than ZC implants. (1.7 ± 1.6 mm vs. 1.6 ± 1.3 mm). All implants in sheep femurs survived. %BIC was not statistically different for one-piece blasted surface Ti (80 ± 19%) versus ZC (76 ± 20%) or ITC^® (75 ± 16 mm); NBC had significantly higher %BIC than ITC (84 ± 17%, p = 0.4). Conclusion: Short-term preclinical results for ZC and Ti one-piece implants showed excellent bone-implant contact in unloaded femoral sites. This differed from the long-term clinical results in older-aged, edentulous participants. While ZC and Ti implants showed equivalent performance, the risks of peri-implantitis and implant loss in older, completely edentulous patients remain a significant factor.     

Twinning-Induced Abnormal Strain Rate Sensitivity and Indentation Creep Behavior in Nanocrystalline Mg Alloy

Nanocrystalline materials exhibit many unique physical and chemical properties with respect to their coarse-grained counterparts due to the high volume fraction of grain boundaries. Research interests on nanocrystalline materials around the world have been lasting over the past decades. In this study, we explored the room temperature strain rate sensitivity and creep behavior of the nanocrystalline Mg–Gd–Y–Zr alloy by using a nanoindentation technique. Results showed that the hardness and creep displacements of the nanocrystalline Mg–Gd–Y–Zr alloy decreased with increasing loading strain rate. That is, the nanocrystalline Mg–Gd–Y–Zr alloy showed negative strain rate sensitivity and its creep behavior also exhibited negative rate dependence. It was revealed that the enhanced twinning activities at higher loading strain rates resulted in reduced hardness and creep displacements. The dominant creep mechanism of the nanocrystalline Mg–Gd–Y–Zr alloy is discussed based on a work-of-indentation theory in this paper.     

Chemical Evaluation of Energy Dispersive X-ray Spectroscopy Analysis of Different Failing Dental Implant Surfaces: A Comparative Clinical Trial

The aim of the present study is to compare two different implant surface chemistries of failing dental implants. Sixteen patients (mean age: 52 ± 8.27 with eight females and eight males) and 34 implants were included in the study. Group-I implants consisted of a blasted/etched surface with a final process surface, while Group-II implants consisted of the sandblasted acid etching (SLA) method. The chemical surface analysis was performed by the energy dispersive X-ray spectroscopy (EDX) method from coronal, middle, and apical parts of each implant. Titanium (Ti) element values were found to be 20.22 ± 15.7 at.% in Group I and 33.96 ± 13.62 at.% in Group-II in the middle of the dental implants. Aluminum (Al) element values were found to be 0.01 ± 0.002 in Group-I and 0.17 ± 0.28 at.% in Group II in the middle of the dental implants, and statistically significant differences were found between the groups for the Al and Ti elements in the middle of the dental implants (p < 0.05). There was a statistically significant difference for the Ti, Al, O, Ca, Fe, P, and Mg elements in the coronal, middle, and apical parts of the implants in the intragroup evaluation (p < 0.05). It is reported that different parts of the implants affected by peri-implant inflammation show different surface chemistries, from coronal to apical, but there is no difference in the implants with different surfaces.     

The Effect of a 10-MDP-Based Dentin Adhesive as Alternative for Bonding to Implant Abutment Materials

Bonding to different dental restorative materials is challenging. This study aimed to evaluate the effect of a 10-MDP-based dentin adhesive on the shear bond strength (SBS) of self-adhesive resin cement (RC) to implant abutment materials. One hundred and twenty specimens were obtained from zirconia (ZO), cobalt-chromium alloy (CoCr), and commercially pure titanium (Ti), which were treated as follows (n = 10): control group—non-treated (CG), 10-MDP-based dentin adhesive (SB), light-cured SB (SB-LC), and zirconia primer (ZP). Blocks of RC were buildup and, after 24 h, were tested for bond strength. Data of SBS (MPa) were submitted to two-way ANOVA and Tukey test (α = 0.05). There was no difference in SBS among materials for CG and ZP, higher SBS were recorded for Ti SB and Ti SB-LC compared to ZO upon the same surface treatments. For the comparisons among treatments, SB-LC showed the highest SBS for CoCr. For ZO and Ti, higher SBS were recorded with SB and SB-LC. No cohesive failures were observed. It was concluded that the surface treatment with 10-MDP-based materials increased the bond strength of the resin cement to abutment materials, which showed to be material dependent.     

Implants Survival Rate in Regenerated Sites with Innovative Graft Biomaterials: 1 Year Follow-Up

In thirteen different dental clinics in Singapore, Spain, Czech Republic and Italy, 504 patients were selected, and 483 dental implants were placed in maxillary sites after alveolar socket preservation (ASP) procedures with an autologous demineralized tooth extracted as graft material from an innovative Tooth Transformer device was obtained. All procedures used were reported in n°638 Ethical Committee surgical protocol of University of Chieti and approved. After 4 months, at dental implant placing, bone biopsies were performed to evaluate the histologic outcomes, and 12 months after implant loading, global implant survival rate, failure percentage and peri-implant bone loss were detected. After ASP, only 27 post-operative complications were observed and after 4 months, bone biopsy histomorphometric analysis showed a high percentage of bone volume (BV) 43.58 (±12.09), and vital new bone (NB) 32.38 (±17.15) with an absence of inflammation or necrosis areas. Twelve months after loading, only 10 dental implants failed (2.3%), with a 98.2% overall implant survival rate, nine cases showed mucositis (1.8%) and eight showed peri-implantitis (1.6%). At mesial sites, 0.43 mm (±0.83) of bone loss around the implants was detected and 0.23 mm (±0.38) at the distal sites with an average value of 0.37 mm (±0.68) (p > 0.568). Several studies with a longer follow-up will be necessary to confirm the preliminary data observed. However, clinical results seem to suggest that the post-extraction socket preservation procedure using innovative demineralized autologous tooth-derived biomaterial may be a predictable procedure to produce new vital bone able to support dental implant rehabilitation of maxilla edentulous sites.     

Surface Roughness and Streptococcus mutans Adhesion on Metallic and Ceramic Fixed Prosthodontic Materials after Scaling

The aim of this study was to evaluate the surface roughness of fixed prosthodontic materials after polishing or roughening with a stainless steel curette or ultrasonic scaler and to examine the effect of these on Streptococcus mutans adhesion and biofilm accumulation. Thirty specimens (10 × 10 × 3 mm³) of zirconia (Zr), pressed lithium disilicate (LDS-Press), milled lithium disilicate glazed (LDS-Glaze), titanium grade V (Ti) and cobalt-chromium (CoCr) were divided into three groups (n = 10) according to surface treatment: polished (C), roughened with stainless steel curette (SC), roughened with ultrasonic scaler (US). Surface roughness values (Sa, Sq) were measured with a spinning disc confocal microscope, and contact angles and surface free energy (SFE) were measured with a contact angle meter. The specimens were covered with sterilized human saliva and immersed into Streptococcus mutans suspensions for bacterial adhesion. The biofilm was allowed to form for 24 h. Sa values were in the range of 0.008–0.139 µm depending on the material and surface treatment. Curette and ultrasonic scaling increased the surface roughness in LDS-Glaze (p < 0.05), Ti (p < 0.01) and CoCr (p < 0.001), however, surface roughness did not affect bacterial adhesion. Zr C and US had a higher bacterial adhesion percentage compared to LDS-Glaze C and US (p = 0.03). There were no differences between study materials in terms of biofilm accumulation.     

The Influence of Surgical Experience and Bone Density on the Accuracy of Static Computer-Assisted Implant Surgery in Edentulous Jaws Using a Mucosa-Supported Surgical Template with a Half-Guided Implant Placement Protocol—A Randomized Clinical Study

The aim of our randomized clinical study was to analyze the influence of surgical experience and bone density on the accuracy of static computer-assisted implant surgery (CAIS) in edentulous jaws using a mucosa-supported surgical template with a half-guided implant placement protocol. Altogether, 40 dental implants were placed in the edentulous jaws of 13 patients (novice surgeons: 18 implants, 6 patients (4 male), age 71 ± 10.1 years; experienced surgeons: 22 implants, 7 patients (4 male), age 69.2 ± 4.55 years). Angular deviation, coronal and apical global deviation and grey level measurements were calculated for all implants by a blinded investigator using coDiagnostiX software. 3DSlicer software was applied to calculate the bone volume fraction (BV/TV) for each site of implant placement. There were no statistically significant differences between the two study groups in either of the primary outcome variables. There was a statistically significant negative correlation between angular deviation and both grey level measurements (R-value: −0.331, p < 0.05) and BV/TV (R-value: −0.377, p < 0.05). The results of the study suggest that surgical experience did not influence the accuracy of implant placement. The higher the bone density at the sites of implant placement, the higher the accuracy of static CAIS.     

Effect of Fabrication Technique on the Microgap of CAD/CAM Cobalt–Chrome and Zirconia Abutments on a Conical Connection Implant: An In Vitro Study

The aim of this in vitro study was to investigate the microgaps at the implant–abutment interface when zirconia (Zr) and CAD/CAM or cast Co–Cr abutments were used. Methods: Sixty-four conical connection implants and their abutments were divided into four groups (Co–Cr (milled, laser-sintered and castable) and Zirconia (milled)). After chewing simulation (300,000 cycles, under 200 N loads at 2 Hz at a 30° angle) and thermocycling (10,000 cycles, 5 to 50 °C, dwelling time 55 s), the implant–abutment microgap was measured 14 times at each of the four anatomical aspects on each specimen by using a scanning electron microscope (SEM). Kruskal–Wallis and pair-wise comparison were used to analyze the data (α = 0.05). Results: The SEM analysis revealed smaller microgaps with Co–Cr milled abutments (0.69–8.39 μm) followed by Zr abutments (0.12–6.57 μm), Co–Cr sintered (7.31–25.7 μm) and cast Co–Cr (1.68–85.97 μm). Statistically significant differences were found between milled and cast Co–Cr, milled and laser-sintered Co–Cr, and between Zr and cast and laser-sintered Co–Cr (p < 0.05). Conclusions: The material and the abutment fabrication technique affected the implant–abutment microgap magnitude. The Zr and the milled Co–Cr presented smaller microgaps. Although the CAD/CAM abutments presented the most favorable values, all tested groups had microgaps within a range of 10 to 150 μm.     

Effects of Implant–Abutment Connection Type and Inter-Implant Distance on Inter-Implant Bone Stress and Microgap: Three-Dimensional Finite Element Analysis

The attainment of a good aesthetic outcome in dental implant treatment requires inter-implant papilla reconstruction, which is very difficult to perform. Maintenance of the inter-implant bone is essential for maintenance of the inter-implant papilla. The aim of this study was to investigate the mechanical influences of the implant–abutment connection type and inter-implant distance on the inter-implant bone by using three-dimensional finite element analysis. Three computer-aided design models of two-piece implants were designed: external connection (EC), internal connection (IC), and conical connection (CC). In each model, two identical implants were placed with inter-implant distances of 3.0, 2.5, and 2.0 mm. The maximum principal stress and microgap were evaluated. The stress values of the inter-implant bone decreased in the following order: IC, EC, and CC. The microgap decreased in the following order: EC, IC, and CC. Regardless of the type of implant–abutment connection, the stress of the inter-implant bone increased as the inter-implant distance decreased. The microgap barely changed as the inter-implant distance decreased. A CC implant is a mechanically advantageous implant–abutment connection type for maintenance of the inter-implant bone. With an inter-implant distance of less than 3.0 mm, use of a CC implant might suppress absorption of the inter-implant bone.     

Biochemical Modification of Titanium Oral Implants: Evidence from In Vivo Studies

The discovery of osseointegration of titanium implants revolutionized the dental prosthesis field. Traditionally, implants have a surface that is processed by additive or subtractive techniques, which have positive effects on the osseointegration process by altering the topography. In the last decade, innovative implant surfaces have been developed, on which biologically active molecules have been immobilized with the aim of increasing stimulation at the implant–biological tissue interface, thus favoring the quality of osseointegration. Among these molecules, some are normally present in the human body, and the techniques for the immobilization of these molecules on the implant surface have been called Biochemical Modification of Titanium Surfaces (BMTiS). Different techniques have been described in order to immobilize those biomolecules on titanium implant surfaces. The aim of the present paper is to present evidence, available from in vivo studies, about the effects of biochemical modification of titanium oral implants on osseointegration.     

Does Simulated Porcelain Firing Influence Corrosion Properties of Casted and Sintered CoCr Alloys?

The aim of the study was to evaluate how heat processing used for dental porcelain firing influences the surface properties of sintered and casted CoCr alloy. Two CoCr alloys, Soft Metal LHK (milling in soft material and sintering) and MoguCera C (casting), were used for the study. The samples were examined using SEM–EDS before and after heat treatment. Next, corrosion examinations (E_corr, j_corr, polarization curve, E_br) were performed. Finally, the samples were evaluated under SEM. Based on the results, the following conclusions might be drawn: 1. Thermal treatment (porcelain firing) did not cause chemical impurities formation on the surface of CoCr alloy; 2. The sintered metal exhibited significantly higher corrosion resistance than the casted one due to its homogeneity of structure and chemical composition; 3. Heat treatment (porcelain firing) decreased the resistance of casted and sintered CoCr alloy to electrochemical corrosion. The reduction in corrosion resistance was significantly higher for the casted alloy than for the sintered alloy; 4. The corrosion resistance decrease might be due to an increased thickness and heterogeneity of oxide layers on the surface (especially for the casted alloy). The development of corrosion process started in the low-density areas of the oxide layers; 5. The sintered metal seems to be a favourable framework material for porcelain fused to metal crowns.     

PICN Nanocomposite as Dental CAD/CAM Block Comparable to Human Tooth in Terms of Hardness and Flexural Modulus

Polymer infiltrated ceramic network (PICN) composites are an increasingly popular dental restorative material that offer mechanical biocompatibility with human enamel. This study aimed to develop a novel PICN composite as a computer-aided design and computer-aided manufacturing (CAD/CAM) block for dental applications. Several PICN composites were prepared under varying conditions via the sintering of a green body prepared from a silica-containing precursor solution, followed by resin infiltration. The flexural strength of the PICN composite block (107.8–153.7 MPa) was similar to a commercial resin-based composite, while the Vickers hardness (204.8–299.2) and flexural modulus (13.0–22.2 GPa) were similar to human enamel and dentin, respectively. The shear bond strength and surface free energy of the composite were higher than those of the commercial resin composites. Scanning electron microscopy and energy dispersive X-ray spectroscopic analysis revealed that the microstructure of the composite consisted of a nanosized silica skeleton and infiltrated resin. The PICN nanocomposite block was successfully used to fabricate a dental crown and core via the CAD/CAM milling process.     

Critical Role of Etching Parameters in the Evolution of Nano Micro SLA Surface on the Ti6Al4V Alloy Dental Implants

The surface of dental implants plays a vital role in early and more predictable osseointegration. SLA (sandblasted large grit and acid-etched) represents the most widely accepted, long-term clinically proven surface. Primarily, dental implants are manufactured by either commercially pure titanium (CP-Ti) or Ti6Al4V ELI alloy. The acid etch behavior of CP-Ti is well known and its effects on the surface microstructure and physicochemical properties have been studied by various researchers in the past. However, there is a lack of studies showing the effect of acid etching parameters on the Ti6Al4V alloy surface. The requirement of the narrow diameter implants necessitates implant manufacturing from alloys due to their high mechanical properties. Hence, it is necessary to have an insight on the behavior of acid etching of the alloy surface as it might be different due to changed compositions and microstructure, which can further influence the osseointegration process. The present research was carried out to study the effect of acid etching parameters on Ti6Al4V ELI alloy surface properties and the optimization of process parameters to produce micro- and nanotopography on the dental implant surface. This study shows that the Ti6Al4V ELI alloy depicts an entirely different surface topography compared to CP-Ti. Moreover, the surface topography of the Ti6Al4V ELI alloy was also different when etching was done at room temperature compared to high temperature, which in turn affected the behavior of the cell on these surfaces. Both microns and nano-level topography were achieved through the optimized parameters of acid etching on Ti6Al4V ELI alloy dental implant surface along with improved roughness, hydrophilicity, and enhanced cytocompatibility.     

Evaluation of Antimicrobial Efficacy and Permeability of Various Sealing Materials at the Implant–Abutment Interface—A Pilot In Vitro Study

The microenvironment of the oral cavity is altered when an implant, a biocompatible foreign body, is inserted into the mouth. Bacteria settle in the tissues in and around the implant due to the passage of microorganisms through the microgap at the connection of the implant and prosthetic abutment. To prevent colonization of the implant by microorganisms, one idea is to use sealing and antimicrobial materials to decontaminate the implant–abutment interface and close the microgap. The purpose of this study is to evaluate the antimicrobial efficacy and permeability of different types of sealing materials at the implant–abutment interface, under static conditions. Three different sealing material (GapSeal gel, Oxysafe gel and Flow.sil) were used for sealing the implant–abutment interfaces in 60 titanium dental implants, which were first contaminated with a solution containing Staphylococcus aureus and Candida albicans for 14 days under an aerobic condition. Results showed that a complete seal against bacterial infection was not formed at the implant–abutment interface, while for fungal infections, only GapSeal material helped to prevent microleakage. Findings of this in vitro study reported that application of sealing material before abutment connection may reduce peri-implant bacterial and fungal population compared with the interface without sealing material.     

Relevant Aspects of Titanium and Zirconia Dental Implants for Their Fatigue and Osseointegration Behaviors

Osseointegration capacity and good mechanical behavior are key to the success of the dental implant. In many investigations, comparisons of properties are made using different dental implant designs and therefore the results can be influenced by the macrodesign of the dental implant. In this work, studies were carried out with the same dental implant model using different roughness and different materials—commercially pure titanium (grade 4) and zirconia. For this purpose, 80 smooth passivated titanium (Ti), 80 smooth zirconia (ZrO₂), and 80 rough passivated titanium (Ti-R) dental implants were used. The samples were characterized by their roughness, wettability, surface energy, residual stresses, and fatigue behavior. The implants were implanted in minipigs for 4 and 12 weeks. The animals were sacrificed, and histological studies were carried out to determine the osseointegration parameters for each of the implantation times. Ti and ZrO₂ dental implants have very similar wettability and surface energy properties. However, the roughness causes a decrease in the hydrophilic character and a decrease of the total surface energy and especially the dispersive component, while the polar component is higher. Due to the compressive residual stresses of alumina sandblasting, the rough dental implant has the best fatigue behavior, followed by Ti and due to the lack of toughness and rapid crack propagation the ZrO₂ implants have the worst fatigue behavior. The bone index contact (BIC) values for 4 weeks were around 25% for Ti, 32% for ZrO₂, and 45% for Ti-R. After 12 weeks the Ti dental implants increased to 42%, for Ti, 43% for ZrO₂, and an important increase to 76% was observed for Ti-R implants. In vivo results showed that the key factor that improves osseointegration is roughness. There was no significant difference between ZrO₂ and Ti implants without sandblasting.     

How Do Parameters of Implant Primary Stability Correspond with CT-Evaluated Bone Quality in the Posterior Maxilla? A Correlation Analysis

The aim of the present study was to evaluate correlations between bone density and implant primary stability, considering various determinants such as age, gender, and geometry of implants (design, diameter). Bone density of edentulous posterior maxillae was assessed by computed tomography (CT)-derived Hounsfield units, and implant primary stability values were measured with insertion torque and resonance frequency analysis (RFA). A total of 60 implants in 30 partially edentulous patients were evaluated in the posterior maxilla with two different types of dental implants. The bone density evaluated by CT-derived Hounsfield units showed a significant correlation with primary stability parameters. The bone quality was more influenced by gender rather than age, and the type of implant was insignificant when determining primary stability. Such results imply that primary stability parameters can be used for objective assessment of bone quality, allowing surgical modifications especially in sites suspected of poor bone quality.     

Exfoliation Resistance,Microstructure, and Oxide Formation Mechanisms of the White Oxide Layer on CP Ti and Ti–Nb–Ta–Zr Alloys

We found that specific biomedical Ti and its alloys, such as CP Ti, Ti–29Nb–13Ta–4.6Zr, and Ti–36Nb–2Ta–3Zr–0.3O, form a bright white oxide layer after a particular oxidation heat treatment. In this paper, the interfacial microstructure of the oxide layer on Ti–29Nb–13Ta–4.6Zr and the exfoliation resistance of commercially pure (CP) Ti, Ti–29Nb–13Ta–4.6Zr, and Ti–36Nb–2Ta–3Zr–0.3O were investigated. The alloys investigated were oxidized at 1273 or 1323 K for 0.3–3.6 ks in an air furnace. The exfoliation stress of the oxide layer was high in Ti–29Nb–13Ta–4.6Zr and Ti–36Nb–2Ta–3Zr–0.3O, and the maximum exfoliation stress was as high as 70 MPa, which is almost the same as the stress exhibited by epoxy adhesives, whereas the exfoliation stress of the oxide layer on CP Ti was less than 7 MPa, regardless of duration time. The nanoindentation hardness and frictional coefficients of the oxide layer on Ti–29Nb–13Ta–4.6Zr suggested that the oxide layer was hard and robust enough for artificial tooth coating. The cross-sectional transmission electron microscopic observations of the microstructure of oxidized Ti–29Nb–13Ta–4.6Zr revealed that a continuous oxide layer formed on the surface of the alloys. The Au marker method revealed that both in- and out-diffusion occur during oxidation in Ti–29Nb–13Ta–4.6Zr and Ti–36Nb–2Ta–3Zr–0.3O, whereas only out-diffusion governs oxidation in CP Ti. The obtained results indicate that the high exfoliation resistance of the oxide layer on Ti–29Nb–13Ta–4.6Zr and Ti-36Nb-2Ta-3Zr-0.3O are attributed to their dense microstructures composing of fine particles, and a composition-graded interfacial microstructure. On the basis of the results of our microstructural observations, the oxide formation mechanism of the Ti–Nb–Ta–Zr alloy is discussed.