ß-type TiNbSn Alloy Plates With Low Young Modulus Accelerates Osteosynthesis in Rabbit Tibiae.

BACKGROUND: Ti6Al4V alloy, which is commonly used for biomedical applications, has a Young modulus (110 GPa) that is higher than that of human cortical bone (11 to 20 GPa). Using an implant with a material with a low Young modulus that enhances load sharing by the bone even more than those made of Ti6Al4V could be beneficial for bone healing and further reduce the potential for stress shielding. A new ß-type TiNbSn alloy has a low Young modulus of approximately 40 to 49 GPa. However, whether the new titanium alloy with a lower Young modulus is advantageous in terms of fracture healing has not been assessed, and a small-animal model seems a reasonable first step in its assessment. QUESTIONS/PURPOSES: To assess the impact of a TiNbSn alloy plate with a lower Young modulus compared with a Ti6Al4V alloy plate on fracture healing, we evaluated: (1) bony bridging and callus volume, (2) new bone formation and remaining cartilage tissue, (3) osteoblast activity in the callus, and (4) mechanical strength and stiffness of the callus in bending. METHODS: Fracture plates manufactured from TiNbSn and Ti6Al4V alloys, which have Young moduli of 49 GPa and 110 GPa, respectively, were compared. The main reason for using rabbits was the high reliability of the three-point bending mechanical test of the rabbit tibia. Forty-two male Japanese white rabbits weighing 2.8 to 3.4 kg were anesthetized. A 5-cm skin incision was made on the medial side in the mid-diaphysis of the right tibia. Eight-hole plates were used, which were 42 mm long, 5 mm wide, and 1.2 mm thick. Plate fixation was performed using three proximal and three distal screws. After the plate was installed, an osteotomy was performed using a 1-mm-wide wire saw to create a standardized tibial transverse osteotomy model with a 1-mm gap. Bone healing was quantitatively assessed by two nonblinded observers using micro-CT (bony bridging and callus volume), histomorphometry (new bone formation and remaining cartilage tissue), immunohistochemistry (osteoblast activity), and mechanical testing (mechanical strength and stiffness in bending). Measurements on nondemineralized specimens were descriptive statistics due to their small number. Four weeks after osteotomy and fixation, 30 rabbits were euthanized to undergo micro-CT and subsequent mechanical testing (n = 12), histomorphometry and immunohistochemistry with demineralized specimens (n = 12), and histomorphometry with a nondemineralized specimen (n = 6). Eight weeks postoperatively, 12 rabbits were euthanized for micro-CT and subsequent mechanical testing. RESULTS: Intramedullary fracture calluses treated with TiNbSn alloy plates had larger bone volumes and more numerous bridging structures than those treated with Ti6Al4V alloy plates at 4 weeks after osteotomy (Ti6Al4V alloy versus TiNbSn alloy: 30 ± 7 mm 3 versus 52 ± 14 mm 3 , mean difference 22 [95% CI 9 to 37]; p = 0.005; ICC 0.98 [95% CI 0.95 to 0.99]). Histologic assessments demonstrated there was greater new bone formation (total callus: Ti6Al4V versus TiNbSn: 16 ± 4 mm 2 versus 24 ± 7 mm 2 , mean difference 8 [95% CI 1 to 16]; p = 0.04; ICC 0.98 [95% CI 0.93 to 0.99]; intramedullary callus: Ti6Al4V versus TiNbSn: 6 ± 4 mm 2 versus 13 ± 5 mm 2 , mean difference 7 [95% CI 1 to 13]; p = 0.02; ICC 0.98 [95% CI 0.95 to 0.99]) and a higher number of osteocalcin-positive cells (Ti6Al4V alloy versus TiNbSn alloy: 1397 ± 197 cells/mm 2 versus 2044 ± 183 cells/mm 2 , mean difference 647 [95% CI 402 to 892]; p < 0.001; ICC 0.98 [95% CI 0.95 to 0.99]) in the TiNbSn alloy group than in the Ti6Al4V alloy group. At 4 weeks after osteotomy, both bone strength and stiffness of the healed bone in the TiNbSn alloy group were higher than those in the Ti6Al4V alloy group (maximum load: Ti6Al4V alloy versus TiNbSn alloy: 83 ± 30 N versus 127 ± 26 N; mean difference 44 [95% CI 8 to 80]; p = 0.02; stiffness: Ti6Al4V alloy versus TiNbSn alloy: 92 ± 43 N/mm versus 165 ± 63 N/mm; mean difference 73 [95% CI 4 to 143]; p = 0.047). Eight weeks after osteotomy, no between-group differences were observed in the strength and stiffness of the healed bone. CONCLUSION: The results of this study indicate that TiNbSn alloy plate with a lower Young modulus resulted in improved bone formation and stiffer callus during the early phase (4 weeks after surgery) but not the later phase (8 weeks after surgery) of bone healing. CLINICAL RELEVANCE: An overly stiff plate may impair callus formation and bone healing. The TiNbSn alloy plate with a low Young modulus improves the early formation of new bone and stiff callus at the osteotomy site compared with the Ti6Al4V alloy plate in the healing process, which may promote bone repair. TiNbSn alloy may be a promising biomaterial for fracture treatment devices. Further research to address concerns about the strength of TiNbSn alloy plates, such as fatigue life and plate fracture, will be necessary for clinical applications, including mechanical tests to verify fatigue life and validation in larger animals with greater body weight.

Mid-term results of a new femoral prosthesis using Ti-Nb-Sn alloy with low Young's modulus.

BACKGROUND: This study was performed to investigate the mid-term results of Ti-Nb-Sn (TNS) alloy stem with a low Young's modulus. METHODS: This study was a multicenter prospective cohort study. A total of 40 primary total hip arthroplasties performed between April 2016 and September 2017 was enrolled in this study. With the unique functional gradient properties by heating treatment, the strength of the proximal portion was enhanced, while the distal portion maintained a low Young's modulus. The surgeries were performed through the posterolateral approach using the TNS alloy stems. Radiographs were taken from immediately after surgeries until 3 years, and stress shielding and subsidence of the stems were evaluated. The incidences of the stem breakage were also assessed. Clinical assessments were performed using Japanese Orthopaedic Association (JOA) and Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) scores. RESULTS: Among the 40 enrolled patients, 36 patients were female and 4 were male. At 3 years after surgery, there were no radiologic signs of loosening, subsidence, or breakage of the stem. Stress shielding was observed in 26 hips (65%). Of 26 hips, 16 hips (40%) were grade 1 and 10 hips (25%) were grade 2. There was no advanced stress shielding. The JOA and JHEQ scores significantly improved compared with the preoperative scores. CONCLUSION: The current study using a new TNS alloy femoral stem showed good clinical outcomes at 3-year follow-up. Radiologically, there was no loosening or subsidence of the stem. The mild stress shielding was observed in 65% of patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21241251 . The date of registration was October 26, 2021. Retrospectively registered.

TiNbSn stems with gradient changes of Young's modulus and stiffness reduce stress shielding compared to the standard fit-and-fill stems.

BACKGROUND: The difference between Young's moduli of the femur and the stem causes stress shielding (SS). TiNbSn (TNS) stem has a low Young's modulus and strength with gradient functional properties during the change in elastic modulus with heat treatment. The aim of this study was to investigate the inhibitory effect of TNS stems on SS and their clinical outcomes compared to conventional stems. METHODS: This study was a clinical trial. Primary THA was performed using a TNS stem from April 2016 to September 2017 for patients in the TNS group. Unilateral THA was performed using a Ti6Al4V alloy stem from January 2007 to February 2011 for patients in the control group. The TNS and Ti6Al4V stems were matched in shape. Radiographs were obtained at the 1- and 3-year follow-ups. Two surgeons independently checked the SS grade and appearance of cortical hypertrophy (CH). The Japanese Orthopaedic Association (JOA) scores before and 1 year after surgery were assessed as clinical scores. RESULTS: None of the patients in the TNS group had grade 3 or 4 SS. In contrast, in the control group, 24% and 40% of patients had grade 3 and 4 SS at the 1- and 3-year follow-ups, respectively. The SS grade was lower in the TNS group than in the control group at the 1- and 3-year follow-ups (p < 0.001). The frequencies of CH in both groups were no significant difference at the 1- and 3-year follow-ups. The JOA scores of the TNS group significantly improved at 1 year after surgery and were comparable to control group. CONCLUSION: The TNS stem reduced SS at 1 and 3 years after THA compared to the proximal-engaging cementless stem, although the shapes of the stems matched. The TNS stem could reduce SS, stem loosening, and periprosthetic fractures. TRIAL REGISTRATION: Current Controlled Trials. ISRCTN21241251. https://www.isrctn.com/search?q=21241251 . The date of registration was October 26, 2021. Retrospectively registered.

Antibacterial Activity of an Anodized TiNbSn Alloy Prepared in Sodium Tartrate Electrolyte.

In this study, we anodized a TiNbSn alloy with low Young's modulus in an electrolyte of sodium tartrate with and without hydrogen peroxide (H2O2). The photo-induced characteristics of the anodized alloy were analyzed for crystallinity and electrochemical conditions with comparisons to the effect with the addition of H2O2. The antibacterial activity was evaluated using methicillin-resistant Staphylococcus aureus and other pathogenic bacteria according to ISO 27447, and time decay antibacterial tests were also conducted. The anodized oxide had a porous microstructure with anatase- and rutile-structured titanium dioxide (TiO2). In contrast, the peaks of rutile-structured TiO2 were accelerated in the anodized TiNbSn alloy with H2O2. The formation of hydroxyl radicals and methylene blue breaching performance under ultraviolet irradiation was confirmed in the anodic oxide on TiNbSn alloy with and without H2O2. The anodic oxide on TiNbSn alloy had a robust antibacterial activity, and no significant difference was detected with or without H2O2. We conclude that anodized TiNbSn alloy with sodium tartrate electrolyte may be a functional biomaterial with a low Young's modulus and an antibacterial function.

Effects of elastic intramedullary nails composed of low Young's modulus Ti-Nb-Sn alloy on healing of tibial osteotomies in rabbits.

Intramedullary nailing is widely performed for internal fixation of fractures. The applicable elasticity of materials composing intramedullary nails remains unclear. The present study aimed to evaluate the effects of the elastic property of ß-type titanium alloy nails on fracture healing compared with conventional Ti-6Al-4V alloy nails using a rabbit tibial osteotomy model. Two types of intramedullary nails composed of ß-type Ti-Nb-Sn alloy (Young's modulus: 37 GPa) or Ti-6Al-4V alloy (Young's modulus: 110 GPa) were used for osteotomy fixation in the tibiae of rabbits. At 4, 8, and 16 weeks postoperatively, microcomputed tomography (micro-CT) and three-point bending tests were performed. Micro-CT images showed that the callus volume was significantly larger in the Ti-Nb-Sn alloy group at 4 and 8 weeks. The callus bone mineral density did not differ at each time point. In mechanical testing, the maximum load was significantly higher at all time points in the Ti-Nb-Sn alloy group. Taken together, the elastic intramedullary nails composed of Ti-Nb-Sn alloy improved the mechanical properties of the bone healing site from the early phase to the remodeling phase. Adequate Young's modulus of the Ti-Nb-Sn alloy enhanced fracture union and bone strength restoration. The Ti-Nb-Sn alloy is a promising biomaterial for fracture fixation devices. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 700-707, 2019.

Improved Osseointegration of a TiNbSn Alloy with a Low Young's Modulus Treated with Anodic Oxidation.

Ti6Al4V alloy orthopedic implants are widely used as Ti6Al4V alloy is a biocompatible material and resistant to corrosion. However, Ti6Al4V alloy has higher Young's modulus compared with human bone. The difference of elastic modulus between bone and titanium alloy may evoke clinical problems because of stress shielding. To resolve this, we previously developed a TiNbSn alloy offering low Young's modulus and improved biocompatibility. In the present study, the effects of sulfuric acid anodic oxidation on the osseointegration of TiNbSn alloy were assessed. The apatite formation was evaluated with Scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and transmission electron microscopy analyses. The biocompatibility of TiNbSN alloy was evaluated in experimental animal models using pull-out tests and quantitative histological analyses. The results of the surface analyses indicated that sulfuric anodic oxidation induced abundant superficial apatite formation of the TiNbSn alloy disks and rods, with a 5.1-µm-thick oxide layer and submicron-sized pores. In vivo, treated rods showed increased mature lamellar bone formation and higher failure loads compared with untreated rods. Overall, our findings indicate that anodic oxidation with sulfuric acid may help to improve the biocompatibility of TiNbSn alloys for osseointegration.

Effects of intramedullary nails composed of a new ß-type Ti-Nb-Sn alloy with low Young's modulus on fracture healing in mouse tibiae.

The influence of Young's moduli of materials on the fracture healing process remains unclear. This study aimed to assess the effects of intramedullary nails composed of materials with low Young's moduli on fracture repair. We previously developed a ß-type Ti-Nb-Sn alloy with low Young's modulus close to that of human cortical bone. Here, we prepared two Ti-Nb-Sn alloys with Young's moduli of 45 and 78 GPa by heat treatment, and compared their effects on fracture healing. Fracture and nailing were performed in the right tibiae of C57BL/6 mice. The bone healing process was evaluated by microcomputed tomography (micro-CT), histomorphometry, and RT-PCR. We found larger bone volumes of fracture callus in the mice treated with the 45-GPa Ti-Nb-Sn alloy as compared with the 78-GPa Ti-Nb-Sn alloy in micro-CT analyses. This was confirmed with histology at day 14, with accelerated new bone formation and cartilage absorption in the 45-GPa Ti-Nb-Sn group compared with the 78-GPa Ti-Nb-Sn group. Acp5 expression was lower in the 45-GPa Ti-Nb-Sn group than in the 78-GPa Ti-Nb-Sn group at day 10. These findings indicate that intramedullary fixation with nails with a lower Young's modulus offer a greater capacity for fracture repair. Our 45-GPa Ti-Nb-Sn alloy is a promising material for fracture treatment implants. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2841-2848, 2018.

Improving stress shielding following total hip arthroplasty by using a femoral stem made of ß type Ti-33.6Nb-4Sn with a Young's modulus gradation.

Stress shielding-related bone loss occurs after total hip arthroplasty because the stiffness of metallic implants differs from that of the host femur. Although reducing stem stiffness can ameliorate the bone resorption, it increases stress at the bone-implant interface and can inhibit fixation. To overcome this complication, a novel cementless stem with a gradient in Young's modulus was developed using Ti-33.6Nb-4Sn (TNS) alloy. Local heat treatment applied at the neck region for increasing its strength resulted in a gradual decrease in Young's modulus from the proximal to the distal end, from 82.1 to 51.0GPa as calculated by a heat transfer simulation. The Young's modulus gradient did not induce the excessive interface stress which may cause the surface debonding. The main purpose of this study was to evaluate bone remodeling with the TNS stem using a strain-adaptive bone remodeling simulation based on finite element analysis. Our predictions showed that, for the TNS stem, bone reduction in the calcar region (Gruen zone 7) would be 13.6% at 2years, 29.0% at 5years, and 45.8% at 10years postoperatively. At 10 years, the bone mineral density for the TNS stem would be 42.6% higher than that for the similar Ti-6Al-4V alloy stem. The stress-strength ratio would be lower for the TNS stem than for the Ti-6Al-4V stem. These results suggest that although proximal bone loss cannot be eliminated completely, the TNS stem with a Young's modulus gradient may have bone-preserving effects and sufficient stem strength, without the excessive interface stress.

Apatite Formation and Biocompatibility of a Low Young's Modulus Ti-Nb-Sn Alloy Treated with Anodic Oxidation and Hot Water.

Ti-6Al-4V alloy is widely prevalent as a material for orthopaedic implants because of its good corrosion resistance and biocompatibility. However, the discrepancy in Young's modulus between metal prosthesis and human cortical bone sometimes induces clinical problems, thigh pain and bone atrophy due to stress shielding. We designed a Ti-Nb-Sn alloy with a low Young's modulus to address problems of stress disproportion. In this study, we assessed effects of anodic oxidation with or without hot water treatment on the bone-bonding characteristics of a Ti-Nb-Sn alloy. We examined surface analyses and apatite formation by SEM micrographs, XPS and XRD analyses. We also evaluated biocompatibility in experimental animal models by measuring failure loads with a pull-out test and by quantitative histomorphometric analyses. By SEM, abundant apatite formation was observed on the surface of Ti-Nb-Sn alloy discs treated with anodic oxidation and hot water after incubation in Hank's solution. A strong peak of apatite formation was detected on the surface using XRD analyses. XPS analysis revealed an increase of the H2O fraction in O 1s XPS. Results of the pull-out test showed that the failure loads of Ti-Nb-Sn alloy rods treated with anodic oxidation and hot water was greater than those of untreated rods. Quantitative histomorphometric analyses indicated that anodic oxidation and hot water treatment induced higher new bone formation around the rods. Our findings indicate that Ti-Nb-Sn alloy treated with anodic oxidation and hot water showed greater capacity for apatite formation, stronger bone bonding and higher biocompatibility for osteosynthesis. Ti-Nb-Sn alloy treated with anodic oxidation and hot water treatment is a promising material for orthopaedic implants enabling higher osteosynthesis and lower stress disproportion.

Fabrication of a high-performance hip prosthetic stem using ß Ti-33.6Nb-4Sn.

This study used severe cold rolling followed by cold swaging of ß Ti-33.6% Nb-4% Sn rods to form a characteristic fiber structure composed of stress-induced α″ martensite with <010> texture and a ß phase with <101> texture, resulting in a material with a low Young's modulus of 40GPa. The material's tensile strength of 1270MPa and fatigue strength of 850MPa were attained by heat treatment at 673K for 5h through fine α precipitation in the fiber structure. A new method of fabricating a high-performance hip prosthetic stem was investigated based on the low Young's modulus and high strength obtained. After fabricating the stem by cold rolling, cold swaging, cold die-forging and machining, its neck region was given higher strength through local heat treatment, while the low Young's modulus remained almost unchanged in a distal portion of the stem. When a stem tip in the distal part was heat treated at 423K, reverse αâ€³â†’ß transformation occurred and the tangent modulus decreased to less than 30GPa, accompanied by stress-induced ß→α″. It was concluded that the method presented herein provided a low Young's modulus of approximately 40GPa in the distal part and high fatigue strength of approximately 850MPa in the neck region of a high-performance hip prosthetic stem.

In-vitro biomechanical evaluation of stress shielding and initial stability of a low-modulus hip stem made of ß type Ti-33.6Nb-4Sn alloy.

Stress shielding-related proximal femoral bone loss after total hip arthroplasty occurs because of the different stiffness of metallic alloy stems and host bone. To overcome this, we fabricated a low-modulus cementless hip stem from ß-type Ti-33.6Nb-4Sn alloy (TNS). Then we evaluated its stiffness, stress shielding, and initial stability compared with a similar Ti-6Al-4V alloy stem. Stiffness was determined by axial compression and cantilever-bending tests. Thirteen triaxial strain gages measured cortical strain. Stress shielding was defined as the percentage of intact strain after stem insertion. To evaluate initial stability, displacement transducers measured axial relative displacement and rotation. Intact and implanted femurs underwent single-leg-stance loading. Axial stiffness was 56% lower in the TNS stem than in the Ti-6Al-4V stem, and bending stiffness of the TNS stem decreased gradually from the proximal region to the distal region, being ≤ 53% that of the Ti-6Al-4V stem, indicating gradation of Young's modulus. The TNS stem decreased stress shielding in the proximal calcar region (A1: 83%, B1: 85% relative to intact cortical strain) without affecting the proximal lateral region (B3: 53%). The initial stabilities of the stems were comparable. These findings indicate that the TNS stem with gradation of Young's modulus minimizes proximal femoral bone loss and biological fixation, improving long-term stability.

Effect of swaging on Young׳s modulus of ß Ti-33.6Nb-4Sn alloy.

The effect of swaging on the Young's modulus of ß Ti-33.6Nb-4Sn rods was investigated by X-ray diffraction, thermography, microstructural observations, deformation simulator analysis and cyclic tensile deformation. Stress-induced α″ martensite was stabilized by swaging, dependent on the diameter reduction rate during swaging. Thermography and deformation simulator analysis revealed that swaged rods were adiabatically heated, and consequently, stress-induced α″ underwent reverse transformation. Young's modulus, which was measured by the slope of the initial portion of the stress-strain curve, decreased from 56GPa in the hot-forged/quenched rod to 44GPa in the rapidly swaged rod with a high reduction rate and to 45GPa in the gradually swaged rod with a low reduction rate. The tangent modulus, which was measured by the slope of the tangent to any point on the stress-strain curve, decreased with strain even in the linear range of the stress-strain curve of the hot-forged/quenched rod and the rapidly swaged rod, while the tangent modulus remained unchanged for the gradually swaged rod. It was found that Young's moduli in swaged ß Ti-33.6Nb-4Sn rods were affected by stabilized α″ martensite. Low Young's modulus of 45GPa and high strength over 800MPa were obtained when the reverse transformation by adiabatic heating was suppressed and the stress-induced α″ was sufficiently stabilized by gradual swaging to a 75% reduction in cross section area.

Microstructure and properties of cross-roll rolled and heat treated metastable TiNbSn alloy.

A (Ti-35mass%Nb)-4mass%Sn alloy was cross-roll rolled with a reduction ratio of 70% in which the roll axes are tilted by ± 5 degrees away from the transverse direction of the rolled sample and then aged at 250 degrees C for 2 h. Cross-roll rolling was found to increase yield strength and Young's modulus, simultaneously. Yield strength was higher in cross-roll rolled than in conventionally rolled at same reduction ratio. Yield and tensile strength further increased by a low temperature ageing by ψ precipitation hardening and microstructure refinement. Yield and tensile strength of the aged 70% cross-roll rolled sample were higher than those of the aged 70% conventionally rolled one.

Mechanical properties and microstructures of ß Ti-25Nb-11Sn ternary alloy for biomedical applications.

The mechanical properties and microstructures of ß Ti-25%Nb-11%Sn ternary alloy rods were investigated for biomedical applications as a function of heat treatment temperature after swaging by an 86% reduction in cross-section area. An as-swaged rod consisting of a ß (bcc) single phase shows a low Young's modulus of 53 GPa, which is interpreted in terms of both the metastable composition of the ß alloy undergoing neither an athermal ω transformation nor a deformation-induced ω transformation and <110>texture development during swaging. Heat treatment at 673 K (400 °C) for 2h leads to a high strength of approximately 1330 MPa and a high spring-back ratio of yield stress to Young's modulus over 15×10(-3), with acceptable elongation. This high strength is attributable to needle-like α precipitates, which are identified by high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) and high-resolution electron microscopy (HREM).

The bone tissue compatibility of a new Ti-Nb-Sn alloy with a low Young's modulus.

A Ti-Nb-Sn alloy was developed as a new ß-type titanium alloy which had a low Young's modulus and high strength. The Young's modulus of the Ti-Nb-Sn alloy was reduced to about 45 GPa by cold rolling, much closer to human cortical bone (10-30 GPa) than that of Ti-6Al-4V alloy (110 GPa) and other ß-type titanium alloys developed for biomedical applications. The tensile strength of the Ti-Nb-Sn alloy was increased to a level greater than that of Ti-6Al-4V alloy by heat treatment after severe cold rolling. In this study the cytotoxicity of Ti-25Nb-11Sn alloy was evaluated in direct contact cell culture tests using metal disks and the bone tissue compatibility - examined using metal rods inserted into the medullary canal of rabbit femurs. The remarkable findings were that: (1) there were no significant differences in the relative growth ratio and relative absorbance ratio between cells grown with the Ti-Nb-Sn alloy, Ti-6Al-4V alloy and CP-Ti in direct contact cell culture tests; (2) there were no significant differences in the load at failure between the Ti-Nb-Sn alloy and Ti-6Al-4V alloy in pull-out metal rods tests; (3) there were no significant differences in new bone formation around metal rods between the Ti-Nb-Sn alloy and Ti-6Al-4V alloy in histological evaluations. The new Ti-Nb-Sn alloy with an elasticity closer to that of human bone is thus considered to be bioinert while also having a high degree of bone compatibility similar to that of Ti-6Al-4V alloy.