1. Introduction
Aseptic implant loosening is the main reason for the revision of total joint replacements [
1]. Implant material-related complications are associated with wear particles, corrosion products, and the mechanical mismatch of the materials to the human bone [
2,
3]. Metal wear particles can stimulate osteoclastic bone resorption [
2] and released metal ions, e.g. from cobalt-chromium and titanium alloys (Co
2+, Cr
3+, Al
3+, V
2+) may cause adverse local [
4,
5,
6] and systematic biological response [
7,
8]. Common-used implant materials lead to alteration of mechanical loading of the periprosthetic bone (stress shielding). The mechanical stimulus on the bone tissue and cells is redcued and thus bone remodeling shifted towards resorption [
2,
3]. These effects are leading to periprosthetic bone loss, potentially causing osteolysis, implant loosening, and increased periprosthetic fracture risk [
9].
Multifunctional hybrid implant materials have been investigated to address these issues [
10,
11,
12,
13,
14,
15,
16,
17,
18]. For example, these materials are supposed to combine advantageous properties of oxide ceramics at the articulating surfaces of the artificial joint and titanium (Ti) alloys at the bone-implant interface. Thus, high wear and corrosion resistance with a lower risk of stress shielding can be achieved [
10,
12,
14,
19]. In previous studies, functionally graded materials manufactured by spark plasma sintering have been investigated [
10,
11,
12,
13,
14,
19]. They are composed of a pure ceramic phase (e. g. Al
2O
3 or Y
2O
3-stabilized ZrO
2), mixed ceramic-titanium phases with continuously decreasing ceramic content, and a titanium or Ti-6Al-4V phase. Other approaches used laser-engineered net shaping to manufacture Ti6Al4V-Al
2O
3 [
15] hybrids or glass solders to join solid ceramic and titanium-based components [
17,
18].
Glass soldering of bioceramics such as Al
2O
3 or ZrO
2 and commercially pure titanium (cp-Ti) has originally been developed for dental applications [
20,
21,
22] but it also demonstrated applicability to the endoprosthetic implant materials like alumina-toughened zirconia ceramics (ATZ) and Ti-6Al-4V [
18]. Processing such hybrid materials involves the application of a biocompatible silica-based glass [
18,
23] to the joining surfaces and a subsequent firing to melt the glass solder. The main reason for a stable and durable connection is the formation of reaction layers during firing [
17,
18,
24], and the mechanical interlocking between glass solder and ceramic or the metal part, respectively [
17]. Mick et al. [
18] used a glass solder (main components: SiO
2, Al
2O
3, Na
2O, KO
2) to fabricate Ti6Al4V-ATZ hybrid materials and reported a bending strength of 118 ± 33 MPa. In addition, Markhoff et al. [
22] showed good interaction of human osteoblasts with a similar glass solder applied as a coating on ATZ bulk material. Nevertheless, the transformation of this technology to endoprosthetic implants, such as the femoral component of a total knee replacement, presents challenges in joining larger and complex shaped surfaces.
Using medical β-titanium (β-Ti) alloys in glass-soldered hybrid materials is a promising approach, since β-Ti alloys possess increased elasticity compared to pure α (cp-Ti) or α+β (Ti-6Al-4V) Ti alloys [
25]. They are mostly composed of biocompatible elements such as Nb, Ta, and Zr [
26,
27,
28], which are highly corrosion resistant [
29,
30] and additionally promote osteogenesis [
31]. Furthermore, β-Ti alloys can be additively manufactured by laser powder bed fusion (PBF-LB/M) [
32], allowing advanced processability, e.g., direct fabrication of complex structures, such as open porous scaffolds or specifically functionalized implant surfaces [
26,
33]. In this context, Ti-35Nb-6Ta (TiNbTa) additively manufactured by PBF-LB/M has been recently investigated [
31,
32]. This alloy has a lower elastic modulus of approx. 54.2 GPa [
31] compared to commercially-used Ti-6Al-4V (115 GPa [
34]). A tensile strength of 651 ± 1.2 MPa and an elongation at break of 21.3 ± 1.2 % was reported, indicating that TiNbTa is also highly ductile [
32]. In addition, human osteoblasts cultured on as printed TiNbTa surfaces showed a gene expression profile of osteogenic differentiation markers, indicating osteoconductive properties [
31].
The present study aims to characterize hybrid TiNbTa-ATZ specimens using additively manufactured TiNbTa components which are joined to ATZ using a biocompatible silica-based glass solder. The manufactured TiNbTa-ATZ joints are structurally and chemically analyzed by backscatter electron (BSE) microscopy and energy-dispersive X-ray spectroscopy (EDX). Furthermore, the hybrid material is characterized by mechanical testing (static and fatigue shear stress) and the influence of artificially aging on static shear strength is analyzed. Hybrid Ti-ATZ specimens are used as a reference. In addition, the cytotoxicity of TiNbTa-ATZ specimens is evaluated and compared with Ti-ATZ and Co-CrMo specimens using an elution assay and human osteoblasts. Furthermore, a simplified functional implant demonstrator of a hybrid material-based femoral component was fabricated, structurally characterized, and analyzed for mechanical strength under biomechanical loading using gait cycles as well as loading to failure.
4. Discussion
Multifunctional hybrid materials have been described to reduce material-related aseptic implant loosening in total joint replacements [
10,
11,
12,
13,
14,
15,
16,
17,
18]. These hybrid materials are composed of an oxide ceramic at the articulating interfaces and a Ti-based material at the bone-implant interface. One feasible technology to combine oxide ceramics with Ti alloys is glass soldering [
17,
18,
20,
21]. Here, we investigated the static and fatigue shear strength, influence of aging, and cytotoxicity of hybrid material specimens consisting of slip-casted ATZ and additively manufactured β-type Ti-35Nb-6Ta joined by a silica-based glass solder. In addition, the biomechanical performance of functional demonstrators of a total knee replacement was analyzed under walking cycles and load-to-failure testing under an extension-flexion loading.
The static shear strength of TiNbTa-ATZ hybrid material (26.4 ± 4.2 MPa) did not differ significantly compared to the reference material (Ti-ATZ) and showed sufficient fatigue strength to withstand 10
7 dynamic shear loading cycles. Furthermore, accelerated aging caused no reduction in the static shear strength of the joined TiNbTa-ATZ specimens. A comparable study investigating Ti-ZrO
2 hybrid materials reported a shear strength of 16.8 ± 4.9 MPa [
24].
To be used as implant material in cementless total joint replacements, the soldered joint of the hybrid material should not represent a predetermined fracture point. In the case of cementless fixated titanium-based implants, the fixation strength between the bone and the implant surface determines the maximum load-bearing capacity. It has been reported that the implant-bone interface strength ranged from 0.5 MPa to 19.7 MPa [
42,
43,
44,
45,
46]. In addition, in the standard to evaluate the shear strength of titanium-based plasma-sprayed coatings, 20 MPa has been defined as minimum requirement [
39]. Therefore, according to the measured properties, the investigated hybrid materials have sufficient strength to ensure that they do not form a flaw when used in endoprosthetic implants. However, during functional loading, the hybrid material is subjected to mixed tensile, shear, and compressive stress [
47]. Investigating the influence of the different stresses occurring simultaneously is complex and requires further studies that go beyond the content of the present study.
The microscopic investigations of the TiNbTa-ATZ fracture surfaces revealed that the strength of the hybrid material is determined by adhesive failure along the interface between glass solder and TiNbTa alloy as well as cohesive fracture of the glass solder, which is in line with previous observations [
18,
20,
24]. Within TiNbTa alloys, oxide films, e.g., TiO
2, Nb
2O
5, and Ta
2O are formed [
29,
30], and the reaction of the chemical compounds in the surface layers with the glass solder is crucial in the formation of the material bond [
17,
18]. Hey et al. [
48] described the formation of Ti
5Si
3 due to the reaction of SiO
2 with Ti using a comparable silica-based glass solder. Furthermore, in a study on the diffusion bonding of Al
2O
3 and cp-Ti, Travessa et al. [
49] described that at 800 °C Al
2O
3 dissolves in the presence of titanium and further reacts with titanium to form an intermetallic Ti
3Al compound. In the process, oxygen diffuses into titanium, and Al-rich compounds accumulate at the interface, which was also observed in our study. In contrast, no chemical reaction of Ti-30Ta and Ti-40Nb with Al
2O
3 has been reported [
50,
51], and also no measurable formation of an interfacial reaction phase of pure Nb with Al
2O
3 [
52]. Therefore, it seems reasonable that the material bond between glass solder and TiNbTa was formed by the reaction of titanium with SiO
2 and Al
2O
3. Moreover, it has been previously described that the formed oxide layer in the titanium material or the interface between the oxide layer and the bulk material was responsible for the failure of interfaces between titanium and glass ceramics [
18,
20]. This was also shown in our present study by the visible deposition of the TiNbTa or cp-Ti on the ATZ fracture surface. The described chemical reactions should be verified in future research focusing on the formation of the intermetallic reaction zone.
Transferring the knowledge gained from glass soldering to more complex and larger joining surfaces is crucial for the development of a hybrid material-based endoprosthetic implant. To gain first experience of the feasibility, we manufactured a simplified functional demonstrator resembling one condyle of the tibiofemoral joint. As we already observed pores in the soldered joints of the shear test specimens, we tried to reduce them by modifying the priming of the joining surfaces. To achieve a constant joint thickness, the titanium components were provided with spacers. Despite these efforts, pores were still visible in the joint gaps. Nevertheless, all specimens survived 10000 walking cycles and TiNbTa-ATZ hybrids showed maximum extension-flexion moments of 40.7 ± 2.2 Nm. The rather small standard deviations indicate that the modification of the priming processes had a positive influence on variations in the mechanical properties.
Given the absence of prior experiences with the investigated hybrid material regarding biomechanical loading scenarios, the walking cycles gave a first impression of the biomechanical performance of the implant demonstrator. We admit that 10000 cycles are not enough to prove fatigue strength under physiological loading. For example, the ISO standard 14243 specifies 5 × 10
6 load cycles corresponding to approximately five years of clinical use. In addition to the walking cycles, subsequent loading to failure was used to determine the maximum extension-flexion moment. Bergmann et al. [
53] reported data of instrumented TKR and defined the EXTREME100 case as the maximum value suitable for studying mechanical safety under severe
in vivo conditions. The flexion moments during walking and jogging were 25.9 Nm and 39.8 Nm, respectively, and significantly higher values of 46.1 Nm and 59.1 Nm have been observed during squatting and stair descent, respectively [
53]. Another study by Dreyer et al. [
54] determined peak values during various physiological motions in a comparable range (26 to 35 Nm). Considering that the maximum extension-flexion moment of the functional demonstrator was observed for a single condyle and that
in vivo loads are measured for a bicondylar TKR, it seems that the bonding strength of the TiNbTa-ATZ hybrid meets the minimum requirement for an endoprosthetic implant. However, as mentioned above, the total knee endoprostheses are subjected to complex loadings by superimposed forces and moments. In addition, the material joint strength should provide a high safety factor that ensures mechanical functionality over a long period. The bonding strength of complex-shaped hybrid material specimens should therefore be improved, e.g., by realizing a form fit of the ATZ and titanium components.
We observed a difference in the maximum extension-flexion moments of TiNbTa-ATZ and Ti-ATZ functional demonstrators, although no significant differences were observed during shear loading tests. For shear loading, the additive manufactured TiNbTa was machined to obtain parallel joining surfaces and afterward sandblasted (see Section 2.2). This procedure led to similar roughness of the different specimens. However, the joining surfaces of the TiNbTa components of the functional demonstrator were not machined, and only sandblasting of the as-printed surface with similar process parameters to cp-Ti components was used. For this reason, the TiNbTa components possessed a higher roughness than those of cp-Ti. In addition to the chemical bond, mechanical interlocking can also majorly contribute to bonding strength [
17], that may have led to the increased joint strength in the rougher TiNbTa demonstrators. However, no study investigated the influence of the surface roughness of additively manufactured TiNbTa components on the bonding strength with a silica-based glass solder so far. Therefore, this might be one factor to further increase bonding strength.
In addition to the mechanical properties, the cytotoxicity of the hybrid materials specimens is relevant for later application as bone implants. In our present study, TiNbTa-ATZ specimens did not impair the vitality of human osteoblasts, whereas Co-28Cr-6Mo decreased cell proliferation and metabolic activity. The cytotoxic effect of released Co- and Cr-ions on human cells has been previously demonstrated in various studies [
4,
5,
6,
7,
8]. In contrast to CoCrMo alloy, the materials based on glass solder and oxide ceramics are highly biocompatible [
22]. In addition, it has been shown that osteoblasts cultured on TiNbTa exhibit a gene differentiation indicating bone formation [
31]. In line with these previous findings, we demonstrated that the hybrid TiNbTa-ATZ material showed no cytotoxic effects
in vitro.
However, this study has some limitations. We observed pores in the soldered interface that reduce the mechanically loaded cross-section area. Such faults may cause local stress concentrations resulting in unexpected failure. The pores are based on entrapped gas, which might come from the evaporation of the polymer-based carrier suspension of the glass solder paste during firing. Minimizing the pore formation is a critical issue to manufacture reliable bonding with glass solders [
23,
55]. The development of technological approaches to prevent these pores was beyond the scope of this present study. In addition, the functional demonstrator represents a simplified implant design. Hence, the observations during biomechanical testing need to be verified with a more complex design, which is closer to the currently used implants.
Further research should focus on parameter characterization for the bonding strength of TiNbTa-ATZ hybrid materials, e.g., by characterizing the influence of the surface roughness or the chemical composition of the glass solder and joining parameters.
Author Contributions
Conceptualization, J.-O. S., A. M., M. W., D. K., J. J., U. L., D. R., C. L., A. J.-H., and R. B.; methodology, J.-O. S., P. H., A. M., M. W., D. K., M.-L. S., U. L., D. R., C. L., A. J.-H., and R. B.; formal analysis, J.-O. S., M.-L. S., and A. J.-H.; investigation, J.-O. S., P. H., M.-L. S., D. K., M. W., A. J.-H., and R. B.; data curation, J.-O. S., P. H. M.-L. S., A. J.-H., and M. W.; writing—original draft preparation, J.-O. S., M.-L. S., and A. J.-H.; writing—review and editing, P. H., A. M., M. W., D. K., J. J., U. L., D. R., C. L., and R. B.; visualization, J.-O. S., M.-L. S., and A. J.-H.; supervision, D. K., A. J.-H., and R. B.; project administration, J.-O. S., and C. L.; funding acquisition, A. M., M. W., D. K., J. J., D. R., U. L., C. L., A. J.-H., and R. B. All authors have read and agreed to the published version of the manuscript.
Figure 1.
Design of the simplified functional demonstrator of a hybrid material-based femoral component for a total knee replacement resembling a part of the tibiofemoral joint. The hybrid material is formed by glass soldering of additivly manufactured TiNbTa to ATZ ceramics and the joining surface of TiNBTa is functionalized with spacers 0.1 mm in height to ensure a homogeneous joint gap (created with Biorender.com).
Figure 1.
Design of the simplified functional demonstrator of a hybrid material-based femoral component for a total knee replacement resembling a part of the tibiofemoral joint. The hybrid material is formed by glass soldering of additivly manufactured TiNbTa to ATZ ceramics and the joining surface of TiNBTa is functionalized with spacers 0.1 mm in height to ensure a homogeneous joint gap (created with Biorender.com).
Figure 2.
Consecutive steps to prime the TiNbTa component of the hybrid material-based functional demonstrator with a) untreated specimen, b) specimen coated with the glass solder, and c) completely primed specimen by stepwise firing and polishing of the glass solder to fill the gap between the designed spacers with the glass solder. For better visualization, the glass solder was dyed blue.
Figure 2.
Consecutive steps to prime the TiNbTa component of the hybrid material-based functional demonstrator with a) untreated specimen, b) specimen coated with the glass solder, and c) completely primed specimen by stepwise firing and polishing of the glass solder to fill the gap between the designed spacers with the glass solder. For better visualization, the glass solder was dyed blue.
Figure 3.
Biomechanical characterization of the hybrid material-based (glass soldered TiNbTa-ATZ or Ti-ATZ) functional demonstrators of the femoral component of a total knee replacement: a) biomechanical loading of the walking cycle in the VIVOTM joint simulator and b) schematic illustration of the flexion movement of the tibiofemoral joint and derived test setup to characterize the maximum bearable extension-flexion moment (created with Biorender.com).
Figure 3.
Biomechanical characterization of the hybrid material-based (glass soldered TiNbTa-ATZ or Ti-ATZ) functional demonstrators of the femoral component of a total knee replacement: a) biomechanical loading of the walking cycle in the VIVOTM joint simulator and b) schematic illustration of the flexion movement of the tibiofemoral joint and derived test setup to characterize the maximum bearable extension-flexion moment (created with Biorender.com).
Figure 4.
Electron microscopic images of a hybrid material of joined alumina-toughened zirconia (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa) using a silica-based glass solder (GS). a,d) BSE of the investigated cross-section, at different magnifications, b,c,e,f) element distribution in the TiNbTa alloy (b), the ATZ ceramic (c), and the glass solder (e, f). Pores are indicated by white arrows.
Figure 4.
Electron microscopic images of a hybrid material of joined alumina-toughened zirconia (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa) using a silica-based glass solder (GS). a,d) BSE of the investigated cross-section, at different magnifications, b,c,e,f) element distribution in the TiNbTa alloy (b), the ATZ ceramic (c), and the glass solder (e, f). Pores are indicated by white arrows.
Figure 5.
Results of the static shear testing and microscopy of the fracture surfaces of glass-soldered TiNbTa-ATZ or Ti-ATZ hybrids. a) static shear strength (data are presented as single values with median and interquartile ranges and statistical significance was determined by a pairwise Kruskal Wallis Test), b) representative fracture surfaces of specimens in the upper and lower quartile of the static strength (1: cohesive failure of the Ti-based component, 2: adhesive failure of the glass solder, 3: imperfections in the glass solder due to spherical pores), c-e) Microscopic images and a depth profile of an ATZ fracture surface of a Ti-ATZ specimen indicating the cohesive failure of the cp-Ti, which led to the deposition of the bulk material on the ATZ surface, d-h) Microscopic images and a depth profile of a TiNbTa fracture surface of a specimen of group 1 indicating spherical pores in the glass solder, i-k) Microscopic images and a depth profile of an cp-Ti fracture surface of a specimen of group 4 indicating networked or branched structures in the glass solder.
Figure 5.
Results of the static shear testing and microscopy of the fracture surfaces of glass-soldered TiNbTa-ATZ or Ti-ATZ hybrids. a) static shear strength (data are presented as single values with median and interquartile ranges and statistical significance was determined by a pairwise Kruskal Wallis Test), b) representative fracture surfaces of specimens in the upper and lower quartile of the static strength (1: cohesive failure of the Ti-based component, 2: adhesive failure of the glass solder, 3: imperfections in the glass solder due to spherical pores), c-e) Microscopic images and a depth profile of an ATZ fracture surface of a Ti-ATZ specimen indicating the cohesive failure of the cp-Ti, which led to the deposition of the bulk material on the ATZ surface, d-h) Microscopic images and a depth profile of a TiNbTa fracture surface of a specimen of group 1 indicating spherical pores in the glass solder, i-k) Microscopic images and a depth profile of an cp-Ti fracture surface of a specimen of group 4 indicating networked or branched structures in the glass solder.
Figure 6.
Cytotoxicity analysis of the glass-soldered hybrid material specimens (TiNbTa-ATZ or Ti-ATZ) using elution testing (elution time 14 and 21 days). Quantification of a) metabolic activity by WST-1 assay and b) cell number by CyQUANT™ assay of human osteoblasts after incubation in diluted eluate for 24 h. Osteoblasts in cell culture medium served as control (dashed line). Data are presented as single values with median and interquartile ranges. Statistical significance was determined by 2-way ANOVA followed by Bonferroni multiple comparison test **p<0.01.
Figure 6.
Cytotoxicity analysis of the glass-soldered hybrid material specimens (TiNbTa-ATZ or Ti-ATZ) using elution testing (elution time 14 and 21 days). Quantification of a) metabolic activity by WST-1 assay and b) cell number by CyQUANT™ assay of human osteoblasts after incubation in diluted eluate for 24 h. Osteoblasts in cell culture medium served as control (dashed line). Data are presented as single values with median and interquartile ranges. Statistical significance was determined by 2-way ANOVA followed by Bonferroni multiple comparison test **p<0.01.
Figure 7.
Structural analysis of the functional demonstrator of the femoral component of a total knee replacement made of alumina-toughened zirconia (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa), joined by a silica-based glass solder (GS): a) illustration of the analysed cross-section, b) BSE of the polished cross-section of the soldered joint; examples of pores in the glass solder are highlighted by white arrows.
Figure 7.
Structural analysis of the functional demonstrator of the femoral component of a total knee replacement made of alumina-toughened zirconia (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa), joined by a silica-based glass solder (GS): a) illustration of the analysed cross-section, b) BSE of the polished cross-section of the soldered joint; examples of pores in the glass solder are highlighted by white arrows.
Table 1.
Overview of the mechanically tested groups, the used hybrid material, test specifications, and the measured cross-section at the soldered joint.
Table 1.
Overview of the mechanically tested groups, the used hybrid material, test specifications, and the measured cross-section at the soldered joint.
Group |
Material |
Specifications |
Cross-section [mm²] |
1 |
TiNbTa-ATZ |
Static shear test |
279.4 ± 0.1 |
2 |
Ti-ATZ |
Static shear test |
280.0 ± 0.3 |
3 |
TiNbTa-ATZ |
Accelerated aging followed by static shear test |
281.0 ± 1.1 |
4 |
Ti-ATZ |
Accelerated aging followed by static shear test |
280.4 ± 0.4 |
5 |
TiNbTa-ATZ |
Fatigue shear test |
280.3 ± 0.8 |
6 |
Ti-ATZ |
Fatigue shear test |
281.9 ± 1.2 |