2023 Volume 64 Issue 8 Pages 1673-1682
In the last years, nanostructured metals prepared by severe plastic deformation (SPD) techniques have emerged as a promising class of advanced biomaterials for load-bearing applications such as orthopedic implants. This is mainly because of the simultaneous improvements in mechanical and biocompatibility properties during the creation of nanostructures. This article provides a brief overview of the effects of SPD techniques in producing nano/ultrafine-grained structures in advanced biomaterials for implant applications. The role of microstructure refinement achieved by SPD and its effect on mechanical properties and biocompatibility, together with processing challenges are reviewed. As advanced biomaterials, pure titanium, and Ti-based alloys which possess a broad range of applications in the biomedical industry are initially discussed. Further, the recent results on high-entropy alloys and metal-protein composites obtained by means of SPD for biomedical purposes are reviewed. The results discussed here clearly demonstrate the beneficial effects of SPD techniques in designing and producing nanostructured advanced biomaterials with exceptional mechanical and functional properties desired for implants.
(a) Vickers microhardness of the Bio-HEA TiAlFeCoNi after HPT processing. Variation of Vickers microhardness against distance from disc center for ingot and sample processed by HPT. For comparison, hardness for TiAlFeCoNi Ti-based biomaterials before HPT processing were included. (b) Nanoindentation load against displacement for ingot (a) and (b) HPT-processed sample. (c) MTT cell viability assay examined by light absorbance at 570 nm and Vickers microhardness for samples of pure Titanium (99.9%), Ti–6Al–7Nb and TiAlFeNiCo before and after processing by HPT.
The severe plastic deformation (SPD) technology is the most powerful method for producing ultrafine-grained (UFG) materials in bulk dimensions.1–3) There are several SPD techniques available and the most established methods employed are high-pressure torsion (HPT),4,5) twist extrusion (TE),6) multi-directional forging (MDF),7) equal-channel angular pressing (ECAP),8,9) accumulative roll-bonding (ARB),10,11) cyclic extrusion and compression (CEC)12) and repetitive corrugation and straightening (RCS).13) In SPD processing, a very large plastic strain is imposed on the material to produce UFG materials with high-angle grain boundaries.14) There are two key features that any method classified as SPD must follow: i) the high strain is imposed without any significant change in the overall dimensions of the workpiece; ii) the shape is retained by using special tool geometries that prevent the free flow of the material and thereby produce a significant hydrostatic pressure.14,15) Under this hydrostatic pressure regime, the straining of material promotes a severe reduction in the grain size down to the submicrometer range (100 nm–1.0 µm) or even to the nanometer range (<100 nm). With the grain size reduction during the nanostructuring of materials, other crystal lattice imperfections such as vacancies, stacking faults, twins, and dislocations are also produced.1–3,14,15)
Since many properties of polycrystalline materials are extremely dependent on the grain size together with the concentration and nature of imperfections, the SPD process has the ability to produce materials with enhanced properties and unusual functionalities. As a first example, it is well known in the field of materials science that a considerable decrease in grain size improves the mechanical properties at room temperature and also provides superplasticity ability at elevated temperatures.16–18) Moreover, not only mechanical properties of materials change after SPD processing, but also surface properties, corrosion resistance and biocompatibility are also greatly affected by nanostructuring.1–5)
In the field of medical applications, the introduction of UFG materials by means of SPD techniques has gained significant attention in the last few decades.19–23) The SPD technology has been proven to be a successful and easy way to fabricate materials with an excellent combination of mechanical properties (such as superior strength, hardness and wear resistance), enhanced corrosion and high biocompatibility with a customized design for the biomedical industry.20,21) Most of the implants used in medical devices are basically metals due to the desired combination of properties required for a biomaterial, such as high strength, toughness, durability and corrosion resistance.20,24,25) The combination of material design and processing by SPD techniques as a way to produce nanostructured biomaterials has proven to be more beneficial compared to the use of conventional biomaterials in the microcrystalline form.24,25) In this sense, nanostructured biomaterials show improved compatibility and bioactivity towards osteoblast and fibroblast cells with significantly increased cell adhesion and proliferation on the surface.22,23) Moreover, the levels of protein adsorption, cell attachment, proliferation and differentiation are higher in nanostructured material compared with conventional materials.23) All these physiological processes associated with the interaction of human cells and the surface of biomaterials are greatly favored at the nanometer scale ensuring good osseointegration.22,23)
Titanium and its alloys are widely used as biomaterials mainly due to their high strength-to-weight ratio, low stiffness, low density and high corrosion resistance.26–32) Indeed, titanium and its alloys have superior biocompatibility in comparison with the conventional biomaterials used in the medical industry such as Co–Cr–Mo and 316L stainless steel.29–34) The advantages of the development of nanostructured titanium and its alloys by means of SPD have introduced them as a new class of advanced biomaterials.20–25,33–35) Several studies reported superior corrosion resistance,36,37) improved mechanical properties (hardness, strength and wear properties),20,21,38) enhanced bacterial adhesion,39,40) improved wettability,41,42) and high bioactivity and cell adhesion43–47) of nanostructured titanium and its alloys processed by ECAP or HPT in comparison with non-processed titanium. The rate of proliferation of osteoblast cells on nanostructured titanium has been reported to be as much as 19 times greater than that on conventional titanium.44) Nanostructured titanium alloys such as Ti–6Al–4V (mass%),48–54) Ti–6Al–7Nb (mass%),55–60) Ti–Nb,61–67) Ti–Mo68–74) and Ti–Nb–Ta–Zr (TNTZ)75–79) prepared by SPD methods also show superior mechanical properties and biocompatibility in comparison with pure titanium and its alloys in a microcrystalline form.48–79) From the commercial point of view, Ti–6Al–4V and Ti–6Al–7Nb alloys already found their way into the market and are used mostly for dental and orthopedic applications.30–34)
Although the literature has reported very promising achievements in nanostructured titanium alloys for biomedical applications, the range and degree of biomaterial sophistication have also dramatically increased due to recent advances in materials science, manufacturing processes, biology and tissue engineering.80,81) In this context, there is a search for new biomaterials with superior mechanical properties and ultra-high biocompatibility in comparison to the existing ones. As an example, high-entropy alloys (HEAs) - especially designed for biomedical applications - can be considered as the most recent class of potential biomaterials which have presented mechanical properties and biocompatibility fairly superior in comparison to the traditional biomaterials such as pure titanium, Ti–6Al–4V, Ti–6Al–7Nb, Co–Cr–Mo and 316L.82–90) In order to enhance mechanical properties, these HEAs designed for biomedical applications can also be processed by means of SPD methods.91,92) Another example of the new generation of advanced biomaterials is the synthesis of metal-protein composites as a new family of biomaterials by means of HPT which exhibit excellent mechanical properties and high biocompatibility.93)
This overview highlights the effects of SPD techniques on advanced biomaterials with a focus on titanium and its alloys, HEAs and metal-protein composites. With this overview, we intend to explore the key aspects of the microstructure refinement of biomedical materials that can justify the enhancement of mechanical properties and biocompatibility. To do so, the review is divided mainly into three sections and each section shows the impact of SPD methods in a different class of biomaterials. The first section is related to titanium alloys, the second section focuses on HEAs, and the last section is dedicated to the review of Ti-protein composites obtained by SPD.
Titanium alloys play an important role in the biomedical field and are considered excellent options for orthopedic implants due to their high strength, low Young’s modulus, high corrosion resistance, good fatigue properties, lightweight and exceptional biocompatibility.26–32) As biomedical alloys, they do not produce cytotoxic and genotoxic effects and allergic and chronic inflammatory reactions in the human body by the release of toxic elements.29,94) In spite of the extensive development of titanium alloys for biomedical applications in the last few years, SPD processing has been used to produce nanostructured titanium alloys with superior properties.37–46) The great interest in nanostructuring of titanium alloys is mainly due to the unique type of microstructure obtained by SPD processing which results in very significant grain refinement and improvement of mechanical, corrosion and biocompatibility properties.19,20) In essence, nanostructured titanium alloys exhibit enhanced strength, low Young’s modulus and better biocompatibility in comparison to counterpart’s microcrystalline materials prepared by conventional melting followed by cold rolling or extrusion process.
Titanium alloys are divided into five categories based on the microstructure obtained after processing: α and near-α alloys (hexagonal close-packed phase), β and near-β alloys (body-centered cubic phase), and duplex or two-phase α + β alloys.95,96) From the commercial point of view, the Ti–6Al–4V and Ti–6Al–7Nb alloys are the most used alloys for dental and orthopedic applications.30–34) These alloys are being used in different fields of orthopedics such as fracture repair, total hip and knee arthroplasty and also in dental implants.27–34) Both alloys are classified as α + β alloys, having the presence of both hexagonal close-packed α and body-centered cubic β structures with Young’s modulus of around 110 GPa. Several studies have demonstrated the positive effects of SPD processing on the microstructure of Ti–6Al–4V48–53) and Ti–6Al–7Nb55–60) alloys with attractive mechanical, corrosion and biocompatibility properties for medical applications. A detailed investigation of the literature reveals that both alloys are mainly processed by the two most well-known SPD methods, ECAP and HPT. More details about the principles of ECAP9) and HPT5) can be found in the previous references.
As a current evolution of the Ti-based alloys used in the biomedical field, β titanium alloys have been considered a new promising class of advanced biomaterials due to the exceptional combination of higher strength and lower Young’s modulus in comparison with the α and α + β alloys. This new generation of β titanium alloys can be represented by Ti–Nb,61–67) Ti–Mo68–74) and Ti–Nb–Ta–Zr (TNTZ)75–79) alloys in a nanostructured form. More details about the effects of SPD processing on the mechanical and biocompatibility properties of Ti–6Al–4V, Ti–6Al–7Nb, Ti–Nb, Ti–Mo and TNTZ alloys are discussed below.
2.1 Ti–6Al–4V alloyOnly a few studies48–50) focused on the improvement of the mechanical and fatigue properties of Ti–6Al–4V ELI (Extra Low Interstitial alloys for biomedical applications) by means of ECAP followed by extrusion and/or thermomechanical treatment. Semenova et al.48) investigated the microstructures and mechanical properties of the Ti–6Al–4V ELI alloy processed by ECAP and extrusion with various morphologies of the α and β phases. They showed that the decrease of volume fraction of α phase results in a more homogeneous structure refinement during ECAP, lower internal stress, and enhanced microstructure stability and mechanical properties. The processed Ti–6Al–4V ELI alloy presented an ultimate tensile strength of UTS ≥1350 MPa while maintaining a ductility of δ ≥ 11%. The fatigue properties of Ti–6Al–4V ELI alloy can also be considerably improved by obtaining UFG structure by ECAP followed by a subsequent thermomechanical treatment.48) The fatigue limit of the UFG Ti–6Al–4V ELI alloy is increased by 70 MPa compared to the coarse-grained counterpart materials. Beyond the fatigue properties, the yield strength (YS) and UTS increased by about 48% and 50%, respectively, whereas the hardness increased by only 11% when compared to the coarse-grained counterpart materials.49,50) Table 1 summarizes the mechanical properties improvement attainable in UFG Ti–6Al–4V alloys in comparison to the reference samples in the coarse-grained state.
By considering the long-term use of Ti–6Al–4V alloy as implants, surface modification can be done to improve the corrosion and biocompatibility properties. Kazemi et al.51) reported superior results of TiN along with the hydroxyapatite (HA) coating on the Ti–6Al–4V substrate surface. The results of cell viability and proliferation of HA/TiN nanocomposite coating demonstrated excellent corrosion resistance and biocompatibility revealing that this coated alloy is a good choice for dental and orthopedic implants.
Recent studies proposed by Lin et al.52,53) examined the surface morphology of HPT-processed Ti–6Al–4V alloy after laser surface treatment. The main idea behind this approach was to explore the potential for combining both a modification of the surface properties and mechanical strength of UFG titanium alloys. The authors reported a very refined microstructure for the Ti–6Al–4V alloy after 10 turns of HPT with a mean grain size of about 50 ± 10 nm. After the laser treatment of HPT-processed Ti–6Al–4V alloy, the surface became hydrophilic, the contact angle increased and the surface gradually transformed from a hydrophilic state to a hydrophobic state. As already established in the medical field, hydrophilic phenomena provide good tissue adhesion in implants and are designed for rapid cell–cell communications.54)
2.2 Ti–6Al–7Nb alloyThere have been several studies that reported the successful achievement of mechanical properties and biocompatibility of Ti–6Al–7Nb alloy by using SPD methods.55–60) As one of the first studies in this direction,55) the ECAP process with thermo-mechanical treatment was applied to the Ti–6Al–7Nb alloy to enhance strength and ductility. The formation of the UFG structure led to higher strength (UTS = 1400 MPa) and ductility (elongation 10%). In recent contributions,56,57) the improvement in mechanical and fatigue properties of Ti–6Al–7Nb alloy was also reported after ECAP with subsequent thermomechanical processing. In a comparison with coarse-grained Ti–6Al–7Nb alloy, the UFG Ti–6Al–7Nb alloy with an average grain size of ∼180 nm showed considerable enhancement of strength from 1020 to 1460 MPa (while keeping a good ductility of 11%) together with 35% enhancement of fatigue endurance limit. Indeed, as the strain increased during ECAP, there was a non-monotonic variation in the density of low- and high-angle grain boundaries of α grains.57) Janeček et al.58) reported the results of the mechanical properties and dislocation structure evolution in Ti–6Al–7Nb alloy processed by HPT up to 15 revolutions. They showed that the microhardness significantly increases from 330 HV to 400 HV with increasing strain. The defect structure is homogenous after 1/2 HPT revolution, while the microhardness becomes homogenous only after 3 HPT revolutions. Table 2 summarizes the mechanical properties improvements attainable in UFG Ti–6Al–7Nb alloy in comparison to the reference samples in the coarse-grained state.
Oliveira et al.59) reported the results of the chemical treatment of UFG Ti–6Al–7Nb alloy after processing by ECAP. Beyond the superior mechanical and fatigue properties obtained for the UFG Ti–6Al–7Nb alloy, phosphoric acid etching combined with alkaline treatment led to bioactivity after the sample was soaked in simulated body fluid (SBF) solution for seven days. This fact showed that a simple chemical treatment can be effective to modify the surface of implants made from high-strength UFG Ti–6Al–7Nb alloy to induce apatite nucleation and growth. Another important issue with the microstructure of UFG materials is their thermal stability. In a study by Bartha et al.,60) the lattice defects and thermal stability of UFG Ti–6Al–7Nb alloy were explored. The Ti–6Al–7Nb alloy was prepared by thermal treatment followed by ECAP and extrusion. The UFG microstructure of Ti–6Al–7Nb alloy was stable up to 440°C, while upon heating to 550°C and to 660°C, the dislocation density decreased and vacancy clusters disappeared. Moreover, enhanced microhardness could be achieved by ECAP followed by aging at 500°C, but the microhardness decreased by heating to 660°C due to ongoing recovery and recrystallization.
Despite the remarkable properties of nanostructured Ti–6Al–4V and Ti–6Al–7Nb alloys, their long-term application as implants is limited by two main reasons: i) the need of reducing Young’s modulus to avoid the so-called stress-shielding effect;24,97) ii) the undesired presence of toxic elements such as vanadium and aluminum (i.e. release of vanadium and aluminum ions) in the alloys that may cause neurodegenerative diseases.98,99) Therefore, there is an urgent demand for developing new classes of titanium alloys with less (or none) toxic elements having a Young’s modulus closer to the human bones. In this direction, there has been a growing interest in the development of β titanium alloys in the last years.30–34) The β titanium alloys have been suggested to possess a perfect combination of higher strength and lower Young’s modulus in comparison with the α and α + β alloys, together with excellent corrosion resistance, enhanced biocompatibility and good formability.30,31) However, the lowest Young’s modulus of β titanium alloys is only obtained after solution treatment and ageing. But, these types of processing routes, induce a fine and uniform precipitation of ω and α phases which are responsible for a significant strengthening of the alloys and this consequently increases the Young’s modulus. So, the challenge is to develop β titanium alloys with high hardness, low Young’s modulus and good biocompatibility. In this sense, SPD techniques have also been used to produce UFG β titanium alloys that can meet all those criteria at the same time. Basically, this new generation of β titanium alloys can be represented by Ti–Nb,61–67) Ti–Mo68–74) and Ti–Nb–Ta–Zr (TNTZ)75–79) alloys in a nanostructured form. The next sub-sections show more details about the new generation of β titanium alloys.
2.3 Ti–Nb alloysPanigrahi et al.61) reported the effects of different SPD methods including hydrostatic extrusion (HE), rolling and folding (R&F) and HPT on the mechanical properties, as well as on the phase and texture evolution of biocompatible Ti–45Nb alloy (mass%). They observed that the fraction of the ω phase in the samples prior to and after SPD processing was too small to affect the Young’s modulus and the initial value of 65 GPa was kept unaltered. Indeed, an increase in the strength (e.g. from 446 ± 14 MPa to 668 ± 10 MPa for HPT and HE samples) and microhardness (e.g. from 1.50 ± 0.04 GPa to 2.47 ± 0.09 GPa for HPT samples) was noticed. The HPT and HE routes were revealed to be effective for biomedical applications as they preserve considerable ductility along with high strength. Another recent study62) reported the influence of grain size on the mechanical properties and high-cycle fatigue response of UFG Ti–45Nb alloy obtained by HPT. The microstructure of UFG Ti–45Nb alloy showed a considerable increase in hardness and strength due to the significant grain refinement while maintaining a low Young’s modulus of about 65 GPa. However, only a slight improvement of the fatigue resistance of the UFG material with superior tensile properties was achieved in comparison with the coarse-grained material. Volker et al.63) showed that the combination of HPT with subsequent heat treatment provides a feasible way to improve the mechanical properties of SPD-deformed β titanium alloys making them suitable for high-strength applications. They used HPT to refine the microstructure of a Ti–45Nb (mass%) alloy to ∼50 nm and reported that after isochronal heat treatment, the HPT-processed samples showed an increase in hardness and strength. Their microstructural studies showed that annealing causes the formation of α-Ti. In the same direction, Korneva et al.64) also confirmed that the combination of HPT followed by annealing could contribute to the improvement of plasticity in HPT-deformed β titanium alloy. After HPT processing of Ti–3Nb (mass%) alloy, a considerable grain refinement took place and the α phase partially transformed into the ω phase; however, after short-term annealing, the grain size slightly increased, and the ω phase transformed back to the α phase. These microstructural features led to an important growth of plasticity in the alloy.
Campos-Quirós et al.65) reported the effects of Niobium content on the microstructure and mechanical properties of Ti–Nb alloys synthesized from the titanium and niobium powders by HPT. Nanostructured Ti–Nb alloys with different amounts of niobium were synthesized by mechanical alloying of the elemental powders using the concept of ultra-SPD66,67) via the HPT process. All synthesized alloys exhibited high hardness and good plasticity; however, the best combination of low elastic modulus and high hardness was obtained for the sample with 25 at% Nb with the values of E = 39 ± 11 GPa (close to the elastic modulus of human bone) and HV = 3.7 ± 0.1 GPa (comparable to the hardest Ti-based biomaterials). Figure 1 shows the effect of niobium content on hardness, elastic modulus, strain-rate sensitivity and plastic work obtained from the nanoindentation and microhardness tests.
Variation of (a) hardness, (b) elastic modulus, (c) strain-rate sensitivity and (d) plastic work with Nb content (at%) for samples after HPT processing for N = 150 turns.65)
Regarding the Ti–15Mo alloys, their microstructure could be extremely refined by means of HPT68–72) or ECAP.73,74) The Ti–Mo alloys exhibited a tensile strength of 690 MPa and a modulus of elasticity of around 78 GPa in a solution-treated condition. Further processing via SPD methods could enhance the strength by introducing a high density of dislocations into the material and reducing its grain size down to 100 nm. However, as a metastable β-type alloy, its mechanical properties are significantly affected by phase transformations during processing and subsequent thermal treatment. The thermodynamically metastable ω phase, which is originally a high-pressure phase in pure titanium, may form during rapid cooling from the β phase in titanium alloy and the presence of ω phase increases strength of the alloy, but causes the embrittlement of the material.100) Subsequent ageing of UFG Ti–Mo alloys could lead to the precipitation of α-phase particles and this phase could act as barrier for dislocation motion and strengthen the material without detrimental embrittlement.101,102) Some other studies also reported enhanced α-phase precipitation in the β-stabilized Ti–Mo alloy after HPT processing.68–72) Xu et al.74) reported the α phase precipitation upon ageing within shear bands in the severely deformed Ti–20Mo material prepared by ECAP. This feature was also confirmed by Bartha et al.73) who showed that the α phase precipitation is accelerated in areas with a higher density of lattice defects, which provide a dense net of preferred sites for diffusion, nucleation and growth. The highest microhardness of 520 HV was found in the Ti–15Mo alloy after deformation by ECAP followed by ageing at temperature of 400°C for 16 h. This high hardness was attributed to the coexistence of the ω phase and the α phase precipitation.
2.5 Ti–Nb–Ta–Zr (TNTZ) alloysAlternative β titanium alloys with less tendency to form the ω phase such as the nanostructured Ti–Nb–Ta–Zr (TNTZ) alloy have also been proposed for medical applications.75–79,103) The special interest in TNTZ alloys is mainly due to their low elastic modulus (<65 GPa) under a solid-solution condition and due to the absence of harmful elements in their compositions. However, the mechanical strength of these alloys is lower than the conventional Ti–6Al–4V ELI alloy. Several studies were devoted to employing of the HPT75–77) or ECAP78,79) methods as a way to improve the mechanical strength and enhance the biocompatibility of TNTZ alloys while keeping their Young’s modulus low. Nakai et al.77) reported the effect of HPT on the microstructure and hardness of the Ti–29Nb–13Ta–4.6Zr (mass%) alloy. A deep inspection of the microstructure of the HPT-processed sample revealed the presence of a single β phase with submicron-sized grains. They showed that the grain refinement obtained by HPT is extremely significant and enhances the mechanical and biomedical properties of the TNTZ alloy used for biomedical applications. In another contribution by Li et al.,79) the results of the UFG Ti–36Nb–2Ta–3Zr alloy prepared via ECAP at room temperature were reported. After 6 ECAP passes, the UFG TNTZ alloy exhibited not only the expected increase in UTS (753.7 MPa) and YS (711.2 MPa), but also a slight increase in elongation (19.1%). The authors suggested that the deformation mechanism of ECAP-processed UFG TNTZ alloy involve two components: first, dislocation activity induced by the strain field imposed during ECAP; and second, the formation of α′′ martensite phase during the early stages of ECAP which eventually transforms into the β phase during continued deformation. For biocompatibility, Ninomi103) reported that the cytotoxicity of the Ti–29Nb–13Ta–4.6Zr (at%) alloy is equivalent to pure titanium, showing the high potential of TNTZ alloys for orthopedic applications.
In the last few decades, a new class of materials so-called high-entropy alloys (HEAs) has influenced the materials science community because of their wide range of exceptional properties. HEAs are defined as multi-principal element alloys composed of five or more principal elements with an atomic fraction between 5 and 35 at%. In these alloys, single-phase or sometimes dual-phase solid solutions are formed due to the entropy contribution in the minimization of the Gibbs free energy.104–106) The crystal structures of HEAs are commonly face-centered-cubic (FCC), body-centered-cubic (BCC) and hexagonal-close-packed (HCP).105) HEAs can show high strength and hardness,107) high wear resistance,108) good corrosion resistance109) and biocompatibility.82–92) Biocompatible HEAs, also called as Bio-HEAs, have been specifically designed for biomedical applications. Bio-HEAs are composed of non-biotoxic and allergy-free elements with good deformability, corrosion resistance, mechanical properties and biocompatibility in comparison to traditional biomaterials such as pure titanium, and Ti–6Al–4V, Ti–6Al–7Nb, Co–Cr–Mo and 316L stainless-steel alloys.82–87) Several potential Bio-HEAs have been developed such as TiNbTaZrMo,82) Ti2.6NbTaZrMo, Ti1.7NbTaZrMo0.5, Ti1.5NbTaZrMo0.5, Ti1.4Nb0.6Ta0.6Zr1.4Mo0.6,83–86) TiZrHfCr0.2Mo, TiZrHfCo0.07Cr0.07Mo,87) TiZrNbTaFe,88) TiZrHfNbTa,89) TiZrTaHfNb and Ti1.5ZrTa0.5Hf0.5Nb.90) These alloys are basically prepared by arc melting, mechanical alloying and additive manufacturing routes. In order to improve the mechanical properties (high hardness and strength and low Young’s modulus) and biocompatibility of Bio-HEAs, SPD techniques have also been recently employed.
The first study on this direction was reported by Edalati et al.91) This study developed a lattice-softened high-entropy alloy TiAlFeCoNi with ultrahigh hardness, low elastic modulus and superior activity for cell proliferation/viability/cytotoxicity by employing imperial data and thermodynamic calculations. The TiAlFeCoNi alloy was prepared by arc melting followed by HPT to control the crystal structure and microstructure. As can be seen in Fig. 2(a) and 2(b), the average hardness increased from 635 HV to 880 HV (due to grain refinement) and the elastic modules decreased from 249–254 GPa to 123–129 GPa (due to phase transformation), after HPT processing. The TiAlFeCoNi alloy showed 260–1020% better cellular metabolic activity compared to pure titanium and Ti–6Al–7Nb alloy, as shown in Fig. 2(c).
(a) Vickers microhardness of the Bio-HEA TiAlFeCoNi after HPT processing. Variation of Vickers microhardness against distance from disc center for ingot and sample processed by HPT. For comparison, hardness for TiAlFeCoNi Ti-based biomaterials before HPT processing were included. (b) Nanoindentation load against displacement for ingot (a) and (b) HPT-processed sample. (c) MTT cell viability assay examined by light absorbance at 570 nm and Vickers microhardness for samples of pure Titanium (99.9%), Ti–6Al–7Nb and TiAlFeNiCo before and after processing by HPT.91)
González-Masís et al.92) reported the use of the HPT method as a synthesis route and examined the effect of the number of elements (i.e. the effect of configurational entropy) on the microstructure and mechanical properties of multi-principal element alloys in the biocompatible Ti–Nb–Zr–Ta–Hf system. Several equiatomic alloys (TiNb, TiNbZr, TiNbZrTa and TiNbZrTaHf) with different configurational entropy were synthesized by the HPT process starting from the elemental powders. The authors reported the existence of nanograined solid solutions with the BCC structure after 50 turns of HPT in all alloys together with a high hardness of 564 HV and a moderate elastic modulus of 79 GPa for the quinary TiNbZrTaHf alloy. In a direct comparison with Ti-based alloys, these results suggested the high potential of the nanostructured HEAs synthesized by the HPT method for biomedical applications.
As discussed in the last sections of this overview, there have been significant research activities in the last few decades to design new biomaterials with adequate mechanical properties and high biocompatibility. Despite remarkable results on mechanical properties and biocompatibility observed for nanostructured Ti-based alloys and Bio-HEAs obtained by means of SPD techniques, there are other aspects related to the biocompatibility of these materials that must be improved.110,111) Surface bioactivity is one of these aspects that controls the protein adsorption onto biomaterial surfaces during the first stages of implantation. Protein adsorption is considered the first and most crucial stage enabling the adhesion of cells on the biomaterial surface, and thus, relevant clinical phenomena such as osseointegration of orthopedic implants proceed during this stage.112–114) To ensure good osseointegration of implant material, two main methods of surface modifications have been used: i) change/control the surface topography with chemical and/or physical methods,115,116) and ii) coatings with proteins or bioactive molecules.117,118) Although coating with proteins is effective to improve surface biocompatibility, the weak connection of protein to the metallic implant can result in delamination and failure of the implant within long-term use.119,120)
Floriano et al.93) introduced metal-protein nanocomposites as new biomaterials with high strength and good biocompatibility. The metal-protein composites were composed of titanium with small amounts of an endogenous protein such as 2 and 5 vol% of BSA (Bovine Serum Albumin). The HPT method was used to synthesize these new composites because the method ensures a good level of mixture and consolidation at the nanometer level between the two phases, and it attains the desirable nanostructure with high hardness for biomedical applications. After HPT processing, the composite showed a good level of mixing between nanograined titanium with sizes around 90 nm and the protein phase, as shown in TEM images in Fig. 3. These microstructural features led to a microhardness similar to nanocrystalline pure titanium and over two times higher than the hardness of coarse-grained pure titanium, as shown in Fig. 4(a). Meanwhile, the nanocomposites processed by HPT exhibited better biocompatibility (including cellular metabolic activity, cell cycle parameters and DNA fragmentation profile) compared to nano-titanium. The best behavior was observed for the composite containing 5% of BSA, as seen in Fig. 4(b). This study opens a pathway for the design and synthesis of a wide range of simple metal-biomolecule nanocomposite biomaterials by means of HPT. Since some biomolecules may decompose or denaturate under high pressure and strain,121) the selection of biomolecules for this new family of composites should be conducted carefully. Here, it should be noted that the application of SPD to design a novel family of materials is not limited to the biomaterials as a wide range of new materials were introduced by the SPD field for hydrogen storage,122,123) room-temperature superplasticity,124) electrical properties,125) optical properties,126) so on.
TEM images for Ti + 5 vol% BSA composite after 5 turns of HPT under 2 GPa. The bright field and darck-field images ((a) and (c)) shows the presence of several titanium UFG with the nanometer with an average grain size of 90 nm. The apparent rings in (b) belong to the titanium hexagonal structure.
(a) Vickers Microhardness and (b) MTT cell viability assay examined by light absorbance at 570 nm for pure titanium and for nanocomposites containing 2 and 5 vol% of BSA produced by 5 turns of HPT under 2 GPa in comparison with hardness of coarse-grained annealed titanium.93)
As covered in this overview, ultrafine-grained materials (UFG) can be considered as the next generation of biomedical materials. In this direction, advanced biomaterials represented by Ti-based alloys (α + β and β alloys), high-entropy alloys and metal-protein composites have demonstrated attractive properties desired for biomedical applications. Severe plastic deformation (SPD) showed to be an excellent and easy option to fabricate UFG biomaterials with an exceptional combination of mechanical properties, such as superior strength, longer fatigue life, hardness and wear resistance, enhanced corrosion resistance and excellent biocompatibility. In essence, UFG materials presented superior mechanical and biocompatibility properties in comparison with their coarse-grained counterparts. Despite the high number of SPD techniques available, most of the advanced biomaterials reviewed in this manuscript are mainly processed by the two most well-known SPD methods, equal-channel angular pressing (ECAP) and high-pressure torsion (HPT). This review systematically demonstrated the improvements in the mechanical properties such as ultimate and yield strength, hardness and fatigue life of ultra-fine grained α + β (Ti–6Al–4V and Ti–6Al–7Nb) and β (Ti–Nb, Ti–Mo and Ti–Nb–Ta–Zr) titanium alloys processed by ECAP and HPT processes.
Despite the benefits obtained in mechanical properties after ECAP and HPT processing, the viability, proliferation, and adhesion of cells cultured on the ultrafine-grained α + β and β titanium alloys are fairly superior to that of conventional microcrystalline counterparts. Despite the remarkable properties observed for UFG Ti-based alloys for the biomedical industry, new classes of advanced biomaterials have come up in the last few years. One of these new classes of advanced biomaterials can be represented by biocompatible high-entropy alloys (Bio-HEAs). The Bio-HEAs processed by SPD techniques presented mechanical properties and biocompatibility superior in comparison to the traditional biomaterials such as pure titanium, and the Ti–6Al–4V (mass%), Ti–6Al–7Nb (mass%), Co–Cr–Mo and 316L alloys. Metal-protein composites are another new class of biomaterials with ultra-high biocompatibility and adequate mechanical properties. Despite good mechanical and biocompatibility properties of severely deformed materials, scaling up the sample size, design of new material for SPD processing and examining the long-term clinical use of these materials are some issues that need to be investigated in future works.
R. Floriano thanks the Brazilian funding agencies for the financial support: grant #2022/03024-7, São Paulo Research Foundation (FAPESP); grant#407900/2021-7, CNPq. The author K. Edalati was supported in part by the MEXT, Japan through Grants-in-Aid for Scientific Research (JP19H05176, JP21H00150 & JP22K18737).
