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materials
Review
Developing Nanostructured Ti Alloys for Innovative
Implantable Medical Devices
Ruslan Z. Valiev 1,2, *, Egor A. Prokofiev 2 , Nikita A. Kazarinov 2 , Georgy I. Raab 1 ,
Timur B. Minasov 3 and Josef Stráský 4
 1   Institute of Physics of Advanced Materials, Ufa State Aviation Technical University, 12 K. Marx street,
     450008 Ufa, Russia; giraab@mail.ru
 2   Laboratory of Mechanics of Advanced Bulk Nanomaterials, Saint Petersburg State University,
     Universitetskiy prospekt 28, Peterhof, 198504 St. Petersburg, Russia; egpro@mail.ru (E.A.P.);
     n.kazarinov@spbu.ru (N.A.K.)
 3   Department of Traumatology and Orthopedics, Bashkir State Medical University, 3 Lenin street, 450008 Ufa,
     Russia; m004@yandex.ru
 4   Department of Physics of Materials, Charles University, Ke Karlovu 3, 121 16 Prague, Czech Republic;
     josef.strasky@gmail.com
 *   Correspondence: ruslan.valiev@ugatu.su
                                                                                                      
 Received: 31 October 2019; Accepted: 14 February 2020; Published: 21 February 2020                   

 Abstract: Recent years have witnessed much progress in medical device manufacturing and the
 needs of the medical industry urges modern nanomaterials science to develop novel approaches for
 improving the properties of existing biomaterials. One of the ways to enhance the material properties
 is their nanostructuring by using severe plastic deformation (SPD) techniques. For medical devices,
 such properties include increased strength and fatigue life, and this determines nanostructured Ti
 and Ti alloys to be an excellent choice for the engineering of implants with improved design for
 orthopedics and dentistry. Various reported studies conducted in this field enable the fabrication of
 medical devices with enhanced functionality. This paper reviews recent development in the field of
 nanostructured Ti-based materials and provides examples of the use of ultra-fine grained Ti alloys
 in medicine.

 Keywords: nanostructured Ti alloys; severe plastic deformation; enhanced strength and fatigue life;
 medical implants with improved design; shape-memory NiTi alloy; functionality

1. Introduction
     Presently, Ti and its alloys represent the top choice when a combination of high strength, light
weight, and affordable cost are required, such as in the area of medical device manufacturing. However,
the clinical demands for implantable medical devices are growing rapidly, and nowadays new Ti
alloys are being investigated in terms of their chemical composition optimization, manufacturing
processes and modification of surface to meet the appropriate medical standards and comply with
regulation [1,2]. One possibility to design and manufacture new materials with enhanced properties
focuses on nanostructuring of metallic materials using the so-called severe plastic deformation
(SPD) techniques, which have become a cutting edge and promising area in materials science and
engineering [3,4].
     Different SPD techniques are applied to refine grains in metallic materials to below micrometer
range or even to the nanosized range. SPD techniques are also efficient for the formation of nanoclusters
and nanoprecipitates of secondary phases, enhancing the mechanical and functional properties of
the materials [4,5]. A whole variety of SPD techniques have been developed and put forward to
provide very high strains (ε > 5) under high applied pressure, such as accumulative roll bonding

Materials 2020, 13, 967; doi:10.3390/ma13040967                                 www.mdpi.com/journal/materials
Developing Nanostructured Ti Alloys for Innovative Implantable Medical Devices - MDPI
Materials 2020, 13, 967                                                                             2 of 16

(ARB), including multiple forging, twist extrusion, and others [6–8]. However, equal channel angular
pressing (ECAP) and high pressure torsion (HPT), introduced already in the pioneering works [3],
remain the most used methods for the production of ultrafine-grained (UFG) materials. Principles of
these techniques, developed devices and microstructure evolution during processing steps have been
thoroughly reviewed in numerous studies [3–7,9,10]. Recently, these deformation techniques have
been further upgraded for practical application [11,12].
     Nanostructuring of metallic materials increases material strength due to work hardening and
grain refinement [13,14], consequently, fatigue life can be also significantly increased by microstructure
refinement [15]. Understanding material processing by SPD techniques is essential for designing of
medical devices with improved functionality as it not only improves mechanical properties but also
affects corrosion and biomedical properties [16–18]. Improved strength and enhanced biomedical
response of a nanostructured material can be efficiently used in dental implants; a stent of such
permanent implant manufactured from nanostructured Ti can be significantly smaller due to the
increased strength and therefore less harmful for a patient [19].
     Recently, materials scientists have been exploring possibilities of improved interaction of
nanostructured materials with body tissues, for instance bones. In this respect, surface modifications of
bulk nanomaterials demonstrate encouraging results [17,18,20,21]. These improvements provide the
possibility for development and design of implantable medical devices that perform better and provide
improved functionality in comparison to their counterparts manufactured from common coarse-grained
materials. This review article outlines the progress in engineering of advanced nanostructured Ti alloys
and medical implants/devices manufactured from those advanced materials.

2. SPD Processing of Nanostructured Titanium Materials

2.1. Commercially Pure Ti
      The first studies devoted to Ti-based materials potentially applicable in medicine were applied to
commercial purity titanium (CP Ti) due to its high biocompatibility with living tissues [22]. Unparalleled
biocompatibility of Ti was the main interest of many clinical studies of medical devices and tools
applied in traumatology, orthopedics, and dentistry. Unfortunately, CP Ti is characterized by reduced
strength when compared to other metallic materials used in biomedical devices such as steels or
cobalt-based alloys. Achieving higher strength level is possible by alloying or thermo-mechanical
processing, but then the Ti-based materials usually lose their biometric response or fatigue performance.
Therefore, SPD processing was considered as an alternative strategy proving that nanostructuring of
CP Ti may become a novel approach to improve the mechanical properties of this material to achieve
its high-performance [13,17,19,20,23]. Apart from enhancing mechanical properties, this strategy
is also advantageous in improving the biological response of the surface of the CP titanium based
products [18,20].
      The first results on nanostructured CP Ti Grade 4 (O–0.34%, Fe–0.3%, C–0.052%, N–0.015%, all
in wt.%, balance–Ti] were achieved by Valiev et al. aiming on manufacturing rods with significantly
enhanced mechanical properties and superior biomedical response for the fabrication of dental
implants [19]. The processing route involved equal-channel angular pressing (ECAP) as an SPD
technique [9] followed by thermo-mechanical treatment by forging and, finally, drawing. Continuous
SPD processing by ECAP-Conform (ECAP-C) and subsequent drawing, was capable of producing rods
with the diameter of 7 mm and the length of 3 m with homogeneous ultrafine-grained (UFG) structure
along the entire length of the rods [23,24]. Furthermore, ECAP-Conform represents an economical
SPD-based fabrication procedure for mass production of ‘nanoTi’.
      After combined severe plastic deformation and thermo-mechanical processing, the grain size was
significantly reduced from 25 µm in the initial Ti rods to 150 nm in the processed material. Figure 1
illustrates the effect of ECAP-C strain on the density of high-angle boundaries (HAB) and mechanical
strength of CP Ti Grade 4 [21].
Developing Nanostructured Ti Alloys for Innovative Implantable Medical Devices - MDPI
Materials 2020, 13, 967                                                                                                       3 of 16
 Materials 2020, 13, 967                                                                                                       3 of 15

       Figure1.1.Influence
      Figure      InfluenceofofECAP-C
                                ECAP-Cstrain  onon
                                         strain  (a)(a)
                                                     grain boundary
                                                        grain        (GB)
                                                               boundary   density,
                                                                        (GB)       (b) yield
                                                                             density,        strength
                                                                                       (b) yield      and (c)
                                                                                                 strength andthe
                                                                                                               (c)
      contribution   of various strengthening  mechanisms     [21].
       the contribution of various strengthening mechanisms [21].

      Table
       Table11shows
                showsthe
                       theimproved
                           improvedmechanical
                                       mechanicalproperties
                                                    propertiesofofCP CPTiTiafter
                                                                            afternanostructuring
                                                                                  nanostructuringby byECAP
                                                                                                       ECAPandand
subsequent   thermomechanical     treatment.  The  strength  of the  nanostructured   titanium
 subsequent thermomechanical treatment. The strength of the nanostructured titanium is doubled  is doubled when
compared    to the conventional
 when compared                    CP titanium.
                     to the conventional    CP The   increase
                                                titanium.   Thein increase
                                                                   strength was   achievedwas
                                                                             in strength    without  reduction
                                                                                               achieved        of
                                                                                                          without
ductility (total elongation  to failure is above the  limit of 10%),   which  is otherwise  commonly
 reduction of ductility (total elongation to failure is above the limit of 10%), which is otherwise     observed
after intensive
 commonly        drawing
              observed     or rolling.
                         after intensive drawing or rolling.

       Table1.1.Mechanical
      Table      Mechanicalproperties
                             propertiesofofcoarse-grained
                                            coarse-grained(CG)
                                                            (CG)and
                                                                 andnanostructured
                                                                     nanostructuredCP
                                                                                    CPGrade
                                                                                       Grade44Ti.
                                                                                               Ti.Annealed
                                                                                                   Annealed
      Ti-6Al-4V  ELI (extra low interstitials) alloy for comparison.
       Ti-6Al-4V ELI (extra low interstitials) alloy for comparison.
                                                                                                        Fatigue
                                                                                         Reduction Fatigue
    State       Processing          UTS, MPaUTS, YS, MPa
                                                      YS,              Elongation,
                                                                        Elongation, % Reduction       Strength at
          State        Processing                                                         Area, % Strength  at
                                               MPa           MPa           %           Area, %        106 Cycles
                                                                                                  106 Cycles
      1         Initial CG Ti           700                530                25             52           340
            1         Initial CG Ti      700                  530          25            52           340
      2     2      nanoTinanoTi     1240 1240             1200
                                                            1200           1212          42 42        620 620
                  Annealed
                       Annealed
      3     3     Ti-6Al-4V              940               840840             1616               45 45              530 530
                     Ti-6Al-4V ELI 940
                     ELI

        Fatigue tests of conventional and nanostructured CP Ti were conducted in air at room
 temperaturetests
       Fatigue          of conventional
                   in accordance         withand   nanostructured
                                                ASTM     E 466-96 with   CP the
                                                                             Ti were   conducted
                                                                                  loading            in airofat20
                                                                                             frequency         roomHztemperature
                                                                                                                        and R = 0.1.
in accordance
 Table   1 showswith  thatASTM        E 466-96
                            the fatigue           with of
                                             strength    thenanoTi
                                                              loading     frequency
                                                                       [17,24]   after of
                                                                                       one20million      R = 0.1.
                                                                                              Hz andcycles          Table 1doubled
                                                                                                                is almost     shows
that  the  fatigue   strength     of nanoTi    [17,24]  after  one   million   cycles  is almost
 when compared to the conventional CP titanium and even exceeds the fatigue performance of the Ti-doubled      when   compared      to
the  conventional       CP  titanium      and   even  exceeds     the fatigue    performance
 6Al-4V alloy [22,25]. Significant enhancement of fatigue properties and improved strength of    of the  Ti-6Al-4V    alloy   [22,25].
Significant
 nanostructuredenhancement
                       Ti allowof  usfatigue     properties
                                        to produce     smaller and  improved
                                                                  sizes           strength
                                                                         of implants    andof   nanostructured
                                                                                              therefore   to reduce  Tithe
                                                                                                                        allow   us to
                                                                                                                             extent  of
produce     smaller    sizes  of  implants
 a surgical intervention (see also Section 3). and  therefore    to reduce    the  extent  of a surgical   intervention     (see also
Section CP3).Ti is known for its considerable biocompatibility which results from the presence of the
       CP Ti is
 protective        known
                oxide    film.for   its considerable
                                Titanium      dioxide TiO biocompatibility
                                                              2 forms naturally   which
                                                                                     on theresults
                                                                                              surfacefrom
                                                                                                        of CPtheTipresence     of the
                                                                                                                    and represents
protective     oxide   film.  Titanium      dioxide
 a stable protective layer on that a mineralized      TiO   2 forms   naturally     on the  surface   of CP   Ti and
                                                                   bone matrix can be attached. This film is usually 5–represents    a
stable
 10nmprotective
          thick andlayer       on that a inert,
                          biologically      mineralized
                                                    thus itbone     matrixacan
                                                               prevents            be attached.
                                                                               potentially        This film
                                                                                              negative         is usually
                                                                                                           reaction          5–10nm
                                                                                                                       between     the
thick   and   biologically    inert,   thus   it
 surrounding body environment and the metal [22].prevents    a potentially     negative   reaction   between     the  surrounding
body NanoTi
        environment withand UFG  thestructure
                                      metal [22]. containing high density of non-equilibrium grain boundaries
       NanoTi
 achieved      bywith
                   SPDUFG      structure
                          is also            containing
                                    characterized      by high    density of
                                                           significantly       non-equilibrium
                                                                             increased    internal grain
                                                                                                     energy boundaries     achieved
                                                                                                               of the material     [3].
by  SPD   is  also characterized       by  significantly    increased    internal   energy   of
 This fact may result in considerable change in the morphology of the oxide film on the materialthe  material   [3]. This   fact may
result  in considerable
 surface.     NanoTi with    change      in thesurface
                                  polished       morphology       of the
                                                           exhibits        oxide filmbiological
                                                                       improved        on the material     surface.
                                                                                                    reaction    of theNanoTi
                                                                                                                          surfacewithas
polished
 confirmed   surface    exhibits
                 by recent          improved
                              studies             biological
                                          in a series           reaction of
                                                        of experiments          the surface
                                                                             through          as confirmed tests
                                                                                        cytocompatibility       by recent
                                                                                                                       usingstudies
                                                                                                                               mouse
in a series of
 fibroblast       experiments
                cells  [20,26–29].through
                                       At the cytocompatibility
                                                 same time, additional   tests using   mouse fibroblast
                                                                                 improvement                  cells [20,26–29].
                                                                                                  of biomedical       propertiesAtof
the  same time, additional
 nanostructured         titanium improvement
                                      can be achieved   of biomedical
                                                               by dedicated properties
                                                                                  surface of modifications
                                                                                             nanostructuredsuch   titanium    can be
                                                                                                                        as chemical
achieved     by   dedicated     surface
 etching or bioactive coatings [17,18].    modifications      such   as chemical     etching   or bioactive    coatings    [17,18].
Developing Nanostructured Ti Alloys for Innovative Implantable Medical Devices - MDPI
Materials  2020,13,
 Materials2020,  13,967
                     967                                                                                        44 ofof1615

 2.2. Titanium Alloys
2.2. Titanium Alloys
       Two-phase (α + β) titanium alloys such as Ti-6Al-4V and Ti-6Al-7Nb continue to be the most
      Two-phase (α + β) titanium alloys such as Ti-6Al-4V and Ti-6Al-7Nb continue to be the most
 important metallic materials in the dental and orthopedic fields due to their excellent mechanical
important metallic materials in the dental and orthopedic fields due to their excellent mechanical
 properties and satisfactory biocompatibility [2,22,30,31].
properties and satisfactory biocompatibility [2,22,30,31].
       Several recent studies reported improved mechanical and functional properties of
      Several recent studies reported improved mechanical and functional properties of nanostructured
 nanostructured titanium alloys.
titanium alloys.
       Microstructure and mechanical properties of Ti-6Al-4V ELI (extra low interstitial alloys for
      Microstructure and mechanical properties of Ti-6Al-4V ELI (extra low interstitial alloys for medical
 medical applications) prepared by SPD are reported in [15,32,33]. Round rods of the two-phase alloy
applications) prepared by SPD are reported in [15,32,33]. Round rods of the two-phase alloy with
 with the diameter of 40 mm (Intrinsic Devices Company, San Francisco, CA, USA) and with chemical
the diameter of 40 mm (Intrinsic Devices Company, San Francisco, CA, USA) and with chemical
 composition: Ti–base, Al–6.0%; V–4.2%; Fe–0.2%; О–0.11%; N–0.0025%; Н–0.002%, С–0.001 (wt.%)
composition: Ti–base, Al–6.0%; V–4.2%; Fe–0.2%; O–0.11%; N–0.0025%; H–0.002%, C–0.001% (wt.%)
 had the grain size of about 8 µm in a cross-section and 20 µm in a longitudinal section. X-ray
had the grain size of about 8 µm in a cross-section and 20 µm in a longitudinal section. X-ray diffraction
 diffraction analysis proved that the volume fractions of α and β phases were approximately 85% and
analysis proved that the volume fractions of α and β phases were approximately 85% and 15%,
 15%, respectively. 250 mm length rods were processed in two steps. The rods were subjected to ECAP
respectively. 250 mm length rods were processed in two steps. The rods were subjected to ECAP via
 via route Bc at 600 °С and subsequently extruded, altogether with total strain of 4.2 [33]. The extrusion
route Bc at 600 ◦ C and subsequently extruded, altogether with total strain of 4.2 [33]. The extrusion
 steps were carried out at 300 °С with the last pass at room temperature for additional strengthening.
steps were carried out at 300 ◦ C with the last pass at room temperature for additional strengthening.
 The rods with the diameter of 18 mm and length up to 300 mm were produced. The rods were finally
The rods with the diameter of 18 mm and length up to 300 mm were produced. The rods were finally
 annealed in the temperature range from 200 °С to 800 °С for 1 h and subsequently cooled in air.
annealed in the temperature range from 200 ◦ C to 800 ◦ C for 1 h and subsequently cooled in air.
       Transmission electron microscopy (TEM) studies showed that SPD leads to a complex UFG
      Transmission electron microscopy (TEM) studies showed that SPD leads to a complex UFG
 structure containing refined grains and subgrains with a mean size of about 300 nm.
structure containing refined grains and subgrains with a mean size of about 300 nm.
       Stress–strain curves for the initial coarse-grained and UFG material shown in Figure 2
      Stress–strain curves for the initial coarse-grained and UFG material shown in Figure 2 demonstrate
 demonstrate that the alloy after grain refinement by SPD underwent significant strengthening.
that the alloy after grain refinement by SPD underwent significant strengthening. Tensile elongation of
 Tensile elongation of the UFG material (curve 2) is reduced from 17% to 9%. Strength/ductility trade
the UFG material (curve 2) is reduced from 17% to 9%. Strength/ductility trade off, however, improved
 off, however, improved after subsequent annealing at 500 °С. The results of tensile tests correspond
after subsequent annealing at 500 ◦ C. The results of tensile tests correspond to the measurement of
 to the measurement of microhardness [32,33].
microhardness [32,33].

      Figure 2. Engineering stress−strain tensile curves of the Ti-6Al-4V ELI alloy: coarse-grained material
      (initial)
        Figure(1);   UFG condition
                 2. Engineering     (2) and UFG
                                stress−strain    condition
                                              tensile curvesafter annealing
                                                             of the            500 ◦alloy:
                                                                            at ELI
                                                                    Ti-6Al-4V        C (3).coarse-grained material
        (initial) (1); UFG condition (2) and UFG condition after annealing at 500 °С (3).
      In accordance with [10], enhancement of the ductility in the UFG material by annealing is clearly
associated  with a decrease
       In accordance           of internal
                        with [10],         elasticof
                                   enhancement      stress  and dislocation
                                                      the ductility          density.
                                                                    in the UFG          Simultaneous
                                                                                  material by annealing additional
                                                                                                           is clearly
strengthening   of the  alloy can  be explained   by the  observed  decrease   in content  of metastable
 associated with a decrease of internal elastic stress and dislocation density. Simultaneous additional    β-phase
after  cooling from
 strengthening         the
                  of the    annealing
                         alloy          temperature.
                               can be explained    by theIts volumedecrease
                                                           observed    fraction in
                                                                                 incontent
                                                                                     the UFG    alloy annealed
                                                                                            of metastable         at
                                                                                                            β-phase
500 ◦
 afterCcooling
         can be higher
                from the than  before annealing,
                            annealing   temperature.as shown   in [10],
                                                        Its volume       due toinquenching
                                                                     fraction                 fromannealed
                                                                                  the UFG alloy     the annealing
                                                                                                               at 500
temperature.    Despite  no  visible particles of any  secondary   phase,   aging
 °С can be higher than before annealing, as shown in [10], due to quenching from theprocesses  might  have  caused
                                                                                                          annealing
grain  boundaryDespite
 temperature.     segregations   associated
                           no visible        with
                                      particles of additional  improvement
                                                   any secondary                of the
                                                                     phase, aging      properties
                                                                                     processes     of the
                                                                                                might     annealed
                                                                                                       have  caused
UFG    material [34].
 grain boundary segregations associated with additional improvement of the properties of the
 annealed UFG material [34].
Developing Nanostructured Ti Alloys for Innovative Implantable Medical Devices - MDPI
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Materials 2020, 13, 967                                                                                                     5 of 15

      Finetuning
      Fine   tuningofofmechanical
                       mechanicalproperties
                                       propertiesby byannealing
                                                       annealingafter
                                                                    afterthe
                                                                          theSPD
                                                                              SPDprocessing
                                                                                     processingisislimited
                                                                                                    limitedmainly
                                                                                                             mainlyby by
 grain  growth   occurring   at elevated   temperatures.     Thermal   stability  of  UFG  structure
grain growth occurring at elevated temperatures. Thermal stability of UFG structure of commercially   of  commercially
 pure Ti
pure   Ti follows
           follows classical
                    classical grain
                              grain growth
                                      growth depending
                                                 depending on on temperature
                                                                  temperature via via Arrhenius
                                                                                       Arrhenius equation
                                                                                                    equation [35]
                                                                                                               [35] and
                                                                                                                    and
 limited  to  approximately    450  ◦ C [36]. Nanostructured α + β exhibit enhanced thermal stability up to
limited to approximately 450 °C [36]. Nanostructured α + β exhibit enhanced thermal stability up to
     ◦ C [37].
 550°C
550      [37].
      Fatigue properties
      Fatigue   properties ofofthe
                                 theTi-6Al-4V
                                       Ti-6Al-4V ELIELI
                                                     alloyalloy
                                                            withwith
                                                                 UFG UFGstructure  were investigated.
                                                                               structure                 High strength
                                                                                           were investigated.     High
 and  enhanced    ductility (1370  MPa    and   12%)  after SPD   processing   and   subsequent
strength and enhanced ductility (1370 МPа and 12%) after SPD processing and subsequent annealing  annealing   at 500 ◦ C;
 resulted
at 500 °С in   an enhancement
            resulted               of fatigue
                     in an enhancement        oflimit to 740
                                                 fatigue      MPa
                                                          limit     after
                                                                to 740  МPа107after
                                                                               cycles
                                                                                    107incycles
                                                                                          comparison     to 600 MPa
                                                                                                in comparison         in
                                                                                                                 to 600
 the initial  coarse-grained   condition    (Figure  3) [32].
МPа in the initial coarse-grained condition (Figure 3) [32].

       Figure 3. Fatigue test results of initial coarse-grained material and UFG material after annealing at
       500 ◦ C,3.1 Fatigue
      Figure       h.      test results of initial coarse-grained material and UFG material after annealing at
      500 °С, 1 h.
       The fatigue limit of the Ti-6Al-4V alloy in UFG condition reported in [32] tested by rotating
 bending
      The was    slightly
            fatigue    limithigher
                               of thethan   the values
                                        Ti-6Al-4V         in [32,38]
                                                      alloy   in UFGproving       thatreported
                                                                          condition     measuredinfatigue     properties
                                                                                                       [32] tested          depend
                                                                                                                      by rotating
 on  the choice   of  the  measurement        technique.
bending was slightly higher than the values in [32,38] proving that measured fatigue properties
depend Achieved     results of
           on the choice      show
                                 the that high strength
                                      measurement           can be achieved in UFG Ti-6Al-4V ELI alloy by processing
                                                        technique.
 by ECAP     and subsequent
      Achieved      results show    thermo-mechanical
                                       that high strengthtreatment.            SelectioninofUFG
                                                                   can be achieved              SPD Ti-6Al-4V
                                                                                                      regimes and  ELIadjustment
                                                                                                                         alloy by
processing by ECAP and subsequent thermo-mechanical treatment. Selection of SPD regimes us
 of processing     parameters       of SPD    processing     such     as temperature,      strain  rate  and  strain   allow    andto
 manipulateofthe
adjustment            grain boundary
                   processing      parametersstructure
                                                   of SPD and    phase morphology
                                                             processing                    in the two-phase
                                                                             such as temperature,                 UFGand
                                                                                                         strain rate     alloy.   As
                                                                                                                              strain
 the result,
allow   us to the   best combination
               manipulate       the grain of    strengthstructure
                                             boundary       and ductility      can bemorphology
                                                                         and phase      achieved along      with
                                                                                                        in the     the improved
                                                                                                                two-phase      UFG
 fatigue
alloy.  Asendurance
            the result,limit.      Enhancement
                            the best   combination    of of
                                                         strength
                                                             strength  and  ductility
                                                                          and  ductilityof the
                                                                                            can biomedical
                                                                                                  be achievedTi-6Al-7Nb
                                                                                                                 along withalloy the
 was reported
improved          in another
             fatigue    endurance comprehensive       study [39].
                                       limit. Enhancement          of In  comparison
                                                                       strength           to Ti-6Al-4V,
                                                                                  and ductility     of thethe  Ti-6Al-7Nb
                                                                                                            biomedical          alloy
                                                                                                                            Ti-6Al-
 represents
7Nb   alloy wasa better
                   reportedchoice   for biomedical
                                in another               use duestudy
                                              comprehensive           to avoiding     the toxic vanadium
                                                                            [39]. In comparison                 [40]. the
                                                                                                     to Ti-6Al-4V,     This    study
                                                                                                                            Ti-6Al-
 shows
7Nb       that
      alloy     processing
             represents         by ECAP
                             a better       andfor
                                       choice     consequent
                                                    biomedicalthermo-mechanical
                                                                     use due to avoidingtreatment
                                                                                                the toxic causing
                                                                                                           vanadium  formation
                                                                                                                        [40]. This of
 UFG structure
study    shows that results    in high strength
                           processing     by ECAP   (1400andMPa)     and ductility
                                                                 consequent            (elongation of 10%).
                                                                                 thermo-mechanical               These achieved
                                                                                                            treatment      causing
 propertiesof
formation     areUFG
                   attractive     for designing,
                          structure                  developing
                                       results in high                and manufacturing
                                                            strength(1400                       of high-performance
                                                                                MPa) and ductility        (elongation ofmedical
                                                                                                                              10%).
 devicesachieved
These      and implants.
                      properties are attractive for designing, developing and manufacturing of high-
       Considering
performance      medical  that    vanadium
                              devices            and partly also aluminum are rather toxic elements and,
                                        and implants.
 simultaneously,
      Considering that   that reducing
                                 vanadiumofand     the partly
                                                         Young’s  alsomodulus
                                                                          aluminum   is required
                                                                                         are ratherfortoxic avoiding
                                                                                                                 elements so-called
                                                                                                                                and,
 stress-shielding that
simultaneously,       [39], reducing
                              the development        of brandmodulus
                                          of the Young’s          new biomedical        alloysfor
                                                                              is required        represents
                                                                                                   avoidingaso-called
                                                                                                                current relevant
                                                                                                                             stress-
 challenge [39],
shielding    for researchers.      A new generation
                     the development          of brand of   newtitanium    alloys must
                                                                    biomedical      alloysprovide    improved
                                                                                             represents           strength,
                                                                                                            a current          better
                                                                                                                          relevant
 biocompatibility,
challenge               and lower
             for researchers.       A Young’s     modulusofthan
                                        new generation                  Ti6Al4V
                                                                   titanium        alloy.
                                                                               alloys      Current
                                                                                        must          research
                                                                                                 provide         focuses
                                                                                                           improved         on new
                                                                                                                         strength,
 alloying
better      systems, in particular
        biocompatibility,       and lowerTi-Nb    and Ti-Mo.
                                              Young’s    modulus than Ti6Al4V alloy. Current research focuses on
       Given the
new alloying        above mentioned
                 systems,                  requirements,
                               in particular   Ti-Nb and Ti-Mo.the interest is drawn to titanium alloys containing high
 content
      Givenof the     phase,mentioned
               theβabove        because this     phase is characterized
                                             requirements,        the interest byislower
                                                                                     drawn  Young’s    modulus
                                                                                               to titanium        in the
                                                                                                              alloys       range of
                                                                                                                       containing
high content of the β phase, because this phase is characterized by lower Young’s modulus in the
range of 55–90 GPa, and thus exhibit lower stress shielding [39,41–43]. Moreover, these Ti alloys are
Developing Nanostructured Ti Alloys for Innovative Implantable Medical Devices - MDPI
Materials 2020, 13, 967                                                                                                   6 of 16

Materials 2020, 13, 967                                                                                                  6 of 15
55–90 GPa, and thus exhibit lower stress shielding [39,41–43]. Moreover, these Ti alloys are designed
designed
to containtoonly
               contain   only non-toxic
                   non-toxic    constituentsconstituents
                                                such as Nb,  suchMo, asZr,
                                                                         Nb,and
                                                                              Mo,   Zr,On
                                                                                  Ta.    andtheTa. On hand,
                                                                                                 other  the other   hand,
                                                                                                                these       these
                                                                                                                       materials
materials   are  characterized     by  comparatively       low    strength,    because    the
are characterized by comparatively low strength, because the lowest Young’s modulus is obtainedlowest    Young’s     modulus    is
obtained   only in treated
only in solution     solutionsingle
                                treated  single
                                      phase       phase
                                               β-Ti        β-TiAchieving
                                                     alloys.      alloys. Achieving
                                                                               low Young’slow Young’s
                                                                                                modulusmodulus
                                                                                                            and highand      high
                                                                                                                        strength
strength   simultaneously
simultaneously                  is a challenging
                    is a challenging    task. Ageing  task.   Ageing treatments
                                                          treatments       that inducethata fineinduce    a fine and
                                                                                                  and uniform           uniform
                                                                                                                   precipitation
precipitation
of ω and α phaseof ω components
                        and α phaseprovides
                                        components       provides
                                                   significant         significant strengthening.
                                                                   strengthening.      On the other hand, On the    other
                                                                                                                 this      hand,
                                                                                                                      inevitably
this  inevitably
increases           increases
            the Young’s          the Young’s
                            modulus                modulus
                                         of the alloy    [41–43].of the
                                                                      Onlyalloy     [41–43].present
                                                                              few studies        Only few     studiesresults
                                                                                                         successful      presentin
successful   results   in development       of thermal     treatments       without    detrimental
development of thermal treatments without detrimental effect on some of the relevant mechanical        effect  on   some   of the
relevant
propertiesmechanical
             [44,45]. properties [44,45].
      Advancements
      Advancements ininthethe        areas
                                 areas       of orthopedics
                                        of orthopedics               and dentistry
                                                           and dentistry       called forcalled     for newforstrategies
                                                                                           new strategies          development for
development      of  new   generation     of β-Ti   alloys    with    reduced    Young’s      modulus
of new generation of β-Ti alloys with reduced Young’s modulus and high strength, which would be more       and   high  strength,
which
suitable would   be more
          for such          suitableRecently,
                     applications.    for such SPDapplications.
                                                        processing   Recently,
                                                                         has beenSPD     processing
                                                                                    proposed            has been
                                                                                                 to fabricate      proposed to
                                                                                                                nanocrystalline
fabricate
β-Ti alloys nanocrystalline      β-Ti alloys
               with high strength,              with highofstrength,
                                         low modulus              elasticitylow andmodulus
                                                                                      excellentofbiocompatibility
                                                                                                     elasticity and excellent
                                                                                                                         [46–51].
biocompatibility      [46–51].   Nanostructuring       of  these    alloys   leads   to  improved
Nanostructuring of these alloys leads to improved strength due to grain refinement and substructure    strength    due  to  grain
refinement    and In
evolution [52].     substructure
                        particular, evolution     [52]. Inβ-Ti
                                     solution treated        particular,
                                                                   Ti15Mosolution       treated
                                                                              alloy, which        β-Ti Ti15Mo
                                                                                               is qualified   for alloy,
                                                                                                                   medical which
                                                                                                                              use,
is qualified  for medical     use, can  be  significantly     refined     by HPT    as  demonstrated
can be significantly refined by HPT as demonstrated in Figure 4a. Grain size can be decreased well         in Figure   4a. Grain
size
below can100
           benm
              decreased     well below
                  [53]. Significant        100 nm [53].apart
                                        disadvantage,         Significant     disadvantage,
                                                                     from limited     size of HPTapartsamples,
                                                                                                         from limited     size of
                                                                                                                   is formation
HPT    samples, is induced
of deformation      formation  ωof   deformation
                                   phase   causing induced        ω phaseofcausing
                                                      sharp increase                    sharp increase
                                                                               elastic modulus       [54]. of elastic modulus
                                                                                                            Subsequent      aging
[54].  Subsequent      aging   of  UFG    Ti15Mo     alloy    leads     to  two-phase      α  +
of UFG Ti15Mo alloy leads to two-phase α + β structure which is also characterized by increased  β  structure    which    is also
characterized    by increased
modulus of elasticity             modulus
                           [55–57].           of elasticity
                                      More promising        is [55–57].    More promising
                                                                using Ti-Nb-Ta-Zr       based is   usingwhich
                                                                                                 alloys    Ti-Nb-Ta-Zr
                                                                                                                  are less based
                                                                                                                           prone
alloys  which   are  less prone   to ω  phase   formation.      Ti-29Nb-13Ta-5Zr         alloy  prepared
to ω phase formation. Ti-29Nb-13Ta-5Zr alloy prepared by HPT exhibited increased yield stress from          by  HPT    exhibited
increased
550 to 800 yield
             MPa withstressunchanged
                             from 550 elastic
                                          to 800 modulus
                                                   MPa with[58,59]. unchanged       elasticmicrostructure
                                                                            Significant       modulus [58,59].       Significant
                                                                                                               refinement     was
microstructure    refinement
recently also achieved            was recently also
                            in Ti-35Nb-6Ta-7Zr          achieved in
                                                     biomedical           Ti-35Nb-6Ta-7Zr
                                                                       alloy  by ECAP (Figure    biomedical
                                                                                                     4b).       alloy by ECAP
(Figure 4b).

                                    (a)                                                  (b)
      Figure 4. Microstructure
      Figure 4.  Microstructureofof
                                  (a)(a) Ti15Mo
                                      Ti15Mo     alloy
                                             alloy     prepared
                                                   prepared     by and
                                                            by HPT  HPT(b)and  (b) Ti-35Nb-6Ta-7ZZr
                                                                           Ti-35Nb-6Ta-7ZZr          alloy
                                                                                            alloy prepared
      prepared
      by ECAP by   ECAP (cross-section).
                (cross-section).

     Microstructural refinement
     Microstructural   refinement in in β-Ti  alloys can
                                         β-Ti alloys  can be
                                                           be also
                                                               also enhanced
                                                                    enhanced by by multiple
                                                                                   multiple twinning
                                                                                              twinning and/or
                                                                                                          and/or
martensitic transformation
martensitic  transformationβ β  →→ α’’α”  [60].
                                       [60].      The nanocrystalline
                                             The nanocrystalline          β-Ti alloys
                                                                    β-Ti alloys        also display
                                                                                also display  excellentexcellent
                                                                                                         in vitro
in vitro biocompatibility
biocompatibility   as shownas shown     by enhanced
                                 by enhanced      cell cell attachment
                                                        attachment    andand  proliferation[48].
                                                                            proliferation    [48].These
                                                                                                   These novel
                                                                                                           novel
nanocrystalline β-Ti
nanocrystalline   β-Tialloys
                       alloyshave
                               havehigh  chances
                                      high        to meet
                                             chances       the challenge
                                                       to meet            of next-generation
                                                                 the challenge                 implant material
                                                                                 of next-generation     implant
with significant
material         prospectsprospects
          with significant   in load bearing
                                       in loadbiomedical    applications.
                                                bearing biomedical    applications.

2.3. Nanostructured
2.3. Nanostructured NiTi
                    NiTi Shape
                         Shape Memory
                               Memory Alloys
                                      Alloys
     NiTi alloys
     NiTi   alloysexhibit unique
                     exhibit     mechanical
                              unique        behavior—shape
                                       mechanical           memory effect
                                                   behavior—shape         (SME)effect
                                                                      memory     and superelasticity,
                                                                                        (SME) and
which  arise from  a transformation between  martensite and austenite phases [61,62]. NiTi alloys
superelasticity, which arise from a transformation between martensite and austenite phases         are
                                                                                              [61,62].
NiTi alloys are important materials which are already used in advanced medical devices due to the
above mentioned mechanical properties and, additionally, due to functional properties such as good
biocompatibility and corrosion resistance in vivo [61,63]. At the same time, new, advanced
Developing Nanostructured Ti Alloys for Innovative Implantable Medical Devices - MDPI
responsible for the shape memory effect [65,66]. During following thermal treatments nanocrystalline
(NC) structure can be obtained in NiTi alloys via crystallization process (Figure 5) [64,67].
Nanocrystalline NiTi alloys with grain size about 20 nm demonstrate very high strength up to 2000
MPa [64].
      Equal
Materials 2020,channel
                13, 967    angular pressing is another SPD processing technique applied for producing                       7 of 16
uniform UFG structure in bulk NiTi alloys. The ECAP processing of NiTi at 400–450 °C results in
formation of UFG structure with grain size of about 200 nm (Figure 5).
important
      UFG materials
               structure which     are already
                            formation      leads used     in advanced
                                                    to significant         medical devices
                                                                       improvement              due to the above
                                                                                           of mechanical       and mentioned
                                                                                                                      functional
mechanical      properties   and,  additionally,     due  to functional    properties   such   as
properties of NiTi-based alloys [64,68–70]. The ultimate tensile strength (UTS) of UFG NiTi alloy good   biocompatibility     and
corrosion
attains     resistance
          1400            in vivois[61,63].
                 MPa, which          50% higherAt thethan
                                                      sameintime,
                                                                CG new,    advanced
                                                                     alloys;   and theapplications
                                                                                           yield stresswill  require
                                                                                                          (YS)         enhanced
                                                                                                                increases    after
properties     (higher   strength,  higher     recovery    strain and   stress,  etc.)  of  NiTi
ECAP from 500 MPa to 1100 MPa (Figure 6a). The functional shape-memory effect of NiTi after ECAP  shape   memory     alloys.
      During
is also  improvedthe past   two6b).
                       (Figure    decades,     there hascompletely
                                      The maximum          been interest     in the application
                                                                          recoverable               of increases
                                                                                          strain εrmax SPD methods  fromto6% NiTi
                                                                                                                               (in
alloys
CG       because
     state)  to 9%the    formation
                      after ECAP and  of nanocrystalline
                                          the maximum recoveryand UFGstressstructures
                                                                                  σrmax allows
                                                                                        reachesenhancing
                                                                                                   1120 MPa,mechanical        and
                                                                                                                 which is twice
functional
more   than theproperties
                   level ofinCGcomparison
                                  alloys (about  to coarse
                                                    500 MPa) grained   materials
                                                                [69]. UFG           [63,64].
                                                                              structure    formation in Ni-rich NiTi alloys
      HPT      processing     of  NiTi   alloys     leads   to  a  transformation
by ECAP results in an emergence of superelasticity at temperature close                  from    crystalline
                                                                                                        to thetohuman
                                                                                                                    amorphous
                                                                                                                            body
phase.     Microstructural       changes      in  deformed     NiTi    during    thermal     treatment
temperature. Superelasticity in UFG NiTi is characterized by a narrow mechanical hysteresis and            are of  key   interest
                                                                                                                              low
as they are
residual        responsible
           strain   [71].       for the shape memory effect [65,66]. During following thermal treatments
nanocrystalline      (NC) structure
      The high-strength        NC and  canUFGbe obtained    in NiTi
                                                   NiTi alloys       alloys
                                                                  with        via crystallization
                                                                         improved      functionalprocess      (Figure 5)
                                                                                                     characteristics      [64,67].
                                                                                                                        are  very
Nanocrystalline        NiTi   alloys   with    grain   size  about    20  nm    demonstrate
promising for medical applications in particular for manufacturing of stents, embolic protection  very   high   strength   up to
2000 MPa
filters, guide[64].
                  wires, and other peripheral vascular devices (see Section 4).

                                 (a)                                                            (b)
      Figure 5. Microstructure
                Microstructure of
                               of (a)
                                   (a)NC
                                      NCand
                                         and(b)
                                             (b)UFG
                                                UFGNiTi
                                                    NiTialloys
                                                         alloysprocessed
                                                                processedby
                                                                          byHPT
                                                                            HPTand
                                                                                andECAP,
                                                                                    ECAP,respectively.
                                                                                          respectively.

     Equal channel angular pressing is another SPD processing technique applied for producing
uniform UFG structure in bulk NiTi alloys. The ECAP processing of NiTi at 400–450 ◦ C results in
formation of UFG structure with grain size of about 200 nm (Figure 5).
     UFG structure formation leads to significant improvement of mechanical and functional properties
of NiTi-based alloys [64,68–70]. The ultimate tensile strength (UTS) of UFG NiTi alloy attains 1400 MPa,
which is 50% higher than in CG alloys; and the yield stress (YS) increases after ECAP from 500 MPa
to 1100 MPa (Figure 6a). The functional shape-memory effect of NiTi after ECAP is also improved
(Figure 6b). The maximum completely recoverable strain εr max increases from 6% (in CG state) to 9%
after ECAP and the maximum recovery stress σr max reaches 1120 MPa, which is twice more than the
level of CG alloys (about 500 MPa) [69]. UFG structure formation in Ni-rich NiTi alloys by ECAP results
in an emergence of superelasticity at temperature close to the human body temperature. Superelasticity
in UFG NiTi is characterized by a narrow mechanical hysteresis and low residual strain [71].
     The high-strength NC and UFG NiTi alloys with improved functional characteristics are very
promising for medical applications in particular for manufacturing of stents, embolic protection filters,
guide wires, and other peripheral vascular devices (see Section 4).
Developing Nanostructured Ti Alloys for Innovative Implantable Medical Devices - MDPI
Materials 2020, 13, 967                                                                                                             8 of 16
Materials 2020, 13, 967                                                                                                           8 of 15

                                    (a)                                                      (b)
                   Mechanical
       Figure6.6.Mechanical
      Figure                    properties
                             properties       of NiTi
                                         of NiTi   alloyalloy
                                                         in CGincondition
                                                                   CG condition    andECAP.
                                                                            and after    after ECAP.     (a) Engineering
                                                                                                (a) Engineering    stress–
       stress–strain
      strain         curves
             curves for     fortests
                        tensile tensile testsstate
                                     in CG      in CG
                                                    (1)state  (1) and
                                                        and after     afterusing
                                                                    ECAP    ECAP   using
                                                                                 4 (2),    4 (2),
                                                                                        8 (3) and812(3)(4)
                                                                                                        and  12 (4)and
                                                                                                           passes   passes
                                                                                                                       (b)
       and  (b) functional properties (ε  max   and  σ  max ) as a function of number of ECAP passes [61].
      functional properties (εr and σ
                                max
                                         r r ) as a function
                                            max
                                                      r          of number of ECAP passes [61].

3.3.Design
    Designof   ofMiniaturized
                   MiniaturizedImplantsImplants
       Enhanced mechanical
       Enhanced       mechanicalproperties
                                         properties   of nanostructured
                                                         of nanostructured    metals    allowallow
                                                                                    metals      development      of medical
                                                                                                        development        of implants
                                                                                                                                medical
 with   better   design,    for  instance     with   a more   subtle    design    which    is
implants with better design, for instance with a more subtle design which is less harmful for less  harmful    for human      body
                                                                                                                                 human[17].
       Application
body [17].               of  stronger     nanostructured        CP   Ti  instead    of common       CG   Ti, allows   for   altering   the
 design    of devices.ofRecently,
       Application          strongerdetailed         computations
                                          nanostructured       CP Ti were
                                                                        insteadconducted
                                                                                   of common  to analyze
                                                                                                   CG Ti, the    possible
                                                                                                             allows          geometries
                                                                                                                     for altering     the
 of  miniplates    for   maxillofacial       surgery    manufactured        from   nanostructured
design of devices. Recently, detailed computations were conducted to analyze the possible                Ti [72].
       CP Ti of
geometries       miniplate
                   miniplates    specified     by ASTMsurgery
                                    for maxillofacial         F 67, manufactured
                                                                       was considered      fromby nanostructured
                                                                                                    Conmet Company            (Moscow,
                                                                                                                        Ti [72].
 Russia)    as the  benchmark         for  redesigning      the  product     dimensions       of
       CP Ti miniplate specified by ASTM F 67, was considered by Conmet Company (Moscow, Russia) mini-plates     manufactured        from
 nanostructured         CP   Ti.  The   mechanical       properties     in  a cross-section
as the benchmark for redesigning the product dimensions of mini-plates manufactured from         of a newly     designed     plate  were
 calculated with CP
nanostructured         the Ti.
                            useTheof estimates
                                       mechanical   of the  fatigue performance
                                                        properties     in a cross-sectionlimit for
                                                                                                of acoarse-grained
                                                                                                      newly designed    Grade
                                                                                                                            plate4 were
                                                                                                                                    CP Ti
 and   nanostructured         Grade     4  CP   Ti.  In practical    use,   the  mini-plates     are
calculated with the use of estimates of the fatigue performance limit for coarse-grained Grade 4 CP   subjected    to  bending     loads,
 therefore
Ti            bending strength
    and nanostructured          Grade  of 4mini-plates     from conventional
                                             CP Ti. In practical                     and nanostructured
                                                                      use, the mini-plates       are subjected  CPtoTibending
                                                                                                                       was compared.
                                                                                                                                  loads,
 The result bending
therefore      indicates strength
                             that the plate     from nanostructured
                                           of mini-plates                    Ti has significantly
                                                                from conventional                      improved bending
                                                                                             and nanostructured            CP strength
                                                                                                                                 Ti was
 and therefore,
compared.       Theitresult
                        is clearly   advantageous
                                indicates      that theoverplatethefrom
                                                                     standard     device currently
                                                                           nanostructured        Ti hasmanufactured
                                                                                                           significantly from      CG Ti.
                                                                                                                             improved
bendingRecently,
             strengththree-dimensional
                           and therefore, finite  it is element      models (FEM) over
                                                         clearly advantageous             were the
                                                                                                 developed
                                                                                                      standard  using   CAEcurrently
                                                                                                                   device       software
 (KOMPAS-3D         v15,
manufactured from CG Ti.   ASCON       Group,     Saint  Petersburg,     Russia)   and   then  imported     into ANSYS      Workbench
 18.2 Recently,
       (ANSYS Inc.,        Canonsburg, PA,
                    three-dimensional                USA)
                                                finite       [73] for
                                                        element         geometry
                                                                    models     (FEM)analysis      of nanoTiusing
                                                                                         were developed         dental CAEimplants.
                                                                                                                               software  In
 addition to static
(KOMPAS-3D            v15,strength,
                              ASCONcalculations
                                           Group, Saint   of virtual   fatigueRussia)
                                                               Petersburg,        testing were      carried
                                                                                             and then         out using
                                                                                                           imported         theANSYS
                                                                                                                         into    built-in
 fatigue    module.       For  all  tested    models,      mesh   sensitivity     testing    was
Workbench 18.2 (ANSYS Inc, Canonsburg, Pennsylvania, U.S.A.) [73] for geometry analysis of nanoTi  performed      in  order    to obtain
 mesh-independent           results.
dental implants. In addition to static strength, calculations of virtual fatigue testing were carried out
usingThe the following      procedure
              built-in fatigue             was used
                                     module.            to assess
                                                  For all   tested possible
                                                                     models,ways meshtosensitivity
                                                                                           miniaturize    the implants.
                                                                                                        testing              The device
                                                                                                                  was performed         in
 with   a standard      geometry      was
order to obtain mesh-independent results.    assumed      to be  made     from   the  conventional      coarse-grained       CP   Ti. The
 model Thewas    designed
             following         in a way was
                            procedure        to obtain
                                                    usednearly     critical
                                                           to assess          stressways
                                                                         possible     state toboth  in terms ofthe
                                                                                                 miniaturize       static   and fatigue
                                                                                                                       implants.      The
 failure.   Afterwards,       the  same     loading    was   applied    to  a model     with
device with a standard geometry was assumed to be made from the conventional coarse-grained    reduced    dimensions       but  with CPthe
 properties     of nano    CP   Ti.
Ti. The model was designed in a way to obtain nearly critical stress state both in terms of static and
fatigueA failure.
           one-stage      dental implant
                     Afterwards,        the samewithloading
                                                        genericwasgeometry
                                                                       appliedwas  to aconsidered
                                                                                         model withinreduced
                                                                                                          the study.     The shape
                                                                                                                     dimensions       butof
 the  implant    is similar    to
with the properties of nano CP Ti. the   implant     geometry     produced      from    nano   CP   Ti by  company      Timplant      s.r.o.
 (Ostrava,    Czech Republic)
       A one-stage                   [74]. Figure
                         dental implant         with 7generic
                                                         shows ageometry
                                                                    technical was
                                                                                drawing     of the geometry
                                                                                       considered                of thisThe
                                                                                                      in the study.       nanoimplant
                                                                                                                               shape of
 with   a corresponding         numerical      model.
the implant is similar to the implant geometry produced from nano CP Ti by company Timplant s.r.o.
(Ostrava, Czech Republic) [74]. Figure 7 shows a technical drawing of the geometry of this
nanoimplant with a corresponding numerical model.
Materials
Materials
 Materials  2020,
          2020,    13,
                13,13,
            2020,      967
                    967967                                                                                         9 of
                                                                                                                9 9of of 15
                                                                                                                      1615

                             (a)
                             (a)                                    (b)
                                                                    (b)                              (c)
                                                                                                     (c)
        Figure
      Figure    7.
             7. 7.
        Figure     Geometry
                Geometry
                   Geometry   of
                            ofof the
                               the
                                 the dental
                                   dental
                                     dental nanoimplant:
                                          nanoimplant:    (a)
                                                       (a)(a)
                                            nanoimplant:      technical
                                                            technical   drawing
                                                                      drawing
                                                              technical         with
                                                                              with
                                                                        drawing      dimensions
                                                                                   dimensions
                                                                                with             in
                                                                                              inin
                                                                                     dimensions  mm;mm;  (b)
                                                                                                      (b)(b)
                                                                                                    mm;      3D
                                                                                                           3D3D
        model;
      model; (c) (c) enlarged
                  enlarged    FEM
                            FEM     mesh.
                                  mesh.
        model; (c) enlarged FEM mesh.

     TheThe
        Theapplied
              applied
             applied loading  scheme
                         loading
                         loading        was inspired
                                   scheme
                                   scheme   was       by theby
                                             was inspired
                                                   inspired   testing
                                                             by        procedures
                                                                  the testing
                                                                 the                 used in the
                                                                        testing procedures
                                                                                procedures       ISOin
                                                                                               used
                                                                                               used   14801
                                                                                                     in the standard.
                                                                                                        the  ISO 14801
                                                                                                            ISO    14801
The  performed
  standard. The
  standard.        calculations
              The performed       revealed
                     performed calculations  that application
                                  calculations revealed
                                                revealed that   of  the  nanoTi
                                                           that application
                                                                application of   allows
                                                                               of the     reduction
                                                                                  the nanoTi
                                                                                       nanoTi allows of the diameter
                                                                                               allows reduction
                                                                                                       reduction ofof the
                                                                                                                      the
ofdiameter
   implant by
  diameter    of  at least
                 implant   10%,
                            by at while
                                  least   20%
                                        10%,   diameter
                                              while  20%  reduction
                                                           diameter     leads to
                                                                       reduction  an  unacceptable
                                                                                   leads  to an      decrease
                                                                                                unacceptable
             of implant by at least 10%, while 20% diameter reduction leads to an unacceptable decrease         of the
                                                                                                               decrease
device’s
  of  the fatigue
  of the   device’sstrength.
          device’s    fatigue Maximal
                      fatigue  strength. principal
                               strength.   Maximalstress
                                           Maximal          zonestress
                                                      principal
                                                      principal    for thezone
                                                                  stress    implant
                                                                           zone       with
                                                                                 for the
                                                                                for         the diameter
                                                                                      the implant
                                                                                           implant        reduced
                                                                                                    with the
                                                                                                   with             by
                                                                                                          the diameter
                                                                                                               diameter
10%  loaded
  reduced by
  reduced     with
             by 10%  a 67.75
                 10% loaded   N  force
                       loaded with     is shown
                                with aa 67.75
                                        67.75 N   in
                                              N forceFigure
                                                 force is    8.
                                                       is shown
                                                          shown in  in Figure
                                                                       Figure 8.
                                                                               8.

      Figure
        Figure  Maximal
             8. 8.
        Figure          principal
                8. Maximal
                   Maximal        stress
                           principal
                           principal     for the
                                      stress
                                      stress  forUFG
                                             for      Ti implant
                                                 the UFG
                                                 the UFG         with awith
                                                           Ti implant
                                                           Ti  implant  10%areduced
                                                                       with a 10%   diameter
                                                                              10% reduced
                                                                                  reduced    and 67.75
                                                                                          diameter
                                                                                          diameter  and
                                                                                                    andN 67.75
                                                                                                         force.
                                                                                                         67.75 NN
        force.
        force.
4. Fabrication and Tests of Medical Nanoimplants
   4. Fabrication
  4.  Fabrication  and Tests
                         Tests of
       Recently, manufacturing
                   and         of Medical
                                  Medical   Nanoimplants
                                   and successful    testing of several medical implants fabricated from
                                            Nanoimplants
nanostructured   Ti  have been
         Recently, manufacturingconsidered
                    manufacturing and      successful[17].
                                            in detail
                                     and successful           Another
                                                        testing         example
                                                                  of several
                                                                      several    of the innovative
                                                                               medical               development
                                                                                         implants fabricated
                                                                                                    fabricated    from
        Recently,                                      testing    of          medical   implants                 from
is nanostructured
   the manufacturing  Ti and
                          havetesting
                                 been of the implant
                                       considered     inpins   designed
                                                           detail   [17]. for surgery
                                                                          Another      in  the
                                                                                     example    bone
                                                                                                 of   tissue
                                                                                                     the      of the
                                                                                                           innovative
  nanostructured Ti have been considered in detail [17]. Another example of the innovative
hip,  which increases
   development       thebone
                  is the       strength and
                          manufacturing   andprevents
                                                testing ofitsthe
                                                         of   fracture
                                                                 implant(Figure  9) [75]. The
                                                                           pins designed
                                                                                designed        pins  of two
                                                                                            for surgery
                                                                                                surgery       types
                                                                                                          in the
                                                                                                             the  bone
  development     is     manufacturing    and  testing      the implant   pins              for           in     bone
   tissue of the hip,  which  increases  bone  strength   and   prevents  its fracture (Figure   9) [75].
  tissue of the hip, which increases bone strength and prevents its fracture (Figure 9) [75]. The pins of The  pins  of
Materials 2020, 13, 967                                                                                                                   10 of 16
Materials 2020, 13, 967                                                                                                                  10 of 15
Materials 2020, 13, 967                                                                                                                  10 of 15
 two types
(Figure     10)(Figure       10) were from
                  were produced           produced        from nanostructured
                                                 nanostructured           Ti rods of Ti   3 mmrodsdiameter
                                                                                                      of 3 mm with diameter verywith
                                                                                                                                  highvery     high
                                                                                                                                         strength
 two
(σ    types
 strength
    = 1300 (σ   (Figure
                   = 1300
               MPa).        10)
                             MPa).
                         These    were   produced
                                       These were
                                  implants      implants from
                                                         usedwerenanostructured
                                                                to studyusedtheir
                                                                               to study   Ti  rods
                                                                                      effecttheir
                                                                                               on theof   3
                                                                                                      effectmm
                                                                                                          boneon  diameter
                                                                                                                    the bone
                                                                                                                 strength        with  very
                                                                                                                              of strength     high
                                                                                                                                             of the
                                                                                                                                 the hip, which
 strength
 hip,  which  (σ  =
                  was1300    MPa).
                         evaluated     These
                                         by     implants
                                              means      of    were
                                                             bench     used
                                                                      testing to   study
                                                                                 [76].   For their
                                                                                               this
was evaluated by means of bench testing [76]. For this purpose, a special device (Figure 11) was usedeffect
                                                                                                      purpose, on  the
                                                                                                                     a   bone
                                                                                                                        special  strength
                                                                                                                                  device    of  the
                                                                                                                                           (Figure
 hip,
to     which
 11)analyze
      was used    was
                the to   evaluated
                         analyze the
                      mechanical        by   means
                                           mechanical
                                        properties      of  bench     testing
                                                              properties
                                                        of implant               [76].
                                                                             of implant
                                                                        systems          For   this
                                                                                     under systems    purpose,
                                                                                               compression          a
                                                                                                            underalong  special  device
                                                                                                                       compression
                                                                                                                             the axis of  (Figure
                                                                                                                                        along   the
                                                                                                                                          the hip.
 11)
 axiswas
Such   of    used
           the
        systems  hip.to Such
                     wereanalyze     the mechanical
                                 systems
                             subjected     towere
                                               a defined     properties
                                                     subjectedload to        of
                                                                             theimplant
                                                                        a defined
                                                                     along         axis load  systems
                                                                                               along
                                                                                          of the    hip,the under
                                                                                                           as  axis of
                                                                                                               well   compression
                                                                                                                      as the   hip,
                                                                                                                          in the     as along
                                                                                                                                        well asthe
                                                                                                                                  perpendicular   in
 axis
 the   of  the   hip.
      perpendicular    Such     systems
                             direction      were
                                           with    a subjected
                                                      force         to
                                                               directed a defined
                                                                           to  the     load
                                                                                     region    along
                                                                                                of  the
direction with a force directed to the region of the greater trochanter to complete fracture at a rate ofthe   axis
                                                                                                           greater   of  the  hip,
                                                                                                                      trochanter    as
                                                                                                                                     to well  as
                                                                                                                                        complete in
5the perpendicular
 fracture
   mm/min      atusing
                    a ratethedirection
                                 of 5 mm
                               INSTRON     with   /a force
                                               5982   min     directed
                                                               using High
                                                       (Instron®,          to the
                                                                         the         region of
                                                                                INSTRON
                                                                               Wycombe,             the greater
                                                                                                   5982               trochanter
                                                                                                             (Instron®,
                                                                                                 Buckinghamshire,             High
                                                                                                                             UK)     toWycombe,
                                                                                                                                        complete
                                                                                                                                   multipurpose
 fracture
one            at a rateUK)
 Buckinghamshire,
      pin dynamometer.          ofAmultipurpose
                                     5total
                                         mm  of 3/ systems
                                                     min  oneusing
                                                                pin      the INSTRON
                                                                weredynamometer.
                                                                        studied:     threeA        5982
                                                                                                total
                                                                                              pins,   a of  (Instron®,
                                                                                                            3 systems
                                                                                                         spiral,  and a were  High
                                                                                                                            spiral     Wycombe,
                                                                                                                                   studied:
                                                                                                                                    + pin     three
                                                                                                                                           system.
 Buckinghamshire,
 pins,   a  spiral,   and    UK)
                             a      multipurpose
                                spiral   + pin   system. one   pin
                                                              As  a  dynamometer.
                                                                     result   [76],    the  A
                                                                                            use total
                                                                                                   of   of  3  systems
                                                                                                       different
As a result [76], the use of different implants demonstrated high efficiency in improving the strength of                  were
                                                                                                                     implants     studied:   three
                                                                                                                                  demonstrated
 pins,
bone    aefficiency
           spiral,
 high tissue      in and
                      the    a spiral
                        in hip.
                            improving   + pinthesystem.
                                  In particular,   strength
                                                       the useAsofof
                                                                  a bone
                                                                     result   [76],
                                                                            tissue
                                                                      a spiral    and the   usehip.
                                                                                       ina the
                                                                                            pin    of the
                                                                                                  in   different     implants
                                                                                                        In bone-implant
                                                                                                             particular,          demonstrated
                                                                                                                             thesystem
                                                                                                                                  use  of made
                                                                                                                                          a spiralit
 high
 and   aefficiency
          pin   in  thein   improving
                          bone-implant       the  strength
                                              system       made of  bone
                                                                   it       tissue
                                                                       possible     toin  the
                                                                                        increase hip.the
possible to increase the axial load resistance by 72.6% in comparison to the tests excluding implants.  In  particular,
                                                                                                            axial  load      the  use
                                                                                                                           resistance  of a
                                                                                                                                         by spiral
                                                                                                                                             72.6%
 and
This  ademonstrated
          pin in the to
 in comparison           bone-implant
                             the prospect
                             the              system
                                   tests excluding        made     itofpossible
                                                            implants.
                                               of integration                      toreinforcement
                                                                                        increase the the
                                                                           This demonstrated
                                                                         surgical                          axial  load
                                                                                                                prospect
                                                                                                            of the         resistance
                                                                                                                     hip made           by 72.6%
                                                                                                                               of integration
                                                                                                                                   of nano   CP Tiof
 in
intocomparison
 surgical               to the
             reinforcement
      clinical    practice     to tests
                                    of theexcluding
                                   prevent   hip           implants.
                                                   madebones.
                                               broken        of nano CP   This    demonstrated
                                                                             Ti into     clinical practicethe prospect
                                                                                                                 to prevent   of broken
                                                                                                                                  integration
                                                                                                                                           bones.of
 surgical reinforcement of the hip made of nano CP Ti into clinical practice to prevent broken bones.

                         Figure 9. The image of the hip after the insertion of reinforcing implants.
                         Figure
                         Figure 9. The image
                                9. The image of
                                             of the
                                                the hip
                                                    hip after
                                                        after the
                                                              the insertion
                                                                  insertion of
                                                                            of reinforcing
                                                                               reinforcing implants.
                                                                                           implants.

                                                                       (a)
                                                                       (a)

                                                                       (b)
                                                                       (b)
        Figure 10.
       Figure  10. Two
                   Twotypes
                       typesof
                             ofthe
                                theimplant
                                     implantsystems
                                             systemsused:
                                                    used: ((a)
                                                          ((a) aa pin;
                                                                  pin; (b)
                                                                        (b) aa spiral)
                                                                               spiral) and
                                                                                       and their
                                                                                            their application
                                                                                                  application using
                                                                                                              using
       Figure
        the    10.
            INSTRONTwo types
                      5982   of the implant
                           dynamometer.
       the INSTRON 5982 dynamometer.        systems used: ((a) a  pin; (b)  a  spiral) and their  application using
       the INSTRON 5982 dynamometer.
Materials 2020, 13, 967                                                                                           11 of 16
Materials 2020, 13, 967                                                                                          11 of 15

                            Figure
                            Figure 11. Testing
                                       Testing procedure of the reinforced hip sample.

                 interesting example
      Another interesting       exampleofofthe  theinnovative
                                                     innovativeapplication
                                                                     application   is the
                                                                                is the    removable
                                                                                       removable        clipping
                                                                                                    clipping       device
                                                                                                              device  for
for  blood   vessels,  tubular    structures,    and    soft  tissues   fabricated   from  UFG
blood vessels, tubular structures, and soft tissues fabricated from UFG NiTi with enhanced shape- NiTi  with   enhanced
shape-memory
memory             effectdesigned
           effect and      and designed     for bleeding
                                      for bleeding    control control
                                                                 duringduring  laparoscopic
                                                                          laparoscopic         operations.
                                                                                          operations.   This This  device
                                                                                                              device  has
has been
been       created
      created   andand    tested
                     tested       in collaboration
                              in collaboration         between
                                                   between     UfaUfa  State
                                                                     State   AviationTechnical
                                                                           Aviation     TechnicalUniversity
                                                                                                   University(USATU)
                                                                                                                (USATU)
and National University of Science and Technology Technology “MISIS”
                                                                  “MISIS” [24].
                                                                            [24].
      The conducted tests demonstrated that the removable   removable clipping devices produced from UFG NiTi        NiTi
alloy obtain   several advantages      when   compared      to the  standard  counterpart.   Table
       obtain several advantages when compared to the standard counterpart. Table 2 provides the    2 provides   the most
important
most         properties
       important           of the clipping
                    properties                device for
                                   of the clipping           the UFG
                                                         device         andUFG
                                                                  for the    conventional    CG alloy. The
                                                                                   and conventional      CG maximum
                                                                                                              alloy. The
opening angle
maximum          of theangle
             opening     jaws, of
                                at which   no residual
                                    the jaws,   at whichdeformation
                                                            no residual was    observed,was
                                                                           deformation     increases         160◦ , which
                                                                                                      up toincreases
                                                                                               observed,               up
is significantly  higher    than  that  of benchmark        CG   alloy.  The value   of the reversible
to 160°, which is significantly higher than that of benchmark CG alloy. The value of the reversible      shape  memory
effect (up
shape       to 4 mm)
        memory         and(up
                   effect    the to
                                  maximum
                                     4 mm) and ratedthe
                                                      force   that develops
                                                          maximum       rated at triggering
                                                                              force          the clipping
                                                                                      that develops         device (upthe
                                                                                                       at triggering    to
0.9 N) also
clipping      doubles
          device   (up in
                        to the
                            0.9 product   from UFG
                                N) also doubles          alloys.
                                                     in the   product from UFG alloys.

               Table 2.
               Table    Service characteristics
                     2. Service characteristics of
                                                of the
                                                   the clipping
                                                       clipping device
                                                                device produced
                                                                       produced from
                                                                                from the
                                                                                     the NITi
                                                                                         NITi alloys.
                                                                                              alloys.

  Material
                Opening  Angleofof
                Opening Angle    the Opening of the
                                        Opening     Jaws
                                                of the    atatReversible
                                                       Jaws    Reversible                Max
                                                                                          MaxRated
                                                                                              Rated Force ofthe
                                                                                                    Force of the
 Material                   ◦
                   theJaws,
                       Jaws, °             Shape
                                        Shape    Memory
                                              Memory       Effect,mm
                                                         Effect,   mm                      Clipping Device,
                                                                                          Clipping  Device, HН
     CG
    CG
Materials 2020, 13, 967                                                                                        12 of 16

and formation of secondary phase precipitations allows for considerable improvement of the strength
and fatigue properties. In the present paper the advantages of nanostructuring were demonstrated for
CP Ti, Ti alloys including new β-Ti alloys as well as the NiTi alloy with shape memory effect. The
approaches to computer design of a number of miniaturized medical implants made from high-strength
nanomaterials have been suggested. In addition, the paper includes the examples of manufacturing
and tests of selected advanced medical devices for traumatology and surgery from Ti nanobiomaterials.
Taking into account the results of recent studies on surface modification, including chemical etching
of nanometals and deposition of bioactive coatings, it is assumed that the developments of Ti-based
nanomaterials opens new possibilities for advanced medical implants and devices with improved
design and functionality.

Author Contributions: R.Z.V. introduced the concept and contents of the present paper, together with co-authors
conducted the analysis and description of the resulting data. E.A.P. prepared the results of studies on the structure
and properties of UFG TiNi alloy with shape memory effect. N.A.K. provided the results of the design of
miniaturized implants (Section 3). G.I.R. provided the description of SPD techniques for processing CP Ti and Ti
alloys to produce UFG structure. T.B.M. introduced the original data on manufacturing and testing of the implant
pins designed for surgery in the bone tissue of the hip. J.S. reviewed the results of studies on biomedical Ti alloys
subjected to SPD processing. All authors have read and agreed to the published version of the manuscript.
Funding: This research was funded by Russian Science Foundation grant № 19-49-02003 and by Ministry of
Education, Youth and Sports of the Czech Republic (project №LTARF18010). The authors gratefully acknowledge
the financial support from Saint Petersburg State University in the framework of Call 3 project (id 26130576 for
R.Z.V., E.A.P. and N.A.K.). This work was also financially by Ministry of Industry and Trade of the Czech Republic
(project № FV20147).
Conflicts of Interest: The authors declare no conflict of interest.

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