WO2016192702A2

WO2016192702A2 - Shaped bodies containing piezo-active calcium titanium oxide, method for the production and excitation thereof and use of piezo-active calcium titanium oxide as piezoelectric molded bodies or a component of piezoelectric molded bodies

Info

Publication number: WO2016192702A2
Application number: PCT/DE2016/000230
Authority: WO
Inventors: Eberhard Burkel; Rico SCHNIERER
Original assignee: Universität Rostock
Priority date: 2015-06-03
Filing date: 2016-06-03
Publication date: 2016-12-08
Also published as: WO2016192702A3; DE102015108865A1

Abstract

The invention relates to molded bodies, in particular implants, comprising piezo-active calcium titanium oxide, including piezo-active doped calcium titanium oxide, the use of such calcium titanium oxide and a method for the production and for the excitation of the molded bodies by electric fields.

Description

Shaped body containing piezoactive calcium titanium oxide, a process for their preparation and excitation and use of piezoactive calcium titanium oxide as a piezoelectric shaped body or component of piezoelectric shaped body

The invention relates to moldings, in particular implants, containing piezoactive calcium titanium oxide, including piezoactive doped calcium titanium oxide, the use of such calcium titanium oxides and a method for producing and for exciting the moldings.

State of the art

An implant is an implanted in the body artificial material that should remain there permanently or at least for a longer period of time. In particular, the present invention relates to permanent implants which are used in plastic or orthopedic surgery as a replacement for attacked or destroyed body parts, in particular bones or as dental implants.

The demand for implants and the requirements for functionality and biocompatibility have been steadily increasing in recent years. Implants are required to have the ability to grow quickly into the bone and make a good connection with the bone. Modern implants should be mechanically stable and combine optimally and in a short time with the body's own tissue, whereby no rejection reaction or even infection should be caused.

Many of the implants currently made are made of titanium or titanium alloys because titanium has long been proven to be a biocompatible material. Pure titanium and Ti-6AI-4V have been widely used as dental and especially as load-bearing orthopedic implants because of their very good biocompatibility, their high mechanical strength and low weight and their resistance to physiological media.

| Confirmation copy | However, the high strength of pure titanium and Ti-6AI-4V, which is well above that of natural bone, also brings with it disadvantages. A weak point of such metallic implants may be their high rigidity, which is significantly higher than that of the bone material. The implant therefore absorbs a large part of the mechanical load and thus relieves the bone. This so-called "stress shielding effect" can have far-reaching consequences: since bones require mechanical stress to regenerate on the one hand in the healing process and on the other hand to retain their strength permanently, the healing can slow down and the relieved bone even over the years dismantle.

Titanium and titanium alloys are e.g. using sintering methods (see F. Zhang et al., "sintering and heat treatment of titanium alloys by pulsed electric current sintering" Chapter 11 in "Sintering Applications", edited by Burcu Ertug, ISBN 978-953-51 -0974-7 , 02/2013) or other additive processes, eg by layering, accessible.

To adapt the mechanical properties of metallic implants to natural bone material, i.a. Alloys and porous structures are proposed, which should positively influence cell growth and bone integration. For example, it is possible to use TiMn compounds are produced which are produced as metallic sponges with coarsely porous structures [F. Zhang, E. Burkel: "Novel Titanium Manganese Alloys and Their Macroporous Foams for Bio- medical Applications Prepared by Field- Assisted Sintering" in "Biomedical Engineer- ing, Trends in Materials Science" edited by A. Laskovski, ISBN: 978-953- 307-513-6, InTech, 2011].

A further possibility is, for example, the modification of the implant surfaces, for example by a coating which makes it possible to design the surface properties independently of the properties of the implant material. Calcium titanium oxide has already been proposed as a material for implant coatings (N. Ohtsu, K. Sato, A. Yanagawa, K. Saito, Y. Imai, T.

Kohgo, A. Yokoyama, K. Asami, T. Hanawa: "CaTi03 coating on titanium for bio-material application - Optimum thickness and tissue response"; Journal of Biomedical Materials Research Part A - J BIOMED MATER RES PART A, vol. 82A, no. 2, pp. 304-315, 2007). Calcium titanium oxide is known as mineral under the name Perowskit. It has the chemical composition CaTi03. Chemically, it is a calcium titanium oxide, also called calcium titanate. Perovskite may contain traces of other metals in addition to calcium and titanium. Instead of calcium, alkali metals, rare earth metals and, more rarely, iron may be present. Niobium and subordinate tantalum and zirconium are also frequently found on the titanium positions. Varieties with a very high content of rare earth metals (especially cerium) are called Knopite, very low-abundance perovskites as Dysanalyt, in a combination of both also called Loparite. Considering the elements frequently contained, the chemical composition of perovskite can also be generally indicated as (Ca, Na, Fe ²⁺ , Ce, Sr) (Ti, Nb) O 3.

Sol-gel processes have already been proposed for the preparation of calcium titanium oxide (cf. EP 255193 B1, DE 3877634 T2 and US 3330697 A). Calcium titanium oxides are known per se and have been the subject of many publications, such as:

US Pat. No. 7,799,268 B2 describes hydroxyapatite-containing piezoelectric shaped bodies. The molded article may further contain calcium titanate in addition to many other components.

- DUBEY, AK, et al.: "Multifunctionality of Perovskites BaTiÜ3 and CaTiÜ3 in a composite with hydroxyapatite as orthopedic implant materials"; Integrated Ferro-electrics 131.1 (2011): 119-126 examines the dielectric properties of barium titanate hydroxyapatite and hydroxypropionate Calcium titanate-hydroxyapatite composites.

FU, D. et al .: "Crystal growth and piezoelectricity of BaTiO 3-CaTiO 3 solid Solution", Appl. Phys. Lett. 93, 012904 (2008) describes solid solutions of Ba-TiO 3-CaTiO 3, which are modified by a reduced amount of calcium titanate.

EP 0331160 A2 describes the production of a ceramic shaped body from particles or fibers of a functional inorganic material and a ceramic made of sintered metal particles. In a long listing is for the

Particles or fibers also called calcium titanate.

US 5830270A describes a semiconductor substrate which is overgrown with perovskites. Calcium titanate is disclosed as a possible layer. However, the piezoelectric effect is attributed to ferroelectrics such as barium titanate.

While barium and strontium titanate are known to be piezoelectric or piezoactive, this has not previously been reported for calcium titanium oxide. Object of the invention

The object of the invention is to provide calcium titanium oxide structures for use as shaped bodies, in particular as implant material, which has piezoelectric properties and combines bioactivity, biocompatibility and elasticity with little technical production effort.

Summary of the invention

According to the invention the object is achieved by a shaped body comprising or consisting of piezoelectric Caiciumtitanoxid, wherein

- The piezoelectric Caiciumtitanoxid to greater than 98 at% consists of Ca, Ti and O and has nanostructure defects or

- The piezoelectric Caiciumtitanoxid with up to 10 atom% and after a

Embodiment with up to 5 atom% - in each case based on all Ca and Ti atoms together - as doping Mg, Mn, Ba, Sr and / or Fe contains,

wherein the shaped body is piezoactive. Preferred embodiments are subject of the dependent claims or described below. According to one embodiment, the shaped body is e.g. at least partially coated with piezoelectric Caiciumtitanoxid and the main body of the molding is made of a different material. According to technical definition, a crystal is required for the generation of a piezoelectric signal, which crystallizes in its ideal structure compulsorily in a non-point-symmetric space group. For the purposes of this invention, however, piezoelectricity is more generally used for an electrical signal which is generated as a result of charge reorientations or charge shifts by mechanical stress and can be measured or inversely generated mechanical deformation by an electrical signal or electric field. A body which has piezoelectric material, which is also referred to herein as piezoactive, without this must be piezoelectric overall.

Caicium titanium oxide is accessible via the sol-gel process with or without doping elements, followed by drying, calcined to obtain a powder. In this process, powders with particle sizes ranging from several nanometers up to several micrometers are accessible. The term calcium titanium oxide in the context of the present invention also encompasses doped calcium titanium oxide. It has surprisingly been found that moldings, in particular medical implants, can advantageously be produced from piezoelectric calcium titanium oxide, or metallic moldings, in particular metallic implants, can advantageously be surface-coated with piezoelectric calcium titanium oxide. In particular, such implants have a modulus of elasticity of less than 70 GPa, preferably 5 GPa-50 GPa (according to DIN EN ISO 14577), in order to trigger a piezoelectric effect by strains as they occur through the body's own motion. Such a piezoelectric effect is suitable for promoting the growth of tissue. On the other hand, it is also possible to excite such a calcium titanium oxide-containing implant with an electric field in order to positively influence the bone regeneration via a mechanical stimulation. For this purpose, the implant can be combined with an outside of the body mounted capacitor or coil assembly for AC field generation in the range 3 Hz to 200 Hz. Detailed description of the invention

Calcium titanium oxide (CaTiO3) is accessible, for example, via the sol-gel process. In this case, soluble salts of titanium (in particular Ti ⁴⁺ ) together with salts of calcium (in particular Ca ²⁺ ) are brought into solution as precursor. The salts are used according to the present invention in approximately equimolar, ie in one

Atomic ratio of Ca to Ti from 0.8 (Ca) to 1 (Ti) to 1 (Ca): 0.8 (Ti), preferably 0.9 (Ca) to 1 (Ti) to 1 (Ca) to 0, 9 (Ti). However, a Ti excess of 0.85 to 0.98 (Ca) to 1 (Ti) or a Ca excess of 1 (Ca) to 0.98 to 0.85 (Ti) can also be present. If doping is to take place, up to 10% of the Ti or Ca atoms can be replaced by other atoms (based on Ca).

TiO 3), in particular selected from the group of Mg, Ba, Sr, Mn or Fe, preferably Mg and / or Fe. For example, a Ca: Ti ratio of 10: 9 (Ca overtoot) and for the doped samples a Ca: Ti: Dot ratio of 10: 9: 1 can be selected.

Suitable solvents for the sol-gel process are organic or aqueous organic solvents, for example the compounds corresponding to the abovementioned organic anions (in each case plus H +). Suitable organic anions (of the salts) are C1 to C8 alkoxylates, preferably C3 or C4 alkoxylates, C1 to C8 carboxylates and, as inorganic anions, nitrates, carbonates, oxides, hydroxides or hydrated oxides, in particular nitrates or carbonates.

The mixture and homogenization were carried out e.g. with the help of an ultrasonic bath and a magnetic stirrer. Subsequently, the gels are dried in a spray dryer. The powders thus obtained were amorphous and contained portions of the solvent. Upon heating to about 300 ° C, the solvents and organic components may be vaporized. Between 550 ° C. and 600 ° C., the crystallization of the main phase of calcium titanium oxide takes place. Typically, the calcium titanium oxides then contain about 90 vol.% And more calcium titanium oxide (CaTiO3) and each up to 5 vol.% Calcium oxide and titanium oxide.

The undoped calcium titanium oxide consists (after calcination) of greater than 98 atomic% of Ca, Ti and O. For doped calcium titanium oxide, up to 10 atomic%, based on all Ca and Ti atoms together, can be doped with Mg, Mn, Ba, Sr and / or Fe, preferably Mg and / or Fe, replaced.

For example, The calcium titanium oxide powder prepared by the sol-gel process, including the doped calcium titanium oxide powder, is compacted into compact calcium titanium oxide molded articles by the process known as field assisted sintering (FAST). This is a pressure assisted pulsed DC sintering process. For this purpose, the material to be processed is introduced into a die and pressed. For heat input, a pulsed current flows directly through the sample as a function of the electrical conductivity of the components. For electrically conductive materials, a significant increase in the compression rate is achieved by the influence of the electric field and the current flow. The compact design of the pressing tool makes it possible to achieve heating and cooling rates of up to 1000 ° C / min.

The precompressed powders are placed in the FAST chamber and then heated to 800 ° C to 1050 ° C, eg under a uniaxial pressure of 50 MPa to 80 MPa in a vacuum or inert gas atmosphere. During the FAST process typically a voltage of less than 5V and a current of 500A to 5000A are chosen. According to one embodiment of the method, the powders used are aligned to a solid body in an electric or magnetic field prior to application of the FAST method and compaction.

The advantages of the FAST process compared to high pressure or high temperature processes for CaTiO3 compaction are low pressure on the MPa scale and high efficiency with a high heating rate of 100 K / min to 1000 K / min, a holding time of a few minutes and a short cooling phase. The method proposed here can be used for energy-efficient production.

A big advantage of the FAST process for the production of calcium titanium oxide is the short process time. This leads to a reduction of the grain growth in the sintering process, whereby a nano- and microstructure in the grain of the material is maintained. This has positive effects on the mechanical and piezoelectric properties of the material. In the production method proposed here, materials having a volume fraction of more than 90% calcium titanium oxide and further phase fractions, depending on the doping, are formed.

The calcium titanium oxide produced by the production method proposed here, whether obtained by the sol-gel method or the sol-gel method followed by the FAST method, exhibits a piezoelectric effect upon the occurrence of mechanical deformation. The strength of this effect can be influenced by the doping. The mechanical loading of the implant generates a charge redistribution through the piezoelectric effect, which can stimulate the behavior of osteoblasts and osteoclasts beyond the mechanical stimulation and thus trigger bone growth impulses. For this it is preferred that the implant undergoes some deformation by physical forces on the implant o- is exposed to an electric or magnetic field, about 1 to 2 times a day for a certain period. The calcium titanium oxide synthesized by the production method proposed here can be directly, via suitable intermediate layers or over a gradient, to a metal or alloy, preferably one having a bone-like modulus of elasticity, such as TiMn, by FAST synthesis or other suitable methods be applied.

By means of the mechanical loading of the implant, bone growth impulses are then released via the piezoelectric effect in the calcium titanium oxide and its surface by means of charge redistributions. It is also advantageous to make the implant structure partially porous, with pore sizes greater than 500 [in order to intensively stimulate the osseointegration, in particular with an open pore structure, which can be flowed through by a liquid medium.

The porous design of a load-bearing implant structure produced by the FAST method or an adaptive method such as rapid prototyping with bone-like elastic properties allows the coating of the inner and outer surfaces with the pure or doped calcium titanium oxide by a suitable method. A suitable method is "RF magnetron sputtering", for example as mentioned in the above-mentioned publication by N. Ohtsu et al., Or dip-coating (dip-coating).

The piezoelectric effect results from the mechanical deformation of a non-point symmetric crystal. The resulting shift of the charge centers induces charge separations and thus dipoles. The calcium titanium oxides produced herein have dislocations, resulting in displacement of local atomic positions.

The theoretically point-symmetric structure of single-crystal CaTiO3 is disturbed (by nanostructure defects such as voids, voids, dislocations, inclusions) to produce a piezoelectric material. The piezoelectric effect is further enhanced by the addition of further elements (doping). The nanostructure defects lead to shifts of local atom positions and lead on average to measurable changes with conventional X-ray diffraction of the typical size of the crystallographic unit cell (Crystallography Opennum Database COD), preferably to relative lattice parameter changes greater than 0.5 per thousand, more preferably from 0.5 to 3 per thousand. The measurement of the lattice parameter changes is described, for example, in: McCusker et al., J. Appl. Cryst. (1999), 32, 36-50. By using polycrystalline CaTiÜ3 with crystallite sizes in the range of 10 nm to 300 nm, preferably 50 nm to 120 nm, determined by X-ray diffraction and the associated interfaces and the FAST method, the piezoelectricity is increased.

In a further embodiment, the shaped body comprises or consists of a metal sponge. The coating of the base body with piezoelectric calcium titanium oxide can be carried out, for example, by sputtering, CVD or direct FAST. (Move?)

EXAMPLES The production method according to the invention is explained below by way of experimental examples.

For the synthesis of calcium titanium oxide, a mixture of the precursors titanisopropoxide and calcium nitrate, each dissolved in ethanol, was used. For the undoped samples a Ca: Ti atomic ratio of 10: 9 and for the doped samples a Ca: Ti: Dot ratio of 10: 9: 1 was chosen. The mixture and homogenization was carried out by means of an ultrasonic bath and a magnetic stirrer. Subsequently, the gels were dried in a spray dryer. The powders thus obtained were amorphous and contained organic matter. Phase transitions up to 650 ° C and crystallization temperatures were measured by a DSC (Differential Scanning Calorimeter). Up to about 300 ° C solvent and organic components are evaporated or burned. Between 550 ° C to 600 ° C, the crystallization of the main phase calcium titanium oxide (about 90%) and the calcium or titanium oxide phases (about 5% each) took place.

After spray drying, all samples were baked at 650 ° C for 2 hours before being sintered to a solid. FAST allowed the compaction of the powders with greatly reduced process times. The calcium titanium oxides were heated at a heating rate of 100 K / min and a maximum pressure of 60 MPa to 1035 ° C and required a retention time of less than 5 minutes.

Using the Archimedean principle, the density of the solid was determined to be 4.01 g / cm ³ . This corresponds to 98% of the theoretical density. The phase proportions and structural nature of the solid-state samples were investigated by X-ray diffraction (XRD) and scanning electron microscopy (SEM). A diffraction spectrum of the Rietveld-Fit sintered calcium titanium oxide solid is shown in FIG

FIG. 1: X-ray diffraction spectrum and partial spectrum of the phase calcium titanium oxide

shown. Using a Rietveld analysis, the existing crystals in the material calcium titanium oxide (93.5%, red) and rutile (6.5%) could be assigned.

The morphology is measured on the basis of the SEM images: FIG. 2 SEM images of the calcined sol-gel synthesized

Calcium titanium oxide powder (left),

Fig. 3 SEM images of the fracture edge of the sintered with FAST potassium titanium oxide solid. The particle sizes of the Calciumtitanoxidpulver be after calcination 1 pm to 10 μιτι, in the sintered solid no individual particles are more visible.

The element-specific X-ray radiation could also be examined at the SEM with an EDX detector:

Fig. 4: EDX spectrum of the pure solid on aluminum support

The intensity distribution was used to estimate the mass ratio of the elements.

For the synthesis of doped piezoelectric calcium titanium oxide, 9.8 ml of titanium isopropoxide (97%, Alfa Aesar) in 67 ml of ethanol (> 99.8%, Sigma Aldrich) and 7 g of calcium nitrate (99%, Alfa Aesar) with 1.2 g of iron Nitrate nonahydrate (98% -101%, Alfa Aesar) dissolved in 25ml ethanol. After a one-hour homogenization of the solutions using an ultrasonic bath and a magnetic stirrer, the Ca-Fe mixture was added dropwise to the titanium solution and homogenized for 24 h with the magnetic stirrer. The drying took place with a Mini Spray Dryer B-290 the company Büchi. The inlet temperature was 190 ° C and the outlet temperature was maintained by varying the spray rate between 100 ° C and 110 ° C. The powder thus obtained was calcined in a Nabertherm RHTH 120-600 / 18 tube furnace at 650 ° C. for 2 hours and then sintered in an HP D 5 FAST plant of FCT Systeme GmbH. For this, 3 g of the calcined powder were placed in a graphite matrix and precompressed with a contact pressure of 40 MPa.

Then a vacuum was created in the sintering chamber and the pressure increased to 60 MPa. The material was heated at 100K / min to 1035 ° C and held at this temperature until complete compression (about 5 min). Thereafter, the material was cooled to room temperature (about 12 minutes) and the chamber was purged with nitrogen as an inert gas.

For the measurement of the piezoelectric effect, a construction was made according to.

Fig. 5: scheme used for measurement setup. Shown is a sample 1, horizontal electrodes 2, a piezoelectric actuator 3, an insulator 4 and a metal shield 5.

The measuring setup consists of a metallic framework, which fixes the sample to be examined between two insulating corundum plates to a piezoactuator.

Using a generator, a sine voltage of 10 Hz and 20 V was applied and converted by the actuator into a dynamic mechanical load of the sample. First, a reference measurement was made with a commercial stacked lead zirconate titanate piezo element (7.95V ± 0.27V) and a zero measurement with glass to determine the noise floor of the measurement (4.5mV ± 0.1mV). All measurements were made several times. The samples used were checked for their conductivity, so that an immediate charge exchange could be excluded by a short circuit. The undoped calcium titanium oxide solid generated a response signal of 78 mV ± 10.1 mV. The height of the piezoelectric signal could be increased to 122 mV ± 12.2 mV by the above iron doping of the calcium titanium oxide. The mechanical properties of the undoped Caiciumtitanoxidfestkörpers were characterized with a CETR Apex microindenter (Bruker Nano) according to DIN EN ISO 14577. At a test force of 750 mN, the modulus of elasticity of the calcium titanium oxide (203 ± 7) is GPa.

Claims

claims

A molded article comprising or consisting of calcium titanium oxide, wherein the calcium titanium oxide is piezoelectric and

- The piezoelectric calcium titanium oxide to greater than 98 atom% of Ca, Ti and

O exists and has nanostructure defects or

- The piezoelectric calcium titanium oxide with up to 10 atom% - based on all Ca and Ti atoms together - contains as doping Mg, Mn, Ba, Sr and / or Fe atoms,

and the shaped body is piezoactive.

2. Shaped body according to claim 1, wherein the shaped body comprises a metallic base body, which itself is not piezoelectric and has been coated on the surface with piezoelectric calcium titanium oxide.

A molded article according to claim 1 or 2, wherein the nanostructure defects are selected from one or more members of the group: vacancies, voids, dislocations, inclusions of Mg, Mn, Ba, Sr and / or Fe atoms, interfaces and Crystallite sizes in the range 10 nm to 300 nm, preferably 50 nm to 120 nm, determined by X-ray diffraction.

4. Shaped body according to at least one of the preceding claims, wherein the nanostructured defects cause lattice parameter changes and the relative lattice parameter changes are preferably 0.5 to 3 parts per thousand.

5. Shaped body according to at least one of the preceding claims, wherein the shaped body has a modulus of elasticity of less than 70 GPa, preferably 5 GPa to 50 GPa.

6. Shaped body according to at least one of the preceding claims, wherein the shaped body or the metallic base body of the shaped body according to claim 2 comprises a metal sponge or consists of this.

7. Shaped body according to at least one of the preceding claims, wherein the shaped body, apart from the piezoelectric calcium titanium oxide, or the metallic base body of the shaped body according to claim 2 of a titanium-based alloy, preferably a titanium / manganese or a titanium / Va - nadium / aluminum alloy.

8. Shaped body according to at least one of the preceding claims, wherein the piezoelectric Caiciumtitanoxid contains as doping Mg and / or Fe. 9. Shaped body according to at least one of the preceding claims, wherein the piezoelectric Caiciumtitanoxid is prepared by sol-gel synthesis, preferably

a) with an atomic ratio of Ca to Ti from 0.8 (Ca) to 1 (Ti) to 1 (Ca): 0.8 (Ti), preferably 0.9 (Ca) to 1 (Ti) to 1 (Ca to 0,

9 (Ti) and in particular from 0.85 to 0.98 (Ca) to 1 (Ti) or 1 (Ca) to 0.98 to 0.85 (Ti) and / or

b) when doping up to 10% of the Ti or Ca atoms are replaced by other atoms.

10. Shaped body according to at least one of the preceding claims, wherein the shaped body consists of piezoelectric Caiciumtitanoxid and the piezoelectric Caiciumtitanoxid is used as a solid body, and the solid body is preferably prepared by sintering by the FAST method or an additive method.

11. Shaped body according to at least one of the preceding claims, wherein the shaped body is an implant, preferably a load-bearing orthopedic implant.

12. Shaped body according to at least one of the preceding claims 2 to 10, wherein the piezoelectric Caiciumtitanoxid is applied directly or via at least one intermediate layer on the metallic base body.

13. Use of calcium titanium oxide as a piezoelectric solid body, wherein the solid body was produced by sintering or an additive process, or as a piezoelectric coating material for a shaped body,

wherein the Caiciumtitanoxid is piezoelectric and consists of greater than 98 atomic% of Ca, Ti and O and nanostructure defects or the Caiciumtitanoxid with up to 10 atom% - related to all Ca and Ti atoms together - as doping Mg, Mn, Ba, Sr and contains / or Fe,

wherein the solid body and the molded body is preferably an implant or part of an implant.

14. Arrangement comprising the shaped body according to one of claims 1 to 12, preferably as an implant, and a source for generating an electric or magnetic field.

15. A method comprising exposing the implant inserted into the body according to claim 11 an electric or magnetic field.

16. Use of the shaped body according to at least one of the preceding claims as an implant, in particular as a bone implant,

17. The use of the shaped body according to claim 16, wherein furthermore an outside of the body mounted capacitor or coil arrangement for the alternating field generation in the range 3 Hz to 200 Hz is used.