Bionic bone biological piezoelectric composite ceramic material and preparation method thereof

Abstract

The invention discloses a bionic bone biological piezoelectric composite ceramic material and a preparation method thereof. The preparation method comprises the following steps: weighing raw materials including barium carbonate, calcium carbonate, titanium dioxide, tin oxide, yttrium oxide and germanium oxide according to a chemical formula of Ba0. 94Ca0. 06T i0. 92Sn0. 08O3 + 0.06 mo l% GeO2 + 0.03 mo l% Y2O3, carrying out ball milling to 1200 DEG C and presintering, sintering at 1440 DEG C, carrying out mixed ball milling with hydroxyapatite, preparing a sheet, sintering at 1300 DEG C, and polarizing to obtain the biological piezoelectric ceramic sheet. The germanium and yttrium doped tin barium titanate calcium-based lead-free piezoelectric ceramic is used as a biological material and has excellent piezoelectric, dielectric and ferroelectric properties, meanwhile, excellent biocompatibility is proved through an in-vitro cell experiment, after the piezoelectric ceramic is compounded with HA, the electrical property of a compound is improved, and the piezoelectric material has a good application prospect. Or the content of the piezoelectric ceramic phase can be reduced when the electrical property matched with the human body is obtained.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and specifically relates to a bionic bone biopiezoelectric composite ceramic material and a preparation method thereof. Background Art

[0002] Bone defects, nonunion, and delayed bone healing caused by factors such as trauma, bone tumors, congenital developmental deformities, and accidents not only bring pain to the patients themselves and their families, but also result in expensive treatment costs. At present, the "gold standard" for the treatment of bone defects is autologous bone transplantation. However, due to the limited quantity of autologous bone and the deficiency of donor site injury, it is difficult to meet the clinical needs. Therefore, the research and development of artificial bone have become a hot topic in clinical research. Constructing a bionic bone repair material with components, structures, and functions can provide a microenvironment more conducive to bone regeneration for cells and accelerate bone healing.

[0003] Studies have found that bone is a hard connective tissue composed of collagen fibers wrapping calcium phosphate nanocrystals. The presence of non-centrosymmetric collagen molecules can generate bioelectric signals such as piezoelectricity, pyroelectricity, and ferroelectricity in living bone, and these clues have been found to play a key role in regulating metabolic activities such as growth, structural remodeling, and fracture healing. Therefore, introducing piezoelectricity (i.e., piezoelectric implants) into biomaterials to stimulate the physiological electric microenvironment and induce osteogenesis has been developed in bone regeneration. When implanted at the fracture site, piezoelectric biomaterials can respond to mechanical deformations caused by biological activities such as cell migration, body movement, or external stimuli and generate charges on their surfaces, transmitting electrical stimulation to tissues, thereby promoting bone regeneration and reconstruction.

[0004] Due to the excellent electrical properties of piezoelectric ceramics and the high hardness and friction coefficient suitable for hard tissues, they have been used to promote cell proliferation, osteogenic differentiation, apatite deposition, and bone formation. The piezoelectric constant of barium titanate (BT) is greater than 190 pC / N, and since its first in vivo experiment in 1980, it has been used as a bone repair material for research. A large number of studies have shown that BT has excellent biocompatibility, bioactivity, and osteogenic properties. To further improve the biocompatibility of piezoelectric materials and form a more effective biological interface with cells, people tend to add matrices with more excellent biocompatibility to piezoelectric ceramics to prepare biopiezoelectric composite materials. Hydroxyapatite (HA) is the main inorganic component of the bone matrix, making it have biocompatibility, bioactivity, and more importantly, osteoconductivity. Therefore, HA-BT composite materials have been developed as bone substitutes to achieve component and electrical function simulation and construct a microenvironment favorable for cells.

[0005] However, once HA is added to piezoelectric ceramics, their piezoelectric properties will drop sharply. Therefore, the HA-BT material system cannot simultaneously have high piezoelectricity and a high HA content, that is, it cannot transmit sufficient electrical stimulation to bone cells / tissues while having a high content of non-biodegradable piezoelectric phases. Therefore, strategies for enhancing the piezoelectric properties of piezoelectric biocomposites need to be explored. Summary of the Invention

[0006] To solve the above technical problems, the present invention provides a biomimetic bone biopiezoelectric composite ceramic material and a preparation method thereof, which have excellent piezoelectric, dielectric, and ferroelectric properties. After being compounded with HA, the electrical properties of the composite are improved.

[0007] To achieve the above objectives, the present invention is realized through the following technical solutions: A preparation method of a biomimetic bone biopiezoelectric composite ceramic material, characterized by being prepared according to the following steps:

[0008] (1) Weigh raw materials barium carbonate, calcium carbonate, titanium dioxide, and tin oxide according to the chemical formula Ba 0.94 Ca 0.06 Ti 0.92 Sn 0.08 O3, and simultaneously weigh 0.03 mol% of yttrium oxide and 0.06 mol% of germanium oxide in terms of the molar amount of Ba 0.94 Ca 0.06 Ti 0.92 Sn 0.08 O3;

[0009] (2) Place the weighed powders in a ball milling jar for ball milling, then dry and sieve to obtain mixed powders;

[0010] (3) Place the uniformly mixed powders in a heating furnace, heat them at a rate of 3 °C / min to 1200 °C for pre-sintering, hold for 2 - 3 hours, and then cool with the furnace to cause solid-phase reactions of the powders. Sieve them with a 120-mesh sample sieve to obtain piezoelectric ceramic powders;

[0011] (4) Put the pre-sintered piezoelectric ceramic powders into a heating furnace and heat them to 1440 °C at a rate of 3 °C / min, hold for 2 hours, and after cooling with the furnace, grind them into powders;

[0012] (5) Put the ground piezoelectric ceramic powders and hydroxyapatite into a ball milling jar according to a mass ratio of 9 - 7:1 - 3 for ball milling. After ball milling, dry and sieve to obtain biopiezoelectric ceramic mixed powders;

[0013] (6) Granulate the biopiezoelectric ceramic mixed powders with paraffin as a binder to make ceramic green sheets;

[0014] (7) Place the green ceramic sheet into a heating furnace, degrease it at 600 °C with a heating rate of 3 °C / min, and then sinter it at 1300 °C for 2 hours with a heating rate of 3 °C / min to obtain a bio-piezoelectric ceramic sheet;

[0015] (8) Polarize it. Add electrodes to the upper and lower surfaces of the ceramic sheet, and then polarize it in a silicone oil bath at room temperature with a DC electric field of 2.5 - 3.5 kV / mm for 30 min to obtain a bio-piezoelectric ceramic sheet.

[0016] In step (1), the purity of barium carbonate is greater than 99.8%, the purity of calcium carbonate is greater than 99.5%, the purity of titanium dioxide is greater than 99.0%, the purity of tin oxide is greater than 99.99%, the purity of yttrium oxide is greater than 99.5%, and the purity of germanium oxide is greater than 99.99%.

[0017] In step (2), when ball-milling, add zirconia balls, the medium is anhydrous ethanol, ball-mill for 12 h, and after drying, sieve it through a 120-mesh sample sieve to obtain a mixed powder.

[0018] In step (5), when ball-milling, add zirconia balls, the medium is anhydrous ethanol, ball-mill for 1 h, and after drying, sieve it through a 120-mesh sample sieve to obtain a mixed powder.

[0019] In step (6), press the green ceramic sheet under a pressure of 10 MPa.

[0020] In step (8), copper sheets are used as electrodes.

[0021] A bio-inspired bone bio-piezoelectric composite ceramic material prepared by the preparation method of the bio-inspired bone bio-piezoelectric composite ceramic material described above.

[0022] Beneficial effects

[0023] In the present invention, when the piezoelectric ceramic is compounded with HA and then sintered, a pore structure can be directly obtained. Because the piezoelectric ceramic is sintered at a high temperature of 1440 °C and then sintered at 1300 °C after compounding. Since the temperature of 1300 °C is relatively low, the shrinkage during sintering is very small, while HA will have a large shrinkage at this temperature. The different shrinkage rates of the two plus the exclusion of the binder result in the generation of pores in the composite, which is beneficial to the proliferation and differentiation behavior of cells. The present invention uses germanium- and yttrium-doped barium calcium strontium titanate-based lead-free piezoelectric ceramics for biological materials, which have excellent piezoelectric, dielectric and ferroelectric properties. At the same time, excellent biocompatibility is demonstrated through in vitro cell experiments. After being compounded with HA, the electrical properties of the composite are improved, or the content of the piezoelectric ceramic phase can be reduced when obtaining electrical properties suitable for the human body. Description of the drawings

[0024] Figure 1 XRD patterns of bio-piezoelectric ceramic composites with different proportion contents in Example 1.

[0025] Figure 2 For the pure piezoelectric ceramics, the biopiezoelectric ceramic composites with different proportion contents, and the SEM surface morphology, surface pore size distribution, shrinkage rate before and after sintering, and porosity of pure HA in Example 1.

[0026] Figure 3 For the piezoelectric constants, ferroelectric properties, and temperature-dependent dielectric permittivity spectra of the pure piezoelectric ceramics and the biopiezoelectric ceramic composites with different proportion contents in Example 1.

[0027] Figure 4 For the CCK-8 OD values, live / dead staining images, and cytoskeleton staining and cell nucleus staining images of the pure piezoelectric ceramics, the biopiezoelectric ceramic composites with different proportion contents, and pure HA in Example 1. Specific implementation mode

[0028] The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0029] Example 1

[0030] The preparation method of the bionic bone biopiezoelectric composite ceramic material is carried out according to the following steps:

[0031] (1) According to the chemical formula Ba 0.94 Ca 0.06 Ti 0.92 Sn 0.08 O3 (BCTSGY), weigh the raw materials barium carbonate, calcium carbonate, titanium dioxide, and tin oxide, and at the same time weigh 0.03 mol% of yttrium oxide and 0.06 mol% of germanium oxide in the molar amount of Ba 0.94 Ca 0.06 Ti 0.92 Sn 0.08 O3. The purity of barium carbonate is greater than 99.8%, the purity of calcium carbonate is greater than 99.5%, the purity of titanium dioxide is greater than 99.0%, the purity of tin oxide is greater than 99.99%, the purity of yttrium oxide is greater than 99.5%, and the purity of germanium oxide is greater than 99.99%.

[0032] (2) Place the weighed powder in a ball mill for ball milling. When ball milling, add zirconia balls, the medium is anhydrous ethanol, ball mill for 12 h, and after drying, sieve through a 120-mesh sample sieve to obtain a mixed powder.

[0033] (3) Place the uniformly mixed powder in a heating furnace, heat it to 1200 °C at a rate of 3 °C / min for pre-sintering, keep it warm for 2 - 3 hours, and then cool it with the furnace to cause solid-phase reaction of the powder, and sieve through a 120-mesh sample sieve to obtain piezoelectric ceramic powder.

[0034] (4) The pre-sintered piezoelectric ceramic powder is placed in a heating furnace and heated to 1440 °C at a rate of 3 °C / min, held for 2 hours, cooled in the furnace, and then ground into powder.

[0035] (5) The ground piezoelectric ceramic powder is mixed with hydroxyapatite and put into a ball mill jar for ball milling. The HA content is prepared according to 0 wt%, 10 wt%, 20 wt%, and 30 wt% of the total mass of the piezoelectric ceramic powder and hydroxyapatite, abbreviated as B-0HA, B-10HA, B-20HA, and B-30HA respectively.

[0036] During ball milling, zirconia balls are added, the medium is anhydrous ethanol, ball milling is carried out for 1 h. After ball milling, it is dried, and after drying, it is sieved through a 120-mesh sample sieve to obtain the mixed powder.

[0037] (6) The bio-piezoelectric ceramic mixed powder is granulated with paraffin as the binder and made into a green ceramic sheet with a diameter of 12 mm and a height of 1.5 mm under a pressure of 10 PMa.

[0038] (7) The green ceramic sheet is placed in a heating furnace, degummed at 600 °C for 2 h at a heating rate of 3 °C / min, and then sintered at 1300 °C for 2 h at a heating rate of 3 °C / min to obtain the bio-piezoelectric ceramic sheet.

[0039] (8) Polarization: Copper sheet electrodes are added to the upper and lower surfaces of the ceramic sheet, and then polarized in a silicone oil bath at room temperature with a DC electric field of 2.5 - 3.5 KV / mm for 30 min to obtain the bio-piezoelectric ceramic sheet.

[0040] Figure 1 In (a), the XRD patterns of piezoelectric ceramics and bio-piezoelectric composite materials with different HA contents are shown. Figure 1 The vertical lines at the bottom of (a) simultaneously show the standard PDF cards of the tetragonal and orthorhombic phases of barium titanate. It can be seen that all samples show corresponding peaks similar to the peritectic structure of BaTiO3, but the intensity decreases with the increase of HA content. The diffraction peaks of pure BCTSGY ceramics (Den-B and B-0HA) match exactly with the standard PDF card of the BT phase and contain no impurity phases, which indicates that although the B-0HA sample has undergone high-temperature treatment, Ca 2+ 、Sn 2+ 、Y 2+ and Ge 2+It is indeed incorporated into the BaTiO3 lattice to form a solid solution. In addition to the single substance in the composite material, peaks corresponding to the secondary phases of CaTiO3 and Ca3(PO4)2 also appear, indicating that BCTSGY reacts with HA or HA decomposes at a temperature of 1300 °C. In addition, compared with the peak of Den-B, the characteristic peak of B-0HA near 45° shifts to a lower angle. After adding HA, the peak of B-10HA shifts to a higher angle, and the peaks of B-20HA and B-30HA shift slightly to a lower angle, and their positions are almost the same.

[0041] In addition, Figure 1 Figure (b) shows the enlarged patterns at 2θ near 45° in all cases. Obvious 45° split peak characteristics are observed in the pure piezoelectric ceramics (Den-B and B-0HA), indicating the coexistence of multiple phases in the prepared material system, manifested as the cubic-tetragonal phase boundary. The coexistence state of multiple phases in B-0HA still exists, which means that the phase structure has not changed after high-temperature treatment. However, when HA is added to the piezoelectric phase, these split peaks disappear and turn into single-mode peaks, and the displayed PPT (polycrystalline phase transformation) also disappears. Combining with the dielectric-temperature spectrum, the piezoelectric ceramics in these composite materials are considered to be orthorhombic phase. The calcium content plays an important role in the phase structure of the BT-based system. The increase in calcium content will cause the phase of the BCST ceramic to change from orthorhombic phase to tetragonal phase. Therefore, due to the addition of HA, the phase structure of the BCTSGY piezoelectric ceramic has changed, which may reduce its electrical properties, especially the piezoelectric constant.

[0042] Figure 2 shows the surface morphologies of biopiezoelectric ceramics with different HA contents. By Figure 2 Figure (a), it can be observed that the grains of the dense piezoelectric ceramic are closely arranged. In Figure 2 Figure (b), B-0HA shows that the piezoelectric phase is irregular particles with relatively large sizes, and the pores between the particles are not closely arranged, with an average size of about 4.42 μm. No sintering necks are formed between the particles, indicating that the sintering temperature is too low to form a dense ceramic. For Figure 2 the morphologies of B-10HA, B-20HA, B-30HA and pure HA samples in Figure (c)-(f), it can be seen that HA fills between the piezoelectric ceramic particles and forms grains, indicating that there is a sintering process of mass transfer between the nano-HA particles at this temperature. Figure 3(g) and (h) show that with the increase in HA content, the relative volume shrinkage rate increases and the porosity decreases. Except for the Den-B sample, pores also exist in other samples. The morphology of the pores tends to be circular, and with the increase in HA content, the average size slightly decreases, being 2.89 μm, 2.76 μm, and 2.22 μm respectively. The formation of pores in the composite ceramics is due to the fact that sintering at 1300 °C makes HA denser and reduces its size, but the presence of piezoelectric ceramic particles hinders shrinkage, thus forming pores. The decrease in pore size is due to the reduction in the content of the piezoelectric ceramic phase, resulting in a decrease in its anti-shrinkage property. Figure 3 The relative volume shrinkage trend in (g) also proves this point. The existence of pores will affect the piezoelectric and biological properties of the composite material. On the one hand, pores will reduce the density of the ceramic, resulting in a decrease in the connectivity of the piezoelectric ceramic, and thus reducing the piezoelectric property. On the other hand, pores provide a microenvironment for the good adhesion and metabolic activities of cells, which is beneficial to the subsequent proliferation and differentiation behaviors of cells.

[0043] Figure 3 (a) shows the change of the piezoelectric constant d 33 after pure BCTSGY and composite materials with different HA contents are polarized with silver sheets and copper sheets as electrodes respectively. It can be seen from the figure that with the increase in HA content, the d 33 of both electrode samples decreases sharply. This is because HA has a high hardness, increasing the "clamping" degree on the substrate. Another reason is that the existence of pores hinders the polarization process of the DC trace, which can be seen from the different piezoelectric constants of the two pure BCTSGY (Den-B and B-0HA). Compared with the samples polarized with silver electrodes, the d 33 value of the samples polarized with copper sheets with the same HA content is lower. This is because silver has a closer contact with the sample surface, which is beneficial to polarization, while the samples polarized with copper sheets accumulate less charge on the surface area without electrodes, so the d 33 value is lower. Although the HA content has a decisive influence on the piezoelectric properties of the composite material, introducing piezoelectric ceramics with high piezoelectric properties can still increase its d 33 value. As shown in (b) of Figure 3 , compared with the BT-HA system, the d33 value of our composite is higher than most of the values reported in the current literature. In this work, when generating the same amount of charge, the HA content is higher, and when it is exposed to cells or living tissues, it is likely to improve the biological response.

[0044] Figure 3(c) and (d) show the ferroelectric hysteresis loops, remnant polarization (Pr), and coercive electric field (Ec) variations of pure BCTSGY and composite ceramics with different HA contents, respectively. The pure piezoelectric ceramics (Den-B and B-0HA) exhibit typical relaxor ferroelectric characteristics, while the addition of HA has a significant impact on the shape of the P-E hysteresis loop. The significant reduction in the maximum polarization and Pr, as well as the increase in Ec, indicate that HA is detrimental to the ferroelectric properties. It is worth noting that the coercive field of B-0HA is reduced compared to that of dense pure BCTSGY, which may be due to the release of residual stress during the sintering process of the B-0HA sample at high temperature.

[0045] Figure 3 (e)-(i) show the dielectric constant (εr) plots of all compositions at selected frequencies in the temperature range from 20 °C to 200 °C. As Figure 3 (e)-(i) shows, the dielectric constant values of pure BCTSGY ceramics (Den-B and B-0HA) increase with increasing temperature and decrease when the temperature exceeds 67 °C. Nevertheless, the dielectric constant value of B-0HA at room temperature is less than that of Den-B. Different from pure BCTSGY, the dielectric constant of the composite ceramics first decreases and then increases with increasing temperature at low frequencies, while it changes little at high frequencies. The dielectric constant at room temperature is one to two orders of magnitude lower than that of Den-B. With the increase in HA content, the dielectric constant decreases, and at 1 kHz and room temperature, the dielectric constants are 130, 75, and 50, respectively. Although these samples show obvious frequency dispersion, their dielectric constant values are higher than those of dry human bone. In addition, there are also differences in the peak shape of pure BCTSGY around 30 °C, indicating the existence of an O-T phase transition, which cannot be detected in the composite samples at this temperature.

[0046] Figure 4(a) shows the results of CCK-8 tests on L929 mouse fibroblasts cultured on each group of materials for 1, 3, and 5 days. The results indicate that with the extension of the co-culture time, the cell viability of all samples continuously increases. In addition, compared with the blank control group, the cell viability of any component of the biopiezoelectric ceramic composite does not significantly decrease at each time point, suggesting that pure piezoelectric ceramics and composite piezoelectric ceramics have excellent biocompatibility. On the first day, the cell survival rate of the B-20HA group is significantly higher than that of other composite groups. However, on the third day, only the cell numbers of the B-0HA, B-10HA, and B-20HA groups are significantly higher than that of the B-30HA group. By the fifth day, there is no significant difference in the cell numbers among the composite groups. In addition, we also selected the polarized B-20HA samples to evaluate the effect of piezoelectric polarization on cell biocompatibility. As shown in the figure, on the first day, the cell number of the polarized B-20HA group (Pol B-20HA) is significantly lower than that of the unpolarized group. On the third and fifth days, there is no significant difference between the two groups, meaning that the polarization of the piezoelectric composite has no negative impact on cell proliferation. Figure 4 (b) shows the live / dead staining of L929 cells cultured on each group of samples for 3 days. Most cells in all groups emit green fluorescence, and only a few cells emit red fluorescence, indicating that neither the piezoelectric ceramics nor the composites are toxic to cells. Figure 4 (c) shows the cytoskeleton staining of cells cultured on the materials for three days. It can be clearly seen from the figure that most cells on each sample are stretched in a spindle or polygonal shape, accompanied by the appearance of pseudopodia. This shows that the prepared biopiezoelectric ceramic composite has good cell biocompatibility.

[0047] Although the embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A preparation method of a bionic bone bio-piezoelectric composite ceramic material, characterized in that, The preparation is carried out according to the following steps: (1) Weigh the raw materials barium carbonate, calcium carbonate, titanium dioxide, and tin oxide according to the chemical formula Ba 0.94 Ca 0.06 Ti 0.92 Sn 0.08 O3. At the same time, weigh 0.03 mol% of yttrium oxide and 0.06 mol% of germanium oxide in terms of the molar amount of Ba 0.94 Ca 0.06 Ti 0.92 Sn 0.08 O3; (2) Place the weighed powder in a ball milling jar for ball milling, then dry and sieve it to obtain a mixed powder; (3) Place the uniformly mixed powder in a heating furnace, heat it up to 1200 °C at a rate of 3 °C / min for pre-sintering, hold for 2 - 3 hours, and then cool it in the furnace to cause solid-phase reaction of the powder. Sieve it with a 120-mesh sample sieve to obtain piezoelectric ceramic powder; (4) Put the pre-sintered piezoelectric ceramic powder into a heating furnace and heat it up to 1440 °C at a rate of 3 °C / min, hold for 2 hours, and after cooling in the furnace, grind it into powder; (5) Put the ground piezoelectric ceramic powder and hydroxyapatite into a ball milling jar in a mass ratio of 9 - 7:1 - 3 for ball milling. After ball milling, dry and sieve it to obtain a bio-piezoelectric ceramic mixed powder; (6) Granulate the bio-piezoelectric ceramic mixed powder with paraffin as a binder to make a green ceramic sheet; (7) Put the green ceramic sheet into a heating furnace, degrease it at 600 °C at a heating rate of 3 °C / min, and then sinter it at 1300 °C at a heating rate of 3 °C / min for 2 hours to obtain a bio-piezoelectric ceramic sheet; (8) Polarize it. Add electrodes to the upper and lower surfaces of the ceramic sheet, and then polarize it in a silicone oil bath at room temperature with a DC electric field of 2.5 - 3.5 KV / mm for 30 min to obtain a bio-piezoelectric ceramic sheet.

2. The preparation method of the bionic bone bio-piezoelectric composite ceramic material according to claim 1, wherein: In step (1), the purity of barium carbonate is greater than 99.8%, the purity of calcium carbonate is greater than 99.5%, the purity of titanium dioxide is greater than 99.0%, the purity of tin oxide is greater than 99.99%, the purity of yttrium oxide is greater than 99.5%, and the purity of germanium oxide is greater than 99.99%.

3. The preparation method of the bionic bone bio-piezoelectric composite ceramic material according to claim 1, characterized in that: In step (2), when ball milling, add zirconia balls, the medium is anhydrous ethanol, ball mill for 12 h, dry and then sieve it with a 120-mesh sample sieve to obtain a mixed powder.

4. The preparation method of the bionic bone bio-piezoelectric composite ceramic material according to claim 3, characterized in that: In step (5), when ball milling, add zirconia balls, the medium is anhydrous ethanol, ball mill for 1 h, dry and then sieve it with a 120-mesh sample sieve to obtain a mixed powder.

5. The preparation method of the bionic bone bio-piezoelectric composite ceramic material according to claim 4, wherein: In step (6), press the green ceramic sheet under a pressure of 10 PMa.

6. The preparation method of the bionic bone bio-piezoelectric composite ceramic material according to any one of claims 1-5, characterized in that: In step (8), the polarization electrode is a copper sheet.

7. A bio-inspired bone bio-piezoelectric composite ceramic material prepared by the preparation method of the bio-inspired bone bio-piezoelectric composite ceramic material according to any one of claims 1 - 6.

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