WO2019179194A1 - 一种聚磷酸钙/硅灰石生物复合陶瓷材料及其制备方法 - Google Patents

一种聚磷酸钙/硅灰石生物复合陶瓷材料及其制备方法 Download PDF

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WO2019179194A1
WO2019179194A1 PCT/CN2018/124147 CN2018124147W WO2019179194A1 WO 2019179194 A1 WO2019179194 A1 WO 2019179194A1 CN 2018124147 W CN2018124147 W CN 2018124147W WO 2019179194 A1 WO2019179194 A1 WO 2019179194A1
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wollastonite
calcium
calcium polyphosphate
ceramic material
cpp
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PCT/CN2018/124147
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English (en)
French (fr)
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陈传忠
周婉利
于慧君
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山东大学
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Priority to AU2018414989A priority Critical patent/AU2018414989B2/en
Publication of WO2019179194A1 publication Critical patent/WO2019179194A1/zh
Priority to ZA2020/06545A priority patent/ZA202006545B/en

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Definitions

  • the invention belongs to the technical field of bio-composite ceramic materials, and particularly relates to a calcium polyphosphate/wollastonite bio-composite ceramic material and a preparation method thereof.
  • Biomedical materials are new high-tech materials used to diagnose, treat, repair or replace diseased tissues, organs or enhance their functions. Biomedical materials help to improve the quality of life and longevity of human beings, but the current population is old. Serious and traumatic, there is an increasing demand for biomedical materials, especially biomaterials suitable for bone tissue engineering, and its research and development has become one of the focuses of medical research.
  • Calcium phosphate-based biomaterials have similar composition to minerals in bones, and have good biodegradability, bioactivity and osteoconductivity. They can be prepared into high-strength functional stents similar to bone structures by molding and sintering processes. The calcium and phosphorus products after degradation of the implant material can be absorbed as raw materials by osteoblasts for new bone reconstruction. Therefore, calcium phosphate-based ceramic materials represented by hydroxyapatite (HA) and ⁇ -tricalcium phosphate ( ⁇ -TCP) have become research hotspots in biomedical materials.
  • HA hydroxyapatite
  • ⁇ -TCP ⁇ -tricalcium phosphate
  • calcium polyphosphate As one of the calcium phosphate ceramics, calcium polyphosphate (CPP) has good biological activity and cells are non-toxic, have controlled biodegradability, and as a bone scaffold material, CPP has ideal mechanical properties and is very well formed with bone. Strong chemical combination; under the action of body fluid medium, CPP can be partially degraded, degraded and broken, and the released energy can ensure the cell activity needs.
  • the degradation products are phosphate, soluble calcium salt, and free calcium and phosphorus ions. The product is beneficial to the growth of cells, and is absorbed and utilized by human tissues, and new tissue is grown without causing an inflammatory reaction of tissues surrounding the host, and no cytotoxicity, thereby better producing bone conduction.
  • calcium polyphosphate has become a new type of bone tissue engineering repair material that is mainly studied by scholars at home and abroad.
  • the preparation process of CPP at home and abroad mainly adopts the preparation process of “melting ⁇ drawing ⁇ water quenching ⁇ drying ⁇ ethanol wet grinding ⁇ forming sintering”. It is easy to cause pollution to the material, resulting in the purity of the medical grade.
  • the polymerization reaction and the crystal transformation temperature are difficult to control during the preparation process, resulting in failure to obtain the desired material properties, limiting the clinical research and application of CPP materials. The launch.
  • wollastonite powder or ceramic has good biological activity in vitro and the ability to induce the deposition of bone-like hydroxyapatite layers. Silicon is considered to be a medium for promoting new bone formation. The formation of the hydroxyapatite layer is beneficial to promote bone conduction and bone regeneration of the material and promote chemical bonding with soft/hard tissues, indicating that wollastonite is a potential bioactive material with broad application prospects.
  • the inventors have long-term technical and practical exploration, using calcium dihydrogen phosphate as a raw material, using a washing and drying-sintering method to prepare a calcium polyphosphate precursor, while using tetraethyl orthosilicate and four
  • the calcium nitrate raw material was prepared by sol-gel method, and a calcium polyphosphate/wollastonite bio-composite ceramic material was successfully prepared by mixing and sintering the two, which can be adjusted by adjusting the proportional relationship between the two. Its structure, mechanical properties, biological activity and degradation properties, so as to prepare suitable properties of biological materials according to actual needs.
  • the present invention adopts the following technical solutions:
  • a calcium polyphosphate/wollastonite biocomposite ceramic material is provided, the composite ceramic material being made of calcium polyphosphate and wollastonite, the mass percentage of the wollastonite It is 5 to 90%; preferably 35 to 70%; further preferably 50 to 70%, still more preferably 50%, 60% or 70%, and most preferably 50%.
  • the calcium polyphosphate is a ⁇ -type calcium polyphosphate
  • the calcium dihydrogen phosphate raw material is heated and calcined by washing with water, and then heated for a period of time to be naturally cooled to obtain a calcium polyphosphate precursor powder;
  • step S3 The calcium polyphosphate/wollastonite composite precursor powder prepared in step S2 is added to the binder for dry pressing molding;
  • the molded sample is calcined and then naturally cooled to obtain a calcium polyphosphate/wollastonite biocomposite ceramic material.
  • the calcination conditions are: a heating rate of 3 to 8 ° C / min (preferably 5 ° C / min), a calcination temperature of 400 to 600 ° C (preferably 500 ° C); a holding time of 1 to 10 h ( Preferably 10h);
  • the Ca(NO 3 ) 2 , Na 2 SiO 3 and (NH 4 ) 2 HPO 4 aqueous solution is 0.5 mol/L;
  • the stirring time is 20 to 28 h (preferably 24 h);
  • the binder is polyvinyl alcohol, the addition amount is 3 to 8% (preferably 5%); the dry pressing molding condition is: 1 Mpa is kept for 1 min;
  • the calcination conditions are: a heating rate of 3 to 8 ° C / min (preferably 5 ° C / min), a calcination temperature of 800 to 900 ° C (preferably 850 ° C); a holding time of 0.05 to 5 h ( Preferably 1.5h);
  • the molded sample is calcined and then naturally cooled to obtain a calcium polyphosphate/wollastonite biocomposite ceramic material.
  • the calcination conditions are: a heating rate of 3 to 8 ° C / min (preferably 5 ° C / min), a calcination temperature of 400 to 600 ° C (preferably 500 ° C); a holding time of 1 to 10 h ( Preferably 10h);
  • the step of preparing the wollastonite precursor comprises:
  • step S2.2 The sol prepared in step S2.1 is placed in a closed container at room temperature, and after forming a gel, it is aged in a constant temperature water bath at 50-70 ° C for 2-4 days to obtain a semi-dry gel. Drying at 110-130 ° C for 18-30 h to obtain a dry gel;
  • step S2.3 The dry gel obtained in the step S2.2 is ball-milled and sieved for 200 mesh to obtain a wollastonite precursor powder of less than 74 ⁇ m;
  • the pre-hydrolysis time is 30 min; the stirring time is 1 h; the HNO 3 concentration is 2 mol/L; the ethyl orthosilicate, nitric acid, deionized water, and calcium nitrate tetrahydrate
  • the ratio is 1: (0.02-0.04): (3-5): (0.6-1); more preferably 1: 0.03: 4: 0.8;
  • the constant temperature water bath temperature is 60 ° C
  • the aging treatment time is 3 days
  • the drying is performed at 120 ° C for 24 hours;
  • the binder is polyvinyl alcohol, the addition amount is 3 to 8% (preferably 5%); the dry pressing molding condition is: 1 Mpa is kept for 1 min;
  • the calcination conditions are: a heating rate of 3 to 8 ° C / min (preferably 5 ° C / min), a calcination temperature of 800 to 900 ° C (preferably 850 ° C); a holding time of 0.05 to 5 h ( Preferably 1.5h);
  • the application includes the use of the composite ceramic material as an implant material in the repair of artificial bone defects.
  • a calcium polyphosphate precursor is prepared by using a calcium dihydrogen phosphate as a raw material, and a calcium polyphosphate precursor is prepared by mixing and sintering, and a calcium polyphosphate/wollastonite biocomposite ceramic material is successfully prepared.
  • the proportional relationship between the two can adjust its organizational structure, mechanical properties, biological activity and degradation properties, so as to prepare biomaterials with suitable properties according to actual needs. It has been verified by experiments that different proportions of composite ceramic materials are immersed in Tris and SBF for 28 days. Different proportions of CPP/WS composite ceramics have undergone different degrees of degradation and are faster than the degradation rate of pure calcium polyphosphate ceramic materials. And a layer of carbonate-containing hydroxyapatite was produced on the surface, indicating that the prepared composite ceramic has good biological activity, and the biological activity of CPP/WS composite ceramic is significantly improved.
  • Figure 1 is a DSC-TGA curve of calcium dihydrogen phosphate, wherein the heating rate is 10 ° C / min;
  • Figure 2 is a comparison of infrared spectra of calcium dihydrogen phosphate and calcium polyphosphate powder
  • Figure 3 is a Raman spectrum of calcium polyphosphate
  • Figure 4 is an XRD spectrum of a powder of calcium polyphosphate kept at different temperatures for 1.5 h; wherein Figure 4 (a) is a calcium polyphosphate sintered at 500 ° C, 600 ° C, 625 ° C, 650 ° C, 700 ° C for 1.5 h. XRD spectrum of the powder; Figure 4 (b) is an XRD spectrum of the sintered powder of the calcium polyphosphate at 800 ° C, 900 ° C, 930 ° C, 950 ° C, 960 ° C for 1.5 h;
  • Figure 5 is an NMR spectrum of the temperature rise to 850 ° C after heating at 500 ° C for different times; wherein Figure 5 (a) is 1 h; Figure 5 (b) is 5 h; Figure 5 (c) is 10 h;
  • FIG. 6 is a partial enlarged view of a solid NMR spectrum of 31 P of three kinds of calcium polyphosphate prepared by holding at 500 ° C for 1 h, 5 h, and 10 h;
  • Figure 7 is a ⁇ -CPP XRD pattern of different degrees of polymerization prepared by incubation at 500 ° C for 1 h, 5 h, and 10 h;
  • Figure 8 is an SEM image of three kinds of calcium polyphosphate prepared by holding at 500 ° C for 1 h, 5 h, and 10 h;
  • Figure 9 is a graph showing changes in compressive strength of three kinds of calcium polyphosphate prepared by holding at 500 ° C for 1 h, 5 h, and 10 h;
  • Figure 10 is an XRD pattern of a calcium polyphosphate material prepared at different calcination temperatures (0, 500, 600, 625, 650, 700 ° C);
  • Figure 11 is an SEM image of different crystalline calcium polyphosphate ceramic materials, wherein Figure 11 (a) is ⁇ -CPP; Figure 11 (b) is ⁇ + ⁇ -CPP; Figure 11 (c) is ⁇ -CPP;
  • Figure 12 is a graph showing the compressive strength of different crystalline calcium polyphosphate ceramic materials
  • Figure 13 is an XRD pattern of a calcium polyphosphate material at different incubation times at 850 °C;
  • Figure 14 is an SEM image of a calcium polyphosphate material at different incubation times at 850 ° C, wherein Figure 14 (a) is 5 min; Figure 14 (b) is 1.5 h, Figure 14 (c) is 3 h;
  • Figure 15 is a graph showing the compressive strength of three kinds of calcium polyphosphate prepared by holding at 850 ° C for 5 min, 1.5 h, and 3 h;
  • Figure 16 is a graph showing the change in compressive strength of calcium phosphate of different particle diameters
  • 17 is an XRD pattern of a CPP/WS biocomposite ceramic material obtained by calcination at 850 ° C for 1.5 h after chemical coprecipitation, wherein (a) is WS; (b) is a CPP/WS biocomposite ceramic material; (c) is CPP;
  • Figure 18 is a DSC-TGA curve of the dried wollastonite precursor powder at 120 ° C, wherein the heating rate is 10 ° C / min;
  • Figure 19 is an XRD diagram of wollastonite under different heat treatment regimes
  • Figure 21 is a graph showing the weight loss curve of a calcium polyphosphate/wollastonite biocomposite ceramic material finally prepared by adding different ratios of calcium polyphosphate and wollastonite in a Tris buffer solution;
  • Figure 22 is a graph showing the pH change of a calcium polyphosphate/wollastonite biocomposite ceramic material prepared by adding different ratios of calcium polyphosphate and wollastonite in a Tris buffer solution for 28 days;
  • Figure 24 is a 28-day weight loss curve of a calcium polyphosphate/wollastonite biocomposite ceramic material prepared by adding different ratios of calcium polyphosphate and wollastonite in a SBF simulated body fluid immersion;
  • Figure 25 is a 28-day pH change curve of a calcium polyphosphate/wollastonite biocomposite ceramic material prepared by adding different ratios of calcium polyphosphate and wollastonite in a SBF simulated body fluid;
  • Fig. 26(a)(a 1 ) is an SEM image and an energy spectrum when degrading 1d, respectively; and
  • Figs. 26(b) and (b 1 ) are respectively an SEM image and an energy spectrum when degrading 7d;
  • (c) and (c 1 ) are the SEM and energy spectra of degradation at 14d, respectively, and
  • Figures 26(d) and (d 1 ) are the SEM and energy spectra of degradation at 28d;
  • Figure 1 is a DSC-TGA diagram of calcium dihydrogen phosphate. It can be seen from the figure that as the temperature increases, the calcium dihydrogen phosphate undergoes multiple weightlessness processes, and the DSC curve shows the enthalpy change in these places, indicating that decomposition reactions occur near 147 ° C and 269 ° C, and Significant weight loss was observed in the TG curve, the former caused by the loss of crystal water from calcium dihydrogen phosphate, which may be caused by the polycondensation reaction. At this stage, the TG curve showed two different weightlessness processes. The weight loss between 237.01-278.41 °C was obvious, and there was no obvious weight loss between 500 and 800 °C.
  • the polycondensation of calcium dihydrogen phosphate has the characteristics of gradual polymerization.
  • a polycondensation occurs near 269 ° C and accompanied by a significant weight loss process, indicating that calcium dihydrogen phosphate rapidly forms dimers or oligomers at this stage;
  • the oligomer continues to polymerize to form a product with high degree of polymerization, but this stage is not accompanied by significant weight loss, especially at 500-600 ° C, almost no weight loss occurs, indicating that the polymerization tends to balance and further improve
  • the polymerization reaction proceeds, and the baseline of the DSC curve tends to be balanced around 800 ° C to indicate that the reaction system tends to be in equilibrium, and the temperature rises to increase the side reaction, resulting in a decrease in the degree of polymerization.
  • the polymerization by the stepwise method is more conducive to increasing the degree of polymerization of calcium polyphosphate.
  • the whole reaction is a solid phase polycondensation reaction. It can be seen from the reaction equation that the more water is produced, the higher the degree of polymerization.
  • the structure of the resulting polymer is related to both the functionality of the various monomers participating in the reaction and to their ratio.
  • the polymerization of the C stage occurs, there may be a product of the A stage, anhydrous calcium dihydrogen phosphate, and a calcium pyrophosphate formed by the B-stage intramolecular dehydration.
  • Figure 2 is a comparison of infrared spectra of calcium dihydrogen phosphate and CPP burnt powder. It can be seen from Fig. 2 that after the high temperature reaction of calcium dihydrogen phosphate, the peak of 3467 cm -1 corresponding to the -OH stretching vibration disappears substantially, which can be preliminarily determined that the polydihydrogen phosphate has undergone polycondensation reaction.
  • ⁇ -Ca(PO 3 ) 2 crystal phase exists mainly before 600 ° C, and the ⁇ -Ca(PO 3 ) 2 crystal phase appears at 625 ° C, 700 ° C - 950 °C, mainly exists in the ⁇ -Ca(PO 3 ) 2 crystal phase, and ⁇ -Ca(PO 3 ) 2 exists in a wide temperature range and is easy to control.
  • Figure 5 is a 31 P-NMR chart of calcium polyphosphate. Only some of the maps are listed in Figure 6, and the assignment of chemical shifts is noted in the figure. As shown in Fig. 5, Q 0 is the chemical shift of the phosphorus atom in orthophosphoric acid, 0 means that there is no shared oxygen atom at this time, and so on, Q 1 is the chemical shift of the chain terminal phosphorus atom, and Q 2 is the phosphorus atom in the linear structure. Chemical shift. As shown in Fig. 6, most of the maps have almost no chemical shift of Q 0 , indicating that the calcium dihydrogen phosphate is completely reacted.
  • Figure 9 is a comparison of the compressive strength of CPP powders with different degrees of polymerization after being sintered to make solid materials. It can be seen from the figure that the compressive strength of materials with different degrees of polymerization also varies with the degree of polymerization. The increase in compressive strength increases.
  • Figure 13 is an XRD pattern of CPP materials at different holding times at 850 ° C.
  • the holding times are (a) 5 min (b) 1.5 h and (c) 3 h, respectively. Comparing the three graphs, it can be seen that with the increase of the holding time, the peak of the strongest peak is getting stronger and stronger, and there is no difference in the XRD peak shape between 5 min and 1.5 h; It can be seen that the morphology of the grain and the grain is not tight at 5 min, and the grain and the grain are closely connected at 1.5 h, but when it is kept for 3 h, a thick amorphous region appears between the grains. This leads to imperfect crystallization of the material, which affects the properties of the material.
  • the compressive strength of the ceramic material increases as the holding time increases. It can be seen from the previous analysis that as the holding time increases, the change is the degree of crystallization of the particles.
  • the compressive strength of ceramic materials may be related to the degree of perfection of crystallization. The more complete the crystallization, the smaller the internal stress of the internal particles of the stent, and the better the mechanical properties are exhibited; on the contrary, the mechanical properties of the stent are worse. However, when the temperature is kept for 3 hours, a thick amorphous region appears between the crystal grains, resulting in imperfect crystal crystallization, which affects the properties of the material.
  • the compressive strength of the ceramic material prepared using the ball mill powder is much higher than that of the other two particle size ranges. This is mainly due to the tightness of the internal binding of the particles. It can be clearly seen from the SEM photograph in the figure that there are many gaps inside the stent prepared from the 80-100 mesh particle size, and the bonding between the particles is not good. Under the action of external force, this combination is prone to collapse, resulting in damage to the structure of the stent, showing a low compressive strength.
  • the stent prepared from the 200-300 mesh particle size is slightly better.
  • the surface area of the ball-milled powder is large, and the particles and the particles are easily in close contact, which provides a possibility for the surface to be closely fused, thereby exhibiting high mechanical strength;
  • the composite powder has a WS phase and a CPP phase.
  • Ethyl orthosilicate (TEOS) was prehydrolyzed in deionized water for 30 min under the catalysis of an appropriate concentration of 2 mol/L of HNO 3 .
  • the corresponding nitrate is mixed into a nearly saturated solution, added to the above hydrolyzed orthosilicate solution, stirred for 1 hour to fully react to form a sol, and then the sol is placed in a closed container and allowed to stand at room temperature for a period of time to obtain a dry gel. After forming a gel, it was aged in a constant temperature water bath at 60 ° C for 72 h. The obtained gel was dried in a dry box at 120 ° C for 24 hours to obtain a dry gel. The xerogel was ball milled in a ball mill and sieved to 200 mesh to obtain a precursor powder having a particle diameter of less than 74 ⁇ m.
  • the sintering temperature of the wollastonite was determined according to the DSC-TGA curve of the wollastonite precursor powder of Fig. 18.
  • the precursor powder is placed in a heat treatment furnace, kept at a certain temperature for a certain period of time, a heating rate, and then cooled with a furnace to obtain a CaO-SiO 2 powder.
  • Figure 19 is an XRD diagram of wollastonite under different heat treatment regimes. As can be seen from Fig. 19, there is a clear amorphous package in the powder X-ray diffraction pattern at 500 ° C for 1.5 h, indicating that the powder is amorphous after heat treatment at 500 ° C. In the DSC-TGA curve, almost no exothermic peak appeared below 600 °C. When the sample was incubated at 850 ° C for 1.5 h, there was a significant WS diffraction peak.
  • Ball Mill Mixing - Dry Pressing Different ratios of CPP (100, 90, 80, 70, 65, 60, 50, 30, 0) and WS (0, 10, 20, 30, 35, 40, 50, 70) 100)
  • the precursor powder is uniformly mixed by ball milling, adding 5% binder polyvinyl alcohol, placed in a ⁇ 10mm mold, 1Mpa is kept for 1min, pressed into a cylinder of ⁇ 10mmx10mm, and placed in a box furnace at 5 °C/min. The temperature is heated and heated to 850 ° C for 1.5 h, and then the calcium phosphate/wollastonite biocomposite ceramic is prepared by natural cooling with the furnace.
  • WS is a wollastonite prepared by a sol-gel method.
  • the complex was found to be a CPP/WS complex.
  • Example 1 The calcium polyphosphate/wollastonite biocomposite ceramic material prepared in Example 1 was placed in a Tris-HCl solution for 28 days to test its degradation characteristics.
  • the degradation rate of the composite ceramic material increases, and the degradation rate is 0.2%-21%.
  • the addition amount is 10%, the degradation rate is about 8 times that of the pure CPP ceramic material; when the addition amount is 100%, the degradation rate is about 70 times that of the pure CPP ceramic material.
  • the pH variation curves of different proportions of ⁇ -CPP/WS composite ceramic materials in Tris buffer solution show that the pH values of different proportions of ceramic materials are basically the same during the soaking process.
  • the overall pH is stable at 7.2-8. between.
  • the pH value first increases, then begins to decrease, and then maintains steady at around 7.3; when the addition amount increases to 30%, it is obvious. It was found that the pH increased continuously in the first 3 days, reaching about 8.2; and after more than 50%, the pH was significantly higher than pure CPP and greater than 7.5. It can be seen from the figure that after adding wollastonite, the pH is relatively high. This indicates that the addition of wollastonite increases the ion exchange rate of the CPP and Tris solutions.
  • Figure 23 shows the surface morphology of CPP/WS composite ceramics in different proportions before and after degradation in Tris buffer solution for 28 days. It is found from the figure that, like the pure CPP ceramic material, after immersion in the Tris buffer solution for 28 days, many small gaps and pores appear on the surface and the surface particles become smaller.
  • Example 2 The calcium polyphosphate/wollastonite biocomposite ceramic material prepared in Example 1 was placed in SBF simulated body fluid for 28 days to test its degradation characteristics.
  • the pH values of different proportions of ceramic materials are basically the same during the soaking process, and the pH is stable at about 7.3 as a whole.
  • the pH value first decreases, and then remains stable at about 7; and after more than 50%, the pH rises continuously in the first 3 days.
  • the pH is significantly higher than pure CPP and stable at around 7.4.
  • the first is the exchange of Ca Si plasma and H + in SBF. In SBF, H + decreases and alkali ions increase, so the pH rises faster.
  • the pH of the solution is reduced to about 7.4.
  • the biological activity of a material has a certain relationship with the rate of ion exchange. The faster the ion exchange, the higher the deposition rate of apatite on the surface of the material.
  • the spherical particles in the figure mainly contain Ca, P, O, C and Si, and the content of Si elements is significantly lower than that of the surface elements of the materials after soaking for 1, 7, and 14 days.
  • Spherical apatite is a typical morphology of HA.
  • the deposit on the surface of the ceramic material is significantly increased.
  • a thick layer of deposits of spherical particles appeared on the surface of the ceramic material, and after drying, cracks appeared on the surface deposited layer.
  • the vibration peak of CO is also becoming more and more obvious.
  • a weak OH stretching vibration peak and a vibration peak of CO appeared.
  • ⁇ -CPP/WS 0: 100 XRD after soaking for 0d, 3d, and 28d in SBF simulated body fluid. It can be seen from the figure that a significant peak of hydroxyapatite was found after 28 days of degradation. Combined with the infrared spectrum and the surface morphology SEM image, it was confirmed that the substance precipitated on the surface of the composite ceramic material was carbonate-containing hydroxyapatite.
  • the mechanism for forming apatite on the surface in SBF is similar to that of silicoalumino-based glass.
  • the Ca 2+ on the surface of the material exchanges with the H + in the SBF.
  • Reaction (1) occurs, and a silicon-rich layer containing ⁇ Si-OH is formed on the surface of the material.
  • the OH - concentration in SBF is relatively increased, the pH value is increased, and the reaction occurs (2), and the surface is negatively charged with ⁇ Si-O - . It adsorbs cations in the SBF to reduce the energy of the system.
  • Ca 2+ in the SBF is adsorbed near the surface of the material, and Ca 2+ further adsorbs PO 3 - 4 , so that a large enough ion concentration on the surface of the material causes the apatite to precipitate.
  • the apatite nucleates on the surface of the material, the apatite will consume calcium and phosphorus in the sbf and spontaneous autocatalysis occurs.
  • the amorphous calcium phosphate layer is deposited on the surface of the material. With the prolongation of the immersion time and the incorporation of impurities such as CO 2 - 3 , the composition and structure of the calcium phosphate layer are adjusted and transformed, and the thermodynamically stable CHA is finally formed. .
  • the reason for the difference in the morphology of the apatite crystals which are newly formed on the surface of the two materials is related to the solution supersaturation.
  • supersaturation is the driving force of crystallization, which has a great influence on the crystal morphology.
  • Hydroxyapatite is a hexagonal system. When the degree of supersaturation is low, the crystal faces of the crystal grow slowly according to the crystal habit, and a worm-like crystal with a relatively long diameter is obtained.
  • CPP dissolution releases Ca and P to increase calcium and phosphorus supersaturation in SBF.
  • the formation of the hydrous silicic acid layer Si(OH) 4 is critical. Therefore, for bioglass ceramics, Si has a strong promoting effect on the mineralization and activity of the material.
  • the simulated body fluid immersion experiment showed that within 28 days, the scaffold material formed these light-based apatite crystallites to form spherical clusters to reduce the surface energy of the material and make the system more stable. After 3 days, the spherical clusters grow up and form a light-based apatite (HCA) layer, which completely covers the surface of the material, indicating that the material has good mineralization ability and biological activity.
  • HCA light-based apatite

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Abstract

一种聚磷酸钙/硅灰石生物复合陶瓷材料及其制备方法，所述复合陶瓷材料由聚磷酸钙和硅灰石制成，所述聚磷酸钙的质量百分含量为5～90％；优选为35～70％，进一步优选为50-70％，更进一步优选为50％、60％或70％，最优选为50％。以磷酸二氢钙为原料，采用水洗干燥-烧结的方法制备了聚磷酸钙前驱体，通过将二者混合烧结成功制备出一种聚磷酸钙/硅灰石生物复合陶瓷材料，通过在调整二者的比例关系可以调节其组织结构，力学性能，生物活性和降解性能，从而根据实际需求制备合适性能的生物材料。

Description

一种聚磷酸钙/硅灰石生物复合陶瓷材料及其制备方法 技术领域
本发明属于生物复合陶瓷材料技术领域，具体涉及一种聚磷酸钙/硅灰石生物复合陶瓷材料及其制备方法。
背景技术
生物医用材料是用来对生物体进行诊断、治疗、修复或替换其病损组织、器官或增进其功能的新型高技术材料生物医用材料有助于提高人类的生活质量和寿命，但目前人口老龄化严重并且创伤增多，人们对生物医用材料特别是适用于骨组织工程的生物材料的需求越来越多，它的研究与开发已经成为医学研究的重点之一。
磷酸钙基生物材料与骨骼中的矿物有着相似的成分，并且具备较好的生物降解性，生物活性和骨传导性，可通过成型、烧结工艺制备成与骨结构相似的高强度功能性支架，植入材料降解后的钙磷产物可以作为原料被成骨细胞吸收用于新骨重建。因此，以羟基磷灰石(HA)、β-磷酸三钙(β-TCP)为代表的磷酸钙基陶瓷材料成为了生物医用材料的研究热点。
作为磷酸钙陶瓷中的一种，聚磷酸钙(CPP)具有良好的生物活性且细胞无毒性，具有可控的生物降解性，同时作为骨支架材料，CPP具有理想的机械性能，与骨形成很强的化学结合；在体液介质的作用下，CPP可发生部分降解，降解断链，释放出的能量可保证细胞活性需要，降解产物有磷酸盐，可溶性钙盐，以及游离钙，磷离子，这些产物有利于细胞的生长，同时被人体组织吸收利用，长出新的组织，且不会引起宿主周围组织的炎症反应，无细胞毒性，从而更好地产生骨传导作用。因此聚磷酸钙成为国内外学者重点研究的一种新型的骨组织工程修复材料。然而由于对CPP的聚合度、晶型转变的温度范围目前还存在分歧，目前国内外对CPP的制备主要采用“熔融→拉丝→水淬→烘干→乙醇湿磨→成型烧结”的制备工艺，容易对材料造成污染，造成纯度达不到医用级别；同时在制备过程中，聚合反应和晶型转变温度也难以控制，导致未能获得理想的材料性能，限制了CPP材料在临床研究和应用方面的开展。
同时，近年来有研究表明硅灰石粉体或陶瓷在体外具有很好的生物活性和诱导沉积类骨羟基磷灰石层的能力，硅元素被认为是促进新骨形成的一个媒介。羟基磷灰石层的形成有利于促进材料的骨传导和骨再生，并促进同软/硬组织形成化学键合作用，这表明硅灰石是一种潜在的、具有广阔应用前景的生物活性材料。然而迄今为止尚未有制备聚磷酸钙/硅灰石生物复合陶瓷材料的报道。
发明内容
针对上述现有技术的不足，发明人经长期的技术与实践探索，以磷酸二氢钙为原料，采用水洗干燥-烧结的方法制备了聚磷酸钙前驱体，同时以正硅酸乙酯和四水硝酸钙原料，采用溶胶凝胶法制备硅灰石前驱体，通过将二者混合烧结成功制备出一种聚磷酸钙/硅灰石生物复合陶瓷材料，通过在调整二者的比例关系可以调节其组织结构，力学性能，生物活性和降解性能，从而根据实际需求制备合适性能的生物材料。
为实现上述目的，本发明采用如下技术方案：
本发明的第一个方面，提供了一种聚磷酸钙/硅灰石生物复合陶瓷材料，所述复合陶瓷材料由聚磷酸钙和硅灰石制成，所述硅灰石的质量百分含量为5～90％；优选为35～70％；进一步优选为50-70％，更进一步优选为50％、60％或70％，最优选为50％。
进一步的，所述聚磷酸钙为β型聚磷酸钙；
本发明的第二个方面，提供上述生物复合陶瓷材料的一种制备方法，包括：
S1.以磷酸二氢钙原料，经水洗干燥后升温煅烧，保温一段时间后自然冷却即得聚磷酸钙前驱体粉末；
S2.配制Ca(NO 3) 2、Na 2SiO 3溶液和(NH 4) 2HPO 4澄清水溶液，并分别用氨水调节pH＝10.5～11.0；将聚磷酸钙前驱体粉末加入Ca(NO 3) 2水溶液，然后将混合聚磷酸钙前驱体粉末的Ca(NO 3) 2水溶液滴入Na 2SiO 3水溶液中生成白色沉淀物，搅拌一段时间后，过滤、并用去离子水和无水乙醇洗涤、滤干后烘干即得原位生成的聚磷酸钙/硅灰石复合前驱体粉末；
S3.向步骤S2.制得的聚磷酸钙/硅灰石复合前驱体粉末加入粘结剂干压成型；
S4.成型试样经煅烧保温，然后自然冷却即得聚磷酸钙/硅灰石生物复合陶瓷材料。
进一步的，所述步骤S1.中，煅烧条件为：升温速率3～8℃/min(优选为5℃/min)，煅烧温度400～600℃(优选为500℃)；保温时间1～10h(优选为10h)；
进一步的，所述步骤S2.中，所述Ca(NO 3) 2、Na 2SiO 3和(NH 4) 2HPO 4水溶液为0.5mol/L；
进一步的，所述步骤S2.中，所述搅拌时间为20～28h(优选为24h)；
进一步的，所述步骤S3.中，粘结剂为聚乙烯醇，添加量为3～8％(优选为5％)；干压成型条件为：1Mpa保压1min；
进一步的，所述步骤S4.中，煅烧条件为：升温速率3～8℃/min(优选为5℃/min)，煅烧温度800～900℃(优选为850℃)；保温时间0.05～5h(优选为1.5h)；
本发明的第三个方面，提供了上述生物复合陶瓷材料的另一种制备方法，包括：
S1.制备聚磷酸钙前驱体：以磷酸二氢钙原料，经水洗干燥后升温煅烧，保温一段时间后自然冷却即得；
S2.制备硅灰石前驱体：以正硅酸乙酯和四水硝酸钙为原料，采用溶胶凝胶法制备硅灰石前驱；
S3.将聚磷酸钙前驱体和硅灰石前驱体按比例混合均匀，加入粘结剂干压成型；
S4.成型试样经煅烧保温，然后自然冷却即得聚磷酸钙/硅灰石生物复合陶瓷材料。
进一步的，所述步骤S1.中，煅烧条件为：升温速率3～8℃/min(优选为5℃/min)，煅烧温度400～600℃(优选为500℃)；保温时间1～10h(优选为10h)；
进一步的，所述步骤S2.中，制备硅灰石前驱体的步骤包括：
S2.1将正硅酸乙酯在硝酸溶液的催化作用下于去离子水中预水解20–60min，然后加入四水硝酸钙，搅拌0.5-2h，充分溶解得清澈溶胶；
S2.2将步骤S2.1制得的溶胶在室温下放置于密闭容器内，待其形成凝胶后，置于50-70℃恒温水浴中老化处理2-4天，得半干态凝胶，在110-130℃条件下干燥18-30h，得干凝胶；
S2.3将步骤S2.2制得的干凝胶进行球磨，并进行200目的筛分，得小于74μm的硅灰石前驱 体粉末；
进一步的，所述步骤S2.1中，预水解时间为30min；搅拌时间为1h；HNO 3浓度为2mol/L；所述正硅酸乙酯、硝酸、去离子水、四水硝酸钙的摩尔比为1：(0.02-0.04)：(3-5)：(0.6-1)；更优选为1:0.03:4:0.8；
进一步的，所述步骤S2.2中，恒温水浴温度为60℃，老化处理时间为3天；在120℃条件下干燥24h；
进一步的，所述步骤S3.中，粘结剂为聚乙烯醇，添加量为3～8％(优选为5％)；干压成型条件为：1Mpa保压1min；
进一步的，所述步骤S4.中，煅烧条件为：升温速率3～8℃/min(优选为5℃/min)，煅烧温度800～900℃(优选为850℃)；保温时间0.05～5h(优选为1.5h)；
本发明的第四个方面，提供了上述复合陶瓷材料作为植入体材料的应用。
进一步的，所述应用包括所述复合陶瓷材料作为植入体材料在人工骨缺损修复中的应用。
本发明的有益效果：
本申请以磷酸二氢钙为原料，采用水洗干燥-烧结的方法制备了聚磷酸钙前驱体，将二者混合烧结成功制备出一种聚磷酸钙/硅灰石生物复合陶瓷材料，通过在调整二者的比例关系可以调节其组织结构，力学性能，生物活性和降解性能，从而根据实际需求制备合适性能的生物材料。经试验验证，所制备的不同比例的复合陶瓷材料经过Tris、SBF浸泡28天，不同比例CPP/WS复合陶瓷都发生了不同程度的降解并且都比纯聚磷酸钙陶瓷材料的降解速率有所加快；并且表面均生产了一层含碳酸根的羟基磷灰石，说明所制备的复合陶瓷具有较好的生物活性，CPP/WS复合陶瓷的生物活性得到显著提高。
附图说明
图1为磷酸二氢钙的DSC-TGA曲线图，其中升温速率10℃/min；
图2为磷酸二氢钙和聚磷酸钙烧料粉末的红外光谱对比图；
图3为聚磷酸钙的拉曼图谱；
图4为聚磷酸钙在不同温度下保温1.5h烧结粉末的XRD谱图；其中图4(a)为聚磷酸钙在500℃、600℃、625℃、650℃、700℃下保温1.5h烧结粉末的XRD谱图；图4(b)为聚磷酸钙在800℃、900℃、930℃、950℃、960℃下保温1.5h烧结粉末的XRD谱图；
图5为在500℃分别保温不同时间后升温到850℃的NMR图谱；其中图5(a)为保温1h；图5(b)为保温5h；图5(c)为保温10h；
图6为在500℃温度下保温1h、5h、10h制得的三种聚磷酸钙的 31P的固体NMR图谱局部放大图；
图7为在500℃温度下保温1h、5h、10h制得的不同聚合度的β-CPP XRD图谱；
图8为在500℃温度下保温1h、5h、10h制得的三种聚磷酸钙的SEM图；
图9为在500℃温度下保温1h、5h、10h制得的三种聚磷酸钙的抗压强度变化图；
图10为不同煅烧温度下(0，500，600，625，650，700℃)制得的聚磷酸钙材料的XRD图；
图11为不同晶型聚磷酸钙陶瓷材料的SEM图，其中图11(a)为γ-CPP；图11(b)为γ+β-CPP；图 11(c)为β-CPP；
图12为不同晶型聚磷酸钙陶瓷材料的抗压强度；
图13为在850℃下，不同保温时间聚磷酸钙材料的XRD图；
图14为在850℃下，不同保温时间聚磷酸钙材料的SEM图，其中，图14(a)为5min；图14(b)为1.5h，图14(c)为3h；
图15为在850℃下保温5min、1.5h、3h制得的三种聚磷酸钙的抗压强度图；
图16为不同粒径聚磷酸钙的抗压强度变化图；
图17为采用化学共沉淀法后在850℃煅烧保温1.5h后得到的CPP/WS生物复合陶瓷材料的XRD图谱，其中，(a)为WS；(b)为CPP/WS生物复合陶瓷材料；(c)为CPP；
图18为120℃下干燥的硅灰石前驱体粉末的DSC-TGA曲线图，其中升温速率10℃/min；
图19为不同热处理制度下的硅灰石的XRD图；
图20为不同比例复合的陶瓷材料在850℃煅烧保温1.5h的XRD图谱，其中，曲线从上到下依次为CPP/WS＝100:0；CPP/WS＝70:30；CPP/WS＝50:50；CPP/WS＝0:100；
图21为添加不同比例聚磷酸钙和硅灰石最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在Tris缓冲溶液中的失重曲线图；
图22为添加不同比例聚磷酸钙和硅灰石最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在Tris缓冲溶液浸泡28天中pH变化曲线；
图23为添加不同比例聚磷酸钙和硅灰石最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在Tris缓冲溶液中浸泡28天前后的SEM图；其中降解前：(a)β-CPP/WS＝100:0；(b)β-CPP/WS＝90:10；(c)β-CPP/WS＝80:20；(d)β-CPP/WS＝70:30；(e)β-CPP/WS＝65:35；(f)β-CPP/WS＝60:40；(g)β-CPP/WS＝50:50；(h)β-CPP/WS＝30:70；(i)β-CPP/WS＝0:100；
降解后：(a 1)β-CPP/WS＝100:0；(b 1)β-CPP/WS＝90:10；(c 1)β-CPP/WS＝80:20；(d 1)β-CPP/WS＝70:30；(e 1)β-CPP/WS＝65:35；(f 1)β-CPP/WS＝60:40；(g 1)β-CPP/WS＝50:50；(h 1)β-CPP/WS＝30:70；(i 1)β-CPP/WS＝0:100；
图24为添加不同比例聚磷酸钙和硅灰石最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液浸泡28天失重变化曲线；
图25为添加不同比例聚磷酸钙和硅灰石最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液浸泡28天pH变化曲线；
图26为添加不同比例聚磷酸钙和硅灰石最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液中降解28天后的SEM图和能谱图；其中(a)β-CPP/WS＝100:0；(b)β-CPP/WS＝90:10；(c)β-CPP/WS＝80:20；(d)β-CPP/WS＝70:30；(e)β-CPP/WS＝65:35；(f)β-CPP/WS＝60:40；(g)β-CPP/WS＝50:50；(h)β-CPP/WS＝30:70；(i)β-CPP/WS＝0:100；
图27为添加比例为β-CPP/WS＝0:100最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF缓冲溶液中降解1d；7d；14；28d的SEM图和能谱图；其中，图26(a)(a 1)分别为降解1d时的SEM图和能谱图；图26(b)和(b 1)分别为降解7d时的SEM图和能谱图；图26(c)和(c 1)分别为降解14d 时的SEM图和能谱图，图26(d)和(d 1)分别为降解28d时的SEM图和能谱图；
图28为添加比例为β-CPP/WS＝0:100最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液中浸泡不同时间的TR-FTIR图；
图29为添加比例为β-CPP/WS＝30:70最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液中浸泡不同时间的SEM图；其中，
(a)0d；(b)14d；(c)21d；(d)28d；
图30为添加比例为β-CPP/WS＝30:70最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液中浸泡不同时间的TR-FTIR图；
图31为添加比例为β-CPP/WS＝50:50最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液中浸泡不同时间的SEM图；其中，
(a)0d；(b)14d；(c)21d；(d)28d；
图32为添加比例为β-CPP/WS＝50:50最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液中浸泡不同时间的TR-FTIR图；
图33为添加比例为β-CPP/WS＝60:40最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液中浸泡不同时间的SEM图；其中，
(a)0d；(b)14d；(c)21d；(d)28d；
图34为添加比例为β-CPP/WS＝60:40最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液中浸泡不同时间的TR-FTIR图；
图35为添加比例为β-CPP/WS＝65:35最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液中浸泡不同时间的SEM图；其中，
(a)0d；(b)14d；(c)21d；(d)28d；
图36为添加比例为β-CPP/WS＝65:35最终制得的聚磷酸钙/硅灰石生物复合陶瓷材料在SBF模拟体液中浸泡不同时间的TR-FTIR图；
图37为添加比例为β-CPP/WS＝0:100在SBF模拟体液中浸泡0d,3d,28d后的XRD图。
具体实施方式
应该指出，以下详细说明都是例示性的，旨在对本申请提供进一步的说明。除非另有指明，本文使用的所有技术和科学术语具有与本申请所属技术领域的普通技术人员通常理解的相同含义。
需要注意的是，这里所使用的术语仅是为了描述具体实施方式，而非意图限制根据本申请的示例性实施方式。如在这里所使用的，除非上下文另外明确指出，否则单数形式也意图包括复数形式，此外，还应当理解的是，当在本说明书中使用术语“包含”和/或“包括”时，其指明存在特征、步骤、操作、器件、组件和/或它们的组合。
以下通过实施例对本发明做进一步解释说明，但不构成对本发明的限制。
实施例1
1聚磷酸钙陶瓷粉末的制备过程：
取磷酸二氢钙原料，用去离子水水洗、搅拌、烘干，然后倒入洁净的坩埚内(因煅烧温度不高， 可用未上釉的陶瓷器皿盛放，并将坩埚放置在箱式炉内，坩埚的上部要加保护措施，防止窑炉落脏)。以4℃/min的速度升到500℃，保温10个小时。待窑炉冷却后，将原料取出，进行研磨。此时原料部分会粘接在坩埚壁上，取中间部分，制得不同聚合度的聚磷酸钙陶瓷粉末前驱体。
1.1聚磷酸钙粉末制备工艺的优化
1.1.1磷酸二氢钙的TG曲线
图1是磷酸二氢钙的DSC-TGA图。从图中可以看出，随着温度的升高，磷酸二氢钙经历了多次失重过程，DSC曲线显示出这些地方的热焓变化，表明在147℃和269℃附近发生了分解反应，并在TG曲线中表现出显著的失重，前者由磷酸二氢钙失去结晶水引起，后者可能是发生缩聚反应引起。TG曲线在这一阶段出现了两次不同的失重过程，237.01-278.41℃之间的失重较明显，500～800℃之间未表现出明显的失重现象。由此可见，磷酸二氢钙的缩聚具有逐步聚合的特性，首先在269℃附近发生一次缩聚而且伴随着显著的失重过程，表明这一阶段磷酸二氢钙迅速生成二聚体或者低聚物；500-800℃时低聚物继续聚合生成高聚合度的产物，不过这一阶段并没有伴随着显著的失重，特别是在500～600℃几乎没有失重发生，表明聚合反应趋于平衡，进一步提高温度则聚合反应继续进行，DSC曲线的基线在800℃附近趋于平衡表明反应体系趋于平衡，继续升温则副反应加剧导致聚合度降低。综上，采用分步法进行聚合更有利于提高聚磷酸钙的聚合度。结合以上的讨论，可以推测磷酸二氢钙缩聚过程反应如下所示：
Figure PCTCN2018124147-appb-000001
整个反应为固相缩聚反应，从反应方程式可以看出产物生成水越多，其聚合度越高。生成聚合物的结构，既与参加反应的各种单体本身的官能度有关，也与它们的配比有关。在C阶段的聚合反应发生时，可能存在A阶段的产物无水磷酸二氢钙和B阶段分子内脱水生成的焦磷酸钙。如果无水磷酸二氢钙在B阶段未完全发生分子内脱水生成焦磷酸钙，C阶段聚合反应发生时存在两种单体，生成的CPP为支化或网状结构，但本实验中从TG图中B阶段的失重率8.182％，可以看出，无水CPP基本在B阶段已经完全发生了分子内脱水生成了焦磷酸钙，作为C阶段聚合反应的单体，因此可以初步判断本实验反应生成的CPP为链状聚合物。
1.1.2红外光谱和拉曼分析
图2是磷酸二氢钙和CPP烧料粉末的红外光谱对比图。从图2可以看出，磷酸二氢钙经过高温反应后，其-OH伸缩振动对应的3467cm -1峰基本消失，这可以初步判定，磷酸二氢钙已经发生了缩聚反应。并且由图3可以看到，在约1278cm -1出现了O-P＝O官能团的非对称伸缩振动峰，在约 1173cm -1和713cm -1处出现了直链P-O-P官能团的伸缩振动峰，这表明，磷酸二氢钙经高温聚合后，产物具有直链结构，初步证明产物即为聚磷酸钙。
1.1.3XRD物相分析
本实验在不同温度条件下制备了聚磷酸钙粉末，并分别对其进行XRD分析。粉末X射线衍射结果是对物质的相进行定性分析的有力工具。当X射线通过晶体时，每一种结晶物质都有各自独特的衍射谱图，其特征可以用各个反射面的晶界间距d和反射线的相对强度来表征。图4(a),(b)分别是聚磷酸钙烧料在500℃、600℃、625℃、650℃、700℃、800℃、900℃、930℃、950℃、960℃下保温1.5h烧结粉末的XRD谱图。从图4(a)中可以看出在600℃以前主要以γ-Ca(PO 3) 2晶相存在，而在625℃时出现了β-Ca(PO 3) 2晶相，700℃-950℃，主要以β-Ca(PO 3) 2晶相存在，并且β-Ca(PO 3) 2存在的温度范围比较宽，容易控制。
1.2不同聚合度对聚磷酸钙陶瓷材料性能的影响
图5是聚磷酸钙的 31P-NMR图谱。图6中仅列出部分图谱，并在图中注明了化学位移的归属。如图5所示，Q 0为正磷酸中磷原子的化学位移，0代表此时没有共用氧原子，以此类推Q 1为链端磷原子的化学位移，Q 2为直链结构中磷原子的化学位移。如图6所示，多数图谱几乎都没有Q 0的化学位移，表明磷酸二氢钙完全反应。通过这些化学位移的峰面积可以计算聚磷酸钙的聚合度:PD＝(Q 0+Q 1+Q 2)/(Q 0+0.5Q 1)。在500℃分别保温1h(a)、5h(b)、10h(c)升温到850℃后聚合度经过计算大约为20、25、28。但从图7中，可以看出三个图谱并没有明显区别，并且晶型并没有发生变化都是β-CPP，只是三强峰的强度发生些许变化。由图8可以看出3种不同聚合度的聚磷酸钙陶瓷材料表面形貌并无很大差异，在500℃温度下保温10h制得的聚磷酸钙的SEM图显示其晶粒分布更细更均匀一些。图9为不同聚合度材料的CPP粉末经烧结后，制成实心材料所测抗压强度的比较，从图中可以看出，不同的聚合度的材料抗压强度也有所不同，随着聚合度的增加，抗压强度增大。
1.3不同晶型对聚磷酸钙陶瓷材料性能的影响
由图10可知，随着温度的升高，由磷酸二氢钙反应生成的物相结构发生变化，625℃以下主要以γ-CPP存在，温度升高逐渐形成β-CPP。图11可以看出，随着温度的升高，不同晶型的聚磷酸钙陶瓷材料表面形貌发生了很大的变化。由片状逐渐变成连接紧密且有韧性的。图12可知，晶型的不同对抗压强度的影响很大，γ-CPP<γ+β-CPP<β-CPP。
1.4不同保温时间对聚磷酸钙陶瓷材料性能的影响
图13为在850℃下，不同保温时间CPP材料的XRD图，保温时间分别为(a)5min(b)1.5h和(c)3h。比较三个图可以看出，随着保温时间的增加，最强峰所在位置的峰越来越强，5min和1.5h在XRD峰形上基本无差异；再结合图14不同保温时间下材料表面形貌可以看出，5min时，晶粒与晶粒之间连接不紧密，1.5h时晶粒与晶粒之间连接紧密，但保温3h时，晶粒之间出现较厚的非晶区域，导致材料结晶不完善，从而影响材料的性能。综合比较可以得出，保温1.5h是最佳的。从图15中可以看出，陶瓷材料的抗压强度随着保温时间的延长而增加。在前面的分析中可以看出，随着保温时间的增加，变化的是颗粒的结晶完善程度。陶瓷材料的抗压缩强度可能与结晶的完善程度相关，结晶越完善，支架的内部粒子的内应力越小，对外就表现出较好的力学性能；反之，支架的力学性 能就要差一些。但保温3h时，晶粒之间出现较厚的非晶区域，导致材料结晶不完善，从而影响材料的性能。
1.5烧料粒径的选择
从图16可以看出，使用球磨粉末制备的陶瓷材料的抗压强度要远高于其它两个粒径范围制备的支架。这主要是由于颗粒内部结合的紧密程度不一样所致。结合图中的SEM照片可以明显的看出由80-100目粒径的烧料制备的支架内部有许多缝隙，颗粒之间的结合不好。在外力的作用下，这种结合容易出现垮塌，导致支架结构破坏，表现出抗压强度很低。由200-300目粒径的烧料制备的支架要稍好一些。而球磨粉末的表面积大，颗粒与颗粒容易紧密接触，为颗粒之间表面紧密融合提供了可能，从而表现出较高的力学强度；
2.采用化学共沉淀法原位生成CPP/WS复合前驱体粉末，二者质量比最终控制为CPP(100、90、80、70、65、60、50、30、0)和WS(0、10、20、30、35、40、50、70、100)，具体的，配制0.5mol/L的Ca(NO 3) 2、Na 2SiO 3和(NH 4) 2HPO 4水溶液，并分别用氨水调节pH＝10.5～11.0；在搅拌下，将聚磷酸钙前驱体粉末加入Ca(NO 3) 2水溶液，然后将混合聚磷酸钙前驱体粉末的Ca(NO 3) 2水溶液滴入Na 2SiO 3水溶液中生成白色沉淀物，加料完毕后继续搅拌24h、过滤、并用去离子水和无水乙醇充分洗涤，滤干后于烘箱中烘干原位生成CPP/WS复合前驱体粉末，加入5％粘结剂聚乙烯醇，放入Φ10mm的模具中，1Mpa保压1min，压制成Φ10mmx10mm的圆柱，放入箱式炉中以5℃/min的速度加热升温至在850℃保温1.5h得到CPP/WS粉末，图17为CPP/WS＝1:1的聚磷酸钙/硅灰石生物复合陶瓷材料的XRD物相分析可知，化学共沉淀法制备的复合粉末具有WS相和CPP相。
实施例2
1.聚磷酸钙前驱体制备方法同实施例1；
2.硅灰石(WS)前驱体粉末的制备：采用溶胶凝胶法CaO-SiO 2。
将正硅酸乙酯(TEOS)在适量浓度为2mol/L的HNO 3催化作用下于去离子水中预水解30min。Si(OC 2H 5) 4+4H 2O→SiO 2+4C 2H 5OH，其中去离子水的摩尔量为正硅酸乙酯摩尔量的4倍，硝酸溶液的摩尔量为正硅酸乙酯摩尔量的0.03倍，进行磁力搅拌。把相应的硝酸盐配成近饱和溶液后加入到上述水解的正硅酸乙酯溶液中，搅拌1h充分反应形成溶胶，然后把溶胶置于密闭容器内在室温下放置一段时间，得干凝胶待其形成凝胶后放入60℃的恒温水浴中老化处理72h。将所得的凝胶放入干燥箱中于120℃干燥24h得到干凝胶。将干凝胶在球磨机中球磨并进行200目筛分，得到粒径小于74μm的前驱体粉末。
根据图18硅灰石前驱体粉末的DSC-TGA曲线，确定硅灰石的烧结温度。将前驱体粉末放入热处理炉中，在一定温度下保温一定时间，升温速率，然后随炉冷却得到CaO-SiO 2粉末。
图19为不同热处理制度下的硅灰石的XRD图。从图19可以看出，在500℃保温1.5h的粉末X射线衍射图谱中有明显的非晶包，说明粉末在500℃时热处理后是无定型态的。在DSC-TGA曲线中，600℃以下几乎没有放热峰出现。当样品在850℃保温1.5h后，有明显的WS衍射峰的出现。
3.不同比例的聚磷酸钙/硅灰石复合陶瓷的制备：
球磨混合-干压成型：将不同配比的CPP(100、90、80、70、65、60、50、30、0)和WS(0、 10、20、30、35、40、50、70、100)前驱体粉末球磨混合均匀，加入5％粘结剂聚乙烯醇，放入Φ10mm的模具中，1Mpa保压1min，压制成Φ10mmx10mm的圆柱，放入箱式炉中以5℃/min的速度加热升温至850℃保温1.5h，然后随炉自然冷却制得聚磷酸钙/硅灰石生物复合陶瓷。
由图20不同比例复合的陶瓷材料在850℃煅烧保温1.5h的XRD图谱可知，同时存在WS相和CPP相。WS为溶胶凝胶法制备的硅灰石。同时结合拉曼分析可知该复合物为CPP/WS复合物。
实施例3
1.性能测试：
1.1将实施例1制备的聚磷酸钙/硅灰石生物复合陶瓷材料放置到Tris-HCl溶液中浸泡28天测试其降解特性。
从图21中可以发现，随着WS添加量的增加，复合陶瓷材料的降解速率也不断增加，降解速率在0.2％-21％。当添加量为10％，降解速率为纯CPP陶瓷材料的8倍左右；当添加量为100％时，降解速率为纯CPP陶瓷材料的70倍左右。
从图22不同比例β-CPP/WS复合陶瓷材料在Tris缓冲溶液中pH变化曲线中发现，不同比例的陶瓷材料在浸泡过程中pH值得变化趋势基本一致，整体来看pH稳定在7.2～8之间。浸泡初期，当添加量为10％、20％时，pH大体与纯CPP变化规律相似，pH值先增大，然后开始下降，然后平稳维持在7.3左右；当添加量增加到30％时，明显发现pH在前3d，pH不断升高，达到8.2左右；并且大于50％后，pH明显高于纯CPP并且大于7.5。由图可以看出，加入硅灰石后，pH都比较高。这说明，硅灰石的加入提高了CPP和Tris溶液的离子交换速率。
图23为不同比例CPP/WS复合陶瓷材料在Tris缓冲溶液中降解28天前后的表面形貌。从图中发现，和纯CPP陶瓷材料一样，在Tris缓冲溶液浸泡28天后，表面也出现了很多微小的缝隙和孔洞并且表面的颗粒变小。
1.2将实施例1制备的聚磷酸钙/硅灰石生物复合陶瓷材料放置到SBF模拟体液中浸泡28天测试其降解特性。
从图24中可以发现，不同比例β-CPP/WS复合陶瓷材料在SBF模拟体液中的失重率整体成增加趋势除了0:100比例，并且明显比在tris缓冲溶液中失重率低，间接的也说明了在陶瓷材料尚有新物质的产生。后续的红外图谱和表面形貌会继续分析新物质的成分。从图中还可以发现当比例上升到65:35后，在21d后新物质的生成速度大于失重速度。
从图25中发现，不同比例的陶瓷材料在浸泡过程中pH值得变化趋势基本一致，整体来看pH稳定在7.3左右。浸泡初期，当添加量为10％、20％时，pH大体与纯CPP变化规律相似，pH值先下降，然后平稳维持在7左右；并且大于50％后，在前3d，pH不断升高，达到8左右，pH明显高于纯CPP并且稳定在7.4左右。浸泡过程中首先是Ca Si等离子和SBF中H +的交换，SBF中H +减少，碱离子增多，所以pH上升比较快。当SBF中Ca 2+、HPO 2- 4、PO 3- 4、OH -和CO 2- 3等离子富集到样品表面形成磷灰石时，溶液的pH值降低至7.4左右稳定不变。一般来说，材料的生物活性与离子交换速率的快慢有一定的关系，离子交换越快，材料表面磷灰石的沉积速率越大。
从图26不同比例的CPP/WS复合陶瓷材料在SBF缓冲溶液中浸泡28天后的表面形貌和EDS 能谱成分分析，表面都形成了有球状颗粒组成的沉积层覆盖，部分球形颗粒发生了团聚，表面沉积层出现了裂纹，这是在干燥过程中产生的。由EDS能谱分析可知，浸泡后新出现的沉积层中主要包含Ca、P、O和C。结合红外图谱检测结果，我们分析可以得出，这几种比例分浸泡后的表面都形成了磷灰石层，说明该复合陶瓷材料具有诱导生成磷灰石的能力。并且，随着硅灰石比例的增加，诱导生成磷灰石的能力增强。
由图27可以看出，浸泡28天后，陶瓷材料表面就出现了一层厚厚的由球形颗粒组成的沉积物。由EDS能谱成分分析可知，图中的球形颗粒主要含有Ca、P、O、C和Si，与浸泡1,7,14天时材料表面元素的含量相比，Si元素含量明显降低。球状磷灰石是HA的典型形貌。
由图28的β-CPP/WS＝0:100在SBF模拟体液中浸泡不同时间的TR-FTIR图可知，在570cm -1,640cm -1，1099cm -1处出现了P-O官能团，在1425cm -1处出现了C-O的振动峰。并且在3430cm -1和1640cm -1处出现了O-H伸缩振动峰。随着浸泡时间的延长，Si-O键逐渐削弱，P-O吸收峰强度增大。
由图29可以看出，β-CPP/WS＝30:70的陶瓷复合材料浸泡14天后，陶瓷材料表面就出现了一层厚厚的由球形颗粒组成的沉积物。并且由图30可知，在570cm -1,640cm -1，1099cm -1处出现了P-O官能团，在1425cm -1处出现了C-O的振动峰。并且在3430cm -1和1640cm -1处出现了O-H伸缩振动峰。随着浸泡时间的延长，Si-O键逐渐削弱，P-O吸收峰强度增大，C-O的振动峰也越来越明显。
图33为β-CPP/WS＝60:40在SBF模拟体液中浸泡不同时间的表面形貌。随着浸泡时间的延长，陶瓷材料表面的沉积物明显增多。在浸泡28天时，陶瓷材料表面就出现了一层厚厚的由球形颗粒组成的沉积物，并且干燥后，表面沉积层出现了裂纹。并且由图34可知，浸泡28天后，在570cm -1,640cm -1，1099cm -1处出现了P-O官能团，在1425cm -1处出现了C-O的振动峰。并且在3430cm -1和1640cm -1处出现了O-H伸缩振动峰。随着浸泡时间的延长，C-O的振动峰也越来越明显。在14天时就出现了微弱的O-H伸缩振动峰和C-O的振动峰。
图37中β-CPP/WS＝0:100在SBF模拟体液中浸泡0d,3d,28d后的XRD。从图中可以发现，降解28天后发现明显的羟基磷灰石的峰。结合红外图谱和表面形貌SEM图，确定在复合陶瓷材料表面沉淀的物质为含碳酸根的羟基磷灰石。
实际上，在SBF中表面形成磷灰石的机理与硅钙基玻璃相似。材料入侵SBF后，材料表面的Ca 2+与SBF中的H +交换。发生反应(1)，在材料表面形成含≡Si-OH的富硅层。同时SBF中的OH -浓度相对升高，pH值升高，发生反应(2)，表面形成带负电的≡Si-O -。其吸附SBF中的阳离子以降低体系的能量。因此，SBF中的Ca 2+被吸附到材料表面附近，Ca 2+进一步吸附PO 3- 4，这样在材料的表面有足够大的离子浓度积使磷灰石沉淀。一旦磷灰石在材料表面成核，磷灰石将消耗sbf中的钙磷，发生自发的自我催化。开始沉积在材料表面的是无定形的钙磷层，随浸泡时间的延长和CO 2- 3等杂质的掺入，钙磷层发生组成、结构上的调整和转化，最终成热力学上稳定的CHA。
≡Si-O-Ca-O-Ca≡+2H +＝2≡Si-OH+Ca 2+           (1)
≡Si-OH+OH -＝≡Si-O -+H 2O                     (2)
本申请中，造成两种材料表面新生的磷灰石晶体形貌不同的原因与溶液过饱和度有关。根据结晶学原理，过饱和度是结晶的动力，对晶体形貌的影响很大。羟基磷灰石为六方晶系，在过饱和度较低时，晶体的各晶面按结晶习性缓慢生长，得到长径比较大的蠕虫状晶体。对复合生物陶瓷而言，CPP溶解释放Ca、P增加SBF中钙、磷过饱和度。大的过饱和度容易造成晶面上各部分过饱和差变大，从而破坏了晶体生长的顺序性，也就破坏了晶体的完整性，使杂质CO 3 2-、Mg 2+等易于进入晶体，改变了晶体的结晶习性，羟基磷灰石不按结晶习性异向生长，而不同程度地变为同向生长，因而得到粒度较小，类似球形的晶体。随反应时间的延长及其它离子的掺杂，钙磷化合物经一系列组成、结构的调整，由初期的无定形态最终矿化为类骨的HCA微晶，这是一种热力学上的稳定相。可见，含水硅酸凝胶层Si(OH) 4的形成十分关键。因此，对于生物玻璃陶瓷来说，Si对材料的矿化和活性具有较强的促进作用。模拟体液浸泡实验显示:在28d内，支架材料形成这些轻基磷灰石微晶聚集成球形晶簇，以降低材料表面能，使体系更加稳定。3d后，球形晶簇长大，堆积形成轻基磷灰石(HCA)层，完全覆盖材料表面，预示着材料具有良好的矿化能力和生物活性。
综上可知，
1)本申请所制备的不同比例的复合陶瓷经过Tris、SBF浸泡28天，不同比例CPP/WS复合陶瓷都发生了不同程度的降解并且都比纯聚磷酸钙陶瓷材料的降解速率有所加快；并且表面均生产了一层含碳酸根的羟基磷灰石，说明所制备的复合陶瓷具有较好的生物活性，CPP/WS复合陶瓷的生物活性得到显著提高。
2)当WS的量达到35％时，在SBF中浸泡14天时就明显发现了类磷灰石的产生，并且形貌呈颗粒状。随着浸泡时间的增加，类含碳酸根的羟基磷灰石的量逐渐增多，且直径逐渐增大，并且当浸泡时间为14天时，在CPP/WS复合陶瓷比例达到50:50时，表面会发现二次形核的含碳酸根的羟基磷灰石聚集体。
以上所述仅为本申请的优选实施例而已，并不用于限制本申请，对于本领域的技术人员来说，本申请可以有各种更改和变化。凡在本申请的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本申请的保护范围之内。

Claims (10)

  1. 一种聚磷酸钙/硅灰石生物复合陶瓷材料，所述复合陶瓷材料由聚磷酸钙和硅灰石制成，所述硅灰石的质量百分含量为5～90％；优选为35～70％；进一步优选为50-70％，更进一步优选为50％、60％或70％，最优选为50％。
  2. 如权利要求1所述的生物复合陶瓷材料，其特征在于，所述聚磷酸钙为β型聚磷酸钙；
  3. 如权利要求1或2所述生物复合陶瓷材料的制备方法，其特征在于，包括：
    S1.以磷酸二氢钙原料，经水洗干燥后升温煅烧，保温一段时间后自然冷却即得聚磷酸钙前驱体粉末；
    S2.配制Ca(NO 3) 2、Na 2SiO 3溶液和(NH 4) 2HPO 4澄清水溶液，并分别用氨水调节pH＝10.5～11.0；将聚磷酸钙前驱体粉末加入Ca(NO 3) 2水溶液，然后将混合聚磷酸钙前驱体粉末的Ca(NO 3) 2水溶液滴入Na 2SiO 3水溶液中生成白色沉淀物，搅拌一段时间后，过滤、并用去离子水和无水乙醇洗涤、滤干后烘干即得原位生成的聚磷酸钙/硅灰石复合前驱体粉末；
    S3.向步骤S2.制得的聚磷酸钙/硅灰石复合前驱体粉末加入粘结剂干压成型；
    S4.成型试样经煅烧保温，然后自然冷却即得聚磷酸钙/硅灰石生物复合陶瓷材料。
  4. 如权利要求3所述的制备方法，其特征在于，所述步骤S1.中，煅烧条件为：升温速率3～8℃/min(优选为5℃/min)，煅烧温度400～600℃(优选为500℃)；保温时间1～10h(优选为10h)。
  5. 如权利要求3所述的制备方法，其特征在于，所述步骤S2.中，所述Ca(NO 3) 2、Na 2SiO 3和(NH 4) 2HPO 4水溶液为0.5mol/L；所述搅拌时间为20～28h(优选为24h)。
  6. 如权利要求3所述的制备方法，其特征在于，所述步骤S3.中，粘结剂为聚乙烯醇，添加量为3～8％(优选为5％)；干压成型条件为：1Mpa保压1min。
  7. 如权利要求3所述的制备方法，其特征在于，所述步骤S4.中，煅烧条件为：升温速率3～8℃/min(优选为5℃/min)，煅烧温度800～900℃(优选为850℃)；保温时间0.05～5h(优选为1.5h)。
  8. 权利要求1或2所述生物复合陶瓷材料的制备方法，其特征在于，包括：
    S1.制备聚磷酸钙前驱体：以磷酸二氢钙原料，经水洗干燥后升温煅烧，保温一段时间后自然冷却即得；
    S2.制备硅灰石前驱体：以正硅酸乙酯和四水硝酸钙为原料，采用溶胶凝胶法制备硅灰石前驱；
    S3.将聚磷酸钙前驱体和硅灰石前驱体按比例混合均匀，加入粘结剂干压成型；
    S4.成型试样经煅烧保温，然后自然冷却即得聚磷酸钙/硅灰石生物复合陶瓷材料。
  9. 如权利要求3所述的制备方法，其特征在于，
    所述步骤S1.中，煅烧条件为：升温速率3～8℃/min(优选为5℃/min)，煅烧温度400～600℃(优选为500℃)；保温时间1～10h(优选为10h)。
    所述步骤S3.中，粘结剂为聚乙烯醇，添加量为3～8％(优选为5％)；干压成型条件为：1Mpa保压1min；
    所述步骤S4.中，煅烧条件为：升温速率3～8℃/min(优选为5℃/min)，煅烧温度800～900℃(优选为850℃)；保温时间0.05～5h(优选为1.5h)。
  10. 如权利要求1或2所述生物复合陶瓷材料或权利要求3-8任一项所述制备方法制备得到的 生物复合陶瓷材料作为植入体材料的应用；
    优选的，所述应用包括所述复合陶瓷材料作为植入体材料在人工骨缺损修复中的应用。
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