CN1462638A - Method for synthesizing artificial bone from carboxylic apatite of coral - Google Patents
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Abstract
An artificial coral hydroxy apatitis (CHA) bone for medical purpose is prepared from coral through hydrothermal reaction in the diammonium hydrogen phosphate plus hydrothermal liquid system under high-temp and high-pressure condition to convert the CaCO3 of coral to Ca5(PO4)3(OH) which is just the artificial bone. Its advantages are high compression strength, high porosity (24.86-65.71%), no toxic by-effect and good biologic compatibility.
Description
Technical Field
The invention relates to an artificial bone for orthopedic medical treatment, in particular to a synthetic method of a Coral Hydroxyapatite (CHA) artificial bone.
Background
Bone defect is a common problem in orthopedics, bone fusion is a common means in orthopedics, thousands of patients are amputated or cut to be disabled because of bone necrosis caused by comminuted fracture or inflammation due to various industrial injuries, traffic accidents and accidents in China every year, and the synthetic artificial bone graft can repair the damaged limbs of the patients, avoid the fracture and the abrasion of the disabilities and relieve the pain of the patients. The preparation of ideal synthetic artificial bone is a major problem which is urgently expected to be solved by the orthopedics medical field.
The hot spot and main content of bone tissue engineering research are focused on several aspects: seed cells, scaffold materials and bioactive factors. Among them, the scaffold material is an important part, and as it relates to an important bone grafting material for bone fusion and bone growth, various scholars explore materials for replacing bones from different fields, and the development of tissue engineering is strongly promoted. The current ideal stent material requirements are as follows: a) (ii) tissue compatibility; b) degradability and degradation rate controllability; c) no antigen effect exists; d) maintaining and enhancing the morphology and phenotype of the cells growing thereon, and enhancing the adhesion and reproduction of the cells, inducing bone regeneration; e) has a certain porosity; f) has certain mechanical strength and the like. According to the process of obtaining the material, the scaffold material can be divided into natural types (xenogenic bone, natural mineral material, collagen, chitosan and fibrin), artificial synthetic types (bioceramics types-medical calcium phosphate, calcium phosphate/hydroxyapatite and biopolymer types-PLA, PGA, POE, PHB) and other different types, and each of the materials has advantages and disadvantages.
The development of bone tissue engineering based on material science brings hope and good prospect for solving the problems of bone defect and spinal fusion in orthopedics and orthopedics. The application of single material and one factor is gradually replaced by the application of composite material and multiple factors, and the research of scaffold material is a basic main carrier of tissue engineering. Compared with various support materials at home and abroad at present, research shows that the artificial bone has advantages and disadvantages, but the artificial bone synthesized by modifying natural mineral materials as raw materials is the most ideal support material in human bone grafting materials. It has the advantages of similar color and luster and microporous structure to human bone, similar chemical components, good compatibility, strong bone forming ability, no toxicity and no side effect, etc.
There have been some reports on the research of using natural mineral material coral as raw material to reform synthetic hydroxyapatite (CHA) artificial bone, but there has been no report on the specific preparation process.
Disclosure of Invention
The invention aims to provide a method for reconstructing and synthesizing a hydroxyapatite (CHA) artificial bone by taking natural mineral material coral as a raw material so as to prepare an ideal synthetic artificial bone and solve the clinical application requirement of a medical bone grafting material.
The present invention uses the alternate substitution of isomorphism generated in mineral structure and the mutual replacement of atom, ion and complex ion in crystal lattice without destroying the crystal lattice structure. Under the condition of high temperature and high pressure, coral is selected as a raw material and sodium hydrogen phosphate (NH)4)2HPO4+ water (H)2O) carrying out an alternate reaction to form hydroxyapatite and reserving a pore structure of the raw material; the chemical reaction formula is as follows:
aragonite hydroxyapatite
The method comprises the following specific steps:
processing natural coral raw material into a sample with a required shape, soaking the sample in deionized distilled water, cleaning the sample by using an ultrasonic cleaner, and then mixing the sample with a diammonium hydrogen phosphate aqueous solution at a temperature of 100-450 ℃ (preferably 180-250 ℃) and a pressure of 100-500 multiplied by 105Reacting for 240-480 hours under the condition of Pa to obtain the CHA artificial bone; soaking the synthesized CHA artificial bone in deionized distilled water,cleaning with an ultrasonic cleaning instrument, and drying and sterilizing at the temperature lower than 100 ℃ to obtain the required CHA artificial bone product; the concentration of the diammonium hydrogen phosphate aqueous solution is 2.5-3.5M (usually saturated aqueous solution), the pH value is 8.3-8.5, and the dosage is more than 1: 2.2 (usually 1: 2.5-4, preferably 1: 3) according to the weight of the raw material sample and the volume of the diammonium hydrogen phosphate aqueous solution.
The synthesis process of the above-described process of the present invention is preferably carried out in an autoclave; the autoclave is preferably a self-sealing autoclave with external heating and internal pressurization.
When the synthesis reaction is carried out in an autoclave, the amount of aqueous diammonium hydrogen phosphate solution used (V)Solutions of) Can be determined according to the volume (V) of the autoclave barrelBarrel body) Volume of solid raw material sample (V)Solid body) And the pressure (P) and temperature (T) used, first from Kennedy H2The corresponding fullness (f) is found in the P-T-f table of O, and then calculated according to the following formula: vSolutions of＝f×VFreedom of movement＝f×(VBarrel body-VSolid body). The physical and chemical properties of the artificial bone synthesized by the Coral Hydroxyapatite (CHA) prepared by the method are as follows:
the artificial bone of Coral Hydroxyapatite (CHA) reconstructed and synthesized from natural mineral material coral has the characteristics of stable performance, white color, microporous structure, no toxic or side effect, good biocompatibility and strong bone forming capability.
(1) Chemical components: the CHA synthesized artificial bone is analyzed by electron microscope energy spectrum (%): 47.91-64.45 parts of CaO; p2O524.86～52.09；TiO 0.05～0.08；CoO 0.04～0.1；NiO 0.02～0.09；AgO20.1～0.12；Na2O 0.13～0.21；FeO 0.01～0.28。
The artificial bone synthesized from Coral Hydroxyapatite (CHA) has stable chemical composition, and CaO/P2O5The ratio is similar to hydroxyapatite in literature, and the product does not contain harmful trace elements and infectious germs.
(2) X-ray diffraction analysis: the CHA synthetic artificial bone was subjected to X-ray diffraction analysis and had the following d-values:
8.169(8.102)，5.3294(5.267)，4.0919(4.063)，3.7509(3.670，3.88)，3.449(3.428，3.43)3.1684(3.160)，3.0889(3.07，3.08)，3.0763(3.070)2.8202(2.804，2.81)，2.7265(2.72)，2.6330(2.622)，1.945(1.942)，1.8915(1.892，1.885)，1.8426(1.840，1.835)，1.8097(1.80，1.801)，1.7807(1.780，1.775)，1.7214(1.7220，1.717)，1.6461(1.645，1.6390)，1.5025(1.507)，1.4771(1.474)，1.4754，1.4351(1.433)
the above data are obtained by synthesizing artificial bone analysis data (d value) for the Coral Hydroxyapatite (CHA) in the outside of the bracket, and by placing a bet on the bracket without a cross line, the data are obtained by analyzing the hydroxyapatite in the literature in the case of the cross line. The artificial bone synthesized by the CHA has the d value similar to that of hydroxyapatite and human bone, so the artificial bone has good biocompatibility and no toxic or side effect.
(3) Electron microscope image processing parameters: in order to understand the structural structure and the change of the porosity of the artificial bone synthesized by the raw material coral and the Coral Hydroxyapatite (CHA), the images are observed and photographed under an electron microscope, the structural structures of the coral and the Coral Hydroxyapatite (CHA) are similar, the electron microscope images are processed by a computer and the porosity, the number of the voids, the diameter, the area and the like of the electron microscope images are counted, and the analysis result shows that the porosity of the CHA synthesized artificial bone is similar to that of the raw material, namely, the synthesized CHA synthesized artificial bone keeps the structural structure of the raw material, and the main parameters of the structure are shown in Table 1.
TABLE 1 coral starting Material and Coral Hydroxyapatite (CHA) Electron microscopy image processing parameters sample name voidfraction/% pore number average diameter/102μ m total pore area/mm2The coral raw material 31.52539.1525.38 CHA artificial bone 24.86-65.7139-74, a few 1630-6781.35-49.3848.44-47.65
(4) Compressive strength: the CHA synthesized artificial bone and the raw material coral are tested for compressive strength: the compressive strength of the CHA synthesized artificial bone is 875-1187 kg/cm2The coral raw material is 557-928 kg/cm2Namely, the compressive strength of the CHA synthetic artificial bone is higher than that of the raw material.
(5) Specific gravity: the specific gravity of the raw material coral is 1.85-2.00 g/cm3The specific gravity of the CHA synthetic artificial bone is 2.00-2.40 g/cm3The amplification is 7.6-30.4%.
(6) Hardness: the hardness of the raw material coral is 3, and the hardness of the CHA synthesized artificial bone is 3.7-3.8, which is higher than the hardness of the raw material coral.
The chemical components of the hydroxyapatite artificial bone material obtained by the method are similar to those of human bones, so that the hydroxyapatite artificial bone material has good biocompatibility and no rejection reaction or antigen reaction. The material has a pore structure, so that liquid can be circulated, liquid and substances are transmitted in the osteogenesis process, and living tissues and biological factors are allowed to be tightly attached to the pore structure, so that the bone growth and fusion are facilitated. Is favorable for the close attachment and regeneration of the living tissue, thereby having good osteogenesis capability. In addition, the material is synthesized under high temperature and high pressure, so that the material has the advantages of no infectious germs, no toxicity, no side effect and the like. The CHA artificial bone material can keep thevolume and the shape of the raw material after synthesis, can be shaped before clinical application, can also be modified in shape according to medical needs during operation, has higher compressive strength and can play a certain supporting role. Therefore, the artificial bone synthesized by the Coral Hydroxyapatite (CHA) obtained by the method is an ideal scaffold material and a bone substitute (bone grafting material). The Coral Hydroxyapatite (CHA) synthesized artificial bone material is applied to tens of animal experiments and more than twenty clinical cases in orthopedics department of general hospitals in Guangzhou military region: animal experiments (experiments on fusion of dog cervical vertebra and limbs and rat myozone dislocation) have good effect, no toxic or side effect, good biocompatibility, good osseointegration due to bone defect and strong osteogenesis capacity; clinical application of 20 cases (4 cases of anterior cervical vertebra, 2 cases of posterior cervical vertebra, 5 cases of posterior lumbar vertebra and 9 cases of four limbs and pelvis) postoperative systematic medical examination shows that patients have no rejection reaction, no toxic or side effect, good bone healing, recovery function after healing and self-care of life. The animal and clinical application prove that the artificial bone synthesized by the Coral Hydroxyapatite (CHA) prepared by the method is a bone grafting material with good performance, is suitable for clinical application, has large product volume and wide bone grafting range.
In addition, the method of the invention has the advantages of lower pressure and temperature conditions, easy operation and control and lower equipment cost; the used raw material is the sarcandra glabra, the source is wide, the price is low, and the product cost can be reduced.
Detailed Description
The present invention isfurther illustrated by the following specific examples.
The CHA artificial bone synthesis process of each example was carried out in an autoclave at high temperature and high pressure and completed in a hydrothermal aqueous system. The equipment used was as follows: 1) autoclave: an externally-heated and internally-pressurized self-tightening type sealed high-pressure kettle is selected, made of GH alloy steel and internally provided with a gold bushing; the autoclave has an inner diameter of 1-20 mm, an inner diameter to an outer diameter of approximately 1: 4, a length of 200-240 mm, and a maximum pressure of 2500 x 105Pa, and the temperature is 600-850 ℃. 2) A high-temperature furnace: the device consists of a hearth, a furnace shell, furnace wires and a heat insulating material, is used for heating the high-pressure kettle, has the diameter of 14cm and the height of 50cm, is wound with a high-temperature resistance wire, has the power of 1000-4000 w and can reach 850 ℃, has the diameter of 60cm and the height of 75cm, and is filled with a pearl soil heat insulating material between the hearth and the furnace shell. 3) Thermocouple: for measuring the experimental temperature of the furnace, a temperature controller, usually a Ni-Cr-Al thermocouple, is usually placed in the furnace. 4) A temperature controller: the temperature error is + -1-5 deg.C for controlling the experimental temperature, the instrument can control the input voltage and current to achieve the purpose of adjusting the temperature, and can measure the experimental temperature at the same time, the instrument model is DWK-702. The method of the invention is adopted. The CHA artificial bone having a volume of (1X 1) to (18X 1.5) cm can be synthesized by the above-mentioned apparatus. Determination of the amount of the medium solution:
after the experimental temperature and pressure conditions are determined, the volume of the kettle barrel, the filling degree corresponding to the free space and a certain temperature and pressure must be known before the reactants are loaded into the kettle, and the required amount of the medium solution to be added is calculated according to the filling degree. The calculation can be performed as follows:
A. autoclave cylinder volume measurement. The volume can be calculated by a volume calculation formula according to the geometric shape of the cylinder. The simple method is to fill the autoclave body with a certain volume of water by using a precision measuring cylinder or a burette to obtain cylinder volume data.
B. And (4) calculating free space. By free space (or effective space) is meant the energy of the gas and liquid in the course of the heating reaction after the gas and liquid in the autoclave have been sealedWhere there is free access, if there is a sample of liquid and solids in the autoclave, then the autoclave free space is equal to the volume of the autoclave minus the volume of all solid samples in the autoclave. E.g. with VFromDenotes the autoclave free space, VCartridgeDenotes the autoclave barrel volume, VFixing deviceRepresenting the total volume of solids charged to the autoclave, VFrom＝VCartridge-VFixing device。
C. And (4) fullness meaning and calculation. The degree of filling (or filling degree) is the percentage of the volume of the reaction solution added to the autoclave at normal temperature and pressure to the free space of the autoclave, for example, the degree of filling is represented by f, and V isLiquid for treating urinary tract infectionDenotes the volume of the reaction solution charged into the autoclave, f ═ VLiquid for treating urinary tract infection/VFrom。
D. P-T-f relation of water under high temperature and high pressure: the pressure in the autoclave is related to the solution filling f and the autoclave heating temperature. A certain functional relation exists among the P-T-f, and if f and T are constant for a certain medium solution, the pressure is also constant. A series of corresponding pressure data are made on pure water solution under various different fullness degrees by a specific high-pressure autoclave of Kennedy, and a pure water P-T-f data relation chart is made (Limegalin Main edition, Experimental geochemistry, 1988, Beijing geological Press, 1-250), and relevant data can be obtained according to the chart.Example (c): the volume of the autoclave cylinder is 15ml, the volume of the solid sample is 0.85ml during the experiment, T is 300 ℃ and P is 1500 multiplied by 10 during the reaction5Pa，
It was required to add as much reaction solution to the autoclave.
Solution: first from Kennedy H2The P-T-f table of O shows that when T is 300 deg.C, P is 1500 × 105When Pa, f is 0.8591, then:
Vsolutions of＝f×VFreedom of movement＝f×(VBarrel body-VSolid body)
＝0.8591×(15-0.85)＝0.8591×14.15
＝12.156ml
When 12.15ml of the autoclave is required, the pressure is 1500 multiplied by 10 when the experimental temperature is 300 DEG C5Pa。
Example 1:
1. 50g (block) of coral, a natural mineral material, was cut into three pieces of 1X 1cm, 2.8X 1.2X 1.5cm and 6.3X 1.5X 0.65cm on a diamond cutter, and weighed 19.0 g.
2. Three raw material samples which are cut are placed in a beaker containing deionized distilled water and cleaned in an ultrasonic cleaner.
3. Designing the synthesis experimental conditions with the pressure of 100X 105Pa, at a temperature of 220 ℃, in an autoclave, the degree of filling of the medium liquid is 0.75 calculated on the volume of the raw material sample, and the amount of medium solution required to be added is calculated on the basis of the degree of filling.
4. The medium was a saturated aqueous solution of diammonium phosphate at a concentration of 3M, and the pH of the solution was 8.5 as measured with a pH meter.
5. Adding the raw material sample and the medium solution into an autoclave, placing a sealing plug according to the procedure of installing the autoclave, adding a large screw cap, tightening and sealing the screw cap on a workbench of the autoclave, and placing the autoclave in a high-temperature furnace.
6. Starting a temperature controller to raise the temperature of the furnace to 220 ℃, keeping the temperature error at +/-2 ℃, keeping the temperature for 240 hours, and fully carrying out the alternate reaction of the raw material sample and the diammonium hydrogen phosphate solution: so as to synthesize the artificial bone of Coral Hydroxyapatite (CHA).
7. Cutting off the current input into the high-temperature furnace in a temperature controller, taking the high-pressure kettle out of the high-temperature furnace, quenching for about 30 minutes, placing the high-pressure kettle on a workbench for installing the high-pressure kettle after the high-pressure kettle is cooled, and lifting the sealing plug to unload the high-pressure kettle.
8. Before taking out the sample, the pH value of the solution in the autoclave after the reaction is determined to be 8, namely the pH value of the solution after the reaction is slightly reduced.
9. And taking out a synthesized productsample from the autoclave, putting the synthesized product sample into a glass beaker filled with deionized water, washing the synthesized product sample for multiple times, soaking the synthesized product sample for 24 hours, then washing the synthesized product sample with the deionized water in an ultrasonic cleaner, and drying the washed product sample in an oven at 60 ℃ to obtain the required CHA synthesized artificial bone product (the weight is 20.8 g).
10. The final CHA artificial bone product samples were subjected to various physicochemical property tests: x-ray diffraction analysis; performing electron microscope energy spectrum analysis; processing and analyzing the image of the electron microscope; compressive strength; and (4) measuring the hardness. The results of each analysis are as follows:
a) x-ray diffraction analysis: the CRA synthesized artificial bone has d value similar to that of hydroxyapatite in literature, and characteristic d value and strength (parenthesis value) are listed as follows:
8.1397(20)，3.8868(27)，3.5009(22)，3.4449(119)，3.1728(26)，3.0909(49)，2.8167(199)，2.7826(138)，2.7265(132)，2.6415(31)，2.6602(52)，2.1592(20)，1.9481(76)，1.8945(35)，1.8426(84)，1.7833(44)，1.7571(45)，1.7226(50)
b) chemical components: according to the energy spectrum analysis of an electron microscope, CaO is 64.45 percent, and P is2O534.94%, S0.34%, Al 0.29%, total amount 100%.
c) Electron microscope image processing parameters: the CHA synthesized artificial bone is observed by an electron microscope to shoot a structural image, and the structural image is processed by computer to calculate the parameters of porosity and the like as follows: the image magnification was 32.16%, the number of pores was 85, and the total pore area was 13410.510 μm2The average pore diameter was130.671 μm.
d) Compressive strength: 1111kg/cm2。
e) Color and intensity: white in color and 3.8 in hardness.
f) Volume: the raw material sample size was retained.
g) The application effect is as follows: two of the CHA synthetic artificial bone samples have the sizes of 2.8 multiplied by 1.4 multiplied by 1.5cm and 6.3 multiplied by 1.5 multiplied by 0.65cm, are clinically applied by department of orthopedics of general hospitals in Guangzhou military districts, have good effect, have no rejection reaction in the treatment process of patients, have no toxic or side effect, have good bone healing, strong bone forming capability, and have good survival and self-care and recovery after healing. The CHA artificial bone grafting material is proved to have excellent quality. Examples 2 to 6:
the synthesis process is as in example 1. The process conditions, chemical composition and porosity parameters for the CHA artificial bone product obtained in each example are shown in tables 2 to 4, respectively.
TABLE 2 different temperature and pressure conditions for the Synthesis of CHA Artificial bone EXAMPLE temperature pressure reaction time before reaction of raw Material weight Medium component concentration after reaction product number (g) (M) pH (. degree. C.) (. times.10)5Pa) (hours) pH2 Dioscorea opposita (NH)4)2HPO4
(CaCO3) 35 +H2O38.32805001688 CHA artificial bone 23 Binhua 5 is similar to 2.5840025001927.8 CHA artificial bone 34 Binhua 5 is similar to 3.58.52001002888 CHA artificial bone 45 Binhua 8 is similar to 38.52703002408 CHA artificial bone 56 Binhua 21 is similar to 3.58.52002003608 CHA artificial bone 6
TABLE 3 Synthesis of chemical composition of artificial bone from human bone, coral starting material and CHA
Examples
Sample name CaO P2O5Fe2O3Na2O TiO2SrO SiO2Ag2O NiO CoO MgO SO2K2Total O numbering control 2a human bone a 64.8529.950.391.870.130.881.260.3799.7 control 1a Arisaema costatum a 98.31.250.59100.142 CHA Artificial bone 263.3735.690.220.070.0399.43 CHA Artificial bone 353.2546.300.080.100.200.071004 CHA Artificial bone 458.9141.091005 CHA Artificial bone 553.1346.480.2099.816 CHA Artificial bone 664.0935.520.3899.99
The electron microscopy energy spectrum composition analysis results in Table 3 show that CaO and P of CHA artificial bone synthesized by the method of the invention under different temperature and pressure conditions2O5The content is similar to that of human bones, so the composition has good compatibility.
TABLE 4 CHA Artificial bone Electron microscopy image processing porosity parameters synthesized under different temperature and pressure conditions example porosity Total pore area average pore diameter
Sample name magnification number of pores
(％) (μm2) (μm2) (μm) control 1a Binchaku a 10044.2029391661.11213505.556131.133 control 1b Bingaku b 5044.20701566644.44422380.653168.807 control 2a human bone a 10051.5536193122.8395364.80182.648 control 2b human bone b 15049.04971254733.32212935.395128.3352 CHA Artificial bone 25051.9216301882001154.83 CHA Artificial bone 35041.9748140900264.504 CHA Artificial bone 45042.82384765001129.845 CHA Artificial bone 55025.8784979408.45911659.6245121.846 CHA Artificial bone 65053.58261899113.33073042.820304.961
The results in Table 4 show that the pore parameters of the CHA artificial bone synthesized by the method under different temperature and pressure conditions are similar to those of human bone, and the CHA artificial bone prepared by the method has good transmission performance to liquid and substances and is an ideal bone grafting material.
Claims (7)
1. A method for synthesizing artificial bone of coral hydroxyapatite is characterized by comprising the following steps: processing natural coral raw material into a sample with a required shape, soaking the sample in deionized distilled water, cleaning with an ultrasonic cleaning instrument, and mixing with diammonium hydrogen phosphate aqueous solution at 100 deg.CThe temperature is 450 ℃ below zero and the pressure is 100 to 800 multiplied by 105Reacting for 240-480 hours under the Pa condition to obtain a hydroxyapatite artificial bone; soaking the synthesized hydroxyapatite artificial bone in deionized distilled water, cleaning with an ultrasonic cleaning instrument, and drying and sterilizing at the temperature lower than 100 ℃ to obtain the desired hydroxyapatite artificial bone product; the concentration of the diammonium hydrogen phosphate aqueous solution is 2.5-3.5M, the pH value is 8.3-8.5, and the dosage is more than 1: 2.2 according to the weight of the raw material sample and the volume of the diammonium hydrogen phosphate aqueous solution.
2. The method according to claim 1, wherein the temperature of the synthesis reaction is 180 to 250 ℃.
3. The process as claimed in claim 1, wherein the aqueous diammonium hydrogen phosphate solution used is a saturated aqueous solution.
4. The method according to claim 1, wherein the aqueous solution of diammonium phosphate is used in an amount of 1: 2.5 to 4 parts by weight of the raw material sample to volume of the aqueous solution of diammonium phosphate.
5. The process as claimed in claim 1, wherein the synthesis is carried out in an autoclave.
6. A process according to claim 5, wherein the autoclave is an externally heated internally pressurized self-sealing autoclave.
7. A process according to claim 5 or 6, characterized in that the amount V of aqueous diammonium hydrogen phosphate solution used isSolutions ofAccording to the volume V of the autoclave barrelBarrel bodyVolume V of solid raw material sampleSolid bodyAnd the pressure P and temperature T used, first from Kennedy H2The corresponding fullness f is found in the P-T-f table of O, and then calculated according to the following formula: vSolutions of＝f×VFreedom of movement＝f×(VBarrel body-VSolid body)。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100384488C (en) * | 2004-05-28 | 2008-04-30 | 梁辉 | Preparation technique of absorbent hydroxyapatite artificial bone |
| CN110201227A (en) * | 2019-06-06 | 2019-09-06 | 杭州口腔医院集团有限公司 | A kind of antibacterial pattern method of the implant surface of 3D printing substrate |
| CN112641539A (en) * | 2021-01-19 | 2021-04-13 | 青岛大学附属医院 | Method for increasing bone volume of personalized coral hydroxyapatite artificial bone block by oral implantation and application thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100384488C (en) * | 2004-05-28 | 2008-04-30 | 梁辉 | Preparation technique of absorbent hydroxyapatite artificial bone |
| CN110201227A (en) * | 2019-06-06 | 2019-09-06 | 杭州口腔医院集团有限公司 | A kind of antibacterial pattern method of the implant surface of 3D printing substrate |
| CN112641539A (en) * | 2021-01-19 | 2021-04-13 | 青岛大学附属医院 | Method for increasing bone volume of personalized coral hydroxyapatite artificial bone block by oral implantation and application thereof |
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