YY/T 1558.3-2017Implants for surgery-Calcium phosphates - Part 3: Hydroxyapatite and beta-tricalcium phosphate bone substitutes (English PDF)

3.1 Terms and definitions

The following terms and definitions apply to this document.

3.1.1 Alpha-tricalcium phosphate

alpha-TCP The crystal structure of the compound is in accordance with the International Diffraction Center Powder Diffraction Database (ICDD) PDF card 09-0348.

Note. Its chemical formula is Ca3(PO4)2.

3.1.2 --tricalcium phosphate beta

beta-TCP The crystal structure of the compound conforms to the ICDD PDF card 09-0169.

Note. Its chemical formula is Ca3(PO4)2.

3.1.3 Bone substitute

It is intended to fill products that cause bone defects caused by trauma or surgery.

3.1.4 Hydroxyapatite

The crystal structure of the compound is consistent with the ICDD PDF card 09-0432 or 72-1243.

Note. Its chemical formula is Ca10(PO4)6(OH)2.

3.1.8 Porosity

The ratio of the total pore volume to the volume of the bulk or granular product.

3.1.9 Tetracalcium phosphate

TTCP The crystal structure characteristics of the compounds conform to the ICDD PDF card 25-1137 or 70-1379.

Note. Its chemical formula is Ca4(PO4)2O.

3.1.10 Osteoconductive material

Note. Bone conduction is a passive feature.

3.1.11 Calcium oxide

The crystal structure of the compound is consistent with the ICDD PDF card 4-0777 or 82-1690.

3.1.12 Beta-tricalcium phosphate density

dbeta-TCP The theoretical density of the dense beta-tricalcium phosphate was 3.07 g/cm 3.

3.1.13 Hydroxyapatite density

The theoretical density of the dense hydroxyapatite is 3.15 g/cm³.

3.2 Symbol

Dr. density of synthetic bone substitutes.

Dth. theoretical density of synthetic bone substitutes. m. the quality of the synthetic bone substitute. V. volume of synthetic bone substitute.

4.2 Crystal phase qualitative and quantitative determination

4.2.1 General

The composition and phase purity should be quantified by X-ray diffraction (XRD) according to ISO 13779-3.

4.2.2 Single-phase hydroxyapatite bone substitute

The hydroxyapatite content should not be less than 95% of the crystalline phase. The content of calcium oxide should not be higher than 1%.

The formula for calculating the content of hydroxyapatite is shown in formula (1). MFHA=100%-MFbeta-TCP-MFalpha-TCP-MFTTCP-MFCaO (1) In the formula. MFHA ---HA content; MFbeta-TCP---beta-TCP content; MFalpha-TCP---alpha-TCP content; MFTTCP---TTCP content; MFCaO ---CaO content.

If the above phase content is below the detection threshold, the content should be considered zero.

4.2.3 Biphasic bone substitute

The absolute value of the crystal phase content of the ratio of hydroxyapatite to beta-tricalcium phosphate should be ±5%.

For example, a 60% HA and 40% TCP combination can be composed of 65% HA and 35% TCP to 55% HA and 45% TCP.

Qualitative determination of other crystalline phase contents. If alpha-tricalcium phosphate (alpha-TCP) is found, it should be indicated in the report.

4.2.4 Single-phase beta-tricalcium phosphate substitute

The content of beta-tricalcium phosphate should not be lower than 95% of the crystalline phase.

The formula for calculating the content of beta-tricalcium phosphate is shown in formula (2). MFbeta-TCP=100%-MFHA (2)

If the HA content is below the detection threshold, the HA content should be considered zero.

Qualitative determination of other crystal phases. If alpha-tricalcium phosphate (alpha-TCP) is found, it should be indicated in the report.

If other crystal phases are present, they should be determined by infrared spectroscopy (FTIR) in accordance with ISO 13779-3.

4.3 Shape and size

The physical shape of the bone substitute, such as granules or lumps, should be indicated. Product size specifications should be determined as follows.

---Block size;

---Particle size. The particle size is determined according to the laser diffraction method of ISO 13320 or the screening method of ISO 2591-1. Laser should be marked Diffraction method parameters D10, D50, D90 or screening method for particle minimum and maximum size.

The volume of the bone substitute should be indicated on the package.

4.4 Porosity

4.4.1 Total porosity

The minimum and maximum porosity of the bone substitute should be indicated and calculated according to equation (3).

- 100% ÷ (3) In the formula. P --- porosity, %;

Dr --- Use a minimum volume of 2cm³ of cuboid bone substitute to determine its size and quality. The balance accuracy of the measured mass is 0.02g, the caliper accuracy of the measured size is at least 0.02mm. Volume of bone substitute (V) according to measured size The result is calculated. The calculation of dr is shown in equation (4). (4) For the calculation of dth, see equation (5).

MFHA MFHA MFbeta-TCP dbeta-TCP ·dHA MFbeta-TCP dbeta-TCP MFHA MFbeta-TCP dbeta-TCP ·dbeta-TCP (5)

If the particles are made by massive pulverization, the porosity of the particles should be detected by the above method before the block pulverization. If the particles are not crushed by blocks When made, the porosity of the particles should be measured by mercury intrusion.

4.4.2 Micropore and Macropore Dimensions

4.4.2.1 Micropores

In order to meet the metallographic cutting of the material, the material can be cut after resin embedding.

Determining the micro-aperture should be one of the methods described in ISO 13383-1 for micropores only, ie scanning electron microscopy of a section of the material The diameter of the micropores was measured in the sheet. When the holes are in contact with each other, an imaginary hole boundary should be drawn and the size measured.

4.4.2.2 Macro hole

4.4.2.2.1 General

Determining the macropore aperture can be measured using Method A or Method B.

4.4.2.2.2 Method A. Scanning Electron Microscopy (SEM)

In order to meet the metallographic cutting of the material, the material can be cut after resin embedding.

Determining the macro aperture should be one of the methods described in ISO 13383-1 for macro holes only, ie scanning electron microscopy of a section of the material The diameter of the hole is measured in the sheet. When the holes are in contact with each other, an imaginary hole boundary should be drawn and the size measured.

4.4.2.2.3 Method B. Micro-focus CT detection

Micro-focus CT can visually display three-dimensional structures (hole shape, wall thickness, uniformity and homogeneity), porosity and pore size distribution.

Porosity is measured by three-dimensional analysis and calculation by measuring micro-focus CT images of several fields of view (FOV, diameter 3mm and height 1.5mm).

The average and standard deviation of the porosity are obtained. The pore size distribution map is plotted by calculating the number of holes in each set of aperture ranges. Recommended image resolution The sample size was 5 mm in diameter and 10 mm in height, which was 6 µm/pixel.

4.4.3 Internal connection

The holes should basically be open and interoperable. The internal connection diameter between the holes shall be determined in accordance with the pressure mercury method of ISO 15901-1.

The principle of the method is to pressurize the mercury into the pores of the sample by changing the pressure. When the pressure is low, the mercury will pass through the larger internal connection, while the high pressure mercury Will pass through a smaller internal connection. The amount of mercury infiltrated into the sample is the volume of the communicating hole in the sample, and the applied pressure is closely related to the inner connecting diameter. Related.

The main peak of mercury infiltration can determine the internal connection diameter, and the amount of all pores with an internal diameter greater than 5 µm should be determined.

Microfocus CT images include 2D and 3D reconstructed images, which provide complementary information, especially in materials with a connection diameter greater than 100 µm When the mercury intrusion method is limited.

Other accepted test methods can also be used for testing the inner connecting diameter.

Specimens with a porosity tolerance greater than ±2% should be tested for the lowest and highest porosity samples.

4.5 Dissolution and pH changes

Although the mechanism of external dissolution of bone substitutes is different from that of in vivo degradation, in vitro dissolution rates are still used to compare the body of different bone substitutes.

Absorptive capacity. Significant changes in pH after implantation can impair bone conduction on the surface of the bone substitute. The purpose of the following test is to measure bone replacement The in vitro dissolution rate of the substance and the pH of the dissolution medium.

The dissolution and dissolution rate of the material should be checked. Three bone substitute samples were placed at (37 ± 1) ° C and pH = 7.3 ± 0.1 TRIS buffer In the liquid, the shaker was loaded at a speed of 200 r/min for 24 h, 48 h and 72 h, respectively. The dissolution rate should be between the initial material mass and the dissolved medium body.

The ratio of the mass of the test material to the volume of the dissolved medium should be 0.1 mg/mL to 4.0 mg/mL as measured under a constant ratio.

The pH was measured after soaking for 0, 24 h, 48 h and 72 h, and the pH change should not exceed 0.3 of the initial value.

The calcium content of the solution should be determined by ICP/AES or AAS or ICP/MS or ion probe methods, and the concentration and time should be plotted. Relationship lines.

4.6 Material mechanical strength measurement

4.6.1 General

The mechanical strength of the bulk bone substitute should be measured by the ball indentation test (see Figure 1) and/or the compressive strength test (see Figure 2).

The mechanical strength measurement of bone substitutes with high porosity (porosity >= 40%) should be tested by ball indentation.

Although the compressive strength test can replace the ball indentation test, the high porosity material ball indentation test is a highly repetitive cycle test method. Description. 1---pressurized column; 2---sphere; 3---sample; 4---Base.

Figure 1 Schematic diagram of ball indentation test Description. 1---pressurized column; 2---sample; 3--- base.

Figure 2 Schematic diagram of compressive strength test Low porosity (porosity < 40%) bone substitute should be measured by compressive strength test.

4.6.2 Instruments, sampling and samples

4.6.2.1 Instrument

4.6.2.1.1 Testing machine

The testing machine shall ensure that the compression force acting on the specimen is constant and that the maximum load applied can be recorded with an accuracy of To 1%.

4.6.2.1.3 Pressurized column

The steel of the sample pressurization column has a hardness of 300 HV or higher (>=30HRC), a thickness of at least 10 mm, and a surface area of at least a sample cross section.

4 times the face. The Ra roughness of the contact surface between the pressurized column and the sample does not exceed 0.40 µm, and the parallelism does not exceed 0.01 mm.

The pressurized column of the ball indentation test shall be designed such that the sphere is centered on the axis of the pressurized column.

4.6.2.1.4 Base

The hardness of the base steel on which the sample is placed is 300 HV or higher (>=30HRC), the thickness should be not less than 10 mm, and the surface area is at least a sample.

4 times the cross section. The Ra roughness of the contact surface with the specimen does not exceed 0.40 µm, and the parallelism does not exceed 0.01 mm.

4.6.2.2 Procedure

4.6.2.2.1 General

For porosity tolerances greater than ±2%, the highest and lowest porosity samples shall be tested for compressive strength.

4.6.2.2.2 Soaking method

Phosphate buffer without calcium and magnesium should be used as the soaking solution.

The sample is immersed in PBS(-) in a vacuum pumped vacuum environment. The amount of PBS(-) should be at least 10 times the sample volume, standard vacuum.

The degree should be 2 x 10^3Pa~3 x 10^3Pa, soaking time (24±1)h, temperature (25±3)°C. The sample should be wiped with water before testing. Alternatively, the test can be carried out under dry conditions.

4.6.2.2.3 Sample placement and loading method

The specimen shall be placed in the center of the base, and the longitudinal axes of the base, specimen, sphere and pressurized column shall be aligned along the loading line. The loading speed was (0.5 ± 0.05) mm/min.

The load data should be fully recorded from the beginning of the test to the damage of the sample.

In the ball indentation test, the sample indentation size should be smaller than the diameter of the cylinder or the length and width of the cube.

In the compression test, the rectangular test piece (see 4.6.2.4.1) shall have a force surface of 10 mm × 10 mm.

4.6.2.2.4 Reuse of pressurized column, pedestal and sphere

When the pressurized column, pedestal, and sphere are reused, the contact surface should be carefully inspected before use. Cannot be removed if there is a depression or defect This part must not be used anymore.

4.6.2.3 Ball indentation test

4.6.2.3.1 Sampling and sample

The amount of sample should be at least 10.

The specimen is usually cylindrical and the standard size should be diameter (10.0 ± 0.1) mm and height (10.0 ± 0.1) mm. The sample can also be long (10.0 ± 0.1) mm cube. The parallelism between the upper and lower sides of the sample shall not exceed 0.1 mm. The verticality of the upper and lower sides of the specimen shall be Not more than 0.1mm.

The diameter or surface diagonal of the specimen should be greater than 10 times the maximum pore size of the specimen. If the sample size is different from the standard, it should be in the report. Marked.

4.6.2.3.2 Test results

In the ball indentation test, the load displacement curve should be drawn from the beginning of the test to the crack of the sample, and the most load-displacement curve of each sample is recorded. Large load and maximum load displacement.

The maximum load (PSi) should be the ball indentation strength (in Newtons, N). The average value of the ball indentation strength and the standard deviation calculation method should be Equations (6) and (7) should be rounded to significant figures. PSi (6) (􀭺PS-PSi)2 N-1 (7) In the formula. 􀭺PS --- average compressive load in Newtons (N); PSi --- Indentation load per sample, in Newtons (N);

SDS---standard deviation of compressive load, in Newton (N); n --- number of samples.

4.6.2.4 Compressive strength test

4.6.2.4.1 Sampling and sample

The amount of sample should not be less than 10.

The sample is typically a cylinder of diameter (10.0 ± 0.1) mm and height (15.0 ± 0.1) mm. The sample can also be long (10.0 ± 0.1) mm, Standard cuboids of width (10.0 ± 0.1) mm and height (15.0 ± 0.1) mm. The parallelism between the upper and lower sides of the sample shall not exceed 0.1 mm. test The verticality of the upper and lower sides of the sample should be no more than 0.1mm.

The diameter or surface diagonal of the specimen should be greater than 10 times the maximum pore size of the specimen. If the sample size is different from the standard, it should be in the report. Marked.

4.6.2.4.2 Test results

In the compressive strength test, the load displacement curve should be drawn from the beginning of the test to the fracture of the sample. Should be recorded in each load and displacement curve Maximum load and maximum load displacement.

The maximum load (PCi) is used to calculate the compressive strength, see equation (8). (8) In the formula.

sigmaCi --- compressive strength of the sample, the unit is Pa (Pa); PCi---the maximum load per test, in Newtons (N);

Ai --- The area of force per sample, in square meters (m2).

When the sample is a cylinder, the calculation method of Ai should be based on equation (9).

- ·delta2i (9) In the formula. deltai---The diameter of each sample, in meters (m).

When the sample is a cube, the calculation method of Ai should be based on equation (10). In the formula. Ii---the square length of each sample square, in meters (m).

The average value and standard deviation of compressive strength shall be calculated according to formula (11) and formula (12), and shall be rounded up according to ISO 80000-1. Enter a valid number. sigmaCi (11) (􀭰sigmaC-sigmaCi)2 N-1 (12) ...