GB/T 41672-2022 English PDF (GBT41672-2022)

This document specifies the technical requirements and test methods for osteoinductive calcium phosphate bioceramics. This document is applicable to osteoinductive calcium phosphate bioceramics for surgical implants.

GB/T 41672-2022
GB
NATIONAL STANDARD OF THE
PEOPLE’S REPUBLIC OF CHINA
ICS 11.040.40
CCS C 35
Implants for Surgery - Osteoinductive Calcium Phosphate
Bioceramics
外科植入物 骨诱导磷酸钙生物陶瓷
ISSUED ON: JULY 11, 2022
IMPLEMENTED ON: AUGUST 1, 2023
Issued by: State Administration for Market Regulation;
Standardization Administration of the People’s Republic of China.
Table of Contents
Foreword ... 3
Introduction ... 4
1 Scope ... 5
2 Normative References ... 5
3 Terms and Definitions ... 6
4 Technical Requirements ... 7
5 Test Methods ... 9
Appendix A (informative) Macropore and Interconnected Pore Structures of Osteoinductive Calcium Phosphate Bioceramics ... 14
Bibliography ... 16
Implants for Surgery - Osteoinductive Calcium Phosphate
Bioceramics
1 Scope
This document specifies the technical requirements and test methods for osteoinductive calcium phosphate bioceramics.
This document is applicable to osteoinductive calcium phosphate bioceramics for surgical implants.
2 Normative References
The contents of the following documents constitute indispensable clauses of this document through the normative references in this text. In terms of references with a specified date, only versions with a specified date are applicable to this document. In terms of references without a specified date, the latest version (including all the modifications) is applicable to this document. GB/T 1480 Metallic Powders - Determination of Particle Size by Dry Sieving GB/T 9724 Chemical Reagent - General Rule for the Determination of pH
GB/T 16886 (all parts) Biological Evaluation of Medical Devices
GB/T 19077 Particle Size Analysis - Laser Diffraction Methods
GB/T 21650.1 Pore Size Distribution and Porosity of Solid Materials by Mercury Porosimetry and Gas Adsorption - Part 1: Mercury Porosimetry
GB/T 23101.3 Implants for Surgery - Hydroxyapatite - Part 3: Chemical Analysis and Characterization of Crystallinity and Phase Purity
YY/T 1447 Implants for Surgery - In Vitro Evaluation for Apatite-forming Ability of Implant Materials
Pharmacopoeia of the People’s Republic of China (4 volumes, Edition 2020) ISO 13383-1:2016 Fine Ceramics (advanced ceramics, advanced technical ceramics) - Microstructural Characterization - Part 1: Determination of Grain Size and Size Distribution 3 Terms and Definitions
The following terms and definitions are applicable to this document.
3.1 Osteoinductivity
Osteoinductivity refers to the phenomenon that mesenchymal cells that can differentiate into various tissue cells are induced to differentiate into osteoblasts or chondroblasts, and finally form bone tissues.
NOTE: whether a material is osteoinductive is usually judged by whether there is new bone tissue formation in the non-bone site (subcutaneous or intramuscular) of the implanted animal. 3.2 Osteoconductivity
Osteoconductivity refers to the phenomenon that bone tissue grows from the implant-bone interface along the surface of the implant or its internal pores, channels or conduits. NOTE: osteoconductivity describes a positive, long-term host response induced by biochemical materials in the bone environment, which is beneficial to accelerate the healing of bone defects and promote the integration between the implant and the original bone. 3.3 Bioceramics
Bioceramics refer to ceramic materials used to achieve specific biological or physiological functions, and can be used to manufacture in vivo repair devices and artificial organs. 3.4 Calcium Phosphate Bioceramics
Calcium phosphate bioceramics refer to a type of bioactive ceramics composed of calcium phosphate that are osteoconductive.
NOTE: it usually refers to hydroxyapatite (HA) ceramics, -tricalcium phosphate (-TCP) ceramics or a composite of the two.
3.5 Osteoinductive Calcium Phosphate Bioceramics
Osteoinductive calcium phosphate bioceramics refer to a type of bioactive ceramics composed of calcium phosphate that are both osteoconductive and osteoinductive.
NOTE: it usually refers to porous complex-phase ceramics composed of hydroxyapatite (HA) and -tricalcium phosphate (-TCP) (HA/-TCP), and other single-phase or complex-phase calcium phosphate ceramics that can induce new bone formation.
3.6 Macropore
Macropore refers to a pore with a diameter of not less than 100 m formed inside the ceramic block or accumulated by particles.
5.1.2.3 Dimensions of granular products: in accordance with the dry sieving method (arbitration method) of GB/T 1480 or the laser diffraction method of GB/T 19077, determine the particle size; the minimum and maximum particle size for the sieving method or the parameters D10, D50 and D90 for the laser diffraction method shall be indicated.
5.2 Physical and Chemical Properties
5.2.1 Atomic ratio of calcium to phosphorus (Ca/P)
In accordance with the stipulations of GB/T 23101.3.
5.2.2 Phase composition and phase content
5.2.2.1 Phase composition: in accordance with the stipulations of GB/T 23101.3. 5.2.2.2 Phase content: in accordance with the stipulations of GB/T 23101.3. 5.2.3 Pore structure
5.2.3.1 Total porosity
The porosity of the material shall be calculated in accordance with Formula (1). Where,
P---the porosity, expressed in (%);
dr---the density of the bioceramics, expressed in (g/cm3);
dth---the theoretical density of the bioceramics, expressed in (g/cm3). When calculating dr, choose a cuboid bone substitute with a minimum volume of 2 cm3, and measure its dimensions and mass. The accuracy of the balance for measuring the mass is 0.02 g, and the accuracy of the Vernier caliper for measuring the dimensions is at least 0.02 mm. The volume of the ceramic is calculated from the measured dimensions. See the calculation formula in Formula (2).
Where,
m---the mass of the ceramic, expressed in (g);
V---the volume of the ceramic, expressed in (cm3).
The formula of calculating dth is shown in Formula (3).
Where,
MFHA---the content of HA (mass fraction), expressed in (%);
MF-TCP---the content of -TCP (mass fraction), expressed in (%);
dHA---the theoretical density of dense HA, take 3.15 g/m3.
d-TCP---the theoretical density of dense -TCP, take 3.07 g/m3.
If the particles are made by block crushing, the porosity of the particles shall be tested by above- mentioned method before block crushing.
If the particles are not made by block crushing, the porosity of the particles shall be tested by the mercury porosimetry in GB/T 21650.1.
5.2.3.2 Macropore diameter
In accordance with the mercury porosimetry (arbitration method) in GB/T 21650.1, or the method described in ISO 13383-1:2016 for macropores, that is, the diameter of the pores is measured in a scanning electron microscope photo of a certain section of the material, conduct the determination. When the pores are in mutual contact, an imaginary pore boundary shall be drawn, then, measure the dimensions.
5.2.3.3 Interconnected pore diameter
In accordance with the mercury porosimetry (arbitration method) in GB/T 21650.1, or other recognized test methods, for example, scanning electron microscope (SEM), etc., conduct the determination. However, the corresponding range of the interconnected pore diameter shall be confirmed in accordance with the characteristics of the corresponding method. 5.2.3.4 Microporosity
Use a cutting machine to randomly cut out a thin slice of the specimen; put the slice in deionized water and ultrasonically clean it, dry it and reserve it for measurement. When determining the micropore diameter, one of the methods only for micropores as described in ISO 13383-1:2016 shall be adopted, that is, to observe the slice with a scanning electron microscope or an optical microscope. When the magnification is 30 times ~ 50 times, after adjusting the image clarity, select a macropore wall that is larger than 100 m, then, magnify the field of view to 3,000 times ~ 10,000 times; respectively observe and measure the size and distribution of the micropores smaller than 10 m on the pore wall; select the field of view and adjust the image clarity for shooting. On the same slice, re-transpose a field of view, and shoot again with the same method.
In accordance with the mercury porosimetry in GB/T 21650.1, determine the microporisity. 5.2.4 Average grain size
In accordance with the stipulations of ISO 13383-1:2016.
5.2.5 pH value
Place 3 ceramic specimens in TRIS buffer solution at (37  1) C and pH = 7.3  0.1; respectively load it on a shaker at 200 r/min for 24 h, 48 h and 72 h. After immersing for 0 h, 24 h, 48 h and 72 h, in accordance with GB/T 9724, measure the pH value. 5.2.6 Trace element content
5.2.6.1 Arsenic
In accordance with the 0822 arsenic salt inspection method in the Pharmacopoeia of the People’s Republic of China (4 volumes, Edition 2020).
5.2.6.2 Cadmium, mercury and lead
In accordance with GB/T 23101.3.
5.2.6.3 Total amount of heavy metal elements
In accordance with the 0821 heavy metal inspection method in the Pharmacopoeia of the People’s Republic of China (4 volumes, Edition 2020).
5.2.6.4 Other trace elements
The determination of other trace elements shall be carried out in accordance with the stipulations of GB/T 23101.3.
5.3 Evaluation of Bone-like Apatite-forming Ability
In accordance with the stipulations of YY/T 1447.
5.4 Biocompatibility Evaluation
In accordance with GB/T 16886 (all parts).
5.5 Evaluation of Osteoinductivity