Bone filling material and preparation method thereof

Abstract

The invention provides a bone filling material and a preparation method thereof, and belongs to the technical field of medical materials. The preparation method comprises the following steps: mixing calcium sulfate hemihydrate, magnesium silicate and silicon oxynitride to obtain mixed powder; and mixing the mixed powder with water to obtain paste, and carrying out self-curing reaction and heat treatment on the paste to obtain the bone filling material. Calcium sulfate hemihydrate, magnesium silicate and silicon oxynitride are used as raw materials for compounding to prepare the bone filling material, magnesium, calcium and silicon ions can be released in the degradation process, the ions have a synergistic effect, the activity of osteoblasts can be remarkably improved, and meanwhile favorable conditions are provided for angiogenesis and bone tissue ingrowth. The nitrogen group is introduced, so that the nitrogen group has antibacterial ability, biological activity and antibacterial performance, has injectability, is suitable for minimally invasive surgery, has in-situ self-curing ability after injection, and has excellent performance in the aspect of promoting bone repair and regeneration.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and in particular to a bone filling material and a preparation method thereof. Background Art

[0002] With the aging of the population and the rising incidence of traumatic diseases, the demand for repairing bone defects and bone tissue damage is increasing, especially in the fields of bone tumor resection, traumatic fractures and spinal fusion. The clinical application of bone filling materials is becoming more and more extensive. The ideal bone filling material should have good biocompatibility, osteoinductivity, mechanical properties, and a match between the degradation rate and the new bone formation rate. However, the existing bone filling materials still have many limitations in performance.

[0003] Although traditional bone filling materials such as hydroxyapatite (HA) and calcium phosphate ceramics (CPC) have excellent biocompatibility and bone integration properties, they lack sufficient osteoinductivity and bioactivity, and have limited mechanical properties, especially in applications in high-load areas, which are difficult to meet clinical needs. In addition, their slow degradation rate can easily lead to incoordination between the filling material and the new bone, thus affecting the repair effect. In addition, infection (especially chronic osteomyelitis) is one of the main complications during bone repair, often caused by bacteria such as Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA). These pathogens can form biofilms on the surface of implant materials, leading to chronic inflammation, bone integration failure, and even implant removal. Therefore, biomaterials need to have both antibacterial and osteogenic properties to improve the success rate of bone repair.

[0004] Therefore, the development of bone filling materials with excellent biological activity, suitable mechanical properties and intelligent antibacterial properties has become one of the hot research directions in the field of biomedical materials. Summary of the invention

[0005] The object of the present invention is to provide a bone filling material and a preparation method thereof, so as to solve the problem that the bone filling material in the prior art cannot take into account both antibacterial properties and osteogenic ability.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a method for preparing a bone filling material, comprising the following steps:

[0008] (1) mixing calcium sulfate hemihydrate, magnesium silicate and silicon oxynitride to obtain a mixed powder;

[0009] (2) The mixed powder and water are mixed, and the obtained paste is subjected to a self-curing reaction and a heat treatment to obtain a bone filling material.

[0010] Preferably, in step (1), the mass ratio of the total mass of magnesium silicate and silicon oxynitride to calcium sulfate hemihydrate is 10-50:100.

[0011] Preferably, the mass ratio of magnesium silicate to silicon oxynitride is 1-2:1-2.

[0012] Preferably, in step (2), the mass ratio of the mixed powder to water is 110-150:25-50.

[0013] Preferably, in step (2), the paste is applied to a porous template and then subjected to a self-curing reaction; the pore size of the porous template is 500 to 2000 μm.

[0014] Preferably, in step (2), the temperature of the self-curing reaction is 20 to 60° C., and the time of the self-curing reaction is 3 to 120 hours.

[0015] Preferably, in step (2), the heat treatment temperature is 150-200° C., and the heat treatment time is 1-2 hours.

[0016] The present invention also provides a bone filling material prepared by the above-mentioned method for preparing the bone filling material, wherein the bone filling material has both biological activity and antibacterial properties.

[0017] Beneficial effects of the present invention:

[0018] (1) The present invention uses calcium sulfate hemihydrate, magnesium silicate and silicon oxynitride as raw materials to prepare a composite bone filling material, which can release magnesium, calcium and silicon ions during the degradation process. The ions have a synergistic effect and can significantly improve the activity of osteoblasts, while providing favorable conditions for angiogenesis and bone tissue ingrowth.

[0019] (2) The bone filling material of the present invention has antibacterial ability by introducing nitrogen groups, has both biological activity and antibacterial properties, is injectable, and is suitable for minimally invasive surgical conditions. It can solidify in situ after injection, which can reduce the risk of infection or reinfection during bone repair and has excellent performance in promoting bone repair and regeneration.

[0020] (3) The mechanical and biological properties can also be optimized by adjusting the ratio of magnesium silicate to silicon oxynitride. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a SEM image of the bone filling material prepared in Example 1 magnified 1000 times;

[0022] Figure 2 This is a SEM image of the bone filling material prepared in Example 1 magnified 5000 times;

[0023] Figure 3This is a SEM image of the bone filling material prepared in Example 1 magnified 142900 times;

[0024] Figure 4 This is a SEM image of the bone filling material prepared in Example 1 magnified 69 times;

[0025] Figure 5 This is a SEM image of the bone filling material prepared in Example 1 magnified 243 times;

[0026] Figure 6 The XRD pattern of the bone filling material prepared in Example 1;

[0027] Figure 7 These are the micro-CT scans of the experimental group and the blank control group after the animal osteogenesis experiment, where a1 and a2 are the scans of the blank control group four weeks later, a3 and a4 are the scans of the blank control group eight weeks later, a5 and a6 are the scans of the blank control group twelve weeks later, b1 and b2 are the scans of the experimental group four weeks later, b3 and b4 are the scans of the experimental group eight weeks later, and b5 and b6 are the scans of the experimental group twelve weeks later. DETAILED DESCRIPTION

[0028] The present invention provides a method for preparing a bone filling material, comprising the following steps:

[0029] (1) mixing calcium sulfate hemihydrate, magnesium silicate and silicon oxynitride to obtain a mixed powder;

[0030] (2) The mixed powder and water are mixed, and the obtained paste undergoes a self-curing reaction to obtain a bone filling material.

[0031] In the present invention, the calcium sulfate hemihydrate, magnesium silicate and silicon oxynitride are preferably in the form of submicron or micron powders.

[0032] Magnesium silicate (MgSiO 3 ) and calcium silicate (CaSiO 3 ) is a new silicate-based material that has attracted widespread attention due to its excellent performance in bone repair. Magnesium silicate can release magnesium ions (Mg 2+ ), which can not only significantly promote the proliferation and differentiation of osteoblasts, but also regulate the local acid-base balance, reduce inflammatory response, and improve the bone repair microenvironment. At the same time, magnesium ions have a certain antibacterial effect and can effectively reduce the risk of postoperative infection. Calcium silicate can release calcium ions (Ca 2+ ) and silicon ions (Si 4+ ), enhance osteogenic activity, promote new bone formation, and accelerate angiogenesis, providing a better microenvironment for bone regeneration. The degradation rate of calcium silicate is relatively moderate, which can provide the necessary support and matrix for the growth of bone tissue.

[0033] Silicon oxynitride (SiON) as a bone filling material has excellent biocompatibility and controllable degradation rate. It can slowly release silicon ions and nitrogen species in the body, promote osteoblast proliferation and induce the expression of bone matrix proteins (such as BMP-2, ALP, COL1). Its surface can quickly form an apatite (HAp) layer to improve its bonding ability with the host bone tissue, and is suitable for the repair of dental, craniofacial and long bone defects. In addition, SiON can be compounded with bioceramics (such as hydroxyapatite) or polymers (such as PLGA) to enhance mechanical properties and osteoinductivity, providing a new solution for bone filling materials. The application of silicon oxynitride (SiON) in bone filling materials not only has excellent biocompatibility and osteoinduction ability, but also exhibits certain antibacterial properties. SiON can release reactive nitrogen species (such as NO, NH 4+ ) and Si ions, which have an inhibitory effect on common bone infection pathogens (such as Staphylococcus aureus and Escherichia coli). Among them, nitrogen species can destroy the bacterial membrane structure and cause leakage of cell contents, while Si ions can interfere with the bacterial growth microenvironment and reduce biofilm formation. In addition, SiON can be compounded with antibacterial elements such as silver (Ag), copper (Cu) or zinc (Zn) to further enhance the antibacterial effect, thereby reducing the risk of implant infection and improving the clinical safety and application prospects of bone filling materials.

[0034] The present invention uses calcium sulfate hemihydrate, magnesium silicate and silicon oxynitride as raw materials, and through the composite of magnesium-based and nitrogen-based materials, it can not only combine the advantages of both, but also optimize the mechanical and biological properties by adjusting the ratio and particle morphology of the two materials. During the degradation process of the bone filling material prepared by composite, the released magnesium, calcium and silicon ions can work synergistically, significantly improve the activity of osteoblasts, and provide favorable conditions for angiogenesis and bone tissue growth. In addition, the introduction of nitrogen base can also combine antibacterial ability.

[0035] In the present invention, in step (1), the mass ratio of the total mass of magnesium silicate and silicon oxynitride to calcium sulfate hemihydrate is 10 to 50:100, preferably 20 to 40:100, and more preferably 30:100.

[0036] In the present invention, the mass ratio of magnesium silicate to silicon oxynitride is 1-2:1-2, preferably 1:1.

[0037] In the present invention, in the step (2), the mass ratio of the mixed powder to water is 110-150:25-50, preferably 110-150:30-45, and more preferably 110-150:40.

[0038] In the present invention, in the step (2), the paste is applied to a porous template and then undergoes a self-curing reaction; the pore size of the porous template is 500 to 2000 μm.

[0039] In the present invention, in the step (2), the paste may be subjected to a self-solidification reaction to obtain a block, which may be ground and sieved.

[0040] In the present invention, in step (2), the temperature of the self-curing reaction is 20-60°C, preferably 20°C, 30°C, 40°C, and the time of the self-curing reaction is 3-120h, preferably 3h, 10h, 24h, 120h.

[0041] In the present invention, in step (2), the heat treatment temperature is 150-200°C, preferably 150°C, 180°C, 190°C, and the heat treatment time is 1-2h, preferably 1.5h.

[0042] The present invention also provides a bone filling material prepared by the above-mentioned method for preparing the bone filling material, wherein the bone filling material has both biological activity and antibacterial properties.

[0043] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0044] Example 1

[0045] 100 g of calcium sulfate hemihydrate powder, 15 g of magnesium silicate powder and 15 g of silicon oxynitride powder were placed in a centrifuge tube, and vibrated for 180 seconds using a vibrator to mix to obtain a mixed powder; 40 g of deionized water was added to the mixed powder, and mixed evenly to obtain a paste; the paste was spread into a porous template (pore size of 500-2000 μm), self-cured at 20° C. for 3 hours, and then demolded to obtain initial particles; finally, the initial particles were treated at 150° C. for 1.5 hours to obtain a granular bone filling material, recorded as bone filling material 1.

[0046] Example 2

[0047] 100 g of calcium sulfate hemihydrate powder, 25 g of magnesium silicate powder and 25 g of silicon oxynitride powder were placed in a centrifuge tube, and vibrated for 180 seconds using a vibrator to mix to obtain a mixed powder; 50 g of deionized water was added to the mixed powder, and mixed evenly to obtain a paste; the paste was applied to a porous template (pore size of 500 to 2000 μm), self-cured at room temperature for 120 hours, and then demolded to obtain initial particles. Finally, the initial particles were treated at 155° C. for 1.5 hours to obtain a granular bone filling material.

[0048] Example 3

[0049] 100 g of calcium sulfate hemihydrate powder, 5 g of magnesium silicate powder and 5 g of silicon oxynitride powder were placed in a centrifuge tube, and vibrated for 180 seconds using a vibrator to mix to obtain a mixed powder; 40 g of deionized water was added to the mixed powder, and mixed evenly to obtain a paste; the paste was placed in an oven, and self-cured at 40° C. for 10 hours to obtain a block; the block was ground and sieved (the sieve opening was 500 to 2000 μm), and the sieved particles were treated at 190° C. for 1.5 hours to obtain a granular bone filling material.

[0050] Example 4

[0051] 100 g of calcium sulfate hemihydrate powder, 10 g of magnesium silicate powder and 5 g of silicon oxynitride powder were placed in a centrifuge tube, and vibrated for 180 seconds using a vibrator to mix to obtain a mixed powder; 25 g of deionized water was added to the mixed powder, and mixed evenly to obtain a paste; the paste was placed in an oven, and self-cured at 40° C. for 120 hours to obtain a block; the block was ground and sieved (the sieve opening was 500 to 2000 μm), and the sieved particles were treated at 190° C. for 1.5 hours to obtain a granular bone filling material.

[0052] The granular bone filling material prepared in Example 1 was subjected to in vitro experiments and animal bone formation experiments:

[0053] (1) In vitro experiments

[0054] The isolated human bone marrow mesenchymal stem cells were cultured to the third generation. Bone filling material 1 (experimental group) was placed in a cell culture medium, placed in a 37°C cell culture incubator for 24 hours, and the mixed solution was filtered to obtain the cell culture medium of the experimental group. The culture medium of the control group was ordinary cell culture medium. The cells were divided into two groups and inoculated into 6-well plates respectively. The control group was cultured with ordinary cell culture medium, and the medium was changed every three days; the experimental group was cultured with culture medium filtered from the static liquid, and the medium was changed every three days. After the cells were cultured for 14 days, the two groups of cells were stained with ALP and Alizarin red. The results showed that the osteogenic ability of the cells cultured in the static liquid of the experimental group was stronger, significantly better than that of the control group.

[0055] (2) Animal osteogenesis experiment

[0056] The experiment selected 3-3.5kg New Zealand white rabbits, anesthetized with phenobarbital through the marginal ear vein, fixed to the operating table, and the left knee joint was disinfected and draped. The skin, fascia and muscle were cut layer by layer to expose the femoral condyle. A hole was drilled with a Kirschner wire to form a channel with a length of 1 cm and a diameter of about 0.5 cm. The animals were divided into two groups: one group was the experimental group, which injected bone filling material 1 into the bone defect; the other group was the blank control group, which did not receive treatment after drilling (no particle injection). After 4, 8, and 12 weeks, the femurs were removed and micro-CT scans were performed to detect the bone formation of the experimental group and the blank control group. The experimental results are shown in Figure 7 The experimental group had obvious bone expansion at the bone defect site, and compared with the blank control group, it had obvious advantages in bone defect repair and induction of regeneration.

[0057] It can be seen from the above embodiments that the present invention provides a bone filling material and a preparation method thereof. The present invention mixes calcium sulfate hemihydrate, magnesium silicate and silicon oxynitride to obtain a mixed powder; then the mixed powder is mixed with water, and the obtained paste is subjected to a self-curing reaction and heat treatment to obtain a bone filling material. The present invention uses calcium sulfate hemihydrate, magnesium silicate and silicon oxynitride as raw materials for composite preparation of bone filling materials. During the degradation process, magnesium, calcium and silicon ions can be released. There is a synergistic effect between the ions, which can significantly improve the activity of osteoblasts and provide favorable conditions for angiogenesis and bone tissue growth. By introducing nitrogen groups, it has antibacterial ability, has both biological activity and antibacterial properties, is injectable, is suitable for minimally invasive surgery, can be in situ after injection, and has excellent performance in promoting bone repair and regeneration.

[0058] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a bone filling material, characterized in that: The steps include: (1) mixing calcium sulfate hemihydrate, magnesium silicate and silicon oxynitride to obtain a mixed powder; (2) The mixed powder and water are mixed, and the obtained paste is subjected to a self-curing reaction and a heat treatment to obtain a bone filling material.

2. The method for preparing a bone filling material according to claim 1, characterized in that: In the step (1), the mass ratio of the total mass of magnesium silicate and silicon oxynitride to calcium sulfate hemihydrate is 10 to 50:

100.

3. The method for preparing a bone filling material according to claim 2, characterized in that: The mass ratio of the magnesium silicate to silicon oxynitride is 1-2:1-2.

4. The method for preparing a bone filling material according to any one of claims 1 to 3, characterized in that: In the step (2), the mass ratio of the mixed powder to water is 110-150:25-50.

5. The method for preparing a bone filling material according to claim 4, characterized in that: In the step (2), the paste is applied to a porous template and then undergoes a self-curing reaction; the pore size of the porous template is 500 to 2000 μm.

6. The method for preparing a bone filling material according to claim 1, 2 or 5, characterized in that: In the step (2), the temperature of the self-curing reaction is 20 to 60° C., and the time of the self-curing reaction is 3 to 120 hours.

7. The method for preparing a bone filling material according to claim 6, characterized in that: In the step (2), the heat treatment temperature is 150 to 200° C., and the heat treatment time is 1 to 2 hours.

8. The bone filling material obtained by the method for preparing a bone filling material according to any one of claims 1 to 7, characterized in that: The bone filling material has both biological activity and antibacterial properties.

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