A 3D printing bone material and its preparation method

Abstract

The present invention discloses a 3D printing bone material and a preparation method thereof, belonging to the technical field of biomedical materials. In terms of parts by weight, the 3D printing bone material comprises the following raw materials: 50-70 parts of bovine bone powder, 8-15 parts of polyetheretherketone, 3-6 parts of methacrylamide gelatin, 5-10 parts of β-tricalcium phosphate, and 4-10 parts of a biological adhesive. The 3D printing bone material provided by the present invention uses bovine bone powder and polyetheretherketone in combination as the main raw materials for 3D printing, supplemented with methacrylamide gelatin, β-tricalcium phosphate, and a biological adhesive in appropriate proportions, to obtain a 3D printing bone material with excellent biocompatibility and the characteristics of promoting osteogenesis, osteoinduction, and osteoconduction, overcoming the biological inertness between polyetheretherketone materials and bone tissues, and providing a new way for the application of polyetheretherketone materials and bovine bone powder in the field of bone graft materials.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a 3D printing bone material and a preparation method thereof. Background Art

[0002] Currently, 3D printing bone materials include autologous bone, titanium metal, artificial ceramics, and bone made from a mixture of xenogeneic bone powder and biological glue. However, due to the need to consider material tissue compatibility and biodegradability when implanted into the human body, the available material sources are limited.

[0003] Polyetheretherketone (PEEK) is a semi-crystalline, high-performance polymer material approved for bone grafting by the U.S. Food and Drug Administration. However, PEEK suffers from bioinertness with bone tissue, significantly limiting its clinical application. Summary of the invention

[0004] The purpose of the present invention is to provide a 3D printing bone material and a preparation method thereof to solve the technical problem of biological inertness between existing polyetheretherketone materials and bone tissue.

[0005] In a first aspect, an embodiment of the present application provides a 3D printing bone material, wherein the 3D printing bone material comprises the following raw materials, measured in parts by weight:

[0006] 50-70 parts of bovine bone powder, 8-15 parts of polyetheretherketone, 3-6 parts of methacrylamide gelatin, 5-10 parts of beta-tricalcium phosphate and 4-10 parts of bioadhesive.

[0007] Furthermore, the ratio X of the weight of the bovine bone powder to the weight of the methacrylamide gelatin, and the ratio Y of the weight of the polyetheretherketone to the weight of the methacrylamide gelatin satisfy the relationship formula 1;

[0008] The first relationship is: 7≤XY≤15.

[0009] Furthermore, the 3D printing bone material comprises, in parts by weight:

[0010] 60-65 parts of bovine bone powder, 10-12 parts of polyetheretherketone, 5 parts of methacrylamide gelatin, 5-10 parts of beta-tricalcium phosphate and 4-10 parts of bioadhesive.

[0011] Furthermore, the bioadhesive is composed of sodium alginate, chitosan and polylactic acid in a weight ratio of (1-3):(2-5):1.

[0012] Furthermore, the 3D printing bone material further comprises, by weight: 0.01 to 0.05 parts of a catalyst-type curing agent and 8 to 10 parts of a solvent.

[0013] Further, the catalyst-type curing agent includes at least one of stannous octoate and dibutyltin dilaurate; the solvent includes at least one of 1,2,3-propanetriol and N-methylpyrrolidone.

[0014] In a second aspect, the embodiments of the present application provide a preparation method of the 3D printing bone material described in the first aspect, and the preparation method includes:

[0015] Obtain bovine bone powder;

[0016] Knead the bovine bone powder and β-tricalcium phosphate, and then grind to obtain a first mixture;

[0017] Perform first stirring and mixing on the first mixture, methacrylamide gelatin, polyetheretherketone, bioadhesive and solvent to obtain a second mixture;

[0018] Add the catalyst-type curing agent to the second mixture and perform second stirring and mixing to obtain a third mixture;

[0019] Remove the solvent from the third mixture, then perform vacuum drying and grinding to obtain the 3D printing bone material.

[0020] Further, the step of obtaining the bovine bone powder includes:

[0021] Cook fresh bovine bone, then perform water washing, drying and segmentation to obtain bovine bone particles;

[0022] Perform degreasing treatment and deantigen treatment on the bovine bone particles, then carbonize at 650°C to 800°C for 0.5 to 1.5 h, and pulverize to obtain bovine bone powder.

[0023] Further, the step of kneading the bovine bone powder and β-tricalcium phosphate in a closed manner, and then grinding to obtain a first mixture includes:

[0024] Add the bovine bone powder and β-tricalcium phosphate to a kneading torque rheometer for kneading, then take out and cool and grind to obtain a first mixture;

[0025] Among them, the working parameters of the kneading torque rheometer include: the rotation speed is 2800 to 3200 rpm, the temperature is 75°C to 90°C, and the kneading time is 8 to 12 minutes.

[0026] Further, the working parameters of the first stirring and mixing include: the temperature is 35°C to 40°C, the rotation speed is 400 to 600 rpm, and the duration is 15 to 60 min; the working parameters of the second stirring and mixing include: the temperature is 40°C to 50°C, the rotation speed is 800 to 900 rpm, and the duration is 10 to 20 min.

[0027] Compared with the prior art, the above solution provided by the embodiment of the present application has at least the following beneficial effects:

[0028] An embodiment of the present application provides a 3D printing bone material. The 3D printing bone material uses bovine bone powder and polyetheretherketone as the main raw materials for 3D printing, supplemented by appropriately proportioned methacrylamide gelatin, β-tricalcium phosphate and bioadhesives, to obtain a 3D printing bone material with excellent biocompatibility and properties of promoting osteogenesis, osteoinduction and osteoconduction. This overcomes the biological inertness between polyetheretherketone materials and bone tissue, and provides a new approach for the application of polyetheretherketone materials and bovine bone powder in the field of bone transplant materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without paying any creative work.

[0030] Figure 1 A flow chart of a method for preparing 3D printed bone materials provided in an embodiment of the present invention. DETAILED DESCRIPTION

[0031] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0032] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below with reference to specific embodiments.

[0033] The overall idea of the technical solution provided by the embodiment of the present invention is as follows:

[0034] In a first aspect, an embodiment of the present application provides a 3D printing bone material, wherein the 3D printing bone material comprises the following raw materials, measured in parts by weight:

[0035] 50-70 parts of bovine bone powder, 8-15 parts of polyetheretherketone, 3-6 parts of methacrylamide gelatin, 5-10 parts of beta-tricalcium phosphate and 4-10 parts of bioadhesive.

[0036] The present application provides a 3D printing bone material, and the functions of each component are as follows:

[0037] Bone meal: Bone meal has good biocompatibility with biological tissues, achieves good bone ingrowth and bone integration with the surrounding bone tissues, is beneficial to improving the biocompatibility of 3D printed bone materials, and is beneficial to reducing the biological inertness existing between pure polyetheretherketone materials and bone tissues.

[0038] Polyetheretherketone: The Young's modulus and density of polyetheretherketone are closer to those of the native bone itself, regulating the mechanical properties of pure bone meal, making the mechanical properties of 3D printed bone materials more matched with those of the native bone, and at the same time can effectively reduce the stress shielding effect and prevent bone loss.

[0039] Methacrylamide gelatin: Methacrylamide gelatin contains a large amount of arginine-glycine-aspartic acid peptides, which can effectively bind tightly to integrins on the cell membrane, promote cell adhesion, contribute to cell ingrowth, and reconstruct and generate new tissues, thereby improving the osteoinductive ability and bone regeneration ability of 3D printed bone materials; at the same time, it also has good biocompatibility and crosslinking ability, which helps to improve the synergistic effect between bone meal and polyetheretherketone.

[0040] β-tricalcium phosphate: β-tricalcium phosphate has excellent biocompatibility. When implanted into the human body, it directly fuses with the bone after implantation into the body, without any local inflammatory reaction or systemic toxic and side effects. At the same time, when used in combination with bone meal, it enhances the bone regeneration ability of bone meal and is beneficial to the growth of new bone.

[0041] Bioadhesive: It improves the adhesion of the material, helps the components and structures to act synergistically, makes the comprehensive performance of the material better, and is suitable for processing and forming during 3D printing.

[0042] Therefore, the present invention uses bone meal and polyetheretherketone in combination as the main raw materials for 3D printing, supplemented by methacrylamide gelatin, β-tricalcium phosphate and bioadhesive with appropriate ratios. The components synergize with each other and jointly act to obtain a 3D printed bone material with excellent biocompatibility and characteristics of promoting osteogenesis, osteoinduction and osteoconduction, overcoming the biological inertness existing between polyetheretherketone materials and bone tissues, and providing a new way for the application of polyetheretherketone materials and bone meal in the field of bone graft materials.

[0043] As an implementation manner of an embodiment of the present application, the ratio X of the weight parts of the bone meal to the weight parts of the methacrylamide gelatin and the ratio Y of the weight parts of the polyetheretherketone to the weight parts of the methacrylamide gelatin satisfy relationship one;

[0044] Relationship one: 7 ≤ X - Y ≤ 15.

[0045] It is found through research in this application that when bovine bone powder and polyetheretherketone are used in combination as the main raw materials for 3D printing, the bio-inertia existing between the pure polyetheretherketone material and bone tissue cannot be effectively reduced. However, adding an appropriate amount of methacrylamide gelatin can significantly improve the synergistic effect between bovine bone powder and polyetheretherketone. Further, through dosage screening experiments, it is found that when the dosage of bovine bone powder and polyetheretherketone satisfies relationship one with the dosage of methacrylamide gelatin as the standard, the comprehensive performance of the 3D printed bone material is better.

[0046] As an implementation manner of an embodiment of this application, by weight, the 3D printed bone material includes:

[0047] 60 - 65 parts of bovine bone powder, 10 - 12 parts of polyetheretherketone, 5 parts of methacrylamide gelatin, 5 - 10 parts of β-tricalcium phosphate, and 4 - 10 parts of bioadhesive.

[0048] Preferably, by weight, the 3D printed bone material includes:

[0049] 60 - 65 parts of bovine bone powder, 10 - 12 parts of polyetheretherketone, 5 parts of methacrylamide gelatin, 5 - 10 parts of β-tricalcium phosphate, and 4 - 10 parts of bioadhesive.

[0050] More preferably, by weight, the 3D printed bone material includes:

[0051] 64 parts of bovine bone powder, 12 parts of polyetheretherketone, 5 parts of methacrylamide gelatin, 7 parts of β-tricalcium phosphate, and 7 parts of bioadhesive.

[0052] As an implementation manner of an embodiment of this application, the bioadhesive is composed of sodium alginate, chitosan, and polylactic acid with a weight ratio of (1 - 3):(2 - 5):1.

[0053] This application selects a bioadhesive composed of sodium alginate, chitosan, and polylactic acid with a weight ratio of (1 - 3):(2 - 5):1, and the obtained 3D printed bone material has better comprehensive performance. In some specific embodiments, the weight ratio of sodium alginate, chitosan, and polylactic acid can be 1:2:1, 1:3:1, 1:4:1, 1:5:1, 2:2:1, 2:3:1, 2:4:1, 2:5:1, 3:2:1, 3:3:1, 3:4:1, 3:5:1, etc., and preferably 2:5:1.

[0054] As an implementation manner of an embodiment of this application, by weight, the 3D printed bone material further includes: 0.01 - 0.05 parts of catalyst-type curing agent and 8 - 10 parts of solvent.

[0055] This application uses a catalyst-type curing agent to control the degradation rate of the 3D printed bone material, which matches the degradation rate of natural human bone; meanwhile, it enhances the effect of the bioadhesive.

[0056] As an implementation manner of an embodiment of this application, the catalyst-type curing agent includes at least one of stannous octoate and dibutyltin dilaurate; the solvent includes at least one of 1,2,3-propanetriol and N-methylpyrrolidone.

[0057] In some specific embodiments, the catalyst-type curing agent may be composed of stannous octoate and dibutyltin dilaurate with a weight ratio of (1-3):(1-2); the solvent may be composed of 1,2,3-propanetriol and N-methylpyrrolidone with a volume ratio of 1:1.

[0058] In a second aspect, an embodiment of this application provides a preparation method of the 3D printed bone material described in the first aspect, as Figure 1 shown, the preparation method includes:

[0059] Obtain bovine bone powder;

[0060] Knead the bovine bone powder and β-tricalcium phosphate, and then grind to obtain a first mixture;

[0061] First stir and mix the first mixture, methacrylamide gelatin, polyetheretherketone, bioadhesive and solvent to obtain a second mixture;

[0062] Add the catalyst-type curing agent to the second mixture and perform a second stirring and mixing to obtain a third mixture;

[0063] Remove the solvent from the third mixture, then perform vacuum drying and grinding to obtain the 3D printed bone material.

[0064] An embodiment of this application provides a preparation method of the 3D printed bone material described in the first aspect. This preparation method first kneads bovine bone powder and β-tricalcium phosphate to obtain a bovine bone powder / β-tricalcium phosphate composite, enhances the bone regeneration ability of the bovine bone powder, is beneficial to the growth of new bone, and realizes the modification treatment of the bovine bone powder; then through stirring and mixing with other components and post-treatments such as solvent removal, vacuum drying, and grinding, the 3D printed bone material is finally obtained. The operation is simple and is beneficial to industrial production. At the same time, since this preparation method adopts some or all of the technical solutions of the 3D printed bone material described in the first aspect above, it at least has all the beneficial effects brought by the technical solutions of the above embodiments, and will not be elaborated here one by one.

[0065] As an implementation manner of an embodiment of this application, the step of obtaining bovine bone powder includes:

[0066] Steam the fresh bovine bones, then wash, dry and cut them to obtain bovine bone particles.

[0067] Perform degreasing and deantigenization treatments on the bovine bone particles, then carbonize them at 650°C to 800°C for 0.5 to 1.5 hours, and pulverize to obtain bovine bone powder.

[0068] In this application, by steaming, degreasing and deantigenizing the fresh bovine bones, their biocompatibility is improved; further, a porous carbonized structure is formed by carbonization, which is beneficial for the composite modification with β-tricalcium phosphate.

[0069] In some specific embodiments, the degreasing and deantigenization treatments can adopt common treatment methods in the art. For example, soak the bovine bone particles in acetone solution for 12 hours, take them out and soak them in ether for 5 hours after the acetone volatilizes to achieve degreasing, and place them in hydrogen peroxide solution with a concentration of 8% to 10% for 5 hours after degreasing to achieve deantigenization.

[0070] As an implementation manner of the embodiment of this application, the step of hermetically kneading the bovine bone powder and β-tricalcium phosphate and then grinding to obtain the first mixture includes:

[0071] Add the bovine bone powder and β-tricalcium phosphate into a kneading torque rheometer for kneading, then take it out, cool and grind to obtain the first mixture;

[0072] Among them, the working parameters of the kneading torque rheometer include: rotation speed of 2800 to 3200 rpm, temperature of 75°C to 90°C, and kneading time of 8 to 12 minutes.

[0073] In some specific embodiments, the working rotation speed of the kneading torque rheometer can be 2800 rpm, 2900 rpm, 3000 rpm, 3100 rpm, 3200 rpm, etc., the working temperature can be 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, etc., and the kneading time can be 8 minutes, 9 minutes, 10 minutes, 11 minutes, 12 minutes, etc.

[0074] As an implementation manner of the embodiment of this application, the working parameters of the first stirring and mixing include: temperature of 35°C to 40°C, rotation speed of 400 to 600 rpm, and duration of 15 to 60 min; the working parameters of the second stirring and mixing include: temperature of 40°C to 50°C, rotation speed of 800 to 900 rpm, and duration of 1 to 20 min.

[0075] Preferably, the working parameters of the first stirring and mixing include: temperature of 35°C, rotation speed of 500 rpm, and duration of 20 min; the working parameters of the second stirring and mixing include: temperature of 45°C, rotation speed of 850 rpm, and duration of 15 min.

[0076] The features and properties of the present invention will be further described in detail below in conjunction with the embodiments.

[0077] Examples 1-7 provide a 3D printing bone material. In parts by weight (unit: g), the 3D printing bone material comprises the following raw materials:

[0078] 50-70 parts of bovine bone powder, 8-15 parts of polyetheretherketone, 3-6 parts of methacrylamide gelatin, 5-10 parts of β-tricalcium phosphate, 4-10 parts of bioadhesive, 0.01-0.05 parts of catalyst-type curing agent, and 8-10 parts of solvent.

[0079] The specific dosages of each component in Examples 1-7 are shown in Table 1. Among them, the bioadhesive in Example 1 is chitosan, the bioadhesive in Example 2 is sodium alginate, and the bioadhesive in Examples 3-7 is composed of sodium alginate, chitosan, and polylactic acid in a weight ratio of 2:5:1; the catalyst-type curing agent in Examples 1-7 is composed of stannous octoate and dibutyltin dilaurate in a weight ratio of 1:2; the solvent in Examples 1-7 is composed of 1,2,3-glycerol and N-methylpyrrolidone in a volume ratio of 1:1; X is the ratio of the weight parts of bovine bone powder to the weight parts of methacrylamide gelatin, and Y is the ratio of the weight parts of polyetheretherketone to the weight parts of methacrylamide gelatin.

[0080] Table 1

[0081]

[0082]

[0083] The preparation method of the 3D printing bone material provided in the above Examples 1-7 comprises the following steps:

[0084] Cook fresh bovine bone, then wash, dry, and divide it to obtain bovine bone particles;

[0085] Perform degreasing treatment and deantigen treatment on the bovine bone particles, then carbonize them at 700°C for 1 h, and pulverize to obtain bovine bone powder;

[0086] Add the bovine bone powder and β-tricalcium phosphate into a kneading torque rheometer for kneading, then take out, cool and grind to obtain a first mixture; wherein, the working parameters of the kneading torque rheometer include: rotation speed of 3000 rpm, temperature of 85 °C, and kneading time of 10 minutes;

[0087] Perform first stirring and mixing on the first mixture, methylacrylamide gelatin, polyetheretherketone, bioadhesive and solvent to obtain a second mixture; wherein, the working parameters of the first stirring and mixing include: temperature of 35 °C, rotation speed of 500 rpm, and duration of 20 min;

[0088] Add a catalyst-type curing agent into the second mixture for second stirring and mixing to obtain a third mixture; wherein, the working parameters of the second stirring and mixing include: temperature of 45 °C, rotation speed of 850 rpm, and duration of 15 min;

[0089] Remove the solvent from the third mixture, then perform vacuum drying and grinding to obtain a 3D printing bone material.

[0090] Comparative Example 1

[0091] This example provides a 3D printing bone material and its preparation method, and the difference from Example 7 is only that: the dosage of methylacrylamide gelatin is adjusted to 0 g (i.e., methylacrylamide gelatin is not added); the remaining steps and parameters are the same.

[0092] Test Example

[0093] In this example, the 3D printing bone materials obtained in Examples 1-7 are respectively used by a 3D printer to print artificial bones for relevant detections such as biocompatibility, and the detection results are shown in Table 2.

[0094] Table 2

[0095]

[0096] Note: The industry standards for artificial bone materials are as follows: heavy metal content (ug / g) < 50, cytotoxicity (MTT method) ≤ Grade 1, hemolysis rate of the leaching solution < 5.0%, sensitization reaction: none.

[0097] In addition, in this example, the 3D printing bone material obtained in Comparative Example 1 is used by a 3D printer to print an artificial bone for detecting the hemolysis rate of the leaching solution, and the detection result of the hemolysis rate of the leaching solution > 5.0%, which does not meet the industry standard.

[0098] In summary, the embodiments of the present application provide a 3D printing bone material. The 3D printing bone material uses bovine bone powder and polyetheretherketone in combination as the main raw materials for 3D printing, supplemented with methylacrylamide gelatin, β-tricalcium phosphate, and a biological adhesive in appropriate ratios, resulting in a 3D printing bone material that has excellent biocompatibility and promotes osteogenesis, osteoinduction, and osteoconduction characteristics, overcoming the biological inertness between polyetheretherketone materials and bone tissue, and providing a new approach for the application of polyetheretherketone materials and bovine bone powder in the field of bone graft materials.

[0099] The various embodiments of the present application may exist in the form of a range; it should be understood that the description in the form of a range is only for convenience and brevity and should not be construed as a rigid limitation on the scope of the present application; therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and individual values within that range. For example, it should be considered that the range description from 1 to 6 has specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and individual numbers within that range, such as 1, 2, 3, 4, 5, and 6, regardless of the range. Additionally, whenever a numerical range is indicated herein, it means including any cited number (fraction or integer) within the indicated range.

[0100] Furthermore, in the description of the specification of the present application, terms such as "including" and "comprising" mean "including but not limited to". In this document, relational terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations.

[0101] The embodiments described above are some, but not all, of the embodiments of the present invention. The detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely represents selected embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts fall within the scope of protection of the present invention.

Claims

1. A 3D printing bone material, characterized in that, The 3D printing bone material, by weight parts, comprises: 64 parts of bovine bone powder, 12 parts of polyetheretherketone, 5 parts of methacrylamide gelatin, 7 parts of β-tricalcium phosphate, 7 parts of bioadhesive, 0.02 parts of catalyst-type curing agent, and 9 parts of solvent; The bioadhesive is composed of sodium alginate, chitosan, and polylactic acid in a weight ratio of 2:5:1; The catalyst-type curing agent is composed of stannous octoate and dibutyltin dilaurate in a weight ratio of 1:2; The solvent is composed of 1,2,3-glycerol and N-methylpyrrolidone in a volume ratio of 1:1; The preparation method of the 3D printing bone material comprises the following steps: Steaming fresh bovine bone, followed by water washing, drying, and segmentation to obtain bovine bone particles; Performing degreasing treatment and deantigen treatment on the bovine bone particles, then carbonizing at 700 °C for 1 h and pulverizing to obtain bovine bone powder; Adding the bovine bone powder and β-tricalcium phosphate into a kneading torque rheometer for kneading, then taking out, cooling, and grinding to obtain a first mixture; wherein, the working parameters of the kneading torque rheometer include: rotation speed of 3000 rpm, temperature of 85 °C, and kneading time of 10 minutes; Performing first stirring and mixing on the first mixture, methacrylamide gelatin, polyetheretherketone, bioadhesive, and solvent to obtain a second mixture; wherein, the working parameters of the first stirring and mixing include: temperature of 35 °C, rotation speed of 500 rpm, and duration of 20 min; Adding the catalyst-type curing agent into the second mixture for second stirring and mixing to obtain a third mixture; wherein, the working parameters of the second stirring and mixing include: temperature of 45 °C, rotation speed of 850 rpm, and duration of 15 min; Removing the solvent from the third mixture, then performing vacuum drying and grinding to obtain the 3D printing bone material.

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