A hydroxyapatite-based bone implant and a method for producing the same

Abstract

The application relates to a hydroxyapatite-based bone implant and a preparation method thereof, and belongs to the technical field of bone implants; the method comprises the following steps: mixing hydroxyapatite and polyvinyl alcohol to obtain a hydroxyapatite-containing raw material; printing the hydroxyapatite-containing raw material by using 3D printing to obtain a bone implant embryo; and immersing the bone implant embryo in a citric acid aqueous solution to increase the strength of the bone implant embryo, so that the bone implant is obtained; the polyvinyl alcohol can react with a 3D printing jetting liquid, a polyvinyl alcohol film is formed between hydroxyapatite particles, the hydroxyapatite particles are bonded together to form the bone implant embryo, and the immersed citric acid aqueous solution can increase the thickness of the micro-polyvinyl alcohol film and enhance the bonding capacity between the particles, so that the mechanical properties of the sample are enhanced; no serious size shrinkage phenomenon is caused, citric acid is an important component in human bones, and the introduction of citric acid into the implant is beneficial to the growth and reproduction of osteoblasts in the subsequent implantation process.

Description

Technical Field

[0001] This application relates to the field of bone implant technology, and in particular to a hydroxyapatite-based bone implant and its preparation method. Background Technology

[0002] Bone defects place a significant burden on individuals and society. Artificial bone grafts offer an effective solution. Traditional metallic bone implant materials, such as titanium alloys, often face challenges related to low bioactivity and stress shielding risks, potentially requiring subsequent surgical intervention. Hydroxyapatite (HA), a major component of natural human bone, exhibits excellent bioactivity and osseointegration capabilities. Therefore, HA has emerged as a promising material for artificial bone applications. However, traditional processing techniques face challenges in producing custom HA ceramic components for bone implants. In contrast, binder jetting (also known as 3DP) is an additive manufacturing technique that uses a nozzle to selectively deposit liquid binder layer by layer onto powdered materials, achieving gradual accumulation of components. This technique offers advantages such as cost-effectiveness and the absence of support structures, and its room-temperature processing capability makes it particularly suitable for printing brittle bioceramics susceptible to thermal residual stress. However, 3DP technology using traditional binders faces nozzle clogging issues due to binder sedimentation, and because HA itself has extremely low hydrolytic properties, jetting pure deionized water cannot achieve the fabrication of HA bone implants. Printing can be achieved by dispersing a solid binder in HA powder and reacting it with deionized water, but this method often results in low mechanical properties, failing to meet clinical application requirements. Chinese invention patent application CN116218421A discloses a binder for binder-jet additive manufacturing of medical porous titanium-based alloys, its preparation method, and its application. Its composition includes polyvinyl alcohol powder, surfactant, dispersant, and water. However, the problem of low strength remains unresolved.

[0003] To increase strength, commonly used post-treatment strengthening methods such as sintering often lead to dimensional shrinkage, while other non-sintering post-treatment methods may introduce substances harmful to the human body. Summary of the Invention

[0004] This application provides a hydroxyapatite-based bone implant and a method for preparing the same, in order to improve the problem of low strength of hydroxyapatite-based bone implants.

[0005] In a first aspect, this application provides a method for preparing a hydroxyapatite-based bone implant, the method comprising:

[0006] Hydroxyapatite and polyvinyl alcohol are mixed to obtain a hydroxyapatite-containing raw material;

[0007] 3D printing was used to print hydroxyapatite-containing raw materials to obtain bone implant embryos;

[0008] The bone implant embryo is immersed in an aqueous solution of citric acid to increase its strength, thereby obtaining a bone implant.

[0009] As an optional implementation, the citric acid aqueous solution has a citric acid concentration of 3% to 8% by mass.

[0010] As an optional implementation, the mass of the polyvinyl alcohol is 20% to 40% of the hydroxyapatite.

[0011] As an optional implementation, the average particle size of the hydroxyapatite is 20–60 μm.

[0012] As an optional implementation, the average particle size of the polyvinyl alcohol is 20-60 μm.

[0013] As an optional implementation, the degree of alcoholysis of the polyvinyl alcohol is 88% or 99%.

[0014] As an optional implementation, the viscosity of the polyvinyl alcohol is 80–110 mPa·s.

[0015] As an optional implementation, the jetting liquid for 3D printing includes pure deionized water or a deionized water-based liquid containing anhydrous ethanol and / or surfactants.

[0016] As an optional implementation, the mixing method is ball milling; the ball milling speed is 40-200 rpm; the ball milling time is 5-7 hours.

[0017] Secondly, this application provides a hydroxyapatite-based bone implant, which is prepared using the method described in the first aspect.

[0018] The technical solutions provided in this application have the following advantages compared with the prior art:

[0019] The method provided in this application involves polyvinyl alcohol reacting with a 3D printing jet to form a polyvinyl alcohol film between hydroxyapatite particles, thus bonding the hydroxyapatite particles together to form a bone implant embryo. Subsequent immersion in a citric acid aqueous solution increases the thickness of the microscopic polyvinyl alcohol film, enhancing the adhesion between particles and thereby improving the mechanical properties of the sample. Compared to existing sintering processes, this method improves the mechanical strength of the sample without sintering, avoids severe dimensional shrinkage, and, since citric acid is an important component of human bone, introducing it into the implant promotes osteoblast growth and proliferation during subsequent implantation. Attached Figure Description

[0020] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with this application and, together with the description, serve to explain the principles of this application.

[0021] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, for those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1 A flowchart illustrating the method provided in the embodiments of this application;

[0023] Figure 2 A schematic diagram of the process provided for an embodiment of this application. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0025] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in this application can be purchased from the market or prepared by existing methods.

[0026] like Figure 1 As shown in the embodiments of this application, a method for preparing a hydroxyapatite-based bone implant is provided, the method comprising:

[0027] S0. The hydroxyapatite powder and polyvinyl alcohol powder are sieved to a specific size, specifically, the average particle size of the hydroxyapatite is 20-60 μm, and the average particle size of the polyvinyl alcohol is 20-60 μm.

[0028] S1. Hydroxyapatite and polyvinyl alcohol are mixed to obtain a hydroxyapatite-containing raw material.

[0029] In some embodiments, the mass of the polyvinyl alcohol is 20% to 40% of the hydroxyapatite.

[0030] In some embodiments, the degree of alcoholysis of the polyvinyl alcohol is 88% or 99%. The viscosity of the polyvinyl alcohol is 80–110 mPa·s.

[0031] In some embodiments, the mixing method employs ball milling; the ball milling speed is 40–200 rpm; and the ball milling time is 5–7 h.

[0032] Specifically, in this embodiment, 20%-40% polyvinyl alcohol powder is added to hydroxyapatite powder by mass fraction, and the powder is mixed for 6 hours at a speed of 40-200 rpm using a horizontal ball mill to ensure uniform mixing of the powder.

[0033] S2. 3D printing was used to print hydroxyapatite-containing raw materials to obtain bone implant embryos;

[0034] In some embodiments, the jetting fluid for 3D printing comprises purified deionized water or a deionized water-based liquid containing anhydrous ethanol and / or surfactants.

[0035] Specifically, in this embodiment, the obtained mixed powder is added to the binder jet 3D printer as a powder bed, and pure deionized water is used as the jet liquid to complete the preparation of the bone implant embryo through 3D printing.

[0036] S3. Immerse the bone implant embryo in an aqueous citric acid solution to increase the strength of the bone implant embryo, thereby obtaining a bone implant.

[0037] In some embodiments, the citric acid aqueous solution has a citric acid concentration of 3% to 8% by mass.

[0038] Specifically, in this embodiment, after the bone implant embryo has dried, it is removed from the powder bed and allowed to stand. A citric acid aqueous solution is prepared at room temperature, consisting of citric acid and deionized water, with a citric acid concentration of 3%-8%. A certain amount of citric acid solution is dripped into the bone implant embryo using a pipette until every part of the embryo is immersed in the solution. The treated embryo is then allowed to dry, resulting in a bone implant with enhanced mechanical strength. In other embodiments, other methods can be used to achieve the immersion of the citric acid aqueous solution. For example, the process of dripping the citric acid solution into the bone implant embryo can be replaced by soaking the embryo in the citric acid solution for an appropriate time.

[0039] Since hydroxyapatite particles themselves are not hydrolyzable, they cannot be formed in spraying techniques using deionized water as the binder. This method addresses this issue by introducing polyvinyl alcohol (PVA) powder. The PVA powder reacts with deionized water to form a PVA film between the hydroxyapatite particles, binding them together. After the sample dries, the formed PVA film remains, completing the preparation of the hydroxyapatite preform. The subsequent addition of citric acid solution further enhances the adhesion between particles by increasing the thickness of the microscopic PVA film, thereby improving the mechanical properties of the sample.

[0040] Existing post-processing strengthening methods typically employ sintering, which, while improving sample strength, results in severe dimensional shrinkage, failing to meet design dimensions. This new method is simple to operate, eliminates the need for sintering, and improves sample mechanical strength. Furthermore, citric acid is an important component of human bone; introducing it into the implant promotes osteoblast growth and proliferation during subsequent implantation.

[0041] Based on a general inventive concept, embodiments of this application also provide a hydroxyapatite-based bone implant, which is prepared using the method provided above.

[0042] The bone implant is prepared based on the above method. The specific steps of the method can be referred to the above embodiments. Since the bone implant adopts some or all of the technical solutions of the above embodiments, it has at least all the beneficial effects brought about by the technical solutions of the above embodiments, which will not be elaborated here.

[0043] The present application is further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the application. Experimental methods in the following embodiments that do not specify specific conditions are generally determined according to national standards. If there is no corresponding national standard, then general international standards, conventional conditions, or conditions recommended by the manufacturer are followed.

[0044] Example 1

[0045] This embodiment uses a hydroxyapatite-based bone implant manufactured by binder spraying additive manufacturing. The average particle size of both hydroxyapatite and polyvinyl alcohol powder after sieving is 30 μm. The polyvinyl alcohol powder used has a degree of alcoholysis of 88% and a viscosity of 80-110 mPa·s. The mass ratio of polyvinyl alcohol powder to hydroxyapatite powder is 1:3, and the mass concentration of the prepared citric acid solution is 5%.

[0046] The specific preparation process is as follows:

[0047] The sieved hydroxyapatite and polyvinyl alcohol powders were placed in a horizontal ball mill at a mass ratio of 1:3, and the mill speed was set to 70 rpm. A small amount of 1 cm diameter zirconium beads were added to thoroughly mix the powder, and the mixing time was 6 hours. The mixed powder was then added to a binder jet additive manufacturing system, and pure deionized water was used as the jetting fluid for printing. The print thickness was set to 0.1 mm. After printing, the entire powder bed was removed and allowed to stand for 4 hours to fully cure and dry the sample. After curing, the sample was removed, and excess powder on the sample surface was removed using compressed air. Using a pipette, 50 μL of the 5% citric acid solution was added dropwise to the sample each time until every part of the sample was completely immersed. The sample was then allowed to stand and dry.

[0048] Example 2

[0049] This embodiment uses a hydroxyapatite-based bone implant manufactured by binder spraying additive manufacturing. The average particle size of both hydroxyapatite and polyvinyl alcohol powder after sieving is 30 μm. The polyvinyl alcohol powder used has a degree of alcoholysis of 88% and a viscosity of 80-110 mPa·s. The mass ratio of polyvinyl alcohol powder to hydroxyapatite powder is 1:4, and the mass concentration of the prepared citric acid solution is 4%.

[0050] The specific preparation process is as follows:

[0051] The sieved hydroxyapatite and polyvinyl alcohol powders were placed in a horizontal ball mill at a mass ratio of 1:4, and the mill speed was set to 70 rpm. A small amount of 1 cm diameter zirconium beads were added to thoroughly mix the powder, and the mixing time was 6 hours. The mixed powder was then added to a binder jet additive manufacturing system, and pure deionized water was used as the jetting fluid for printing. The print thickness was set to 0.2 mm. After printing, the entire powder bed was removed and allowed to stand for 4 hours to fully cure and dry the sample. After curing, the sample was removed, and excess powder on the sample surface was removed using compressed air. Using a pipette, 50 μL of the 4% citric acid solution was added dropwise to the sample each time until every part of the sample was completely immersed. The sample was then allowed to stand and dry.

[0052] Comparative Example 1

[0053] This comparative example uses a binder-sprayed additive manufacturing process to produce a hydroxyapatite-based bone implant. The average particle size of both the hydroxyapatite and polyvinyl alcohol powders after sieving is 30 μm. The polyvinyl alcohol powder used has a degree of hydrolysis of 88% and a viscosity of 80-110 mPa·s. The mass ratio of polyvinyl alcohol powder to hydroxyapatite powder is 1:3.

[0054] The specific preparation process is as follows:

[0055] The sieved hydroxyapatite and polyvinyl alcohol powders were placed in a horizontal ball mill at a mass ratio of 1:3, and the mill speed was set to 70 rpm. A small amount of 1 cm diameter zirconium beads were added to thoroughly mix the powder, and the mixing time was 6 hours. The mixed powder was then added to a binder jet additive manufacturing system, and pure deionized water was used as the jetting fluid for printing. The print layer thickness was set to 0.1 mm. After printing, the entire powder bed was removed and allowed to stand for 4 hours to fully cure and dry the sample. After curing, the sample was removed, and excess powder on the sample surface was removed using compressed air.

[0056] Comparative Example 2

[0057] This comparative example uses a binder-sprayed additive manufacturing process to produce a hydroxyapatite-based bone implant. The average particle size of both the hydroxyapatite and polyvinyl alcohol powders after sieving is 30 μm. The polyvinyl alcohol powder used has a degree of hydrolysis of 88% and a viscosity of 80-110 mPa·s. The mass ratio of polyvinyl alcohol powder to hydroxyapatite powder is 1:4.

[0058] The specific preparation process is as follows:

[0059] The sieved hydroxyapatite and polyvinyl alcohol powders were placed in a horizontal ball mill at a mass ratio of 1:4, with the mill speed set to 70 rpm. A small amount of 1 cm diameter zirconium beads were added to thoroughly mix the powder, and the mixing time was 6 hours. The mixed powder was then added to a binder jet additive manufacturing system, using purified deionized water as the jetting fluid for printing, with a print layer thickness set to 0.2 mm. After printing, the entire powder bed was removed and allowed to stand for 4 hours to fully cure and dry the sample. After curing, the sample was removed, and excess powder on the sample surface was removed using compressed air.

[0060] The porosity, compressive strength, and compressive modulus of the bone implants prepared in Examples 1 and 2 and Comparative Examples 1 and 2 were tested using the following methods:

[0061] Porosity testing method: The mass is measured using an electronic balance, and the porosity is calculated based on Archimedes' principle.

[0062] Test methods for yield strength and compressive modulus: Tensile tests shall be conducted in accordance with GB / T 228.1-2010 standard.

[0063] The results are shown in the table below:

[0064] Example 1 67.8％ 7.2MPa 95.2MPa Example 2 75.1％ 5.2MPa 70.2MPa Comparative Example 1 67.8％ 6.8MPa 70.2MPa Comparative Example 2 75.1％ 4.7MPa 49.3MPa

[0065] As shown in the table above, the bone implants prepared using the method provided in the embodiments of this application have improved compressive strength and compressive modulus, especially the improvement in compressive modulus is particularly significant. Under high porosity conditions, post-processing can achieve mechanical properties close to those of human trabecular bone (compressive strength 2-10 MPa, compressive modulus 100 MPa), indicating that immersion in citric acid solution is effective in improving the mechanical properties of the samples.

[0066] Various embodiments of this application may exist in the form of a range; it should be understood that the description in the form of a range is merely for convenience and brevity and should not be construed as a hard limitation on the scope of this application; therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and single numerical 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 single numbers within the range, such as 1, 2, 3, 4, 5, and 6, regardless of the range. Furthermore, whenever a numerical range is referred to herein, it means including any referenced number (fraction or integer) within the referred range.

[0067] In this application, unless otherwise stated, directional terms such as "upper" and "lower" specifically refer to the orientation shown in the accompanying drawings. Furthermore, in the description of this application, the terms "comprising," "including," etc., mean "including but not limited to."

[0068] In this document, relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, without necessarily requiring or implying any actual relationship or order between these entities or operations. In this document, "and / or" describes the association between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A alone, A and B simultaneously, or B alone. A and B can be singular or plural. In this document, "at least one" means one or more, and "more than" means two or more. "At least one," "at least one of the following," or similar expressions refer to any combination of these items, including any combination of single or plural items. For example, "at least one of a, b, or c," or "at least one of a, b, and c," can both represent: a, b, c, ab (i.e., a and b), ac, bc, or abc, where a, b, and c can be single or multiple.

[0069] The above description is merely a specific embodiment of this application, enabling those skilled in the art to understand or implement this application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this application. Therefore, this application is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features claimed herein.

Claims

1. A method for preparing a hydroxyapatite-based bone implant, characterized in that, The method includes: Hydroxyapatite and polyvinyl alcohol are mixed to obtain a hydroxyapatite-containing raw material; 3D printing was used to print hydroxyapatite-containing raw materials to obtain bone implant embryos; The bone implant embryo is immersed in an aqueous solution of citric acid to increase the strength of the bone implant embryo, thereby obtaining a bone implant; The 3D printing is a binder jetting 3D printing, and the jetting liquid for the 3D printing includes pure deionized water or a deionized water-based liquid containing anhydrous ethanol and / or surfactants.

2. The method for preparing the hydroxyapatite-based bone implant according to claim 1, characterized in that, The citric acid aqueous solution has a citric acid concentration of 3% to 8% by mass.

3. The method for preparing the hydroxyapatite-based bone implant according to claim 1, characterized in that, The mass of the polyvinyl alcohol is 20% to 40% of the hydroxyapatite.

4. The method for preparing the hydroxyapatite-based bone implant according to claim 1, characterized in that, The average particle size of the hydroxyapatite is 20~60μm.

5. The method for preparing the hydroxyapatite-based bone implant according to claim 1, characterized in that, The average particle size of the polyvinyl alcohol is 20~60μm.

6. The method for preparing the hydroxyapatite-based bone implant according to claim 1, characterized in that, The degree of alcoholysis of the polyvinyl alcohol is 88% or 99%.

7. The method for preparing the hydroxyapatite-based bone implant according to claim 1, characterized in that, The viscosity of the polyvinyl alcohol is 80~110 mPa•s.

8. The method for preparing the hydroxyapatite-based bone implant according to claim 1, characterized in that, The mixing method employs ball milling; the ball milling speed is 40~200 rpm; the ball milling time is 5~7 hours.

9. A hydroxyapatite-based bone implant, characterized in that, The bone implant is prepared by the method described in any one of claims 1 to 8.

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