Polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices and preparation method and application thereof

Abstract

This invention provides a polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices, its preparation method, and its applications. The invention utilizes a melt blending method to prepare composite materials with different formulation ratios under optimal process conditions. When the zinc-doped hydroxyapatite content is 10%, the composite material exhibits the best thermal stability and mechanical properties (tensile strength of 63.2 MPa). The composite material shows the lowest rate of flexural performance degradation after 20 days of degradation. In vitro degradation experiments demonstrate that the mechanical properties of the composite material can be altered by changing the zinc-doped hydroxyapatite content, and the degradation rate can be modified by changing the zinc-doped hydroxyapatite content to meet the requirements of the implantation site. Cytotoxicity experiments show that an appropriate zinc ion concentration can promote the cell activity of mouse osteoblasts.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and in particular to a polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices, its preparation method, and its application. Background Technology

[0002] In the field of biomaterials science, hydroxyapatite is a promising bioactive material with a close-packed hexagonal crystal structure. Under stable lattice conditions, some ionic sites in hydroxyapatite can be freely replaced, allowing calcium ions to substitute for various metal ions, thereby altering the physical and chemical characteristics of hydroxyapatite and its mechanical properties both in vivo and in vitro.

[0003] The complex bone tissue structure of the human body contains many metal ions, such as calcium ions. 2+ Fe 2+ / Fe 3+ and Zn 2+ These metal ions play a crucial role; they are not only key components of many enzymes but also participate in cell signaling processes and maintain the body's metabolic homeostasis. For example, zinc ions (Zn...) 2+ Doping can affect the lattice constant and stability of hydroxyapatite, thereby altering its physical and chemical properties; magnesium ions (Mg 2+ Strontium ions can replace some calcium ions, altering the solubility and bioactivity of hydroxyapatite; 2+ It has similar chemical properties to calcium ions, and its doping can enhance the bioactivity of hydroxyapatite and play a role in bone repair.

[0004] Zinc ions, the most abundant trace metal element in bones, not only act as cofactors for many enzymes but also play a crucial role in inhibiting bacterial growth and regulating cell proliferation, differentiation, and gene expression. Polylactic acid (PLA) is a polymer material with good biocompatibility and biodegradability, characterized by non-toxicity and good thermoforming properties. Its degradation products can participate in human metabolism, making it suitable as a cell growth carrier material in tissue engineering and widely used in clinical tissue repair. Current technologies disclose the composite of nano-hydroxyapatite with PLA to impart osteogenic activity, but there is no evidence of zinc-doped hydroxyapatite composites with PLA for use as a bone repair material. Summary of the Invention

[0005] In view of the above-mentioned shortcomings or improvement needs of the prior art, the present invention provides a polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices, its preparation method and application.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] In a first aspect, the present invention provides a method for preparing a polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices, comprising the following steps:

[0008] Polylactic acid and zinc-doped hydroxyapatite were mixed to obtain a mixture;

[0009] The mixture was placed in an internal mixer for melt blending to obtain a composite.

[0010] The composite material was first hot-pressed and then cold-pressed to obtain a polylactic acid / zinc-doped hydroxyapatite composite material.

[0011] Preferably, in the step of melting and blending the mixture in an internal mixer, the internal mixer temperature is controlled at 180–190°C, the screw speed at 110–120 r / min, and the melting and blending time at 7–10 min.

[0012] Preferably, in the step of hot pressing followed by cold pressing of the composite, the hot pressing specifically includes:

[0013] The composite was preheated at 210–220°C for 6–10 min, and then held at 210–220°C and 10–12 MPa for 5–10 min.

[0014] Preferably, in the step of hot pressing and then cold pressing of the composite, the cold pressing specifically includes: holding the hot-pressed composite at a temperature of 20-25°C and a pressure of 10-12 MPa for 5-10 minutes.

[0015] Preferably, the mass fraction of zinc-doped hydroxyapatite in the mixture is 5-20%.

[0016] Preferably, the zinc-doped hydroxyapatite in the mixture has a mass fraction of 10%.

[0017] Preferably, the method for preparing the zinc-doped hydroxyapatite includes the following steps:

[0018] The phosphate salt solution was heated to 78–82°C under an inert atmosphere, and then zinc salt solution and calcium salt solution were added dropwise to the phosphate salt solution. After the addition was completed, the pH of the system was adjusted to 8.8–9.2 to obtain a mixed solution.

[0019] Add a dispersant to the mixture and maintain the reaction at 78-82℃ for 3-4 hours. After the reaction is complete, filter, wash and dry to obtain zinc-doped hydroxyapatite.

[0020] Preferably, the calcium salt solution is prepared as follows:

[0021] Calcium nitrate tetrahydrate is added to water to obtain a calcium salt solution; the concentration of the calcium salt solution is 0.1–0.2 mol / L.

[0022] The method for preparing the phosphate salt solution is as follows:

[0023] Ammonium dihydrogen phosphate dodecahydrate is added to water to obtain a phosphate salt solution; the concentration of the phosphate salt solution is 0.05–0.1 mol / L.

[0024] The zinc salt solution is prepared as follows:

[0025] Zinc nitrate hexahydrate is added to water to obtain a zinc salt solution; the concentration of the zinc salt solution is 0.01–0.2 mol / L.

[0026] The dispersant is sodium polyacrylate;

[0027] The mass of the dispersant is 0.5% to 2% of the mass of the mixture;

[0028] The volume ratio of the calcium salt solution, zinc salt solution, and phosphate salt solution is (9-10):(1-2):(10-11).

[0029] Secondly, the present invention also provides a polylactic acid / zinc-doped hydroxyapatite composite material, which is prepared by the aforementioned preparation method.

[0030] Thirdly, the present invention also provides the application of the polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices prepared by the preparation method described above, or the polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices described above, in the preparation of bone repair materials.

[0031] The polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices of the present invention, its preparation method, and its application have the following advantages over the prior art:

[0032] 1. The present invention relates to a method for preparing polylactic acid / zinc-doped hydroxyapatite composite materials. Using polylactic acid as the matrix and zinc-doped hydroxyapatite as the reinforcement, polylactic acid / zinc-doped hydroxyapatite composite materials with different formulation ratios were prepared by melt blending under optimal process conditions. Relevant characterizations confirmed the successful preparation of polylactic acid-zinc-doped hydroxyapatite. When the content of zinc-doped hydroxyapatite was 10%, the composite material exhibited the best thermal stability and mechanical properties (tensile strength of 63.2 MPa). Furthermore, at this formulation, the composite material showed the lowest rate of flexural performance degradation after 20 days of degradation; simultaneously, the polylactic acid / zinc-doped hydroxyapatite composite material exhibited higher tensile strength compared to the polylactic acid / nano-hydroxyapatite composite material; this is due to the zinc ion (Zn) content. 2+The partial replacement of calcium sites in the hydroxyapatite (HA) lattice induces lattice distortion, increases crystal defect density, and makes the bond between polylactic acid and nano-hydroxyapatite more compact, thereby giving the composite material better mechanical properties.

[0033] 2. In vitro degradation experiments demonstrated that the mechanical properties of polylactic acid / zinc-doped hydroxyapatite composites can be altered by changing the zinc-doped hydroxyapatite content. The degradation rate of the composite can be modified by changing the zinc-doped hydroxyapatite content, thus meeting the requirements of the implantation site. Furthermore, zinc ions are continuously released during degradation; low concentrations of zinc ions promote osteoblast differentiation by activating the TGF-β / Smad pathway signaling system.

[0034] 3. Cytotoxicity experiments showed that an appropriate concentration of zinc ions could promote the cell activity of mouse osteoblasts. Attached Figure Description

[0035] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0036] Figure 1 Infrared spectra of zinc-doped hydroxyapatite (Zn-HA) used in Example 1, polylactic acid / zinc-doped hydroxyapatite composites with different formulation ratios prepared in Examples 1-4, and polylactic acid material PLA prepared in Comparative Example 1.

[0037] Figure 2 The graphs show the TG(a) and DTG(b) curves of the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composite materials with different formulation ratios prepared in Examples 1 to 4, and the polylactic acid material PLA prepared in Comparative Example 1 at 0 to 600 °C.

[0038] Figure 3 The heating curves (a) and cooling curves (b) of DSC for the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composites with different formulation ratios prepared in Examples 1 to 4, and the polylactic acid material prepared in Comparative Example 1 are shown.

[0039] Figure 4 The XRD spectra of the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composites with different formulation ratios prepared in Examples 1 to 4, and the polylactic acid material prepared in Comparative Example 1 are shown.

[0040] Figure 5 The tensile strengths of the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composites with different formulation ratios prepared in Examples 1 to 4, and the polylactic acid material prepared in Comparative Example 1 are:

[0041] Figure 6 The tensile strength of the polylactic acid material prepared in Comparative Example 1 and the polylactic acid / nanohydroxyapatite composite materials in Comparative Examples 2-5;

[0042] Figure 7 Tensile fracture surface morphology of the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, polylactic acid / zinc-doped hydroxyapatite composite materials with different formulation ratios prepared in Examples 1 to 4, and polylactic acid material prepared in Comparative Example 1.

[0043] Figure 8 (a) shows the bending properties of polylactic acid / zinc-doped hydroxyapatite composites with different formulation ratios after 0, 5, 10, and 20 days of degradation. Figure 8 (b) The amount of Zn ions released by 10wt% PLA / Zn-HA after degradation for 0, 5, 10, and 20 days in Example 2;

[0044] Figure 9 This is a graph showing the cell viability of mouse osteoblasts in a 10wt% PLA / Zn-HA extract in Example 2.

[0045] Figure 10 The graph shows the cell viability of mouse osteoblasts in the 10wt% PLA / nHA extract in Comparative Example 3. Detailed Implementation

[0046] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0047] In the description of this invention, it should be understood that the orientation or positional relationship indicated by terms such as "above" is based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship in which the product of this invention is usually placed when in use, or the orientation or positional relationship in which those skilled in the art are usually understood. It is only for the convenience of describing this invention and simplifying the description, and is not intended to indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, it should not be construed as a limitation of this invention.

[0048] The order in which the embodiments are described below is not intended to limit the preferred order of the embodiments. Furthermore, in the description of this application, the term "comprising" means "including but not limited to". Various embodiments of the invention 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 rigid limitation on the scope of the invention; 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. Additionally, whenever a numerical range is indicated herein, it means including any referenced number (fraction or integer) within the indicated range.

[0049] This application provides a method for preparing a polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices, comprising the following steps:

[0050] Polylactic acid and zinc-doped hydroxyapatite were mixed to obtain a mixture;

[0051] The mixture was placed in an internal mixer for melt blending to obtain a composite.

[0052] The composite material was first hot-pressed and then cold-pressed to obtain a polylactic acid / zinc-doped hydroxyapatite composite material.

[0053] In some embodiments, in the step of placing the mixture in an internal mixer for melt blending, the internal mixer temperature is controlled at 180–190°C, the screw speed at 110–120 r / min, and the melt blending time at 7–10 min.

[0054] In some embodiments, the step of hot-pressing the composite followed by cold-pressing specifically includes:

[0055] The composite was preheated at 210–220°C for 6–10 min, and then held at 210–220°C and 10–12 MPa for 5–10 min.

[0056] In some embodiments, the step of hot-pressing the composite followed by cold-pressing specifically includes: holding the hot-pressed composite at a temperature of 20-25°C and a pressure of 10-12 MPa for 5-10 minutes.

[0057] In some embodiments, the mass fraction of zinc-doped hydroxyapatite in the mixture is 5-20%.

[0058] In some embodiments, the mass fraction of zinc-doped hydroxyapatite in the mixture is 10%.

[0059] In some embodiments, the preparation method of zinc-doped hydroxyapatite includes the following steps:

[0060] S1. Heat the phosphate salt solution to 78-82℃ under an inert atmosphere, then add zinc salt solution and calcium salt solution dropwise to the phosphate salt solution. After the addition is complete, adjust the pH of the system to 8.8-9.2 to obtain a mixed solution.

[0061] S2. Add a dispersant to the mixture and maintain the reaction at 78-82℃ for 3-4 hours. After the reaction is complete, filter, wash and dry to obtain zinc-doped hydroxyapatite.

[0062] In some embodiments, the calcium salt solution is prepared as follows:

[0063] Calcium nitrate tetrahydrate is added to water to obtain a calcium salt solution; the concentration of the calcium salt solution is 0.1–0.2 mol / L.

[0064] The method for preparing phosphate salt solutions is as follows:

[0065] Ammonium dihydrogen phosphate dodecahydrate is added to water to obtain a phosphate salt solution; the concentration of the phosphate salt solution is 0.05–0.1 mol / L.

[0066] The method for preparing zinc salt solution is as follows:

[0067] Zinc nitrate hexahydrate is added to water to obtain a zinc salt solution; the concentration of the zinc salt solution is 0.01–0.2 mol / L.

[0068] The dispersant is sodium polyacrylate;

[0069] The mass of the dispersant is 0.5% to 2% of the mass of the mixture;

[0070] The volume ratio of calcium salt solution, zinc salt solution, and phosphate salt solution is (9-10):(1-2):(10-11).

[0071] In some embodiments, the inert atmosphere includes at least one of nitrogen, helium, neon, and argon.

[0072] Preferably, in some embodiments, the method for preparing zinc-doped hydroxyapatite includes the following steps:

[0073] S1. Transfer the phosphate salt solution to a nitrogen-protected three-necked reaction flask, add a magnetic stir bar, and purge with nitrogen to remove oxygen. Heat the mixture in an oil bath to 78–82°C, and add calcium salt solution dropwise at a rate of 1–2 drops / second using a constant flow pump. Simultaneously, add zinc salt solution dropwise at a rate of 1–2 drops / 10 seconds using a separatory funnel to achieve precise control of the Zn / Ca molar ratio. Adjust the pH of the system to 9.0 ± 0.2 in real time (titrated with ammonia (5 wt%) and double-verified with alkaline pH test paper) to obtain a mixed solution.

[0074] S2. Add sodium polyacrylate dispersant to the mixture at a rate of 0.5-2% of the mixture mass, and simultaneously perform ultrasonic-assisted dispersion (ultrasonication at 40 kHz for 5 min); maintain the reaction temperature at 78-82℃ for 3-4 hours to ensure directional crystal growth.

[0075] S3. After the reaction is complete, the reaction solution is allowed to settle overnight, then filtered through a Buchner funnel (0.22 μm filter membrane), washed three times with deionized water (the washing solution volume is three times the product volume); ultrasonic-assisted purification (ultrasonication at 40 kHz for 10-15 min) followed by a second filtration to remove residual impurities; vacuum drying at 80 °C overnight, and grinding to obtain agglomerated zinc-doped hydroxyapatite powder.

[0076] In some embodiments, before mixing polylactic acid and zinc-doped hydroxyapatite, the method further includes drying polylactic acid and zinc-doped hydroxyapatite at a temperature of 40–50°C for 10–15 h respectively.

[0077] Based on the same inventive concept, the present invention also provides a polylactic acid / zinc-doped hydroxyapatite composite material, which is prepared by the above-described preparation method.

[0078] In some embodiments, the present invention also provides the application of the polylactic acid / zinc-doped hydroxyapatite composite material prepared by the above-described preparation method or the above-described polylactic acid / zinc-doped hydroxyapatite composite material in the preparation of bone repair materials.

[0079] The following specific embodiments further illustrate the polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices of this application, its preparation method, and its application. This section further illustrates the content of the present invention in conjunction with specific embodiments, but should not be construed as limiting the present invention. Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in the art.

[0080] In the following embodiments, the preparation method of zinc-doped hydroxyapatite includes the following steps:

[0081] S1. Transfer the phosphate salt solution to a nitrogen-protected three-necked reaction flask, add a magnetic stir bar, and purge with nitrogen to remove oxygen; heat to 80°C using an oil bath, and add calcium salt solution dropwise at a rate of 1 drop / second using a constant flow pump, while simultaneously adding zinc salt solution dropwise at a rate of 1 drop / 10 seconds using a separatory funnel to achieve precise control of the Zn / Ca molar ratio; adjust the pH of the system to 9.0 in real time to obtain a mixed solution;

[0082] S2. Add sodium polyacrylate dispersant to the mixture at a concentration of 1% of the mixture mass, and simultaneously perform ultrasonic-assisted dispersion (ultrasonication at 40 kHz for 5 min); maintain the reaction temperature at 80°C for 3 hours to ensure directional crystal growth.

[0083] S3. After the reaction is complete, the reaction solution is allowed to settle overnight, then filtered through a Buchner funnel (0.22 μm filter membrane), washed three times with deionized water, purified by ultrasonication (sonicated at 40 kHz for 10-15 min), and filtered a second time to remove residual impurities. After vacuum drying at 80 °C overnight, the powder is ground to obtain agglomerated zinc-doped hydroxyapatite powder.

[0084] The preparation method for the calcium salt solution is as follows:

[0085] Calcium nitrate tetrahydrate was added to water to obtain a calcium salt solution; the concentration of the calcium salt solution was 0.11 mol / L.

[0086] The method for preparing phosphate salt solutions is as follows:

[0087] Ammonium dihydrogen phosphate dodecahydrate was added to water to obtain a phosphate salt solution; the concentration of the phosphate salt solution was 0.06 mol / L.

[0088] The method for preparing zinc salt solution is as follows:

[0089] Zinc nitrate hexahydrate was added to water to obtain a zinc salt solution; the concentration of the zinc salt solution was 0.01 mol / L.

[0090] The dispersant is sodium polyacrylate;

[0091] The volume ratio of calcium salt solution, zinc salt solution, and phosphate salt solution is 9:1:10.

[0092] In the zinc-doped hydroxyapatite prepared above, the molar percentage of zinc is 10%, corresponding to a mass fraction of 6.35%.

[0093] The preparation method of nano-hydroxyapatite in the following comparative examples includes the following steps:

[0094] S1. Transfer the phosphate salt solution to a nitrogen-protected three-necked reaction flask, add a magnetic stir bar, and purge with nitrogen to remove oxygen; heat to 80°C using an oil bath, and add calcium salt solution dropwise at a rate of 1 drop / second using a constant flow pump; adjust the pH of the system to 9.0 in real time to obtain a mixture;

[0095] S2. Add sodium polyacrylate dispersant to the mixture at a concentration of 1% of the mixture mass, and simultaneously perform ultrasonic-assisted dispersion (ultrasonication at 40 kHz for 5 min); maintain the reaction temperature at 80°C for 3 hours to ensure directional crystal growth.

[0096] S3. After the reaction is complete, the reaction solution is allowed to settle overnight, then filtered through a Buchner funnel (0.22 μm filter membrane), washed three times with deionized water, purified by ultrasonication (sonicated at 40 kHz for 10-15 min), and filtered a second time to remove residual impurities. After vacuum drying at 80 °C overnight, the powder is ground to obtain agglomerated nano-hydroxyapatite powder.

[0097] The preparation method for the calcium salt solution is as follows:

[0098] Calcium nitrate tetrahydrate was added to water to obtain a calcium salt solution; the concentration of the calcium salt solution was 0.11 mol / L.

[0099] The method for preparing phosphate salt solutions is as follows:

[0100] Ammonium dihydrogen phosphate dodecahydrate was added to water to obtain a phosphate salt solution; the concentration of the phosphate salt solution was 0.06 mol / L.

[0101] The dispersant is sodium polyacrylate;

[0102] The volume ratio of calcium salt solution to phosphate salt solution is 1:1.

[0103] Example 1

[0104] This application provides a method for preparing a polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices, comprising the following steps:

[0105] S1. Polylactic acid and zinc-doped hydroxyapatite were dried at 40°C for 12 hours respectively.

[0106] Dry polylactic acid and zinc-doped hydroxyapatite (Zn-HA) were mixed to obtain a mixture; wherein the mass fraction of zinc-doped hydroxyapatite in the mixture was 5% and the mass fraction of polylactic acid was 95%.

[0107] S2. Place the mixture in an internal mixer and melt-blend at 180°C and a screw speed of 110 r / min for 7 min to obtain the composite.

[0108] S3. The composite is first hot-pressed and then cold-pressed to obtain a polylactic acid / zinc-doped hydroxyapatite composite material (denoted as 5wt% PLA / Zn-HA).

[0109] In the steps of hot pressing followed by cold pressing of the composite, the hot pressing specifically includes:

[0110] The composite was preheated at 210°C for 6 min, and then held at 210°C and 10 MPa for 5 min.

[0111] The cold pressing process specifically includes: holding the hot-pressed composite at a temperature of 25°C and a pressure of 10 MPa for 5 minutes.

[0112] Example 2

[0113] The preparation method of the polylactic acid / zinc-doped hydroxyapatite composite material provided in this application embodiment is the same as that in Example 1, except that the mass fraction of zinc-doped hydroxyapatite in the mixture is 10% and the mass fraction of polylactic acid is 90%, and the prepared polylactic acid / zinc-doped hydroxyapatite composite material is denoted as 10wt% PLA / Zn-HA.

[0114] Example 3

[0115] The preparation method of the polylactic acid / zinc-doped hydroxyapatite composite material provided in this application embodiment is the same as that in Example 1, except that the mass fraction of zinc-doped hydroxyapatite in the mixture is 15% and the mass fraction of polylactic acid is 85%, and the prepared polylactic acid / zinc-doped hydroxyapatite composite material is denoted as 15wt% PLA / Zn-HA.

[0116] Example 4

[0117] The preparation method of the polylactic acid / zinc-doped hydroxyapatite composite material provided in this application embodiment is the same as that in Example 1, except that the mass fraction of zinc-doped hydroxyapatite in the mixture is 20% and the mass fraction of polylactic acid is 80%, and the prepared polylactic acid / zinc-doped hydroxyapatite composite material is denoted as 20wt% PLA / Zn-HA.

[0118] Comparative Example 1

[0119] This comparative example provides a method for preparing polylactic acid material, which is the same as in Example 1, except that zinc-doped hydroxyapatite is not added. The specific preparation process is as follows:

[0120] S1. Dry polylactic acid at 40°C for 12 hours;

[0121] Dry polylactic acid was placed in a mixer and melt-blended at 180°C and a screw speed of 110 r / min for 7 min to obtain the composite.

[0122] S3. The composite is first hot-pressed and then cold-pressed to obtain polylactic acid material (denoted as PLA);

[0123] In the steps of hot pressing followed by cold pressing of the composite, the hot pressing specifically includes:

[0124] The composite was preheated at 210°C for 6 min, and then held at 210°C and 10 MPa for 5 min.

[0125] The cold pressing process specifically includes: holding the hot-pressed composite at a temperature of 25°C and a pressure of 10 MPa for 5 minutes.

[0126] Comparative Example 2

[0127] This comparative example provides a method for preparing a polylactic acid / nanohydroxyapatite composite material, including the following steps:

[0128] S1. Polylactic acid and nano-hydroxyapatite were dried at 40℃ for 12 hours respectively.

[0129] Dry polylactic acid (PLA, CAS No.: 26100-51-6) and zinc-doped hydroxyapatite (Zn-HA) were mixed to obtain a mixture; wherein the mass fraction of nano-hydroxyapatite in the mixture was 5% and the mass fraction of polylactic acid was 95%.

[0130] S2. Place the mixture in an internal mixer and melt-blend at 180°C and a screw speed of 110 r / min for 7 min to obtain the composite.

[0131] S3. The composite is first hot-pressed and then cold-pressed to obtain polylactic acid / nanohydroxyapatite composite material (denoted as 5wt% PLA / nHA);

[0132] In the steps of hot pressing followed by cold pressing of the composite, the hot pressing specifically includes:

[0133] The composite was preheated at 210°C for 6 min, and then held at 210°C and 10 MPa for 5 min.

[0134] The cold pressing process specifically includes: holding the hot-pressed composite at a temperature of 25°C and a pressure of 10 MPa for 5 minutes.

[0135] Comparative Example 3

[0136] This comparative example provides a method for preparing a polylactic acid / nanohydroxyapatite composite material, which is the same as Comparative Example 2, except that the mass fraction of nanohydroxyapatite in the mixture is 10% and the mass fraction of polylactic acid is 90%. The prepared polylactic acid / nanohydroxyapatite composite material is denoted as 10wt% PLA / nHA.

[0137] Comparative Example 4

[0138] This comparative example provides a method for preparing a polylactic acid / nanohydroxyapatite composite material, which is the same as Comparative Example 2, except that the mass fraction of nanohydroxyapatite in the mixture is 15% and the mass fraction of polylactic acid is 85%. The prepared polylactic acid / nanohydroxyapatite composite material is denoted as 15wt% PLA / nHA.

[0139] Comparative Example 5

[0140] This comparative example provides a method for preparing a polylactic acid / nanohydroxyapatite composite material, which is the same as Comparative Example 2, except that the mass fraction of nanohydroxyapatite in the mixture is 20% and the mass fraction of polylactic acid is 80%. The prepared polylactic acid / nanohydroxyapatite composite material is denoted as 20wt% PLA / nHA.

[0141] Performance Characterization

[0142] Figure 1 The infrared spectra are those of the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composite materials with different formulation ratios prepared in Examples 1 to 4, and the polylactic acid material PLA prepared in Comparative Example 1.

[0143] from Figure 1 As can be seen from the infrared spectrum of the pure polylactic acid (PLA) material prepared in Comparative Example 1, the 1759 cm⁻¹ value is... -1 and 1185cm -1 The stretching vibrations at 2944 cm⁻¹ indicate the presence of ester bonds in the polylactic acid molecule, corresponding to the C=O and COC groups. -1 and 2995cm -1 The absorption peak at 563 cm⁻¹ corresponds to the stretching vibrations of CH and -CH₃. In the infrared spectrum of zinc-doped hydroxyapatite (Zn-HA), the peak at 563 cm⁻¹ corresponds to the stretching vibrations of CH and -CH₃. -1 and 605cm -1 The absorption peak at 3430 cm⁻¹ is a characteristic peak of the phosphate γ⁴ vibrational mode. -1The absorption peak at [location] is a characteristic peak of the hydroxyl group, corresponding to the stretching vibration of the hydroxyl group. The incorporation of zinc did not affect the functional groups of the nano-hydroxyapatite. Compared with polylactic acid and zinc-doped hydroxyapatite, the infrared spectra of the polylactic acid / zinc-doped hydroxyapatite composites prepared in Examples 1-4 show that the composites possess all the characteristic peaks of both polylactic acid and zinc-doped hydroxyapatite, with no significant peak shift in position. This indicates that no chemical bonding reaction occurred between polylactic acid and zinc-doped hydroxyapatite, and only physical blending was involved.

[0144] Figure 2 The graphs show the TG(a) and DTG(b) curves of the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composite materials with different formulation ratios prepared in Examples 1 to 4, and the polylactic acid material PLA prepared in Comparative Example 1 at 0 to 600 °C.

[0145] from Figure 2 It can be seen that the sample exhibits certain thermal stability within a temperature range of 100–300℃. The temperature corresponding to a 5 wt% mass loss in pure polylactic acid material is 303.8℃. With the increase of zinc-doped hydroxyapatite content, the Ta of the composite material increases. 5％ The values ​​showed a trend of first increasing and then decreasing, specifically 321.6℃, 331.8℃, 329.8℃, and 311.3℃. This is because when the content of added zinc-doped hydroxyapatite is low, the addition of zinc-doped hydroxyapatite acts as a nucleating agent, promoting the crystallization of polylactic acid (PLA) and making it less prone to molecular chain movement at high temperatures, thus improving its thermal stability. When the content of added zinc-doped hydroxyapatite is too high, the zinc-doped hydroxyapatite agglomerates within the PLA, worsening its interfacial compatibility with the PLA matrix and leading to microcracks or voids at the interface. These defects reduce the thermal stability of the PLA matrix. The maximum thermogravimetric temperature did not differ significantly among the samples, indicating that zinc-doped hydroxyapatite did not alter the kinetic characteristics of the PLA decomposition reaction. This indicates that the dispersion state of zinc-doped hydroxyapatite in the composite material has a limited impact on the decomposition mechanism of polylactic acid (PLA). When the experimental temperature reaches 600℃, the PLA matrix completely decomposes thermally, leaving only zinc-doped hydroxyapatite particles that are difficult to decompose thermally. Therefore, the final residual amount in the experiment can be regarded as the actual composite amount of zinc-doped hydroxyapatite. The residual proportions of each group are 0%, 4.4%, 10.8%, 14.2%, and 17.5%, respectively, indicating that zinc-doped hydroxyapatite was successfully incorporated into PLA during the melt blending process of PLA and zinc-doped hydroxyapatite with minimal loss.

[0146] Figure 3The heating curves (a) and cooling curves (b) of DSCs for the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composites with different formulation ratios prepared in Examples 1 to 4, and the polylactic acid material prepared in Comparative Example 1 are shown.

[0147] from Figure 3 (a) shows that the heating curves of pure polylactic acid and polylactic acid / zinc-doped hydroxyapatite composites have different T values. g Within the temperature range of 57–59℃. Considering testing errors, the T value of the composite material... g The glass transition temperature (TVT) remained essentially unchanged. This indicates that no chemical reaction occurred between zinc-doped hydroxyapatite and polylactic acid (PLA). Zinc-doped hydroxyapatite existed only as a physical filler, without altering the molecular chain mobility of PLA, which is consistent with infrared spectroscopy results. The crystallization transition temperature of pure PLA is 107.6℃, and its melting transition temperature is 161.9℃. In contrast, with the addition of zinc-doped hydroxyapatite, the TVT of the composite material... cc (Crystallization transformation temperature) shifts to the left, T m The melt transition temperature shifts to the right. This indicates that the addition of zinc-doped hydroxyapatite can improve the nucleation efficiency and thermal stability of polylactic acid (PLA) crystallization. The increased crystallization rate can be attributed to zinc-doped hydroxyapatite acting as a nucleation site, inducing heterogeneous nucleation of PLA; the improved thermal stability may be due to the addition of zinc-doped hydroxyapatite promoting PLA crystallization, thereby increasing the melting temperature of the composite material.

[0148] from Figure 3 As shown in the cooling curve of (b), compared with pure polylactic acid material, the polylactic acid / zinc-doped hydroxyapatite composite material with added zinc has a cold crystallization peak. This may be because the presence of zinc-doped hydroxyapatite acts as a heterogeneous nucleating agent during the cooling process of polylactic acid, promoting the crystallization of polylactic acid.

[0149] Figure 4 The XRD spectra are those of the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composites with different formulation ratios prepared in Examples 1 to 4, and the polylactic acid material prepared in Comparative Example 1.

[0150] Polylactic acid (PLA) is a semi-crystalline polymer, and its characteristic peaks typically appear at 2θ = 16.8°. Figure 4As can be seen, the XRD pattern of pure polylactic acid (PLA) shows a broadened and symmetrical diffraction peak at 2θ = 16.8°, indicating that PLA exists in both crystalline and amorphous regions at this point, consistent with its crystallinity. After adding zinc-doped hydroxyapatite to PLA, the peak at 2θ = 16.8° sharpens, indicating that the addition of zinc-doped hydroxyapatite transforms the amorphous region of PLA into a crystalline region. This may be because zinc-doped hydroxyapatite acts as a nucleating agent in the PLA system, and with increasing content, the number of nucleation sites increases, thus improving the crystallinity of the composite material. When the zinc-doped hydroxyapatite content is too high, the particle aggregation effect becomes more pronounced, making the crystallization point formation unstable and leading to a decrease in crystallization efficiency, which is consistent with DSC analysis. The particle diffraction peaks of zinc-doped hydroxyapatite are consistent with the standard card (JCPDS 74-0566) for hydroxyapatite, exhibiting characteristic diffraction peaks of the (002), (211), (300), and (130) crystal planes. When zinc-doped hydroxyapatite is added to pure polylactic acid, these characteristic peaks of zinc-doped hydroxyapatite appear in the XRD pattern of the composite material. Furthermore, the intensity of the corresponding peaks increases with the increase of zinc-doped hydroxyapatite content, indicating that zinc-doped hydroxyapatite was successfully incorporated into the polylactic acid composite material during the melt blending process of polylactic acid and zinc-doped hydroxyapatite, and the proportion corresponds to the formulation ratio, which is consistent with the thermogravimetric analysis results.

[0151] Figure 5 The tensile strengths are those of the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composites with different formulation ratios prepared in Examples 1-4, and the polylactic acid material prepared in Comparative Example 1. Figure 5 In the text, 1, 2, 3, 4, and 5 represent PLA in Comparative Example 1, 5 wt% PLA / Zn-HA in Example 1, 10 wt% PLA / Zn-HA in Example 2, 15 wt% PLA / Zn-HA in Example 3, and 20 wt% PLA / Zn-HA in Example 4, respectively.

[0152] Figure 6 The tensile strength of the polylactic acid material prepared in Comparative Example 1 and the polylactic acid / nanohydroxyapatite composite materials in Comparative Examples 2-5 is shown. Figure 6 In the table, 1, 2, 3, 4, and 5 represent PLA in Comparative Example 1, 5 wt% PLA / nHA in Comparative Example 2, 10 wt% PLA / nHA in Comparative Example 3, 15 wt% PLA / nHA in Comparative Example 4, and 20 wt% PLA / nHA in Comparative Example 5, respectively.

[0153] Tensile strength was tested according to GB / T 1040-92 standard.

[0154] Depend on Figure 5It is known that the tensile strength of pure polylactic acid (PLA) is 61.5 MPa. After adding zinc-doped hydroxyapatite, the tensile strength of PLA-zinc-doped hydroxyapatite exhibits a trend of first increasing and then decreasing. When the added zinc-doped hydroxyapatite content is 10 wt%, the tensile strength reaches its maximum value of 63.2 MPa. This is because PLA and zinc-doped hydroxyapatite have poor compatibility. When the zinc-doped hydroxyapatite content is too low, the interfacial bonding between PLA and zinc-doped hydroxyapatite may be insufficient, leading to a decrease in stress transfer efficiency within the material. Poor interfacial bonding makes the composite material more prone to delamination or fracture under external force. When the zinc-doped hydroxyapatite content is too high, the zinc-doped hydroxyapatite will agglomerate within the PLA matrix, increasing internal defects in the PLA material. These defects act as stress concentration points, easily leading to material fracture under stress.

[0155] from Figure 6 As can be seen, after incorporating nano-hydroxyapatite into polylactic acid (PLA), the tensile strength of the composite material exhibits a trend of first increasing and then decreasing. When the content of nano-hydroxyapatite is 10 wt%, the tensile strength of the composite material reaches its maximum value of 62.5 MPa, slightly higher than that of pure PLA. This change can be explained by the following: due to the poor compatibility between PLA and nano-hydroxyapatite, when the content of nano-hydroxyapatite in the composite material is too low, the interfacial bonding between PLA and nano-hydroxyapatite may be insufficient, leading to a decrease in stress transfer efficiency within the material. Poor interfacial bonding makes the composite material more prone to delamination or fracture under external force. When the content of nano-hydroxyapatite is too high, nano-hydroxyapatite will agglomerate within the PLA matrix, increasing internal defects in the PLA material. These defects act as stress concentration points, easily leading to material fracture under stress.

[0156] Furthermore, by Figure 5 and Figure 6 The comparison shows that the polylactic acid / zinc-doped hydroxyapatite composite material has higher tensile strength than the polylactic acid / nano-hydroxyapatite composite material and pure polylactic acid. Specifically, the tensile strength of pure polylactic acid increases from 61.5 MPa to 63.2 MPa (an increase of 2.76%), and the tensile strength of polylactic acid / nano-hydroxyapatite composite material increases from 62.5 MPa to 63.2 MPa (an increase of 1.12%). The polylactic acid / zinc-doped hydroxyapatite composite material of this invention has superior mechanical properties compared to pure polylactic acid and polylactic acid / nano-hydroxyapatite composite material. The performance improvement mechanism is: lattice strengthening effect: zinc ions (Zn... 2+ The polylactic acid (PLA) partially replaces the calcium sites in the hydroxyapatite (HA) lattice, causing lattice distortion and increasing the crystal defect density. This makes the bond between PLA and nano-hydroxyapatite tighter, resulting in better mechanical properties and a lower degradation rate in the composite material.

[0157] Figure 7 The images show the tensile fracture surface morphology of the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composite materials prepared in Examples 1-4 with different formulation ratios, and the polylactic acid material prepared in Comparative Example 1; wherein, (a) is PLA in Comparative Example 1, (b) is 5 wt% PLA / Zn-HA in Example 1, (c) is 10 wt% PLA / Zn-HA in Example 2, (d) is 15 wt% PLA / Zn-HA in Example 3, and (e) is 20 wt% PLA / Zn-HA in Example 4.

[0158] Depend on Figure 7 The morphology shows that the tensile fracture surface of pure polylactic acid (PLA) is relatively smooth and flat, without obvious granular or bony structures, indicating that pure PLA has high brittleness and poor toughness. When zinc-doped hydroxyapatite is added to PLA, the surface roughness of the composite material increases significantly, indicating a slight improvement in toughness. Furthermore, when the zinc-doped hydroxyapatite content is low (5–10 wt%), the zinc-doped hydroxyapatite is relatively uniformly dispersed in PLA, with no large agglomerates observed. However, when the zinc-doped hydroxyapatite content is too high (15–20 wt%), large aggregates of zinc-doped hydroxyapatite filler are observed to form in the PLA matrix. Moreover, the number of zinc-doped hydroxyapatite aggregates increases with increasing zinc-doped hydroxyapatite content. This will affect the mechanical properties of the composite material to some extent, reducing its thermodynamic and mechanical properties.

[0159] In vitro degradation analysis of polylactic acid / zinc-doped hydroxyapatite composites

[0160] During bone grafting, the material degrades within the body, while new bone tissue continuously grows and develops, gradually replacing the degraded portion of the material. Ideally, the degradation rate of the scaffold should correspond to the growth rate of the bone tissue. Therefore, in vitro degradation experiments are needed to evaluate the applicability of polylactic acid / zinc-doped hydroxyapatite composite materials in the field of bone repair.

[0161] Specifically, the pure polylactic acid (PLA) prepared in Comparative Example 1 and the polylactic acid / zinc-doped hydroxyapatite composite materials with different formulation ratios prepared in Examples 1-4 were placed in 125 mL bottles made of high-density polyethylene containing phosphate buffer solution (pH 7.4±0.1) at a ratio of 1 g / 20 mL. The bottles were placed in a temperature-controlled shaker at (37±1) °C and shaken at 200 r / min. The bending properties of the materials were then tested at 0 days, 5 days (120 h), 10 days, and 20 days.

[0162] Figure 8 (a) Graph showing the flexural properties (flexural strength tested according to GB / T 9341-2000 standard) of polylactic acid / zinc-doped hydroxyapatite composites with different formulation ratios after 0, 5, 10, and 20 days of degradation. 1, 2, 3, 4, and 5 represent PLA in Comparative Example 1, 5 wt% PLA / Zn-HA in Example 1, 10 wt% PLA / Zn-HA in Example 2, 15 wt% PLA / Zn-HA in Example 3, and 20 wt% PLA / Zn-HA in Example 4, respectively.

[0163] according to Figure 8 Data from (a) shows that after 20 days of degradation, the flexural strength of the polylactic acid (PLA) material decreased from 62.1 MPa to 57.8 MPa, a decrease of 6.9%. The flexural strength of the composites with zinc-doped hydroxyapatite contents of 5 wt%, 10 wt%, 15 wt%, and 20 wt% decreased by 7.5%, 5.5%, 7.1%, and 9.5% respectively after 20 days, showing a trend of first decreasing and then increasing. The composite with the lowest flexural performance degradation rate was observed when the zinc-doped hydroxyapatite content was 10 wt%. Furthermore, the flexural performance degradation rate of the composite material changed with the zinc-doped hydroxyapatite content, indicating that the degradation rate of PLA can vary with the zinc-doped hydroxyapatite content. Therefore, theoretically, the degradation rate of the composite material can be altered by changing the zinc-doped hydroxyapatite content, thereby meeting the requirements of the implantation site.

[0164] Figure 8 (b) The graph shows the ion release of 10 wt% PLA / Zn-HA in Example 2 after 0, 5, 10, and 20 days of degradation. As can be seen from the graph, the composite material continuously releases zinc ions with increasing degradation time. The release of zinc ions decreases over time, which may be because the initial zinc ions released originate from the zinc-doped hydroxyapatite on the surface of the composite material. After the zinc element in the surface zinc-doped hydroxyapatite is removed, the zinc-doped hydroxyapatite inside the composite material is blocked by polylactic acid, making it difficult for it to release zinc, thus reducing the zinc ion release rate. Whether the released zinc element can promote bone repair needs to be verified through biological experiments.

[0165] Figure 9 To determine the cell viability of mouse osteoblasts in the 10wt% PLA / Zn-HA extract in Example 2, the specific experimental method is as follows:

[0166] (1) The polylactic acid / zinc-doped hydroxyapatite composite material with a content of 10wt% was sterilized by ultraviolet light, and then soaked in DMEM solution at a ratio of 10mg / 10mL. After 24h, the extract was diluted to 0.8mg / mL, 0.5mg / mL, 0.2mg / mL and 0.1mg / mL respectively.

[0167] (2) Take 200 μL of the above-prepared extract and add it to a 24-well plate (each well contains 5000 MC3T3 cells). There are three parallel samples for each experimental group. Compare with the blank group with fresh culture medium solution. Place the well plate in a cell culture incubator at 37℃ for 24 h.

[0168] (3) Add 30 μL of MTT solution to each well and continue incubation in an incubator for 4 h. Then add 200 μL of LDMSO culture medium and shake in a shaker for 15 min at a constant temperature.

[0169] (4) Take 100 μL of the above liquid in each well of the 24-well plate and detect the absorbance value at the UV absorption peak of 492 nm.

[0170] (5) Using the absorbance value of the blank group as the control, calculate the ratio of the absorbance value of the experimental group to that of the control group, and evaluate the cell viability.

[0171] according to Figure 9 Data shows that the cell viability of polylactic acid / zinc-doped hydroxyapatite composite material with 10 wt% zinc doped hydroxyapatite decreased with increasing concentration. Within the range of 0.1 mg / mL to 0.8 mg / mL, the survival rates of mouse osteoblasts were 99.5%, 95.7%, 92.3%, and 91.0%, respectively. Compared to pure polylactic acid, the polylactic acid / zinc-doped hydroxyapatite composite material exhibits good biocompatibility at low concentrations, but its bioactivity decreases at excessively high concentrations. This may be because the effect of zinc ions on cells is concentration-dependent. When the extract concentration is too low, the zinc ion concentration is also low, and zinc ions have a certain promoting effect on the activity of mouse osteoblasts. Conversely, when the extract concentration is too high, the zinc ion concentration is too high, which can damage the integrity of the mouse osteoblast cell membrane, leading to cell death. Therefore, when incorporating zinc ions into hydroxyapatite, the zinc ion concentration must be strictly controlled. Furthermore, within the extract concentration range of 0.1-0.8 mg / mL, the cell activity of mouse osteoblasts remained above 90%, indicating that the composite material still exhibits good biocompatibility.

[0172] Following the same method described above, the cell viability of mouse osteoblasts in the 10 wt% PLA / nHA extract of Comparative Example 3 was tested, and the results are as follows: Figure 10 As shown.

[0173] Adding 10 wt% nano-hydroxyapatite to pure polylactic acid (PLA) improved its biocompatibility: within the same concentration range, cell viability was 98.6%, 94.4%, 93.6%, and 93.8%, respectively. This is likely because nano-hydroxyapatite releases hydroxide ions in the culture medium, neutralizing the hydrogen ions produced by PLA degradation and maintaining pH stability, thereby increasing cell metabolic activity and cell viability.

[0174] Furthermore, by Figures 9-10 The comparison shows that, at extract concentrations of 0.1–0.8 mg / mL, in the low concentration range, the 10 wt% PLA / Zn-HA extract of this invention significantly improved the survival rate of mouse osteoblasts compared to the 10 wt% PLA / nHA extract in Comparative Example 3. At 0.1 mg / mL, the survival rate increased from 98.6% to 99.5%. This is because the polylactic acid / zinc-doped hydroxyapatite composite material of this invention releases zinc ions, and low concentrations of zinc ions (<0.2 mg / mL) promote osteoblast differentiation by activating the TGF-β / Smad pathway signaling pathway.

[0175] In summary:

[0176] This invention utilizes a melt blending method to prepare polylactic acid / zinc-doped hydroxyapatite composite materials with varying zinc-doped hydroxyapatite content. These composite materials can be used in research on bone repair. Specific conclusions are as follows:

[0177] (1) Polylactic acid (PLA) / zinc-doped hydroxyapatite composites with different formulation ratios were prepared by melt blending under optimal process conditions using PLA as the matrix and zinc-doped hydroxyapatite as the reinforcement. Characterization confirmed the successful preparation of PLA-zinc-doped hydroxyapatite composites. When the zinc-doped hydroxyapatite content was 10%, the composite exhibited the best thermal stability and mechanical properties (tensile strength of 63.2 MPa). Furthermore, at this formulation ratio, the composite showed the lowest rate of flexural performance degradation after 20 days of degradation; simultaneously, the PLA / zinc-doped hydroxyapatite composite exhibited higher tensile strength compared to the PLA / nano-hydroxyapatite composite; this is due to the zinc ion (Zn) content. 2+ The partial replacement of calcium sites in the hydroxyapatite (HA) lattice induces lattice distortion, increases crystal defect density, and makes the bond between polylactic acid and nano-hydroxyapatite more compact, thereby giving the composite material better mechanical properties.

[0178] (2) In vitro degradation experiments demonstrated that the mechanical properties of polylactic acid / zinc-doped hydroxyapatite composites can be altered by changing the zinc-doped hydroxyapatite content. The degradation rate of the composite can be changed by altering the zinc-doped hydroxyapatite content, thus meeting the requirements of the implantation site. Furthermore, zinc ions are continuously released during degradation; low concentrations of zinc ions promote osteoblast differentiation by activating the TGF-β / Smad pathway signaling pathway.

[0179] (3) Cytotoxicity experiments showed that an appropriate concentration of zinc ions can promote the cell activity of mouse osteoblasts.

[0180] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. Application of a polylactic acid / zinc-doped hydroxyapatite composite material in the preparation of bone repair materials; The preparation method of the polylactic acid / zinc-doped hydroxyapatite composite material includes the following steps: Polylactic acid and zinc-doped hydroxyapatite were mixed to obtain a mixture; The mixture was placed in an internal mixer for melt blending to obtain a composite. The composite was first hot-pressed and then cold-pressed to obtain a polylactic acid / zinc-doped hydroxyapatite composite material. In the steps of hot pressing followed by cold pressing of the composite, the hot pressing specifically includes: The composite was preheated at 210-220℃ for 6-10 min, and then held at 210-220℃ and 10-12 MPa for 5-10 min. In the step of hot pressing the composite first and then cold pressing, the cold pressing specifically includes: holding the hot-pressed composite at a temperature of 20~25℃ and a pressure of 10~12MPa for 5~10min. The zinc-doped hydroxyapatite in the mixture has a mass fraction of 10%. The preparation method of the zinc-doped hydroxyapatite includes the following steps: The phosphate salt solution was heated to 78-82℃ under an inert atmosphere, and then zinc salt solution and calcium salt solution were added dropwise to the phosphate salt solution. After the addition was completed, the pH of the system was adjusted to 8.8-9.2 to obtain a mixed solution. Add a dispersant to the mixture and maintain the reaction at 78-82℃ for 3-4 hours. After the reaction is complete, filter, wash and dry to obtain zinc-doped hydroxyapatite. The concentration of the calcium salt solution is 0.1~0.2 mol / L; The concentration of the phosphate salt solution is 0.05~0.1 mol / L; The concentration of the zinc salt solution is 0.01~0.2 mol / L; The volume ratio of the calcium salt solution, zinc salt solution, and phosphate salt solution is (9~10):(1~2):(10~11).

2. The application as described in claim 1, characterized in that, In the step of melting and blending the mixture in an internal mixer, the temperature of the internal mixer is controlled at 180~190℃, the screw speed is 110~120 r / min, and the melting and blending time is 7~10min.

3. The application as described in claim 1, characterized in that, The method for preparing the calcium salt solution is as follows: Add calcium nitrate tetrahydrate to water to obtain a calcium salt solution; The method for preparing the phosphate salt solution is as follows: Ammonium dihydrogen phosphate dodecahydrate is added to water to obtain a phosphate salt solution; The zinc salt solution is prepared as follows: Zinc nitrate hexahydrate is added to water to obtain a zinc salt solution; The dispersant is sodium polyacrylate; The mass of the dispersant is 0.5 to 2% of the mass of the mixture.

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