Polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation instrument as well as preparation method and application of polylactic acid / zinc-doped hydroxyapatite composite material

Abstract

The invention provides a polylactic acid / zinc-doped hydroxyapatite composite material for a bone fixation instrument as well as a preparation method and application of the polylactic acid / zinc-doped hydroxyapatite composite material. According to the invention, composite materials with different formula ratios are prepared by adopting a melt blending method under optimal process conditions. When the content of the zinc-doped hydroxyapatite is 10%, the composite material has optimal thermal stability and mechanical properties (the tensile strength is 63.2 MPa). After the composite material is degraded for 20 days, the reduction rate of the bending property is the lowest; an in-vitro degradation experiment proves that the mechanical property of the composite material can be changed by changing the content of the zinc-doped hydroxyapatite, and the degradation rate of the composite material can be changed by changing the content of the zinc-doped hydroxyapatite, so that the requirement of an implanted part is met. A cytotoxicity experiment shows that a proper concentration of zinc ions can promote the cell viability of mouse osteoblasts.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices, and a preparation method and application thereof. Background Art

[0002] In the field of biomaterials science, hydroxyapatite is a highly regarded bioactive material with a hexagonal close-packed lattice structure. While maintaining a stable lattice structure, some ionic sites in hydroxyapatite can be freely replaced, allowing calcium ions to be substituted with various metal ions, thereby altering the physical and chemical characteristics of hydroxyapatite, as well as its mechanical properties both in vivo and in vitro.

[0003] In the complex bone tissue structure of the human body, there are many metal ions, such as Ca 2+ 、Fe 2+ / Fe 3+ and Zn 2+ These metal ions play a vital role. They are not only the key components of many enzymes, but also participate in cell signal transduction processes and maintain the body's metabolic balance. For example, zinc ions (Zn 2+ ) doping can affect the lattice constant and stability of hydroxyapatite, thereby changing its physical and chemical properties; magnesium ions (Mg 2+ ) can replace some calcium ions, changing the solubility and biological activity of hydroxyapatite; strontium ions (Sr 2+ ) has similar chemical properties to calcium ions, and its doping can enhance the biological activity of hydroxyapatite and play a role in bone repair.

[0004] Zinc ions, the most abundant trace metal element in bone, are not only cofactors for a variety of enzymes but also play a key role in inhibiting bacterial growth and regulating cell proliferation, differentiation, and gene expression. Polylactic acid (PLA) is a biocompatible and biodegradable polymer material that is non-toxic, thermoformable, and its degradation products participate in human metabolism. In tissue engineering, it can meet the requirements of a cell growth carrier material and is widely used in clinical tissue repair. Currently, existing technologies disclose the compounding of nano-hydroxyapatite with polylactic acid to impart osteogenic activity to the material, but there is no description of the compounding of zinc-doped hydroxyapatite with polylactic acid and its application as a bone repair material. Summary of the Invention

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

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

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

[0008] mixing polylactic acid and zinc-doped hydroxyapatite to obtain a mixture;

[0009] placing the mixture in an internal mixer for melt blending to obtain a composite;

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

[0011] Preferably, in the step of placing the mixture in an internal mixer for melt blending, the temperature of the internal mixer is controlled to be 180-190° C., the screw speed is controlled to be 110-120 r / min, and the melt blending time is controlled to be 7-10 min.

[0012] Preferably, in the step of first hot pressing and then cold pressing the composite, the hot pressing specifically includes:

[0013] The composite is preheated at a temperature of 210-220° C. for 6-10 minutes, and then maintained at a temperature of 210-220° C. and a pressure of 10-12 MPa for 5-10 minutes.

[0014] Preferably, in the step of first hot pressing and then cold pressing the composite, the cold pressing specifically comprises: maintaining 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 mass fraction of zinc-doped hydroxyapatite in the mixture is 10%.

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

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

[0019] A dispersant is added to the mixed solution, and the mixture is kept to react at 78-82° C. for 3-4 hours. After the reaction is completed, the mixture is filtered, washed, and dried to obtain zinc-doped hydroxyapatite.

[0020] Preferably, the preparation method of the calcium salt solution is:

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

[0022] The preparation method of the phosphate solution is:

[0023] Adding ammonium dihydrogen phosphate dodecahydrate to water to obtain a phosphate solution; the concentration of the phosphate solution is 0.05 to 0.1 mol / L;

[0024] The preparation method of the zinc salt solution is:

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

[0026] The dispersant is sodium polyacrylate;

[0027] The mass of the dispersant is 0.5-2% of the mass of the mixed liquid;

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

[0029] In a second aspect, the present invention further provides a polylactic acid / zinc-doped hydroxyapatite composite material, which is prepared using the above-mentioned preparation method.

[0030] In a third aspect, the present invention further provides a use of the polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices prepared by the preparation method or the polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices in the preparation of bone repair materials.

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

[0032] 1. The preparation method of the polylactic acid / zinc-doped hydroxyapatite composite material of the present invention uses polylactic acid as a matrix and zinc-doped hydroxyapatite as a reinforcement, and adopts a melt blending method to prepare polylactic acid / zinc-doped hydroxyapatite composite materials with different formula ratios under optimal process conditions. Related characterization proves the successful preparation of polylactic acid-zinc-doped hydroxyapatite. When the content of zinc-doped hydroxyapatite is 10%, the composite material has the best thermal stability and mechanical properties (tensile strength is 63.2MPa). In addition, under the secondary ratio, the bending performance decrease rate is the lowest after the composite material is degraded for 20 days; at the same time, the polylactic acid / zinc-doped hydroxyapatite composite material has higher tensile strength than the polylactic acid / nanohydroxyapatite composite material; this is because zinc ions (Zn 2+) partially replaces the calcium sites in the hydroxyapatite (HA) lattice, causing lattice distortion and increasing the crystal defect density, making the combination of polylactic acid and nano-hydroxyapatite closer, thereby making the composite material have better mechanical properties;

[0033] 2. In vitro degradation experiments demonstrated that the mechanical properties of the polylactic acid / zinc-doped hydroxyapatite composite can be modified by varying the zinc-doped hydroxyapatite content. The degradation rate of the composite can be adjusted by varying the zinc-doped hydroxyapatite content to meet the requirements of the implant site. Furthermore, zinc ions are continuously released during the degradation process. Low concentrations of zinc ions promote osteoblast differentiation by activating the TGF-β / Smad signaling pathway.

[0034] 3. Cytotoxicity experiments showed that appropriate zinc ion concentrations can promote the cell activity of mouse osteoblasts. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive effort.

[0036] Figure 1 The infrared spectra 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;

[0037] Figure 2 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 DSC temperature rise curves (a) and cooling curves (b) 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 prepared in Comparative Example 1;

[0039] Figure 4 XRD spectra 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 prepared in Comparative Example 1;

[0040] Figure 5 The tensile strength 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 prepared in Comparative Example 1;

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

[0042] Figure 7 These are tensile fracture surface morphologies 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 prepared in Comparative Example 1;

[0043] Figure 8 (a) Flexural properties of PLA / Zn-doped HA composites with different formulation ratios after degradation for 0, 5, 10, and 20 days; Figure 8 (b) Zn ion release of 10 wt% 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 survival rate of mouse osteoblasts in the 10 wt% PLA / Zn-HA extract in Example 2;

[0045] Figure 10 This is a graph showing the cell survival rate of mouse osteoblasts in the 10 wt% PLA / nHA extract in Comparative Example 3. DETAILED DESCRIPTION

[0046] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0047] In the description of the present invention, it should be understood that the directions or positions indicated by “upper” and the like are based on the directions or positions shown in the accompanying drawings, or are the directions or positions in which the product of the invention is usually placed when in use, or are the directions or positions commonly understood by those skilled in the art. These directions or positions are only for the convenience of describing the present invention and simplifying the description, and are not intended to indicate or imply that the device or component referred to must have a specific direction, be constructed and operated in a specific direction, and therefore should not be understood as a limitation on the present invention.

[0048] The order of description of the following embodiments is not intended to limit the preferred order of the embodiments. In addition, in the description of this application, the term "including" means "including but not limited to". Various embodiments of the present invention may be presented 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 understood 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 the range. For example, the range description from 1 to 6 should be considered to have 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., as well as single numbers within the range, such as 1, 2, 3, 4, 5 and 6, regardless of the range. In addition, whenever a numerical range is indicated herein, it is meant to include any cited number (fractional or integer) within the indicated range.

[0049] The present invention provides a method for preparing a polylactic acid / zinc-doped hydroxyapatite composite material for a bone fixation device, comprising the following steps:

[0050] mixing polylactic acid and zinc-doped hydroxyapatite to obtain a mixture;

[0051] placing the mixture in an internal mixer for melt blending to obtain a composite;

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

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

[0054] In some embodiments, in the step of first hot pressing and then cold pressing the composite, the hot pressing specifically includes:

[0055] The composite is preheated at a temperature of 210-220° C. for 6-10 minutes, and then maintained at a temperature of 210-220° C. and a pressure of 10-12 MPa for 5-10 minutes.

[0056] In some embodiments, in the step of hot pressing and then cold pressing the composite, the cold pressing specifically includes: maintaining 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 method for preparing zinc-doped hydroxyapatite comprises the following steps:

[0060] S1. Heating the phosphate salt solution to 78-82° C. under an inert atmosphere, then dropwise adding the zinc salt solution and the calcium salt solution to the phosphate salt solution, and adjusting the pH of the system to 8.8-9.2 after the dropwise addition is completed to obtain a mixed solution;

[0061] S2. Add a dispersant to the mixed solution, and then keep the reaction at 78-82° C. for 3-4 hours. After the reaction is completed, filter, wash, and dry to obtain zinc-doped hydroxyapatite.

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

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

[0064] The preparation method of phosphate solution is:

[0065] Adding ammonium dihydrogen phosphate dodecahydrate to water to obtain a phosphate solution; the concentration of the phosphate solution is 0.05 to 0.1 mol / L;

[0066] The preparation method of zinc salt solution is:

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

[0068] The dispersant is sodium polyacrylate;

[0069] The mass of the dispersant is 0.5-2% of the mass of the mixed liquid;

[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 comprises the following steps:

[0073] S1. Transfer the phosphate salt solution to a nitrogen-protected three-necked reaction flask, add a magnetic stirrer, and introduce nitrogen to exclude oxygen; heat the mixture to 78-82° C. in an oil bath, add the calcium salt solution dropwise at a rate of 1-2 drops per second using a constant flow pump, and simultaneously add the zinc salt solution dropwise at a rate of 1-2 drops per 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 (titration with ammonia water (5 wt%) and double verification with alkaline pH test paper) to obtain a mixed solution;

[0074] S2. Add sodium polyacrylate dispersant to the mixed solution in an amount of 0.5-2% by mass of the mixed solution, and simultaneously disperse with ultrasound (ultrasound at 40 kHz for 5 min); maintain the reaction temperature at 78-82° C. for 3-4 hours to ensure directional growth of crystals;

[0075] S3. After the reaction is completed, the reaction solution is allowed to settle overnight, filtered through a Buchner funnel (0.22 μm filter membrane), and washed three times with deionized water (the amount of washing solution is 3 times the volume of the product); ultrasonic-assisted purification (ultrasound at 40 kHz for 10 to 15 minutes) is performed, followed by a second filtration to remove residual impurities; vacuum drying at 80°C overnight is performed, and agglomeration-free zinc-doped hydroxyapatite powder is obtained after grinding.

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

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

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

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

[0080] In the following examples, 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 stirrer, and introduce nitrogen to exclude oxygen; heat to 80°C in an oil bath, add the calcium salt solution dropwise at a rate of 1 drop / second using a constant flow pump, and simultaneously add the 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 system pH to 9.0 in real time to obtain a mixed solution;

[0082] S2. Sodium polyacrylate dispersant was added to the mixture in an amount of 1% by mass of the mixture, and ultrasonic dispersion was performed (ultrasound at 40 kHz for 5 min); the reaction temperature was maintained at 80° C. for 3 hours to ensure directional growth of the crystals;

[0083] S3. After the reaction is completed, the reaction solution is allowed to settle overnight, filtered through a Buchner funnel (0.22 μm filter membrane), and washed three times with deionized water; ultrasonic-assisted purification (ultrasound at 40 kHz for 10 to 15 minutes) is performed, followed by a second filtration to remove residual impurities; vacuum drying at 80° C. overnight, and grinding to obtain agglomeration-free zinc-doped hydroxyapatite powder;

[0084] Wherein, the preparation method of calcium salt solution is:

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

[0086] The preparation method of phosphate solution is:

[0087] Adding ammonium dihydrogen phosphate dodecahydrate to water to obtain a phosphate solution; the concentration of the phosphate solution is 0.06 mol / L;

[0088] The preparation method of zinc salt solution is:

[0089] Add zinc nitrate hexahydrate to water to obtain a zinc salt solution; the concentration of the zinc salt solution is 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] The molar proportion of zinc element in the zinc-doped hydroxyapatite prepared above is 10%, corresponding to a mass fraction of 6.35%.

[0093] In the following comparative example, the preparation method of nano-hydroxyapatite comprises the following steps:

[0094] S1. Transfer the phosphate salt solution to a nitrogen-protected three-necked reaction flask, add a magnetic stirrer, and introduce nitrogen to exclude oxygen; heat to 80° C. in an oil bath, and add the 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 mixed solution;

[0095] S2. Sodium polyacrylate dispersant was added to the mixture in an amount of 1% by mass of the mixture, and ultrasonic dispersion was performed (ultrasound at 40 kHz for 5 min); the reaction temperature was maintained at 80° C. for 3 hours to ensure directional growth of the crystals;

[0096] S3. After the reaction is completed, the reaction solution is allowed to settle overnight, filtered through a Buchner funnel (0.22 μm filter membrane), and washed three times with deionized water; ultrasonic-assisted purification (ultrasound at 40 kHz for 10 to 15 minutes) is performed, followed by a second filtration to remove residual impurities; vacuum drying at 80°C overnight is performed, and a non-agglomerated nano-hydroxyapatite powder is obtained after grinding;

[0097] Wherein, the preparation method of calcium salt solution is:

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

[0099] The preparation method of phosphate solution is:

[0100] Adding ammonium dihydrogen phosphate dodecahydrate to water to obtain a phosphate solution; the concentration of the phosphate solution is 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] The present invention provides a method for preparing a polylactic acid / zinc-doped hydroxyapatite composite material for a bone fixation device, comprising the following steps:

[0105] S1, drying polylactic acid and zinc-doped hydroxyapatite at 40°C for 12h respectively;

[0106] Mixing dried polylactic acid and zinc-doped hydroxyapatite (Zn-HA) to obtain a mixture; wherein the mass fraction of the zinc-doped hydroxyapatite in the mixture is 5% and the mass fraction of the polylactic acid is 95%;

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

[0108] S3, hot pressing the composite and then cold pressing it to obtain a polylactic acid / zinc-doped hydroxyapatite composite material (denoted as 5 wt% PLA / Zn-HA);

[0109] In the step of first hot pressing the composite and then cold pressing it, the hot pressing specifically includes:

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

[0111] The cold pressing specifically includes: maintaining 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 the embodiment of the present application 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%. The prepared polylactic acid / zinc-doped hydroxyapatite composite material is recorded as 10wt% PLA / Zn-HA.

[0114] Example 3

[0115] The preparation method of the polylactic acid / zinc-doped hydroxyapatite composite material provided in the embodiment of the present application 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%. The prepared polylactic acid / zinc-doped hydroxyapatite composite material is recorded as 15wt% PLA / Zn-HA.

[0116] Example 4

[0117] The preparation method of the polylactic acid / zinc-doped hydroxyapatite composite material provided in the embodiment of the present application 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%. The prepared polylactic acid / zinc-doped hydroxyapatite composite material is recorded as 20wt% PLA / Zn-HA.

[0118] Comparative Example 1

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

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

[0121] The dried polylactic acid was placed in an internal mixer and melt-blended at 180° C. and a screw speed of 110 r / min for 7 minutes to obtain a composite;

[0122] S3, hot pressing the composite and then cold pressing it to obtain a polylactic acid material (denoted as PLA);

[0123] In the step of first hot pressing the composite and then cold pressing it, the hot pressing specifically includes:

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

[0125] The cold pressing specifically includes: maintaining 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, comprising the following steps:

[0128] S1, drying polylactic acid and nanohydroxyapatite at 40°C for 12h respectively;

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

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

[0131] S3, hot pressing the composite and then cold pressing it to obtain a polylactic acid / nanohydroxyapatite composite material (denoted as 5 wt% PLA / nHA);

[0132] In the step of first hot pressing the composite and then cold pressing it, the hot pressing specifically includes:

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

[0134] The cold pressing specifically includes: maintaining 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 recorded 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 recorded 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 recorded as 20wt% PLA / nHA.

[0141] Performance Characterization

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

[0143] from Figure 1 It can be seen that in the infrared spectrum of the pure polylactic acid material PLA prepared in Comparative Example 1, 1759 cm -1 and 1185cm -1 The stretching vibration of C=O and COC groups indicates the presence of ester bonds in the polylactic acid molecule. -1 and 2995cm -1 The absorption peak at 563 cm corresponds to the stretching vibration of CH and -CH3. -1 and 605cm -1 The absorption peak at 3430cm is the characteristic peak of the γ4 vibration mode of phosphate. -1The absorption peak at is the characteristic peak of hydroxyl groups, corresponding to the stretching vibration of hydroxyl groups. The incorporation of zinc does not affect the functional groups of nanohydroxyapatite. The infrared spectra of the polylactic acid / zinc-doped hydroxyapatite composites prepared in Examples 1 to 4 are compared with those of polylactic acid and zinc-doped hydroxyapatite. The composites have all the characteristic peaks of zinc-doped hydroxyapatite and polylactic acid, and the peak positions are not significantly shifted, indicating that there is no chemical bonding reaction between polylactic acid and zinc-doped hydroxyapatite, and only physical blending is involved.

[0144] Figure 2 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 formula 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 from the figure that the sample has a certain thermal stability in the temperature range of 100-300℃. The temperature corresponding to the mass loss of pure polylactic acid material is 303.8℃ when the mass loss is 5wt%. With the increase of the content of zinc-doped hydroxyapatite, the T 5％ The temperatures showed a trend of first increasing and then decreasing, reaching 321.6°C, 331.8°C, 329.8°C, and 311.3°C, respectively. This is because when the content of zinc-doped hydroxyapatite is low, as the zinc-doped hydroxyapatite is added, the zinc-doped hydroxyapatite acts as a nucleating agent to promote the crystallization of polylactic acid, making it less likely for the molecular chain of polylactic acid to move at high temperatures, thereby improving its thermal stability. When the content of zinc-doped hydroxyapatite is too high, the zinc-doped hydroxyapatite agglomerates inside the polylactic acid, causing its interfacial compatibility with the polylactic acid matrix to deteriorate, resulting in microcracks or voids at the interface. These defects reduce the thermal stability of the polylactic acid matrix. The maximum thermal weight loss temperatures in each group of samples are not much different, indicating that zinc-doped hydroxyapatite does not change the kinetic characteristics of the polylactic acid decomposition reaction. This indicates that the dispersion state of zinc-doped hydroxyapatite in the composite material has limited effect on the decomposition mechanism of polylactic acid. When the experimental temperature reaches 600°C, the polylactic acid matrix is completely thermally decomposed, leaving only zinc-doped hydroxyapatite particles that are difficult to thermally decompose. 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 mixed into polylactic acid during the melt blending process of polylactic acid and zinc-doped hydroxyapatite without much loss.

[0146] Figure 3The DSC temperature rise curve (a) and cooling curve (b) of the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composite materials with different formula ratios prepared in Examples 1 to 4, and the polylactic acid material prepared in Comparative Example 1.

[0147] from Figure 3 From the heating curves of (a), we can see that the T g In the range of 57~59℃. Taking into account the test error, the T g (Glass transition temperature) has basically not changed. This shows that there is no chemical reaction between zinc-doped hydroxyapatite and polylactic acid. Zinc-doped hydroxyapatite only exists as a physical filler and does not change the mobility of polylactic acid molecular chains. This is consistent with the infrared test results. The crystallization transition temperature of pure polylactic acid is 107.6℃ and the melting transition temperature is 161.9℃. In comparison, with the addition of zinc-doped hydroxyapatite, the T cc (Crystallization transition temperature) shifts left, T m The melting transition temperature (MLT) shifts to the right. This indicates that the addition of zinc-doped hydroxyapatite improves the nucleation efficiency and thermal stability of PLA crystallization. The increased crystallization rate can be attributed to the zinc-doped hydroxyapatite acting as nucleation sites, inducing heterogeneous nucleation of PLA. The improved thermal stability is likely due to the addition of zinc-doped hydroxyapatite promoting the crystallization of PLA, thereby increasing the melting temperature of the composite.

[0148] from Figure 3 From the cooling curve in (b), it can be seen that compared with pure PLA material, the PLA / Zn-doped hydroxyapatite composite material with the addition of Zn-doped hydroxyapatite has a cold crystallization peak. This may be because during the cooling process of PLA, the presence of Zn-doped hydroxyapatite plays the role of a heterogeneous nucleating agent, promoting the crystallization of PLA.

[0149] Figure 4 These are XRD spectra 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 prepared in Comparative Example 1.

[0150] Polylactic acid is a semi-crystalline polymer, and its characteristic peak usually appears at 2θ=16.8°. Figure 4As can be seen in the XRD pattern of pure PLA, a broad and symmetrical diffraction peak is observed at 2θ = 16.8°, indicating the coexistence of crystalline and amorphous regions in the PLA, consistent with its crystallization characteristics. After the addition of zinc-doped hydroxyapatite to PLA, the peak at 2θ = 16.8° in the composite material sharpens, indicating that the addition of zinc-doped hydroxyapatite causes the amorphous region of PLA to transition toward a crystalline region. This is likely because zinc-doped hydroxyapatite acts as a nucleating agent in the PLA system. As the zinc-doped hydroxyapatite content increases, the number of sites available for crystallization nucleation increases, leading to improved crystallinity in the composite. When the zinc-doped hydroxyapatite content is too high, the agglomeration of the particles becomes more pronounced, resulting in unstable crystallization sites and a decrease in crystallization efficiency, which is consistent with the DSC analysis. The diffraction peaks of zinc-doped hydroxyapatite particles are consistent with the standard card of hydroxyapatite (JCPDS 74-0566), with characteristic diffraction peaks of crystal planes such as (002), (211), (300), and (130). When zinc-doped hydroxyapatite is added to pure polylactic acid, these characteristic peaks of zinc-doped hydroxyapatite appear in the XRD spectrum of the composite material. As the content of zinc-doped hydroxyapatite increases, the intensity of the corresponding peaks also increases, indicating that zinc-doped hydroxyapatite is successfully mixed into the polylactic acid composite material during the melt blending process of polylactic acid and zinc-doped hydroxyapatite, and corresponds to the formulation ratio, which is consistent with the thermogravimetric analysis results.

[0151] Figure 5 It is the tensile strength of the zinc-doped hydroxyapatite (Zn-HA) used in Example 1, the polylactic acid / zinc-doped hydroxyapatite composite materials with different formula ratios prepared in Examples 1 to 4, and the polylactic acid material prepared in Comparative Example 1. Figure 5 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 It is the tensile strength of the polylactic acid material prepared in Comparative Example 1 and the polylactic acid / nanohydroxyapatite composite materials in Comparative Examples 2 to 5. Figure 6 %, 15 wt % PLA / nHA in Comparative Example 4, and 20 wt % PLA / nHA in Comparative Example 5, respectively.

[0153] The tensile strength is tested according to GB / T 1040-92 standard.

[0154] Depend on Figure 5It can be seen that the tensile strength of pure polylactic acid is 61.5MPa. After the addition of zinc-doped hydroxyapatite, the tensile strength of polylactic acid-zinc-doped hydroxyapatite shows a trend of first increasing and then decreasing. When the content of zinc-doped hydroxyapatite added is 10wt%, the tensile strength reaches a maximum value of 63.2MPa. This is because the compatibility of polylactic acid and zinc-doped hydroxyapatite is poor. When the content of zinc-doped hydroxyapatite is too low, the interface bonding between polylactic acid and zinc-doped hydroxyapatite may not be sufficient, resulting in a decrease in the efficiency of stress transfer within the material. Poor interface bonding will make the composite material more prone to delamination or fracture when subjected to external force. When the content of zinc-doped hydroxyapatite is too high, zinc-doped hydroxyapatite will agglomerate in the polylactic acid matrix, increasing the internal defects of the polylactic acid material. These defects will act as stress concentration points, which can easily cause the material to fracture when subjected to force.

[0155] from Figure 6 It can be seen that after compounding nanohydroxyapatite in polylactic acid, the tensile strength of the composite material shows a trend of first increasing and then decreasing. When the content of nanohydroxyapatite is 10wt%, the tensile strength of the composite material reaches a maximum value of 62.5MPa, which is slightly higher than that of pure polylactic acid. The above changes are explained by the fact that due to the poor compatibility between polylactic acid and nanohydroxyapatite, when the content of nanohydroxyapatite composite material is too low, the interface bonding between polylactic acid and nanohydroxyapatite may not be sufficient, resulting in reduced efficiency of stress transfer within the material. Poor interface bonding will make the composite material more prone to delamination or fracture when subjected to external force. When the content of nanohydroxyapatite is too high, nanohydroxyapatite will agglomerate in the polylactic acid matrix, increasing the internal defects of the polylactic acid material. These defects will act as stress concentration points, which can easily cause the material to fracture when subjected to force.

[0156] Further, by Figure 5 and Figure 6 By comparison, it can be seen that the polylactic acid / zinc-doped hydroxyapatite composite material has higher tensile strength than the polylactic acid / nanohydroxyapatite composite material and pure polylactic acid; specifically, compared with pure polylactic acid, the tensile strength is increased from 61.5MPa to 63.2MPa (an increase of 2.76%), and compared with the polylactic acid / nanohydroxyapatite composite material, the tensile strength is increased from 62.5MPa to 63.2MPa (an increase of 1.12%). The polylactic acid / zinc-doped hydroxyapatite composite material of the present invention has better mechanical properties than pure polylactic acid and polylactic acid / nanohydroxyapatite composite materials, and the performance improvement mechanism is: lattice strengthening effect: zinc ions (Zn 2+ ) partially replaces the calcium sites in the hydroxyapatite (HA) lattice, causing lattice distortion, increasing the crystal defect density, and making the combination of polylactic acid and nano-hydroxyapatite tighter, thereby making the composite material have better mechanical properties and lower degradation rate.

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

[0158] Depend on Figure 7 From the morphology, it can be seen that the tensile fracture surface of pure polylactic acid is relatively smooth and flat, without obvious particles and bone-like structures, indicating that pure polylactic acid has high brittleness and poor toughness. When zinc-doped hydroxyapatite is added to polylactic acid, the surface roughness of the composite material increases significantly, indicating that the toughness of the composite material is slightly improved. In addition, when the zinc-doped hydroxyapatite content of the composite is low (5-10wt%), the zinc-doped hydroxyapatite is dispersed more evenly in the polylactic acid, and larger agglomerates are observed. When the zinc-doped hydroxyapatite content is too high (15-20wt%), it can be observed that the zinc-doped hydroxyapatite filler forms large aggregates in the polylactic acid matrix. And as the content of zinc-doped hydroxyapatite increases, the aggregates of zinc-doped hydroxyapatite increase. This will affect the mechanical properties of the composite material to a certain extent, reducing the thermodynamic and mechanical properties of the composite material.

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

[0160] During the bone grafting process, the material degrades within the body, while new bone tissue continuously grows and develops, gradually replacing the degraded material. Ideally, the scaffold's degradation rate would correspond to the growth rate of bone tissue. Therefore, in vitro degradation experiments are necessary to evaluate the applicability of polylactic acid / zinc-doped hydroxyapatite composites for 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 formula ratios prepared in Examples 1 to 4 were placed in a 125 mL bottle made of high-density polyethylene filled with phosphate buffer solution (pH 7.4±0.1) at a ratio of 1 g / 20 mL, placed in a constant temperature-controlled oscillator at (37±1)°C, and shaken at 200 r / min. The bending properties of the materials were then sampled and tested at 0 days, 5 days (120 h), 10 days, and 20 days.

[0162] Figure 8 (a) Flexural properties of polylactic acid / zinc-doped hydroxyapatite composites with different formulation ratios after 0, 5, 10, and 20 days of degradation (flexural strength tested according to GB / T 9341-2000). 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 The data in (a) show that after 20 days of degradation, the flexural strength of the polylactic acid material decreased from 62.1 MPa to 57.8 MPa, a decrease of 6.9%. When the zinc-doped hydroxyapatite content was 5wt%, 10wt%, 15wt%, and 20wt%, the flexural strength of the composite material decreased by 7.5%, 5.5%, 7.1%, and 9.5%, respectively, after 20 days, showing a trend of first decreasing and then increasing. When the zinc-doped hydroxyapatite content was 10wt%, the composite material had the lowest rate of decrease in flexural performance after degradation. In addition, it can be observed that the rate of decrease in flexural performance of the composite material changes with the change in the zinc-doped hydroxyapatite content, indicating that the degradation rate of polylactic acid can change with the change in the zinc-doped hydroxyapatite content. Therefore, in theory, the degradation rate of the composite material can be changed by changing the zinc-doped hydroxyapatite content to meet the requirements of the implantation site.

[0164] Figure 8 (b) is the ion release of 10wt% PLA / Zn-HA in Example 2 after 0, 5, 10, and 20 days of degradation. The images show that the composite material continues to release zinc ions as the degradation time increases. As time increases, the amount of zinc ion release shows a decreasing trend. This may be because the zinc ions initially released come from the zinc-doped hydroxyapatite on the surface of the composite material. After the zinc in the surface zinc-doped hydroxyapatite is absorbed, the zinc-doped hydroxyapatite from the interior of the composite material is blocked by polylactic acid, making it difficult to release zinc, resulting in a reduced release rate of zinc ions. Whether the released zinc can promote bone repair still needs to be verified through biological experiments.

[0165] Figure 9 The cell survival rate of mouse osteoblasts in the 10 wt% PLA / Zn-HA extract in Example 2 is as follows:

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

[0167] (2) 200 μL of the extract prepared above was added to a 24-well plate (each well containing 5000 MC3T3 cells), with three parallel samples for each experimental group, and compared with a blank group of fresh culture medium solution. The plate was placed in a cell culture incubator at 37°C for 24 h.

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

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

[0170] (5) The absorbance value of the blank group was used as the control sample, and the ratio of the absorbance value of the experimental group to it was calculated to evaluate the cell survival rate.

[0171] according to Figure 9 Data from the study show that the cell viability of the polylactic acid / zinc-doped hydroxyapatite composite containing 10 wt% zinc-doped hydroxyapatite decreased with increasing concentration. From 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 with pure polylactic acid, the polylactic acid / zinc-doped hydroxyapatite composite exhibited good biocompatibility at low concentrations, but its bioactivity decreased at high concentrations. This may be due to the concentration-dependent effect of zinc ions on cells. When the extract concentration was too low, the zinc ion concentration was too low, and zinc ions had a certain promoting effect on the activity of mouse osteoblasts. Conversely, when the extract concentration was too high, the zinc ion concentration was too high, which damaged the integrity of the mouse osteoblast cell membrane and led to cell death. Therefore, when selecting zinc ions for incorporation into hydroxyapatite, the zinc ion concentration must be strictly controlled. In addition, within the extract concentration range of 0.1-0.8 mg / mL, the cell activity of mouse osteoblasts was above 90%, indicating that the composite material still had good biocompatibility.

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

[0173] However, adding 10 wt% of nanohydroxyapatite to pure polylactic acid improved its biocompatibility: within the same concentration range, the cell viability was 98.6%, 94.4%, 93.6%, and 93.8%, respectively. This may be because nanohydroxyapatite releases hydroxide ions in the culture medium, neutralizing hydrogen ions produced by polylactic acid degradation and maintaining a stable pH in the culture medium, thereby increasing cell metabolic activity and cell survival.

[0174] Further, by Figures 9-10 By comparison, at a concentration of 0.1 to 0.8 mg / mL, in the low concentration range, the 10 wt% PLA / Zn-HA extract of the present invention significantly improved the survival rate of mouse osteoblasts compared with 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 the present invention releases zinc ions, and low concentrations of zinc ions (<0.2 mg / mL) promote osteoblast differentiation by activating the TGF-β / Smad signaling pathway.

[0175] In summary:

[0176] The present invention uses a melt blending method to prepare polylactic acid / zinc-doped hydroxyapatite composite materials with different zinc-doped hydroxyapatite contents. The composite materials can be used in research in the field of bone repair. The specific conclusions are as follows:

[0177] (1) With polylactic acid as the matrix and zinc-doped hydroxyapatite as the reinforcement, polylactic acid / zinc-doped hydroxyapatite composites with different formulation ratios were prepared by melt blending under optimal process conditions. Relevant characterizations proved the successful preparation of polylactic acid-zinc-doped hydroxyapatite. When the content of zinc-doped hydroxyapatite was 10%, the composite material had the best thermal stability and mechanical properties (tensile strength of 63.2MP). In addition, under the sub-ratio, the bending performance degradation rate of the composite material was the lowest after 20 days of degradation; at the same time, the polylactic acid / zinc-doped hydroxyapatite composite material had higher tensile strength than the polylactic acid / nanohydroxyapatite composite material; this is because the zinc ion (Zn 2+ ) partially replaces the calcium sites in the hydroxyapatite (HA) lattice, causing lattice distortion and increasing the crystal defect density, making the combination of polylactic acid and nano-hydroxyapatite closer, thereby making the composite material have better mechanical properties;

[0178] (2) In vitro degradation experiments demonstrated that the mechanical properties of the polylactic acid / zinc-doped hydroxyapatite composite material can be altered by changing the content of zinc-doped hydroxyapatite. The degradation rate of the composite material can be modified by changing the content of zinc-doped hydroxyapatite to meet the requirements of the implantation site. In addition, zinc ions are continuously released during the degradation process, and low concentrations of zinc ions promote osteoblast differentiation by activating the TGF-β / Smad 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 in the scope of protection of the present invention.

Claims

1. A polylactic acid / zinc-doped hydroxyapatite composite material for bone fixation devices and a preparation method thereof, characterized in that: The following steps are involved: mixing polylactic acid and zinc-doped hydroxyapatite to obtain a mixture; placing the mixture in an internal mixer for melt blending to obtain a composite; The composite is firstly hot-pressed and then cold-pressed to obtain a polylactic acid / zinc-doped hydroxyapatite composite material.

2. The method for preparing the polylactic acid / zinc-doped hydroxyapatite composite material according to claim 1, wherein: In the step of placing the mixture in an internal mixer for melt blending, the temperature of the internal mixer is controlled to be 180-190° C., the speed of the screw is controlled to be 110-120 r / min, and the melt blending time is controlled to be 7-10 min.

3. The method for preparing the polylactic acid / zinc-doped hydroxyapatite composite material according to claim 1, wherein: In the step of first hot pressing the composite and then cold pressing it, the hot pressing specifically includes: The composite is preheated at a temperature of 210-220° C. for 6-10 minutes, and then maintained at a temperature of 210-220° C. and a pressure of 10-12 MPa for 5-10 minutes.

4. The method for preparing the polylactic acid / zinc-doped hydroxyapatite composite material according to claim 1, wherein: In the step of first hot pressing the composite and then cold pressing the composite, the cold pressing specifically includes: maintaining the hot pressed composite at a temperature of 20-25° C. and a pressure of 10-12 MPa for 5-10 minutes.

5. The method for preparing the polylactic acid / zinc-doped hydroxyapatite composite material according to claim 1, wherein: The mass fraction of zinc-doped hydroxyapatite in the mixture is 5-20%.

6. The method for preparing the polylactic acid / zinc-doped hydroxyapatite composite material according to claim 5, wherein: The mass fraction of zinc-doped hydroxyapatite in the mixture is 10%.

7. The method for preparing the polylactic acid / zinc-doped hydroxyapatite composite material according to claim 1, wherein: The preparation method of the zinc-doped hydroxyapatite comprises the following steps: The phosphate salt solution is heated to 78-82° C. under an inert atmosphere, and then the zinc salt solution and the calcium salt solution are added dropwise to the phosphate salt solution. After the addition is completed, the pH of the system is adjusted to 8.8-9.2 to obtain a mixed solution; A dispersant is added to the mixed solution, and the mixture is kept to react at 78-82° C. for 3-4 hours. After the reaction is completed, the mixture is filtered, washed, and dried to obtain zinc-doped hydroxyapatite.

8. The method for preparing the polylactic acid / zinc-doped hydroxyapatite composite material according to claim 1, wherein: The preparation method of the calcium salt solution is: Calcium nitrate tetrahydrate is added to water to obtain a calcium salt solution; the concentration of the calcium salt solution is 0.1 to 0.2 mol / L; The preparation method of the phosphate solution is: Adding ammonium dihydrogen phosphate dodecahydrate to water to obtain a phosphate solution; the concentration of the phosphate solution is 0.05 to 0.1 mol / L; The preparation method of the zinc salt solution is: Adding zinc nitrate hexahydrate to water to obtain a zinc salt solution; the concentration of the zinc salt solution is 0.01 to 0.2 mol / L; The dispersant is sodium polyacrylate; The mass of the dispersant is 0.5-2% of the mass of the mixed liquid; The volume ratio of the calcium salt solution, the zinc salt solution and the phosphate salt solution is (9-10):(1-2):(10-11).

9. A polylactic acid / zinc-doped hydroxyapatite composite material, characterized in that: The preparation method is as described in any one of claims 1 to 8.

10. Use of the polylactic acid / zinc-doped hydroxyapatite composite material prepared by the preparation method according to any one of claims 1 to 8 or the polylactic acid / zinc-doped hydroxyapatite composite material according to claim 9 in preparing bone repair materials.

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