Modified polylactic acid fiber, calcium phosphate cement with gradient degradability, and preparation method

Abstract

The application relates to the technical field of bone tissue engineering materials, in particular to a modified polylactic acid fiber, a gradient-degradable calcium phosphate bone cement and a preparation method. The modified polylactic acid fiber comprises the following components in parts by weight: 85-100 parts of polylactic acid, 5-15 parts of a nucleating agent, 2-5 parts of a plasticizer and 0.2-0.5 parts of a surfactant. The crystallinity and degradation rate of the polylactic acid are changed by adjusting the combination ratio of the modified material of the polylactic acid, so that the modified polylactic acid fiber with different degradation properties is obtained. The modified polylactic acid fiber with different degradation properties is combined to prepare the calcium phosphate bone cement with multi-stage gradient degradation which can be accurately controlled, a plurality of gradient degradation processes are formed in the bone repair stage, and the bone tissue growth speed can be perfectly adapted through control, so that the calcium phosphate bone cement is suitable for the field of bone repair and is especially suitable for bone defects caused by orthopedic diseases related to the elderly.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of bone tissue engineering materials, in particular to a modified polylactic acid fiber, a calcium phosphate bone cement capable of gradient degradation and a preparation method. BACKGROUND

[0002] Bone is an important tissue organ of the human body. In recent years, the number of cases of bone defects caused by various reasons such as traffic accidents and orthopedic diseases is increasing. In addition, China is currently entering an aging society, and orthopedic diseases related to the elderly are increasing. Under this background, artificial bone replacement materials for repairing bone damage have become a focus of medical research, and the demand for bone repair biomaterials is also increasing.

[0003] Calcium phosphate bone cement (CPC) stands out among many bone tissue engineering materials because of the following advantages: (1) good biocompatibility, calcium phosphate will form hydroxyapatite after hydration, which is the same as the inorganic components of human bone tissue; (2) self-curing at body temperature, without the need for high-temperature sintering; (3) arbitrary plasticity, meeting the needs of different bone shapes in practice; (4) has a microporous structure, the presence of pores is conducive to the repair and reconstruction of bone tissue. Although calcium phosphate bone cement has these advantages, which basically meet the requirements of bone repair materials, the micropores in the solidified body of calcium phosphate bone cement are mostly sub-micron or nanoscale micropores, which leads to the growth of new bone tissue only on the surface of the calcium phosphate bone cement, which is not conducive to the ingrowth of new bone tissue. Therefore, the preparation of calcium phosphate bone cement with high porosity and gradient degradation has attracted the attention of many researchers.

[0004] Polylactic acid (PLA) is one of the most studied polyester biodegradable materials, and is a safe organic material approved by the US FDA for use in clinical and biomedical industries, with good biocompatibility and biodegradability. The use of polylactic acid mixed with calcium phosphate bone cement can achieve the preparation of high-porosity calcium phosphate bone cement. However, for human bone repair, the degradation rate of polylactic acid is too fast, and a large amount of degradation products produced at the same time can cause excessive local acidity and damage to cells and tissues. In addition, the degradation rate of polylactic acid is too fast, and does not match the speed of bone tissue reconstruction. Especially for the elderly, cell growth is even slower, and the ingrowth of new bone tissue requires a longer process. At this time, the large number of pores with larger pore sizes will cause a serious reduction in the mechanical properties of the calcium phosphate bone cement, which cannot withstand the original weight. Therefore, it is of great significance to use modified polylactic acid with different degradation rates to prepare calcium phosphate bone cement with multiple degradation gradients.

[0005] Chinese invention patent CN104288833A uses polyethylene glycol (PEG) as an initiator to synthesize a biodegradable polymer PEG-b-PLGA through ring-opening polymerization, and uses the polymer as a drug carrier in bone cement, and to some extent solves the problem of excessive acid product content in the degradation process of polylactic acid-glycolic acid copolymer (PLGA) to cause inflammation. The above Chinese invention patent solves the problem of too many acid products by reducing the degradation rate of polylactic acid, but blindly reducing the degradation rate of PLA will cause the problem that bone tissue cannot grow into the bone tissue in the early stage of degradation, so in practice a multi-level gradient degradation should be formed, and the degradation rate is adjusted to match the growth rate of bone tissue. Chinese invention patent CN101461963A adds natural and synthetic high molecular materials to calcium phosphate bone cement to prepare a bone tissue engineering scaffold material with gradient degradation by using the different degradation rates of the two high molecular materials, but the degradation rate of the natural high molecular material is too fast, the regulation ability is limited, and the price is expensive. The above Chinese invention patents do not achieve adjustable degradation rate, so the prior art still needs to be improved and developed. SUMMARY

[0006] In view of the shortcomings of the prior art, the purpose of the present application is to provide a modified polylactic acid fiber, a calcium phosphate bone cement with gradient degradation and a preparation method, aiming to solve the problem of uncontrollable degradation rate of existing biodegradable materials and mismatch with the growth rate of bone tissue.

[0007] The technical solution of the present application is as follows:

[0008] A modified polylactic acid fiber, wherein the modified polylactic acid fiber comprises the following components by weight fraction:

[0009] Polylactic acid 85-100 parts, nucleating agent 5-15 parts, plasticizer 2-5 parts, and surfactant 0.2-0.5 parts.

[0010] The modified polylactic acid fiber provided by the present application can be used to prepare a calcium phosphate bone cement with a multi-level degradation gradient, and can form multiple gradient degradation processes during bone repair, and can perfectly adapt to the growth rate of bone tissue through regulation, and can adjust the degradation gradient according to the application field, and is suitable for the field of bone repair, especially for bone defects caused by orthopedic diseases related to the elderly.

[0011] Further, the molecular weight of the polylactic acid is 80000-120000 g / mol, and the PDI is less than 2.0.

[0012] Within this molecular weight range, polylactic acid has both processability and mechanical strength. If the molecular weight is too high, the melt index of polylactic acid is low, and processing is difficult. If the molecular weight is too low, the mechanical properties of the modified polylactic acid fiber prepared are low, and the failure is fast.

[0013] Further, the nucleating agent is talcum powder and polyglycolic acid; the mass ratio of the talcum powder to the polyglycolic acid is 1:1-4:1; the talcum powder is superfine talcum powder, and the particle size is 1500-3000 mesh.

[0014] Further, the plasticizer is polyethylene glycol; the molecular weight of the polyethylene glycol is 5000-10000 g / mol.

[0015] Further, the surfactant is polyvinylpyrrolidone.

[0016] A preparation method of the modified polylactic acid fiber as described above, comprising the following steps:

[0017] The polylactic acid and the nucleating agent are dried in a vacuum atmosphere, and the polylactic acid, the nucleating agent, the plasticizer, and the surfactant are mixed in proportion to form a blend; the drying temperature is 80-120℃;

[0018] The blend is extruded through an extruder and granulated through a cutting machine to obtain a modified polylactic acid material, which is then dried;

[0019] The modified polylactic acid material is obtained by melt spinning, winding, and drawing to obtain a modified polylactic acid fiber material;

[0020] The modified polylactic acid fiber material is screened after being cut to obtain a modified polylactic acid fiber;

[0021] The length of the modified polylactic acid fiber is 0.5-2.0 mm.

[0022] Further, the mixing process is carried out by a high-speed mixer, the rotation speed of the high-speed mixer is 1500-2000 r / min; the temperature of the extruder is 170-200℃, and the rotation speed is 50-75 r / min;

[0023] The temperature of the melt spinning is 200-250℃; the winding speed is 1000-1500 m / min.

[0024] The application discloses a calcium phosphate bone cement with gradient degradation, wherein the calcium phosphate bone cement is solidified by a solid phase and a solidification liquid; the ratio of the solidification liquid to the solid phase is 0.3-0.7 ml:1 g; the solid phase comprises calcium phosphate powder and hydroxymethyl cellulose; the solid phase further comprises at least one modified biodegradable fiber; when the solid phase comprises two or more than two modified biodegradable fibers, the degradation speed of each modified biodegradable fiber is different; the modified biodegradable fiber is a modified polylactic acid fiber as described above; the concentration of the solidification liquid is 0.35-0.5 mol / L; the hydroxymethyl cellulose accounts for 1.5% of the total mass of the solid phase, the modified polylactic acid fiber accounts for 1.5%-4.5% of the total mass of the solid phase, and the balance is the calcium phosphate powder.

[0025] Further, the calcium phosphate powder is one or more than two of alpha-tricalcium phosphate, beta-tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, anhydrous calcium hydrogen phosphate, dihydrate calcium hydrogen phosphate, calcium dihydrogen phosphate, calcium pyrophosphate, hydroxyapatite, fluorapatite, strontium apatite and carbon-containing apatite; the solidification liquid is one or more than two of normal saline, sodium citrate solution and sodium hydrogen phosphate solution.

[0026] A preparation method of the calcium phosphate bone cement with gradient degradation as described above, wherein the preparation method comprises the following steps:

[0027] Preparation of the modified polylactic acid fiber;

[0028] Mixing the calcium phosphate powder, the hydroxymethyl cellulose, the modified polylactic acid fiber and the solidification liquid to form a slurry with plasticity;

[0029] Injecting the slurry into a mold, applying pressure, sealing and curing to form a molded product.

[0030] The application adopts polyvinylpyrrolidone as a surfactant to modify polylactic acid in combination with superfine talc powder, the polyvinylpyrrolidone can reduce the agglomeration of the superfine talc powder, improves the crystallinity of the polylactic acid while maintaining good biocompatibility, biodegradability and mechanical properties, and thus realizes the regulation of the degradation speed of the modified polylactic acid fiber. By combining modified polylactic acid fibers with different degradation properties, the application can realize the accurate regulation of the multi-stage gradient degradation in the calcium phosphate bone cement, forms multiple gradient degradation processes in the bone repair stage, and can perfectly adapt to the bone tissue growth speed through regulation, and can regulate the degradation gradient according to application fields, and is suitable for the field of bone repair, and is especially suitable for bone defects caused by orthopedic diseases related to the elderly. DETAILED DESCRIPTION

[0031] The application provides a modified polylactic acid fiber, a calcium phosphate bone cement with a gradient degradation and a preparation method. In order to make the purpose, technical scheme and effect of the application more clear and explicit, the application is further described in detail below. It should be understood that the specific embodiments described herein are only used to explain the application and not to limit the application.

[0032] The modified polylactic acid fiber provided in the application has good biocompatibility and biodegradability. By adding nucleating agents and plasticizers in different proportions, the modified polylactic acid fiber has different crystallization degrees, so as to further regulate the mechanical strength and degradation performance.

[0033] Specifically, the modified polylactic acid fiber comprises the following components in parts by weight:

[0034] 85-100 parts of polylactic acid, 5-15 parts of nucleating agent, 2-5 parts of plasticizer and 0.2-0.5 parts of surfactant.

[0035] The modified polylactic acid fiber provided by the application can be used to prepare a calcium phosphate bone cement with a multi-stage degradation gradient. The calcium phosphate bone cement can form multiple gradient degradation processes in the bone repair stage, can perfectly adapt to the growth rate of bone tissue through regulation, and can regulate the degradation gradient according to the application field, and is suitable for the field of bone repair, especially for bone defects caused by orthopedic diseases related to the elderly.

[0036] Further, the molecular weight of the polylactic acid is 10000-350000 g / mol, and PDI < 2.0. Preferably, the molecular weight of the polylactic acid is 80000-120000 g / mol, and PDI < 2.0. Within this molecular weight range, the polylactic acid has both processability and mechanical strength. If the molecular weight is too high, the melt index of the polylactic acid is low, and the processing is difficult. If the molecular weight is too low, the mechanical properties of the modified polylactic acid fiber prepared are low, and the failure is fast.

[0037] Further, the nucleating agent is a combination of talc and polyglycolic acid (PGA), and the mass ratio of talc to polyglycolic acid is 1:1-4:1. The nucleating agent is mainly used to improve the crystallization performance of polylactic acid. The combination of inorganic particles and organic nucleating agent in an appropriate ratio can promote each other.

[0038] Preferably, the talc is medical grade ultra-fine talc with a particle size of 1500-3000 mesh. The specific surface area of the talc with small particle size is larger, and more spherulites are obtained, which has a greater influence on the mechanical properties and crystallization performance of the calcium phosphate bone cement composite material, and is beneficial to the regulation of the calcium phosphate bone cement.

[0039] Further, the plasticizer is polyethylene glycol (PEG), and the molecular weight of the selected polyethylene glycol is 5000-10000 g / mol. The use of polyethylene glycol as a plasticizer can improve the mechanical properties of polylactic acid.

[0040] Further, the surfactant is polyvinylpyrrolidone (PVP). In this application, polyvinylpyrrolidone is used as a surfactant to modify polylactic acid with superfine talc powder. Polyvinylpyrrolidone can reduce the agglomeration of superfine talc powder, improve the crystallinity of polylactic acid while maintaining good biocompatibility, biodegradability and mechanical properties, and further control the degradation rate.

[0041] The application also provides a preparation method of the modified polylactic acid fiber as described above, which specifically comprises the following steps:

[0042] (1) Put polylactic acid and nucleating agent into a vacuum drying oven, dry for 10 h at 80-120°C to remove water, and then put polylactic acid, nucleating agent, plasticizer and surfactant into a high-speed mixer in proportion to obtain a blend;

[0043] The speed of the high-speed mixer is 1500-2000 r / min, which is beneficial to the rapid and sufficient mixing of the materials.

[0044] (2) Use a double-screw extruder to prepare a modified polylactic acid material, use a cutting machine to granulate, and then put it into an oven to dry for 24 h;

[0045] Further, the temperature of the extruder is 170-200°C, and the speed is 50-75 r / min.

[0046] (3) Use a spinning machine to melt spin, wind and draw to obtain a modified polylactic acid fiber material, cut the modified polylactic acid fiber material to obtain a modified polylactic acid fiber, and sieve the modified polylactic acid fiber with the desired length with a sieve;

[0047] Further, the cut modified polylactic acid fiber can be used for subsequent preparation of calcium phosphate bone cement;

[0048] Further, the temperature of the melt spinning is 200-250°C, and the winding speed is 1000-1500 m / min;

[0049] Further, the length of the cut modified polylactic acid fiber is 0.5-2.0 mm. The use of the modified polylactic acid fiber with a length in this range in calcium phosphate bone cement can form pores of hundreds of microns without affecting the injection performance of the calcium phosphate bone cement.

[0050] The application also provides a gradient-degradable calcium phosphate bone cement solidified by a solid phase and a solidification liquid. The solidification liquid and the solid phase are mixed at a ratio of 0.3-0.7 ml:1 g to obtain a mixed bone cement composite material, and the concentration of the solidification liquid is 0.35-0.5 mol / L.

[0051] The solid phase comprises calcium phosphate powder and hydroxymethyl cellulose.

[0052] Further, the solid phase further comprises at least one modified biodegradable fiber, and the addition of the modified biodegradable fiber can improve the porosity and mechanical strength of the calcium phosphate bone cement.

[0053] Further, when the solid phase comprises two or more modified biodegradable fibers, the degradation rates of the modified biodegradable fibers are different. By adding modified biodegradable fibers with different degradation properties to the calcium phosphate bone cement, the degradation rate of the prepared calcium phosphate bone cement can be controlled to further adapt to the growth rate of bone tissue.

[0054] Further, the modified biodegradable fiber is a modified polylactic acid fiber as described above. By introducing the modified polylactic acid fiber with good biocompatibility and biodegradability into the calcium phosphate bone cement, the modified polylactic acid fiber will leave pores in situ after degradation, and the pores will gradually increase with the degree of degradation, forming macropores with a pore size of more than 100 microns, providing space for the growth of new bone tissue, promoting the repair and reconstruction of bone tissue, and achieving the purpose of treating certain diseases through slow release of drugs during the degradation process. In addition, the mechanical properties of the calcium phosphate bone cement are also improved to some extent. By adjusting the combination ratio of the modified materials in the modified polylactic acid fiber, modified polylactic acid fibers with different degradation properties can be obtained. By combining the use of modified polylactic acid fibers with different degradation properties, a controllable gradient-degradable calcium phosphate bone cement can be obtained, which can meet the growth needs of different bone tissues in practice.

[0055] Further, the hydroxymethyl cellulose accounts for 1.5% of the total mass of the solid phase. The added hydroxymethyl cellulose can improve the injectability of the calcium phosphate bone cement.

[0056] Further, the modified polylactic acid fiber accounts for 1.5%-4.5% of the total mass of the solid phase, and the balance is calcium phosphate powder. Without affecting the injectability of the calcium phosphate bone cement, the addition of the modified polylactic acid fiber can introduce pores of hundreds of microns, which is beneficial to the adhesion and growth of bone tissue. The proportion of the mixed modified polylactic acid fiber is not easy to be too large, and too large will affect the injection performance of the calcium phosphate bone cement, and too small is not conducive to the formation of high porosity in the calcium phosphate bone cement.

[0057] Further, the calcium phosphate powder includes one or more of α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate, calcium dihydrogen phosphate, calcium pyrophosphate, hydroxyapatite, fluorapatite, strontium apatite, and carbonate-containing apatite.

[0058] Further, the solidification liquid is one or more of deionized water, normal saline, a sodium citrate solution, and a sodium hydrogen phosphate solution. The composition of the solidification liquid has a great influence on the pH of the solidification liquid, which in turn affects the setting time of the calcium phosphate bone cement after mixing. Different compositions of the solidification liquid can be compounded in specific applications to control the setting speed of the calcium phosphate bone cement.

[0059] The application also provides a preparation method of the gradient-degradable calcium phosphate bone cement as described above, which specifically includes the following steps:

[0060] (1) Preparation of modified polylactic acid fibers.

[0061] (2) Mixing of the calcium phosphate powder, hydroxymethyl cellulose, and modified polylactic acid fibers, and mixing of the mixture with the solidification liquid to form a slurry with plasticity.

[0062] (3) Placing the slurry in a stainless steel cylindrical mold with an inner diameter of 6 mm and a height of 12 mm and applying a pressure of 0.7 MPa, sealing and solidifying for 1 h, and then demolding. The pressure used is the pressure simulated when the calcium phosphate bone cement is injected into the human body using a syringe, further reducing the application of the calcium phosphate bone cement.

[0063] In the application, by controlling the proportion of the modified material, modified polylactic acid fibers with different modification degrees can be prepared. The modified polylactic acid fibers with different modification degrees have different crystallinity and degradation rates. Modified polylactic acid fibers A, B, C, and D are prepared by adjusting the proportions of nucleating agents and plasticizers. The modified polylactic acid fibers A, B, C, and D have different degradation properties. The detailed proportions of the modified polylactic acid fibers A, B, C, and D are shown in Table 1. Talcum powder can become a nucleation center, heterogeneous nucleation occurs, and polylactic acid is more likely to crystallize, so it is often used as a nucleating agent to improve the crystallinity of polylactic acid. The proportion of nucleating agents in the modified polylactic acid fibers A, B, C, and D decreases in turn, the crystallization performance of the material gradually decreases, and the degradation rate of the prepared modified polylactic acid fibers A, B, C, and D gradually increases. The specific properties are shown in Table 2.

[0064] Crystallization performance test:

[0065] In order to study the effect of nucleating agents on the crystallization performance of polylactic acid, XRD tests were performed on samples of modified polylactic acid fibers A, B, C, and D. The crystallinity was determined based on the strongest diffraction peak.

[0066] Modified polylactic acid fiber degradation rate test:

[0067] The modified polylactic acid fibers A, B, C and D were placed in SBF simulated body fluid for immersion degradation, and after 10 days, the weight attenuation was measured after drying.

[0068] Table 1

[0069] Modified polylactic acid fiber Poly-lactic acid (g) Talc (g) Polyglycolic acid (g) Polyethylene glycol (g) A 85 9 3 3 B 90 9 3 3 C 100 8 2 2 D 100 5 2 2

[0070] Table 2

[0071] Modified polylactic acid fiber Material crystallinity improvement (%) Fiber degradation rate reduction (%) A 32% 45% B 24% 38% C 14% 27% D 8% 15%

[0072] According to the degradation rate difference of the modified polylactic acid fibers, a calcium phosphate bone cement with multiple gradient degradation can be prepared. The modified polylactic acid fibers with different degradation rates prepared are combined with calcium phosphate powder and hydroxymethyl cellulose as the solid phase components of the calcium phosphate bone cement, wherein the hydroxymethyl cellulose accounts for 1.5% of the total mass of the solid phase, and the modified polylactic acid fiber accounts for 1.5%-4.5% of the total mass of the solid phase. By changing the combination of modified polylactic acid fibers A-D, the gradient degradation rate of the calcium phosphate bone cement is regulated. Then the uniformly mixed solid phase component is mixed with a curing liquid, wherein the ratio of the curing liquid to the solid phase is 0.3-0.7 ml:1 g, and the concentration of the curing liquid is 0.35-0.5 mol / L.

[0073] The application is further illustrated by specific examples below.

[0074] Example 1

[0075] First, the polylactic acid and ultrafine talc powder were placed in a vacuum drying oven and dried at 100°C for 10h to remove water. Then 85g of polylactic acid, 9g of ultrafine talc powder, 3g of polyglycolic acid, 3g of polyethylene glycol and 0.5g of polyvinylpyrrolidone were placed in a high-speed mixer to obtain a blend, wherein the high-speed mixer speed was 2000r / min. A modified polylactic acid material was prepared using a twin-screw extruder, wherein the extruder temperature was 180°C and the speed was 50r / min. The material was granulated using a cutting machine and then placed in an oven for drying for 24h to obtain the modified polylactic acid material. Then the modified polylactic acid material was melt-spun, wound and drawn using a spinning machine, wherein the melt spinning temperature was 210°C and the winding speed was 1000 m / min. The modified polylactic acid fiber material was cut into modified polylactic acid fiber-A and sieved using a sieve, and the length of the modified polylactic acid fiber-A was 0.5-2mm.

[0076] Example 2

[0077] The same as the preparation method of Example 1, except that 90 g of polylactic acid, 9 g of superfine talc powder, 3 g of polyglycolic acid, 3 g of polyethylene glycol, and 0.5 g of polyvinylpyrrolidone were used. Modified polylactic acid fiber-B was prepared, and the length of the modified polylactic acid fiber-B was 0.5-2 mm.

[0078] Example 3

[0079] The same as the preparation method of Example 1, except that 100 g of polylactic acid, 8 g of superfine talc powder, 2 g of polyglycolic acid, 2 g of polyethylene glycol, and 0.3 g of polyvinylpyrrolidone were used. Modified polylactic acid fiber-C was prepared, and the length of the modified polylactic acid fiber-C was 0.5-2 mm.

[0080] Example 4

[0081] The same as the preparation method of Example 1, except that 100 g of polylactic acid, 5 g of superfine talc powder, 2 g of polyglycolic acid, 2 g of polyethylene glycol, and 0.3 g of polyvinylpyrrolidone were used. Modified polylactic acid fiber-D was prepared, and the length of the modified polylactic acid fiber-D was 0.5-2 mm.

[0082] Example 5

[0083] Double-gradient degradable calcium phosphate cement: 950 mg of α-tricalcium phosphate powder, 15 mg of hydroxymethyl cellulose, 15 mg of modified polylactic acid fiber-A, and 20 mg of modified polylactic acid fiber-B were mixed, and after uniform mixing, a sodium citrate solution was mixed to form a slurry with plasticity, wherein the concentration of the sodium citrate solution was 0.5 mol / L, and the ratio of the sodium citrate solution to the solid phase powder was 0.45 ml / g. The slurry was placed in a stainless steel cylindrical mold with an inner diameter of 6 mm and a height of 12 mm, and a pressure of 0.7 MPa was applied. After sealing and curing for 1 hour, the shaped product was demolded. According to the properties of the modified polylactic acid fiber-A and the modified polylactic acid fiber-B, the obtained calcium phosphate cement had a double-gradient degradation performance.

[0084] Example 6

[0085] Double-gradient degradable calcium phosphate cement: 950 mg of α-tricalcium phosphate powder, 15 mg of hydroxymethyl cellulose, 15 mg of modified polylactic acid fiber-A and 20 mg of modified polylactic acid fiber-C are mixed, and after being uniformly mixed, a slurry with plasticity is formed by mixing with a sodium citrate solution, wherein the concentration of the sodium citrate solution is 0.5 mol / L, and the ratio of the sodium citrate solution to the solid phase powder is 0.45 ml / g. The slurry is placed in a stainless steel cylindrical mold with an inner diameter of 6 mm and a height of 12 mm, and a pressure of 0.7 MPa is applied. After sealing and curing for 1 hour, the shaped product is demolded. According to the properties of the modified polylactic acid fiber-A and the modified polylactic acid fiber-C, the obtained calcium phosphate cement has a double-gradient degradation performance.

[0086] Example 7

[0087] Double-gradient degradable calcium phosphate cement: 950 mg of α-tricalcium phosphate powder, 15 mg of hydroxymethyl cellulose, 15 mg of modified polylactic acid fiber-A and 20 mg of modified polylactic acid fiber-C are mixed, and after being uniformly mixed, a slurry with plasticity is formed by mixing with a sodium citrate solution, wherein the concentration of the sodium citrate solution is 0.5 mol / L, and the ratio of the sodium citrate solution to the solid phase powder is 0.45 ml / g. The slurry is placed in a stainless steel cylindrical mold with an inner diameter of 6 mm and a height of 12 mm, and a pressure of 0.7 MPa is applied. After sealing and curing for 1 hour, the shaped product is demolded. According to the properties of the modified polylactic acid fiber-A and the modified polylactic acid fiber-C, the obtained calcium phosphate cement has a double-gradient degradation performance.

[0088] Example 8

[0089] Double-gradient degradable calcium phosphate cement: 950 mg of α-tricalcium phosphate powder, 15 mg of hydroxymethyl cellulose, 15 mg of modified polylactic acid fiber-A and 20 mg of modified polylactic acid fiber-C are mixed, and after being uniformly mixed, a slurry with plasticity is formed by mixing with a sodium citrate solution, wherein the concentration of the sodium citrate solution is 0.5 mol / L, and the ratio of the sodium citrate solution to the solid phase powder is 0.45 ml / g. The slurry is placed in a stainless steel cylindrical mold with an inner diameter of 6 mm and a height of 12 mm, and a pressure of 0.7 MPa is applied. After sealing and curing for 1 hour, the shaped product is demolded. According to the properties of the modified polylactic acid fiber-A and the modified polylactic acid fiber-C, the obtained calcium phosphate cement has a double-gradient degradation performance.

[0090] Performance test

[0091] (1) The environmental pH value caused by the degradation products in the entire degradation process of the calcium phosphate cement of Examples 5-8 was tested, and the results are shown in Table 3.

[0092] (2) The compressive strength of the calcium phosphate bone cement prepared in Examples 5-8 was tested by a universal testing machine with a loading speed of 1 mm / min. After 10 days of degradation in SBF, the samples were taken out, dried and then tested again. The results are shown in Table 3.

[0093] (3) The calcium phosphate bone cement prepared in Examples 5-8 was degraded in SBF. After 3, 10, 20 and 30 days, the samples were taken out, dried and then measured by scanning electron microscopy. The results are shown in Table 4.

[0094] Table 3

[0095] Degradation gradient pH value Compressive strength (MPa) Compressive strength after 10 days (MPa) Example 5 Double degradation gradient 6.42 44.8 29.5 Example 6 Double degradation gradient 6.86 45.7 31.8 Example 7 Triple degradation gradient 7.01 44.4 34.3 Example 8 Quadruple degradation gradient 7.25 42.6 39.2

[0096] Table 4

[0097] Average pore size after 3 days (μm) Average pore size after 10 days (μm) Average pore size after 20 days (μm) Average pore size after 30 days (μm) Example 5 122 235 251 265 Example 6 105 162 244 253 Example 7 57 179 231 279 Example 8 51 115 192 297

[0098] The calcium phosphate bone cement matrix with different degradation gradients has similar compressive strength at the initial stage of degradation when the modified polylactic acid fiber has not yet degraded. With the degradation of the modified polylactic acid fiber, the porosity of the calcium phosphate bone cement gradually increases, resulting in a decrease in the compressive strength of the calcium phosphate bone cement. As shown in Tables 3 and 4, the bi- gradient degradation calcium phosphate bone cement of Example 5 and Example 6 has a faster degradation speed of the added modified polylactic acid fiber A, and thus forms pores faster. The large increase in porosity leads to a faster decay of the mechanical properties. The multi- gradient degradation of the calcium phosphate bone cement of Example 7 and Example 8 has a relatively slow pore formation process, and the mechanical properties maintain a high strength in the same time. By using the modified polylactic acid fiber provided in the present application, and further using modified polylactic acid fibers with different degradation properties, a controllable gradient degradation of the calcium phosphate bone cement can be obtained, which can meet the growth needs of different bone tissues in practice.

[0099] It should be understood that the application of the present application is not limited to the above examples, and those of ordinary skill in the art can make improvements or changes according to the above description, and all such improvements and changes shall fall within the scope of protection of the present application.

Claims

1. A gradient degradable calcium phosphate bone cement, characterized in that: The invention is formed by solidifying a solid phase and a solidifying liquid; the ratio of the solidifying liquid to the solid phase is 0.3-0.7 ml:1 g; the solid phase comprises calcium phosphate powder and hydroxymethyl cellulose; the solid phase also comprises two or more modified biodegradable fibers, wherein the modified biodegradable fibers are modified polylactic acid fibers with different degradation rates; the concentration of the solidifying liquid is 0.35-0.5 mol / L; the hydroxymethyl cellulose accounts for 1.5% of the total mass of the solid phase, the modified polylactic acid fibers account for 1.5%-4.5% of the total mass of the solid phase, and the balance is the calcium phosphate powder; The modified polylactic acid fiber comprises the following components in parts by weight: 85-100 parts of polylactic acid, 5-15 parts of nucleating agent, 2-5 parts of plasticizer and 0.2-0.5 parts of surfactant; The nucleating agents are talc and polyglycolic acid; The surfactant is polyvinyl pyrrolidone.

2. The gradient degradable calcium phosphate bone cement according to claim 1, wherein The molecular weight of the polylactic acid is 80,000-120,000 g / mol, and PDI is less than 2.

0.

3. The gradient degradable calcium phosphate bone cement according to claim 1, wherein The mass ratio of the talc powder to the polyglycolic acid is 1:1-4:1; the talc powder is ultrafine talc powder with a particle size of 1500-3000 meshes.

4. The gradient degradable calcium phosphate bone cement according to claim 1, characterized in that The plasticizer is polyethylene glycol; the molecular weight of the polyethylene glycol is 5000-10000 g / mol.

5. The gradient degradable calcium phosphate bone cement according to claim 1, characterized in that The preparation method of the modified polylactic acid fiber comprises the following steps: The polylactic acid and the nucleating agent are dried in a vacuum atmosphere, and the polylactic acid, the nucleating agent, the plasticizer and the surfactant are mixed in proportion to form a blend; the drying temperature is 80-120° C.; The blend is extruded through an extruder, granulated through a cutter to obtain a modified polylactic acid material, and then dried; The modified polylactic acid material is melt-spinned, wound, and drawn to obtain a modified polylactic acid fiber material; The modified polylactic acid fiber material is cut and then sieved to obtain modified polylactic acid fiber; The length of the modified polylactic acid fiber is 0.5-2.0 mm.

6. The gradient-degradable calcium phosphate bone cement according to claim 5, characterized in that The mixing process is carried out by a high-speed mixer, the speed of the high-speed mixer is 1500-2000r / min; the temperature of the extruder is 170-200°C, and the speed is 50-75r / min; The temperature of the melt spinning is 200-250° C.; the speed of the winding is 1000-1500 m / min.

7. The gradient-degradable calcium phosphate bone cement according to claim 1, characterized in that The calcium phosphate powder is one or more of α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate, calcium dihydrogen phosphate, calcium pyrophosphate, hydroxyapatite, fluorapatite, strontium apatite and carbonate-containing apatite; the solidifying liquid is one or more of physiological saline, sodium citrate solution and sodium hydrogen phosphate solution.

8. A method for preparing a gradient-degradable calcium phosphate bone cement according to any one of claims 1 to 7, characterized in that: The following steps are involved: preparing modified polylactic acid fibers; The calcium phosphate powder, hydroxymethyl cellulose, modified polylactic acid fiber and curing liquid are mixed to form a plastic slurry; The slurry is injected into a mold, pressure is applied, and the mold is sealed and then cured, and the mold is demoulded.