阅读说明：本技术 一种具有中空贯通结构的磷酸钙骨水泥、制备方法及其应用 (calcium phosphate bone cement with hollow through structure, preparation method and application thereof ) 是由 车七石 单玲星 刘少辉 张俊辉 赵澎 于 2019-10-17 设计创作，主要内容包括：本发明公开了一种具有中空贯通结构的磷酸钙骨水泥、制备方法及其应用,属于磷酸钙骨水泥技术领域,所述的中空贯通结构的磷酸钙骨水泥包括固相和固化液,所述固相包括磷酸钙粉末、纤维混合物,所述纤维混合物为可吸收纤维与纤维蛋白纤维,所述可吸收纤维的直径为100-500μm,长度为：0.5mm-1.5mm,优选地,所述可吸收纤维的直径为200-400μm。制得的磷酸钙骨水泥可以形成三维联通的大孔,促进细胞的黏附,增殖并可提高骨水泥的力学强度。(The invention discloses calcium phosphate cement with a hollow through structure, a preparation method and application thereof, belonging to the technical field of calcium phosphate cement, wherein the calcium phosphate cement with the hollow through structure comprises a solid phase and a curing liquid, the solid phase comprises calcium phosphate powder and a fiber mixture, the fiber mixture is an absorbable fiber and a fibrin fiber, the diameter of the absorbable fiber is 100-500 mu m, and the length of the absorbable fiber is as follows: 0.5mm to 1.5mm, preferably, the absorbable fiber has a diameter of 200 and 400 μm. The prepared calcium phosphate bone cement can form three-dimensional communicated macropores, promote cell adhesion and proliferation and improve the mechanical strength of the bone cement.)

1. The calcium phosphate cement with the hollow through structure is characterized by comprising a solid phase and a curing liquid, wherein the solid phase comprises calcium phosphate powder and a fiber mixture, the fiber mixture is an absorbable fiber and a fibrin fiber, the diameter of the absorbable fiber is 100-: 0.5mm to 1.5mm, preferably, the absorbable fiber has a diameter of 200 and 400 μm.

2. the calcium phosphate cement according to claim 1, wherein the mass fraction of absorbable fibers in the solid phase is 5-25%, the mass fraction of calcium phosphate powder is 75-95%, preferably the mass fraction of absorbable fibers in the solid phase is 10-20%, the mass fraction of calcium phosphate powder is 80-90%; the solid phase and the curing liquid are mixed into paste according to the weight ratio of 1 (0.3-0.8), and preferably, the solid phase and the curing liquid are mixed into paste according to the weight ratio of 1: 0.4.

3. The calcium phosphate bone cement according to claim 1, wherein the setting fluid is a physiological saline, a phosphate solution, a citric acid solution or a sodium citrate solution, preferably the phosphate solution is disodium hydrogen phosphate.

4. The calcium phosphate bone cement of claim 1, wherein the absorbable fiber is a PLGA fiber, preferably the weight ratio of PGA to PLA in the PLGA copolymer is (65-90) to (35-10), preferably the weight ratio of PGA to PLA in the PLGA copolymer is 75: 25.

5. The calcium phosphate cement of claim 1, wherein the calcium phosphate powder is selected from the group consisting of: one or more 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 carbonic acid apatite.

6. The calcium phosphate cement according to claim 1, wherein the fiber mixture comprises, in mass percent: 70-95% of absorbable fiber and 5-30% of fibrin, and preferably, the fiber mixture comprises the following components in percentage by mass: 75-85% of absorbable fiber and 15-25% of fibrin, wherein the fiber mixture comprises the following components in percentage by mass: 80% absorbable fiber, 20% fibrin.

7. The calcium phosphate cement according to claim 1, wherein the fibrin fibers are prepared as follows:

Carrying out high-voltage electrostatic spinning on the fibrinogen solution with the concentration of 15-30%, setting the voltage to be 10-18kV, setting the spinning speed to be 0.8-1.2ml/h, receiving the electrospun fiber by using a metal carrier, and cutting the fiber into fibrin fiber with the length of 0.5-1.5 mm.

8. The process for the preparation of calcium phosphate bone cement according to any of claims 1 to 7, characterized in that it comprises the following steps:

(1) Mixing absorbable fibers with fibrin fibers to obtain a fiber mixture;

(2) Mixing calcium phosphate powder with the fiber mixture;

(3) Adding the curing liquid, and mixing the solid phase and the curing liquid into paste according to the weight ratio of 1 (0.3-0.8) to obtain the calcium phosphate cement.

9. The method for preparing calcium phosphate cement according to claim 8, wherein:

Preferably, 85 mass percent of calcium a-phosphate powder is mixed with 15 mass percent of the fiber mixture in the step 2), and preferably, the solidifying liquid in the step 3) is Na2HPO4 solution with the mass percent of 4%.

10. Use of the calcium phosphate cement according to any one of claims 1 to 7 in a bone repair material.

Technical Field

The invention relates to the technical field of calcium phosphate bone cement, in particular to calcium phosphate bone cement with a hollow through structure, a preparation method and application thereof.

Background

calcium Phosphate Cement (CPC) was developed successfully by Borwn and Chow in the last 90 th century, and is a non-ceramic type hydroxyapatite artificial bone material with self-curing property. Solid-phase powder and solidifying liquid are mixed according to a certain proportion to form slurry which is easy to shape, self-solidifying is carried out in a short time, and the final hydration product is apatite which is similar to the inorganic component and crystal structure of human bone tissue. CPCs have good osteoconductivity and biocompatibility.

Polylactic-co-glycolic acid (PLGA) is an ester high polymer obtained by copolymerizing Lactide (LA) and Glycolide (GA), has good biocompatibility and complete biodegradability, and has safety for being used as a controlled release system in a human body for a long time, but the material itself has certain defects, such as low mechanical strength, poor plasticity and weak osseointegration force.

The PLGA is added into the bone cement to make the performances of the PLGA and the bone cement complement to form an ideal bone cement material.

As the pores in the CPC solidified body are mostly submicron and nanometer pores and lack communicated macropores with the diameter of more than 100 micrometers, the new bone tissue only crawls and replaces on the surface of the CPC, which is not beneficial to the new bone tissue to grow into the material and is not beneficial to the early formation of blood vessels, and the material can be degraded slowly, the degradation time is usually more than one year, and a few of the degradation time is even more than two years, so that the bone defect repair process is longer. Thereby affecting the effect of bone repair and limiting the clinical application thereof.

However, calcium phosphate cement as a scaffold for bone tissue engineering can form a microporous structure, but the pore diameter and the communication degree of pores do not meet clinical requirements, and the material strength is insufficient.

Patent CN107881650A discloses a method for preparing nanofiber membrane with core/shell embedded structure by coaxial double-layer electrospinning and its application, which discloses the preparation of nanofiber by coaxial double-layer electrospinning technology, however, since the polymer material is wrapped by fibrin, the degradation of fibrin requires the participation of plasmin, the degradation process is the degradation of the shell layer in the nanofiber at first, the core layer is exposed, therefore, the degradation of the polymer material inside is later than that of fibrin, and the application of the material in bone cement requires the degradation of the polymer material of the core layer by fibrin, which is not favorable for the growth of cells.

Disclosure of Invention

The invention aims to provide calcium phosphate bone cement with a hollow through structure, and the bone cement obtained by the technical scheme disclosed by the invention is suitable for bone tissue ingrowth and promotes bone cell adhesion and tissue ingrowth.

The hollow through structure can provide a three-dimensional space for cells to live, is favorable for cell adhesion growth, extracellular matrix precipitation, nutrition and oxygen entry, metabolite discharge, vascular and nerve growth and bone repair.

The minimum pore diameter of the bone tissue growth is 100 microns, the pore diameter distribution of 200-500 microns is more suitable for the bone tissue growth, and a suitable space and mechanical environment can be provided for the adhesion of bone cells and the tissue growth.

Specifically, the invention adopts the following technical scheme:

The calcium phosphate cement with a hollow through structure is characterized by comprising a solid phase and a curing liquid, wherein the solid phase comprises a-tricalcium phosphate and a fiber mixture, the fiber mixture is an absorbable fiber and a fibrin fiber, the diameter of the absorbable fiber is 100-500 mu m, and the length of the absorbable fiber is as follows: 0.5mm-1.5 mm.

preferably, the absorbable fiber has a diameter of 200-400 μm.

Preferably, the mass fraction of absorbable fiber in the solid phase is 5% -25%, and the mass fraction of calcium phosphate powder is 75-95%. Preferably, the mass fraction of the absorbable fiber is 10-20%, and the mass fraction of the calcium phosphate powder is 80-90%; the solid phase and the curing liquid are mixed into paste according to the weight ratio of 1 (0.3-0.8), and preferably, the solid phase and the curing liquid are mixed into paste according to the weight ratio of 1: 0.4.

Preferably, the solidifying liquid is normal saline, phosphate solution, citric acid solution or sodium citrate solution, and preferably, the phosphate solution is disodium hydrogen phosphate.

Preferably, the absorbable fiber is a PLGA fiber.

PLGA is polylactic acid-glycolic acid, the weight ratio of PGA to PLA in the PLGA copolymer is (65-90): (35-10), and preferably, the weight ratio of PGA to PLA in the PLGA copolymer is 75: 25.

Preferably, the fiber mixture comprises the following components in percentage by mass: 70-95% of absorbable fiber and 5-30% of fibrin, and preferably, the fiber mixture comprises the following components in percentage by mass: 75-85% of absorbable fiber and 15-25% of fibrin, wherein the fiber mixture comprises the following components in percentage by mass: 80% absorbable fiber, 20% fibrin.

Preferably, the preparation method of the fibrin fiber is as follows:

Carrying out high-voltage electrostatic spinning on the fibrinogen solution with the concentration of 15-30%, setting the voltage to be 10-18kV, setting the spinning speed to be 0.8-1.2ml/h, receiving the electrospun fiber by using a metal carrier, and cutting the fiber into fibrin fiber with the length of 0.5-1.5 mm.

Preferably, 450 mg of human fibrinogen is weighed, dissolved in 2.25 ml of hexafluoroisopropanol solution, stirred, added with 0.25ml of normal saline and stirred again to prepare 18% fibrinogen solution;

And (2) carrying out high-voltage electrostatic spinning on the fibrinogen solution, setting the voltage to be 15kV and the spinning speed to be 1.0 ml/h, receiving the electrospun fiber by using a metal carrier, obtaining electrostatic spinning fibrin after 2.5 hours, and cutting the fiber into fibrin fiber with the length of 0.5-1.5 mm.

Still another object of the present invention is to provide a method for preparing calcium phosphate cement, which is characterized in that:

1) Absorbable fibers are mixed with fibrin fibers to obtain a fiber mixture.

2) Calcium phosphate powder is mixed with the fiber mixture.

3) Adding the solid phase and the curing liquid according to the weight ratio of 1 (0.3-0.8) to be mixed into paste to obtain the calcium phosphate cement.

Preferably, 85% by mass of calcium a-phosphate powder is mixed with 15% by mass of the fiber mixture.

Preferably, the solidifying liquid in the step 3) is a Na2HPO4 solution with the mass fraction of 4%.

Still another object of the present invention is to provide the use of the above calcium phosphate cement in bone repair materials.

The degradation speed of the PLGA fiber is faster than that of the fibrin fiber, the fibrin fiber and the degradable fiber PLGA are mixed, the PLGA is degraded to form a through macropore, the fibrin fiber has the function of adhering cells, and when osteoblasts or other growth factors pass through the macropore, the fibrin fiber is adhered to promote the growth of bone tissues.

through the technical scheme, the beneficial effects obtained by the invention comprise that:

1) The calcium phosphate cement prepared by the invention can form a three-dimensionally communicated macroporous structure with the diameter of 200-.

2) The fibrin fiber can promote the adhesion of cells on a channel, is beneficial to the transportation and gas exchange of nutrient substances and metabolic products, promotes the adhesion, proliferation and differentiation of cells, is beneficial to the formation and growth of bone tissues and blood vessels, and improves the bone repair effect.

3) The PLGA fiber added in the invention can improve the mechanical strength of the bone cement.

Detailed Description

To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to specific examples. It will be understood by those skilled in the art that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.