WO2017059654A1

WO2017059654A1 - Method for preparing self-foaming porous composite bone repair scaffold

Info

Publication number: WO2017059654A1
Application number: PCT/CN2016/075332
Authority: WO
Inventors: 李吉东; 李�根; 左奕; 李玉宝; 邹琴; 张利
Original assignee: 四川大学
Priority date: 2015-10-08
Filing date: 2016-03-02
Publication date: 2017-04-13
Also published as: CN105148326A

Abstract

A method for preparing a self-foaming porous composite bone repair scaffold, a calcium phosphate salt-polyurethane composite material, and use thereof in the preparation of a porous scaffold material. Said method comprises: in the process of synthesizing a calcium phosphate salt-polyurethane composite material, uniformly compounding into a material an aqueous foaming agent in the form of crystal water of a calcium phosphate salt, the crystal water reacting, under certain conditions, with an isocyanate in the polyurethane system to generate a CO₂ gas, thereby achieving self-foaming molding, and preparing a porous calcium phosphate salt-polyurethane composite bone repair scaffold. The calcium phosphate salt-polyurethane composite material comprises: a polyurethane monomer, a chain extender and one or more calcium phosphate salt(s); the calcium phosphate salt(s) at least comprising a crystal water-containing calcium phosphate salt.

Description

Preparation method of self-foaming porous composite bone repairing stent

Technical field

The invention relates to a preparation method of a therapeutic material, in particular to a preparation method of a self-foaming porous composite bone repairing stent, and to a calcium phosphate salt-polyurethane composite material and application thereof in preparing the porous scaffold material.

Background technique

Porous scaffold materials, as materials and structural templates, play an important role in bone tissue engineering. Appropriate bionic pore structure is the key to whether the porous scaffold can exert optimal osteogenic efficiency. Although porous scaffold materials have made great progress in the research and application of bone tissue engineering, there are widespread problems such as mechanical properties of scaffold materials, mismatched degradation of natural bone regeneration, uneven pores, poor connectivity, etc., making cells and tissues difficult. The penetration grows into the inside of the stent, and only grows on the periphery of the stent, and the material transportation is hindered, which is not conducive to the renewal of the local tissue, so that the stent material has a large gap from the clinical application.

Polyurethane is a block polymer composed of a hard segment and a soft segment. Different physical and chemical properties and degradation properties can be obtained by selecting different soft and hard segments or adjusting the ratio of soft and hard segments according to different requirements, because of its good biocompatibility, The advantages of flexible compatibility and performance of blood compatibility have been widely recognized in the field of tissue engineering. Chinese patent CN103495203A reports a preparation method of a honeycomb polyurethane stent containing disulfide bonds by using a biological vine template method, but the method is difficult to apply to preparing a composite porous stent by using a polyurethane-based composite material containing a relatively large viscosity. Porous scaffolds prepared from calcium phosphate-polyurethane biomimetic composites have shown good bioactivity and biocompatibility. Since the isocyanate present in the polyurethane-based material system can react with water to form CO ₂ gas, the polyurethane-based porous scaffold often uses water as a foaming agent in the preparation process. Li Limei et al. “Interfacial structure and mechanical properties of alcohol-modified castor oil-based polyurethane/n-HA composite scaffolds” (Inorganic Materials Journal, 2013, 28(8): 811-817), etc. A nano-apatite/polyurethane porous composite scaffold was prepared by a foaming agent. Although the foaming agent water is safe and has no toxic side effects, the calcium phosphate-polyurethane composite system has a large viscosity with the reaction, and the foaming agent water is difficult to be uniformly mixed therein, thereby affecting the uniformity of the pore structure of the stent.

Summary of the invention

In view of the above, the present invention provides a simple and easy method for preparing a composite bone repair stent having uniform pore controllability.

The preparation method of the self-foaming porous composite bone repairing stent comprises the following steps:

The calcium phosphate substance containing the calcium hydrogen phosphate crystal hydrate and/or the calcium dihydrogen phosphate crystal hydrate is used as an inorganic filler, and is uniformly compounded in the polyurethane system to form a composite material in the polyurethane synthesis process, and is higher than the crystal hydrate of calcium hydrogen phosphate. The product and/or the calcium dihydrogen phosphate crystal hydrate is aged for 1-48 hours under the temperature condition of decomposing the crystal water.

Calcium phosphates also include hydroxyapatite, tricalcium phosphate, calcium pyrophosphate and octacalcium phosphate.

The mass ratio of the calcium phosphate-based substance in the composite material is preferably from 10 to 65 wt%.

The mass ratio of the crystal water in the calcium phosphate material to the composite material is 0.05 to 10%, preferably 0.2 to 2%.

Polyurethane is a block polymer formed by polymerizing a polyether polyol or a polyester polyol with an isocyanate.

In order to prepare a self-foaming porous composite bone repair scaffold with antibacterial function, the calcium phosphate substance is doped with nano silver, silver silver, silver nitrate, silver sulfadiazine, copper sulfate, copper nitrate, copper chloride, zinc sulfate, zinc nitrate and At least one of zinc chloride.

The maximum allowable range of ripening is 75 to 150 ° C, preferably 85 to 125 ° C, and the ripening time is 1 to 48 hours, preferably the ripening time is 2 to 24 hours. The water molecules produced by the decomposition of the crystalline hydrate can react with the isocyanate in the synthetic polyurethane system to form CO ₂ as an excellent foaming agent with no toxic side effects. With the curing and curing of the composite system, a novel calcium phosphate-polyurethane is obtained. Self-foaming composite bone repair scaffold material.

In the above preparation method, since the calcium hydrogen phosphate crystal hydrate CaHPO ₄ · 2H ₂ O gradually loses crystal water at a temperature higher than 75 ° C, if the calcium phosphate substance is selected to contain calcium hydrogen phosphate crystal hydrate, the preferred ripening foam The temperature is 85 to 100 °C. During the ripening process, the temperature of the ripening is increased, and the pores of the matured product are correspondingly increased. When the curing temperature is lower than 85 °C, the crystal water of calcium hydrogen phosphate in the composite system cannot be fully released, and it is difficult to obtain a porous scaffold having a high porosity and pore penetration; when the curing temperature is 90 ° C, the curing curing foaming The pore size is uniform, about 300-500 μm; when the curing temperature is higher than 100 ° C, the reaction of decomposing and losing crystal water is too fast, and the obtained scaffold pore is too large, uneven, and the mechanical strength is poor.

When the calcium phosphate material is selected from the calcium dihydrogen phosphate crystal hydrate as the foaming agent water source, the calcium dihydrogen phosphate crystal hydrate Ca(H ₂ PO ₄ ) ₂ ·H ₂ O gradually loses crystallinity at a temperature higher than 100 ° C. The preferred foaming and ripening temperature for water is from 105 to 130 °C.

If the curing temperature is less than 100 ° C, the polymerization of polyurethane in the composite material is insufficient, and the mechanical properties of the prepared stent are low. After being formed by the composite stent, it can be aged at a higher temperature for a certain period of time, which can improve the mechanical properties of the composite stent. If the composite material of calcium hydrogen phosphate crystal hydrate (CaHPO ₄ · 2H ₂ O) is aged at 90 ° C for 24 hours, the obtained porous stent can be aged at 110 ° C for 24 hours, and its mechanical properties can be more than doubled.

The calcium phosphate substance may be calcium hydrogen phosphate crystal hydrate and/or calcium dihydrogen phosphate crystal hydrate and hydroxyapatite, Phosphate such as tricalcium phosphate, calcium pyrophosphate and octacalcium phosphate is used in combination. The content of crystal water contained in the calcium phosphate salt directly affects the pore structure of the prepared scaffold. The content of the crystal water can be achieved by adjusting the amount of the calcium hydrogen phosphate crystal hydrate and/or the calcium dihydrogen phosphate crystal hydrate. The higher the proportion of crystallization water in the composite system, the higher the porosity and pore size of the prepared scaffold and the lower the mechanical properties. Experimental studies show that the crystallization water content in the composite system is 0.05-10%, preferably 0.2-2%.

The self-foaming porous composite bone repairing stent prepared by the invention provides a method for uniformly mixing the foaming agent water in the form of calcium phosphate salt crystal water in the synthesis process of the calcium phosphate salt-polyurethane composite material, and letting it be under certain conditions. The release of crystal water reacts with isocyanate in the polyurethane system to form CO ₂ gas, and self-foaming of the composite system is realized, and a calcium phosphate-polyurethane composite bone repair scaffold having porosity and uniform pores is prepared. The in-situ self-foaming method is simple and easy, especially foaming into a uniform polyurethane-based polymer, which can overcome the foaming material pores caused by water, etc., which are difficult to be uniformly added to a relatively high viscosity polymer material system as a foaming agent. The problem of unevenness can also avoid the influence of impurities on the material properties, so that the uniform and interpenetrating pore structure can be easily formed in the prepared scaffold material structure, and the porosity in the scaffold material and the pore size can be realized. The material has appropriate degradability, so that the excellent biological properties, degradation properties, high porosity of the stent and high pore penetration are perfectly combined to meet the requirements of clinical high performance tissue engineering scaffolds, and the application prospect is broad. .

The present invention also provides a calcium phosphate-polyurethane composite comprising the following components:

a polyurethane and one or more calcium phosphate salts; wherein the calcium phosphate salt comprises at least one calcium phosphate salt containing water of crystallization.

Further, the calcium phosphate salt has a weight percentage of 10 to 60%.

Further, the weight percentage of the crystal water is from 0.36 to 8%.

Further, the polyurethane is prepared from the following raw materials:

Isophorone diisocyanate or 4,4'-methylene dicyclohexyl diisocyanate;

Polyethylene glycol

Chain extender.

Further, the calcium phosphate salt containing the crystal water is selected from the group consisting of CaHPO ₄ · 2H ₂ O or Ca(H ₂ PO ₄ ) ₂ · H ₂ O.

Further, the calcium phosphate salt further includes any one or more of hydroxyapatite, tricalcium phosphate, calcium pyrophosphate or octacalcium phosphate.

Further, the chain extender is selected from the group consisting of 1,4-butanediol.

The invention also finds use of the composite material in the preparation of a porous scaffold material.

The invention also provides a calcium phosphate salt-polyurethane porous scaffold material, which is prepared by curing the composite material Prepared.

Further, the calcium phosphate salt-polyurethane porous scaffold material has a porosity of 80.3%-82.2%.

Further, the calcium phosphate-polyurethane porous scaffold material has a compressive strength of 3.6 to 3.8 MPa.

The calcium phosphate salt-polyurethane composite material provided by the invention uniformly crystallizes the calcium phosphate salt crystal water in the material. In the preparation of the porous scaffold material, as the starting material, without adding additional foaming agent water, it is only necessary to release the crystal water to react with the isocyanate in the polyurethane system under certain conditions to form CO ₂ gas. The self-foaming molding of the composite material system is realized, and a calcium phosphate-polyurethane composite bone repairing stent having porosity and uniform pores is prepared. The method is simple and the obtained porous scaffold material has good mechanical properties.

It is apparent that various other modifications, substitutions and changes can be made in the form of the above-described embodiments of the present invention.

The above content of the present invention will be further described in detail below by way of specific embodiments in the form of embodiments. However, the scope of the above-mentioned subject matter of the present invention should not be construed as being limited to the following examples. Any technique implemented based on the above description of the present invention is within the scope of the present invention.

DRAWINGS

1 is a scanning electron micrograph of a porous stent prepared by foaming at 80 degrees in Example 1.

2 is a scanning electron micrograph of a porous stent prepared by foaming at 90 degrees in Example 1.

3 is a scanning electron micrograph of a porous stent prepared by foaming at 100 degrees in Example 1.

4 is a scanning electron micrograph of a porous composite bone repair stent prepared by foaming at 110 degrees in Example 1.

Figure 5 is a scanning electron micrograph of the porous stent prepared in Example 2.

Figure 6 is a scanning electron micrograph of the porous stent prepared in Example 3.

Figure 7 is a scanning electron micrograph of the porous stent prepared in Example 6.

Figure 8 is a scanning electron micrograph of the porous stent prepared in Example 12.

detailed description

The above content of the present invention will be further described in detail below in conjunction with the specific embodiments of the embodiments shown in the drawings. However, the scope of the above-mentioned subject matter of the present invention should not be construed as being limited to the following examples. Various alterations and modifications may be made without departing from the spirit and scope of the invention.

Isophorone diisocyanate, 4,4'-methylene dicyclohexyl diisocyanate, polyethylene glycol and chain extender were purchased from Shanghai Aladdin Reagent Co., Ltd., all of which were of analytical grade.

Example 1

According to Li Limei et al. “Interfacial structure and mechanical properties of alcohol-modified castor oil-based polyurethane/n-HA composite scaffold materials” (Inorganic Materials Journal, 2013, 28(8): 811-817), crystallized with calcium hydrogen phosphate The hydrate hydrate replaces the nano hydroxyapatite in the literature to prepare a calcium hydrogen phosphate-polyurethane composite prepolymer. That is, under the protection of nitrogen, 15 g of glycerin-modified castor oil (GCO) was added to a three-necked flask, and the oil bath was heated to 70 ° C to maintain a certain strength under mechanical stirring conditions, and calcium hydrogen phosphate crystal hydrate powder was added (over 300 13 g of mesh sieve, which was thoroughly mixed with castor oil. 15 g of IPDI was gradually added dropwise (the molar ratio of castor oil to IPDI was 1:1.5), and the reaction gave a calcium hydrogen phosphate crystal hydrate/polyurethane composite prepolymer. Then, 0.05 mL of catalyst stannous octoate was added to react for about 0.5 h, and then 0.5 mL of chain extender 1,4-butanediol was added to continue the reaction for 2 hours to obtain a viscous composite material, and calcium hydrogen phosphate in the calcium hydrogen phosphate-polyurethane composite material. The crystalline hydrate is about 30% by weight, correspondingly containing about 6% by weight of bound water as a foaming agent, and the viscous calcium hydrogen phosphate-polyurethane composite material is placed in a mold at 80, 90, 100, 110 ° C conditions, respectively. The undercooking foaming was carried out for 24 hours. After curing, a self-foaming porous composite bone repair scaffold is obtained.

The scanning electron micrographs of the foamed stents prepared at different temperatures are shown in Figure 1-4.

Example 2

The calcium hydrogen phosphate-hydroxyapatite-polyurethane composite prepolymerization was prepared by replacing the nano-hydroxyapatite in the literature with a calcium hydrogen phosphate crystal hydrate and a hydroxyapatite mixture according to the method described in the literature of Example 1. , hydrogen phosphate: hydroxyapatite weight ratio of 1:2; then add 0.5mL chain extender 1,4-butanediol and continue the reaction for 2h, to obtain a viscous composite, calcium hydrogen phosphate-hydroxyphosphate The calcium hydrogen phosphate crystal hydrate in the stone-polyurethane composite material is about 20% by weight, correspondingly containing about 4% by weight of bound water as a foaming agent; and the viscous calcium hydrogen phosphate-hydroxyapatite-polyurethane composite material is placed In the mold, the foaming was aged at 90 ° C for 24 hours. After curing, a self-foaming porous composite bone repair scaffold was obtained, and the porosity was determined to be 80.3±1.2% three times. The scanning electron micrograph before aging is shown in Fig. 5. After re-aging treatment at 110 ° C for 24 hours, the compressive strength was increased from 1.5. MPa before treatment to 3.6 MPa.

Example 3

The calcium hydrogen phosphate-hydroxyapatite-polyurethane composite prepolymerization was prepared by replacing the nano-hydroxyapatite in the literature with a calcium hydrogen phosphate crystal hydrate and a hydroxyapatite mixture according to the method described in the literature of Example 1. , hydrogen phosphate: hydroxyapatite weight ratio of 1:1; then add 0.5mL chain extender 1,4-butanediol and continue the reaction for 2h, to obtain a viscous composite, calcium hydrogen phosphate-hydroxyphosphate The calcium hydrogen phosphate crystal hydrate in the stone-polyurethane composite material is about 15% by weight, correspondingly containing about 3% by weight of bound water as a foaming agent; and the viscous calcium hydrogen phosphate-hydroxyapatite-polyamide The ester composite was placed in a mold and matured and foamed at 90 ° C for 24 hours. After curing, a self-foaming porous composite bone repair scaffold was obtained with a porosity of 82.2±2.1%. The scanning electron micrograph before aging is shown in Fig. 6. After re-aging treatment at 110 ° C for 24 hours, the compressive strength was increased from 1.7.MPa before treatment to 3.8 MPa.

Example 4

According to the method reported in the literature of Example 1, the calcium hydrogen phosphate-polyurethane composite prepolymer was prepared by replacing the nano-hydroxyapatite in the literature with calcium hydrogen phosphate crystal hydrate, and then 0.5 mL of chain extender 1 was added. After 4-butanediol was further reacted for 2 hours to obtain a viscous composite material. The calcium hydrogen phosphate-polyurethane composite material had a calcium hydrogen phosphate crystal hydrate of about 40% by weight, and correspondingly contained about 8 wt% of bound water as a foaming agent. The viscous calcium hydrogen phosphate-polyurethane composite material was placed in a mold and aged and foamed at 110 ° C for 4 hours. After curing, a self-foaming porous composite bone repair scaffold is obtained.

Example 5

According to the method reported in the literature of Example 1, the calcium hydrogen phosphate-polyurethane composite prepolymer was prepared by replacing the nano-hydroxyapatite in the literature with calcium hydrogen phosphate crystal hydrate, and then 0.5 mL of chain extender 1 was added. After 4-butanediol is further reacted for 2 hours to obtain a viscous composite material. The calcium hydrogen phosphate-polyurethane composite material has a calcium hydrogen phosphate crystal hydrate of about 10% by weight, and correspondingly contains about 2% by weight of bound water as a foaming agent. The viscous calcium hydrogen phosphate-polyurethane composite material was placed in a mold and aged and foamed at 100 ° C for 12 hours. After curing, a self-foaming porous composite bone repair scaffold is obtained.

Example 6

According to the method reported in the literature described in Example 1, the nano-hydroxyapatite was replaced by a mixture of calcium hydrogen phosphate crystal hydrate and hydroxyapatite, and the weight ratio of calcium hydrogen phosphate:hydroxyapatite was 1:2. A calcium hydrogen phosphate-hydroxyapatite-polyurethane composite prepolymer was obtained, and then 0.5 mL of a chain extender 1,4-butanediol was added to continue the reaction for 2 hours to obtain a viscous composite material; calcium hydrogen phosphate-hydroxyapatite The calcium hydrogen phosphate crystal hydrate in the stone-polyurethane composite material is about 10% by weight, correspondingly contains about 2% by weight of bound water as a foaming agent; and the viscous calcium hydrogen phosphate-hydroxyapatite-polyurethane composite material is placed In the mold, the foaming was aged at 90 ° C for 24 hours. After curing, a self-foaming porous composite bone repair scaffold is obtained. The structure of the porous scaffold is shown in Figure 7.

Example 7

According to the method reported in the literature of Example 1, a calcium hydrogen phosphate-tricalcium phosphate-polyurethane composite prepolymer was prepared by replacing the nano-hydroxyapatite in the literature with a calcium hydrogen phosphate crystal hydrate and a tricalcium phosphate mixture. Calcium hydrogen phosphate: tricalcium phosphate weight ratio is 1:1; then add 0.5mL chain extender 1,4-butanediol and continue to react for 2h to obtain a viscous complex In the composite material, the calcium hydrogen phosphate-tricalcium phosphate-polyurethane composite material has a calcium hydrogen phosphate crystal hydrate of about 10% by weight, correspondingly contains about 2% by weight of bound water as a foaming agent; and the viscous calcium hydrogen phosphate-phosphoric acid The tricalcium-polyurethane composite material was placed in a mold and aged and foamed at 90 ° C for 24 hours. After curing, a self-foaming porous composite bone repair scaffold is obtained.

Example 8

The calcium dihydrogen phosphate-hydroxyapatite-polyurethane composite was prepared by replacing the nano-hydroxyapatite in the literature with the calcium dihydrogen phosphate crystal hydrate and the hydroxyapatite mixture according to the method reported in the literature described in Example 1. Prepolymer, calcium dihydrogen phosphate: hydroxyapatite weight ratio of 1:2; then add 0.5mL chain extender 1,4-butanediol and continue the reaction for 2h, to obtain a viscous composite material, calcium dihydrogen phosphate - Hydroxyapatite-polyurethane composite material, calcium dihydrogen phosphate crystal hydrate is about 10% by weight, correspondingly containing about 0.7% by weight of bound water as a foaming agent; viscous calcium dihydrogen phosphate - hydroxy phosphate The stone-polyurethane composite was placed in a mold and matured and foamed at 120 ° C for 24 hours. After curing, a self-foaming porous composite bone repair scaffold is obtained.

Example 9

According to the method reported in the literature described in the first embodiment, calcium dihydrogen phosphate crystal hydrate and tricalcium phosphate mixture were substituted for the nano hydroxyapatite in the literature to prepare calcium dihydrogen phosphate-hydroxyapatite-polyurethane composite material. Polymer, calcium dihydrogen phosphate: tricalcium phosphate weight ratio is 1:7; then add 0.5mL chain extender 1,4-butanediol and continue the reaction for 2h to obtain a viscous composite material, calcium dihydrogen phosphate-phosphoric acid The tricalcium-polyurethane composite material has a calcium phosphate salt of about 40% by weight, a calcium dihydrogen phosphate crystal hydrate of about 5% by weight, and correspondingly contains about 0.36% by weight of bound water as a foaming agent; and a viscous calcium dihydrogen phosphate. The tricalcium phosphate-polyurethane composite material was placed in a mold and aged and foamed at 150 ° C for 2 hours. After curing, a self-foaming porous composite bone repair scaffold is obtained.

Example 10

According to Liu Haohuai et al., "Mechanical and Thermal Properties of Nano-HA/PU Composites" (Journal of Composite Materials, 2010, 27(3): 61-66), replacing nano-hydroxyl groups in the literature with calcium hydrogen phosphate crystal hydrate Apatite, a calcium hydrogen phosphate-polyurethane composite prepolymer is prepared. That is, the calcium hydrogen phosphate crystal hydrate/polyurethane composite material is prepared by a prepolymerization method. In the reaction, the ratio of the number of moles of -NCO to the total number of moles of -OH (polyol and chain extender) was 1.05:1. The ratio of the number of moles of hydroxyl groups of the polyethylene glycol in the polyol to the number of moles of hydroxyl groups in the castor oil is 1:2. First, 15 mL of polyethylene glycol and 20 mL of castor oil were placed in a three-necked flask equipped with a motorized stirrer and a vacuum nozzle, and vacuum-decompressed at 110 to 120 ° C for 1.5 to 2 hours. Then, the temperature was lowered to 75 ° C, and 20 mL of 4,4'-methylenedicyclohexyl diisocyanate and 0.05 mL of stannous octoate were added under a nitrogen atmosphere. Constant temperature reaction for 3.5h, making it fully and 4,4'-methylene Dicyclohexyl diisocyanate is reacted, at which time an -NCO-terminated prepolymer is obtained. Then, the temperature was lowered to 50 ° C, and the prepolymer was uniformly dispersed by adding 10 mL of acetone, and 0.5 mL of a chain extender 1,4-butanediol was further added dropwise. After the reaction for 0.5 h, 11 g of calcium hydrogen phosphate crystal hydrate was added, and the acetone solution was slowly added to maintain the mass fraction of the polyurethane in the solution at 50%. After stirring for 6 hours, a viscous composite material was obtained, and the calcium hydrogen phosphate-polyurethane was obtained. The calcium hydrogen phosphate crystal hydrate in the composite material is about 40% by weight, correspondingly containing about 8wt% of bound water as a foaming agent; the viscous calcium hydrogen phosphate-polyurethane composite material is placed in a mold at 85 ° C Mature foaming for 24 hours. After curing, a self-foaming porous composite bone repair scaffold is obtained.

Example 11

According to the method reported in the literature of Example 10, the calcium hydrogen phosphate-hydroxyapatite-polyurethane composite prepolymerization was prepared by replacing the nano-hydroxyapatite in the literature with a mixture of calcium hydrogen phosphate crystal hydrate and hydroxyapatite. , calcium hydrogen phosphate: hydroxyapatite weight ratio is 1:2; then slowly add acetone solution to maintain the mass fraction of polyurethane in the solution at 50%, after stirring for 6h, to obtain a viscous composite material, calcium hydrogen phosphate - Hydroxyapatite-polyurethane composite material has a calcium hydrogen phosphate crystal hydrate of about 20% by weight, correspondingly containing about 4% by weight of bound water as a foaming agent; and a viscous calcium hydrogen phosphate-hydroxyapatite-polyurethane The composite material was placed in a mold and aged and foamed at 90 ° C for 48 hours. After curing, a self-foaming porous composite bone repair scaffold is obtained.

Example 12

According to the method reported in the literature of Example 10, calcium dihydrogen phosphate crystal hydrate and hydroxyapatite mixture were substituted for the nano hydroxyapatite in the literature to prepare calcium dihydrogen phosphate-hydroxyapatite-polyurethane composite. Prepolymer, calcium dihydrogen phosphate: hydroxyapatite weight ratio is 1:2; then slowly add acetone solution to maintain the mass fraction of polyurethane in the solution at 50%, stirring for 6h, to obtain a viscous composite; The calcium dihydrogen phosphate-hydroxyapatite-polyurethane composite material has a calcium dihydrogen phosphate crystal hydrate of about 20% by weight, correspondingly containing about 1.5% by weight of bound water as a foaming agent; and a viscous calcium dihydrogen phosphate- The hydroxyapatite-polyurethane composite was placed in a mold and matured and foamed at 125 ° C for 24 hours. After curing, a self-foaming porous composite bone repair scaffold is obtained. The structure of the porous scaffold is shown in Fig. 8.

Claims

The preparation method of the self-foaming porous composite bone repairing stent is characterized in that the method comprises the following steps:

The calcium phosphate substance containing the calcium hydrogen phosphate crystal hydrate and/or the calcium dihydrogen phosphate crystal hydrate is used as an inorganic filler, and is uniformly compounded in the polyurethane system to form a composite material in the polyurethane synthesis process, and is higher than the crystal hydrate of calcium hydrogen phosphate. The product and/or the calcium dihydrogen phosphate crystal hydrate is aged for 1-48 hours under the temperature condition of decomposing the crystal water.
The method for preparing a self-foaming porous composite bone repairing stent according to claim 1, wherein the calcium phosphate substance further comprises one of hydroxyapatite, tricalcium phosphate, calcium pyrophosphate and octacalcium phosphate. Or a variety.
The method for preparing a self-foaming porous composite bone repairing stent according to claim 1 or 2, wherein the mass ratio of the calcium phosphate-based substance in the composite material is 10 to 65 wt%.
The method for preparing a self-foaming porous composite bone repairing stent according to any one of claims 1 to 3, wherein a mass ratio of the crystal water in the calcium phosphate material to the composite material is 0.05 to 10%.
The method for preparing a self-foaming porous composite bone repairing stent according to any one of claims 1 to 3, wherein the polyurethane is formed by polymerization of a polyether polyol or a polyester polyol and an isocyanate compound. Segment polymer.
The method for preparing a self-foaming porous composite bone repairing stent according to any one of claims 1 to 3, wherein the calcium phosphate substance is doped with nano silver, silver phosphate, silver nitrate, silver sulfadiazine, At least one of copper sulfate, copper nitrate, copper chloride, zinc sulfate, zinc nitrate, and zinc chloride.
A calcium phosphate-polyurethane composite characterized in that it comprises the following components:

a polyurethane and one or more calcium phosphate salts; wherein the calcium phosphate salt comprises at least one calcium phosphate salt containing water of crystallization.
The composite material according to claim 7, wherein the calcium phosphate salt has a weight percentage of from 10 to 60%.
The composite material according to claim 7 or 8, wherein the weight percentage of the crystal water is from 0.36 to 8%.
The composite material according to any one of claims 7 to 9, wherein the polyurethane is prepared from the following materials:

Isophorone diisocyanate or 4,4'-methylene dicyclohexyl diisocyanate;

Polyethylene glycol

Chain extender.
The composite material according to any one of claims 7 to 9, wherein the calcium phosphate salt containing calcium silicate is selected from the group consisting of CaHPO 4 · 2H 2 O or Ca(H 2 PO 4 ) 2 · H 2 O.
The composite material according to any one of claims 7 to 11, wherein the calcium phosphate salt further comprises any one or more of hydroxyapatite, tricalcium phosphate, calcium pyrophosphate or octacalcium phosphate. Kind.
The composite material according to any one of claims 7 to 9, wherein the chain extender is selected from the group consisting of 1,4-butanediol.
Use of the composite of any of claims 7-13 in the preparation of a porous scaffold material.
A calcium phosphate-polyurethane porous scaffold material, which is prepared by aging a composite material according to any one of claims 7-13.
The calcium phosphate salt-polyurethane porous scaffold material according to claim 15, wherein the calcium phosphate salt-polyurethane porous scaffold material has a porosity of 80.3% to 82.2%.
The calcium phosphate salt-polyurethane porous scaffold material according to claim 15 or 16, wherein the calcium phosphate salt-polyurethane porous scaffold material has a compressive strength of 3.6 to 3.8 MPa.