CN109260505B

CN109260505B - Multi-component bone adhesive material and using method thereof

Info

Publication number: CN109260505B
Application number: CN201811338239.4A
Authority: CN
Inventors: 郑震; 肖海军; 朱祺; 王新灵
Original assignee: Shanghai Jiaotong University
Current assignee: Shanghai Jiaotong University
Priority date: 2018-11-12
Filing date: 2018-11-12
Publication date: 2021-02-09
Anticipated expiration: 2038-11-12
Also published as: CN109260505A

Abstract

The invention provides a multi-component bone adhesive material, which relates to the field of medical materials and comprises an isocyanate composition, a castor oil polyalcohol composition, a catalyst and inorganic particles with the particle size of 10nm-100um, wherein the inorganic particles contain water-absorbing sulfate and insoluble calcium salt, and the water-absorbing sulfate is distributed on the surfaces of the inorganic particles. The invention also provides a using method of the multi-component bone bonding material, the obtained bonding material has the advantages of high bone bonding strength, no influence on the growth of broken bones and the like, is particularly suitable for the environment with the body temperature of a human body, and overcomes the negative influence on the performance of the bonding material in the environment with water.

Description

Multi-component bone adhesive material and using method thereof

Technical Field

The invention relates to the field of medical materials, in particular to a multi-component bone adhesive material and a using method thereof.

Background

The medical bone adhesive is a novel fracture fixing material, is commonly used for attaching fine bone fragments and artificial implants to living bones or for small-area repair and reconstruction of bones, has the advantages of convenient operation, strong applicability and the like, and can overcome the problems of complex operation, easy secondary injury and easy infection of external fixation or metal internal fixation.

In recent years, medical bone adhesives (also referred to as bone adhesives) that are commonly used are classified into organic bone adhesives and inorganic bone adhesives. The organic bone adhesive is mostly formed of polymethyl methacrylate (PMMA) and a mixture thereof, and the polymer is polymerized at room temperature in the presence of an initiator from an acrylic monomer, such as Methyl Methacrylate (MMA). Because of its convenient use, it has applications in bone defect, bone tumor, fracture, artificial joint adhesion and fixation, etc. However, these conventional organic bone adhesive glues based on PMMA have the following disadvantages: during the process of bone bonding and curing, the great heat released by the glue layer can cause damage to surrounding tissues; PMMA is generally not readily degraded or absorbed by the body, which may cause inflammation at the site, increase the risk of infection, and may inhibit the growth of new bone from the fracture. The inorganic bone adhesive glue with calcium and phosphorus as main components has the characteristics of no toxicity, no stimulation, good biocompatibility, safety, bone conductivity and the like, but generally speaking, the glue is brittle, has low bonding strength to broken bones, and is not widely applied in practice.

Medical bone adhesives should meet the following requirements: (1) safe and reliable, non-toxic, and has no three causes (carcinogenesis, teratogenesis and mutagenesis); (2) has good biocompatibility and does not hinder the self healing of human tissues; (3) can be used in an environment with blood and interstitial fluid (water is present); (4) the rapid bonding can be realized at normal temperature and normal pressure; (5) the adhesive has good adhesive strength and durability, and the adhesive part has certain elasticity and toughness; (6) the product has no irritation to human body tissue during application; (7) after the use effect is achieved, the biological agent can be gradually degraded, absorbed and metabolized; (8) the antibacterial agent is self-sterile and has better antibacterial effect.

Polyurethane has been tried as an organic bone cement in clinical trials in the early 50 s of the last century and has been forced to be discontinued due to the poor adhesion of the polyurethane cement used at that time to bone, the high infection rate and complications. By the nineties of the last century, modified polyurethane adhesive systems have been developed, such as US 5266608; thereafter, the development of polyurethane bone cement materials aimed at improving bone adhesion strength and reducing clinical adverse reactions has been continued, wherein the polyurethane bone cement (Kryptonite) using castor oil polyol as soft segment, which is approved by the U.S. food and drug administration^TM) Most prominent. The polyurethane bone cement comprises castor oil modified based castor oilFillers such as oil polyols, isocyanates, and beta-calcium phosphate are mixed during surgery to form a cement paste, while forming a rigid porous polymer prior to the sealing operation. Such bone adhesives have been used clinically in surgeries such as sternal closure, skull adhesion, etc., as shown in patents US8211458B2 and US 20050031578.

Currently, the modified polyurethane bone cement still has several challenges when used for bonding to human bone, including: due to the limitation of human body application, the temperature of the polyurethane bone cement is the temperature suitable for the human body, and the heat generated in the reaction can not exceed 50-60 ℃ so as to avoid burning skin tissues and causing human body injury. Meanwhile, clinically, within a short time (generally about 30 minutes), the bone adhesion reaches a certain initial adhesion strength. In addition, a large amount of blood and interstitial fluid are often generated on the wounded surface of a human body, and the water-carrying environment has a great negative effect on the performance of the polyurethane material. Because a large amount of water consumes isocyanate groups and generates a large amount of urea bonds, the adhesive strength of the material is influenced on one hand, and the reaction ratio of the components is changed on the other hand, so that the final adhesive property of the material is influenced.

Therefore, in view of the above problems, those skilled in the art need to design a bone adhesive material more suitable for the body temperature environment of human body from the viewpoint of formulation and process, so as to reduce the influence of blood and tissue fluid on the bone adhesive performance as much as possible, and at the same time, not to cause short-term or long-term adverse effects on human body.

Disclosure of Invention

In view of the above-mentioned defects of the prior art, the technical problem to be solved by the invention is to improve the formula and process of the polyurethane bone cement, which is suitable for being used in the environment with human body temperature and overcomes the negative influence on the performance of the cement in the environment with water.

In order to achieve the above object, the present invention provides a multi-component bone adhesive material comprising an isocyanate composition, a castor oil polyol composition, a catalyst, inorganic particles having a particle size of 10nm to 100um, and the inorganic particles containing a water-absorbing sulfate and a sparingly soluble calcium salt, wherein the water-absorbing sulfate is distributed on the surface of the inorganic particles.

The main components of the skeleton are mainly composed of inorganic components containing calcium and phosphorus. The inorganic component is added into the bone bonding material, so that the structure close to the inner bone of a human body can be prepared, and the growth and regeneration of broken bones are facilitated. The inorganic particles of the present invention contain at least two inorganic components including water-absorbing sulfate and sparingly soluble calcium salt, wherein the role of the calcium salt component has been explained in many patents, but in bone adhesive materials, the incorporation of water-absorbing sulfate has not been mentioned in previous reports.

When the bone adhesive material is used, bleeding of blood and tissue fluid in the human body may be encountered, and although the reaction rate of the isocyanate group with water is slow, the liquid dilutes the mixed solution of the unreacted polyurethane, greatly reduces the reaction rate of NCO and hydroxyl, and thus the performance of the bone adhesive material is greatly impaired. In the presence of the water-absorbing sulfate, the liquid around the bonding material can be converted into a solid state within a certain time, which can ensure smooth polyurethane reaction at medium and low temperature to a great extent. To achieve this effect, specific requirements are imposed on the composition, morphology, structure of the inorganic particles. In the present invention, it was found that the inorganic particles have a particle size of 10nm to 100 μm and contain a water-absorbing sulfate and a sparingly soluble calcium salt, wherein the water-absorbing sulfate is distributed on the surface of the inorganic particles, and the effect can be achieved.

In the preferred embodiment of the invention, anhydrous magnesium sulfate is used and distributed on the surface of the insoluble calcium carbonate. Anhydrous magnesium sulfate has a strong drying ability, rapidly generates a water-containing crystalline compound after absorbing water, and is commonly used industrially for drying organic compounds. A feasible method for preparing the anhydrous magnesium sulfate inorganic particles with distributed surfaces is to filter a saturated solution of refined magnesium sulfate, add other inorganic particles of a bone binding material, cool and crystallize under stirring, centrifugally separate, and dry and dehydrate at the temperature of 200-250 ℃ to prepare the inorganic particles with the surface compounded with the anhydrous magnesium sulfate.

In the embodiment of the present invention, the amount of anhydrous magnesium sulfate is suitably selected depending on the environment of use, the amount of bleeding and the amount of interstitial fluid. According to the principle, similar substances which are easy to absorb water can be adopted, and similar effects can be achieved on the premise of not influencing the polyurethane reaction.

In the multi-component bone adhesive material of the present invention, the sparingly soluble calcium salt may be selected from one or more of calcium carbonate, β -tricalcium phosphate, hydroxyapatite and the like.

In particular embodiments of the present invention, the castor oil polyol composition is a castor oil diol and a castor oil triol. Preferably, 100 parts by weight of the castor oil triol further comprises 0.5 to 3 parts by weight of water. The modified polyol after castor oil esterification is harmless to human bodies, and is easier to degrade when broken bones are formed compared with petroleum-based polyester polyol and polyether polyol. The invention finds that the addition of a small amount of water in the castor oil triol has the following two advantages: 1. after water reacts with isocyanate groups, micropores are formed in a bone adhesion system, and an adhesive layer beneficial to the growth of bone cells can be obtained by controlling the opening rate and the pore size; 2. the reaction is exothermic, and the reaction temperature of the polyurethane is increased to a certain extent by controlling the use process, so that the mechanical property of the bone adhesive material is improved. Of course, the amount of water should not be too high, and it should be avoided that the temperature of the portion of the bone cement material in contact with the human body rises too high to exceed the acceptable range for the human body.

In the multi-component bone-adhesive material of the present invention, the isocyanate composition is preferably an isocyanate composition containing two or more-NCO groups. The isocyanate may be selected from aliphatic, cycloaliphatic and aromatic isocyanate mixtures, more preferably hydrogenated aromatic isocyanate compositions. The present inventors have found that when the isocyanate composition is a hydrogenated aromatic isocyanate composition containing two or more-NCO groups, the adhesive effect of the bone adhesive material is more excellent.

The quick reaction between the isocyanate group and the hydroxyl group at normal temperature or near human body temperature is met, and the selection of a correct catalyst system is important. Such a polycondensation reaction is generally called a resinification or gelation reaction, and the molecular weight increases after the reaction, and the adhesiveness, mechanical properties and molding characteristics of the polymer are exhibited. In order that the bone cement material does not become an obstacle to the growth of human bone tissue in the human body, an alternative is to build fine, uniform cells in the formed cement structure, as is described in patent US 20050220771. However, due to the complexity of the catalytic purpose and due to the high standard requirements of use in the human body, the catalytic systems used in different technologies can only be determined experimentally and are highly novel and specific.

In a specific embodiment of the present invention, the catalyst is a combination of a gel reaction catalyst and a foaming catalyst, preferably an amine catalyst which is non-toxic or low-toxic to human body, more preferably one or more of 1, 2-dimethylimidazole solution, triethylene diamine solution, pentamethyldiethylenetriamine and the like, or modified tertiary amine.

The bone adhesive material has the characteristics of strong adhesiveness, high mechanical strength, good bone conductivity, contribution to the growth and regeneration of broken bones, safety to human bodies and the like, is suitable for the environment with the body temperature of the human bodies, and overcomes the negative influence on the performance of the adhesive in the environment with water. Has good application prospect in human bone repair such as cancellous bone and hard bone tissue adhesion.

The invention also provides a specific use method of the multi-component bone adhesive material, which comprises the following steps:

step 1, uniformly mixing isocyanate micromolecules or oligomers with castor oil dihydric alcohol according to the mol ratio of functional group NCO/OH of 1-1.3, and reacting at 60-90 ℃ to synthesize an isocyanate-terminated polyurethane prepolymer;

step 2, adding a catalyst into the castor oil triol or the mixture of the castor oil triol and the castor oil diol to be uniformly dissolved to obtain a triol composition;

and 3, uniformly mixing the polyurethane prepolymer, the ternary alcohol composition and inorganic particles with the particle size of 10nm-100um according to the proportion: wherein the molar ratio of functional groups NCO/OH is 1-1.1, the inorganic particles represent 10-50 wt.% of the total weight; the inorganic particles contain water-absorbing sulfate and insoluble calcium salt, wherein the water-absorbing sulfate is distributed on the surface of the inorganic particles; the feeding sequence comprises inorganic particles, polyurethane prepolymer and a ternary alcohol composition; mixing for 3-8 min, coating, such as coating on the fracture surface, preferably applying certain pressure on the fracture to maintain normal adhesion of the fracture surface, and finishing the bone adhesion after 15-30 min.

The synthesis method of the step 1 can easily obtain the polyurethane prepolymer with long-term storage through the conventional chemical technology. 0.5-3 parts by weight of water (based on the weight of the castor oil triol) can be added to the castor oil triol in step 2. If a mixture of the castor oil dihydric alcohol and the castor oil trihydric alcohol is used in the step 2, the viscosity of the liquid in use can be reduced, and the two components of the polyurethane can be uniformly mixed. In the step 3, when anhydrous magnesium sulfate exists on the surface of the inorganic particle, the use effect of the binding material is greatly influenced, before an experiment, inorganic particles with different anhydrous magnesium sulfate contents can be prepared, and different inorganic particles are selected according to specific medical environment when in use.

The conception, the specific structure and the technical effects of the present invention will be further described with reference to the accompanying drawings to fully understand the objects, the features and the effects of the present invention.

Drawings

Fig. 1 is a graph showing the change in external temperature of a bone cement material according to a preferred embodiment of the present invention.

Detailed Description

The technical contents of the preferred embodiments of the present invention will be more clearly and easily understood by referring to the drawings attached to the specification. The present invention may be embodied in many different forms of embodiments and the scope of the invention is not limited to the embodiments set forth herein.

Description of the reagents used

The following reagents, not indicated by manufacturer, were purchased from Sigma-Aldrich and used as received without treatment.

MDI: 4,4' -diphenylmethane diisocyanate;

HMDI: 4, 4-diisocyanate dicyclohexylmethane;

HXDI: hydrogenated dimethylene benzene diisocyanate, mitsui chemical co;

M20S: polymeric MDI having an NCO content of 30.74% by weight, BASF Limited;

POLYCIN D290: castor oil glycol, Vanderues (Shanghai) trade, Inc.;

POLYCIN T400: castor oil triol, Vanderues (Shanghai) trade, Inc.;

catalyst DM: tosoh (Shanghai) Biotech, Inc.;

catalyst F: tosoh (Shanghai) Biotech, Inc.;

pentamethyldiethylenetriamine: shanghai Aladdin Biotechnology Ltd;

pentamethyldipropylene triamine: shanghai Aladdin Biotechnology Ltd;

calcium carbonate: the grain diameter is 3-5 um;

β -tricalcium phosphate (TCP): the grain diameter is 3 um;

hydroxyapatite (HA): the grain diameter is 10 um;

anhydrous magnesium sulfate: chemical reagents of the national drug group Shanghai Co., Ltd;

defoaming agent: DB-100, Dow chemical Co., Ltd;

surfactant (b): pluronic F108, Pasteur Chemicals, Inc.

Determination of NCO content in polyurethane prepolymer

And (3) after the isocyanate micromolecules and oligomers react with the castor oil dihydric alcohol, obtaining a polyurethane prepolymer, measuring the content of NCO groups in the polyurethane prepolymer by adopting a di-n-butylamine titration method, and accurately calculating the use amount of the castor oil trihydric alcohol composition required by the final polyurethane reaction according to the content.

Quantitative preparation of inorganic particles containing anhydrous magnesium sulfate

Filtering saturated solution of refined magnesium sulfate, adding insoluble calcium salt such as calcium carbonate powder with hydrophilic surface, cooling and crystallizing under slow stirring, centrifuging, and drying and dehydrating at 250 deg.C under 200-. The content of anhydrous magnesium sulfate in the inorganic particles can be determined by calculating the mass of the residue (inorganic component hardly soluble in water) after washing and drying for many times to a constant weight.

Inorganic particles containing anhydrous magnesium sulfate at about 20 wt.% and 50 wt.% were prepared, respectively.

In vitro bone adhesion test

Before the experiment, the cooled and preserved porcine cancellous bone is selected and cut into small pieces which are polished into 5 multiplied by 18 multiplied by 32mm³Is divided into two rectangular blocks with equal volume and the cross section area is 5 multiplied by 18mm²After polishing the section, using cotton dipping solution to wipe the section to be bonded, keeping the surface to be bonded wet, and uniformly coating the prepared polyurethane adhesive. After the two bones are adhered, fixing the two bones, respectively placing the two bones in three different environments, and taking out the two bones after post-curing for 24 hours to test the adhesive property of the sample.

Here the three different environments are: environment 1, the bone is not directly contacted with moisture after being bonded; environment 2, placing the bonded bones in a cotton ball soaked in PBS buffer solution; environment 3, bone was placed in PBS buffer after bonding.

Method for testing adhesive property of sample

(1) Water absorption (mass percent): the adhesive material is mixed in a mold and then cured and molded, and after being placed at room temperature for 24 hours, the water absorption of the adhesive material is measured in water to characterize the degree of opening in the adhesive layer.

(2) In vitro bone adhesion strength: the in vitro bone adhesion strength was measured by an INSTRON 4465 electronic universal tester with a stress sensor of 2KN and a tensile rate of 5mm/min at room temperature.

(3) Compressive strength and compressive modulus: the test is carried out at room temperature by using an INSTRON 4465 type electronic universal tester and a stress sensor 2KN, wherein the compression rate is 2mm/min, and the compression strain limit is 50%. Sample specification:

h is a cylinder of 13 mm. The compressive strength and compressive modulus of the sample were measured.

Example 1

Heating and vacuumizing POLYCIN D290 (castor oil diol) in a 150ml three-necked bottle with a nitrogen and stirrer to remove water for 2h, adding MDI (4,4' -diphenylmethane diisocyanate) and M20S (polymeric MDI) in a molar ratio of 7/3 according to the NCO/OH (molar ratio of 1.05), heating to 80 ℃, introducing nitrogen to protect and reacting for 3h to obtain light brown transparent polyurethane prepolymer. And (3) sampling and titrating after the synthesis reaction of the polyurethane prepolymer is finished, and calculating the mass fraction of the isocyanic acid radical.

Adding 0.5 wt.% of a mixture of a catalyst F and pentamethyldiethylenetriamine (the mass ratio is 9/1) and 1 wt.% of pure water into the POLYCIN T400, and uniformly mixing the mixture and the pure water according to the weight of the POLYCIN T400 to obtain a ternary alcohol composition.

Testing of in vitro bone adhesion properties: according to the formula of example 1 in table 1, calcium carbonate powder, polyurethane prepolymer and triol composition are sequentially added into a plastic container, stirred for about 3-5min at normal temperature, coated on the surface of a broken bone, subjected to in vitro bone adhesion experiment in an environment 1, and an infrared temperature sensing gun is used for detecting the external temperature of a glue layer, so that a graph 1 is obtained. As can be seen from fig. 1, the temperature rise of the heat released by the adhesive layer has no influence on human tissues, and is suitable for the human body temperature environment.

TABLE 1

Remarking:

1. according to the amount of the moisture in the environment where the bone adhesive material is located, three typical use environments are selected in the experiment for later maintenance: environment 1, the bone is not directly contacted with moisture after being bonded; environment 2, placing the bonded bones in a cotton ball soaked in PBS buffer solution; environment 3, placing the bonded bone in a PBS buffer solution;

2. for all examples in the table, the polyurethane prepolymers were synthesized at the ratio NCO/OH ═ 4, where OH is provided by POLYCIN D290;

3. the water content (%) in the triol is calculated as PolyCIN T400 by weight.

Example 2

Compared with example 1, the formulation process was unchanged except that calcium carbonate was changed to β -tricalcium phosphate. Likewise, in vitro bone adhesion experiments were performed in environment 1.

Example 3

Compared with example 1, the formulation process is unchanged except that calcium carbonate is replaced by hydroxyapatite. Likewise, in vitro bone adhesion experiments were performed in environment 1.

Example 4

Compared with example 1, the other formulation process is not changed except that 1 wt.% of catalyst F and pentamethyldiethylenetriamine (9/1 in mass ratio) mixture is added into the POLYCIN T400, and 2 wt.% of pure water is added. Likewise, in vitro bone adhesion experiments were performed in environment 1.

Example 5

Compared with example 1, the formulation process was unchanged except for the replacement of MDI (4,4' -diphenylmethane diisocyanate) with HMDI (4, 4-diisocyanate dicyclohexylmethane). Likewise, in vitro bone adhesion experiments were performed in environment 1.

Example 6

In comparison with example 1, the formulation was not modified, except that MDI (4,4' -diphenylmethane diisocyanate) was replaced by HXDI (hydrogenated dimethylene diisocyanate). Likewise, in vitro bone adhesion experiments were performed in environment 1.

Example 7

The in vitro bone adhesion experiment was performed in environment 2, except that the calcium carbonate was changed to calcium carbonate with 20 wt.% anhydrous magnesium sulfate on the surface, as compared to example 1, and the formulation process was not changed.

Example 8

The in vitro bone adhesion experiment was performed in environment 3, except that the calcium carbonate was changed to calcium carbonate with 50 wt.% anhydrous magnesium sulfate on the surface, as compared to example 1, and the formulation process was not changed.

Comparative example 1

Compared with the embodiment 1, the ternary alcohol composition does not contain water, and other formulation processes are not changed. Likewise, in vitro bone adhesion experiments were performed in environment 1.

Comparative example 2

In comparison to example 5, the formulation process was unchanged, but in vitro bone adhesion experiments were performed in environment 2.

Comparative example 3

The water content of the triol composition was reduced to 1 wt.% compared to example 4, and the other formulation processes were unchanged, but in vitro bone adhesion experiments were performed in environment 3.

The results of the in vitro bone adhesion experiments of examples 1 to 8 and comparative examples 1 to 3 are shown in table 2.

TABLE 2

Remarking: directly observing the growth condition of broken bones in the animal body for 1-3 months, and comprehensively evaluating as better + +; good +; generally + -; poor x.

The effects of the present invention will be further explained by the following description:

in example 1, 1 wt.% of water was added to the castor oil triol, which produced a microcellular foam effect during the polyurethane reaction, thereby facilitating the growth of bone cells. On the contrary, comparative example 1 does not contain water, and is not good for bone tissue repair due to low porosity of the adhesive material.

In example 2 and example 3, different inorganic particles were used, and also a better bone adhesion effect was obtained within the particle size range defined in the present invention. Due to the difference in reactivity of the small isocyanate molecules, the same sizing process measured slightly lower bone bond strength in examples 5 and 6 than the MDI-made bone cement, but did not impede the growth of fractured bones.

In example 7 and example 8, the characteristic that anhydrous magnesium sulfate can absorb water rapidly is utilized skillfully, and in the sizing process, the moisture in interstitial fluid and blood near the glue layer can be converted into crystal water rapidly to form a solid state, so that the isocyanate group of polyurethane can react with the hydroxyl group in the polyol, and the bonding performance is not influenced by the moisture in the environment.

Furthermore, it was surprisingly found that in examples 7 and 8, the incorporation of anhydrous magnesium sulfate on the surface of the inorganic particles resulted in a greater open porosity in the glue layer without adversely affecting the bone adhesion strength. This effect directly causes a large decrease in the bone bonding strength in comparative examples 2 and 3.

The foregoing detailed description of the preferred embodiments of the invention has been presented. It should be understood that numerous modifications and variations could be devised by those skilled in the art in light of the present teachings without departing from the inventive concepts. Therefore, the technical solutions available to those skilled in the art through logic analysis, reasoning and limited experiments based on the prior art according to the concept of the present invention should be within the scope of protection defined by the claims.

Claims

1. A multi-component bone adhesive material comprises an isocyanate composition, a castor oil polyol composition and a catalyst, and is characterized by further comprising inorganic particles with the particle size of 10nm-100um, wherein the inorganic particles contain water-absorbing sulfate and slightly soluble calcium salt, and the water-absorbing sulfate is distributed on the surface of the slightly soluble calcium salt.

2. The multi-component bone adhesive material of claim 1, wherein the water-absorbing sulfate salt is anhydrous magnesium sulfate and is distributed on the surface of the poorly soluble calcium salt.

3. The multi-component bone adhesive material of claim 1, wherein the poorly soluble calcium salt is selected from the group consisting of: calcium carbonate, beta-tricalcium phosphate and hydroxyapatite.

4. The multi-component bone adhesive material according to any one of claims 1 to 3, wherein the castor oil polyol composition is a castor oil diol and a castor oil triol.

5. The multi-component bone adhesive material of claim 4, wherein 100 parts by weight of the castor oil triol further comprises 0.5 to 3 parts by weight of water.

6. The multi-component bone adhesive material according to any one of claims 1 to 3, wherein the isocyanate composition is an isocyanate composition containing two or more-NCO groups.

7. The multi-component bone adhesive material according to any one of claims 1 to 3, wherein the isocyanate composition is a hydrogenated aromatic isocyanate composition.

8. The multi-component bone adhesive material according to any one of claims 1 to 3, wherein the catalyst is a combination of a gel reaction catalyst and a foaming catalyst, wherein the gel reaction catalyst is an amine catalyst.

9. The multi-component bone adhesive material according to claim 8, wherein the amine-based catalyst is selected from the group consisting of: one or more of 1, 2-dimethyl imidazole solution, triethylene diamine solution, pentamethyl diethylene triamine and pentamethyl dipropylene triamine.

10. A method of using a multi-component bone cement comprising the steps of:

and 3, adding and uniformly mixing the polyurethane prepolymer, the triol composition and inorganic particles with the particle size of 10nm-100um according to the proportion: wherein the molar ratio of functional groups NCO/OH is from 1 to 1.1, the inorganic particles represent from 10 to 50 wt.% of the total weight; the inorganic particles contain water-absorbing sulfate and insoluble calcium salt, wherein the water-absorbing sulfate is distributed on the surface of the inorganic particles; the feeding sequence comprises inorganic particles, polyurethane prepolymer and a ternary alcohol composition; mixing for 3-8 min, and coating.