Preparation method and application of polyglutamic acid modified polyurethane

Abstract

The invention discloses a preparation method and application of polyglutamic acid modified polyurethane, belongs to the technical field of polyurethane material processing, and aims to provide a polyurethane material which has both shape memory performance and biocompatibility, can promote cell adhesion, growth and differentiation, is used for bone regeneration, improves osteogenesis efficiency, and improves osteogenesis quality. The invention relates to a preparation method of polyglutamic acid modified polyurethane, which comprises the following steps: dissolving gamma-benzyl-L-glutamic acid N-carboxylic acid anhydride in dioxane, and carrying out ring opening polymerization and post-treatment under the action of an initiator to obtain a gamma-benzyl-L-glutamic acid polymer. The shape memory performance and biocompatibility of the polyurethane material are effectively improved, cell adhesion, growth and differentiation can be promoted, the polyurethane material is used for bone regeneration, and the osteogenesis efficiency is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of polyurethane materials, and particularly relates to a preparation method and application of polyglutamic acid modified polyurethane. Background Art

[0002] Bone tissue usually has endogenous self-healing and regeneration abilities, but large-sized bone defects caused by trauma, age, congenital factors, etc. are still difficult to repair. In recent years, bone tissue engineering has been widely used to improve bone regeneration.

[0003] Bone fillers with shape memory properties can be compressed into a temporary shape and implanted into the damaged area, and then restored to the original shape at the bone defect site to provide a supporting role for bone tissue. This shape memory property is beneficial to reducing the damage to the patient's original bone during bone transplantation, and after restoring the original shape, it can contact the surrounding bone tissue and increase friction, reducing the possibility of loosening.

[0004] Polyglutamic acid can improve the activity of bone morphogenetic protein-2 (BMP-2), enhance bone inductivity, and polyglutamic acid is negatively charged, which helps to accelerate the deposition of hydroxyapatite, and has great potential in bone tissue engineering applications.

[0005] In view of the technical research in this regard, a solution is now proposed. Summary of the Invention

[0006] The purpose of the present invention is to provide a preparation method and application of polyglutamic acid modified polyurethane, aiming to provide a polyurethane material with both shape memory performance and biocompatibility, and capable of promoting cell adhesion, growth and differentiation, for bone regeneration to improve osteogenic efficiency.

[0007] The purpose of the present invention can be achieved by the following technical solutions:

[0008] A preparation method of polyglutamic acid modified polyurethane includes the following steps:

[0009] S1. Dissolve γ-benzyl-L-glutamic acid N-carboxylic anhydride in dioxane, carry out ring-opening polymerization under the action of an initiator, and perform post-treatment to obtain a γ-benzyl-L-glutamic acid polymer;

[0010] S2. Hydrolyze the benzyl group on the γ-benzyl-L-glutamic acid polymer molecule with an acid to obtain a L-glutamic acid polymer;

[0011] S3. Under the protection of an inert gas, carry out a prepolymerization reaction of a polyisocyanate and a polymer diol in the presence of a catalyst to obtain an isocyanate group double-capped prepolymer, and then carry out a polymerization reaction of the obtained isocyanate group double-capped prepolymer with a keto group-containing polyol chain extender to obtain a polyurethane;

[0012] S4. Through the Schiff base reaction, covalently link the L-glutamic acid polymer and polyurethane to prepare the polyglutamic acid modified polyurethane.

[0013] Further, in step S1, the dosage ratio of γ-benzyl-L-glutamic acid N-carboxylic anhydride, dioxane, and initiator is 1 g: 30 mL: 40 mg, the reaction temperature is 25 - 30 °C, the reaction time is 3 days, the initiator is an amino compound, and the post-treatment includes: after the reaction is completed, add ether to the reaction system, stir and disperse for 30 - 50 min, filter by suction, wash the filter cake with ether twice and then drain it by suction, transfer the filter cake to an oven at 30 - 35 °C, and vacuum dry to constant weight to obtain the γ-benzyl-L-glutamic acid polymer.

[0014] Further, the preparation method of the L-glutamic acid polymer is: dissolve the γ-benzyl-L-glutamic acid polymer in trifluoroacetic acid, add an acid catalyst to the reaction system, keep the temperature at 28 - 32 °C, stir and react for 60 - 80 min, add ether to the reaction system, precipitate, centrifuge to collect the precipitate, and freeze-dry to obtain the L-glutamic acid polymer.

[0015] Further, the dosage ratio of the γ-benzyl-L-glutamic acid polymer, trifluoroacetic acid, acid catalyst, and ether is 1 g: 25 mL: 2 g: 250 mL, and the acid catalyst is one or more of H2SO4, HBr, HCl, and HF.

[0016] Further, the molar ratio of the isocyanate group in the polyisocyanate to the hydroxyl group in the polymer diol is 1.5 - 3; the molar ratio of the hydroxyl group in the keto-group-containing polyol chain extender to the hydroxyl group in the polymer diol is 0.5 - 2; the input mass of the catalyst is 0.1 - 1.5% of the input mass of the polymer diol.

[0017] Further, the polyisocyanate is selected from one or more of hexamethylene diisocyanate, toluene diisocyanate, isophorone diisocyanate, diphenylmethane diisocyanate, dicyclohexylmethane diisocyanate, and lysine diisocyanate.

[0018] Further, the polymer diol is selected from one or more of polyethylene glycol, polyglycolic acid diol, and polycaprolactone diol, and the molecular weight of the polymer diol is 1000 - 5000.

[0019] Further, the keto-group-containing polyol chain extender is one or more of 1,3-dihydroxyacetone, 1,5-dihydroxy-3-pentanone, 2,4-dihydroxy-3-pentanone, glyceraldehyde, D-threose, and curcumin;

[0020] Further, the catalyst is selected from one or more of stannous octoate, stannous chloride, dibutyltin dilaurate, and 1,8-diazabicycloundecene.

[0021] Further, in step S4, the preparation method of the polyglutamic acid modified polyurethane is as follows: dissolve the polyurethane and the L-glutamic acid polymer in tetrahydrofuran, mix and stir at room temperature for 24 h, cast the film and volatilize, and then dry it under vacuum to obtain the polyglutamic acid modified polyurethane material.

[0022] Further, the dosage ratio of the polyurethane, the L-glutamic acid polymer, and tetrahydrofuran is 19 - 49 g: 0.6 - 1 g: 100 mL.

[0023] An application of the polyglutamic acid modified polyurethane, applying the polyglutamic acid modified polyurethane prepared according to a preparation method of the polyglutamic acid modified polyurethane in bone defect repair as a shape memory filling material.

[0024] The present invention has the following beneficial effects:

[0025] 1. In the preparation method of the polyglutamic acid modified polyurethane provided by the present invention, firstly, an amino compound is used as an initiator to prepare amino-terminated PLGA, then a chain extender containing a ketone group is used to prepare a polyurethane material with a ketone group in the main chain, and finally, the PLGA and the polyurethane main chain are covalently linked by the Schiff base reaction between the ketone group and the amino group. The introduction of PLGA improves the hydrophilicity of the polyurethane material, can improve the adhesion of cells on the material surface, and promotes the proliferation and differentiation of cells, so that the obtained polyurethane material has the application potential in the biomedical field.

[0026] 2. PLGA itself has a molecular structure of α helix, and its introduction can play a role of "molecular spring" in the polyurethane material. When the material is subjected to stress, it dissociates hydrogen bonds to assist in dissipating energy, thereby improving the mechanical properties of the material. The good biocompatibility of the composite material enables it to be applied to the treatment of bone defect repair. Description of the Drawings

[0027] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the following drawings are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained according to these drawings;

[0028] Figure 1 It is the synthesis reaction equation of the L-glutamic acid polymer in the present invention;

[0029] Figure 2 It is the synthesis reaction equation of the polyurethane in Example 1 of the present invention;

[0030] Figure 3 It is the synthesis reaction equation of polyglutamic acid modified polyurethane in Example 1 of the present invention;

[0031] Figure 4 It is the 1 1H-NMR spectrum of γ-benzyl-L-glutamic acid polymer (PBLG) and L-glutamic acid polymer (PLGA) prepared in Preparation Example 1 of the present invention;

[0032] Figure 5 It is the 1H-NMR spectra of polyurethane (PU) prepared in Comparative Preparation Example 1, polyurethane (PU) prepared in Example 1, and polyglutamic acid modified polyurethane (PU-PLGA) of the present invention 1 H-NMR spectrum;

[0033] Figure 6 It is the mechanical property analysis diagram of polyglutamic acid modified polyurethane specimens prepared in Examples 1-4 and Comparative Example 1 of the present invention;

[0034] Figure 7 It is the shape memory effect photos of polyglutamic acid modified polyurethane specimens prepared in Examples 1-4 and Comparative Example 1 of the present invention;

[0035] Figure 8 It is the shape fixation rate and shape recovery rate of polyglutamic acid modified polyurethane specimens prepared in Examples 1-4 and Comparative Example 1 of the present invention;

[0036] Figure 9 It is the columnar analysis diagram of cell survival rate of polyglutamic acid modified polyurethane specimens prepared in Examples 1-4 and Comparative Example 1 of the present invention;

[0037] Figure 10 It is the OD values of polyglutamic acid modified polyurethane specimens prepared in Examples 1-4 and Comparative Example 1 of the present invention co-cultured with cells for 1-3 days. Detailed implementation manners

[0038] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0039] Example 1

[0040] This example provides a preparation method of polyglutamic acid modified polyurethane applied to bone defect repair, including the following steps:

[0041] S1. Prepare γ-benzyl-L-glutamic acid polymer

[0042] Weigh: 1 g of γ-benzyl-L-glutamic acid N-carboxyanhydride and 30 mL of dioxane, add them to a reaction flask and stir until the system dissolves. Add 40 mg of ethylenediamine to the reaction flask. Under the environment of 25 °C, stir vigorously for 3 days. Add 300 mL of ether to the reaction flask, stir and disperse for 30 min, filter by suction. Wash the filter cake with ether twice and then drain it. Transfer the filter cake to a drying oven at 30 °C and dry it under vacuum until constant weight to obtain γ-benzyl-L-glutamic acid polymer.

[0043] S2. Preparation of L-glutamic acid polymer

[0044] Weigh: 1 g of γ-benzyl-L-glutamic acid polymer and 25 mL of trifluoroacetic acid, add them to a reaction flask and stir. Add 2 g of 33 wt% HBr solution to the reaction flask. Under the environment of 28 °C, keep stirring and reacting for 60 min. Add 250 mL of ether to the reaction flask to precipitate. Centrifuge at 10000 rpm to collect the precipitate. Lyophilize the precipitate in a lyophilizer at -30 °C to obtain L-glutamic acid polymer.

[0045] S3. Preparation of polyurethane

[0046] Weigh 3 g of polycaprolactone diol with a molecular weight of 1000, and calculate the molar amount of hydroxyl groups in polycaprolactone diol;

[0047] According to n NCO / n 聚己内酯二醇-OH = 1.5, calculate the dosage of hexamethylene diisocyanate and weigh it according to the calculated amount for standby;

[0048] According to n 扩链剂-OH / n 聚己内酯二醇-OH = 0.5, calculate the dosage of 1,3-dihydroxyacetone and weigh it according to the calculated amount for standby;

[0049] Under the protection of argon, add 3 g of polycaprolactone diol, the calculated amount of hexamethylene diisocyanate, 15 mL of N,N-dimethylformamide and 3 mg of stannous octoate to the reaction flask in sequence. After sealing the reaction flask, place it in an oil bath at 80 °C and react for 2 h. Add the calculated amount of 1,3-dihydroxyacetone to the reaction flask. After sealing the reaction flask, place it at 80 °C and continue to react for 6 h. Lower the temperature of the reaction flask to room temperature. Add 150 mL of anhydrous methanol to the reaction flask. Lower the temperature of the reaction flask to 5 °C. Filter by suction. Wash the filter cake with methanol and then drain it. Transfer the filter cake to a drying oven at 60 °C and dry it under vacuum until constant weight to obtain polyurethane.

[0050] S4. Preparation of polyglutamic acid modified polyurethane

[0051] Weigh: 19 g of polyurethane, 1 g of L-glutamic acid polymer and 100 mL of tetrahydrofuran are added to a reaction flask and stirred. The reaction is carried out at room temperature for 24 h. After film casting and volatilization, it is dried in vacuum to obtain a polyglutamic acid modified polyurethane material.

[0052] Example 2

[0053] This example provides a preparation method of polyglutamic acid modified polyurethane for bone defect repair, including the following steps:

[0054] S1. Prepare γ-benzyl-L-glutamic acid polymer

[0055] Weigh: 1 g of γ-benzyl-L-glutamic acid N-carboxylic anhydride and 30 mL of dioxane are added to a reaction flask and stirred until the system is dissolved. 40 mg of n-propylamine is added to the reaction flask. Under the environment of 27 °C, it is vigorously stirred and reacted for 3 days. 300 mL of ether is added to the reaction flask, stirred and dispersed for 40 min, filtered by suction. The filter cake is washed twice with ether and then dried by suction. The filter cake is transferred to a drying oven at 33 °C and dried in vacuum to constant weight to obtain γ-benzyl-L-glutamic acid polymer.

[0056] S2. Prepare L-glutamic acid polymer

[0057] Weigh: 1 g of γ-benzyl-L-glutamic acid polymer and 25 mL of trifluoroacetic acid are added to a reaction flask and stirred. 2 g of 37 wt% HCl solution is added to the reaction flask. Under the environment of 30 °C, it is kept warm and stirred for 70 min. 250 mL of ether is added to the reaction flask to precipitate. It is centrifuged at 10000 rpm to collect the precipitate. The precipitate is freeze-dried in a freeze dryer at -30 °C to obtain L-glutamic acid polymer.

[0058] S3. Prepare polyurethane

[0059] Weigh 3 g of polycaprolactone diol with a molecular weight of 2000, and calculate the molar amount of hydroxyl groups in the polymer diol;

[0060] According to n NCO / n 聚己内酯二醇-OH =2, calculate the dosage of hexamethylene diisocyanate and weigh it according to the calculated amount for standby;

[0061] According to n 扩链剂-OH / n 聚己内酯二醇-OH =1.3, calculate the dosage of 2,4-dihydroxy-3-pentanone and weigh it according to the calculated amount for standby;

[0062] Under the protection of argon, 3 g of polycaprolactone diol, hexamethylene diisocyanate, 15 mL of N,N-dimethylformamide and 9 mg of dibutyltin dilaurate were successively added to the reaction flask. After sealing the reaction flask, it was placed in an oil bath at 80 °C and reacted for 2 h. 2,4-Dihydroxy-3-pentanone was added to the reaction flask. After sealing the reaction flask, it was continued to react at 80 °C for 6 h. The temperature of the reaction flask was lowered to room temperature, 150 mL of anhydrous methanol was added to the reaction flask, the temperature of the reaction flask was lowered to 5 °C, filtered by suction, the filter cake was washed with methanol and then dried by suction. The filter cake was transferred to a drying oven at 65 °C and vacuum dried to constant weight to obtain polyurethane.

[0063] S4. Preparation of polyglutamic acid modified polyurethane

[0064] Weigh: 19 g of polyurethane, 0.8 g of L-glutamic acid polymer and 100 mL of tetrahydrofuran were added to the reaction flask and stirred, and reacted at room temperature for 24 h. After casting and volatilizing, it was vacuum dried to obtain polyglutamic acid modified polyurethane material.

[0065] Example 3

[0066] This example provides a preparation method of polyglutamic acid modified polyurethane applied to bone defect repair, including the following steps:

[0067] S1. Preparation of γ-benzyl-L-glutamic acid polymer

[0068] Weigh: 1 g of γ-benzyl-L-glutamic acid N-carboxylic anhydride and 30 mL of dioxane were added to the reaction flask and stirred until the system was dissolved. 40 mg of n-hexylamine was added to the reaction flask. Under the environment of 30 °C, it was vigorously stirred and reacted for 3 days. 300 mL of diethyl ether was added to the reaction flask, stirred and dispersed for 50 min, filtered by suction, the filter cake was washed with diethyl ether twice and then dried by suction. The filter cake was transferred to a drying oven at 35 °C and vacuum dried to constant weight to obtain γ-benzyl-L-glutamic acid polymer.

[0069] S2. Preparation of L-glutamic acid polymer

[0070] Weigh: 1 g of γ-benzyl-L-glutamic acid polymer and 25 mL of trifluoroacetic acid were added to the reaction flask and stirred. 2 g of 50 wt% H2SO4 was added to the reaction flask. Under the environment of 32 °C, it was kept warm and stirred for 80 min. 250 mL of diethyl ether was added to the reaction flask to precipitate. The precipitate was centrifuged and collected at 10000 rpm. The precipitate was freeze-dried in a freeze dryer at -30 °C to obtain L-glutamic acid polymer.

[0071] S3. Preparation of polyurethane

[0072] Weigh 3 g of polyethylene glycol with a molecular weight of 5000 and calculate the molar amount of hydroxyl groups in polyethylene glycol;

[0073] According to n NCO / n 聚乙二醇-OH = 3, calculate the dosage of isophorone diisocyanate, and weigh it according to the calculated amount for standby;

[0074] According to n 扩链剂-OH / n 聚乙二醇-OH = 2, calculate the dosage of glyceraldehyde, and weigh it according to the calculated amount for standby;

[0075] Under the protection of argon, add 3 g of polymer diol, polyisocyanate, 15 mL of N,N-dimethylformamide and 15 mg of stannous chloride to the reaction flask in sequence. After sealing the reaction flask, place it in an oil bath at 80 °C and react for 2 h. Add glyceraldehyde to the reaction flask, seal the reaction flask and continue to react at 80 °C for 6 h. Lower the temperature of the reaction flask to room temperature, add 150 mL of anhydrous methanol to the reaction flask, lower the temperature of the reaction flask to 5 °C, filter by suction. After the filter cake is washed with methanol and then dried by suction, transfer the filter cake to a drying oven at 70 °C and vacuum dry to constant weight to obtain polyurethane.

[0076] S4. Preparation of polyglutamic acid modified polyurethane

[0077] Weigh: 19 g of polyurethane, 0.7 g of L-glutamic acid polymer and 100 mL of tetrahydrofuran, add them to the reaction flask and stir. React at room temperature for 24 h. After casting and volatilizing, dry it under vacuum to obtain polyglutamic acid modified polyurethane material.

[0078] Example 4

[0079] The difference between this Example 4 and Example 3 is that in step S4, the dosage of L-glutamic acid polymer is 0.6 g.

[0080] Comparative Example 1

[0081] The difference between this Comparative Example and Example 1 is that in step S3, 1,4-butanediol is used to replace 1,3-dihydroxyacetone in an equimolar amount.

[0082] Performance test:

[0083] Refer to the standard GB / T 1040.3-2006 "Plastics - Determination of tensile properties - Part 3: Test conditions for films and sheets" to test the tensile strength and elongation at break of the polyglutamic acid modified polyurethane materials prepared in Examples 1-4 and Comparative Example 1. The specific test results are shown in Table 1 below.

[0084] Table 1 - Data table for detecting the tensile properties of samples

[0085]

[0086] It can be seen from the test results that adding a small amount of polyglutamic acid prepared by the solution provided by the present invention can significantly improve the mechanical properties of the material.

[0087] The polyglutamic acid-modified polyurethane materials prepared in Examples 1-4 and Comparative Example 1 were shaped in a 45°C water bath, fixed at -5°C, and restored to the original shape in a 45°C water bath. The shape fixation rate and shape recovery rate were calculated based on the spline length to test the shape memory performance of the specimens. The specific results are shown in Table 2 below.

[0088] Table 2 - Data table of shape memory test of specimens

[0089]

[0090] It can be seen from the test results that Examples 1-4 and the comparative example all have a relatively high shape fixation rate and shape recovery rate, close to 100%.

[0091] The biological safety of the polyglutamic acid-modified polyurethane materials prepared in Examples 1-4 and Comparative Example 1 was detected by a CCK-8 kit. The polyglutamic acid-modified polyurethane samples were prepared into films of 2×2 mm in size and co-cultured with cells. The original culture medium was aspirated and replaced with a culture medium containing CCK-8 and incubated for 2 hours on days 1-3, respectively. The absorbance value at 450 nm was detected and the cell survival rate was calculated. The cell survival rate is shown in Table 3 below.

[0092] Table 3 - Data table of biological safety test of specimens

[0093]

[0094] It can be seen from the test results that after the polyurethane films provided in Examples 1-4 and Comparative Example 1 were co-cultured with cells for 1-3 days, the cell survival rate was greater than 80%, proving that the material has high biological safety.

[0095] The above content is only an example and illustration of the structure of the present invention. Those skilled in the art of the present technology can make various modifications or supplements to the described specific embodiments or use similar methods for substitution, as long as they do not deviate from the structure of the invention or exceed the scope defined by the claims of the present invention, they should fall within the protection scope of the present invention.

[0096] In the description of this specification, the descriptions referring to terms such as "one embodiment", "example", "specific example", etc. mean that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in a suitable manner in any one or more embodiments or examples.

[0097] The preferred embodiments of the present invention disclosed above are only used to help illustrate the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to only the specific embodiments. Obviously, many modifications and variations can be made according to the content of this specification. These embodiments are selected and specifically described in this specification in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can well understand and utilize the present invention. The present invention is only limited by the claims and their full scope and equivalents.

Claims

1. A preparation method of polyglutamic acid modified polyurethane, characterized in that, It includes the following steps: S1. Dissolve γ-benzyl-L-glutamic acid N-carboxylic anhydride in dioxane, carry out ring-opening polymerization under the action of an initiator, and perform post-treatment to obtain a γ-benzyl-L-glutamic acid polymer; S2. Hydrolyze the benzyl group on the γ-benzyl-L-glutamic acid polymer molecule with an acid to obtain a L-glutamic acid polymer; S3. Under the protection of an inert gas, carry out a prepolymerization reaction of a polyisocyanate and a polymer diol in the presence of a catalyst to obtain an isocyanate group-terminated prepolymer, and then carry out a polymerization reaction of the obtained isocyanate group-terminated prepolymer with a keto-group-containing polyol chain extender to obtain a polyurethane; S4. Through a Schiff base reaction, covalently connect the L-glutamic acid polymer and the polyurethane to prepare a polyglutamic acid-modified polyurethane.

2. The preparation method of a polyglutamic acid-modified polyurethane according to claim 1, characterized in that, In step S1, the dosage ratio of γ-benzyl-L-glutamic acid N-carboxylic anhydride, dioxane, and the initiator is 1 g: 30 mL: 40 mg, the reaction temperature is 25-30 °C, the reaction time is 3 days, the initiator is an amino compound, and the post-treatment includes: after the reaction is completed, add ether to the reaction system, stir and disperse for 30-50 min, carry out suction filtration, wash the filter cake with ether twice and then drain it, transfer the filter cake to a drying oven at 30-35 °C, and vacuum dry to constant weight to obtain a γ-benzyl-L-glutamic acid polymer.

3. The preparation method of a polyglutamic acid-modified polyurethane according to claim 1, wherein, The preparation method of the L-glutamic acid polymer is: dissolve the γ-benzyl-L-glutamic acid polymer in trifluoroacetic acid, add an acid catalyst to the reaction system, keep warm and stir the reaction at 28-32 °C for 60-80 min, add ether to the reaction system, precipitate, centrifuge to collect the precipitate, and freeze-dry to obtain the L-glutamic acid polymer.

4. The preparation method of a polyglutamic acid-modified polyurethane according to claim 3, characterized in that, The dosage ratio of the γ-benzyl-L-glutamic acid polymer, trifluoroacetic acid, the acid catalyst, and ether is 1 g: 25 mL: 2 g: 250 mL, and the acid catalyst is one or more of H2SO4, HBr, HCl, and HF.

5. The preparation method of a polyglutamic acid-modified polyurethane according to claim 1, characterized in that, The molar ratio of the isocyanate group in the polyisocyanate to the hydroxyl molar number in the polymer diol is 1.5-3; the molar ratio of the hydroxyl group in the keto-group-containing polyol chain extender to the hydroxyl molar number in the polymer diol is 0.5-2; the input mass of the catalyst is 0.1-1.5% of the input mass of the polymer diol.

6. The preparation method of a polyglutamic acid-modified polyurethane according to claim 5, characterized in that, The polyisocyanate is selected from one or more of hexamethylene diisocyanate, toluene diisocyanate, isophorone diisocyanate, diphenylmethane diisocyanate, dicyclohexylmethane diisocyanate, and lysine diisocyanate; the polymer diol is selected from one or more of polyethylene glycol, polyglycolic acid diol, and polycaprolactone diol, and the molecular weight of the polymer diol is 1000-5000; the keto-group-containing polyol chain extender is one or more of 1,3-dihydroxyacetone, 1,5-dihydroxy-3-pentanone, 2,4-dihydroxy-3-pentanone, glyceraldehyde, D-threose, and curcumin, and the catalyst is selected from one or more of stannous octoate, stannous chloride, dibutyltin dilaurate, and 1,8-diazabicycloundecene.

7. The preparation method of a polyglutamic acid-modified polyurethane according to claim 1, characterized in that, In step S4, the preparation method of the polyglutamic acid modified polyurethane is as follows: Dissolve polyurethane and poly-L-glutamic acid in tetrahydrofuran, mix and stir at room temperature for 24 h, cast the film, evaporate, and then dry it under vacuum to obtain the polyglutamic acid modified polyurethane material.

8. The preparation method of a polyglutamic acid-modified polyurethane according to claim 7, characterized in that, The dosage ratio of the polyurethane, poly-L-glutamic acid and tetrahydrofuran is 19-49 g: 0.6-1 g: 100 mL.

9. Application of polyglutamic acid modified polyurethane, characterized in that, Apply the polyglutamic acid modified polyurethane prepared by the preparation method of a polyglutamic acid modified polyurethane according to any one of claims 1-8 to bone defect repair as a shape memory filling material.

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