Polyurethane sponge and its preparation method and application

Abstract

A polyurethane sponge and its preparation method and application, relating to the field of medical material technology, solves the problems of poor biocompatibility, poor biodegradation effect, lack of antibacterial properties of traditional polyurethane materials, and decreased mechanical rigidity of existing amino acid-based polyurethane materials. The preparation steps of the present invention are: an amino acid compound containing a hydroxyl group in a side chain is prepared by a condensation reaction to obtain a chain extender amino acid cyclic dipeptide; polyethylene glycol is heated, vacuum dehydrated, mixed and dissolved with N, N-dimethylformamide, and reacted with diisocyanate after cooling to generate a prepolymer; the prepolymer and the chain extender undergo nucleophilic addition reaction to extend the chain, and the prepolymer continues to undergo nucleophilic addition reaction with natural amino acid monomers to prepare a polyurethane elastomer; divalent metal ions are loaded onto the elastomer, and after freeze-drying, a polyurethane sponge is prepared. The polyurethane sponge prepared by the present invention has excellent degradability, biocompatibility and antibacterial properties, and can be applied to the biomedical field.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and in particular to a polyurethane sponge and a preparation method and application thereof. Background Art

[0002] Medical sponges, as indispensable auxiliary materials in the medical field, are widely used in wound dressings and postoperative hemostasis applications due to their soft, skin-friendly, and biocompatible properties. Polyurethane sponges are a mainstream choice due to their excellent elasticity and liquid adsorption capacity. These materials are typically formed through the addition polymerization of polyols, isocyanates, and chain extenders. The choice and dosage of chain extenders have a crucial impact on the mechanical properties, thermal stability, biocompatibility, and degradation properties of polyurethane materials. Currently, the most widely used chain extenders are diols and diamines, but these chain extenders suffer from poor biocompatibility and slow degradation. For example, while 1,4-butanediol and ethylenediamine can significantly improve the mechanical properties of polyurethane, their degradation time in vivo is typically several months to two years, and in vitro degradation time is even longer, reaching several months to several years. Ethylenediamine also has poor biocompatibility, which may cause adverse reactions in organisms. Furthermore, while the porous structure of these polyurethane materials provides excellent liquid adsorption properties, it also provides a suitable habitat for bacteria. Bacteria easily attach and multiply within the pores of polyurethane sponges, forming biofilms. This will in turn affect the adsorption and mechanical properties of the polyurethane sponge, which may cause wound infection, prolong healing time, and even cause serious complications. This seriously limits the application of polyurethane materials in the medical and environmentally friendly fields.

[0003] To overcome these issues, researchers are developing rapidly degradable polyurethane materials by introducing biobased materials. Amino acid-based polyurethanes contain amino (-NH2) and carboxyl (-COOH) groups within their structures, which can be incorporated into the polyurethane chain as chain extenders or soft segment components, forming ester and amide bonds that are susceptible to hydrolysis or enzymatic degradation, effectively improving the poor compatibility of traditional polyurethanes. However, the introduction of readily degradable units such as ester bonds and amino acids into amino acid-based polyurethanes often reduces the rigidity of the polyurethane material, leading to deterioration in mechanical properties such as mechanical strength and wear resistance, hindering its practical application and widespread adoption.

[0004] Therefore, developing a polyurethane material with excellent biocompatibility, degradability and mechanical strength is of great practical significance, which can promote the rapid development of polyurethane materials in the biomedicine field while meeting the urgent needs of green and low-carbon development. Summary of the Invention

[0005] In order to solve the problems of poor biocompatibility, poor biodegradation effect, lack of antibacterial properties of traditional polyurethane materials, and decreased mechanical rigidity of existing amino acid-based polyurethane materials, the present invention proposes a polyurethane sponge and its preparation method and application.

[0006] A method for preparing a polyurethane sponge comprises the following steps:

[0007] S1: dissolving an amino acid compound containing a hydroxyl group on a side chain in ethylene glycol, heating and refluxing the mixture under inert gas protection, pouring the reaction solution into deionized water, filtering the precipitate, washing the precipitate, and then vacuum drying the precipitate to prepare an amino acid cyclic dipeptide;

[0008] S2: Polyethylene glycol (PEG) is heated and dehydrated under vacuum conditions, N,N-dimethylformamide (DMF) is added and stirred to dissolve, the temperature is lowered, and diisocyanate is added to react to form a prepolymer;

[0009] S3: adding amino acid cyclic dipeptide to the prepolymer for reaction, and then adding amino acid monomer to react after the reaction to prepare a polyurethane elastomer;

[0010] S4: Soaking the polyurethane elastomer in a metal ion solution, loading the metal ions having both antibacterial and cross-linking promoting effects onto the elastomer, freeze-molding the polyurethane elastomer, taking it out and freeze-drying it to prepare a polyurethane sponge.

[0011] Furthermore, the amino acid compound in S1 is one or a combination of two of serine, tyrosine, threonine, and hydroxyproline.

[0012] Furthermore, the heating temperature in S1 is 170-200°C; the reflux time is 12-24 h; the step of washing the precipitate is: washing with deionized water 3 times and reflux washing with ethanol 5 times; and the drying temperature is 80°C.

[0013] Furthermore, the diisocyanate is any one of hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI), 4,4'-diphenylmethane diisocyanate (MDI), 1,4-diisocyanate butane (BDI), and 4,4'-dicyclohexylmethane diisocyanate (HMDI).

[0014] Furthermore, the molecular weight of the PEG in S2 is 400-6000; the heating temperature is 100-120°C; the dehydration time is 1-4 h; the cooling is to 60-80°C; the molar ratio of the diisocyanate to PEG is 2.0-3.0:1, and the reaction time is 2 h.

[0015] Furthermore, the molar ratio of -NCO in the prepolymer to -OH in the amino acid cyclic dipeptide in S3 is 1:0.1-0.9, the reaction temperature of the prepolymer and the amino acid cyclic dipeptide is 80-90°C, and the reaction time is 6-24 h.

[0016] Furthermore, the amino acid monomer in S3 is any one of glycine, serine, threonine, alanine, aspartic acid, and glutamic acid; the molar ratio of -NCO in the prepolymer to -OH in the amino acid monomer is 1:0.1~0.9, and the time for adding the amino acid monomer to react is 0.5~2 h.

[0017] Furthermore, the metal ion in S4 is any one of zinc ion, copper ion, manganese ion, cadmium ion, and gallium ion, and the concentration of the metal ion solution is 0.05~0.5 mol / L; the immersion time is 12~24 h; the freeze molding temperature is -15~-30℃, and the freeze molding time is 6~24 h; the freeze drying time is 24~48 h.

[0018] A polyurethane sponge is prepared by the above preparation method.

[0019] An application of the polyurethane sponge is in the field of biomedicine.

[0020] Compared with the existing technology, the present invention solves the problems of poor biocompatibility, poor biodegradation effect, lack of antibacterial properties of traditional polyurethane materials, and reduced mechanical rigidity of existing amino acid-based polyurethane materials. The specific beneficial effects are:

[0021] 1. Enhanced degradability and biocompatibility: The present invention uses amino acid cyclic dipeptide as a chain extender to prepare polyurethane sponge. Amino acid cyclic dipeptide is a bio-based chain extender of natural origin. The peptide bonds in its molecular structure can be specifically recognized and gradually degraded by proteases in the human body, making the polyurethane sponge have controllable biodegradability. The degradation products are small molecules such as amino acids, which can participate in the human body's metabolic cycle, avoiding the toxic residues and slow degradation rate problems that may be caused by traditional chemical chain extenders. In addition, the cyclic dipeptide structure has a molecular configuration similar to the natural tissue environment, which enhances the affinity between the material and biological tissues, significantly improves the biocompatibility of the polyurethane sponge, and reduces cytotoxicity and immune rejection reactions. In actual application, the polyurethane sponge can gradually degrade into a colloid after absorbing blood and tissue fluid and flow out of the body, which helps the smooth process of cell adhesion, growth and repair.

[0022] 2. Enhanced antibacterial properties: This invention utilizes the coordination effect between carboxyl groups (-COOH) in polyurethane elastomers and metal ions to stably complex and load antibacterial metal ions (zinc, copper, manganese, cadmium, gallium, etc.) within the material. The synergistic antibacterial effect of metal ions and amino acids imparts long-lasting and highly effective antibacterial properties to the polyurethane sponge. This coordination and complexation method not only enhances the fixation of metal ions, reduces their loss in body fluids or the external environment, and improves safety, but also achieves a sustained release of metal ions, continuously releasing low concentrations of antibacterial factors, effectively inhibiting bacterial attachment and growth on the material surface, reducing the risk of infection and accelerating wound healing.

[0023] 3. Enhanced mechanical properties: The present invention forms a dense and stable cross-linked network structure through the synergistic effect of amino acid cyclic dipeptide chain extender and metal ions, which effectively improves the overall compression stiffness of the material, enabling the polyurethane sponge to maintain good deformation recovery and support capabilities under pressure, providing a strong guarantee for its stability and safety in clinical use.

[0024] 4. Performance Control: This invention achieves multi-dimensional adjustment of the degradability, water absorption, and mechanical properties of the polyurethane sponge by regulating the type of amino acid cyclic dipeptide and the concentration of metal ions. Cyclic dipeptides of different structures and properties can give the polyurethane material a controllable biodegradation rate, adapting to the material degradation cycle requirements of different medical applications. At the same time, by adjusting the degree of complexation between metal ions and carboxyl groups, the hydrophilicity and microporous structure of the material can be effectively adjusted, enhancing its water absorption rate and liquid retention capacity to meet the needs of high-exudate wound management. In addition, the rigid structure of the cyclic dipeptide and the synergistic effect of metal ion cross-linking significantly enhance the mechanical strength of the material, making the sponge flexible while also having good structural stability and durability. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 A synthetic route for amino acid cyclic dipeptides;

[0026] Figure 2 is the H NMR spectrum of tyrosine cyclic dipeptide;

[0027] Figure 3 Reaction roadmap for polyurethane medical sponge;

[0028] Figure 4 This is the concentration-antibacterial activity relationship diagram of polyurethane sponge against Escherichia coli;

[0029] Figure 5 This is the antibacterial effect of polyurethane sponge on Escherichia coli. DETAILED DESCRIPTION

[0030] In order to make the technical solution of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the specification of the present invention. It should be noted that the following embodiments are only used to better understand the technical solution of the present invention and should not be understood as limiting the present invention.

[0031] Example 1.

[0032] S1: Dissolve 40 g of tyrosine in 110 mL of ethylene glycol, heat the reaction system to 190°C under inert gas protection, and reflux for 24 h; pour the reaction solution into 800 mL of deionized water for precipitation, then filter the precipitate, wash the precipitate with deionized water 3 times, and then wash the precipitate with ethanol reflux 5 times, and vacuum dry at 80°C to prepare the product tyrosine cyclic dipeptide. Figure 1 is a synthetic route of amino acid cyclic dipeptide, in which R1 is a C1~12 hydrocarbon group, and R2 is a H atom or a tert-butyloxycarbonyl group; Figure 2 This is the H NMR spectrum of a tyrosine cyclic dipeptide. As can be seen, the multiplets at 6.8–7.5 ppm clearly correspond to the aromatic ring hydrogens, indicating that the tyrosine residue's benzene ring structure is intact. The α-hydrogen at 4.09 ppm and the benzyl CH2 hydrogen signals at 2.8–3.2 ppm are consistent with theoretical results, both showing multiplets and demonstrating clear coupling between hydrogen atoms. The spectrum is free of unusual peaks, with clear peak shapes and a well-defined distribution, demonstrating the molecule's strong conformational rigidity and confirming that the two tyrosine residues have successfully condensed to form a stable cyclic dipeptide structure.

[0033] S2: Heat 10.0 g of PEG (molecular weight 1000) to 120°C, dehydrate under vacuum for 1.5 h, add DMF and stir to dissolve, then cool to 80°C, and continue to add 4.2 g of HDI and react for 2 h to generate a prepolymer.

[0034] S3: 1.6 g of tyrosine cyclodipeptide was added to the prepolymer and reacted for 12 h. After the reaction, 0.37 g of glycine was added and reacted at 80°C for 2 h to prepare a polyurethane elastomer.

[0035] S4: The polyurethane elastomer was soaked in a 0.1 mol / L copper nitrate solution for 24 h and frozen at -20°C for 12 h to form the elastomer. The elastomer was then taken out and freeze-dried for 48 h to prepare a polyurethane medical sponge.

[0036] like Figure 3This is a reaction diagram for the production of polyurethane medical sponges. Here, R1 is a C1-C12 hydrocarbon group, R2 is a hydrogen atom or a tert-butyloxycarbonyl group, R3 is a C3-C12 hydrocarbon group, R4 is an amino acid side chain, and n is a natural number between 3 and 12. As shown in the figure, amino acids with hydroxyl (-OH) side chains undergo condensation to form amino acid cyclic dipeptides, which serve as chain extenders through nucleophilic addition reactions between the hydroxyl groups and some isocyanate (-NCO) groups in the prepolymer. The remaining isocyanate groups in the prepolymer then undergo nucleophilic addition reactions with the amino (-NH2) groups of the natural amino acid monomers to produce a polyurethane elastomer. Furthermore, the carboxyl (-COOH) groups in the polyurethane elastomer complex with metal ions through coordination, loading the elastomer with metal ions that have both antimicrobial and cross-linking properties.

[0037] Example 2.

[0038] The difference between this embodiment and embodiment 1 is that tyrosine in embodiment 1 S1 is replaced by threonine to prepare threonine cyclic dipeptide, and polyurethane elastic material and polyurethane medical sponge are prepared according to the same preparation method, preparation conditions and feeding molar ratio as in embodiment 1.

[0039] Example 3.

[0040] The difference between this embodiment and embodiment 1 is that the tyrosine in embodiment 1 S1 is replaced with serine to prepare serine cyclic dipeptide, and the polyurethane elastic material and polyurethane medical sponge are prepared according to the same preparation method, preparation conditions and feeding molar ratio as in embodiment 1.

[0041] Example 4.

[0042] This Example differs from Example 3 in that the serine cyclic dipeptide is prepared according to the preparation method of Example 3, the molar ratio of -OH in the serine cyclic dipeptide to -NCO in the prepolymer is reduced, and the molar ratio of -NH2 in the glycine monomer to -NCO in the prepolymer is increased. The specific preparation method is as follows: 10.0 g of PEG with a molecular weight of 1000 is heated to 120°C, dehydrated under vacuum for 1.5 hours, added with DMF, stirred and dissolved, and then cooled to 80°C. 4.2 g of HDI is then added and reacted for 2 hours to produce a prepolymer. 0.4 g of serine cyclic dipeptide is added to the prepolymer and reacted for 12 hours. After the reaction is completed, 0.62 g of glycine is added and the reaction is continued at 80°C for 2 hours to produce a polyurethane elastomer. The polyurethane elastomer is soaked in a 0.1 mol / L copper nitrate solution for 24 hours, frozen at -20°C for 12 hours to form, removed, and freeze-dried for 48 hours to produce a polyurethane medical sponge.

[0043] Example 5.

[0044] The difference between this embodiment and embodiment 4 is that the concentration of the copper nitrate solution is 0.3 mol / L, and the rest of the preparation method, preparation conditions and feeding molar ratio are the same as those in embodiment 4, and a polyurethane medical sponge is prepared.

[0045] Example 6.

[0046] The difference between this embodiment and embodiment 4 is that the concentration of the copper nitrate solution is 0.6 mol / L, and the rest of the preparation method, preparation conditions and feeding molar ratio are the same as those in embodiment 4, and a polyurethane medical sponge is prepared.

[0047] Example 7.

[0048] The difference between this embodiment and embodiment 1 is that glycine in S3 of embodiment 1 is replaced by aspartic acid, and polyurethane elastic material and polyurethane medical sponge are prepared according to the same preparation method, preparation conditions and feeding molar ratio as in embodiment 1.

[0049] Comparative Example 1.

[0050] The difference between this comparative example and Example 1 is that glycine in S3 of Example 1 is replaced by 2,2-dihydroxymethylpropionic acid (DMPA), and the rest of the preparation method, preparation conditions and feeding molar ratio are the same as those in Example 1 to prepare a polyurethane sponge.

[0051] Comparative Example 2.

[0052] The difference between this comparative example and Example 1 is that the polyurethane elastomer in S4 of Example 1 is not immersed in the copper nitrate solution, and the rest of the preparation method, preparation conditions and feeding molar ratio are the same as those in Example 1 to prepare a polyurethane sponge.

[0053] Performance testing:

[0054] (1) Compression performance test: Determine the compressive strength of polyurethane sponge in accordance with GB / T8813-2008.

[0055] (2) The calculation formula of porosity is as follows:

[0056] Porosity = [1-sponge mass / (sponge volume × polyurethane density)] × 100%.

[0057] (3) Water absorption test: After drying, weigh the polyurethane sponge and record its weight (m1). Then, immerse it completely in deionized water for 1 hour and take it out and weigh it (m2). The water absorption rate = (m2-m1) / m1*100%.

[0058] The following table shows the performance test results of the polyurethane medical sponges prepared in Examples 1-6 and the polyurethane sponges prepared in Comparative Examples 1 and 2. It can be seen from the table that Examples 1-7 of the present invention effectively regulate the structure and performance of the polyurethane sponge by adjusting the types and ratios of amino acids and cyclic dipeptides. Among them, Example 7 uses aspartic acid containing two carboxyl structures to replace glycine containing only one carboxyl group, which significantly enhances the degree of ionic crosslinking between polymer chains at the molecular level. The enhancement is mainly attributed to the coordination reaction of the carboxyl group with the metal ion under aqueous conditions to form a stable crosslinked network, thereby improving the mechanical properties of the material. In contrast, although the DMPA used in Comparative Example 1 has good hydrophilicity and the sponge formed has a larger pore size and higher water absorption, it does not have multi-site ionic crosslinking ability, resulting in the compressive strength of the prepared material being only 9 kPa, which is significantly lower than the various embodiments of the present invention. The amino acid structure selected by the present invention effectively improves the comprehensive performance of the polyurethane sponge while providing synergistic antibacterial properties, and is more suitable for the needs of biomedical materials.

[0059]

[0060] Antibacterial experiment:

[0061] Minimum inhibitory concentration (MIC) determination: Use a pipette to add 200 μL of LB broth medium to the outer wells of a 96-well plate. Add 100 μL of the polyurethane sponge sample extract prepared in Examples 1-6 and Comparative Examples 1-2 (test sample group) or sterile water (blank control group) and 100 μL of bacterial suspension to the remaining wells. Place the plate in a 37°C incubator for incubation. After the bacteria have grown for 3 hours, remove the plate. Pipet the bacterial suspension in the test sample group and blank control group wells to mix thoroughly. Remove half of the bacterial suspension from the plate and add an equal volume of LB broth. Place the plate in a 37°C incubator for incubation. After 24 hours of bacterial growth, remove the plate, shake the plate for 60 seconds, and measure the absorbance (measured value / control value) in a 600 nm microplate reader. The test is meaningful only when there is obvious bacterial growth in the blank control well. The MIC for that group is the clear state with no colonies. Measure the optical density at 600 nm, and calculate the bacterial survival rate according to formula (1).

[0062]

[0063] Minimum Bactericidal Concentration (MBC) Determination: Use a pipette to add 200 μL of LB broth to the outer wells of a 96-well plate. Add 100 μL of the polyurethane sponge sample extracts prepared in Examples 1-6 and Comparative Examples 1-2 (test sample groups) or sterile water (blank control group) and 100 μL of bacterial suspension to the remaining wells. Incubate in a 37°C incubator. After 3 hours of bacterial growth, remove the wells. Mix the bacterial suspension in the wells of the test sample and blank control groups by pipetting. Remove half of the bacterial suspension from the wells and add an equal volume of LB broth. Incubate in a 37°C incubator. After 24 hours of bacterial growth, remove the wells. Mix the bacterial suspension in the wells of the test sample and blank control groups by pipetting. Aspirate 100 μL of each well onto a pre-marked agar plate. Cover the plate and spread the bacterial suspension using 4 mm glass beads until the entire plate is covered. Incubate the plate in a 37°C incubator overnight. The next day, the colony growth on each plate was observed. The minimum drug concentration in the culture medium tube when the number of growing colonies was less than 0.1% of the inoculum volume was the minimum bactericidal concentration (MBC) of the drug.

[0064] like Figure 4 and Figure 5 The figures show the concentration-antibacterial activity relationship and antibacterial effect of polyurethane sponges against E. coli, respectively. As can be seen from the figures, the polyurethane medical sponge prepared in Example 1 has a MIC and MBC of 0.78 μg / mL against E. coli, demonstrating significant antibacterial activity and strong inhibitory capacity against E. coli. In contrast, the sponge prepared in Comparative Example 1, which was prepared by loading only metal ions without further amino acid chain extension, had a MIC and MBC of 6.25 μg / mL against E. coli. The sponge prepared in Comparative Example 2, which was prepared without cation loading, showed no significant antibacterial activity, indicating that the amino acid structure itself does not possess an effective antibacterial effect. It also demonstrates that the addition of metal ions can synergistically inhibit bacterial growth around wounds and reduce the risk of infection.

[0065] This invention uses a naturally derived bio-based amino acid cyclic dipeptide as a chain extender to prepare a polyurethane sponge. This enhances the polyurethane sponge's biodegradability, avoiding the potential toxic residues and slow degradation associated with traditional chemical chain extenders. Furthermore, the cyclic dipeptide structure possesses a molecular configuration similar to that of natural tissue environments, enhancing the material's affinity for biological tissues and significantly improving the polyurethane sponge's biocompatibility. Furthermore, the invention utilizes the coordination interaction between the carboxyl (-COOH) groups in the polyurethane elastomer and metal ions to stably complex and load metal ions with antimicrobial activity within the material. The synergistic antimicrobial effect of the metal ions and amino acids imparts long-lasting and highly effective antibacterial properties to the polyurethane sponge. The synergistic effect of the amino acid cyclic dipeptide chain extender and the metal ions forms a dense and stable cross-linked network, effectively enhancing the material's overall mechanical strength and ensuring the sponge possesses both flexibility and structural stability and durability.

[0066] In summary, the present invention uses amino acid cyclic dipeptides as chain extenders to prepare polyurethane sponges. Using amino acid cyclic dipeptides as naturally derived bio-based chain extenders, the polyurethane sponges possess controllable biodegradability and significantly improve their biocompatibility. Furthermore, the present invention imparts long-lasting and highly effective antibacterial properties to the polyurethane sponges through the synergistic antibacterial effects of metal ions and amino acids. The synergistic effects of the amino acid cyclic dipeptide chain extender and metal ions form a dense and stable cross-linked network structure, effectively improving mechanical properties and providing strong guarantees for their stability and safety in biomedical applications.

[0067] The description of the above embodiments is only used to help understand the method of the present invention and its core idea. It should be pointed out that for those skilled in the art, without departing from the principles of the present invention, several improvements and modifications may be made to the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention. The above description of the disclosed embodiments enables professionals in this field to implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but will conform to the widest range consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a polyurethane sponge, characterized in that: The method comprises the following preparation steps: S1: dissolving an amino acid compound containing a hydroxyl group on a side chain in ethylene glycol, heating and refluxing the mixture under inert gas protection, pouring the reaction solution into deionized water, filtering the precipitate, and then washing and vacuum drying to obtain an amino acid cyclic dipeptide; S2: heating polyethylene glycol, dehydrating it under vacuum conditions, adding N,N-dimethylformamide, stirring and dissolving it, cooling it, and continuously adding diisocyanate to react and form a prepolymer; S3: adding amino acid cyclic dipeptide to the prepolymer for reaction, and then adding amino acid monomer to react after the reaction to obtain a polyurethane elastomer; S4: soaking the polyurethane elastomer in a metal ion solution, freeze-molding the polyurethane elastomer, taking it out and freeze-drying it to obtain a polyurethane sponge; The molar ratio of diisocyanate to polyethylene glycol in step S2 is 2.0-3.0:1; The metal ion in step S4 is any one of zinc ion, copper ion, manganese ion, cadmium ion and gallium ion.

2. The method for preparing a polyurethane sponge according to claim 1, wherein The amino acid compound in S1 is one or a combination of two of serine, tyrosine, threonine, and hydroxyproline.

3. The method for preparing a polyurethane sponge according to claim 1, wherein The heating temperature in S1 is 170-200°C; the reflux time is 12-24 h; the steps of washing the precipitate are: washing with deionized water 3 times and ethanol reflux washing 5 times; the drying temperature is 80°C.

4. The method for preparing a polyurethane sponge according to claim 1, wherein The diisocyanate is any one of hexamethylene diisocyanate, toluene diisocyanate, 4,4'-diphenylmethane diisocyanate, 1,4-diisocyanate butane, and 4,4'-dicyclohexylmethane diisocyanate.

5. The method for preparing a polyurethane sponge according to claim 1, wherein The molecular weight of the polyethylene glycol in S2 is 400-6000; the heating temperature is 100-120° C.; the dehydration time is 1-4 h; the cooling temperature is reduced to 60-80° C.; and the reaction time is 2 h.

6. The method for preparing a polyurethane sponge according to claim 1, wherein The molar ratio of -NCO in the prepolymer to -OH in the amino acid cyclic dipeptide in S3 is 1:0.1-0.9, the reaction temperature of the prepolymer and the amino acid cyclic dipeptide is 80-90° C., and the reaction time is 6-24 h.

7. The method for preparing a polyurethane sponge according to claim 1, wherein The amino acid monomer in S3 is any one of glycine, serine, threonine, alanine, aspartic acid, and glutamic acid; the molar ratio of -NCO in the prepolymer to -OH in the amino acid monomer is 1:0.1~0.9, and the time for adding the amino acid monomer to react is 0.5~2 h.

8. The method for preparing a polyurethane sponge according to claim 1, wherein The concentration of the metal ion solution in S4 is 0.05~0.5 mol / L; the soaking time is 12~24 h; the freeze molding temperature is -15~-30°C, the freeze molding time is 6~24 h; and the freeze drying time is 24~48 h.

9. A polyurethane sponge, characterized in that: The method is prepared according to any one of claims 1 to 8.

10. A use of the polyurethane sponge according to claim 9, characterized in that: Used in the preparation of biomedical materials.

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