Biological material with self-repairing function, artificial heart valve and preparation method of artificial heart valve

Abstract

The invention discloses a biological material with a self-repairing function, an artificial heart valve and a preparation method of the artificial heart valve. The biological material with the self-repairing function is a thin film material of a TPU-Upy polymer with a quadruple hydrogen bond unit Upy in a main chain, has a dynamic network cross-linked structure, and has excellent mechanical properties and biocompatibility while having a good self-repairing function at body temperature. The valve leaflet material of the artificial heart valve contains a biological material with a self-repairing function, and compared with traditional mechanical valves, biological valves and polymer valves, the artificial heart valve has good biocompatibility and higher mechanical property and self-repairing performance, and the service life of the artificial heart valve is prolonged.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to a biomaterial with self-healing function, an artificial heart valve, and a method for preparing the same. Background Technology

[0002] Currently, there are no effective drugs for valvular heart disease, and treatment still relies on the transplantation of artificial heart valves. The main types of artificial heart valves used clinically are mechanical valves and bioprosthetic valves. Mechanical valves are prone to thrombosis, so patients need to take anticoagulants for life after surgery. Bioprosthetic valves (mainly made from bovine pericardium, porcine pericardium, and porcine aorta) are cross-linked with glutaraldehyde, making them prone to denaturation and calcification, resulting in a shorter lifespan. With the development of polymer materials, more and more polymer materials are being applied in the field of biomedical materials. Polymer materials generally have good biocompatibility, blood flow, anti-calcification properties, and durability. However, compared to traditional mechanical and bioprosthetic grafts, polymer materials still face the problem of long-term fatigue tearing without the ability to self-repair after implantation. Summary of the Invention

[0003] The purpose of this invention is to provide a biomaterial with self-healing function, an artificial heart valve and its preparation method, and to solve the functional defects of existing polymer materials and artificial heart valves.

[0004] According to a first aspect of the present invention, a biomaterial with self-healing function is provided, wherein the biomaterial is a polymer TPU-Upy containing four hydrogen bond units Upy in its main chain; the molecular structure of the polymer TPU-Upy is as follows: Figure 1 As shown.

[0005] According to a second aspect of the present invention, a method for preparing a biomaterial with self-healing function as described in the first aspect is provided, comprising the following steps:

[0006] Preparation of Upy intermediate: Hexamethylene diisocyanate (HDI) and 2-amino-4-hydroxy-6-methylpyrimidine (MIC) were mixed and reacted at a ratio of 5:1 to 10:1. After removing impurities with a drying agent, the first product was obtained.

[0007] Preparation of Upy chain extender: The first product, 2-amino-2-methyl-1,3-propanediol AMPD in a molar ratio of 1:1.5 to 1:2 and the first solvent are mixed and reacted to obtain Upy chain extender;

[0008] Preparation of TPU prepolymer: Hexamethylene diisocyanate (HDI) and polybutanediol (PTMG) were mixed with a second solvent at a molar ratio of 2:1 to 3:1 and subjected to a catalytic reaction to obtain TPU prepolymer;

[0009] Preparation of TPU-Upy polymer film: After preheating the TPU prepolymer, 1,4-butanediol BDO, the Upy chain extender, the TPU prepolymer, and a third solvent are mixed to carry out a chain extension reaction to obtain TPU-Upy polymer. The TPU-Upy polymer is then cast into a mold, vacuum degassed, and dried to obtain a TPU-Upy polymer film. The mass ratio of 1,4-butanediol BDO to the Upy chain extender is 1:0.1 to 1:0.8, and the mass ratio of the TPU prepolymer to the Upy chain extender is 1:1 to 1:3.

[0010] Furthermore, the average molecular weight of the polybutanediol is 550 Da to 750 Da.

[0011] Furthermore, all preparation processes are carried out in a vacuum or inert gas environment.

[0012] Furthermore, in the preparation step of the Upy intermediate, HDI and MIC are mixed and vacuum dried for 30 min to 60 min, and then replaced with inert gas 3 to 6 times; the reaction system is reacted at 80℃ to 120℃ for 20 h to 30 h; after the reaction is completed, the reaction system is cooled to room temperature and washed with a desiccant to remove impurities.

[0013] Furthermore, in the preparation process of the Upy chain extender, the first solvent is dimethyl sulfoxide (DMSO); the reaction system is reacted at 50℃~70℃ for 50min~70min, after the reaction is completed, the reaction system is cooled to room temperature, deionized water is added to the reaction system for washing, and the precipitate is dried after centrifugation to obtain the Upy chain extender.

[0014] Furthermore, in the step of preparing the TPU prepolymer, the second solvent includes one or a combination of two or more of N,N-dimethylformamide (DMF), tetrahydrofuran, and hexafluoroisopropanol; the catalytic reaction is carried out at 70℃~90℃ for 200min~300min, and after the NCO groups in the reaction system reach the specified value, the temperature is lowered to room temperature to obtain the TPU prepolymer; the catalytic reaction system also includes a 0.05%~0.2% (by mass) dibutyltin dilaurate (DBTL) catalyst.

[0015] Furthermore, in the step of preparing the TPU-Upy polymer film, the third solvent includes one or a combination of two or more of N,N-dimethylformamide (DMF), tetrahydrofuran, and hexafluoroisopropanol; the preheating temperature of the TPU prepolymer is 45℃~55℃, the chain extension reaction is carried out at 50℃~70℃ for 1.5~3h, and the TPU-Upy polymer is obtained by vacuum degassing after the reaction is completed; the catalytic reaction system also includes a 0.05%~0.2% (by mass) dibutyltin dilaurate (DBTL) catalyst.

[0016] According to a third aspect of the present invention, an artificial heart valve is provided, wherein the leaflet material of the artificial heart valve comprises a self-healing biomaterial prepared as described in the first aspect of the present invention.

[0017] According to a fourth aspect of the present invention, a method for preparing an artificial heart valve as described in the third aspect of the present invention is provided, comprising the steps of:

[0018] TPU-Upy polymer is poured into a mold and vacuum degassed at 30-50°C for 40-50 minutes, followed by drying for 45-55 hours to obtain TPU-Upy film.

[0019] The TPU-Upy film is cut into the shape of leaflets to obtain valve leaflets, which are then fixed onto a stent to obtain an artificial heart valve.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] 1. The self-healing biomaterial provided by this invention is a polymer TPU-Upy with a main chain structure containing four hydrogen bond units Upy. It possesses a dynamic cross-linked network structure and exhibits excellent self-repair capabilities against microcracks and localized damage at body temperature, effectively extending the material's service life and enabling its reuse. Furthermore, as a biomaterial, polymer TPU-Upy is prepared from non-toxic and harmless raw materials, exhibiting excellent biocompatibility.

[0022] 2. The biomaterial with self-healing function provided by this invention has better mechanical properties than existing self-healing polymer materials and has a wider range of applications.

[0023] 3. The preparation method of the biomaterial with self-healing function provided by the present invention has mild conditions, high yield, and is suitable for large-scale production.

[0024] 4. The leaflet material of the artificial heart valve provided by the present invention includes biomaterials with self-repair function, and has the excellent mechanical properties of mechanical valves and the biocompatibility of biological valves. In addition, it has better mechanical properties and self-repair ability than existing polymer material valves, and its service life is extended.

[0025] 5. The artificial heart valve preparation method provided by this invention is simple, efficient, stable, and low in cost, which is conducive to large-scale production in the later stage and the product has good economic benefits. Attached Figure Description

[0026] Other features, objects, and advantages of the present invention will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings:

[0027] Figure 1This is a schematic diagram of the molecular structure of polymer TPU-Upy in one embodiment of the present invention;

[0028] Figure 2 This is a schematic diagram of the mechanical performance test results of an artificial heart valve in one embodiment of the present invention;

[0029] Figure 3 This is a schematic diagram of the test results of the self-repair performance of the artificial heart valve in one embodiment of the present invention;

[0030] Figure 4 This is a schematic diagram of the recalcification performance test results of an artificial heart valve in one embodiment of the present invention;

[0031] Figure 5 This is a schematic diagram of the experimental results of artificial heart valve muscle implantation in one embodiment of the present invention. Detailed Implementation

[0032] The following will describe in more detail, with reference to schematic diagrams, a self-healing biomaterial, an artificial heart valve, and a method for preparing the present invention. Preferred embodiments of the invention are shown. It should be understood that those skilled in the art can modify the invention described herein while still achieving its advantageous effects. Therefore, the following description should be understood as being of general knowledge to those skilled in the art and is not intended to limit the invention.

[0033] For clarity, not all features of the actual embodiments are described. In the following description, well-known functions and structures are not detailed in detail, as they would obscure the invention with unnecessary detail. It should be understood that in the development of any actual embodiment, numerous implementation details must be made to achieve the developer's specific objectives, such as changes from one embodiment to another according to limitations related to the system or business. Furthermore, it should be understood that such development work may be complex and time-consuming, but is merely routine work for those skilled in the art.

[0034] The invention is described more specifically by way of example in the following paragraphs with reference to the accompanying drawings. The advantages and features of the invention will become clearer from the following description and claims.

[0035] In an embodiment of the present invention, a biomaterial with self-healing function is provided. The biomaterial is a polymer TPU-Upy containing four hydrogen bond units Upy in its main chain; the molecular structure of polymer TPU-Upy is as follows: Figure 1 As shown.

[0036] TPU, used in artificial heart valves, exhibits excellent fatigue resistance and is not easily damaged during long-term use. Furthermore, TPU material has good blood compatibility, low calcification risk, and is less prone to thrombosis during use, helping to maintain long-term valve function and hemodynamic stability in patients. Compared to mechanical and bioprosthetic valves, TPU material is easier to process and cut, resulting in lower production costs. This invention introduces Upy units into the TPU material. Upy units can form multiple hydrogen bonds. As a non-covalent interaction, hydrogen bonds can respond rapidly to material damage, achieving self-repair through bond breakage and reformation, thereby restoring the material's complete performance. Combining these two materials can solve the problems of short lifespan and high thrombosis risk in traditional mechanical and bioprosthetic valves, as well as the fatigue tearing problem of polymeric material valves.

[0037] The embodiments of the present invention also provide a method for preparing biomaterials with self-healing function, comprising the following steps:

[0038] The glassware used in the following steps is vacuum dried for 24 hours in advance.

[0039] Preparation of the Upy intermediate: Hexamethylene diisocyanate (HDI) and 2-amino-4-hydroxy-6-methylpyrimidine (MIC) in a molar ratio of 6:1 were placed in a three-necked flask and dried under vacuum for 30 min, followed by purging with nitrogen or argon three times. A spherical condenser, vent, and stirrer were installed to construct the reaction apparatus. The reaction system was placed in a nitrogen or argon atmosphere to prevent the isocyanate groups (-NCO) in the synthesized product Upy from reacting with moisture in the air. The three-necked flask was placed in an oil bath and heated to 100°C for 24 h. After the reaction was completed, the mixture was cooled to room temperature. Hexane (dried for 48 h using molecular sieves) was added to the reaction system, and the mixture was repeatedly washed to remove unreacted HDI. The white powder solid collected was the isocyanate-terminated intermediate Upy-NCO.

[0040] Preparation of Upy chain extender:

[0041] The reactants 2-amino-2-methyl-1,3-propanediol (AMPD) and Upy-NCO were placed in a three-necked flask with a molar ratio of Upy-NCO to AMPD of 1:1.5. Dimethyl sulfoxide (DMSO) was added to completely dissolve the reactants. The reaction system was placed in a nitrogen or argon atmosphere and heated to 60°C for 1 hour. After the reaction was complete, the system was cooled to room temperature, and deionized water was added three times to remove residual DMSO. The reaction product was centrifuged at 1000 rpm for 10 minutes. The white solid was dried in a vacuum oven to obtain the Upy chain extender.

[0042] Preparation of TPU prepolymer:

[0043] Using N,N-dimethylformamide (DMF) as a solvent, hexamethylene diisocyanate (HDI) and polybutanediol (PTMG) were mixed in a molar ratio of 2:1, and 0.1% (w / w) of dibutyltin dilaurate (DBTL) catalyst was added. The mixture was placed in a nitrogen or argon atmosphere and reacted at 80°C for 4 hours. The NCO group content in the reaction system was measured according to standard GB / T 12009.4. After reaching the specified value, the mixture was cooled to room temperature to obtain the TPU prepolymer.

[0044] Preparation of TPU-Upy polymer films:

[0045] The TPU prepolymer was preheated at 50°C, and Upy chain extender and TPU prepolymer were added separately. 1,4-Butanediol (BDO) was also added to the reaction system. The addition of BDO is beneficial for moisturizing and softening the polymer film, making the film softer and improving the durability of the leaflets. The mass ratio of BDO to Upy chain extender was 2:1. DMF solvent was added to completely dissolve the reactants. 0.1% (w / w) of dibutyltin dilaurate (DBTL) catalyst was added, and the reaction was carried out at 60°C for 2 hours in a nitrogen or argon atmosphere. The reaction product was transferred to a vacuum drying oven for vacuum degassing for 15-20 minutes, then poured into a 2mm high PTFE tray. The tray was leveled with a scraper and placed in a vacuum drying oven for vacuum degassing at 40°C for 40 minutes. After removing the bubbles, vacuum drying was continued for 48 hours to obtain the TPU-Upy polymer film, which is a biomaterial with self-healing function.

[0046] The method for preparing self-healing biomaterials provided by this invention achieves a polymer yield of up to 95%, with mild reaction conditions, low raw material costs, and is suitable for large-scale production.

[0047] The present invention also provides an artificial heart valve, wherein the leaflet material of the artificial heart valve includes a biomaterial with self-healing function.

[0048] The present invention also provides a method for preparing an artificial heart valve, comprising the following steps:

[0049] The shape of the leaflet is designed according to the valve specifications, and the TPU-Upy polymer film provided by this invention is cut into the leaflet shape using a laser cutting machine.

[0050] The leaflets are fixed to the support using an ultrasonic or high-frequency welding machine to form a valve.

[0051] This invention provides a self-healing biomaterial and an artificial heart valve. As a biomaterial, in addition to self-healing, it should also possess good biocompatibility and mechanical properties. The mechanical properties, self-healing performance, and biological properties of the self-healing biomaterial provided by this invention were tested, with mechanical valves, biological valves, and polymer valves selected as control groups. The test results are as follows:

[0052] Performance testing of artificial heart valve materials:

[0053] 1. Mechanical Property Testing: Tensile strength is an important indicator of a material's mechanical properties. Tensile strength tests were conducted on three parallel sets of samples of existing artificial heart valve materials such as bovine pericardium, polytetrafluoroethylene, polyurethane, and the TPU-Upy film artificial heart valve material provided in this invention. The test results are as follows: Figure 1 As shown.

[0054] Depend on Figure 1 The test results show that the sample containing Upy forms a three-dimensional physical cross-linking network based on quadruple hydrogen bonds in the macromolecular network, which enhances the interaction force between the molecular chains of the material and the tensile strength. Therefore, the artificial heart valve provided by this invention is not easily fatigued or damaged in vivo and has better durability.

[0055] 2. Self-healing performance test: The TPU-Upy film material provided by this invention was cut to form a 5*5mm sample. The material was scratched with a clean scalpel and heated to 37±2℃. The scratches were observed and photographed under a polarizing microscope. The test results are as follows: Figure 2 As shown in Table 1, the TPU-Upy film repair efficiency is calculated using the following formula: TPU-Upy repair efficiency = (initial scratch width - scratch width after 2 hours of repair) / initial scratch width * 100%.

[0056] Depend on Figure 2 As shown in Table 1, after damage to the TPU-Upy film material, at 37°C, the scratches narrowed significantly within 30 minutes, and the scratches were essentially healed. Furthermore, after 2 hours, the scratches largely disappeared, and the material's appearance was essentially restored. Therefore, the artificial heart valve provided by this invention possesses significant self-healing capabilities, effectively addressing the performance defects of existing heart valve leaflet materials that are prone to fatigue tearing during use.

[0057] Table 1. TPU-Upy Repair Efficiency Table

[0058]

[0059] 3. Biological performance testing

[0060] Biocompatibility is crucial for the application of artificial valves. Biocompatibility is divided into two aspects: blood compatibility and tissue compatibility. Blood compatibility is the primary factor; when medical biomaterials come into direct or indirect contact with blood, they activate the coagulation mechanism in the body, releasing coagulation factors and triggering a cascade reaction that leads to platelet adhesion and activation. Complement and immune proteins in the thrombus also participate in this process, ultimately resulting in thrombus formation. Tissue compatibility observes and studies the various physical and chemical changes and bodily reactions caused by short-term and long-term contact between the implanted material and body tissues. Within tissue compatibility, cytotoxicity testing evaluates the biological response of biomaterials or their extracts after contact with body tissues and is an important indicator of biological evaluation.

[0061] (1) Hemolysis test:

[0062] The hemolysis experiment involved collecting 10 mL of blood from the heart of a healthy New Zealand rabbit and adding 0.5 mL of a 20 g / L potassium oxalate solution to prepare fresh anticoagulated rabbit blood. 8 mL of this fresh anticoagulated rabbit blood was then diluted with 10 mL of physiological saline. For each tube containing the experimental TPU-Upy film, a surface area of ​​60 cm² was added... 2 The sample was 6cm. 2 Add 10 mL of sodium chloride injection solution per tube at a ratio of / mL; add 10 mL of sodium chloride injection solution per tube for the negative control group; add 10 mL of distilled water per tube for the positive control group. Perform three parallel operations per group. After incubating all tubes in a 37℃ water bath for 30 min, add 0.2 mL of diluted rabbit blood to each tube, mix gently, and continue incubating at 37℃ for 60 min. Pour out the liquid from the tube and centrifuge at 800g for 5 min. Collect the supernatant and measure the absorbance at 545 nm using an ELISA reader. Calculate the hemolysis rate: Hemolysis rate (%) = 100 x (AB) / (CB), where: A: absorbance of the experimental sample; B: absorbance of the negative control; C: absorbance of the positive control. The test results are shown in Table 2.

[0063] Table 2. Hemolysis Rate Test of TPU-Upy Film

[0064] sample absorbance Hemolysis rate % negative control 0.031 0 Positive control 4.241 100 PU-Upy film 0.049 0.43

[0065] As can be seen from the hemolysis rate calculation results in Table 2, the hemolysis rate of TPU-Upy film is 0.43%, which meets the requirement of <5% for samples conforming to standard GB / T 16886.4-2003.

[0066] (2) Recalcification experiment:

[0067] The recalcification test, also known as plasma calcification time, refers to the time required for the intrinsic coagulation process to recover, and is a screening test for the intrinsic coagulation system. This test involves reintroducing calcium ions into decalcified plasma, causing soluble fibrinogen to convert into soluble fibrin, which then cross-links to form a thrombus. The longer the plasma clotting time, the better the blood compatibility; that is, blood compatibility is directly proportional to recalcification time. The sample suspension and the added calcium... 2+ Platelet-depleted plasma was reacted for 2 hours, and its time-kinetic curve was measured using an ELISA reader. A clear inflection point was observed when white filamentous material (fibrin filaments) appeared; this time was recorded as the recalcification time of the sample. To improve the reproducibility of the experimental results, T1 / 2max was used as the recalcification time in this experiment.

[0068] Five suspensions of TPU-Upy membrane at different concentrations were prepared sequentially using physiological saline: 0.2 mg / mL, 0.4 mg / mL, 0.6 mg / mL, 0.8 mg / mL, and 1.0 mg / mL. After incubating the prepared TPU-Upy membrane suspensions at 37°C for 30 min, 0.1 mL of 0.025 mol / L CaCl2 solution and 0.1 mL of platelet-rich plasma (PPP) were added to each suspension. Then, 0.1 mL of each concentration was added to a 96-well plate, and the recalcification time kinetics were measured at 405 nm using a microplate reader. Each experiment was repeated three times, and the average value was taken. Control group: 0.1 mL CaCl2 + 0.1 mL plasma. The test results are as follows: Figure 3 As shown.

[0069] Depend on Figure 3 The test results show that the recalcification time of the control group was approximately 13.8 min. Compared with the control group, the recalcification time of TPU-Upy film sample solutions of different concentrations was prolonged, and the recalcification time increased significantly with increasing concentration. The longest recalcification time was observed at a concentration of 1.0 mg / mL, reaching 24.9 min. These experimental results demonstrate that the TPU-Upy film has good blood compatibility.

[0070] (3) Muscle implantation experiment:

[0071] The tests were conducted according to the methods recommended in the national standard GB / T 16886.6-2015 "Biological evaluation of medical devices - Part 6: Local reaction test after implantation".

[0072] Healthy adult rabbits were used as experimental animals in this experiment. After routine disinfection, the skin of the experimental animals was implanted into the muscle approximately 2 cm from the spine on both sides of the midline. Both experimental and control samples were implanted. Animals were euthanized painlessly with excessive CO2 at 1, 4, 13, and 26 weeks post-implantation. The implants and surrounding tissues were excised for gross observation, fixed in 10% neutral buffered formalin, and then dissected. Neither the experimental nor control samples were removed. The dissected tissue blocks were dehydrated with graded alcohol, embedded in paraffin, sectioned, stained with hematoxylin and eosin (HE), and then subjected to histopathological observation and evaluation. The experimental results are as follows: Figure 4 As shown.

[0073] like Figure 4 As shown, the local reaction of the implanted material was evaluated by gross and microscopic observation of the muscle tissue at 1, 4, 13, and 26 weeks post-implantation. The results showed that the rabbits generally fared well after implantation, with no deaths, infections, or other adverse complications. At 1 week post-operation, the main reaction in the tissue surrounding the material was inflammatory cell infiltration and edema, likely caused by local material irritation and postoperative stress. At 4, 13, and 26 weeks post-operation, the inflammatory cells around the implanted material gradually disappeared, and a stable fibrous envelope gradually formed. No obvious abnormalities were observed in the surrounding muscle tissue grossly and microscopically. This indicates that the material stabilized with the surrounding muscle tissue over time. The absence of necrosis or inflammation suggests that the material is non-toxic to the surrounding muscle tissue, indicating a good local reaction after implantation.

[0074] In summary, the self-healing biomaterial, artificial heart valve, and preparation method provided in this embodiment result in an artificial heart valve with the following beneficial effects:

[0075] 1. The self-healing biomaterial provided by this invention is a polymer TPU-Upy with a main chain structure containing four hydrogen bond units Upy. It possesses a dynamic cross-linked network structure and exhibits excellent self-repair capabilities against microcracks and localized damage at body temperature, effectively extending the material's service life and enabling its reuse. Furthermore, as a biomaterial, polymer TPU-Upy is prepared from non-toxic and harmless raw materials, exhibiting excellent biocompatibility.

[0076] 2. The biomaterial with self-healing function provided by this invention has better mechanical properties than existing self-healing polymer materials and has a wider range of applications.

[0077] 3. The preparation method of the biomaterial with self-healing function provided by the present invention has mild conditions and a yield of up to 95%, making it suitable for large-scale production.

[0078] 4. The leaflet material of the artificial heart valve provided by the present invention includes biomaterials with self-repair function, and has the excellent mechanical properties of mechanical valves and the biocompatibility of biological valves. In addition, it has better mechanical properties and self-repair ability than existing polymer material valves, and its service life is extended.

[0079] 5. The artificial heart valve preparation method provided by this invention is simple, efficient, stable, and low in cost, which is conducive to large-scale production in the later stage and the product has good economic benefits.

[0080] The above are merely preferred embodiments of the present invention and do not constitute any limitation on the present invention. Any equivalent substitutions or modifications made by those skilled in the art to the technical solutions and content disclosed in the present invention without departing from the scope of the present invention shall be deemed to have remained within the protection scope of the present invention.

Claims

1. A biomaterial with self-healing function, characterized in that, The biomaterial is a thin film material of TPU-Upy polymer containing four hydrogen bond units Upy in the main chain; the TPU-Upy polymer has the following molecular structure:

2. A method for preparing a biomaterial with self-healing function as described in claim 1, characterized in that, Includes the following steps: Preparation of Upy intermediate: Hexamethylene diisocyanate (HDI) and 2-amino-4-hydroxy-6-methylpyrimidine (MIC) in a molar ratio of 5:1 to 10:1 were mixed and reacted. After removing impurities with a drying agent, the first product was obtained. Preparation of Upy chain extender: The first product, 2-amino-2-methyl-1,3-propanediol AMPD in a molar ratio of 1:1.5 to 1:2 and the first solvent are mixed and reacted to obtain Upy chain extender; Preparation of TPU prepolymer: Hexamethylene diisocyanate (HDI) and polybutanediol (PTMG) in a molar ratio of 2:1 to 3:1 are mixed with a second solvent and subjected to a catalytic reaction to obtain TPU prepolymer; Preparation of TPU-Upy polymer film: After preheating the TPU prepolymer, 1,4-butanediol BDO, the Upy chain extender, the TPU prepolymer, and a third solvent are mixed to carry out a chain extension reaction to obtain TPU-Upy polymer. The TPU-Upy polymer is then cast into a mold, vacuum degassed, and dried to obtain a TPU-Upy polymer film. The mass ratio of 1,4-butanediol BDO to the Upy chain extender is 1:0.1 to 1:0.8, and the mass ratio of the TPU prepolymer to the Upy chain extender is 1:1 to 1:

3.

3. The method for preparing the self-healing biomaterial according to claim 2, characterized in that, The average molecular weight of the polybutanediol is 550 Da to 750 Da.

4. The method for preparing the self-healing biomaterial according to claim 2, characterized in that, The preparation process is carried out in a vacuum or inert gas environment.

5. The method for preparing a biomaterial with self-healing function according to claim 2, characterized in that, In the preparation steps of the Upy intermediate, HDI and MIC are mixed and vacuum dried for 30 min to 60 min, and then replaced with inert gas 3 to 6 times; the reaction system is reacted at 80℃ to 120℃ for 20 h to 30 h; after the reaction is completed, the reaction system is cooled to room temperature and washed with a desiccant to remove impurities.

6. The method for preparing a biomaterial with self-healing function according to claim 2, characterized in that, In the preparation of the Upy chain extender, the first solvent is dimethyl sulfoxide (DMSO); the reaction system is reacted at 50℃~70℃ for 50min~70min. After the reaction is completed, the reaction system is cooled to room temperature, deionized water is added to the reaction system for washing, and the precipitate is centrifuged and dried to obtain the Upy chain extender.

7. The method for preparing a self-healing biomaterial according to claim 2, characterized in that, In the step of preparing the TPU prepolymer, the second solvent includes one or a combination of two or more of N,N-dimethylformamide (DMF), tetrahydrofuran, and hexafluoroisopropanol; the catalytic reaction is carried out at 70℃ to 90℃ for 200 min to 300 min, and after the NCO groups in the reaction system reach the specified value, the temperature is lowered to room temperature to obtain the TPU prepolymer; the catalytic reaction system also includes a 0.05% to 0.2% (by mass) dibutyltin dilaurate (DBTL) catalyst.

8. The method for preparing a biomaterial with self-healing function according to claim 2, characterized in that, In the step of preparing TPU-Upy polymer film, the third solvent includes one or a combination of two or more of N,N-dimethylformamide (DMF), tetrahydrofuran, and hexafluoroisopropanol; the catalytic reaction system further includes a dibutyltin dilaurate (DBTL) catalyst with a mass fraction of 0.05% to 0.2%; the preheating temperature of the TPU prepolymer is 45℃ to 55℃; the chain extension reaction is carried out at 50℃ to 70℃ for 1.5 to 3 hours; after the reaction is completed, the TPU-Upy polymer is poured into a mold and vacuum degassed at 30℃ to 50℃ for 40 to 50 minutes, followed by drying for 45 to 55 hours to obtain the TPU-Upy film.

9. An artificial heart valve, characterized in that, The leaflet material of the artificial heart valve includes the biomaterial with self-healing function as described in claim 1.

10. A method for preparing an artificial heart valve, characterized in that, Including the following steps: The TPU-Upy film is cut into the shape of leaflets to obtain valve leaflets, which are then fixed onto a stent to obtain an artificial heart valve.

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