Self-healing polyurethane elastomer in liquid environment as well as preparation method and application of self-healing polyurethane elastomer

Abstract

The invention belongs to the field of polyurethane elastomers, and discloses a self-healing polyurethane elastomer in a liquid environment as well as a preparation method and application thereof. The main chain structure of the self-healing polyurethane elastomer is polyurethane-urea which takes polydimethylsiloxane (PDMS) as a soft segment and takes diisocyanate and 3, 3 '-dithiodipropionyl hydrazide (DPH) as hard segments. Wherein a hydrophobic PDMS soft segment in a main chain not only provides high elasticity and realizes efficient closing, but also prevents water molecules from permeating into a polymer network, so that the synergistic self-healing process of a dynamic covalent bond (-S-S-) and a high-density hydrogen bond in a hard segment is accelerated. The self-healing polyurethane elastomer has excellent mechanical properties, biocompatibility and self-repairing capability in a moist environment in vivo, and is particularly suitable for rapid closing and functional recovery of frequently punctured or damaged parts in biomedical instruments such as hemodialysis, artificial blood vessels, heart stents and heart valves.

Description

Technical Field

[0001] The invention belongs to the field of polyurethane elastomers and relates to a self-healing polyurethane elastomer in a liquid environment and a preparation method and application thereof. Background Art

[0002] Polyurethane is known as one of the world's six major synthetic materials. The hard segment in its structure is rich in urethane bonds, and the significant differences in chemical configuration and physical properties between it and the soft segment lead to the formation of a typical microphase separation structure, which gives the material excellent elasticity, wear resistance and mechanical strength. By regulating the composition and properties of the soft segment, the overall performance of polyurethane can be precisely adjusted. With the above advantages, polyurethane has been widely used in the field of biomedical polymer materials and has become one of the commonly used functional matrix materials. However, compared with the ability of organisms to automatically repair themselves after damage, traditional polyurethane materials often irreversibly lose their structural integrity and function after damage, and lack self-healing ability, which limits their further application in long-term service and intelligent medical devices.

[0003] Self-healing polyurethanes, through a multi-stage repair mechanism involving dynamic reversible chemical bonds and non-covalent interactions, offer innovative solutions for vascular damage caused by frequent punctures, such as hemodialysis, microcracks in heart stents under pulsating loads, and the self-repair of material fatigue and surface damage in heart valves during high-frequency cycling. These self-healing strategies are categorized as extrinsic self-repair (using microcapsule / microtube networks to trigger the release of repair agents) and intrinsic self-repair (using dynamic covalent bonds and non-covalent interactions to construct self-healing materials). Given the high biosafety requirements for blood-contact materials such as artificial blood vessels, heart stents, and heart valves, and the potential for immune or coagulation risks associated with the release of repair agents, structurally integrated intrinsic self-healing strategies hold greater promise for research and application.

[0004] However, unlike the traditional in vitro self-healing process, the dynamic healing of self-healing polyurethane in the blood-tissue fluid biphasic environment faces the problem of interference from water molecules. The main optimization strategies include: (1) introducing dynamic bonds that can be regulated by water molecules, such as catechol-boronate, but its hydrolytic stability needs to be improved; (2) using water molecules as plasticizers to accelerate the reconstruction of hydrogen bonds; (3) using dynamic bonds that are not easily affected by water, such as CF bond dipole-dipole interaction; (4) enhancing the hydrophobicity of the polymer to reduce the penetration of water molecules. Although the first two strategies can promote healing by using the water environment, they will weaken the mechanical properties of the elastomer and the self-healing ability under water-free conditions. In contrast, improving the hydrophobicity of the polymer is a research direction with greater application potential. However, although enhancing hydrophobicity can improve mechanical strength and self-healing efficiency, it is easy to lead to the risk of thrombosis and bacterial infection. In addition, the existing materials have a slow repair speed at 37°C, which is difficult to meet the clinical needs of hemodialysis artificial blood vessels to stop bleeding within seconds to minutes. Therefore, the development of self-healing polyurethane elastomers with both efficient self-healing ability in vivo and good biocompatibility remains a key research direction. Summary of the Invention

[0005] In view of this, in order to address the problems of low self-healing efficiency, insufficient biocompatibility and potential coagulation and infection risks of existing self-healing polyurethane elastomers in liquid environments, under blood contact conditions, the present invention intends to prepare a self-healing polyurethane elastomer with rapid self-healing ability in a blood-tissue fluid two-phase medium through molecular structure design of the polyurethane elastomer. It has excellent mechanical properties, biocompatibility and self-repair ability in a moist environment in the body, and is particularly suitable for the rapid closure and functional recovery of frequently punctured or damaged areas in biomedical devices such as hemodialysis, artificial blood vessels, heart stents and heart valves.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] The first technical purpose of the present invention is to provide a self-healing polyurethane elastomer, which is a polyurethane-urea with polydimethylsiloxane (PDMS) as a soft segment and diisocyanate and 3,3'-dithiodipropionylhydrazide (DPH) as a hard segment.

[0008] Furthermore, the diisocyanate is selected from one or more of isophorone diisocyanate (IPDI), hexamethylene diisocyanate (HDI), 4,4'-methylenebis(phenyl isocyanate) (MDI), 2,6-toluene diisocyanate (2,6-TDI), 2,4-toluene diisocyanate (2,4-TDI), and 4,4'-dicyclohexylmethane diisocyanate (HMDI).

[0009] Furthermore, the molar ratio of the polydimethylsiloxane (PDMS), diisocyanate and 3,3'-dithiodipropionylhydrazide (DPH) is 1:0.4-2:0.2-1.

[0010] Taking diisocyanate IPDI as an example, the preparation process of its self-healing polyurethane elastomer is as follows:

[0011] .

[0012] The self-healing polyurethane described above imparts excellent mechanical strength, toughness, and puncture resistance. The hydrophobic PDMS soft segment in the backbone not only provides high elasticity and efficient closure, but also prevents water molecules from penetrating the polymer network, thereby accelerating the synergistic self-healing process of the dynamic covalent bonds (-SS-) and high-density hydrogen bonds in the hard segment. The self-healing mechanism is as follows: .

[0013] The second technical purpose of the present invention is to provide a method for preparing the self-healing polyurethane elastomer as described above, which specifically comprises the following steps:

[0014] First, 10 g of methyl 3,3'-dithiopropionate was dissolved in 100 mL of anhydrous methanol. Then, 16.18 g of 80% hydrazine hydrate solution was slowly added dropwise to the above solution. After reacting at room temperature for 24 h, the suspension was centrifuged to obtain a white product. The product was washed with anhydrous methanol and dried to obtain a white powder of 3, 3-dithiodipropionohydrazide (DPH). Then, a linear self-healing poly(urethane-urea) elastomer (SHPU) was prepared using polydimethylsiloxane (PDMS-2000) as the soft segment and isophorone diisocyanate (IPDI) and 3, 3'-dithiodipropionohydrazide (DPH) as the hard segments.

[0015] The third technical purpose of the present invention is to provide a use of the self-healing polyurethane elastomer as described above in a self-healing, wearable artificial blood vessel.

[0016] The wall of the self-healing and perforating artificial blood vessel has a three-layer composite structure, wherein the middle layer is the self-healing polyurethane elastomer (SHPU) as described above; the inner layer of the wall is an anticoagulant hydrogel layer (SBMA-IL); and the outer layer is an antibacterial hydrogel layer (SBMA@PVP-OL).

[0017] Self-healing polyurethane elastomers are prepared into self-healing polyurethane pipes through extrusion molding, 3D printing and mold method. The inner diameter of the pipe is 1.5-30 mm, the wall thickness is 50-2000 µm, and the shapes of the pipe include straight, conical, forked and stepped.

[0018] Optionally, the anti-coagulation hydrogel layer is a coating formed on the substrate surface by simultaneously initiating graft cross-linking polymerization of a zwitterionic monomer and a water-soluble cross-linking agent on the surface of an intermediate layer polyurethane substrate previously activated by a surface initiator and in an aqueous solution; the aqueous solution contains a zwitterionic monomer, a water-soluble cross-linking agent and a water-soluble initiator;

[0019] The polymer coating has a friction coefficient of less than 0.005 in an aqueous medium and a surface Young's modulus of 10-60 kPa; the zwitterionic monomer is at least one or more of methacryloylethyl sulfobetaine, 2-methacryloyloxyethyl phosphorylcholine, and carboxylic acid betaine methacrylate; the water-soluble crosslinker is a combination of a chemical crosslinker and a physical crosslinker; the chemical crosslinker is at least one or more of N,N-methylenebisacrylamide, N,N-bis(acryloyl)cystamine, ethylene glycol dimethacrylate, and carboxylic acid betaine dimethacrylate, and the physical crosslinker is selected from N-acryloylglycine amide; the surface initiator is one of benzophenone, 4-methylbenzophenone, isopropylthioxanthone, benzoyl peroxide, or azobisisobutyronitrile; and the water-soluble initiator is a photoinitiator or a thermal initiator selected from one of Irgacure-2959, α-ketoglutaric acid, ammonium persulfate, or potassium persulfate.

[0020] Optionally, the preparation process of the antibacterial hydrogel layer on the surface of the polyurethane substrate is as follows:

[0021] The polymerization of vinyl pyrrolidone (NVP), a physical crosslinker N-acryloylglycine amide (NAGA), a zwitterionic monomer, and a chemical crosslinker is simultaneously initiated in an aqueous solution and on the surface of an intermediate layer polyurethane substrate that has been pre-activated by a surface initiator. After polymerization, the outer surface coating is immersed in an iodine-ethanol solution to obtain an outer surface antibacterial coating through the complexation of NVP and iodide ions.

[0022] The zwitterionic monomer is at least one or more of methacryloylethyl sulfobetaine, 2-methacryloyloxyethyl phosphorylcholine, and carboxylic acid betaine methacrylate;

[0023] The chemical crosslinking agent is at least one or more of N, N-methylenebisacrylamide (MBA), N, N-bis(acryloyl)cystamine (MSBA), ethylene glycol dimethacrylate (EBA), and carboxylic acid betaine dimethacrylate (CBBA).

[0024] Furthermore, the concentration of the zwitterionic monomer in the raw materials of the antibacterial hydrogel layer is 5 wt%-10 wt%, the concentration of vinyl pyrrolidone is 5 wt%-40 wt%, the chemical crosslinker accounts for 0 wt%-20 wt% of the mass of the vinyl pyrrolidone monomer, the physical crosslinker N-acryloylglycine amide accounts for 0 wt%-50 wt% of the mass of the vinyl pyrrolidone monomer, and the water-soluble initiator accounts for 0.5 wt%-20 wt% of the mass of the vinyl pyrrolidone monomer; and the water-soluble initiator Irgacu-2959 accounts for 8 wt% of the mass of the vinyl pyrrolidone monomer;

[0025] After the outer surface coating is formed, the concentration of the iodine-ethanol solution used for immersion is 1 wt%-10 wt%, and the immersion time is 1-8 hours.

[0026] The self-healing mechanism of the inner and outer coatings is as follows: .

[0027] The fourth technical purpose of the present invention is to provide a use of the self-healing polyurethane elastomer as described above in artificial heart valve leaflets.

[0028] The leaflets of the artificial heart valve have a three-layer composite structure, the middle layer is the self-healing polyurethane elastomer (SHPU) as described above, and the inner and outer layers are both anti-coagulation hydrogel layers;

[0029] The material composition and surface modification process of the anticoagulant hydrogel layer are the same as above.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] (1) Excellent self-healing performance in liquid environment

[0032] The material of the present invention can achieve rapid and reliable self-repair in liquid environments such as blood and tissue fluid, breaking through the problems of weak self-healing performance and low efficiency of existing polyurethane in body fluids, and significantly improving the sealing and safety of implantable devices in situations such as puncture and injury.

[0033] (2) Internal self-healing mechanism and high safety

[0034] The material does not require external repair agents or stimulation conditions, and relies on the reversible action between molecular chains to achieve spontaneous repair at room temperature, avoiding the risk of repair agent leakage. It is more suitable for long-term implantation and high-safety medical device applications.

[0035] (3) Multifunctional integration and strong adaptability

[0036] Through layered structure design, the material has multiple properties such as anticoagulant, antibacterial, and lubricating, meeting various needs under complex physiological environments; at the same time, it has good mechanical strength and processing adaptability, and is suitable for large-scale preparation of various types of devices such as artificial blood vessels and artificial heart valves. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are merely embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying any creative work.

[0038] Figure 1 The self-healing polyurethane elastomer prepared in Example 1 1 H-NMR.

[0039] Figure 2 The stress-strain curves of samples with different PDMS-2000, IPDI, and DPH ratios (P:I:D).

[0040] Figure 3 The compliance and burst pressure of the self-healing polyurethane pipe prepared in Example 1.

[0041] Figure 4 This is the self-healing process of the self-healing polyurethane elastomer prepared in Example 1 in PBS solution.

[0042] Figure 5 This is an SEM image of the healing process of the self-healing polyurethane elastomer prepared in Example 1 after puncture and scratching in PBS solution.

[0043] Figure 6 This is the SEM image of the cross section of the self-healing polyurethane pipe after coating modification.

[0044] Figure 7 This is the curve of the cumulative release of iodide ions from the outer antibacterial hydrogel coating over time.

[0045] Figure 8 This is a comparison chart of the continuous sterilization performance of the pipeline surface before and after antibacterial coating modification.

[0046] Figure 9 SEM images of the hydrogel coating on the inner and outer surfaces at different times after puncture.

[0047] Figure 10 This is an analysis of the vascular patency performance of the artificial blood vessel prepared in Example 1 9 months after implantation into the pig carotid artery.

[0048] Figure 11This is a cross-sectional SEM image of the artificial heart valve leaflet prepared in Example 11. DETAILED DESCRIPTION

[0049] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0050] The term "embodiment" is used herein specifically to describe any embodiment as "exemplary," and should not be construed as superior or preferable to other embodiments. Performance indicators in the embodiments of this application were tested using conventional testing methods in the art, unless otherwise specified. It should be understood that the terms used in this application are intended solely to describe specific implementations and are not intended to limit the disclosure herein.

[0051] Unless otherwise specified, the technical and scientific terms used herein have the same meanings as commonly understood by ordinary technicians in the technical field to which this application belongs; other experimental methods and technical means not specifically specified in this application refer to experimental methods and technical means commonly used by ordinary technicians in this field.

[0052] In order to better illustrate the content of this application, numerous specific details are provided in the specific examples below. It should be understood by those skilled in the art that this application can be implemented without certain specific details. In the examples, some methods, means, instruments, equipment, etc. well known to those skilled in the art are not described in detail in order to highlight the main purpose of this application.

[0053] Under the premise of no conflict, the technical features disclosed in the embodiments of this application can be combined arbitrarily, and the resulting technical solutions belong to the contents disclosed in the embodiments of this application.

[0054] The invention discloses a preparation method of a self-healing polyurethane elastomer in a liquid environment and application of the self-healing and wearable artificial blood vessels and artificial heart valves.

[0055] For a better understanding of the present invention, the present invention is further specifically described below through the following examples, but it should not be understood as limiting the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the above invention content are also considered to fall within the scope of protection of the present invention.

[0056] Example 1

[0057] Preparation of self-healing polyurethane elastomer:

[0058] Preparation of a self-healing polyurethane elastomer: First, 10 g of methyl 3,3'-dithiopropionate was dissolved in 100 mL of anhydrous methanol. Then, 16.18 g of an 80% hydrazine hydrate solution was slowly added dropwise to the solution. After reacting at room temperature for 24 h, the suspension was centrifuged to obtain a white product. The product was washed with anhydrous methanol and dried to obtain 3,3-dithiodipropionohydrazide (DPH) as a white powder. A linear self-healing poly(urethane-urea) elastomer (SHPU) was then prepared using polydimethylsiloxane (PDMS-2000) as the soft segment and isophorone diisocyanate (IPDI) and 3,3'-dithiodipropionohydrazide (DPH) as the hard segments.

[0059] Different self-healing polyurethanes were prepared by adjusting the molar ratio of PDMS-2000, IPDI, and DPH. The molar ratio of PDMS-2000, IPDI, and DPH prepared in this embodiment was 1:1.4:0.4. The specific preparation method is as follows:

[0060] 5g of PDMS was added to a three-necked flask, and nitrogen was pumped in three times to remove air. The mixture was then heated to 100°C under vacuum and stirred for 2 hours to remove moisture. The temperature was then lowered to 80°C. 0.796g of IPDI and 0.04g of the catalyst dibutyltin dilaurate (DBTDL) were dissolved in 5mL of toluene and slowly added dropwise to the flask under nitrogen. After a 3-hour reaction, 0.238g of DPH was dissolved in a mixture of 35mL of N,N-dimethylacetamide (DMAc) and 30mL of toluene and added dropwise to the reaction system. The mixture was stirred under nitrogen for 4 hours. Upon completion of the reaction, a colorless, transparent polymer solution with a certain viscosity was obtained. After the reaction system cooled to room temperature, the polymer solution was poured into a watch glass and dried in an oven at 70°C for 12 hours. The toluene and DMAc solvents were removed to obtain a colorless, transparent self-healing polyurethane elastomer.

[0061] Preparation of self-healing polyurethane pipes: Self-healing polyurethane elastomers can be prepared into self-healing polyurethane pipes through extrusion molding, 3D printing and mold method. 3D printing is used as an example below.

[0062] First, the synthesized self-healing polyurethane elastomer sample was cut into blocks and then processed into a wire with a diameter of 1.75 mm using a micro extruder for fused deposition modeling (FDM) 3D printing. The nozzle temperature of the micro extruder was set to 140 °C and the extrusion speed was 10 rpm. Using a computer design system, an FDM printer with a nozzle diameter of 0.4 mm was used to print self-healing polyurethane elastomer pipes with a diameter of 5 mm and a wall thickness of 200 µm to meet the needs of different indications. The chemical composition, mechanical properties and self-healing properties of the prepared self-healing polyurethane elastomer pipes are shown in Figure 2. Figure 1-Figure 5 As shown in Table 1:

[0063] Table 1 Properties of the self-healing polyurethane pipe prepared in Example 1

[0064] Self-healing efficiency: the ratio of the fracture strain of the original sample after 2 minutes of repair after complete incision in 37°C PBS solution

[0065] Preparation of the inner surface anticoagulant coating: Following the applicant's previously authorized patent (CN116003692B), the prepared self-healing polyurethane elastomer tubing was flushed and completely dried with a nitrogen stream. One end of the tubing was then sealed, and a benzophenone-ethanol solution was poured from the other end, soaking at 25°C for 3 minutes. Excess benzophenone and ethanol solutions were then recovered, rinsed, and dried with nitrogen.

[0066] Next, a zwitterionic polymer precursor solution was prepared. Specifically, sulfobetaine methacrylate (SBMA), N-acryloylglycinamide (NAGA), a chemical crosslinker, carboxybetaine dimethacrylate (CBMAX), and a photoinitiator, Irgacure 2959, were dissolved in deionized water. The precursor solution contained 20 wt% SBMA, 20% NAGA as the physical crosslinker, 10% CBMAX as the chemical crosslinker, and 10% Irgacure 2959 as the photoinitiator. Finally, one end of the benzophenone-activated tubing was sealed, and the zwitterionic polymer precursor solution was injected into the tubing lumen from the other end. The tubing was then uniformly irradiated with 365 nm UV light. Subsequently, the adsorbed materials on the inner surface of the tubing were repeatedly rinsed with copious amounts of deionized water, resulting in the preparation of SBMA-IL on the inner surface of the self-healing polyurethane elastomer tubing. The treated sample was dried with nitrogen at room temperature.

[0067] Preparation of the external antibacterial coating: After cleaning the external surface of the tubing, it was thoroughly dried with a nitrogen stream. The tubing was then sealed at both ends with clamps and immersed in a benzophenone-ethanol solution for 5 minutes. The sample was then rinsed with deionized water and alcohol to remove unreacted benzophenone and dried with nitrogen. The tubing was then immersed in a prepolymer solution consisting of N-vinylpyrrolidone (NVP), NAGA, SBMA, N,N'-methylenebisacrylamide (MBA), and a photoinitiator (Irgacu-2959). Polymerization was performed under 365nm UV light to form a hydrogel polymer on the tubing surface. The prepolymer solution contained 8wt% of the zwitterionic monomer and 20wt% of the vinylpyrrolidone. The chemical crosslinker accounted for 7wt% of the vinylpyrrolidone monomer, the physical crosslinker N-acryloylglycineamide accounted for 25wt% of the vinylpyrrolidone monomer, and the water-soluble initiator accounted for 8wt% of the vinylpyrrolidone monomer. After the outer surface coating is formed, the pipe modified with the outer surface hydrogel coating is immersed in a 5 wt% iodine-ethanol solution for 6 h, wherein I2 is H + I3 - The iodine complex exists in a crystalline form and forms hydrogen bonds with the amide groups in the hydrogel coating, resulting in stable attachment of iodine to the surface. To remove free iodine from the substrate, the substrate was first washed three times with ethanol and then immersed in n-heptane for 24 hours. Washing was continued until the wash solution was colorless and no free iodine could be detected by ultraviolet-visible spectroscopy (UV-Vis). SBMA@PVP-OL was then prepared on the outer surface of the self-healing polyurethane elastomer tubing. The prepared SH-ECG was then thoroughly dried under a nitrogen stream and sterilized using H2O2 low-temperature plasma before packaging.

[0068] Examples 2-5

[0069] The same procedures as in Example 1 were followed, except that the ratio of the soft and hard segments of the polyurethane used in the intermediate layer (PDMS-2000:IPDI:DPH, hereinafter referred to as P:I:D) was varied. The tensile strength, burst pressure, compliance, suture strength, and self-healing rate of polyurethanes with varying soft and hard segment ratios and natural blood vessels were measured, as shown in Table 2.

[0070] Table 2 Performance of self-healing polyurethane pipes prepared with different ratios of soft and hard segments prepared in Examples 2-5

[0071] As shown in Table 2, increasing the hard segment content improves the material's tensile strength, burst pressure, and suture strength, but decreases its compliance and self-healing rate. When the PDMS-2000: IPDI: DPH ratio is 1: 1.4: 0.4, the mechanical properties of the tubing match those of natural blood vessels, with a healing rate of 85% ± 7%, meeting the requirements for artificial blood vessels.

[0072] Examples 6-10

[0073] The method of Example 1 was followed, and the operation was the same as in Example 1, except that the type of diisocyanate was changed, and the physical and chemical properties of the self-healing polyurethane pipes prepared with different types of diisocyanates were measured.

[0074] Table 3 Properties of self-healing polyurethane pipes prepared from different types of diisocyanates prepared in Examples 6-10

[0075] IPDI: isophorone diisocyanate; HDI: 1,6-hexamethylene diisocyanate; MDI: 4,4'-methylene bis(phenyl isocyanate); 2,6-TDI: 2,6-toluene diisocyanate; 2,4-TDI: 2,4-toluene diisocyanate; HMDI: 4,4'-dicyclohexylmethane diisocyanate

[0076] It can be seen from Table 3 that with the introduction of benzene ring in diisocyanate or the increase of steric hindrance effect, the tensile strength, suture strength and burst pressure of the material increase, the compliance decreases, and the self-healing and efficiency decrease.

[0077] Example 11

[0078] According to the preparation method of self-healing polyurethane in Example 1, the operation is the same as in Example 1, except that the polyurethane is molded in a mold to form a self-healing polyurethane elastomer sheet, and then the anti-coagulation coating as described in Example 1 is modified on the inner and outer surfaces to prepare an artificial heart valve leaflet.

[0079] Furthermore, the self-healing polyurethane elastomer prepared by the present invention and the characterization method of its application in artificial blood vessels and heart valve leaflets are disclosed as follows:

[0080] (1) Tensile strength test: In this experiment, a universal material testing system (Instron, Norwood, MA, USA) equipped with a 2519-104 sensor was used to evaluate the tensile strength of the samples. The test contents included ultimate tensile strength and radial loading-unloading behavior. During the test, the sample was mounted in the radial direction between two sets of parallel hooks made of stainless steel wire with a diameter of 1 mm, and the test was carried out under the action of radial tension. The experiment used a 50 N range force sensor and the loading rate was set at 2 mm / min until the sample broke.

[0081] (2) Self-healing efficiency: The self-healing polyurethane artificial blood vessel samples were cut into long strips of 50 mm × 10 mm and immersed in a phosphate-buffered saline (PBS) solution at 37°C for 10 minutes to achieve pre-hydration. Subsequently, the specimens were fractured along their width, and the cut interfaces were quickly realigned to achieve preliminary closure. The samples were immersed in PBS for another 2 minutes while maintaining interfacial contact, then removed and subjected to tensile testing to evaluate the self-healing ability of the material.

[0082] Puncture and scratch tests: Samples were cut longitudinally and pretreated in phosphate-buffered saline (PBS) at 37°C. Subsequently, multiple holes and scratches were created on the sample surface using a syringe needle to simulate mechanical damage. After the damage treatment, the samples remained in the 37°C PBS solution, and samples were taken at set time points to observe their self-healing behavior. To prevent the self-healing process from continuing after sampling, the samples were immediately cooled to -20°C and freeze-dried after each sampling, effectively terminating the self-healing reaction. All samples treated at different time points were observed and analyzed under a scanning electron microscope (SEM) to evaluate the repair effect of damage such as scratches and holes.

[0083] (3) Compliance test: The compliance test device consists of a programmable injection pump and a pressure monitoring meter, which is used to control and record the deformation behavior of the lumen structure under different internal pressures. By adjusting the injection and withdrawal rates of the injection pump, precise control of the pressure in the closed fluid circuit is achieved. During the test, the diameter change of the sample is measured using a vernier caliper. Compliance is characterized by the relative radial expansion degree under unit pressure difference, and the calculation formula is as follows:

[0084]

[0085] Where P1 is the low pressure value and P2 is the high pressure value, both expressed in mmHg. RP1 and RP2 represent the diameters at pressures P1 and P2, respectively. Compliance is expressed as the percentage change in diameter per 100 mmHg.

[0086] (4) Burst pressure test: After the sample is fully swollen to equilibrium in phosphate buffered saline (PBS), it is connected to a pressure loading device. Subsequently, PBS solution is injected into the sample lumen at a constant rate of 50 mmHg / s, causing the internal pressure to rise continuously and stabilize. During the pressurization process, the internal pressure changes are monitored in real time. When the sample ruptures, the corresponding instantaneous pressure value is recorded as the burst pressure of the material.

[0087] (5) Suture strength test: An 8-0 suture was used to penetrate the vascular wall 2 mm inward from the end of the artificial blood vessel to form a fixed point. Subsequently, a tensile load was applied to the suture at a constant rate of 50 mm / min until the suture was completely torn and penetrated the artificial blood vessel wall. The maximum tensile force required during this process was recorded and this value was used as the suture strength index of the artificial blood vessel.

[0088] (6) Fatigue resistance test: To evaluate the fatigue resistance of artificial blood vessels, a pulsating accelerated fatigue test method was used. Under a constant temperature of 37°C, the artificial blood vessel sample was connected to a pulsating fatigue test device (model: INVS-06, manufacturer: CARE Measurement & Control Co., Ltd), and physiological saline was injected into its cavity as a circulating medium. The device applied a periodic pulse load with a frequency of 50 Hz and a pressure range of 80-160 mmHg, and the sample was continuously operated for up to 380 million cycles. The diameter and compliance of the sample were measured and compared before and after the test to determine its fatigue tolerance under long-term dynamic load.

[0089] (7) Analysis of coating surface morphology and thickness: A field emission scanning electron microscope (HITACHI S-4800, manufacturer: Hitachi) was used to observe and characterize the surface morphology and cross-sectional thickness of the sample coating. To improve the conductivity of the sample and obtain a clear image, the sample surface was metal-coated for approximately 60 seconds under an inert atmosphere (argon) before scanning. Subsequently, high-resolution images of the coating surface and cross-section were obtained under imaging parameters with an acceleration voltage of 3 kV and a working distance within the range of 10–15 mm to evaluate its microstructural characteristics and thickness uniformity.

[0090] (8) Protein Adhesion Test: The amount of protein adsorption was determined using the BCA protein quantitative method, and the reagent used was the BCA protein detection kit. This method is based on the following principle: Under alkaline conditions, the peptide bonds in proteins can absorb Cu² + Reduction to Cu + , the generated Cu +The ion forms a purple complex with two molecules of BCA (bisaminocyclohexane tetraacetic acid). This complex exhibits a strong absorption peak at 562 nm, and its absorbance is linearly related to protein concentration. The model protein used in this experiment is bovine serum albumin (BSA). Following the kit instructions, standard BSA solutions were prepared at varying concentrations of 0, 2.5, 5, 10, 20, 40, and 200 μg / mL. The absorbance of each standard solution at 562 nm was measured. A standard curve was plotted with absorbance on the horizontal axis and protein concentration on the vertical axis for subsequent quantitative analysis of protein adsorption in samples.

[0091] (9) Surface Young's modulus test: A desktop nanoindentation tester (model: PIUMA) was used to measure the surface mechanical properties of the zwitterionic polymer coating modified on the substrate surface. The specific test indicator was Young's modulus. During the test, a spherical indenter with a radius of 48.5 mm was used to load and probe the coating sample pre-soaked in PBS solution. The test area was 100 μm × 100 μm, and data was collected using a 5 × 5 matrix method with a measurement point spacing of 20 μm, achieving a detailed scan and evaluation of the Young's modulus distribution within the area.

[0092] (10) Surface friction coefficient test: The friction coefficient of the sample surface was measured using a CSM friction and wear tester. Before the test, the sample was pre-soaked in deionized water at a constant temperature of 25°C to ensure that it was in a stable wet state. During the test, a glass ball with a diameter of 3 mm was used as a loading probe and moved on the sample surface at a sliding speed of 30 mm / min. The sliding stroke was set to 20 mm. The friction coefficient was calculated by comparing the friction force recorded in real time to the applied normal load (800 μN).

[0093] (11) Platelet adhesion test: First, fresh whole blood collected from New Zealand white rabbits was processed using a commercial whole blood platelet separation kit to separate platelet-rich plasma (PRP). The treated samples were incubated with PRP at 37°C for 2 hours to complete the contact process between platelets and the material surface. Subsequently, the samples were divided into an unwashed group and a PBS rinse group, and were fixed in a 2.5% glutaraldehyde fixative for 2 hours. After fixation, the samples were dehydrated in a gradient of 50%, 60%, 70%, 80%, 90% and 100% anhydrous ethanol solutions, with each gradient treatment time being 30 minutes. After dehydration, all samples were naturally dried at room temperature for 24 hours. The dried samples were imaged using a scanning electron microscope (SEM, model: HITACHI S-4800, Hitachi). The effect of the material surface on platelet activation was evaluated by analyzing the morphology of platelets on the surface of the unwashed group; at the same time, the number of residual platelets in the washed group was observed to determine the anti-platelet adhesion performance of the coating.

[0094] (12) Antibacterial performance / antibacterial adhesion performance test: Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus were selected as pathogenic bacteria models. The artificial blood vessels with antibacterial coating on the outer surface were immersed in 1 mL of Escherichia coli or Staphylococcus aureus suspension (1×10 8 The samples were placed in 24-well plates (1000 CFU / mL) and incubated at 37°C on a shaker for 12 hours. After removing the bacterial suspension, the tubes were rinsed three times with PBS to remove unadhered bacteria. The tubes were then immersed in PBS containing 4% glutaraldehyde and stored at 4°C overnight. The samples were then dehydrated using a gradient of 20% ethanol, followed by 20 minutes of dehydration each time using 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% ethanol. Finally, the bacterial adhesion on the catheter surface was observed using scanning electron microscopy to confirm the antibacterial adhesion efficacy of the coating.

[0095] In order to quantitatively evaluate the antibacterial adhesion effect of the coating, 1 mL of bacterial suspension (1 × 10 8 CFU / mL) were co-incubated with artificial blood vessels sterilized by UV for 30 minutes in a 37°C incubator for 12 hours. All catheters were then rinsed three times with sterile PBS to remove loosely adhered bacteria. Next, all samples were ultrasonically treated in 2 mL of sterile PBS to detach bacteria firmly adhered to the sample surface. After repeating the same conditions five times, a total of 10 mL of PBS containing bacteria was collected. Bacteria were diluted to an appropriate concentration and inoculated onto LB agar plates. The plates were then incubated at 37°C for 12 hours. The number of colonies formed was determined by plate count, and the antimicrobial adhesion efficacy of the coating was evaluated.

[0096] Since iodine ions in the coating are complexed by hydrogen bonds, iodine can be slowly released in the body to kill bacteria. Therefore, the present invention evaluates the bactericidal effect of the system in vitro.

[0097] 100 μL of Escherichia coli or Staphylococcus aureus suspension (1 × 10 8 CFU / mL) was inoculated into LB agar medium, and then the sample sterilized by UV for 30 min was placed on the medium and cultured in a constant temperature incubator at 37 °C for 12 h, and the formation of inhibition zone was observed.

[0098] In order to quantitatively determine the bactericidal effect of the coating, the present invention immersed the sample after UV sterilization for 30 minutes into 1 mL of a suspension containing Escherichia coli or Staphylococcus aureus (1×10 8 CFU / mL) and cultured in a 37°C constant temperature shaker for 12 hours. The samples were taken out and the suspension after co-culture was appropriately diluted and inoculated onto LB agar plates. The plates were then cultured in a 37°C constant temperature incubator for 12 hours. The number of colonies formed was determined by the plate count method to evaluate the in vitro bactericidal effect of the coating.

[0099] (13) Pig carotid artery end-to-end anastomosis experiment: Male Bama pigs aged 3 to 4 months and weighing 55–75 kg were selected as experimental animals. Anesthesia was induced by intramuscular injection of ketamine (dose: 20 mg / kg) and thiazide (dose: 2 mg / kg), followed by infusion of fentanyl and propofol via the auricular vein to maintain general anesthesia. During the operation, the animals were intubated with a 7 mm endotracheal tube connected to a positive pressure ventilator for respiratory support, and the oxygen supply rate was set at 1.2 L / min.

[0100] During the procedure, the skin of the neck was opened and the target carotid artery was isolated. Two hemostats were used to clamp the proximal and distal segments. The middle segment was then excised, and the graft was anastomosed end-to-end to the stump using 6-0 monofilament suture. Following the procedure, the muscle layer, subcutaneous tissue, and skin were sutured layer by layer using absorbable monofilament suture. Nine months after surgery, tissue samples were collected for histological analysis to assess the biological response of the implant.

[0101] After implantation, Doppler ultrasound imaging was used to noninvasively assess blood flow patency in the graft. This was performed using a veterinary digital color Doppler ultrasound diagnostic system (SIUI Apogee 3100V, China) in superficial structural imaging mode. The graft implantation site was determined based on the anatomical location of the carotid artery and synchronized pulse fluctuations. Ultrasound examinations acquired three-dimensional color flow images, pulse synchronization signals, and real-time blood flow velocity data. The red and blue colors in the Doppler flow spectrum indicate antegrade and retrograde blood flow, respectively.

[0102] Specifically, Figure 1The self-healing polyurethane elastomer prepared in Example 1 1 H-NMR. Figure 1 As can be seen, δ = 4.21 ppm and δ = 9.07 ppm represent proton peaks from primary and secondary amines, respectively. Two sets of methylene proton peaks also appear at δ = 2.4 ppm and δ = 2.89 ppm. The area ratio of the four peaks is 2:1:2:2. Analysis confirmed that the designed healing polyurethane elastomer was successfully prepared.

[0103] Figure 2 The stress-strain curves of samples with different PDMS-2000, IPDI, and DPH ratios (P:I:D) are shown in Figure 2. Figure 2 As can be seen, when the PDMS-2000: IPDI: DPH ratio is 1:2:1, the material's maximum fracture stress reaches 10 MPa and the strain approaches 650%, indicating high toughness and strength. As the hard segment content decreases, the material's maximum fracture stress decreases, but its toughness increases.

[0104] Figure 3 The compliance and burst pressure of the self-healing polyurethane pipe prepared in Example 1.

[0105] Figure 5 This is an SEM image of the healing process of the self-healing polyurethane elastomer prepared in Example 1 after puncture and scratching in PBS solution. Figure 5 It can be seen that after being completely cut off in 37°C PBS solution, the SHPU has basically completed self-repair after only 2 minutes, indicating that it has the self-repair properties in a fast liquid environment.

[0106] Figure 6 The SEM image of the cross section of the self-healing polyurethane pipe after coating modification. Figure 6 It can be seen that the SBMA-IL anticoagulant coating and the SBMA@PVP-OL antibacterial coating can evenly modify the inner and outer surfaces of the polyurethane elastomer pipe and form a tight bond with the substrate without any gaps.

[0107] Figure 7 The curve of the cumulative release of iodine ions from the outer antibacterial hydrogel coating changes with time. Figure 7 It can be seen that the outer antibacterial coating can maintain the release of iodine ions for more than one week, and early postoperative infection of artificial arteriovenous fistula often occurs 5 to 7 days after surgery, which can meet clinical anti-infection needs.

[0108] Figure 8 The following is a comparison of the continuous sterilization performance of the pipeline surface before and after the antibacterial coating is modified. Figure 8 It can be seen that the outer antibacterial coating has a good bactericidal effect.

[0109] Figure 9The SEM images of the hydrogel coating on the inner and outer surfaces at different times after puncture. Figure 9 It can be seen that after the inner and outer coatings are punctured, self-healing can basically be completed within 20 minutes.

[0110] Figure 10 The vascular patency performance of the artificial blood vessel prepared in Example 1 was analyzed after 9 months of implantation into the pig carotid artery. Figure 10 It can be seen that after artificial blood vessels are implanted into the body, they can maintain patency for a long time.

[0111] The above description of the disclosed embodiments is intended to enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is intended to conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A self-healing polyurethane elastomer, characterized in that: The self-healing polyurethane elastomer is a polyurethane-urea having polydimethylsiloxane (PDMS) as a soft segment and diisocyanate and 3,3'-dithiodipropionylhydrazide (DPH) as a hard segment.

2. The self-healing polyurethane elastomer according to claim 1, characterized in that The diisocyanate is selected from one or more of isophorone diisocyanate (IPDI), hexamethylene diisocyanate (HDI), 4,4'-methylene bis(phenyl isocyanate) (MDI), 2,6-toluene diisocyanate (2,6-TDI), 2,4-toluene diisocyanate (2,4-TDI), and 4,4'-dicyclohexylmethane diisocyanate (HMDI).

3. The self-healing polyurethane elastomer according to claim 1, characterized in that The molar ratio of polydimethylsiloxane (PDMS), diisocyanate and 3,3'-dithiodipropionylhydrazide (DPH) is 1:0.4-2:0.2-1.

4. A method for preparing a self-healing polyurethane elastomer according to claim 1, characterized in that: The method specifically comprises the following steps: First, 10 g of methyl 3,3'-dithiopropionate was dissolved in 100 mL of anhydrous methanol. Then, 16.18 g of 80% hydrazine hydrate solution was slowly added dropwise to the above solution. After reacting at room temperature for 24 h, the suspension was centrifuged to obtain a white product. The product was washed with anhydrous methanol and dried to obtain a white powder of 3, 3-dithiodipropionohydrazide (DPH). Then, a linear self-healing poly(urethane-urea) elastomer was prepared using polydimethylsiloxane (PDMS-2000) as the soft segment and isophorone diisocyanate (IPDI) and 3, 3'-dithiodipropionohydrazide (DPH) as the hard segments.

5. Use of the self-healing polyurethane elastomer according to claim 1 in self-healing, wearable artificial blood vessels and artificial heart valves.

6. The use according to claim 5, characterized in that The wall of the self-healing, i.e., penetrating artificial blood vessel and the leaflets of the artificial heart valve have a three-layer composite structure, wherein the middle layer is the self-healing polyurethane elastomer as claimed in claim 1; Moreover, the inner layer of the self-healing and wearable artificial blood vessel wall is an anticoagulant hydrogel layer SBMA-IL, and the outer layer is an antibacterial hydrogel layer SBMA@PVP-OL; The inner layer and the outer layer of the leaflet of the artificial heart valve are both anti-thrombotic and anti-calcification zwitterionic hydrogel coatings.

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