Degradable piezoelectric artificial blood vessel and preparation method thereof

Abstract

The application discloses a degradable piezoelectric artificial blood vessel and a preparation method thereof, and relates to the technical field of artificial blood vessel preparation. The degradable piezoelectric artificial blood vessel comprises a first guide layer, which is provided in a tubular shape and defines a pipeline channel for blood circulation, is used for guiding blood flow, cell adhesion and tissue repair; a piezoelectric functional layer, which is sleeved on the outside of the first guide layer, is used for converting the radial force signal of blood pressure into an electric signal; and a second guide layer, which is arranged on the outside of the piezoelectric functional layer, is used for fixing the piezoelectric functional layer and guiding cell adhesion and tissue repair. The above design avoids the direct contact between the molecular ferroelectric material and the body fluid environment, and facilitates the molecular ferroelectric material to play the function of signal extraction in the body. The piezoelectric functional layer comprises a fiber membrane modified by a molecular ferroelectric material, and the fibers are arranged along the radial direction of the blood vessel, so that the mechanical performance of the artificial blood vessel is enhanced, and the durability of the artificial blood vessel is improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of piezoelectric sensing and artificial blood vessel preparation, and particularly relates to a degradable piezoelectric artificial blood vessel and a preparation method thereof. BACKGROUND

[0002] In the treatment of vascular lesions, artificial blood vessel replacement is the only solution to rescue critically ill patients, but there are risks such as anastomotic port embolization and calcification after the artificial blood vessel is implanted in the body. Vascular calcification can reduce the elasticity of the blood vessel, thereby causing the elastic modulus of the blood vessel to increase, and thrombosis can cause the blood flow rate to slow down, both of which can cause the blood pressure at the artificial blood vessel replacement site to abnormally increase. Therefore, early detection of postoperative abnormalities, timely warning and effective intervention are the key to improving the success rate of artificial blood vessel replacement surgery.

[0003] At present, piezoelectric sensors with real-time blood pressure monitoring function are mainly implanted to detect abnormal blood pressure conditions.

[0004] However, the existing piezoelectric sensors have the following defects: 1) traditional piezoelectric materials such as lead zirconate titanate (PZT) and barium titanate (BTO) represented by piezoelectric ceramics contain heavy metal elements, have poor bioactivity, low endothelialization degree and poor compliance, and piezoelectric polymers represented by polyvinylidene fluoride (PVDF) are usually non-degradable, and the above-mentioned materials do not meet the requirements of artificial blood vessels, and usually need to be implanted directly into the blood vessel, which requires secondary surgery for removal; 2) the introduction of hard piezoelectric materials such as piezoelectric ceramics can reduce the mechanical strength of flexible artificial blood vessels, making them prone to cracking and failure under the impact of multiple blood pressures; 3) after the piezoelectric sensor enters the body fluid environment, the bound charges generated by the piezoelectric material in the piezoelectric sensor are easily neutralized due to the non-insulating system containing electrolytes in the body fluid environment, which seriously affects the sensitivity of the piezoelectric sensor, and even leads to the failure of the sensor, affecting the monitoring effect. SUMMARY

[0005] The main purpose of the present application is to provide a degradable piezoelectric artificial blood vessel and a preparation method thereof, which aims to solve the problems of non-degradable implantable piezoelectric sensors, the need for secondary surgery for removal, and the loss of sensitivity in the prior art.

[0006] To achieve the above-mentioned purpose, the present application provides a degradable piezoelectric artificial blood vessel, comprising:

[0007] A first guide layer is provided in a tubular shape, which defines a pipeline channel for blood flow, and is used for guiding blood flow, cell adhesion and tissue repair;

[0008] A piezoelectric functional layer is sleeved on the outside of the first guide layer, and the piezoelectric functional layer is used for converting the radial force signal of the blood pressure into an electric signal; and

[0009] A second guide layer is arranged outside the piezoelectric functional layer, and is used for fixing the piezoelectric functional layer and guiding cell adhesion and tissue repair.

[0010] The piezoelectric functional layer comprises a fiber membrane with adsorbed molecular ferroelectric material, and at least part of the fibers in the fiber membrane are arranged in the circumferential direction of the blood vessel.

[0011] In an embodiment, the thickness of the first guide layer is 30-100 μm; and / or,

[0012] The thickness of the piezoelectric functional layer is 100-200 μm; and / or,

[0013] The thickness of the second guide layer is 20-50 μm; and / or,

[0014] The inner diameter of the degradable piezoelectric artificial blood vessel is 2-6 mm.

[0015] In an embodiment, the piezoelectric functional layer further comprises an electrode, a wire and a waterproof layer, the electrode and the wire are arranged on both sides of the fiber membrane, and the waterproof layer is arranged on the side of the electrode away from the fiber membrane.

[0016] The application further provides a preparation method of the degradable piezoelectric artificial blood vessel, comprising the following steps:

[0017] S10, mixing the oriented fiber membrane with a molecular ferroelectric material solution, drying, and precipitating crystals to obtain a piezoelectric functional layer;

[0018] S20, obtaining a first guide layer and a second guide layer, nesting the piezoelectric functional layer between the first guide layer and the second guide layer, and making the first guide layer, the piezoelectric functional layer and the second guide layer inseparable to obtain a degradable piezoelectric artificial blood vessel.

[0019] In an embodiment, in step S10, the oriented fiber membrane comprises a single oriented fiber membrane; and / or,

[0020] The raw material of the oriented fiber membrane comprises a natural polymer material, and the natural polymer material comprises at least one of silk fibroin, cellulose, chitosan, collagen, hyaluronic acid and gelatin.

[0021] In an embodiment, the preparation method of the oriented fiber membrane comprises an electrospinning technology.

[0022] In an embodiment, the inner diameter of the metal needle of the electrospinning technology is 0.4-0.6 mm; and / or,

[0023] The push injection speed of the electrospinning technology is 1.0-2.0 mL / h; and / or,

[0024] The spinning voltage of the electrospinning technology is 10-15 kV; and / or,

[0025] The receiving distance of the electrospinning technology is 10-15 cm; and / or,

[0026] The spinning temperature of the electrospinning technology is 20-40℃; and / or,

[0027] The spinning humidity of the electrospinning technology is <5%.

[0028] In an embodiment, in step S10: the molecular ferroelectric material includes any one of ImClO4, [Hdabco]ClO4; and / or,

[0029] The mass concentration of the molecular ferroelectric material in the solution of the molecular ferroelectric material is 0.05-0.6 g / mL.

[0030] In an embodiment, in step S20:

[0031] The method for obtaining the first guide layer includes an electrospinning technology; and / or,

[0032] The method for obtaining the second guide layer includes an electrospinning technology; and / or,

[0033] The raw material of the first guide layer includes at least one of polylactic acid and polycaprolactone; and / or,

[0034] The raw material of the second guide layer includes at least one of polylactic acid and polycaprolactone.

[0035] The application provides a degradable piezoelectric artificial blood vessel and a preparation method thereof, the degradable piezoelectric artificial blood vessel comprises a first guide layer arranged in a tubular shape and defining a pipeline channel for blood circulation, used for guiding blood flow, cell adhesion and tissue repair; a piezoelectric functional layer sleeved outside the first guide layer, used for converting a force signal of blood pressure into an electric signal; and a second guide layer arranged outside the piezoelectric functional layer, used for fixing the piezoelectric functional layer and guiding cell adhesion and tissue repair; the above design avoids direct contact between a molecular ferroelectric material and a body fluid environment, facilitates the molecular ferroelectric material to play a function of signal extraction in the body, improves the durability of the molecular ferroelectric material and the sensitivity and accuracy of detection, and can realize in-situ real-time monitoring of postoperative blood pressure. The molecular ferroelectric material is a biocompatible material and has good sensitivity, and the sensitivity of blood pressure detection is improved. The piezoelectric functional layer comprises a modified molecular ferroelectric material fiber membrane, part of the fibers of which are arranged along the radial direction of the blood vessel, the mechanical properties of the artificial blood vessel are enhanced, and the resistance to radial blood pressure impact and the durability are improved. BRIEF DESCRIPTION OF DRAWINGS

[0036] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or prior art description. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can also be obtained according to the structures shown in the drawings without creative labor for those skilled in the art.

[0037] Figure 1 A physical diagram of the degradable piezoelectric artificial blood vessel in example 4 provided by the present application implanted in the carotid artery of a rabbit;

[0038] Figure 2 A structural schematic diagram of the degradable piezoelectric artificial blood vessel in example 1 provided by the present application;

[0039] Figure 3 A structural schematic diagram of the piezoelectric functional layer in the degradable piezoelectric artificial blood vessel in example 1 provided by the present application;

[0040] Figure 4 A polarization electric hysteresis loop diagram and a dielectric constant diagram of the ImClO4 material in example 4 provided by the present application;

[0041] Figure 5 A result diagram of a toxicity test of ImClO4 with different concentrations on human umbilical vein endothelial cells in example 4 provided by the present application;

[0042] Figure 6 A result diagram of a toxicity test of ImClO4 with different concentrations on smooth muscle cells in example 4 provided by the present application;

[0043] Figure 7 Micrograph of the fiber membrane with single orientation in Example 4 provided by the present application;

[0044] Figure 8 Tensile strain curve of the fiber membrane with and without orientation in Example 4 provided by the present application;

[0045] Figure 9 Real-time electrical signal diagram of the degradable piezoelectric artificial blood vessel in Example 4 provided by the present application along with the blood flow after being implanted in vivo;

[0046] Figure 10 Natural degradation result diagram of the degradable piezoelectric artificial blood vessel in Example 4 provided by the present application in 0.5M sodium hydroxide at 37℃ environment.

[0047] Explanation of the reference signs:

[0048] 100, degradable piezoelectric artificial blood vessel; 1, first guide layer; 2, piezoelectric functional layer; 21, fiber membrane; 22, electrode; 23, wire; 24, waterproof layer; 3, second guide layer.

[0049] The implementation, functional features and advantages of the present application will be further described with reference to the accompanying drawings in conjunction with the embodiments. DETAILED DESCRIPTION

[0050] In order to make the purpose, technical solutions and advantages of the embodiments of the present application more clear, the technical solutions in the embodiments of the present application will be described clearly and completely below. The specific conditions not mentioned in the embodiments are carried out according to the conventional conditions or the conditions suggested by the manufacturer. The reagents or instruments not mentioned by the manufacturer are all conventional products that can be purchased in the market. In addition, the meaning of "and / or" appearing in the full text includes three parallel solutions. Taking "A and / or B" as an example, it includes A solution, or B solution, or A and B solutions. In addition, the technical solutions of each embodiment can be combined with each other, but it must be based on the fact that the ordinary skilled in the art can realize it. When the combination of technical solutions appears contradictory or unachievable, it should be considered that the combination of technical solutions does not exist and is not within the protection scope of the present application. Based on the embodiments in the present application, all other embodiments obtained by the ordinary skilled in the art without creative labor are within the protection scope of the present application.

[0051] In the treatment of vascular lesions, artificial blood vessel replacement is the only solution to rescue critically ill patients, but artificial blood vessels often have risks such as embolization and calcification after being implanted in the body. Vascular calcification can reduce vascular elasticity and increase vascular elastic modulus, and thrombosis can cause blood flow to slow down, both of which can cause abnormal blood pressure at the artificial blood vessel replacement site. Therefore, early detection of postoperative abnormalities, timely warning and effective intervention are the key to improving the success rate of artificial blood vessel replacement surgery.

[0052] At present, the abnormal blood pressure condition is mainly detected by implanting an intelligent artificial blood vessel with real-time blood pressure monitoring function. Such degradable piezoelectric artificial blood vessels can realize in-situ blood pressure monitoring.

[0053] However, the existing degradable piezoelectric artificial blood vessels have the following defects: 1) Traditional piezoelectric materials such as lead zirconate titanate (PZT) and barium titanate (BTO) represented by piezoelectric ceramics contain heavy metal elements, have poor bioactivity, low endothelialization degree and poor compliance, and piezoelectric polymers represented by polyvinylidene fluoride (PVDF) are usually not degradable. The above-mentioned materials do not meet the requirements of artificial blood vessels, and usually need to be implanted directly into the blood vessel, which requires a second operation to remove; 2) The stiffness of traditional piezoelectric materials is much greater than that of natural blood vessels in the human body, and the implantation of hard piezoelectric materials such as piezoelectric ceramics may reduce the mechanical strength of flexible artificial blood vessels and cause the blood vessels to become rigid, making them prone to cracking and failure under the impact of multiple blood pressures; 3) One of the basic characteristics of piezoelectric materials is the ability to generate electric charge under mechanical stress (i.e. piezoelectric effect). After the piezoelectric sensor is implanted in the body fluid environment, the bound electric charge generated on the surface of the piezoelectric material in the piezoelectric sensor can easily attract and combine with the counterions in the body fluid, causing the electric charge to be quickly neutralized. This not only weakens or even eliminates the original piezoelectric effect, but also seriously affects its sensitivity, and even causes the sensor to fail, affecting the monitoring effect.

[0054] Therefore, the present application provides a degradable piezoelectric artificial blood vessel 100, comprising:

[0055] A first guide layer 1 is provided in a tubular shape, which defines a pipeline channel for blood flow, for guiding blood flow, cell adhesion and tissue repair;

[0056] A piezoelectric functional layer 2 is sleeved on the outside of the first guide layer 1, and the piezoelectric functional layer 2 is used to convert the radial force signal of blood pressure into an electric signal; and

[0057] A second guide layer 3 is provided on the outside of the piezoelectric functional layer 2, and the second guide layer 3 is used to fix the piezoelectric functional layer 2 and guide cell adhesion and tissue repair;

[0058] The piezoelectric functional layer 2 includes a fiber membrane 21 with adsorbed molecular ferroelectric material, and at least part of the fibers in the fiber membrane 21 are arranged in the circumferential direction of the blood vessel.

[0059] In the technical scheme, the degradable piezoelectric artificial blood vessel 100 includes a first guide layer 1 in a tubular shape, which defines a pipeline channel for blood circulation, and is used for guiding blood flow, cell adhesion and tissue repair; a piezoelectric functional layer 2, which is sleeved outside the first guide layer 1, is used for converting the radial force signal of blood pressure into an electric signal; and a second guide layer 3, which is arranged outside the piezoelectric functional layer 2, is used for fixing the piezoelectric functional layer 2 and guiding cell adhesion and tissue repair; the above design avoids direct contact between the molecular ferroelectric material and the body fluid environment, facilitates the function of the molecular ferroelectric material in extracting signals in the body, improves the durability, sensitivity and accuracy of the molecular ferroelectric material, and can realize in-situ real-time monitoring of postoperative blood pressure. The piezoelectric functional layer 2 includes a fiber membrane 21 modified by a molecular ferroelectric material, and at least part of the fibers in the fiber membrane 21 are arranged in the radial direction of the blood vessel, which enhances the mechanical properties of the artificial blood vessel, increases the ability of the artificial blood vessel to resist radial blood pressure impact, and improves the durability of the artificial blood vessel; the molecular ferroelectric material is a biocompatible material with good sensitivity, which improves the sensitivity of blood pressure detection. Figure 1 A physical diagram of the degradable piezoelectric artificial blood vessel 100 implanted in the carotid artery of a rabbit.

[0060] As a new type of ferroelectric material, the molecular ferroelectric body has the characteristics of solution preparation, no high-temperature sintering, low cost and simple process. Most molecular ferroelectric bodies can be dissolved in inorganic solutions and are suitable for degradable and recyclable electronic products. The molecular ferroelectric material can spontaneously convert mechanical energy into electric energy without external power supply.

[0061] In some embodiments of the present application, the thickness of the first guide layer 1 is 30 μm to 100 μm. The thickness of the first guide layer 1 can be 30 μm, 50 μm or 100 μm, and the thickness of the first guide layer 1 in the appropriate range can ensure cell adhesion and test sensitivity; when the first guide layer 1 is too thick, the blood flow impact will cause part of the radial pressure to be absorbed, thereby weakening the force on the piezoelectric functional layer 2, and thus reducing the test sensitivity.

[0062] In some embodiments of the present application, the thickness of the piezoelectric functional layer 2 is 100 μm to 200 μm. The thickness of the piezoelectric functional layer 2 can be 100 μm, 150 μm or 200 μm, and the thickness of the piezoelectric functional layer 2 in the appropriate range can ensure good test sensitivity and blood vessel mechanical properties.

[0063] In some embodiments of the present application, the thickness of the second guide layer 3 is 20-50 μm. The thickness of the second guide layer 3 can be 20 μm, 30 μm or 50 μm, and the thickness of the second guide layer 3 in the appropriate range can ensure good waterproofness and mechanical properties of the blood vessel.

[0064] In some embodiments of the present application, the inner diameter of the degradable piezoelectric artificial blood vessel 100 is 2-6 mm. The inner diameter of the degradable piezoelectric artificial blood vessel 100 can be 2 mm, 5 mm or 6 mm, and the inner diameter in the appropriate range can ensure that the piezoelectric artificial blood vessel extracts signals efficiently in the body, while also helping to promote the adhesion and growth of endothelial cells, thereby maintaining the biocompatibility and functionality of the blood vessel inner wall.

[0065] In some embodiments of the present application, the piezoelectric functional layer 2 further comprises an electrode 22, a wire 23 and a waterproof layer 24, the electrode 22 and the wire 23 are arranged on both sides of the fiber membrane 21, and the waterproof layer 24 is arranged on the side of the electrode 22 away from the fiber membrane 21.

[0066] The electrode 22 comprises a molybdenum electrode, which combines the characteristics of biocompatibility and degradability.

[0067] The wire 23 comprises a molybdenum wire, and molybdenum is a metal with strong corrosion resistance and good biocompatibility, which is especially suitable for use as a conductive path in a wet environment in the body. The high melting point and good electrical conductivity of molybdenum ensure stable transmission of electrical signals even in complex or dynamic physiological environments, providing reliable connection protection for the effective operation of the piezoelectric functional layer 2.

[0068] The waterproof layer 24 comprises a polylactic acid film, which is a dense and hydrophobic degradable material. As the waterproof layer 24, it has good biocompatibility, and the waterproof layer 24 wraps the fiber membrane 21 modified with molecular ferroelectric material, which can avoid the contact of the molecular ferroelectric material in the fiber membrane 21 modified with molecular ferroelectric material with the blood environment or the body fluid environment, avoid the dissolution of the molecular ferroelectric material in water, thereby reducing the probability of leakage failure of the molecular ferroelectric material, improving the charge utilization rate, and improving the stability of the molecular ferroelectric material and the sensitivity of the sensor.

[0069] The present application also provides a preparation method of the above-mentioned degradable piezoelectric artificial blood vessel 100, comprising the following steps:

[0070] S10, mixing the oriented fiber membrane with the molecular ferroelectric material solution, drying, and precipitating crystals to obtain the piezoelectric functional layer 2;

[0071] S20, obtaining the first guide layer 1 and the second guide layer 3, nesting the piezoelectric functional layer 2 between the first guide layer 1 and the second guide layer 3, and making the first guide layer 1, the piezoelectric functional layer 2 and the second guide layer 3 inseparable in turn to obtain the degradable piezoelectric artificial blood vessel 100.

[0072] Step S10 includes the following steps:

[0073] S11, soaking the oriented fiber film in a molecular ferroelectric solution, drying, and precipitating crystals to obtain a piezoelectric film;

[0074] S12, fixing the wire 23 and the electrode 22 on both sides of the piezoelectric film to obtain the first piezoelectric functional layer;

[0075] S13, fixing the waterproof layer 24 on both sides of the first piezoelectric functional layer to obtain the piezoelectric functional layer 2.

[0076] In step S11, the thickness of the oriented fiber film is 100-200 μm, and preferably 200 μm. The oriented fiber film is soaked in a molecular ferroelectric solution to prepare a piezoelectric film by drying and crystallization, which facilitates the orientation of the molecular ferroelectric to crystallize, thereby enhancing the piezoelectric performance of the piezoelectric film.

[0077] In step S12, the fixing method includes hot pressing technology, the hot pressing temperature is 100-120℃, and the hot pressing time is 5-10 minutes. The hot pressing temperature can be 100℃, 110℃ or 120℃, and the hot pressing time can be 5 minutes, 7 minutes or 10 minutes. The hot pressing temperature and time in the appropriate range can ensure that the wire 23 and the electrode 22 are more closely attached to the piezoelectric film, thereby exerting its piezoelectric effect and improving the detection sensitivity.

[0078] In step S13, the preparation method of the waterproof layer 24 includes solution flow casting film forming method, and compared with the first guide layer 1 and the second guide layer 3, the waterproof layer 24 is more dense.

[0079] In step S10, the drying temperature is 20-70℃, and the drying temperature can be 30℃, 50℃ or 70℃. The drying temperature in the appropriate range can ensure the drying degree of the piezoelectric functional layer 2, which is beneficial to subsequent implantation in the living body. Preferably, the drying temperature is 20-40℃.

[0080] It should be noted that in step S10, the fibers in the oriented fiber film can be unidirectional or multidirectional, i.e. multiple orientations, as long as the ability of the artificial blood vessel to resist radial blood pressure impact is increased.

[0081] In the technical scheme of the present application, preferably, all the materials used are biocompatible and degradable in vivo, which is beneficial to cell regeneration after surgery, can be naturally degraded in vivo after the function of early monitoring is completed, does not need to be removed by secondary surgery, improves the success rate of surgery, and reduces the pain of patients.

[0082] In some embodiments of the present application, in step S10, the oriented fiber membrane comprises a single oriented fiber membrane. Compared with other membranes containing randomly oriented or multiple oriented fibers, the single oriented fiber membrane is characterized in that all the fibers are arranged in the same direction in an orderly manner. The single orientation of the fibers can significantly enhance the tensile strength and elastic modulus of the membrane in the fiber orientation direction. This is because the arrangement of the fibers forms a highly ordered structure, which can more effectively disperse stress and reduce the generation and propagation of cracks, thereby improving the overall durability of the material. Secondly, the fibers are arranged in the same direction, which guides the crystallization of the molecular ferroelectric solution along the fiber arrangement, enhances the orientation of the molecular ferroelectric, and thus improves the piezoelectric performance.

[0083] In some embodiments of the present application, in step S10, the raw material of the oriented fiber membrane comprises a natural polymer material, and the natural polymer material comprises at least one of silk fibroin, cellulose, chitosan, collagen, hyaluronic acid and gelatin. That is, the natural polymer material can contain any one of silk fibroin, cellulose, chitosan, collagen, hyaluronic acid and gelatin, or can contain two or more of silk fibroin, cellulose, chitosan, collagen, hyaluronic acid and gelatin at the same time, all of which belong to the protection scope of the present application. By providing the oriented fiber membrane, the mechanical properties and conductive properties of the oriented fiber membrane are better.

[0084] In some embodiments of the present application, the preparation method of the oriented fiber membrane comprises electrospinning technology. Compared with other methods, the electrospinning technology can prepare fibers with a diameter as low as nanometers, which is beneficial to enhancing the sensing performance of the fibers.

[0085] In some embodiments of the present application, the inner diameter of the metal needle of the electrospinning technology is 0.4-0.6 mm; the push injection speed of the electrospinning technology is 1.0-2.0 mL / h; the spinning voltage of the electrospinning technology is 10-15 kV; the receiving distance of the electrospinning technology is 10-15 cm; the spinning temperature of the electrospinning technology is 20-40℃; and the spinning humidity of the electrospinning technology is <5%.

[0086] The inner diameter of the metal needle can be 0.4 mm, 0.5 mm or 0.6 mm; the injection speed can be 1.0-2.0 mL / h, 1.0-2.0 mL / h or 1.0-2.0 mL / h; the spinning voltage can be 10-15 kV, 10-15 kV or 10-15 kV; the receiving distance can be 10-15 cm, 10-15 cm or 10-15 cm; the spinning temperature can be 20-40℃, 20-40℃ or 20-40℃; and the spinning humidity can be 4%, 3% or 1%. The parameters of the above electrospinning technology can ensure that a stable, continuous and uniform fiber bundle is spun within a suitable range.

[0087] In some embodiments of the present application, in step S10, the molecular ferroelectric material includes any one of ImClO4 or [Hdabco]ClO4. The [Hdabco]ClO4 is triethylenediamine perchlorate, and the ImClO4 is imidazole perchlorate. The ImClO4 has excellent piezoelectric properties, and its piezoelectric voltage constant g 33 = 257 x 10 -3 Vm / N, which is about 6 times that of traditional lead zirconate titanate (PZT, g 33 = 40 x 10 -3 Vm / N). The ImClO4 has an ultra-low coercive field (Ec = 6.4 kV / cm, which is Figure 4 100 times smaller than that of non-degradable piezoelectric polymer PVDF (Ec = 700 kV / cm), which means that the ImClO4 only needs a very small external electric field to be fully polarized, showing excellent piezoelectric properties. At the same time, the ImClO4 has good cell compatibility and blood compatibility. When the ImClO4 is used as an analysis ferroelectric material, the obtained degradable piezoelectric artificial blood vessel 100 can realize high-sensitivity blood pressure detection while not affecting the full degradation characteristics and mechanical strength of the artificial blood vessel.

[0088] In some embodiments of the present application, in step S10, the mass concentration of the molecular ferroelectric material in the molecular ferroelectric material solution is 0.05-0.6 g / mL. The mass concentration of the molecular ferroelectric material in the molecular ferroelectric material solution can be 0.05 g / mL, 0.2 g / mL or 0.6 g / mL, and the mass concentration within a suitable range can ensure that the degradable piezoelectric artificial blood vessel 100 material has good mechanical strength and durability. Preferably, the concentration is 0.4 g / mL.

[0089] In some embodiments of the present application, in step S20, the method for obtaining the first guide layer 1 includes electrospinning technology, and the method for obtaining the second guide layer 3 includes electrospinning technology. The electrospinning technology can better control the size of the first guide layer 1 and the second guide layer 3.

[0090] It should be noted that the porous luminal surface of the artificial blood vessel plays an important role in stabilizing the intima and helping cell infiltration: the porous luminal surface enhances the permeability of the tissue around the graft, serving as an anchoring effect.

[0091] In some embodiments of the present application, in step S20, the raw material of the first guide layer 1 comprises at least one of polylactic acid and polycaprolactone, and the raw material of the second guide layer 3 comprises at least one of polylactic acid and polycaprolactone. That is, the raw material of the first guide layer 1 can be polylactic acid, polycaprolactone, or a mixture of polylactic acid and polycaprolactone. Preferably, when the raw material of the first guide layer 1 is a mixture of polylactic acid and polycaprolactone, the mass ratio of the polylactic acid to the polycaprolactone is 1:1.5, and the mass ratio of the polylactic acid to the polycaprolactone can be 1:1, 1:1.5, or 1:2. The mass ratio within the appropriate range can ensure that the first guide layer 1 has biocompatibility and degradability while improving the compliance of the artificial blood vessel. Similarly, the raw material of the second guide layer 3 can be polylactic acid, polycaprolactone, or a mixture of polylactic acid and polycaprolactone. When the raw materials of the first guide layer 1 and the second guide layer 3 are both mixtures of polylactic acid and polycaprolactone, the mass ratio of polylactic acid to polycaprolactone in the second guide layer 3 and the first guide layer 1 can be different or the same. Preferably, the mass ratio is 1:1.5.

[0092] The technical solutions of the present application will be further described in detail below in combination with specific embodiments and drawings. It should be understood that the following embodiments are only used to explain the present application and not to limit the present application.

[0093] Embodiment 1

[0094] A degradable piezoelectric artificial blood vessel 100, comprising:

[0095] A first guide layer 1 in a tubular shape, which defines a pipeline channel for blood circulation, for guiding blood flow, cell adhesion and tissue repair;

[0096] A piezoelectric functional layer 2 arranged outside the first guide layer 1, the piezoelectric functional layer 2 is used to convert the radial force signal of blood pressure into an electrical signal; and,

[0097] A second guide layer 3 arranged outside the piezoelectric functional layer 2, the second guide layer 3 is used to fix the piezoelectric functional layer 2 and guide cell adhesion and tissue repair;

[0098] The piezoelectric functional layer 2 comprises an ImClO4 modified fiber membrane 21, and the fibers in the fiber membrane 21 are arranged in the radial direction of the blood vessel.

[0099] The thickness of the first guide layer 1 is 30 μm; the thickness of the piezoelectric functional layer 2 is 100 μm; the thickness of the second guide layer 3 is 20 μm; and the inner diameter of the degradable piezoelectric artificial blood vessel 100 is 2 mm.

[0100] The structure schematic diagram of the degradable piezoelectric artificial blood vessel 100 and the structure schematic diagram of the piezoelectric functional layer 2 of the embodiment are shown in Figure 1 and Figure 2 respectively.

[0101] Embodiment 2

[0102] Compared with Embodiment 1, except that the thickness of the first guide layer 1 is 50 μm; the thickness of the piezoelectric functional layer 2 is 155 μm; the thickness of the second guide layer 3 is 33 μm; and the inner diameter of the degradable piezoelectric artificial blood vessel 100 is 3.5 mm, other conditions are the same as those in Embodiment 1.

[0103] Embodiment 3

[0104] Compared with Embodiment 1, except that the thickness of the first guide layer 1 is 100 μm; the thickness of the piezoelectric functional layer 2 is 200 μm; the thickness of the second guide layer 3 is 50 μm; and the inner diameter of the degradable piezoelectric artificial blood vessel 100 is 6 mm, other conditions are the same as those in Embodiment 1.

[0105] Embodiment 4

[0106] A degradable piezoelectric artificial blood vessel 100 and a preparation method thereof, comprising the following steps:

[0107] 1) Dissolve regenerated silk fibroin in hexafluoroisopropanol, and add polycaprolactone to prepare a mixed solution; in this example, the mass fraction of regenerated silk fibroin is 15%, the mass fraction of polycaprolactone is 5%, and the solvent is hexafluoroisopropanol; the electrospinning receiving substrate is aluminum foil, and the electrospinning parameters are as follows: the inner diameter of the metal needle is 0.5 mm, the injection speed is 2.0 mL / h, the spinning voltage is 15 kV, the receiving distance is 15 cm, the spinning temperature is 40°C, and the thickness of the degradable nanofiber membrane is 100 μm.

[0108] 2) Cut the above-mentioned fiber membrane into a square of 3 cm×3 cm, completely immerse it in a molecular ferroelectric ImClO4 solution, dry it, precipitate crystals, and obtain a piezoelectric membrane. The concentration of the ImClO4 solution is 0.5 g / mL, the soaking time is 30 minutes, the precipitation temperature is 50°C, and the precipitation time is 15 minutes.

[0109] 3) The lead wire 23 and the electrode 22 are thermally pressed and fixed on both sides of the piezoelectric film to obtain a first piezoelectric functional layer. The electrode used is a 2 cm x 2 cm polylactic acid-pyrrole electrode, the lead wire is a molybdenum lead wire, the thermal pressing temperature is 120°C, and the time is 5 minutes.

[0110] 4) A polylactic acid film waterproof layer 24 with a thickness of 50 μm is prepared by a solution flow casting method, the polylactic acid film waterproof layer 24 is fixed on both sides of the first piezoelectric functional layer, and the sealing machine is used for sealing to complete the packaging of the first piezoelectric functional layer to obtain a piezoelectric functional layer 2.

[0111] 5) Polylactic acid is dissolved in hexafluoroisopropanol to prepare a mixed solution. The mass fraction of polylactic acid is 15%. The spinneret receiver is replaced with a metal rod with a diameter of 2 mm, and the electrospinning voltage is 10 kV. A first guide layer 1 and a second guide layer 3 with an inner diameter of 2 mm and a thickness of 50 μm are prepared.

[0112] 6) The piezoelectric functional layer 2 obtained in step 4) is rolled into a tubular shape and fixed between the first guide layer 1 and the second guide layer 3 obtained in step 5).

[0113] Example 5

[0114] Compared with Example 4, the following differences exist:

[0115] In step 1), polylactic acid is used instead of polycaprolactone, the mass fraction of regenerated silk fibroin is 10%, the mass fraction of polylactic acid is 5%, and the inner diameter of the metal needle is 0.4 mm;

[0116] In step 2), the crystallization temperature is 40°C, and the time is 20 minutes;

[0117] In step 3), the thermal pressing temperature is 100°C, and the time is 8 minutes;

[0118] In step 5), the spinneret receiver is replaced with a metal rod with a diameter of 2.5 mm.

[0119] Comparative Example 1

[0120] Compared with Example 4, in addition to the use of unoriented fiber film, the other aspects are the same as those of Example 4.

[0121] Performance Test

[0122] The ImClO4 material in Example 4 is detected by the electric hysteresis loop, and the detection method is the Sawyer-Tower method, and the results are shown in Figure 4 .

[0123] As can be seen from Figure 4 , the imidazole perchlorate is a standard square electric hysteresis loop, and the saturation polarization at room temperature (293 K) is 9.6 μC / cm2 ImClO4 can reach saturation polarization under an electric field of 15 kV / cm, which is 2 orders of magnitude lower than that of ferroelectric polymers, indicating that the saturation polarization electric field of ImClO4 is lower than that of ferroelectric polymers. Due to the low saturation polarization electric field of ImClO4, the material exhibits super-high electric clamping strength.

[0124] The biocompatibility of the imidazole perchlorate material in Example 4 was detected by CCK-8 cytotoxicity test, and the results are shown in Figure 5 、 Figure 6 .

[0125] It can be seen from Figure 5 that the imidazole perchlorate concentration of 1 mg / mL can be considered as non-toxic to endothelial cells; it can be seen from Figure 6 that the imidazole perchlorate concentration of 0.1 mg / mL can be considered as non-toxic to smooth muscle cells.

[0126] The fibrous membrane in Example 4 was observed by electron microscopy, and the results are shown in Figure 7 .

[0127] It can be seen from Figure 7 that the fibers form a uniform oriented structure.

[0128] The fibrous membrane in Example 4 and Comparative Example 1 was subjected to mechanical testing, and the results are shown in Figure 8 .

[0129] It can be seen from Figure 8 that the method of oriented spinning gives the spinning membrane stronger mechanical properties.

[0130] After the degradable piezoelectric artificial blood vessel 100 in Example 4 was implanted into the body through a rabbit carotid artery replacement operation, the real-time electrical signal graph with blood flow was detected. The results are shown in Figure 9 .

[0131] It can be seen from Figure 9 that the integrated piezoelectric blood vessel can detect the heart rate, and through calculation, it can match the heart rate of the rabbit under anesthesia.

[0132] The degradable piezoelectric artificial blood vessel 100 in Example 4 was placed in 0.5M sodium hydroxide at 37°C and naturally degraded, and the results are shown in Figure 10 .

[0133] It can be seen from Figure 10 that the structure of the degradable piezoelectric artificial blood vessel 100 is almost completely degraded after 4 days.

[0134] In conclusion, the degradable piezoelectric artificial blood vessel 100 has good biocompatibility, strong mechanical properties and blood pressure resistance, and detection sensitivity.

[0135] The above merely describes the preferred embodiments of the present application, and is not intended to limit the patent scope of the present application. The present application can have various modifications and changes for those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the patent protection scope of the present application.

Claims

1. A degradable piezoelectric vascular graft, characterized by, The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel.

2. The degradable piezoelectric vascular graft of claim 1, wherein, The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel.

3. A method of producing a degradable piezoelectric vascular graft according to any one of claims 1 to 2, characterized by, The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel.

4. The method for preparing the biodegradable piezoelectric artificial blood vessel as described in claim 3, characterized in that, The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel.

5. The method for preparing the biodegradable piezoelectric artificial blood vessel as described in claim 4, characterized in that, The application relates to a degradable piezoelectric artificial blood vessel.

6. The method of claim 5, wherein the biodegradable piezoelectric vascular graft is prepared by the steps of: The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel.

7. The method for preparing the biodegradable piezoelectric artificial blood vessel as described in claim 3, characterized in that, The application relates to a degradable piezoelectric artificial blood vessel. The application relates to a degradable piezoelectric artificial blood vessel.

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