CN117918997A - Artificial electronic blood vessel and preparation method thereof - Google Patents
Artificial electronic blood vessel and preparation method thereof Download PDFInfo
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- CN117918997A CN117918997A CN202410190512.2A CN202410190512A CN117918997A CN 117918997 A CN117918997 A CN 117918997A CN 202410190512 A CN202410190512 A CN 202410190512A CN 117918997 A CN117918997 A CN 117918997A
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Abstract
The application discloses an artificial electronic blood vessel and a preparation method thereof, wherein the artificial electronic blood vessel comprises an artificial blood vessel and a blood flow monitoring device, the artificial blood vessel replaces a damaged blood vessel to reconstruct blood circulation, the blood flow monitoring device is wrapped on the periphery of the artificial blood vessel, the blood flow monitoring device monitors the blood flow in the artificial blood vessel in the arterial vascular system in the form of pulse wave, and then index information is output to indicate the blood flow health condition in the artificial blood vessel. Thereby realizing the real-time blood flow monitoring of the artificial blood vessel in situ after operation. The artificial electronic blood vessel provided by the application can timely discover the thrombosis phenomenon at the vascular site of the human tube after operation, and provides a foundation for the discovery and repair of early injury of vascular grafts. The blood flow condition can be monitored in real time through the integrated artificial electronic blood vessel after operation, so that abnormality is found in time and treatment is given, the risk of postoperative thrombus occurrence is reduced, and the long-term patency rate of the small-caliber artificial blood vessel is improved.
Description
Technical Field
The application relates to the technical field of biomedicine, in particular to an artificial electronic blood vessel and a preparation method thereof.
Background
Cardiovascular disease is now one of the worldwide diseases with high mortality, and the development of small diameter vascular prostheses (diameter <6 mm) is of great importance for arterial bypass surgery. However, vascular prostheses often cause platelet adhesion after implantation due to the delayed formation of endothelialization, thereby initiating thrombosis. Clinical data show that acute thrombosis of bypass parts can occur within 72 hours after operation, restenosis can even occur within one year, and the probability is 40%. Secondary occlusion often requires complex surgery with mortality rates as high as 5% and only 25% of failed grafts can be effectively saved.
Clinical studies have shown that less invasive procedures including drug delivery and local angioplasty may be helpful in repairing early lesions of vascular grafts at an early stage, thereby minimizing the need for secondary surgery. Thus, in early stages, particularly during the first week, timely identification of abnormalities at the implant site is critical for postoperative recovery. Achieving long-term and in-situ monitoring of blood flow signals in the human body in a complex physiological environment after surgery is a great challenge.
Disclosure of Invention
The application provides an artificial electronic blood vessel and a preparation method thereof, which are used for realizing in-situ monitoring of blood flow signals implanted into the blood vessel.
In a first aspect, the present application provides an artificial electronic blood vessel comprising: the blood flow monitoring device is wrapped on the periphery of the artificial blood vessel; the artificial blood vessel is used for replacing a damaged blood vessel to reconstruct blood circulation; the blood flow monitoring device is used for monitoring the blood flow in the arterial vascular system in the form of pulse waves in the artificial blood vessel and outputting index information for representing the blood flow health condition in the artificial blood vessel.
In a second aspect, the present application provides a method for preparing an artificial blood vessel of an artificial electronic blood vessel, the method comprising:
dissolving TPU powder into a mixed solution of dimethylformamide DMF and dichloromethane to obtain TPU spinning solution; loading TPU spinning solution into an injector, selecting a stainless steel rod as a fiber collector, applying constant voltage between a needle head and the stainless steel rod collector, rotating a stainless steel receiving rod at a set first rotating speed, and collecting and setting a first time length to obtain tubular TPU nanofibers of the artificial blood vessel;
Dissolving PCL powder in isopropanol HFIP to obtain PCL spinning solution; filling PCL spinning solution into an injector, selecting the tubular TPU nanofiber obtained by the method as a fiber collector, wrapping two ends of the fiber collector by using tinfoil to obtain two ends of electrodes, applying constant voltage between a needle head and the fiber collector, collecting the axially ordered PCL nanofiber at a set second rotating speed for a set second period of time, obtaining the tubular PCL nanofiber of the artificial blood vessel, and overturning the tubular TPU nanofiber and the tubular PCL nanofiber into an inner layer and an outer layer of the tubular PCL nanofiber integrally to obtain the artificial blood vessel.
In a third aspect, the present application provides a method for preparing a blood flow monitoring device for an artificial electronic blood vessel, the method comprising:
Polypyrrole PPy with a nanowire structure on the surface is used as a friction layer and an electrode; a PDMS film with a nanowire structure on the surface is used as another friction layer; gold nanofibers attached to the back of the PDMS film are used as electrodes; the whole device is packaged by polyurethane adhesive tape/Parylene and is wrapped on the surface of an artificial blood vessel;
The gold nanofiber is prepared by sputtering gold particles on the surface of an ordered polyvinyl alcohol PVA nanofiber prepared by electrostatic spinning, transferring the gold particles to the back surface of PDMS in water, obtaining a gold nanofiber electrode with good adhesion on the back surface of PDMS after transferring, packaging the whole device by a polyurethane adhesive tape, and sputtering a Parylene coating on the surface.
The application provides an artificial electronic blood vessel and a preparation method thereof, wherein the artificial electronic blood vessel comprises: the blood flow monitoring device is wrapped on the periphery of the artificial blood vessel; the artificial blood vessel is used for replacing a damaged blood vessel to reconstruct blood circulation; the blood flow monitoring device is used for monitoring the blood flow in the arterial vascular system in the form of pulse waves in the artificial blood vessel and outputting index information for representing the blood flow health condition in the artificial blood vessel.
The technical scheme has the following advantages or beneficial effects:
The artificial electronic blood vessel comprises an artificial blood vessel and a blood flow monitoring device, wherein the artificial blood vessel replaces a damaged blood vessel to reconstruct blood circulation, the blood flow monitoring device is wrapped on the periphery of the artificial blood vessel, monitors blood flow in the artificial blood vessel in the arterial vascular system in a pulse wave mode, and then outputs index information to indicate the blood flow health condition in the artificial blood vessel. Thereby realizing the real-time blood flow monitoring of the artificial blood vessel in situ after operation. The artificial electronic blood vessel provided by the application can timely discover the thrombosis phenomenon at the vascular site of the human tube after operation, and provides a foundation for the discovery and repair of early injury of vascular grafts. The blood flow condition can be monitored in real time through the integrated artificial electronic blood vessel after operation, so that abnormality is found in time and treatment is given, the risk of postoperative thrombus occurrence is reduced, and the long-term patency rate of the small-caliber artificial blood vessel is improved.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are needed in the description of the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of an artificial electronic blood vessel structure provided by the application;
FIG. 2 is a schematic diagram of an artificial blood vessel structure provided by the application;
FIG. 3 is a schematic diagram of a blood flow monitor device according to the present application;
FIG. 4 is a schematic view of an artificial electronic blood vessel structure provided by the application;
FIG. 5 is a schematic diagram of the process for preparing an artificial blood vessel according to the present application;
FIG. 6 is a schematic diagram of a blood flow monitoring device according to the present application;
FIG. 7 is a schematic diagram of an artificial electronic blood vessel according to the present application;
FIG. 8 is a schematic diagram of an artificial electronic blood vessel according to the present application;
FIG. 9 is a cross-sectional view of an artificial blood vessel and a scanning electron microscope SEM schematic of an ordered PCL and an unordered TPU;
FIG. 10 is a schematic view of an artificial blood vessel prepared by electrostatic spinning of PCL/TPU;
FIG. 11 is a schematic view of a Scanning Electron Microscope (SEM) of the blood flow monitor device according to the present application;
FIG. 12 is a schematic view of a blood vessel graft and pulse wave and respiratory wave provided by the present application;
FIG. 13 is a schematic diagram showing the repair and endothelialization process of different blood vessels according to the present application;
Fig. 14 is a schematic diagram of blood flow monitoring provided by the present application.
Detailed Description
For the purposes of making the objects and embodiments of the present application more apparent, an exemplary embodiment of the present application will be described in detail below with reference to the accompanying drawings in which exemplary embodiments of the present application are illustrated, it being apparent that the exemplary embodiments described are only some, but not all, of the embodiments of the present application.
It should be noted that the brief description of the terminology in the present application is for the purpose of facilitating understanding of the embodiments described below only and is not intended to limit the embodiments of the present application. Unless otherwise indicated, these terms should be construed in their ordinary and customary meaning.
The terms first, second, third and the like in the description and in the claims and in the above-described figures are used for distinguishing between similar or similar objects or entities and not necessarily for describing a particular sequential or chronological order, unless otherwise indicated. It is to be understood that the terms so used are interchangeable under appropriate circumstances.
The terms "comprises," "comprising," and "having," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a product or apparatus that comprises a list of elements is not necessarily limited to all elements explicitly listed, but may include other elements not expressly listed or inherent to such product or apparatus.
The term "module" refers to any known or later developed hardware, software, firmware, artificial intelligence, fuzzy logic, or combination of hardware or/and software code that is capable of performing the function associated with that element.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present application, and not for limiting the same; although the application has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the application.
The foregoing description, for purposes of explanation, has been presented in conjunction with specific embodiments. The illustrative discussions above are not intended to be exhaustive or to limit the embodiments to the precise forms disclosed above. Many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles and the practical application, to thereby enable others skilled in the art to best utilize the embodiments and various embodiments with various modifications as are suited to the particular use contemplated.
Fig. 1 is a schematic view of an artificial electronic blood vessel structure provided by the present application, where the artificial electronic blood vessel includes: a blood vessel 11 and a blood flow monitoring device 12 wrapped around the periphery of the blood vessel;
The artificial blood vessel 11 is used for replacing a damaged blood vessel to reconstruct blood circulation;
The blood flow monitoring device 12 is used for monitoring the blood flow in the arterial vascular system in the form of pulse waves in the artificial blood vessel and outputting index information for representing the blood flow health condition in the artificial blood vessel.
The application aims to provide an artificial electronic blood vessel, which can timely discover thrombus and perform intervention treatment through real-time postoperative blood flow monitoring so as to solve the problem of low long-term patency rate of a small-caliber artificial blood vessel. As shown in fig. 1, the inside of the artificial blood vessel is used to replace the damaged blood vessel for revascularization during surgery. Damaged blood vessels include tissue damaged or diseased blood vessels. Abnormal blood circulation in the damaged blood vessel, normal blood flow in the artificial blood vessel after the artificial blood vessel replaces the damaged blood vessel, and blood circulation reconstruction is realized. The artificial electronic blood vessel is positioned at the outer side, is attached to and wrapped on the blood flow monitoring device at the periphery of the artificial blood vessel, and is used for realizing real-time monitoring on the blood flow condition in the artificial blood vessel.
Specifically, the blood flow monitoring device monitors the blood flow in the arterial vascular system in the form of pulse waves within the artificial blood vessel, and outputs index information for characterizing the blood flow health condition within the artificial blood vessel. In particular, the blood flow monitoring device may be a mechanical sensor, the blood flow monitoring device operating based on triboelectric effects. Along with the alternate contraction and relaxation of the heart, blood flows in the whole arterial vascular system in the form of pulse waves, is perceived by a blood flow monitoring device in the form of pressure waves, and then outputs an electric signal, wherein the electric signal is index information capable of representing the blood flow health condition in an artificial blood vessel. Optionally, the electrical signal is transmitted to a blood flow monitoring device such as an electrometer in a wired manner or transmitted to a blood flow monitoring device such as a mobile terminal in a wireless manner, where the mobile terminal is, for example, a mobile phone terminal. With the arrival of ventricular systole and diastole, the blood flow monitoring device generates induced charges so as to convert pulse waves into voltage waves and realize the output of electric signals.
The artificial electronic blood vessel comprises an artificial blood vessel and a blood flow monitoring device, wherein the artificial blood vessel replaces a damaged blood vessel to reconstruct blood circulation, the blood flow monitoring device is wrapped on the periphery of the artificial blood vessel, monitors blood flow in the artificial blood vessel in the arterial vascular system in a pulse wave mode, and then outputs index information to indicate the blood flow health condition in the artificial blood vessel. Thereby realizing the real-time blood flow monitoring of the artificial blood vessel in situ after operation. The artificial electronic blood vessel provided by the application can timely discover the thrombosis phenomenon at the vascular site of the human tube after operation, and provides a foundation for the discovery and repair of early injury of vascular grafts. The blood flow condition can be monitored in real time through the integrated artificial electronic blood vessel after operation, so that abnormality is found in time and treatment is given, the risk of postoperative thrombus occurrence is reduced, and the long-term patency rate of the small-caliber artificial blood vessel is improved.
Fig. 2 is a schematic view of an artificial blood vessel structure provided by the application, which comprises polycaprolactone PCL nanofiber 111 in an inner layer and thermoplastic polyurethane TPU nanofiber 112 in an outer layer.
The polycaprolactone PCL nanofiber 111 can promote directional migration of endothelial cells from an autologous blood vessel to an artificial blood vessel, so that endothelialization process of the artificial blood vessel is accelerated. The thermoplastic polyurethane TPU nanofibers 112 have similar mechanical strength and elasticity as natural blood vessels, providing the mechanical properties required for cyclic expansion and contraction of the blood vessels. Specifically, the polycaprolactone PCL nanofibers are axially and orderly arranged along the artificial blood vessel; the thermoplastic polyurethane TPU nanofibers are arranged in an unordered manner. The polycaprolactone PCL nanofibers are orderly arranged along the axial direction of the artificial blood vessel, and the orientation of the polycaprolactone PCL nanofibers is consistent with the blood flow direction, so that the blood flow resistance can be effectively reduced, and the risk of thrombus occurrence is reduced. The unordered arrangement of the thermoplastic polyurethane TPU nanofibers can better provide the mechanical properties required by the periodic expansion and contraction of blood vessels. And, by performing oxygen plasma treatment on the artificial blood vessel including the polycaprolactone PCL nanofiber in the inner layer and the thermoplastic polyurethane TPU nanofiber in the outer layer, hydrophilicity of the artificial blood vessel can be improved to facilitate cell adhesion.
Fig. 3 is a schematic structural diagram of a blood flow monitoring device according to the present application, which sequentially includes, from outside to inside, a first encapsulation layer 121, a polypyrrole Ppy layer 122, a polydimethylsiloxane PDMS layer 123, a gold nanofiber layer 124, and a second encapsulation layer 125. The surfaces of the polypyrrole Ppy layer and the polydimethylsiloxane PDMS layer are respectively provided with a nanowire structure.
Polypyrrole Ppy layer with nanowire structure on the surface is used as a friction layer and an electrode; a PDMS layer with a nanowire array structure on the surface is used as another friction layer; gold nanofibers attached to the back of the PDMS film are used as electrodes; the whole device is encapsulated by polyurethane adhesive tape/Parylene and is wrapped on the surface of the fiber-based artificial blood vessel. The nanowire array and the PPy nanowire on the surface of the PDMS film have good structural complementarity. The gold nanofiber is prepared by sputtering gold particles on the surface of an ordered polyvinyl alcohol PVA nanofiber prepared by electrostatic spinning, and then transferring the gold particles to the back surface of PDMS in water, and the PVA is dissolved in the water, so that a gold nanofiber electrode with good adhesion is obtained on the back surface of PDMS after transferring. The whole device is encapsulated by polyurethane adhesive tape, and then a Parylene coating is sputtered on the surface to realize water resistance.
Wrapping the blood flow monitoring device based on the triboelectric effect on the periphery of the artificial blood vessel to obtain the integrated artificial electronic blood vessel. Because the two have similar mechanical properties, the introduction of the blood flow monitoring device does not affect the function of the artificial blood vessel. The blood flow monitoring device operates based on triboelectric effects. With the alternating systole and diastole of the heart, blood flows in the form of pulse waves throughout the arterial vasculature and is perceived by the blood flow monitoring device as pressure waves, and then electrical signals are transmitted to the electrometer in a wired manner or to the cell phone end in a wireless manner. During ventricular systole, the sudden expansion of the artery brings the two triboelectric layers into contact, resulting in the generation of triboelectric charges. With the arrival of diastole, vasoconstriction causes separation of the triboelectric layer, thereby generating induced charges on the electrodes, which convert the pulse wave into a voltage wave.
Fig. 4 is a schematic view of the structure of an artificial electronic blood vessel provided by the present application, where the artificial electronic blood vessel further includes a blood flow monitoring device 13 connected to the blood flow monitoring device;
The blood flow monitoring device 12 is configured to output, to the blood flow monitoring device 13, the index information for characterizing the blood flow health condition in the artificial blood vessel;
the blood flow monitoring device 13 is configured to display the index information.
Specifically, the blood flow monitoring device is, for example, an electrometer, a mobile terminal, or the like. If the blood flow monitoring device is an electrometer, the blood flow monitoring device is connected with the blood flow monitoring device through a wire, the polypyrrole Ppy layer and the gold nanofiber layer in the blood flow monitoring device are respectively connected with the wire, and the other end of the wire is connected with the blood flow monitoring device. If the blood flow monitoring device is a mobile terminal, the blood flow monitoring device is connected with the blood flow monitoring device through a wireless module.
Based on the artificial electronic blood vessel provided by the application, medical staff can timely discover the thrombus phenomenon at the vascular site of the post-operation human tube through the blood flow monitoring device, and a foundation is provided for the discovery and repair of early injury of vascular grafts. The blood flow condition can be monitored in real time through the integrated artificial electronic blood vessel after operation, so that abnormality is found in time and treatment is given, the risk of postoperative thrombus occurrence is reduced, and the long-term patency rate of the small-caliber artificial blood vessel is improved.
In the present application, the length of the artificial blood vessel is 1cm to 5cm, the diameter is 1.5mm to 5mm, and the wall thickness is 100 μm to 500 μm. The surfaces of the polypyrrole Ppy layer and the polydimethylsiloxane PDMS layer are respectively provided with a nanowire structure. The length of the nanowire in the nanowire structure is 0.5-2 μm, and the diameter is 20-100 μm.
Fig. 5 is a schematic diagram of a preparation process of an artificial blood vessel provided by the application, which comprises the following steps:
S101: dissolving TPU powder into a mixed solution of dimethylformamide DMF and dichloromethane to obtain TPU spinning solution; and loading the TPU spinning solution into an injector, selecting a stainless steel rod as a fiber collector, applying constant voltage between a needle head and the stainless steel rod collector, rotating a stainless steel receiving rod at a set first rotating speed, and collecting and setting a first time length to obtain the tubular TPU nanofiber of the artificial blood vessel.
S102: dissolving PCL powder in isopropanol HFIP to obtain PCL spinning solution; filling PCL spinning solution into an injector, selecting the tubular TPU nanofiber obtained by the method as a fiber collector, wrapping two ends of the fiber collector by using tinfoil to obtain two ends of electrodes, applying constant voltage between a needle head and the fiber collector, collecting the axially ordered PCL nanofiber at a set second rotating speed for a set second period of time, obtaining the tubular PCL nanofiber of the artificial blood vessel, and overturning the tubular TPU nanofiber and the tubular PCL nanofiber into an inner layer and an outer layer of the tubular PCL nanofiber integrally to obtain the artificial blood vessel.
The application prepares the artificial blood vessel by an electrostatic spinning technology, wherein the preparation of the artificial blood vessel comprises the preparation of TPU nanofiber and the preparation of PCL nanofiber. In preparing the TPU nanofibers, the TPU dope is first prepared. The TPU powder is dissolved in the mixed solution of dimethylformamide DMF and dichloromethane to obtain the TPU spinning solution. Alternatively, the volume ratio of dimethylformamide DMF to dichloromethane in the mixture of dimethylformamide DMF and dichloromethane is 3:1. A TPU dope with a concentration of 37.5 wt.% was obtained. The TPU dope is charged into a syringe equipped with a 21G needle, and the flow rate is controlled at 1mL h -1. Stainless steel bars are selected as fiber collectors, the size of the stainless steel bars is between 1.5mm and 5mm, a constant voltage of 20kV is applied between the needle head and the stainless steel bar collector, and the distance between the needle head and the stainless steel bar collector is 15cm. The stainless steel receiving bar rotates at a set first rotational speed, for example 200rpm. And collecting and setting a first time length to obtain the tubular TPU nanofiber of the artificial blood vessel. The first time period is set to be, for example, 1 hour to 3 hours.
In preparing PCL nanofiber, PCL spinning solution is prepared first. I.e. the PCL powder was dissolved in isopropanol HFIP to give a 20wt% PCL dope. The PCL dope was charged into a syringe equipped with a 21G needle, and the flow rate was controlled at 1mL h -1. The obtained tubular TPU nanofiber is used as a fiber collector, two ends of the TPU nanofiber are wrapped by tin paper to obtain two end electrodes, a constant voltage of 20kV is applied between a needle head and the fiber collector, and the distance between the needle head and a stainless steel rod collector is 15cm. The stainless steel receiving rod is rotated at a set second rotational speed, which is set to a relatively slow rotational speed, for example 50rpm. And after collecting and setting the second time length, obtaining tubular PCL nanofiber of the artificial blood vessel, and overturning the tubular TPU nanofiber and the tubular PCL nanofiber into an inner layer and an outer layer integrally to obtain the artificial blood vessel. The second period of time is set to, for example, 15 minutes to 30 minutes.
Fig. 6 is a schematic diagram of a preparation process of the blood flow monitoring device provided by the application, which comprises the following steps:
s201: polypyrrole PPy with a nanowire structure on the surface is used as a friction layer and an electrode; a PDMS film with a nanowire structure on the surface is used as another friction layer; gold nanofibers attached to the back of the PDMS film are used as electrodes; the whole device is packaged by polyurethane adhesive tape/Parylene and is wrapped on the surface of the artificial blood vessel.
S202: the gold nanofiber is prepared by sputtering gold particles on the surface of an ordered polyvinyl alcohol PVA nanofiber prepared by electrostatic spinning, transferring the gold particles to the back surface of PDMS in water, obtaining a gold nanofiber electrode with good adhesion on the back surface of PDMS after transferring, packaging the whole device by a polyurethane adhesive tape, and sputtering a Parylene coating on the surface.
The blood flow monitoring device based on the triboelectric effect mainly comprises a friction layer, an electrode layer and a packaging layer, wherein polypyrrole PPy with a nanowire structure on the surface is used as one friction layer and one electrode; the PDMS film with the nanowire array structure on the surface is used as the other friction layer of the blood flow monitoring device; gold nanofibers attached to the back of the PDMS film are used as electrodes; the whole device is encapsulated by polyurethane adhesive tape/Parylene and is wrapped on the surface of the fiber-based artificial blood vessel. In the nanowire array structure, the length of the nanowire is 0.5-2 microns, the diameter is 20-100 microns, the array density is controllable, and the nanowire array on the surface of the PDMS film and the PPy nanowire have good structural complementarity. The gold nanofiber is prepared by sputtering gold particles on the surface of an ordered polyvinyl alcohol PVA nanofiber prepared by electrostatic spinning, and then transferring the gold particles to the back surface of PDMS in water, and the PVA is dissolved in the water, so that a gold nanofiber electrode with good adhesion is obtained on the back surface of PDMS after transferring. The whole device is packaged by polyurethane adhesive tape, and then Parylene is sputtered on the surface to realize water resistance.
The preparation process of the PPy nanowire is as follows:
The PPy nanowires are prepared by an electrochemical polymerization process. 5 ml of pyrrole monomer Py are dissolved in 100 ml of NaClO 4 solution 0.3mol L -1. Electropolymerization was carried out in a three-electrode electrochemical workstation in which conductive glass ITO,4cm 2cm, pt and Ag/AgCl were used as working electrode, counter electrode and reference electrode, respectively. The reaction was carried out at a potential of 0.8V for 300 seconds to 500 seconds. Subsequently, a gold film was deposited on the PPy film by magnetron sputtering 50w for 500 s. PPy nanowires were then synthesized by further electrochemical deposition. Specifically, 1mM p-toluenesulfonic acid p-TSA was added to 51mL of sodium dihydrogen phosphate 0.2mol L -1 and 49mL of sodium dihydrogen phosphate 0.2mol L -1. After stirring until the mixture is dissolved, 1ml of Py monomer is added. Then, the PPy-gold film and the platinum electrode are respectively used as a working electrode and a counter electrode, and electropolymerization is carried out for 1.5-2h under the current density of 0.6mAcm -2, so as to obtain the PPy nanowire.
The preparation process of the PDMS nanowire is as follows:
PDMS films with a thickness of about 60 μm were obtained by spin coating and drying. Subsequently, gold nanoparticles were deposited on the PDMS film by magnetron sputtering as a mask. PDMS nanowires were then prepared by inductively coupled plasma etching ICP. The gas flow rates of Ar, O 2, and CF 4 were 15, 10, and 30sccm, respectively, and the chamber pressure was 1-2Pa. The power supply for generating the high density plasma was 400W and the power supply for accelerating the plasma ions in the inductively coupled cavity was 100W. The density and length of the nanowires are controlled by adjusting the gold nanoparticle mask density and plasma etching time, respectively.
Wrapping the blood flow monitoring device based on the triboelectric effect on the periphery of the artificial blood vessel to obtain the integrated artificial electronic blood vessel. Because the artificial blood vessel and the blood flow monitoring device have similar mechanical properties, the function of the artificial blood vessel is not affected by the introduction of the mechanical sensor. The blood flow monitoring device operates based on triboelectric effects. With the alternating systole and diastole of the heart, blood flows in the form of pulse waves throughout the arterial vasculature and is perceived by the blood flow monitoring device as pressure waves, and then electrical signals are transmitted to the electrometer in a wired manner or to the cell phone end in a wireless manner. During ventricular systole, the sudden expansion of the artery brings the two triboelectric layers into contact, resulting in the generation of triboelectric charges. With the arrival of diastole, vasoconstriction causes separation of the triboelectric layer, thereby generating induced charges on the electrodes, which convert the pulse wave into a voltage wave.
The application provides an artificial electronic blood vessel for vascular repair and postoperative blood flow monitoring, comprising:
the fiber-based bionic artificial blood vessel is used for replacing a lesion or damaged blood vessel and realizing blood circulation reconstruction;
the adaptive blood flow monitoring device is used for monitoring blood flow in situ after operation, so that thrombus after operation can be found in time.
Wherein, the fiber-based bionic artificial blood vessel consists of an inner layer and an outer layer. The inner layer is an axially ordered polycaprolactone PCL nanofiber, so that cell migration can be promoted, and endothelialization process can be accelerated; the outer layer is an unordered thermoplastic polyurethane TPU nanofiber, and provides the mechanical strength and elasticity required by the blood vessel.
Wherein, blood flow monitoring device carries out postoperative blood flow monitoring based on triboelectric effect, comprises following structure: a PDMS film with a nanowire array structure on the surface is used as a friction layer of the blood flow monitoring device; gold nanofibers attached to the back of the PDMS film are used as electrodes; polypyrrole PPy with a nanowire structure on the surface is used as another friction layer and an electrode; the whole device is encapsulated by polyurethane adhesive tape/Parylene and is wrapped on the surface of the fiber-based artificial blood vessel.
In some embodiments of the application, the fiber-based vascular prosthesis has a length of 1-5cm, a diameter of 1.5-5mm, and a thickness of 100-500 μm. In some embodiments of the application, the nanowires have a length of 0.5-2 microns and a diameter of 20-100 microns. The nanowire array and the PPy nanowire on the surface of the PDMS film have good structural complementarity.
In order to solve the problems that the existing small-caliber artificial blood vessel is easy to generate acute thrombus after being transplanted and has low long-term patency rate, the application provides an artificial electronic blood vessel which accelerates the endothelialization process of the blood vessel through bionic design. In addition, blood flow is monitored in real time through an integrated mechanical sensor after operation, so that abnormality is found in time and treatment is given, the risk of postoperative thrombus occurrence is reduced, and the long-term patency rate of the small-caliber artificial blood vessel is improved.
Fig. 7 is a schematic structural diagram of an artificial electronic blood vessel provided by the application, wherein the artificial electronic blood vessel comprises a fiber-based bionic artificial blood vessel and a blood flow monitoring device based on a triboelectric effect, and the blood flow monitoring device sequentially comprises a first packaging layer, a polypyrrole Ppy layer, a polydimethylsiloxane PDMS layer, a gold nanofiber layer and a second packaging layer from the outer side to the inner side. The blood flow monitoring device is, for example, a mechanical sensor. Fig. 8 is a schematic diagram of an artificial electronic blood vessel according to the present application.
The fiber-based bionic artificial blood vessel is prepared by an electrostatic spinning technology. Wherein the inner layer is polycaprolactone PCL nanofiber orderly along the axial direction of the blood vessel. In one aspect, the structure promotes directional migration of endothelial cells from the autologous vascular graft to the vascular graft, thereby accelerating the endothelialization process of the vascular graft. On the other hand, the orientation is consistent with the blood flow direction, so that the blood flow resistance can be effectively reduced, and the risk of thrombus occurrence is reduced. The outer layer of the artificial blood vessel is disordered Thermoplastic Polyurethane (TPU) nanofiber, and the material has mechanical strength and elasticity similar to those of a natural blood vessel, so that the mechanical properties required by periodic expansion and contraction of the blood vessel are provided.
Fig. 9 is a cross-sectional view of an artificial blood vessel and a scanning electron microscope SEM schematic of an ordered PCL and an unordered TPU. FIG. 9 a is a cross-sectional view of an artificial blood vessel; b is a Scanning Electron Microscope (SEM) schematic diagram of the ordered PCL; c is a Scanning Electron Microscope (SEM) schematic of the disordered TPU. The hydrophilicity of the artificial blood vessel is enhanced by oxygen plasma treatment to facilitate cell adhesion. In general, the fiber-based vascular prosthesis has a length of 1-5cm, a diameter of 1.5-5mm, and a thickness of 100-500 μm, which can be controlled by adjusting the electrospinning receiver and the spinning time period.
FIG. 10 is a schematic diagram of an artificial blood vessel of PCL/TPU prepared by electrostatic spinning, wherein TPU powder is dissolved in a mixed solution of Dimethylformamide (DMF) and dichloromethane (volume ratio is 3:1) to obtain TPU spinning solution with concentration of 37.5 wt%; dissolving PCL powder in isopropanol (HFIP) to obtain 20wt% PCL spinning solution; the spinning solutions were each loaded into a syringe equipped with a 21G needle, and the flow rate was controlled at 1mL h -1. Stainless steel bars (1.5-5 mm) were chosen for the fiber collector. A constant voltage of 20kV was applied between the needle and the stainless steel rod collector at a distance of 15cm. The stainless steel receiving bar was rotated at 200rpm while collecting the unordered TPU tubes. After 1-3 hours of collection, wrapping two ends of the TPU pipe by using tinfoil to obtain electrodes at two ends, and collecting the PCL nanofiber which is axially ordered under slow rotation for 15-30 minutes. To improve the hydrophilicity of the vascular prosthesis to facilitate cell adhesion, the nanofiber tube was treated with oxygen plasma for 3 minutes (O 2 flow 50sccm, power 50W). Finally, the inner and outer layers of the tube were inverted to obtain a PCL/TPU vascular prosthesis.
Fig. 11 is a schematic view of a Scanning Electron Microscope (SEM) of the blood flow monitoring device provided by the present application. Fig. 11 a is a schematic view of a Scanning Electron Microscope (SEM) of polypyrrole PPy with a nanowire structure on the surface, b is a schematic view of a Scanning Electron Microscope (SEM) of a PDMS film with a nanowire array structure on the surface, and c is a schematic view of a Scanning Electron Microscope (SEM) of gold nanofibers. Blood flow monitoring devices (mechanical sensors) based on triboelectric effects mainly consist of a friction layer, an electrode layer and a packaging layer. Wherein polypyrrole PPy with a nanowire structure on the surface is used as a friction layer and an electrode; a PDMS film with a nanowire array structure on the surface is used as another friction layer of the mechanical sensor; gold nanofibers attached to the back of the PDMS film are used as electrodes; the whole device is encapsulated by polyurethane adhesive tape/Parylene and is wrapped on the surface of the fiber-based artificial blood vessel. In the nanowire array structure, the length of the nanowire is 0.5-2 microns, the diameter is 20-100 microns, the array density is controllable, and the nanowire array on the surface of the PDMS film and the PPy nanowire have good structural complementarity. The gold nanofiber is prepared by sputtering gold particles on the surface of ordered polyvinyl alcohol (PVA) nanofiber prepared by electrostatic spinning, and then transferring the gold particles to the back surface of PDMS in water, and because PVA is dissolved in water, a gold nanofiber electrode with good adhesion is obtained on the back surface of PDMS after transfer. The whole device is packaged by polyurethane adhesive tape, and then Parylene is sputtered on the surface to realize water resistance.
The effect of the artificial electronic blood vessel provided by the application will be described in detail with reference to the accompanying drawings.
Alternative example 1:
the artificial electronic blood vessel was sterilized by glutaraldehyde and then immersed in heparin (70U mL -1) for about 4 hours. It was then used to replace the left carotid artery of New Zealand rabbits (male, 3-4 kg, 6 months old). Heparin was injected intravenously at the rabbit's ear margin prior to surgery. After anesthesia with pentobarbital sodium, a1 cm section of the left carotid artery was severed and replaced with an artificial electronic blood vessel (2 mm in diameter and 1 cm in length) by an end-to-end anastomosis procedure. Two weeks after the operation, heparin (20U kg -1) was injected intravenously for anticoagulation.
After completion of the vascular graft, the blood flow monitoring device in the artificial electronic blood vessel was connected to an electrometer (Keithley 6514) to monitor the output voltage. As a result, as shown in fig. 12, a pulse wave of about 240 times per minute was observed in fig. 12. At the same time, significant respiratory waves can be observed, and respiratory waves and pulse waves can be easily distinguished due to significant differences in frequency and amplitude.
Blood vessel grafts were harvested 3 months after surgery and hematoxylin and eosin staining (H & E) and immunofluorescent staining (CD 31 and α -SMA) were performed to assess the repair and endothelialization progress of electronic blood vessels. The results are shown in FIG. 13. It can be seen in fig. 13 that the surface of the vascular prosthesis or the vascular prosthesis is covered by remodeled tissue, and that the layer of tissue covering the lumen of the graft is smooth and continuous, similar to the tissue structure in natural blood vessels. Immunofluorescent staining was then performed using CD31 and α -SMA as markers of functional endothelial and smooth muscle cell regeneration, respectively, and it was seen that the graft lumen was completely encapsulated by cd31+ endothelial cell layers, with a thickness of 2.6-2.8 μm, coverage exceeding 88%. The close association between endothelial cell layers and smooth muscle layers is very similar to the structure of autologous blood vessels.
Alternative example 2:
The method of example 2 referring to example 1, the differences from example 1 are specifically as follows: after completion of the vascular graft in example 1, heparin (20U kg -1) was intravenously injected for 3 days, and heparin anticoagulation treatment was stopped for the 4 th day after the operation to induce acute thrombosis. And synchronously evaluating the blood flow condition of the transplanting part through Doppler color Doppler ultrasound and an artificial electronic blood vessel sensor. As a result, as shown in fig. 14, clear pulse waves and respiratory waves were observed after the vascular replacement surgery. After stopping the anticoagulation treatment (7 days after operation), the pulse wave signal amplitude was greatly reduced, while the respiratory wave was still visible, indicating the blockage of angiogenesis. The in-vivo real-time monitoring result is consistent with the Doppler ultrasound result.
In summary, the present application provides an artificial electronic blood vessel exhibiting excellent long-term patency without intimal hyperplasia, thrombosis or vasodilation in an implant for 3 months, promoting vascular endothelialization and revascularization. In a key period after vascular replacement surgery, the integrated pressure sensor based on the triboelectric effect can monitor the hemodynamic state of an implantation site in real time, so that abnormal conditions can be monitored in time, and a low-invasive treatment method is adopted, so that the risk of progressive thrombosis is reduced.
Unless otherwise known, the numerical parameters in this specification and the attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure. In particular, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about". In general, the meaning of expression is meant to include a variation of + -10% in some embodiments, a variation of + -5% in some embodiments, a variation of + -1% in some embodiments, and a variation of + -0.5% in some embodiments by a particular amount.
While the foregoing is directed to embodiments of the present invention, other and further details of the invention may be had by the present invention, it should be understood that the foregoing description is merely illustrative of the present invention and that no limitations are intended to the scope of the invention, except insofar as modifications, equivalents, improvements or modifications are within the spirit and principles of the invention.
While preferred embodiments of the present application have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. It is therefore intended that the following claims be interpreted as including the preferred embodiments and all such alterations and modifications as fall within the scope of the application.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present application without departing from the spirit or scope of the application. Thus, it is intended that the present application also include such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.
Claims (10)
1. An artificial electronic blood vessel, comprising: the blood flow monitoring device is wrapped on the periphery of the artificial blood vessel;
The artificial blood vessel is used for replacing a damaged blood vessel to reconstruct blood circulation;
The blood flow monitoring device is used for monitoring the blood flow in the arterial vascular system in the form of pulse waves in the artificial blood vessel and outputting index information for representing the blood flow health condition in the artificial blood vessel.
2. The artificial electronic blood vessel of claim 1, wherein the artificial blood vessel comprises polycaprolactone PCL nanofibers in an inner layer and thermoplastic polyurethane TPU nanofibers in an outer layer.
3. The artificial electronic blood vessel of claim 2, wherein the polycaprolactone PCL nanofibers are ordered along the axial direction of the artificial blood vessel; the thermoplastic polyurethane TPU nanofibers are arranged in an unordered manner.
4. The artificial electronic blood vessel of claim 1, wherein the blood flow monitoring device comprises, in order from the outside to the inside, a first encapsulation layer, a polypyrrole Ppy layer, a polydimethylsiloxane PDMS layer, a gold nanofiber layer, and a second encapsulation layer.
5. The artificial electronic blood vessel of claim 4, further comprising a blood flow monitoring device coupled to the blood flow monitoring device;
the blood flow monitoring device is used for outputting the index information used for representing the blood flow health condition in the artificial blood vessel to the blood flow monitoring device;
the blood flow monitoring device is used for displaying the index information.
6. The artificial electronic blood vessel according to claim 1, wherein the artificial blood vessel has a length of 1cm to 5cm, a diameter of 1.5mm to 5mm, and a wall thickness of 100 μm to 500 μm.
7. The artificial electronic blood vessel according to claim 4, wherein the surfaces of the polypyrrole Ppy layer and the polydimethylsiloxane PDMS layer have nanowire structures, respectively.
8. The artificial electronic blood vessel according to claim 7, wherein the nanowires in the nanowire structure have a length of 0.5 μm to 2 μm and a diameter of 20 μm to 100 μm.
9. A method of preparing an artificial electronic blood vessel according to any one of claims 1 to 8, wherein the method comprises:
dissolving TPU powder into a mixed solution of dimethylformamide DMF and dichloromethane to obtain TPU spinning solution; loading TPU spinning solution into an injector, selecting a stainless steel rod as a fiber collector, applying constant voltage between a needle head and the stainless steel rod collector, rotating a stainless steel receiving rod at a set first rotating speed, and collecting and setting a first time length to obtain tubular TPU nanofibers of the artificial blood vessel;
Dissolving PCL powder in isopropanol HFIP to obtain PCL spinning solution; filling PCL spinning solution into an injector, selecting the tubular TPU nanofiber obtained by the method as a fiber collector, wrapping two ends of the fiber collector by using tinfoil to obtain two ends of electrodes, applying constant voltage between a needle head and the fiber collector, collecting the axially ordered PCL nanofiber at a set second rotating speed for a set second period of time, obtaining the tubular PCL nanofiber of the artificial blood vessel, and overturning the tubular TPU nanofiber and the tubular PCL nanofiber into an inner layer and an outer layer of the tubular PCL nanofiber integrally to obtain the artificial blood vessel.
10. A method of manufacturing the blood flow monitoring device based on an artificial electronic blood vessel according to any one of claims 1 to 8, the method comprising:
Polypyrrole PPy with a nanowire structure on the surface is used as a friction layer and an electrode; a PDMS film with a nanowire structure on the surface is used as another friction layer; gold nanofibers attached to the back of the PDMS film are used as electrodes; the whole device is packaged by polyurethane adhesive tape/Parylene and is wrapped on the surface of an artificial blood vessel;
The gold nanofiber is prepared by sputtering gold particles on the surface of an ordered polyvinyl alcohol PVA nanofiber prepared by electrostatic spinning, transferring the gold particles to the back surface of PDMS in water, obtaining a gold nanofiber electrode with good adhesion on the back surface of PDMS after transferring, packaging the whole device by a polyurethane adhesive tape, and sputtering a Parylene coating on the surface.
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