CN117599261A - Visual artificial vascular stent and preparation method and application thereof - Google Patents
Visual artificial vascular stent and preparation method and application thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of vascular stents, and particularly discloses a visual artificial vascular stent, a preparation method and application thereof. The raw materials of the visual artificial vascular stent comprise AIE molecules and degradable high polymer materials, wherein the mass ratio of the AIE molecules to the degradable high polymer materials is (0.01-0.05): 1. the invention also provides a preparation method and application of the visual artificial vascular stent. The visual artificial vascular stent has excellent photo-thermal antibacterial anti-infection performance besides good near infrared two-region imaging effect and longer high-quality imaging time. The visual artificial vascular stent has good biocompatibility, the porous compact three-dimensional reticular structure can effectively avoid the thrombus problem of the implanted blood vessel, is favorable for cell attachment and growth, can avoid side effects such as allergy, injury, renal function damage, radiation and the like formed by radiography in vascular grafting and vascular imaging, can realize noninvasive imaging observation without operation, and has good clinical application prospect.
Description
Technical Field
The invention relates to the technical field of vascular stents, in particular to a visual artificial vascular stent, a preparation method and application thereof.
Background
At present, cardiovascular and related diseases are developed into one of the diseases with highest mortality rate, the life and health of human beings are seriously threatened, and autologous vascular surgical transplantation is a common treatment means for cardiovascular diseases, but the number of autologous blood vessels is limited, so that the clinical surgical needs are met, and artificial blood vessels become ideal schemes for improving the vascular transplantation treatment rate. At present, an artificial blood vessel prepared by polytetrafluoroethylene or polyurethane materials is widely applied to large-caliber blood vessel transplantation operation, however, for small-caliber blood vessels with the inner diameter smaller than 6mm, the internal blood flow speed is slower, the blood flow environment is more complex, so that the smoothness of the blood vessel is difficult to evaluate in real time in the implantation process, and the problems of poor endothelialization of the blood vessel, blockage of the blood vessel and the like are easy to occur after long-term implantation in vivo. The current clinical blood vessel patency assessment mostly adopts an arterial angiography technology, and angiographies blood vessels at a target position through blood vessels injection contrast agent and complex imaging equipment. In addition, the implanted artificial vascular stent is mostly made of non-degradable polymer materials such as polytetrafluoroethylene, and the like, so that bacterial infection is very easy to occur in the in-vivo implantation process, inflammatory reaction of an implantation part is caused, and great risks are brought to vascular implantation operation.
The development of fluorescent biological imaging technology has wide application prospect in aspects such as brain depth imaging, vascular imaging, tumor visualization and the like. In recent years, near infrared two-region fluorescence imaging (NIR II, wavelength of 1000-1700 nm) is an emerging imaging technology with the advantages of high depth, low background interference, high resolution and the like due to the fact that the defect of low imaging depth of a traditional near infrared one-region tissue is overcome. At present, materials such as quantum dots, rare earth doped nanoparticles, small molecule dyes, semiconductor polymer based nanoparticles, and single-walled carbon nanotubes have been widely reported for near infrared two-region fluorescence imaging, and small molecule dyes represented by indocyanine green (ICG) have been approved for clinical treatment by the FDA in the united states. However, in a complex physiological environment in an organism, the planar molecular structure of the fluorescent dye is easy to dissipate energy in a non-radiative transition form in an aggregation state, namely, aggregation-induced quenching effect, and finally, the imaging effect of the fluorescent material in the body is greatly reduced, and the clinical use effect is seriously affected. The Aggregation-induced emission (AIE) material overcomes the Aggregation quenching effect of the traditional fluorescent material, and the Aggregation-induced emission (AIE) prepared AIE has the effect that molecules show more Aggregation and brighter under Aggregation states such as biological imaging and the like, and has great clinical application prospect in the field of biological imaging. When the AIE material is used for vascular imaging, due to the complex physiological environment, blood circulation and cell metabolism in vivo, the AIE material is difficult to realize long-term in-situ high-quality imaging effect, and is unfavorable for long-term in-situ imaging monitoring.
In view of the above-mentioned various technical problems of the related art, there is a need for a visual artificial vascular stent having antibacterial and anti-infection capabilities and long-term high-quality in-situ imaging capabilities, so as to realize imaging monitoring and antibacterial and anti-inflammatory of an implanted artificial blood vessel under in vitro non-invasive conditions.
Disclosure of Invention
The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the present invention provides a visual artificial vascular stent. The visual artificial vascular stent disclosed by the invention uses an Aggregation-induced emission (AIE) material as a fluorescent component to be added into a degradable high polymer material, so that the visual artificial vascular stent has the technical effects of more remarkable fluorescent imaging effect and longer time; the visual artificial vascular stent has good cell compatibility and adhesion performance, also has good photothermal antibacterial effect and broad-spectrum sterilization performance, avoids side effects such as allergy, injury, renal function damage, radiation and the like formed by arterial angiography, can realize noninvasive imaging observation without operation, and has good clinical application prospect.
The invention also provides a preparation method of the visual artificial vascular stent.
The invention also provides application of the visual artificial vascular stent and a preparation method thereof.
In a first aspect of the present invention, there is provided a visual artificial vascular stent, the preparation raw materials comprising: AIE molecules, degradable polymeric materials; wherein the mass ratio of the AIE molecules to the degradable high polymer material is (0.01-0.05): 1.
in some embodiments of the present invention, the mass ratio of the AIE molecule to the degradable polymeric material is (0.015-0.04): 1.
in some preferred embodiments of the present invention, the mass ratio of the AIE molecule to the degradable polymeric material is (0.02-0.03): 1.
in some embodiments of the invention, the AIE molecule is a near infrared two-region fluorescence imaging AIE molecule.
Compared with the traditional fluorescent imaging material, the aggregation-induced emission (AIE) material has better fluorescent imaging effect, higher optical/chemical stability and fluorescence intensity, and can meet the requirements of in-situ imaging with high signal to noise ratio of different tissue depths.
The AIE molecules used in the scheme of the invention are provided with long alkyl bifurcation side chains with different chain lengths, and molecular movement rotation in a solid state is promoted reversely, so that the near infrared two-region imaging effect and the photo-thermal conversion performance of the molecular material are greatly improved, and the near infrared imaging and photo-thermal antibacterial effects of the visual artificial vascular stent are provided.
The AIE molecule used in the scheme of the invention contains a large pi conjugated donor-acceptor structure, wherein the donor structure is tetraphenyl ethylene with the excitation state intramolecular movement capability, and the acceptor structure contains one or more of vinyl acetone, benzothiazole, pyridinium, pyrazine, naphthalimide and pyrrolidine.
In some embodiments of the invention, the degradable polymeric material is selected from biocompatible degradable polymeric materials approved by the U.S. food and drug administration (Food and Drug Administration, FDA).
In some preferred embodiments of the present invention, the degradable polymeric material is selected from at least one of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, sodium alginate, chitosan, hyaluronic acid, polyglycolic acid, polydioxanone.
The proposal of the invention selects the FDA approved biocompatible degradable polymer material as the base material of the artificial vascular stent, thereby meeting the safety requirement of clinical implantation of blood vessels.
In some more preferred embodiments of the present invention, the degradable polymeric material is selected from at least one of polylactic acid-glycolic acid copolymer, polycaprolactone.
In some embodiments of the invention, the feedstock further comprises a solvent.
In some preferred embodiments of the present invention, the solvent is selected from at least one of N, N-dimethylformamide, tetrahydrofuran, acetone, dimethyl sulfoxide, dichloromethane, chloroform, absolute ethanol, hexafluoroisopropanol.
In some more preferred embodiments of the present invention, the solvent is selected from at least one of N, N-dimethylformamide, tetrahydrofuran, acetone.
In some more preferred embodiments of the present invention, the solvent is selected from two of N, N-dimethylformamide, tetrahydrofuran, acetone.
In some embodiments of the invention, the vascular stent is cylindrical.
In some embodiments of the invention, the vascular stent has an inner diameter in the range of 1-10 mm.
In some preferred embodiments of the present invention, the vascular stent has an inner diameter ranging from 1 to 6mm.
In some more preferred embodiments of the present invention, the vascular stent has an inner diameter ranging from 2 to 4mm.
In a second aspect of the present invention, there is provided a method for preparing a visual artificial vascular stent according to the first aspect of the present invention, comprising the steps of:
s1, dissolving AIE molecules in a solvent, adding a degradable polymer material, and stirring for dissolution to obtain micro-nano processing stock solution;
s2, preparing the nanofiber vascular stent from the micro-nano processing stock solution by using a micro-nano processing technology, and obtaining the visual artificial vascular stent.
According to the scheme, the AIE nanofiber visual vascular stent is prepared by combining an AIE molecular material with high-efficiency near infrared two-region imaging and photo-thermal sterilization functions and an electrospun nanofiber material. The AIE nanofiber vascular stent has higher imaging brightness and long-term effectiveness, and can realize noninvasive visual monitoring on the blood flow condition and the smoothness of the implanted vascular stent after carrier implantation for several weeks.
The invention selects the polymer material with good biocompatibility which is approved by the FDA in the United states as the base material of the vascular stent, and prepares the nanofiber vascular stent by utilizing the micro-nano processing technology. By doping AIE molecules into the nanofiber substrate, the stent is endowed with visualization and antibacterial functions together with the nanofiber stent.
In some embodiments of the invention, the method of dissolving the AIE molecule of step S1 comprises ultrasonic agitation and stirring.
In some preferred embodiments of the present invention, the method of dissolution of the AIE molecule described in step S1 is ultrasonic oscillation.
In some embodiments of the invention, the ultrasonic oscillation has a frequency of 20-40 KHz for 5-15 min.
In some preferred embodiments of the present invention, the frequency of the ultrasonic oscillation is 25-35 khz, and the time is 8-12 min.
In some embodiments of the invention, the micro-nano processing technology is selected from one of 3D printing, electrospinning, non-woven fabrics, and template casting.
In some preferred embodiments of the invention, the micro-nano processing technique is electrospinning.
In some embodiments of the present invention, when the micro-nano processing technology is electrostatic spinning, the mass fraction of the degradable polymer material in the micro-nano processing stock solution in the step S1 is 10-25%.
In some preferred embodiments of the present invention, when the micro-nano processing technology is electrostatic spinning, the mass fraction of the degradable polymer material in the micro-nano processing stock solution in the step S1 is 13-20%.
In some embodiments of the present invention, when the micro-nano processing technology is used for pouring a non-woven fabric or a template, the mass fraction of the degradable polymer material in the micro-nano processing stock solution in the step S1 is 50-90%.
In some embodiments of the invention, the nanofiber vascular stent has a fiber diameter ranging from 0.5 to 1.5 μm.
In some preferred embodiments of the present invention, the nanofiber vascular stent has a fiber diameter ranging from 0.8 to 1.2 μm.
In a third aspect of the present invention, the present invention provides the use of the method for preparing a visualized vascular stent according to the first aspect and the visualized vascular stent according to the second aspect in vascular grafting, vascular imaging, and preparation of a product for treating cardiovascular related diseases.
In some embodiments of the invention, the product comprises a vascular stent, an artificial blood vessel.
The beneficial effects of the invention at least comprise:
(1) Compared with the traditional fluorescent imaging material, the aggregation-induced emission (AIE) material used by the invention has better fluorescent imaging effect, higher optical/chemical stability and fluorescence intensity, and can meet the requirements of in-situ imaging with high signal to noise ratio of different tissue depths.
(2) The AIE molecule used in the invention has good near infrared two-region imaging effect and excellent photo-thermal antibacterial anti-infection performance, and the AIE material is applied to an artificial vascular stent, so that the AIE material can effectively transplant drug-resistant bacterial infection of surrounding tissues during and after the artificial vascular stent is transplanted into a body, and has higher application value and good clinical application prospect.
(3) The artificial vascular stent is prepared from electrospun nanofibers, has a three-dimensional network structure similar to an extracellular matrix, can effectively avoid the thrombus problem of the implanted blood vessel, ensures the long-term smoothness of the implanted blood vessel, is favorable for the attached growth of cells, has better cell compatibility and can not cause hemolysis. In addition, the invention selects the FDA approved biocompatible degradable high polymer material as the base material of the artificial vascular stent, thereby meeting the safety requirement of clinical implantation of blood vessels.
(4) The artificial vascular stent and the artificial blood vessel which can be subjected to in-situ fluorescence imaging can avoid the use of contrast agents, avoid side effects such as allergy, injury, renal function damage, radiation and the like formed by arterial angiography, and can realize noninvasive imaging observation without operation. The near infrared two-region imaging is clearer and more visual, the implantable artificial blood vessel visual observation function is provided by combining the portable near infrared imaging equipment, and a more convenient, efficient and low-cost reference means is provided for artificial blood vessel functional evaluation.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.
Drawings
The invention is further described with reference to the accompanying drawings and examples, in which:
FIG. 1 is an excitation and emission spectrum of AIE molecules used in the present invention;
FIG. 2 is an electron microscope view of the surface of the visual artificial blood vessel stent prepared in example 1 of the present invention;
FIG. 3 is an electron microscope view of the surface of a visual artificial blood vessel stent prepared in example 2 of the present invention;
FIG. 4 is a cross-sectional electron microscope view of a visual artificial blood vessel stent prepared in example 1 of the present invention;
FIG. 5 is a view of a cell electron microscope for a cell compatibility test in an experimental example of the present invention;
FIG. 6 is a graph showing the hemolysis of each group of hemolysis experiments in the experimental example of the present invention;
FIG. 7 is a graph showing the antibacterial conditions of each group of antibacterial tests in the experimental example of the present invention;
FIG. 8 is a graph showing the short-term photostability measurement results of a fluorescence imaging effect experiment in an experimental example of the present invention;
fig. 9 is a measurement result of long-term light stability of a fluorescence imaging effect experiment in an experimental example of the present invention.
Detailed Description
The conception and the technical effects produced by the present invention will be clearly and completely described in conjunction with the embodiments below to fully understand the objects, features and effects of the present invention. It is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments, and that other embodiments obtained by those skilled in the art without inventive effort are within the scope of the present invention based on the embodiments of the present invention.
The specific conditions are not specified in the specific embodiments and are carried out according to conventional conditions or conditions suggested by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Unless otherwise indicated, the term "room temperature" in the present invention means 25.+ -. 5 ℃.
The term "about" in the present invention means that the allowable error is within + -2% unless otherwise specified.
The AIE molecule used in the specific embodiment is a near infrared two-region AIE molecule, which is purchased from the high-grade research institute of aggregation-induced emission and has the product model of AIE1010, the excitation wavelength of the AIE molecule is 720nm, the emission wavelength is 1010nm, and the excitation and emission spectra are shown in figure 1.
Example 1
The embodiment provides a visual artificial vascular stent, which comprises the following steps:
(1) Adding 20mg of near infrared AIE molecules into a solvent obtained by mixing 3.5mL of N, N-dimethylformamide and 3.5mL of tetrahydrofuran, and carrying out ultrasonic oscillation at 30kHz for 10min to completely dissolve the AIE molecules, thereby obtaining a uniformly dissolved AIE solution, and preserving in a dark place;
(2) Adding 1g of Polycaprolactone (PCL) into the AIE solution obtained in the step (1), magnetically stirring at room temperature for 3 hours, completely dissolving PCL to obtain a uniformly mixed electrostatic spinning precursor solution, and standing for 0.5 hour to completely eliminate bubbles in the solution, wherein the mass fraction of PCL is about 13%;
(3) And (3) carrying out micro-nano processing treatment on the electrostatic spinning precursor liquid obtained in the step (2) by using an electrostatic spinning technology, wherein parameters of electrostatic spinning are set as follows: the injection speed of the electrostatic spinning solution is 1mL/h, the spinning voltage is 13kV, the receiving distance is 15cm, and the diameter of a spinning nozzle is 0.7mm;
(4) Collecting the electrostatic spinning nanofiber by using a roller with the diameter of 2mm, wherein the receiving rotating speed is 1000rpm, and the receiving time is 1h;
(5) Vacuum drying the prepared AIE micro-nanofiber artificial blood vessel, and soaking and sterilizing with 75% alcohol.
Example 2
The embodiment provides a visual artificial vascular stent, which comprises the following steps:
(1) Adding 30mg of AIE molecules into a solvent obtained by mixing 2g of N, N-dimethylformamide and 2g of acetone, and carrying out ultrasonic oscillation at 40kHz for 3min to completely dissolve the AIE molecules, thereby obtaining a uniformly dissolved AIE solution, and preserving the solution in a dark place;
(2) Adding 1g of polylactic acid-glycolic acid copolymer (PLGA) into the AIE solution obtained in the step (1), magnetically stirring for 3 hours at room temperature, completely dissolving PLGA to obtain a uniformly mixed electrostatic spinning precursor solution, and standing for 0.5 hour to completely eliminate bubbles in the solution, wherein the mass fraction of PLGA is about 20%;
(3) And (3) carrying out micro-nano processing treatment on the electrostatic spinning precursor liquid obtained in the step (2) by using an electrostatic spinning technology, wherein parameters of electrostatic spinning are set as follows: the injection speed of the electrostatic spinning solution is 0.8mL/h, the spinning voltage is 15kV, the receiving distance is 20cm, and the diameter of a spinning nozzle is 0.9mm;
(4) Collecting the electrostatic spinning nanofiber by using a roller with the diameter of 4mm, wherein the receiving rotating speed is 2000rpm, and the receiving time is 2 hours;
(5) Vacuum drying the prepared AIE micro-nanofiber artificial blood vessel, and soaking and sterilizing with 75% alcohol.
Example 3
This example provides a preparation of a visual artificial vascular stent, which differs from example 1 only in that: 20mg of AIE molecules in example 1 were replaced with 40mg of AIE molecules.
Comparative example 1
This comparative example provides for the preparation of a fluorescence visualized vascular stent, which differs from example 1 only in that: the AIE molecule in example 1 was replaced with indocyanine green (ICG).
Comparative example 2
This comparative example provides for the preparation of a fluorescence visualized vascular stent, which differs from example 1 only in that: the AIE molecule in example 1 was replaced with methylene blue.
Comparative example 3
This comparative example provides for the preparation of a fluorescence visualized vascular stent, which differs from example 1 only in that: 20mg of AIE molecules from example 1 were replaced with 30mg of indocyanine green.
Comparative example 4
This example provides a preparation of a visual artificial vascular stent, and the difference between this comparative example and example 1 is only that: 20mg of AIE molecules in example 1 were replaced with 100mg of AIE molecules.
Comparative example 5
This example provides a preparation of a visual artificial vascular stent, and the difference between this comparative example and example 1 is only that: 20mg of AIE molecules in example 1 were replaced with 150mg of AIE molecules.
Test case
The surface topography of the visualized vascular stents prepared in examples 1 and 2 of the present invention was examined using a scanning electron microscope (SEM, SU8200 model) and the results are shown in fig. 2 and 3, respectively. The PCL & AIE composite electrospun fiber membrane of example 1 shown in FIG. 2 has a uniform three-dimensional network structure with an average diameter of network fibers of about 800nm, and the PLGA & AIE composite electrospun fiber membrane of example 2 shown in FIG. 3 also has a uniform three-dimensional network structure with an average diameter of network fibers of about 1.2 μm.
The cross section of the visualized vascular stent prepared in example 1 of the present invention was further examined by using a scanning electron microscope, and the result is shown in fig. 4, and fig. 4 shows the porous dense three-dimensional network structure of the visualized vascular stent of example 1.
Experimental example
1. Cell compatibility evaluation experiment of visual artificial vascular stent
Cutting PCL & AIE composite electrostatic spinning fiber membrane prepared in example 1 into rectangle of 4cm×5cm, soaking in 75% ethanol for 30min for sterilization, air drying, washing with PBS twice to remove ethanol residue, placing PCL & AIE composite electrostatic spinning fiber membrane in cell culture dish, inoculating with density of 2×10 4 Individual/cm 2 NIH 3T3 cells of (C) at 37℃with 5% CO 2 Cells were fixed with 4% paraformaldehyde, dehydrated with ethanol, and observed on PCL & AIE composite electrospun fiber membranes using SEM (SU 8200 type) at an accelerating voltage of 5kV for 3 days.
The observed cell morphology results are shown in fig. 5, and fig. 5 shows the growth state of cells on the fibrous membrane provided in example 1, shows that the cell growth state is good, the cell spreading state is good, no dead cells are present, and the visual artificial vascular stent provided in example 1 is suitable for cell attachment, has no adverse effect on cell growth proliferation and spreading attachment, and has high cell compatibility.
2. Cell proliferation experiment of visual artificial vascular stent
The effect of artificial blood vessels on cell proliferation was visualized by cell proliferation experiments, which used cell count Kit-8 (CCK-8) to evaluate the cytotoxicity of AIE composite electrospun fiber membranes.
The composite electrospun fiber membranes prepared in examples 1 to 3, comparative example 1, comparative example 2, comparative example 4 and comparative example 5 and the PCL fiber membrane without fluorescent dye were treated as blank by the method of the foregoing experimental procedure, and the inoculation density was 1×10 4 Individual/cm 2 Human Umbilical Vein Endothelial Cells (HUVEC) at 37deg.C, 5% CO 2 The cells are stained by CCK-8 and incubated for 2 hours, and the optical density of the cells at 450nm is tested by a multifunctional enzyme-labeled instrument, so that the proliferation cell activity (%) of HUVEC cells on AIE composite electrostatic spinning fiber membranes is obtained, and the cell activity is calculated by the following steps: the cell viability of the highest cell density group was calculated from the optical density ratio at 100% and the results are shown in Table 1.
Table 1 Effect of visualized vascular stent cells prepared in examples on cell proliferation
From the above test results, it is known that the artificial vascular stent prepared by using the AIE molecule as the fluorescent dye in the scheme of the invention has no adverse effect on the proliferation activity of cells, and when the amount of the AIE molecule is increased, as in example 3, the mass ratio of the AIE molecule to the biocompatible polymer reaches 0.04:1, a certain adverse effect is generated on the proliferation of cells, but the activity of cells still reaches about 85% compared with a blank control, and when the amount of the AIE molecule is increased continuously, the proliferation activity of cells is greatly influenced; furthermore, comparative examples 1 and 2 using indocyanine green and methylene blue have a small influence on the cell proliferation activity to a different extent.
3. Visual artificial vascular stent hemolysis experiment
The degree of influence of the visualized artificial vascular stent on the haemolytic performance of fresh blood is an important index for evaluating biocompatibility. In the experiment, female SD rats with the weight of 200-250 g are selected as blood taking objects, and blood samples are collected by utilizing blood taking needles and vacuum blood taking tubes containing heparin sodium. The red blood cells were collected by centrifugation in a physiological saline solution at 4℃for 3 times at 1500rpm for 15min, and then resuspended in the physiological saline solution to prepare a working solution having a red blood cell concentration of 2% (w/v).
The visual artificial vascular stent prepared in the examples 1-3 with the same mass, the PCL fibrous membrane without AIE molecules, the normal saline and the deionized water are respectively added to the bottom of a 1.5mL centrifuge tube, the normal saline is used as a negative control group, the deionized water is used as a positive control group, the PCL fibrous membrane without AIE molecules is used as a blank group, the separated erythrocyte suspension working solution is added into the centrifuge tube, the incubation is carried out for 3 hours at 37 ℃, the centrifugation is carried out, the hemoglobin content in the supernatant is measured under the absorbance of 540nm by using a spectrophotometer, and then the erythrocyte hemolysis performance caused by the sample is evaluated.
As a result, as shown in FIG. 6, PCL on the abscissa of the graph is a blank group, 2AIE is a visual artificial vascular stent with the mass ratio of AIE to biocompatible polymer of example 1 being 0.02:1, 3AIE is a visual artificial vascular stent with the mass ratio of AIE to biocompatible polymer of example 2 being 0.03:1, 4AIE is a visual artificial vascular stent with the mass ratio of AIE to biocompatible polymer of example 3 being 0.04:1, NC is a negative control physiological saline, and PC is positive control deionized water. The result shows that the visual artificial vascular stent of the scheme of the invention does not influence the hemolysis of red blood cells and has good biocompatibility.
4. Antibacterial test of visual artificial vascular stent
Resistant staphylococcus aureus (Methicillin-resistant Staphylococcus aureus, MRSA) and resistant escherichia coli (Methicillin-resistant Escherichia coli) were selected to evaluate the antimicrobial properties of the visualized vascular stents.
The MRSA is firstly cultured and activated in Luria-Bertani (LB) liquid medium at 37 ℃, and MRSA bacterial cells are collected by centrifugation to 10 6 The CFU/mL concentration was resuspended. Composite electrospinning using 75% ethanolAfter the fiber membrane was sterilized, the fiber membrane was cut into a rectangle of 1cm×1cm, 1mL of MRSA bacterial suspension was added to each well of the 6-well plate to cover the fiber membrane, and the mixture was cultured in a bacterial incubator at 37℃for 24 hours, the cell suspension was smeared on LB solid medium, and cultured in a bacterial incubator at 37℃for 24 hours, and irradiated with a laser (vinca femtosecond 808 laser) of 0.8mW/cm2 intensity at a height of 13cm for 10 minutes, and the colony number was detected by using a plate count method.
The results are shown in fig. 7, and the results show that the sterilization efficiency is gradually increased along with the increase of the AIE molecular dosage in the visual vascular stent, and when the mass ratio of the AIE molecules in the visual vascular stent to the biocompatible polymer is 0.04:1, the laser irradiation can achieve the complete sterilization of the drug-resistant staphylococcus aureus and the drug-resistant escherichia coli almost after 10 minutes, so that the application of the AIE molecules in the vascular stent can achieve very good photo-thermal sterilization effect and broad-spectrum sterilization performance.
5. Fluorescent imaging effect experiment of visual artificial blood vessel stent
The visualized vascular stents prepared in example 1 and comparative example 1 were subjected to a fluorescence imaging experiment, and the fluorescence imaging quality of the artificial vascular stents was measured under 808nm laser irradiation using a small animal living body imaging system (Series III 900/1700) at a time interval of 10min. The test results are shown in fig. 8, and the results show that the visual vascular stent of the scheme of the invention not only has higher fluorescence intensity, but also has obviously stronger optical stability with the increase of irradiation time.
The results of long-term test of the visualized vascular stents prepared in example 1 and comparative example 1 implanted in the carotid artery of mice under 808nm laser irradiation using a living animal imaging system (Series III 900/1700) are shown in FIG. 9, and the signal intensity of the visualized vascular stent according to the present invention is still 1/3 or more of the signal intensity of the first day even at the scale of the 10-day laser irradiation test, whereas the corresponding comparative example 1 using indocyanine green fluorescent dye, the signal intensity of which was already close to 0 at the 4-day irradiation, indicate that the visualized vascular stent according to the present invention has significantly longer high-quality fluorescence imaging time.
In conclusion, the AIE fluorescence visualization artificial vascular stent prepared by the scheme has more remarkable fluorescence imaging effect, has longer time of high-quality fluorescence imaging, and the electrospun nanofiber provides a solid medium for the AIE material, so that the contrast ratio and the signal to noise ratio of near infrared imaging can be remarkably improved, and the high signal to noise ratio in-situ imaging with different tissue depths can be satisfied; the visual artificial vascular stent also has good cell compatibility and attachment performance, does not cause hemolysis, has a three-dimensional network structure of nanofibers similar to extracellular matrix, and can effectively avoid the thrombus problem of the implanted blood vessel; in addition, the vascular stent main body material adopts biodegradable polymer materials approved by FDA, so that the safety requirement of clinical implantation is completely met; the AIE molecules in the visual artificial vascular stent provided by the scheme of the invention not only have good imaging effect on blood vessels, but also have good photothermal antibacterial effect and broad-spectrum sterilization performance, can meet the requirement of effectively inhibiting drug-resistant bacterial infection of surrounding tissues during artificial vascular grafting, and has good clinical application prospects. The visual artificial blood vessel can be directly used as an artificial blood vessel implant for in-situ fluorescence imaging, so that the use of contrast agents is greatly avoided, the side effects of allergy, injury, kidney function damage, radiation and the like formed by arterial angiography are completely eradicated, noninvasive imaging observation can be realized without operation, and the visual observation function of the implanted artificial blood vessel is provided by combining portable near infrared imaging equipment, so that a reference means is provided for functional assessment of the artificial blood vessel.
While the embodiments of the present invention have been described in detail, the present invention is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present invention within the knowledge of those skilled in the art. Furthermore, embodiments of the invention and features of the embodiments may be combined with each other without conflict.
Claims (10)
1. The visual artificial vascular stent is characterized by comprising the following raw materials: AIE molecules, degradable polymeric materials;
wherein the mass ratio of the AIE molecules to the degradable high polymer material is (0.01-0.05): 1.
2. the visualized vascular stent of claim 1, wherein the AIE molecules are near infrared two-zone fluorescence imaging AIE molecules.
3. The visualized vascular stent of claim 1, wherein the degradable polymeric material is selected from at least one of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, sodium alginate, chitosan, hyaluronic acid, polyglycolic acid, polydioxanone.
4. The visualized vascular stent of claim 1, wherein the material further comprises a solvent.
5. The visualized vascular stent of claim 4, wherein the solvent is selected from at least one of N, N-dimethylformamide, tetrahydrofuran, acetone, dimethyl sulfoxide, dichloromethane, chloroform, absolute ethanol, hexafluoroisopropanol.
6. The visualized vascular stent of claim 1, wherein the vascular stent is cylindrical with an inner diameter in the range of 1-10 mm.
7. A method for preparing a visual artificial vascular stent according to any one of claims 1 to 6, comprising the steps of:
s1, dissolving AIE molecules in a solvent, adding a degradable polymer material, and stirring for dissolution to obtain micro-nano processing stock solution;
s2, preparing the nanofiber vascular stent from the micro-nano processing stock solution by using a micro-nano processing technology, and obtaining the visual artificial vascular stent.
8. The method for preparing a visualized vascular stent according to claim 7, wherein the method for dissolving the AIE molecules in step S1 comprises ultrasonic oscillation and stirring.
9. The method for preparing a visual artificial vascular stent according to claim 7, wherein the micro-nano processing technology is selected from one of 3D printing, electrostatic spinning, non-woven fabrics and template pouring.
10. Use of a visualized vascular stent according to any one of claims 1 to 6 or a method of preparation according to any one of claims 7 to 9 for vascular grafting, vascular imaging, for the preparation of a product for the treatment of cardiovascular related diseases.
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