CN111000661A - Composite artificial blood vessel and preparation method thereof - Google Patents
Composite artificial blood vessel and preparation method thereof Download PDFInfo
- Publication number
- CN111000661A CN111000661A CN202010092160.9A CN202010092160A CN111000661A CN 111000661 A CN111000661 A CN 111000661A CN 202010092160 A CN202010092160 A CN 202010092160A CN 111000661 A CN111000661 A CN 111000661A
- Authority
- CN
- China
- Prior art keywords
- nanofiber
- blood vessel
- nanofiber layer
- artificial blood
- layer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- Dispersion Chemistry (AREA)
- Physics & Mathematics (AREA)
- Fluid Mechanics (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Biophysics (AREA)
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- Prostheses (AREA)
Abstract
The invention relates to a composite artificial blood vessel and a preparation method for preparing the artificial blood vessel, wherein the artificial blood vessel has a double-layer tubular structure and comprises a first nanofiber layer arranged on an inner layer and a second nanofiber layer arranged on an outer layer, the first nanofiber layer is in fit connection with the second nanofiber layer, the first nanofiber layer is formed by rolling one, two or more layers of nanofiber membranes, the second nanofiber layer is of an integrally formed structure, and microporous structures are arranged on the first nanofiber layer and the second nanofiber layer.
Description
Technical Field
The invention relates to an artificial blood vessel, in particular to a composite artificial blood vessel and a preparation method thereof.
Background
The vascular system includes the heart, blood vessels and blood. The heart delivers fresh blood to various parts of the body via large and small blood vessels for the exchange of nutrients and waste products in the body to ensure the proper function of the organs. However, due to various arterial and venous vessel defects caused by atherosclerosis, hemangioma, traumatic injury and other causes, the repair treatment such as replacement, bypass and the like of a blood vessel part corresponding to a pathological change needs to be carried out by adopting blood vessel substitutes with different diameters through surgical operations. The blood vessel substitutes generally comprise autologous blood vessels, xenogeneic blood vessels, allogeneic blood vessels and artificial blood vessels, and since the autologous blood vessels are often limited by factors such as the age of a patient, the existing vascular diseases and the like and the source of the xenogeneic blood vessels and the allogeneic blood vessels is a problem, a large amount of artificial blood vessels are clinically needed to repair diseased blood vessels.
Electrospinning technology was proposed for the preparation of nanofiber materials as early as the 1930 s, but has not been in full use until recently. Compared with the traditional spinning technology, the electrostatic spinning technology can obtain finer fibers, and can effectively control the diameter of the fibers and the shape of a textile, in addition, the nanofiber material prepared by the electrostatic spinning technology has larger specific surface area and higher porosity, can simulate the microstructure of extracellular matrix, and has good biocompatibility. There have been many studies on the preparation of degradable nanofiber small-caliber artificial blood vessels (2-5 mm in diameter) by electrospinning, and it is expected that the degradable artificial blood vessels will regenerate autologous lesion blood vessels. However, the average pore size of electrospun nanofiber materials is usually less than 2 microns, and the diameters of smooth muscle cells and fibroblasts are 10-50 microns, so that the smooth muscle cells and fibroblasts can only slightly infiltrate into the blood vessel wall before the fibers are greatly degraded and broken, and are difficult to infiltrate and generate new blood vessel tissues in large quantities, which limits the speed of blood vessel regeneration. After the artificial blood vessel is implanted into a body, the mechanical property of the artificial blood vessel depends on the mechanical property of the nano fibers in the blood vessel wall and the mechanical property of the new tissue, when the nano fibers start to degrade greatly and break, the fibers basically lose the strength and elasticity, and at the moment, if the new tissue with certain mechanical property is not generated, the strength and elasticity of the artificial blood vessel are basically lost. When the artificial blood vessel does not have strength and elasticity, the vessel wall may collapse due to external pressure or rupture due to insufficient pressure of blood flow, thereby failing the revascularization procedure.
Disclosure of Invention
The invention provides a composite artificial blood vessel for solving the problem that smooth muscle cells and fibroblasts are difficult to infiltrate in large quantity before fibers of the existing electrostatic spinning nanofiber artificial blood vessel are degraded in large quantity and broken, and the artificial blood vessel enables the degradable nanofiber small-caliber artificial blood vessel to realize three-dimensional infiltration of autologous cells and regeneration of neogenetic tissues before the fibers begin to degrade in large quantity, so that the blood vessel still has good strength and elasticity when the fibers are degraded in large quantity.
The technical scheme adopted by the invention is as follows: a composite artificial blood vessel is of a double-layer tubular structure and comprises a first nanofiber layer arranged on an inner layer and a second nanofiber layer arranged on an outer layer, wherein the first nanofiber layer is attached to the second nanofiber layer, the first nanofiber layer is formed by rolling one, two or more layers of nanofiber membranes, the second nanofiber layer is of an integrally formed structure, and microporous structures are arranged on the first nanofiber layer and the second nanofiber layer;
the thickness of the first nanofiber layer is 50-100 microns, the average pore diameter of the microporous structure is 0.6-1.2 microns, and the average diameter of the fibers of the first nanofiber layer is 200-1000 nanometers;
the thickness of the second nanofiber layer is 200-600 microns, the average pore diameter of the microporous structure is 20-100 microns, and the average diameter of the fibers of the second nanofiber layer is 500-1400 nanometers.
Further, the nanofiber membrane forming the first nanofiber layer has a thickness of 5 to 50 micrometers.
Further, the first nanofiber layer is a collagen and caprolactone lactate copolymer nanofiber layer. The collagen has good biocompatibility and good hydrophilicity. Good biocompatibility, can reduce rejection reaction when the artificial blood vessel is used; good hydrophilicity is favorable for the adhesion of endothelial cells, so that the artificial blood vessel can be quickly endothelialized, and the formation of thrombus can be reduced. The lactic acid caprolactone copolymer is a degradable high-molecular synthetic material, has good biocompatibility and mechanical property, and can ensure that the nanofiber layer 1 has good strength and elasticity.
Further, the second nanofiber layer is a caprolactone lactate copolymer nanofiber layer. The lactic acid caprolactone copolymer is a degradable high-molecular synthetic material, has good biocompatibility and mechanical property, and can ensure that the nanofiber layer 2 has good strength and elasticity.
Further, the diameter of the artificial blood vessel is 2-5mm, and the wall thickness of the artificial blood vessel is 250-700 microns.
Further, the second nanofiber layer is prepared by pouring 30% -50% nanofiber solution into a mold.
The invention also provides a preparation method of the composite artificial blood vessel, which comprises the following steps
Preparing a first spinning solution, and preparing a first nanofiber membrane by using the first spinning solution through an electrostatic spinning method;
winding the first nanofiber membranes with the set number of layers on a mold rod to form a hollow tubular shape as a first nanofiber layer, and bonding the first nanofiber membranes of each layer through hot-pressing compounding;
preparing a second spinning solution, and preparing a second nanofiber membrane by an electrostatic spinning method by using the second spinning solution;
shearing the second nanofiber membrane, placing the second nanofiber membrane in deionized water, and uniformly dispersing fibers in the deionized water by using a high-speed refiner to obtain a nanofiber solution;
placing a first hollow tubular nanofiber layer in a mold cavity, arranging a gap with a set distance between the outer wall of the first nanofiber layer and the inner wall of the mold cavity, and pouring the nanofiber solution into the mold cavity to fill the gap between the outer wall of the first nanofiber layer and the inner wall of the mold cavity with the nanofiber solution;
forming a second nanofiber layer after the nanofiber solution is formed in the die cavity, wherein the second nanofiber layer is connected with the first nanofiber layer to form the artificial blood vessel;
and (3) performing crosslinking treatment on the artificial blood vessel after demolding.
Further, the first spinning solution is a spinning solution blended by collagen/caprolactone lactate copolymer, the second spinning solution is caprolactone lactate copolymer spinning solution, and the solvent of the first spinning solution and the second spinning solution is hexafluoroisopropanol.
Further, the mass ratio of the collagen/caprolactone lactate copolymer is 50:50 or 25:75, the concentration of the first spinning solution is 6% -12%, the concentration of the second spinning solution is 6% -12%, and the concentration of the nanofiber solution is 30% -50%.
Further, after the nanofiber solution is poured, freezing the mold provided with the first nanofiber layer and the nanofiber solution at a low temperature for 1-6 hours, and then carrying out freeze drying;
soaking the crosslinked artificial blood vessel in purified water for 5-10 min, and drying in an air-blast drying oven at 40-55 deg.C for 30-120 min to obtain the final desired composite artificial blood vessel.
Further, the more detailed preparation method comprises the following steps: the method comprises the following steps:
a. preparing a spinning solution blended by collagen/PLCL, wherein the mass ratio of the collagen/PLCL is 50:50 or 25:75, the concentration of the spinning solution is 6-12%, and the solvent is hexafluoroisopropanol;
b. b, preparing a nanofiber membrane with the thickness of 5-50 microns by using the spinning solution prepared in the step a through an electrostatic spinning method, wherein the spinning voltage is 8-20 kV;
c. winding a certain number of layers of nanofiber membranes on the stainless steel rod according to the thickness of the nanofiber layer 1 by using the nanofiber membrane prepared in the step b, and preparing the nanofiber layer 1 by hot-pressing compounding at the temperature of 45-55 ℃;
d. preparing a PLCL spinning solution, wherein the concentration of the spinning solution is 6-12%, and the solvent is hexafluoroisopropanol;
e. d, using the spinning solution prepared in the step d, preparing a PLCL nanofiber membrane by an electrostatic spinning method, shearing the PLCL nanofiber membrane into pieces, placing the pieces into deionized water, uniformly dispersing fibers by using a high-speed homogenizer to prepare a nanofiber solution with the concentration of 30-50%, and carrying out vacuum degassing treatment on the nanofiber solution before use;
f. and e, sleeving the first nanofiber layer prepared in the step c on an inner core of the blood vessel mold, sleeving an outer mold of the blood vessel mold to wrap the first nanofiber layer, and pouring the nanofiber solution prepared in the step e into a gap between the first nanofiber layer and the outer mold of the blood vessel mold. Standing and fixing the blood vessel preparation device, freezing the blood vessel preparation device in a low-temperature refrigerator at minus 80 ℃ for 1 to 6 hours, and then transferring the blood vessel preparation device to a freeze dryer for freeze drying;
g. and removing the freeze-dried artificial blood vessel from the blood vessel mold, and performing cross-linking treatment on the artificial blood vessel by using a genipin solution, wherein the concentration of the genipin solution is 0.5-2.0%, the dissolving temperature of the genipin solution is 37 ℃, the solvent is a blend of water and ethanol, and the volume ratio of the water to the ethanol is 80: 20. Soaking the artificial blood vessel into genipin solution for crosslinking, wherein the crosslinking time is 0.5-24 h, and the crosslinking temperature is 37 ℃. Genipin is a natural cross-linking agent, is mainly extracted from gardenia serving as a raw material, has the cytotoxicity of 1/10000 of glutaraldehyde which is a traditional cross-linking agent, and has the advantages of low toxicity and good cell compatibility besides high cross-linking efficiency similar to that of a traditional artificially synthesized chemical cross-linking agent. After genipin is used for crosslinking, the biodegradability and the mechanical property of the collagen material can be improved to a certain extent;
h. and g, soaking the artificial blood vessel prepared in the step g in purified water for 5-10 minutes, and then drying the artificial blood vessel in an air-blast drying oven at the drying temperature of 40-55 ℃ for 30-120 minutes.
The beneficial effects produced by the invention comprise:
1. the pore diameter of the second nanofiber layer is much larger than that of a common nanofiber material prepared by an electrostatic spinning technology, and is in the same order of magnitude as the diameters of smooth muscle cells and fibroblasts, so that the three-dimensional infiltration of autologous cells and the regeneration of new tissues can be realized before the fibers start to be degraded in a large amount, blood vessels still have good strength and elasticity when the fibers are degraded in a large amount, and the success rate of a blood vessel regeneration operation is improved.
2. Good biocompatibility, can reduce rejection reaction when the artificial blood vessel is used; good hydrophilicity is favorable for the adhesion of endothelial cells, so that the artificial blood vessel can be quickly endothelialized, and the formation of thrombus can be reduced. The lactic acid caprolactone copolymer is a degradable high-molecular synthetic material, has good biocompatibility and mechanical property, and can ensure that the first nanofiber layer has good strength and elasticity. The lactic acid caprolactone copolymer is a degradable high-molecular synthetic material, has good biocompatibility and mechanical property, and can ensure that the nanofiber layer 2 has good strength and elasticity.
3. The composite artificial blood vessel can realize the three-dimensional growth of autologous cells and the regeneration of new tissues before the fibers begin to degrade in a large amount, so that the blood vessel still has better strength and elasticity when the fibers degrade in a large amount, and the success rate of the blood vessel regeneration operation is improved. The composite artificial blood vessel is expected to be widely applied in the field of blood vessel regeneration. The method is simple to operate, good in repeatability and high in economic benefit.
Drawings
FIG. 1 is a schematic cross-sectional view of a blood vessel;
fig. 2 is a schematic view of a vascular processing die.
In the figure, 1, a first nanofiber layer, 2, a second nanofiber layer, 3, an inner core, 4 and an outer mold.
Detailed Description
The present invention is explained in further detail below with reference to the drawings and the specific embodiments, but it should be understood that the scope of the present invention is not limited to the specific embodiments.
As shown in fig. 1, the composite artificial blood vessel of the present invention has a double-layer tubular structure, which includes a first nanofiber layer 1 disposed on an inner layer and a second nanofiber layer 2 disposed on an outer layer, wherein the first nanofiber layer 1 is attached to the second nanofiber layer 2, the first nanofiber layer 1 is formed by rolling one, two or more nanofiber films, the second nanofiber layer 2 is an integrally formed structure, and the first nanofiber layer 1 and the second nanofiber layer 2 are both provided with a microporous structure;
the thickness of the first nanofiber layer 1 is 50-100 microns, the average pore diameter of the microporous structure is 0.6-1.2 microns, and the average diameter of the fibers of the first nanofiber layer 1 is 200-1000 nanometers; the thickness of the second nanofiber layer 2 is 200-600 microns, the average pore diameter of the microporous structure is 20-100 microns, and the average diameter of the fibers of the second nanofiber layer 2 is 500-1400 nanometers.
The nanofiber membrane forming the first nanofiber layer 1 has a thickness of 5 to 50 μm. The first nanofiber layer 1 is a collagen and caprolactone lactate copolymer nanofiber layer. The collagen has good biocompatibility and good hydrophilicity. Good biocompatibility, can reduce rejection reaction when the artificial blood vessel is used; good hydrophilicity is favorable for the adhesion of endothelial cells, so that the artificial blood vessel can be quickly endothelialized, and the formation of thrombus can be reduced. The caprolactone lactate copolymer is a degradable high-molecular synthetic material, has good biocompatibility and mechanical properties, and can ensure that the first nanofiber layer 1 has good strength and elasticity.
The second nanofiber layer 2 is a caprolactone lactate copolymer nanofiber layer. The lactic acid caprolactone copolymer is a degradable high-molecular synthetic material, has good biocompatibility and mechanical property, and can ensure that the nanofiber layer 2 has good strength and elasticity. The second nanofiber layer 2 is prepared by pouring 30% -50% nanofiber solution into a mold.
The diameter of the artificial blood vessel is 2-5mm, and the wall thickness of the artificial blood vessel is 250-700 microns.
The preparation method of the artificial blood vessel comprises the following steps: the method comprises the following steps:
a. preparing a spinning solution blended by collagen/PLCL, wherein the mass ratio of the collagen/PLCL is 50:50 or 25:75, the concentration of the spinning solution is 6-12%, and the solvent is hexafluoroisopropanol;
b. b, preparing a nanofiber membrane with the thickness of 5-50 microns by using the spinning solution prepared in the step a through an electrostatic spinning method, wherein the spinning voltage is 8-20 kV;
c. winding a certain number of nanofiber membranes on the stainless steel bar according to the thickness of the first nanofiber layer 1 by using the nanofiber membrane prepared in the step b, and preparing the nanofiber layer 1 by hot-pressing compounding at 45-55 ℃;
d. preparing a PLCL spinning solution, wherein the concentration of the spinning solution is 6-12%, and the solvent is hexafluoroisopropanol;
e. d, using the spinning solution prepared in the step d, preparing a PLCL nanofiber membrane by an electrostatic spinning method, shearing the PLCL nanofiber membrane into pieces, placing the pieces into deionized water, uniformly dispersing fibers by using a high-speed homogenizer to prepare a nanofiber solution with the concentration of 30-50%, and carrying out vacuum degassing treatment on the nanofiber solution before use;
f. and e, sleeving the first nanofiber layer 1 prepared in the step c on an inner core 3 of a blood vessel mold, sleeving an outer mold 4 of the blood vessel mold to wrap the first nanofiber layer 1, and pouring the nanofiber solution prepared in the step e into a gap between the first nanofiber layer 1 and the outer mold 4 of the blood vessel mold. Standing and fixing the blood vessel preparation device, freezing the blood vessel preparation device in a low-temperature refrigerator at minus 80 ℃ for 1 to 6 hours, and then transferring the blood vessel preparation device to a freeze dryer for freeze drying;
g. and removing the freeze-dried artificial blood vessel from the blood vessel mold, and performing cross-linking treatment on the artificial blood vessel by using a genipin solution, wherein the concentration of the genipin solution is 0.5-2.0%, the dissolving temperature of the genipin solution is 37 ℃, the solvent is a blend of water and ethanol, and the volume ratio of the water to the ethanol is 80: 20. Soaking the artificial blood vessel into genipin solution for crosslinking, wherein the crosslinking time is 0.5-24 h, and the crosslinking temperature is 37 ℃. Genipin is a natural cross-linking agent, is mainly extracted from gardenia serving as a raw material, has the cytotoxicity of 1/10000 of glutaraldehyde which is a traditional cross-linking agent, and has the advantages of low toxicity and good cell compatibility besides high cross-linking efficiency similar to that of a traditional artificially synthesized chemical cross-linking agent. After genipin is used for crosslinking, the biodegradability and the mechanical property of the collagen material can be improved to a certain extent;
h. and g, soaking the artificial blood vessel prepared in the step g in purified water for 5-10 minutes, and then drying the artificial blood vessel in an air-blast drying oven at the drying temperature of 40-55 ℃ for 30-120 minutes.
Example 1
Preparing a spinning solution of blended collagen/PLCL (lactic acid caprolactone copolymer), wherein the mass ratio of the collagen/PLCL is 50:50, the concentration of the spinning solution is 10% w/v, and the solvent is hexafluoroisopropanol. The nanofiber membrane with the thickness of 10 microns is prepared by an electrostatic spinning method, the spinning voltage is 12kV, the prepared nanofiber membrane is wound on a stainless steel rod with the thickness of 3.0mm for 7 layers, the first nanofiber layer 1 is prepared by hot pressing compounding at the temperature of 50 ℃, and the thickness of the first nanofiber layer 1 is 56 microns.
A PLCL spinning solution was prepared with a concentration of 8% and a solvent of hexafluoroisopropanol. The PLCL nanofiber membrane is prepared by an electrostatic spinning method, then the PLCL nanofiber membrane is cut into pieces, the pieces are placed in deionized water, a high-speed homogenizer is used for uniformly dispersing fibers, a nanofiber solution with the concentration of 35% is prepared, and vacuum degassing treatment is needed before the nanofiber solution is used.
Sleeving the prepared first nanofiber layer 1 on an inner core 3 of a blood vessel processing mold, sleeving a blood vessel mold outer mold 4, enabling the outer mold 4 to wrap the first nanofiber layer 1, and pouring 35% nanofiber solution into a gap between the first nanofiber layer 1 and the blood vessel mold outer mold 4. The blood vessel preparation apparatus was left to stand and fixed in a low-temperature refrigerator at-80 ℃ and was subjected to freezing treatment for 3 hours, followed by transferring to a freeze-dryer for freeze-drying.
And removing the freeze-dried artificial blood vessel from the blood vessel mold, and performing crosslinking treatment on the artificial blood vessel by using a genipin solution, wherein the concentration of the genipin solution is 1.0%, the dissolving temperature of the genipin solution is 37 ℃, the solvent is a blend of water and ethanol, and the volume ratio of the water to the ethanol is 80: 20. Soaking the artificial blood vessel into genipin solution for crosslinking, wherein the crosslinking time is 3h, and the crosslinking temperature is 37 ℃. Soaking the crosslinked artificial blood vessel in purified water for 5-10 min, and drying in a forced air drying oven at 50 deg.C for 60 min.
The inner diameter of the prepared composite artificial blood vessel is 3.0mm, the thickness of the tube wall is 350 micrometers, the thickness of the first nanofiber layer 1 is 56 micrometers, and the thickness of the second nanofiber layer 2 is 294 micrometers. The pore size of the first nanofiber layer 1 was 0.8 microns and the pore size of the second nanofiber layer 2 was 81 microns.
Example 2
Preparing a spinning solution blended by collagen/PLCL, wherein the mass ratio of the collagen/PLCL is 25:75, the concentration of the spinning solution is 9% w/v, and the solvent is hexafluoroisopropanol. The nanofiber membrane with the thickness of 10 microns is prepared by an electrostatic spinning method, the spinning voltage is 12kV, the prepared nanofiber membrane is wound on a 4.0mm stainless steel rod for 8 layers, the first nanofiber layer 1 is prepared by hot pressing compounding at 50 ℃, and the thickness of the first nanofiber layer 1 is measured to be 62 microns by a laser diameter measuring instrument.
A PLCL spinning solution was prepared with a concentration of 8% and a solvent of hexafluoroisopropanol. The PLCL nanofiber membrane is prepared by an electrostatic spinning method, then the PLCL nanofiber membrane is cut into pieces, the pieces are placed in deionized water, a high-speed homogenizer is used for uniformly dispersing fibers, a nanofiber solution with the concentration of 40% is prepared, and vacuum degassing treatment is needed before the nanofiber solution is used.
Sleeving the prepared first nanofiber layer 1 on an inner core 3 of a blood vessel processing mold, sleeving a blood vessel mold outer mold 4, enabling the outer mold 4 to wrap the first nanofiber layer 1, and pouring 40% nanofiber solution into a gap between the first nanofiber layer 1 and the blood vessel mold outer mold 4. The blood vessel preparation apparatus was left to stand and fixed in a low-temperature refrigerator at-80 ℃ and was subjected to freezing treatment for 3 hours, followed by transferring to a freeze-dryer for freeze-drying.
And removing the freeze-dried artificial blood vessel from the blood vessel mold, and performing crosslinking treatment on the artificial blood vessel by using a genipin solution, wherein the concentration of the genipin solution is 1.0%, the dissolving temperature of the genipin solution is 37 ℃, the solvent is a blend of water and ethanol, and the volume ratio of the water to the ethanol is 80: 20. Soaking the artificial blood vessel into genipin solution for crosslinking, wherein the crosslinking time is 3h, and the crosslinking temperature is 37 ℃. Soaking the crosslinked artificial blood vessel in purified water for 5-10 min, and drying in a forced air drying oven at 50 deg.C for 60 min.
The inner diameter of the prepared composite artificial blood vessel is 4.0mm, the thickness of the tube wall is 450 micrometers, the thickness of the first nanofiber layer 1 is 62 micrometers, and the thickness of the second nanofiber layer 2 is 388 micrometers. The pore size of the first nanofiber layer 1 was 0.7 microns and the pore size of the second nanofiber layer 2 was 59 microns.
Example 3
Preparing a spinning solution blended by collagen/PLCL, wherein the mass ratio of the collagen/PLCL is 25:75, the concentration of the spinning solution is 9% w/v, and the solvent is hexafluoroisopropanol. The nanofiber membrane with the thickness of 6 microns is prepared by an electrostatic spinning method, the spinning voltage is 12kV, the prepared nanofiber membrane is wound on a stainless steel rod with the thickness of 2.5mm for 15 layers, the first nanofiber layer 1 is prepared by hot pressing compounding at the temperature of 50 ℃, and the thickness of the first nanofiber layer 1 measured by a laser diameter measuring instrument is 78 microns.
A PLCL spinning solution was prepared, the concentration of the spinning solution being 6% and the solvent being hexafluoroisopropanol. Preparing a PLCL nanofiber membrane by an electrostatic spinning method, then cutting the PLCL nanofiber membrane into pieces, placing the pieces into deionized water, uniformly dispersing fibers by using a high-speed refiner, and preparing a nanofiber solution with the concentration of 50%, wherein the nanofiber solution needs to be subjected to vacuum degassing treatment before use;
sleeving the prepared first nanofiber layer 1 on an inner core 3 of a blood vessel processing mold, sleeving a blood vessel mold outer mold 4, enabling the outer mold 4 to wrap the first nanofiber layer 1, and pouring 50% nanofiber solution into a gap between the first nanofiber layer 1 and the blood vessel mold outer mold 4. The blood vessel preparation apparatus was left to stand and fixed in a low-temperature refrigerator at-80 ℃ and was subjected to freezing treatment for 3 hours, followed by transferring to a freeze-dryer for freeze-drying.
And removing the freeze-dried artificial blood vessel from the blood vessel mold, and performing crosslinking treatment on the artificial blood vessel by using a genipin solution, wherein the concentration of the genipin solution is 1.0%, the dissolving temperature of the genipin solution is 37 ℃, the solvent is a blend of water and ethanol, and the volume ratio of the water to the ethanol is 80: 20. Soaking the artificial blood vessel into genipin solution for crosslinking, wherein the crosslinking time is 3h, and the crosslinking temperature is 37 ℃. Soaking the crosslinked artificial blood vessel in purified water for 5-10 min, and drying in a forced air drying oven at 50 deg.C for 60 min.
The inner diameter of the prepared composite artificial blood vessel is 2.5mm, the thickness of the tube wall is 260 microns, the thickness of the first nanofiber layer 1 is 78 microns, and the thickness of the second nanofiber layer 2 is 182 microns. The pore size of the first nanofiber layer 1 was 0.7 microns and the pore size of the second nanofiber layer 2 was 29 microns.
As shown in fig. 2, the blood vessel processing mold mentioned in embodiments 1 to 3 includes an inner core 3 and an outer mold 4, the outer mold 4 is a hollow columnar structure, the inner core 3 is inserted into a hollow cavity of the outer mold 4, the hollow cavity of the outer mold 4 is coaxial with the inner core 3, after the first nanofiber layer 1 is sleeved on the inner core 3, the inner core 3 is placed into the hollow cavity of the outer mold 4, a gap is formed between the first nanofiber layer 1 and an inner wall of the hollow cavity, and the nanofiber solution is poured into the gap for molding.
The above description is only a preferred embodiment of the present invention, and the present invention is not limited to the content of the embodiment. It will be apparent to those skilled in the art that various changes and modifications can be made within the technical scope of the present invention, and any changes and modifications made are within the protective scope of the present invention.
Claims (10)
1. A composite artificial blood vessel is characterized in that: the artificial blood vessel is of a double-layer tubular structure and comprises a first nanofiber layer arranged on an inner layer and a second nanofiber layer arranged on an outer layer, wherein the first nanofiber layer is in fit connection with the second nanofiber layer, the first nanofiber layer is formed by rolling one, two or more layers of nanofiber membranes, the second nanofiber layer is of an integrally formed structure, and microporous structures are arranged on the first nanofiber layer and the second nanofiber layer;
the thickness of the first nanofiber layer is 50-100 microns, the average pore diameter of the microporous structure is 0.6-1.2 microns, and the average diameter of the fibers of the first nanofiber layer is 200-1000 nanometers;
the thickness of the second nanofiber layer is 200-600 microns, the average pore diameter of the microporous structure is 20-100 microns, and the average diameter of the fibers of the second nanofiber layer is 500-1400 nanometers.
2. The composite type artificial blood vessel according to claim 1, wherein: the nanofiber membrane forming the first nanofiber layer has a thickness of 5-50 microns.
3. The composite type artificial blood vessel according to claim 1, wherein: the first nanofiber layer is a collagen and lactic acid caprolactone copolymer nanofiber layer.
4. The composite type artificial blood vessel according to claim 1, wherein: the second nanofiber layer is a caprolactone lactate copolymer nanofiber layer.
5. The composite type artificial blood vessel according to claim 1, wherein: the diameter of the artificial blood vessel is 2-5mm, and the wall thickness of the artificial blood vessel is 250-700 microns.
6. The composite type artificial blood vessel according to claim 1, wherein: the second nanofiber layer is prepared by pouring 30% -50% nanofiber solution into a mold.
7. A preparation method of a composite artificial blood vessel is characterized by comprising the following steps: comprises the following steps
Preparing a first spinning solution, and preparing a first nanofiber membrane by using the first spinning solution through an electrostatic spinning method;
winding the first nanofiber membranes with the set number of layers on a mold rod to form a hollow tubular shape as a first nanofiber layer, and bonding the first nanofiber membranes of each layer through hot-pressing compounding;
preparing a second spinning solution, and preparing a second nanofiber membrane by an electrostatic spinning method by using the second spinning solution;
shearing the second nanofiber membrane, placing the second nanofiber membrane in deionized water, and uniformly dispersing fibers in the deionized water by using a high-speed refiner to obtain a nanofiber solution;
placing a first hollow tubular nanofiber layer in a mold cavity, arranging a gap with a set distance between the outer wall of the first nanofiber layer and the inner wall of the mold cavity, and pouring the nanofiber solution into the mold cavity to fill the gap between the outer wall of the first nanofiber layer and the inner wall of the mold cavity with the nanofiber solution;
forming a second nanofiber layer after the nanofiber solution is formed in the die cavity, wherein the second nanofiber layer is connected with the first nanofiber layer to form the artificial blood vessel;
and (3) performing crosslinking treatment on the artificial blood vessel after demolding.
8. The method for preparing a composite artificial blood vessel according to claim 7, wherein: the first spinning solution is a spinning solution blended by collagen/caprolactone lactate copolymer, the second spinning solution is caprolactone lactate copolymer spinning solution, and the solvent of the first spinning solution and the second spinning solution is hexafluoroisopropanol.
9. The method for preparing a composite artificial blood vessel according to claim 8, wherein: the mass ratio of the collagen/caprolactone lactate copolymer is 50:50 or 25:75, the concentration of the first spinning solution is 6% -12%, the concentration of the second spinning solution is 6% -12%, and the concentration of the nanofiber solution is 30% -50%.
10. The method for preparing a composite artificial blood vessel according to claim 7, wherein: after the nanofiber solution is poured, freezing the mold provided with the first nanofiber layer and the nanofiber solution at a low temperature for 1-6 hours, and then carrying out freeze drying;
soaking the crosslinked artificial blood vessel in purified water for 5-10 min, and drying in an air-blast drying oven at 40-55 deg.C for 30-120 min to obtain the final desired composite artificial blood vessel.
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| CN112439094A (en) * | 2020-12-01 | 2021-03-05 | 紫水晶(山西)再生医学科技有限公司 | Artificial blood vessel based on bioactive glass material and preparation method thereof |
| CN112843334A (en) * | 2021-01-13 | 2021-05-28 | 东华大学 | Bionic trachea constructed by three-dimensional printing composite aerogel and preparation method thereof |
| CN115990293A (en) * | 2023-01-30 | 2023-04-21 | 博裕纤维科技（苏州）有限公司 | Preparation method of medical multi-layer self-supporting medicine-carrying shell-core structure nanofiber tube |
| CN116036387A (en) * | 2023-01-30 | 2023-05-02 | 博裕纤维科技（苏州）有限公司 | Preparation method of external-wrapping type drug-loaded visual nanofiber artificial vascular stent |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112439094A (en) * | 2020-12-01 | 2021-03-05 | 紫水晶(山西)再生医学科技有限公司 | Artificial blood vessel based on bioactive glass material and preparation method thereof |
| CN112843334A (en) * | 2021-01-13 | 2021-05-28 | 东华大学 | Bionic trachea constructed by three-dimensional printing composite aerogel and preparation method thereof |
| CN112843334B (en) * | 2021-01-13 | 2022-07-08 | 东华大学 | Bionic trachea constructed by three-dimensional printing composite aerogel and preparation method thereof |
| CN115990293A (en) * | 2023-01-30 | 2023-04-21 | 博裕纤维科技（苏州）有限公司 | Preparation method of medical multi-layer self-supporting medicine-carrying shell-core structure nanofiber tube |
| CN116036387A (en) * | 2023-01-30 | 2023-05-02 | 博裕纤维科技（苏州）有限公司 | Preparation method of external-wrapping type drug-loaded visual nanofiber artificial vascular stent |
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