CN111000660B - 3D printing artificial blood vessel and preparation method thereof - Google Patents
3D printing artificial blood vessel and preparation method thereof Download PDFInfo
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- CN111000660B CN111000660B CN202010092153.9A CN202010092153A CN111000660B CN 111000660 B CN111000660 B CN 111000660B CN 202010092153 A CN202010092153 A CN 202010092153A CN 111000660 B CN111000660 B CN 111000660B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
- A61F2/06—Blood vessels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y10/00—Processes of additive manufacturing
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- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/0007—Electro-spinning
- D01D5/0015—Electro-spinning characterised by the initial state of the material
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- D—TEXTILES; PAPER
- D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
- D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
- D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
- D04H1/70—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
- D04H1/72—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
- D04H1/728—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2240/001—Designing or manufacturing processes
- A61F2240/002—Designing or making customized prostheses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0014—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
- A61F2250/0023—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in porosity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/22—Materials or treatment for tissue regeneration for reconstruction of hollow organs, e.g. bladder, esophagus, urether, uterus
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- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Dermatology (AREA)
- Textile Engineering (AREA)
- Vascular Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Materials Engineering (AREA)
- Dispersion Chemistry (AREA)
- Manufacturing & Machinery (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Prostheses (AREA)
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Abstract
The invention relates to a 3D printing artificial blood vessel and a preparation method thereof, comprising the following steps: preparing a nano fiber membrane compounded by a bioactive material/elastomer polymer through electrostatic spinning; cutting the nanofiber membrane, and uniformly dispersing the nanofiber membrane in a solvent to prepare nanofiber solutions for 3D printing with different concentrations; printing nanofiber solutions with different concentrations layer by layer at low temperature according to the concentration by using a 3D printing technology to obtain an artificial blood vessel semi-finished product, wherein the nanofiber concentration in the nanofiber solution used for printing is gradually reduced from the inner layer to the outer layer of the artificial blood vessel; and (3) placing the semi-finished product of the artificial blood vessel in a low-temperature environment for freezing treatment to obtain the artificial blood vessel with gradient pore size distribution. The artificial blood vessel prepared by the method does not leak blood in the operation, and the structure of the blood vessel wall bionic extracellular matrix is beneficial to the three-dimensional growth of cells.
Description
Technical Field
The invention relates to an artificial blood vessel, in particular to a 3D printing 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 through large and small blood vessels for exchange of nutrients and waste products in the body to ensure proper functioning of the organs. However, atherosclerosis, hemangioma, external force wound and other causes various arterial and venous vascular defects, and repair treatment such as replacement, bypass and the like of the corresponding lesion vascular parts is needed by adopting vascular substitutes with different diameters through surgical operation. The vascular substitutes generally comprise autologous blood vessels, xenogeneic blood vessels, allogeneic blood vessels and artificial blood vessels, and a large amount of artificial blood vessels are clinically needed to repair diseased blood vessels because the autologous blood vessels are often limited by factors such as age of patients, existing vascular diseases and the like and the source problems of the xenogeneic blood vessels and the allogeneic blood vessels.
There are various problems with the artificial blood vessels that are currently commercialized: an expanded polytetrafluoroethylene (ePTFE) artificial blood vessel, a needle eye exists at a suture position, and blood is easy to bleed during and after operation; and the pore diameter of the pipe wall is smaller, so that cells are not easy to grow in three dimensions. The dacron (PET) artificial blood vessel has a rough inner surface, and is easy to form thrombus; and the pore diameter of the tube wall is larger, blood leakage is easy to occur in the operation, and the PET blood vessel generally adopts the operation of pre-coagulation or biological coating to avoid the problem of blood leakage in the operation. And the commercial artificial blood vessels are standardized products, the diameters and the wall thicknesses of the blood vessels are fixed, and the actual lesion blood vessel sizes of each patient are difficult to be completely matched.
At present, no artificial blood vessel which can simultaneously meet the requirement of no blood leakage in operation, has bionic extracellular matrix on the wall of a blood vessel, is favorable for three-dimensional growth of cells and can be customized according to the actual lesion blood vessel size of a patient does not exist clinically.
Disclosure of Invention
The invention aims to provide an artificial blood vessel which does not leak blood in operation and has a structure of a blood vessel wall bionic extracellular matrix, thereby being beneficial to three-dimensional cell ingrowth.
In order to achieve the above purpose, the technical scheme adopted is as follows: the invention provides a method for preparing a blood vessel by using a microporous structure, which comprises a plurality of nanofiber layers in the radial direction, wherein each nanofiber layer is provided with a microporous structure, the pore diameter of the micropores of the nanofiber layer from inside to outside is gradually increased, and the pore diameter range of the microporous structure arranged on the nanofiber layer of the innermost layer of the blood vessel is 0.5-10 microns.
Further, the nanofiber layer is a bioactive material/elastomeric polymer composite layer.
The invention also provides a preparation method of the D-printed artificial blood vessel, which comprises the following steps of
S01, preparing a nano fiber membrane compounded by a bioactive material/elastomer polymer through electrostatic spinning;
s02, cutting the nanofiber membrane, placing the nanofiber membrane in a solvent for uniform dispersion, and preparing and generating nanofiber solutions for 3D printing with different concentrations;
s03, printing nanofiber solutions with different concentrations layer by layer at low temperature according to the concentration by using a 3D printing technology to obtain an artificial blood vessel semi-finished product, wherein the nanofiber concentration in the nanofiber solution used for printing is gradually reduced from the inner layer to the outer layer of the artificial blood vessel;
s04, placing the artificial blood vessel semi-finished product in a low-temperature environment for freezing treatment to obtain the artificial blood vessel with gradient pore size distribution. The nanofiber is used as a printing matrix, so that the blood vessel wall can simulate the structure of an extracellular matrix.
Further, the freezing treatment is freezing treatment at-80 ℃, and then the artificial blood vessel with the pore size gradient distribution is prepared by freeze drying.
Further, the bioactive material is one or more of collagen, hyaluronic acid, elastin, gelatin and silk fibroin. All the materials have good biocompatibility and hydrophilic performance. Good biocompatibility, can reduce rejection reaction when the artificial blood vessel is used; good hydrophilicity, favorability for adhesion of endothelial cells, rapid endothelialization of artificial blood vessels, and reduced thrombosis.
Further, the elastomer polymer is one or two of lactic acid-caprolactone copolymer or polyurethane. Both PLCL (lactic acid-caprolactone copolymer) and PU (polyurethane) materials have good elasticity and strength. The composite nanofiber is prepared by blending the elastomer polymer and the bioactive material, so that the artificial blood vessel can be ensured to have better elasticity and strength.
Further, the mass content of the bioactive material and the elastomer polymer is as follows: 20% -50% of bioactive material, 50% -80% of elastomer polymer. The content of the elastomer polymer is not less than 50%, and the strength and elasticity of the artificial blood vessel can be ensured.
Further, spinning parameters for preparing the bioactive material/elastomer polymer composite nanofiber membrane by electrostatic spinning are as follows: the solvent used in spinning is one or more of hexafluoroisopropanol, tetrahydrofuran, N-dimethylformamide or 2-butanone, and the concentration of the spinning solution is as follows: 6% -12% w/v, and the liquid feeding speed during electrostatic spinning is 1mL/h-3mL/h.
Further, the solvent of the nanofiber solution for 3D printing is one or two of water, tertiary butanol and glycerol, the nanofiber concentration of the nanofiber solution for 3D printing is 20% -80% (w/v), and the nanofiber solution for 3D printing is subjected to vacuum degassing treatment before 3D printing.
Further, the outer diameter and the length of the artificial blood vessel are 3D printed, and the artificial blood vessel is obtained through CT scanning files of the receptor diseased blood vessel. And then determining the wall thickness of the required artificial blood vessel according to clinical experience according to the blood vessel type of the lesion blood vessel, generating a 3D blood vessel model through optimization reconstruction, and finally converting the model into an STL file which can be identified by 3D printing equipment for later use.
Further, after 3D printing is finished, rapidly transferring the artificial blood vessel semi-finished product to a low-temperature refrigerator at-80 ℃ for freezing, and after the freezing treatment is carried out for 1-3 hours, carrying out freeze drying treatment on the artificial blood vessel.
Further, the artificial blood vessel is printed in 6 layers, and the nanofiber concentration and the layer thickness in the nanofiber solution used in the radial printing from inside to outside are respectively as follows: the concentration of the 1 st layer is 70-80%, and the thickness of the layer is 10-250 micrometers; the concentration of the layer 2 is 60% -75%, and the thickness of the layer is 10 micrometers-350 micrometers; the concentration of the layer 3 is 50% -65%, and the thickness of the layer is 10 micrometers-450 micrometers; the concentration of the 4 th layer is 40% -55%, and the thickness of the layer is 10 micrometers-550 micrometers; the concentration of the 5 th layer is 30% -45%, and the thickness of the layer is 10 micrometers-650 micrometers; the concentration of the 6 th layer is 20% -35%, and the thickness of the layer is 10-750 microns.
Further, the artificial blood vessel is printed in 6 layers, the layers 1 to 6 are sequentially arranged from inside to outside, the layers 1 to 6 contain micropores, the pore diameters of the micropores from the layers 1 to 6 are gradually increased, and the pore diameter range of the layer 1 is 0.5-10 microns; the pore diameter of the 2 nd layer ranges from 5 micrometers to 20 micrometers; the pore diameter of the 3 rd layer ranges from 10 micrometers to 40 micrometers; the pore diameter of the 4 th layer ranges from 20 micrometers to 80 micrometers; the pore diameter of the 5 th layer ranges from 40 micrometers to 160 micrometers; the pore size of layer 6 ranges from 80 microns to 320 microns. The aperture of the 1 st layer and the 2 nd layer of the artificial blood vessel is smaller, so that the artificial blood vessel can not leak blood in operation when in use. The apertures of the 3 rd layer, the 4 th layer, the 5 th layer and the 6 th layer of the artificial blood vessel are larger, which is beneficial for the three-dimensional growth of cells along the wall of the blood vessel, so that the blood vessel and the autologous tissue are fused into a whole.
The artificial blood vessels with the same diameter, the same length and the same wall thickness have the advantages that the mechanical strength of the blood vessels is improved, but the compliance is reduced along with the increase of the content of the whole materials. The increase of the content of the whole material is realized by increasing the concentration of the nanofiber solution for printing, the porosity is reduced after the concentration of the nanofiber solution for printing is increased, and the whole material is increased.
The invention also provides the 3D printing artificial blood vessel prepared based on the preparation method.
The beneficial effects of the invention include: (1) The 3D printing artificial blood vessel disclosed by the invention has the advantages that blood does not leak in an operation, and the structure of the blood vessel wall bionic extracellular matrix is beneficial to the three-dimensional growth of cells. Furthermore, the vascular prosthesis of the present invention can be customized to the actual lesion vessel size of the patient. The 3D printing artificial blood vessel can be widely applied to blood vessel replacement and blood vessel bypass operation.
(2) 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 3D printed vascular prosthesis of the present invention;
FIG. 2 is a flow chart of a method for preparing a 3D printed vascular prosthesis according to the invention;
FIG. 3 is a schematic diagram of the principle of the 3D printing head and sample stage of the present invention;
in the figure, 1 st layer, 2 nd layer, 3 rd layer, 4 th layer, 5 th layer, 6 th layer, 7 th layer, first solution, 8 th layer, second solution, 9 th layer, third solution, 10 th layer, fourth solution, 11 th layer, fifth solution, 12 th layer, sixth solution, 13 th layer, sample stage, 14 th layer, and motor.
Detailed Description
The invention will be explained in further detail below with reference to the drawings and the specific embodiments, but it should be understood that the scope of protection of the invention is not limited to the specific embodiments.
As shown in FIG. 1,3D printed artificial blood vessel comprises six layers, including 1 st layer, 2 nd layer, 3 rd layer, 4 th layer, 5 th layer, and 6 th layer from inside to outside, and is prepared by the method shown in FIG. 2, including
1) The bioactive material/elastomer polymer composite nanofiber membrane is prepared through electrostatic spinning.
2) Cutting the nanofiber membrane, and uniformly dispersing the fibers in a solvent by using a high-speed refiner;
3) The nanofiber solutions for 3D printing with different concentrations are prepared and generated, and the nanofiber solutions are sequentially a first solution 7, a second solution 8, a third solution 9, a fourth solution 10, a fifth solution 11 and a sixth solution 12, as shown in fig. 3.
4) Printing nanofiber solutions with different concentrations layer by layer at low temperature by using a 3D printing technology to prepare an artificial blood vessel semi-finished product;
5) Then freezing at-80 ℃;
6) And obtaining the artificial blood vessel with the pore size gradient distribution through freeze drying.
Wherein, the outside diameter and the length of the artificial blood vessel are printed in 3D mode, and the artificial blood vessel is obtained through CT scanning files of the receptor pathological change blood vessel. And then determining the wall thickness of the required artificial blood vessel according to clinical experience according to the blood vessel type of the lesion blood vessel, generating a 3D blood vessel model through optimization reconstruction, and finally converting the model into an STL file which can be identified by 3D printing equipment for later use.
As shown in fig. 3, the device for printing includes a sample stage and a motor, wherein the first solution 7, the second solution 8, the third solution 9, the fourth solution 10, the fifth solution 11 and the sixth solution 12 are all sprayed to the sample stage 13, the motor 14 drives the sample stage 13 to rotate, three-dimensional printing in the circumferential direction is realized, and the temperature range of the sample stage is as follows: after the solution comes out of the spray head at the temperature of 30 ℃ to 0 ℃, the solution is printed on a sample stage, the temperature of the whole sample stage is relatively low, and the solution can be quickly solidified. The solution will flow without solidifying and will not remain in a certain shape.
Example 1
Preparing a collagen/caprolactone lactate copolymer composite nanofiber membrane by electrostatic spinning, wherein the spinning parameters are as follows: the mass ratio of the collagen to the caprolactone lactate copolymer is 25:75, the solvent is hexafluoroisopropanol, the concentration of the spinning solution is 10%, and the spinning feed rate is 1.5mL/h.
Cutting nanofiber membrane, placing into glycerol solvent, and dispersing fiber uniformly by high-speed refiner to obtain collagen/caprolactone copolymer nanofiber solution with concentration of 75%, 65%, 55%, 45%, 35% and 25%. And (3) carrying out vacuum degassing treatment on the nanofiber solution for later use.
The outer diameter of the artificial blood vessel is 5.8mm and the length is 23mm through the CT scanning file of the receptor pathological change blood vessel. The wall thickness of the required artificial blood vessel is determined to be 350 microns according to clinical experience, then a 3D blood vessel model is generated through optimization reconstruction, and finally the model is converted into an STL file which can be identified by 3D printing equipment for later use.
The artificial blood vessel semi-finished product is prepared by using a 3D printing technology and using nanofiber solutions with different concentrations to print at low temperature layer by layer from inside to outside, wherein the layer 1 is 75% of nanofiber solution, and the layer thickness is 50 microns; layer 2 used 65% nanofiber solution with a layer thickness of 50 microns; layer 3 using a 55% nanofiber solution with a layer thickness of 50 microns; layer 4 uses 45% nanofiber solution with a layer thickness of 50 microns; layer 5 uses a 35% nanofiber solution with a layer thickness of 75 microns; layer 6 used 25% nanofiber solution with a layer thickness of 75 microns. In 3D printing, the temperature of the sample stage 13 is: -20 ℃.
Rapidly transferring the semi-finished product of the artificial blood vessel to a low-temperature refrigerator at-80 ℃ for freezing, and finally performing freeze drying treatment on the artificial blood vessel after 3 hours of freezing treatment.
The artificial blood vessel A prepared by the method.
The aperture of each layer of the prepared artificial blood vessel wall is measured by adopting a PMI aperture meter, and the method specifically comprises the following steps: cutting a sample to be measured into a circle with the diameter of about 5 mm; wetting a sample with a wetting liquid, and then placing the sample into an adapter plate; sealing, opening an air inlet valve, and introducing air into the test box; with the increase of pressure, the maximum pore diameter (or bubble point pore diameter) of the sample is opened firstly, then smaller and smaller pores are opened, a dry curve and a wet curve are displayed on a test interface, a semi-dry curve is obtained by taking one half of the numerical value of each point on the dry curve, and the average pore diameter can be calculated by taking the pressure value at the intersection point of the semi-dry curve and the corresponding wet curve. Layers 1 to 6 contain micropores, and the pore diameters of the micropores of layers 1 to 6 are gradually increased, and the pore diameter of layer 1 is 1.2 micrometers; layer 2 has a pore size of 10.5 microns; layer 3 has a pore size of 25.1 microns; the pore size range of layer 4 is 52.5 microns; the pore size range of layer 5 is 100.6 microns; the pore size range of layer 6 was 160.4 microns.
Testing of the water permeability of the vascular prosthesis: one end of the artificial blood vessel is fixed on the water seepage instrument, and the other end is sealed by a metal clip. The water valve of the water seepage instrument was opened to fill the artificial blood vessel, and the volume of water seeping from the wall of the vessel was measured within 10 minutes at a water pressure of (16.0.+ -. 0.3) kPa. The prepared artificial blood vessel has water seepage of 0 at 16 kPa.
The biocompatibility of vascular prosthesis a was determined by contacting cultured cells with the extract, and its cytotoxicity was measured as grade 0 by observation of cell morphology, proliferation and inhibition effects.
The compliance of the vascular stent in a wet state is measured by a customized vascular compliance testing device, the testing device mainly simulates the pressure of human blood flow on the vascular wall to expand, and the change of the inner diameter of the blood vessel during the expansion and contraction is recorded, so that the size of the compliance is calculated. The calculation method is as follows: % company= [ (R) P2 -R P1 ）/R P1 ]/(P 2 -P 1 )×10 4 Wherein R is the inner diameter of human hematopoietic vessel, R P1 Is the inner diameter at a pressure of 80mmHg, R P2 Is the inner diameter at 120mmHg, P 1 =80mmHg，P 2 =120 mmHg. The compliance of the vascular prosthesis was calculated to be 4.6% by testing.
Example 2
Preparing a silk fibroin/caprolactone lactate copolymer composite nanofiber membrane by electrostatic spinning, wherein the spinning parameters are as follows: the mass ratio of the silk fibroin to the lactic acid caprolactone copolymer is 20:80, the solvent is hexafluoroisopropanol, the concentration of the spinning solution is 11.5%, and the spinning solution feeding speed is 1mL/h.
Cutting the silk fibroin/caprolactone lactate copolymer nanofiber membrane, placing the cut silk fibroin/caprolactone lactate copolymer nanofiber membrane into deionized water, and uniformly dispersing the fibers by using a high-speed refiner to prepare and generate collagen/caprolactone lactate copolymer nanofiber solutions with the concentration of 80%, 70%, 60%, 50%, 40% and 25%. And (3) carrying out vacuum degassing treatment on the nanofiber solution for later use.
The outer diameter of the artificial blood vessel is determined to be 4.5mm and the length is determined to be 30mm through the CT scanning file of the receptor pathological blood vessel. The wall thickness of the required artificial blood vessel is determined to be 300 micrometers according to clinical experience, then a 3D blood vessel model is generated through optimization reconstruction, and finally the model is converted into an STL file which can be identified by 3D printing equipment for later use.
The artificial blood vessel semi-finished product is prepared by using a 3D printing technology and using nanofiber solutions with different concentrations from inside to outside in a layer-by-layer low-temperature printing mode, wherein the layer 1 is 80% nanofiber solution, and the layer thickness is 40 microns; layer 2 uses 70% nanofiber solution with a layer thickness of 40 microns; layer 3 uses a 60% nanofiber solution with a layer thickness of 40 microns; layer 4 uses a 50% nanofiber solution with a layer thickness of 40 microns; layer 5 uses 40% nanofiber solution with a layer thickness of 70 microns; layer 6 used 25% nanofiber solution with a layer thickness of 70 microns. In 3D printing, the temperature of the sample stage 13 is: -20 ℃.
Rapidly transferring the semi-finished product of the artificial blood vessel to a low-temperature refrigerator at-80 ℃ for freezing, and finally performing freeze drying treatment on the artificial blood vessel after 3 hours of freezing treatment.
The artificial blood vessel B prepared by the method.
The aperture of each layer of the prepared artificial blood vessel wall is measured by adopting a PMI aperture meter, and the method specifically comprises the following steps: cutting a sample to be measured into a circle with the diameter of about 5 mm; wetting a sample with a wetting liquid, and then placing the sample into an adapter plate; sealing, opening an air inlet valve, and introducing air into the test box; with the increase of pressure, the maximum pore diameter (or bubble point pore diameter) of the sample is opened firstly, then smaller and smaller pores are opened, a dry curve and a wet curve are displayed on a test interface, a semi-dry curve is obtained by taking one half of the numerical value of each point on the dry curve, and the average pore diameter can be calculated by taking the pressure value at the intersection point of the semi-dry curve and the corresponding wet curve. The 1 st layer 1 to the 6 th layer 6 contain micropores, and the pore diameters of the 1 st layer 1 to the 6 th layer 6 are gradually increased, and the pore diameter of the 1 st layer 1 is 1.0 micron; layer 2 has a pore size of 4.3 microns; layer 3 has a pore size of 20.1 microns; the pore size range of layer 4 is 38.5 microns; the pore size range of layer 5 is 80.2 microns; the pore size range of layer 6 is 150.4 microns.
Testing of the water permeability of the vascular prosthesis: one end of the artificial blood vessel is fixed on the water seepage instrument, and the other end is sealed by a metal clip. The water valve of the water seepage instrument was opened to fill the artificial blood vessel, and the volume of water seeping from the wall of the vessel was measured within 10 minutes at a water pressure of (16.0.+ -. 0.3) kPa. The prepared artificial blood vessel has water seepage of 0 at 16 kPa.
The biocompatibility of vascular prosthesis a was determined by contacting cultured cells with the extract, and its cytotoxicity was measured as grade 0 by observation of cell morphology, proliferation and inhibition effects.
The compliance of the vascular stent in a wet state is measured by a customized vascular compliance testing device, the testing device mainly simulates the pressure of human blood flow on the vascular wall to expand, and the change of the inner diameter of the blood vessel during the expansion and contraction is recorded, so that the size of the compliance is calculated. The calculation method is as follows: % company= [ (R) P2 -R P1 ）/R P1 ]/(P 2 -P 1 )×10 4 Wherein R is the inner diameter of human hematopoietic vessel, R P1 Is the inner diameter at a pressure of 80mmHg, R P2 Is the inner diameter at 120mmHg, P 1 =80mmHg，P 2 =120 mmHg. The compliance of the vascular prosthesis was calculated to be 5.1% by testing.
Example 3
Preparing a collagen/polyurethane composite nanofiber membrane by electrostatic spinning, wherein the spinning parameters are as follows: the mass ratio of the collagen to the polyurethane is 30:70, the concentration of the spinning solution is 9.6%, and the spinning solution feeding speed is 1.2mL/h.
Cutting nanofiber membrane, and dispersing the nanofiber in tert-butanol solvent with a high-speed refiner to obtain collagen/caprolactone lactate copolymer nanofiber solution with concentration of 75%, 70%, 55%, 50%, 35% and 25%. And (3) carrying out vacuum degassing treatment on the nanofiber solution for later use.
The outer diameter of the artificial blood vessel is 3.4mm and the length is 16mm through the CT scanning file of the receptor pathological change blood vessel. The wall thickness of the required artificial blood vessel is determined to be 250 micrometers according to clinical experience, then a 3D blood vessel model is generated through optimization reconstruction, and finally the model is converted into an STL file which can be identified by 3D printing equipment for later use.
The artificial blood vessel semi-finished product is prepared by using a 3D printing technology and using nanofiber solutions with different concentrations to print at low temperature layer by layer from inside to outside, wherein the layer 1 is 75% of nanofiber solution, and the layer thickness is 50 microns; layer 2 uses 70% nanofiber solution with a layer thickness of 40 microns; layer 3 uses a 55% nanofiber solution with a layer thickness of 40 microns; layer 4 uses a 50% nanofiber solution with a layer thickness of 40 microns; layer 5 uses a 35% nanofiber solution with a layer thickness of 40 microns; layer 6 used 25% nanofiber solution with a layer thickness of 40 microns. In 3D printing, the temperature of the sample stage 13 is: -20 ℃.
Rapidly transferring the semi-finished product of the artificial blood vessel to a low-temperature refrigerator at-80 ℃ for freezing, and finally performing freeze drying treatment on the artificial blood vessel after 3 hours of freezing treatment.
The artificial blood vessel C prepared by the method.
The aperture of each layer of the prepared artificial blood vessel wall is measured by adopting a PMI aperture meter, and the method specifically comprises the following steps: cutting a sample to be measured into a circle with the diameter of about 5 mm; wetting a sample with a wetting liquid, and then placing the sample into an adapter plate; sealing, opening an air inlet valve, and introducing air into the test box; with the increase of pressure, the maximum pore diameter (or bubble point pore diameter) of the sample is opened firstly, then smaller and smaller pores are opened, a dry curve and a wet curve are displayed on a test interface, a semi-dry curve is obtained by taking one half of the numerical value of each point on the dry curve, and the average pore diameter can be calculated by taking the pressure value at the intersection point of the semi-dry curve and the corresponding wet curve. Layers 1 to 6 contain micropores, and the pore diameters of the micropores of layers 1 to 6 are gradually increased, and the pore diameter of layer 1 is 1.3 micrometers; layer 2 has a pore size of 4.5 microns; layer 3 has a pore size of 24.6 microns; the pore size range of layer 4 is 40.2 microns; the pore size range of layer 5 is 98.5 microns; the pore size range of layer 6 was 165.1 microns.
Testing of the water permeability of the vascular prosthesis: one end of the artificial blood vessel is fixed on the water seepage instrument, and the other end is sealed by a metal clip. The water valve of the water seepage instrument was opened to fill the artificial blood vessel, and the volume of water seeping from the wall of the vessel was measured within 10 minutes at a water pressure of (16.0.+ -. 0.3) kPa. The prepared artificial blood vessel has water seepage of 0 at 16 kPa.
The biocompatibility of vascular prosthesis a was determined by contacting cultured cells with the extract, and its cytotoxicity was measured as grade 0 by observation of cell morphology, proliferation and inhibition effects.
The compliance of the vascular stent in a wet state is measured by a customized vascular compliance testing device, the testing device mainly simulates the pressure of human blood flow on the vascular wall to expand, and the change of the inner diameter of the blood vessel during the expansion and contraction is recorded, so that the size of the compliance is calculated. The calculation method is as follows: % company= [ (R) P2 -R P1 ）/R P1 ]/(P 2 -P 1 )×10 4 Wherein R is the inner diameter of human hematopoietic vessel, R P1 Is the inner diameter at a pressure of 80mmHg, R P2 Is the inner diameter at 120mmHg, P 1 =80mmHg，P 2 =120 mmHg. The compliance of the vascular prosthesis was calculated to be 3.8% by testing.
The above is only a preferred embodiment of the present invention, and the present invention is not limited to the contents of the embodiment. Various changes and modifications within the technical scope of the present invention will be apparent to those skilled in the art, and any changes and modifications are intended to be within the scope of the present invention.
The above is only a preferred embodiment of the present invention, and the present invention is not limited to the contents of the embodiment. Various changes and modifications within the technical scope of the present invention will be apparent to those skilled in the art, and any changes and modifications are intended to be within the scope of the present invention.
Claims (10)
1. The preparation method of the 3D printing artificial blood vessel is characterized by comprising the following steps of: comprises the following steps
S01, preparing a nano fiber membrane compounded by a bioactive material/elastomer polymer through electrostatic spinning;
s02, cutting the nanofiber membrane, placing the nanofiber membrane in a solvent for uniform dispersion, and preparing and generating nanofiber solutions for 3D printing with different concentrations;
s03, printing nanofiber solutions with different concentrations layer by layer at low temperature according to the concentration by using a 3D printing technology to obtain an artificial blood vessel semi-finished product, wherein the nanofiber concentration in the nanofiber solution used for printing is gradually reduced from the inner layer to the outer layer of the artificial blood vessel;
s04, placing the artificial blood vessel semi-finished product in a low-temperature environment for freezing treatment to obtain the artificial blood vessel with gradient pore size distribution.
2. The method for preparing a 3D printed vascular prosthesis according to claim 1, wherein: the bioactive material is one or more of collagen, hyaluronic acid, elastin, gelatin and silk fibroin.
3. The method for preparing a 3D printed vascular prosthesis according to claim 1, wherein: the elastomer polymer is one or two of lactic acid-caprolactone copolymer or polyurethane.
4. The method for preparing a 3D printed vascular prosthesis according to claim 1, wherein: the mass content of the bioactive material and the elastomer polymer is as follows: 20% -50% of bioactive material, 50% -80% of elastomer polymer.
5. The method for preparing a 3D printed vascular prosthesis according to claim 1, wherein: the spinning parameters for preparing the bioactive material/elastomer polymer composite nanofiber membrane by electrostatic spinning are as follows: the solvent used in spinning is one or more of hexafluoroisopropanol, tetrahydrofuran, N-dimethylformamide or 2-butanone, and the concentration of the spinning solution is as follows: 6% -12% w/v, and the liquid feeding speed during electrostatic spinning is 1mL/h-3mL/h.
6. The method for preparing a 3D printed vascular prosthesis according to claim 1, wherein: the solvent of the nanofiber solution for 3D printing is one or two of water, tertiary butanol and glycerol, the nanofiber concentration of the nanofiber solution for 3D printing is 20% -80% (w/v), and the nanofiber solution for 3D printing is subjected to vacuum degassing treatment before 3D printing.
7. The method for preparing a 3D printed vascular prosthesis according to claim 1, wherein: the artificial blood vessel is printed in 6 layers, and the nanofiber concentration and the layer thickness in nanofiber solution used in the radial printing from inside to outside are respectively as follows: the concentration of the 1 st layer is 70-80%, and the thickness of the layer is 10-250 micrometers; the concentration of the layer 2 is 60% -75%, and the thickness of the layer is 10 micrometers-350 micrometers; the concentration of the layer 3 is 50% -65%, and the thickness of the layer is 10 micrometers-450 micrometers; the concentration of the 4 th layer is 40% -55%, and the thickness of the layer is 10 micrometers-550 micrometers; the concentration of the 5 th layer is 30% -45%, and the thickness of the layer is 10 micrometers-650 micrometers; the concentration of the 6 th layer is 20% -35%, and the thickness of the layer is 10-750 microns.
8. The method for preparing a 3D printed vascular prosthesis according to claim 1, wherein: the artificial blood vessel is printed in 6 layers, the layers 1 to 6 are sequentially arranged from inside to outside, the layers 1 to 6 contain micropores, the pore diameters of the micropores from the layers 1 to 6 are gradually increased, and the pore diameter range of the layer 1 is 0.5-10 microns; the pore diameter of the 2 nd layer ranges from 5 micrometers to 20 micrometers; the pore diameter of the 3 rd layer ranges from 10 micrometers to 40 micrometers; the pore diameter of the 4 th layer ranges from 20 micrometers to 80 micrometers; the pore diameter of the 5 th layer ranges from 40 micrometers to 160 micrometers; the pore size of layer 6 ranges from 80 microns to 320 microns.
9. A 3D printed vascular prosthesis, characterized in that: is prepared by the method of any one of claims 1-8.
10. The 3D printed vascular prosthesis of claim 9, wherein: the artificial blood vessel comprises a plurality of nanofiber layers in the radial direction, wherein each nanofiber layer is provided with a microporous structure, the pore diameter of the micropores of the nanofiber layer from inside to outside is gradually increased, and the pore diameter range of the microporous structure arranged on the nanofiber layer of the innermost layer of the artificial blood vessel is 0.5-10 microns.
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| CN104841013A (en) * | 2015-05-04 | 2015-08-19 | 东华大学 | Composite nanofiber/nano yarn double-layer intravascular stent and preparation method thereof |
| KR20170006909A (en) * | 2015-07-10 | 2017-01-18 | 한국기계연구원 | Bio tubular scaffold for fabricating artificial vascular and the fabricating method thereof |
| CN108186162A (en) * | 2017-12-06 | 2018-06-22 | 江苏百优达生命科技有限公司 | A kind of three-decker composite artificial blood vessel |
| CN108452383A (en) * | 2018-03-06 | 2018-08-28 | 中山大学 | A kind of preparation method and application of 3D printing artificial blood vessel |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104841013A (en) * | 2015-05-04 | 2015-08-19 | 东华大学 | Composite nanofiber/nano yarn double-layer intravascular stent and preparation method thereof |
| KR20170006909A (en) * | 2015-07-10 | 2017-01-18 | 한국기계연구원 | Bio tubular scaffold for fabricating artificial vascular and the fabricating method thereof |
| CN108186162A (en) * | 2017-12-06 | 2018-06-22 | 江苏百优达生命科技有限公司 | A kind of three-decker composite artificial blood vessel |
| CN108452383A (en) * | 2018-03-06 | 2018-08-28 | 中山大学 | A kind of preparation method and application of 3D printing artificial blood vessel |
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