CN108814767B - A kind of preparation facilities and preparation method of small-caliber artificial blood vessel microcellular structure - Google Patents
A kind of preparation facilities and preparation method of small-caliber artificial blood vessel microcellular structure Download PDFInfo
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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
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C41/00—Shaping by coating a mould, core or other substrate, i.e. by depositing material and stripping-off the shaped article; Apparatus therefor
- B29C41/02—Shaping by coating a mould, core or other substrate, i.e. by depositing material and stripping-off the shaped article; Apparatus therefor for making articles of definite length, i.e. discrete articles
- B29C41/04—Rotational or centrifugal casting, i.e. coating the inside of a mould by rotating the mould
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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
- 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
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Abstract
The present invention provides the preparation facilities and preparation method of a kind of small-caliber artificial blood vessel microcellular structure, belongs to artificial blood vessel's technical field.The preparation facilities is made of small-caliber artificial blood vessel preparation facilities and micropore preparation facilities；The small-caliber artificial blood vessel preparation facilities includes fixed bracket, motor, round tube mold, heating device, lifting platform and dropper；The micropore preparation facilities includes air pump, flow valve, connecting tube, spray canister, the second connecting rod and the second fixture.The present invention also provides the methods that above-mentioned apparatus prepares small-caliber artificial blood vessel microcellular structure.Apparatus and method of the present invention is suitable for soluble all macromolecule materials the organic solvent lower than 160 DEG C of boiling points, the conditions such as rate and centrifugal force are bloated by adjusting particle species, size, gas, the small-bore micropore artificial blood vessel with different pore sizes, specific surface area can be prepared.The present invention has the function of that the small-caliber artificial blood vessel of microcellular structure has and is conducive to vascular endothelial cell proliferation.
Description
Technical field
The invention belongs to artificial blood vessel's technical fields, and in particular to a kind of preparation dress of small-caliber artificial blood vessel microcellular structure
It sets and preparation method.
Background technique
With the development of economy and the variation of people life style, on the morbidity and mortality of cardiovascular disease continue
It rises.There are a large amount of patients to need to carry out vascular transplant every year, especially blood vessel bypass transfer operation, therefore, clinic is to osculum
The demand of diameter artificial blood vessel (internal diameter < 6mm) is very high.However, small-caliber vascular caused by thrombosis and endometrial hyperplasia is narrow again
It is narrow, often result in transfer operation failure.Therefore, the blood compatibility for improving small-caliber artificial blood vessel becomes research hotspot.
A large number of studies show that vascular endothelial cell has antithrombus formation, inhibits platelet aggregation and smooth muscle cell disease
The function of rationality proliferation, therefore, small-caliber artificial blood vessel early stage, quickly endothelialization was that blood at a specified future date is logical after maintaining it to implant
A smooth highly important strategy.Currently, realize small-caliber artificial blood vessel endothelialization mainly have endothelial cell in vitro plantation and
Endothelial cell internal in-situ comes to the surface two methods, and the latter one mainly use the means of material surface modification and micropore preparation.
Microcellular structure can be enhanced vascular endothelial cell small-caliber artificial blood vessel inner surface proliferation, grow into and sprawl, and then accelerate
Endothelial cell process, prevents thrombosis.
Currently, the preparation of small-caliber artificial blood vessel microcellular structure is mainly the following method: will by method of electrostatic spinning
Polymer solution or melt-blowing are simultaneously collected, thus be made with microcellular structure artificial blood vessel (Biomaterials, 2010,
31(15):4313-4321.)；Pole mold is immersed repeatedly in polymer/salt grain suspension using dipping-percolation, it is dry
Dissolution salt grain is afterwards to obtain small-bore micropore artificial blood vessel (Chinese Reconstructive surgery magazine, 2005,19 (1): 64-69.)；
By by the method for polymer solution rapid freezing prepare porous artificial blood vessel (J Biomed Mater Res, 1992,26
(11):1489-1502.)；Using the method for laser-induced thermal etching prepare micropore artificial blood vessel (Biomed Mater Res, 1996,31
(1):27-33.)。
Summary of the invention
The object of the present invention is to provide the preparation facilities and preparation method of a kind of small-caliber artificial blood vessel microcellular structure, the party
Device needed for method is simple and convenient to operate, and is adjusted by material and preparation parameter, can accurately be prepared the micropore of small-caliber artificial blood vessel
Structure.
Present invention firstly provides a kind of preparation facilities of small-caliber artificial blood vessel microcellular structure, by small-caliber artificial blood vessel system
Standby device and micropore preparation facilities form；
The small-caliber artificial blood vessel preparation facilities includes fixed bracket, motor, round tube mold, heating device, lifting
Platform and dropper, the fixation bracket include that fixed link, first connecting rod and the first fixture, fixed link are fixed on stationary plane
On, one end of first connecting rod moves up and down along fixed link and can be fixed on any position of fixed link, first connecting rod it is another
The fixing end of one end and the first fixture is rotatablely connected, and the first fixture is relative to connecting rod pitching movement, the clamping end of the first fixture
Clamp one end of motor；The axis of motor is mutually perpendicular to support bracket fastened axis, one end of round tube mold and the rotation of motor
Axis is fixedly connected, and the other end is open end, and round tube mold rotates under the drive of the rotary shaft of motor along axis；Lifting platform is placed
On stationary plane, heating device is placed on lifting platform, and is located at the lower section of round tube mold, is adjusted under the drive of lifting platform high
Position is spent, heating device heats round tube mold by hot-air, and dropper is used to contain and opening to round tube mold
It puts and Polymer Solution is added dropwise on the inner wall at end；
The micropore preparation facilities includes air pump, flow valve, connecting tube, spray canister, the second connecting rod and the second fixture,
The air pump is placed on stationary plane, and one end of air pump is connected by one end of connecting tube and flow valve, flow valve
The other end is connected by one end of connecting tube and spray canister, and the other end outer end face of spray canister is vacantly placed in round tube mold cavity, spray canister
Interior placement particle, one end of the second connecting rod move up and down along fixed link and can be fixed on any position of fixed link, and second connects
The rotation connection of the fixing end of the other end of extension bar and the second fixture, the clamping end of the second fixture clamp spray canister, and spray canister is in the second folder
Adjustable position and angle under the drive of tool.
Preferably, the internal diameter of the round tube mold is 3.00~6.00mm, length < 300.00mm.
The present invention also provides the methods that above-mentioned apparatus prepares small-caliber artificial blood vessel microcellular structure, comprising:
Step 1: the preparation of small-caliber artificial blood vessel
1) Polymer Solution is prepared
High molecular material is completely dissolved in organic solvent of the boiling point lower than 160 DEG C under room temperature or heating, is formed dense
Degree is the Polymer Solution of 0.01~1.00g/mL；
2) centrifugation coating
It controls motor and round tube mold rotation is first driven with the revolving speed of 10~1000rpm, by Polymer Solution Dropping feeder
It is added drop-wise on the inner wall of the open end of round tube mold, promotes revolving speed to 100~3000rpm, pass through rotation the first fixture adjustment electricity
The axis angulation of the axis and fixed link of machine and round tube mold is 20~70 °, makes Polymer Solution in centrifugal force and gravity
It is evenly applied under effect on the inner wall of round tube mold, forms the liquid film of uniformly continuous, then by motor and the axis of round tube mold
Line is adjusted to vertical with the axis of fixed link, starts heating devices heat, the organic solvent in Polymer Solution is made to evaporate into liquid
The surface of film judges whether thickness reaches the pipe thickness of required small-caliber artificial blood vessel, reaches, execute step in after leather hard
It is rapid 3), not up to, repeat step 2)；
3) it selects
If the small-caliber artificial blood vessel tube wall of preparation is single layer structure, step 2 is directly executed；If the small-bore people of preparation
Work vascular wall is multilayered structure, and repeating step 1) needs to step 3) until executing step 2 after the completion of multilayered structure coating
To illustrate that the coating sequence of multilayered structure is from outside to inside；
Step 2: the preparation of microcellular structure
1) device is adjusted
Heating device and dropper are removed, micropore preparation facilities is installed, adjusts angle and the position of round tube mold and spray canister
It sets, so that spray canister and round tube mold is in same axis, and spray canister outlet outer end face is vacantly placed in round tube mold cavity；
2) particle covers small-caliber artificial blood vessel inner wall
Start motor and round tube mold rotation is driven with the revolving speed of 10~100rpm, starts air pump, controlled by flow valve
Air velocity is 0.1~4.0L/min, and the particle in spray canister disturbs under airflow function, and sprays from spray canister with air-flow
Out, uniform fold is being in the small-caliber artificial blood vessel inner wall of leather hard；
3) particle is inlayed
Micropore preparation facilities is removed, motor and round tube die location and angle are adjusted, keeps it vertical with fixed bracket axis,
Starting motor simultaneously increases its revolving speed to 10~3000rpm, and particle is made to be embedded in the artificial blood of leather hard under the action of the centrifugal force
Then pipe internal surface is installed heating device and is started, until solvent volatilizees completely；
4) it post-processes
Round tube mold is removed, demoulds, obtains embedding fine-grained small-caliber artificial blood vessel, particle is completely removed completely, is dried
Dry, finishing obtains the small-caliber artificial blood vessel with microcellular structure.
Preferably, the high molecular material in the step 1 in natural or artificial synthesized high molecular material one
Kind is several；The natural macromolecular material is fibroin albumen or collagen；Artificial synthesized high molecular material be polyurethane,
Polylactic acid, polycaprolactone or polyolefin.
Preferably, the heating temperature of the heating device of the step 1 be 50~150 DEG C, heating time be 1~
120min。
Preferably, motor and the axis of spray canister are parallel with fixed bracket axis in the step 2, and spray canister outlet is outer
End face is away from the open end section 1mm of circular hole mould.
Preferably, the particle of the step 2 is particulate inorganic material, organic material particle or metal material particle
It is one or more of.
Preferably, the particulate inorganic material is NaCl, NH4One in Cl, KCl, glass, quartz or ceramic particle
Kind is several；Organic material particle is one or more of paraffin, polystyrene, polyethylene or polypropylene microparticle；Metal material
Material particle is one or more of iron, copper or lead particle.
Preferably, the method that particle removes in the step 2 is ultrasonic method or dissolution method.
Preferably, the small-caliber artificial blood vessel tube wall with microcellular structure is single or multi-layer structure, and wall thickness is
0.02~1.00mm, length are 20.00~200.00mm, and internal diameter is 2.00~6.00mm, and pore size is 1~1000 μm.
Compared with prior art, the invention has the benefit that
The present invention provides the preparation facilities and preparation method of a kind of small-caliber artificial blood vessel microcellular structure, and this method is to use
Sandblasting principle, i.e. particle under the action of air-flow uniform fold in be in leather hard small-caliber artificial blood vessel inner wall, and from
It is embedded in its inner surface under mental power function, is then heated to solvent and volatilizees completely, demoulds, removes particle, dry, finishing, finally
Obtain the small-caliber artificial blood vessel with microcellular structure.This device and method is suitable in the organic solvent for being lower than 160 DEG C of boiling points
In soluble all macromolecule materials, by adjust particle species, size, gas bloat the conditions such as rate and centrifugal force, can make
The standby small-bore micropore artificial blood vessel with different pore sizes, specific surface area.Preparation facilities of the present invention is simple, operation
It is convenient, the microcellular structure of small-caliber artificial blood vessel can be finely controlled, and then increase its specific surface area, be conducive to blood vessel endothelium
Cell Proliferation.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of the preparation facilities of small-caliber artificial blood vessel microcellular structure of the present invention；
Fig. 2 is the structural schematic diagram of the preparation facilities of small-caliber artificial blood vessel of the present invention；
Fig. 3 is the photo figure of the small-caliber artificial blood vessel with microcellular structure of the embodiment of the present invention 1；
Fig. 4 is the SEM figure of the small-caliber artificial blood vessel with microcellular structure of the embodiment of the present invention 1；
Fig. 5 is the photo figure of the small-caliber artificial blood vessel with microcellular structure of the embodiment of the present invention 2；
Fig. 6 is the SEM figure of the small-caliber artificial blood vessel with microcellular structure of the embodiment of the present invention 2；
Fig. 7 is the photo figure of the small-caliber artificial blood vessel with microcellular structure of the embodiment of the present invention 3；
Fig. 8 is the SEM figure of the small-caliber artificial blood vessel with microcellular structure of the embodiment of the present invention 3；
Fig. 9 is the photo figure of the small-caliber artificial blood vessel with microcellular structure of the embodiment of the present invention 4；
Figure 10 is the SEM figure of the small-caliber artificial blood vessel with microcellular structure of the embodiment of the present invention 4；
Figure 11 is the small-caliber artificial blood vessel training with microcellular structure of blank small-bore blood vessel sample and embodiment 2,3,4
SEM figure after blood-nourishing endothelial cell.
In Fig. 1 and Fig. 2,1, fixed bracket, 1-1, fixed link, 1-2, first connecting rod, 1-3, the first fixture, 2, motor,
3, round tube mold, 4, heating device, 5, lifting platform, 6, dropper, 7, air pump, 8, flow valve, 9, connecting tube, 10, spray canister,
11, the second connecting rod, the 12, second fixture.
Specific embodiment
For a further understanding of the present invention, the preferred embodiment of the invention is described below, but it is to be understood that this
A little descriptions are only further explanation the features and advantages of the present invention, rather than limiting to the claimed invention.
A kind of preparation facilities of small-caliber artificial blood vessel microcellular structure of the present invention, as shown in Figs. 1-2, by small-caliber artificial blood
Pipe preparation facilities and micropore preparation facilities composition；
The small-caliber artificial blood vessel preparation facilities includes fixed bracket, motor 2, round tube mold 3, heating device 4, rises
Platform 5 and dropper 6 drop, wherein and the fixation bracket includes fixed link 1-1, first connecting rod 1-2 and the first fixture 1-3,
Fixed link 1-1 is fixed on stationary plane (generally station), and one end of first connecting rod 1-2 can move down on fixed link 1-1
The fixing end of any position that is dynamic and being fixed on fixed link 1-1, the other end of first connecting rod 1-2 and the first fixture 1-3 turn
Dynamic connection, the first fixture 1-3 clamp motor 2 relative to first connecting rod 1-2 pitching movement, the clamping end of the first fixture 1-3
One end；By adjusting the junction of first connecting rod 1-2 and the first fixture 1-3, the axis and fixed bracket of motor 2 can be adjusted
Axis angle, can generally be adjusted within the scope of 0~180 °, the axis of motor 2 is mutually perpendicular to support bracket fastened axis,
One end of round tube mold 3 is fixedly connected with the rotary shaft of motor 2, and the other end is open end, rotation of the round tube mold 3 in motor 2
It is rotated under the drive of axis along axis；Lifting platform 5 is placed on stationary plane, and heating device 4 is placed on lifting platform 5, in lifting platform 5
Drive under adjust height and position, heating device 4 heats round tube mold 3 by hot-air, and position is according to round tube mould
The position of tool 3 is adjusted, positioned at the lower section of round tube mold 3；Dropper 6 is for containing and to the open end of round tube mold 3
Inner wall on be added dropwise Polymer Solution, dropper 6 preferably uses dropper, pipettor or syringe.
According to the present invention, the material of the round tube mold 3 is preferably metal material, inorganic material or high molecular material；
The metal material is preferably stainless steel, aluminium or copper；Inorganic material is preferably glass or ceramics；High molecular material is preferably poly-
Tetrafluoroethene.
According to the present invention, the size of the round tube mold 3 is determined according to the size of artificial blood vessel to be prepared, usually interior
Diameter is preferably 3.00~6.00mm, length < 300.00mm.
According to the present invention, the heating device 4 is using hot air, and heating temperature is adjustable and range is
30~200 DEG C, wind direction can carry out all directions adjusting, preferably hair dryer according to requirement of experiment.
The micropore preparation facilities includes air pump 7, flow valve 8, connecting tube 9, spray canister 10, the second connecting rod 11 and
Two fixtures 12, the air pump 7 are placed on stationary plane, and one end of air pump 7 passes through one end of connecting tube 9 and flow valve 8
The other end of connection, flow valve 8 is connect by connecting tube 9 with one end of spray canister 10, and the other end outer end face of spray canister 10 is vacantly set
It is intracavitary in round tube mold 3, particle is placed in spray canister 10, one end of the second connecting rod 11 moves up and down along fixed link 1-1 and can consolidate
It is scheduled on any position of fixed link 1-1, the fixing end of the other end of the second connecting rod 11 and the second fixture 12 is rotatablely connected, and second
The clamping end of fixture 12 clamps spray canister 10, spray canister 10 adjustable position and angle under the drive of the second fixture 12.
The method that above-mentioned apparatus prepares small-caliber artificial blood vessel microcellular structure, comprising:
Step 1: the preparation of small-caliber artificial blood vessel
1) Polymer Solution is prepared
High molecular material is completely dissolved in organic solvent of the boiling point lower than 160 DEG C under room temperature or heating, is formed dense
Degree is the Polymer Solution of 0.01~1.00g/mL；
Wherein, high molecular material is not particularly limited, and the material according to the artificial blood vessel that need to be prepared determines, Ke Yiwei
Natural macromolecular material, such as fibroin albumen, collagen, or artificial synthesized high molecular material, such as polyurethane, poly- cream
Acid, polycaprolactone, polyolefin etc., and high molecular material can be one or more mixture；Organic solvent is not also special
Limitation, can play dissolution and boiling point is lower than 160 DEG C, preferably n,N-Dimethylformamide, chloroform, acetone, first
One of benzene, methanol, ethyl alcohol, ether, tetrahydrofuran, methylene chloride or hexafluoroisopropanol or a variety of mixtures；It dissolved
Journey can carry out also carrying out under Elevated Temperature Conditions at room temperature, and the temperature range of Elevated Temperature Conditions is generally 30~100 DEG C；
It should be noted that the concentration of Polymer Solution must in 0.01~1.00g/mL, if concentration < 0.01g/mL or
> 1.00g/mL, since concentration is excessively dilute or feeding-up, Polymer Solution under the action of the centrifugal force cannot be on the inner wall of round tube mold 3
Form uniform, continuous liquid film；It is preferred that Polymer Solution concentration is 0.10~0.50g/mL.
2) centrifugation coating
Control motor 2 first drives round tube mold 3 to rotate with the revolving speed of 10~1000rpm, Polymer Solution is used, dress is added dropwise
On the inner wall for setting the open end that 6 are added drop-wise to round tube mold 3, revolving speed is promoted to 100~3000rpm, by rotating the first fixture 1-3
The axis angulation of the axis and fixed link 1-1 that adjust motor 2 and round tube mold 3 is 20~70 °, preferably 40~50 °, more
It preferably 45 °, is evenly applied to Polymer Solution under centrifugal force and gravity on the inner wall of round tube mold 3, is formed equal
Even continuous liquid film, then by the axis trimming of motor 2 and round tube mold 3 to, starting heating vertical with the axis of fixed link 1-1
Device heating 4, the surface for making the organic solvent in Polymer Solution evaporate into liquid film judge whether thickness reaches in after leather hard
To the pipe thickness of required small-caliber artificial blood vessel, reach, execute step 3), not up to, repeats step 2)；
The each dripping quantity of the Dropping feeder 6 is preferably 0.1~4.0mL, the specific heating temperature of heating device 4 and
Time need to be arranged according to the boiling point of organic solvent, and preferable temperature is 50~150 DEG C, and heating time is preferably 1~120min；
3) it selects
If the small-caliber artificial blood vessel tube wall of preparation is single layer structure, step 2 is directly executed；If the small-bore people of preparation
Work vascular wall is multilayered structure, and repeating step 1) needs to step 3) until executing step 2 after the completion of multilayered structure coating
To illustrate that the coating sequence of multilayered structure is from outside to inside；
Step 2: the preparation of microcellular structure
1) device is adjusted
Heating device 4 and dropper 6 are removed, micropore preparation facilities is installed, adjusts the angle of round tube mold 3 and spray canister 10
And position, so that spray canister 10 and round tube mold 3 is in same axis, preferably makes motor and the axis of spray canister and fixed bracket axis flat
Row, it is intracavitary that the outlet of spray canister 10 outer end face is vacantly placed in round tube mold 3；It is cut away from circular hole mould away from open end it is preferred that spray canister exports outer end face
Face 1mm；
2) particle covers small-caliber artificial blood vessel inner wall
Start motor 2 and drive round tube mold 3 to rotate with the revolving speed of 10~500rpm, starts air pump 7, pass through flow valve 8
Control air velocity is 0.1~4.0L/min, and the particle in spray canister 10 disturbs under airflow function, and with air-flow from spray canister
It is sprayed in 10, uniform fold is being in the small-caliber artificial blood vessel inner wall of leather hard；
3) particle is inlayed
Micropore preparation facilities is removed, motor 2 and 3 position of round tube mold and angle are adjusted, it is made to hang down with fixed bracket axis
Directly, start motor 2 and increase its revolving speed to 10~3000rpm, particle is made to be embedded in the people of leather hard under the action of the centrifugal force
Then work vascular inner surface is installed heating device 4 and is started, until solvent volatilizees completely；
The particle refers to particle size in 1~1000 μm of particle, and preferably particulate inorganic material, organic material is micro-
The one or more of grain or metal material particle.The particulate inorganic material is preferably NaCl, NH4Cl, KCl, glass, quartz
Or one or more of ceramic particle；Organic material particle is preferably in paraffin, polystyrene, polyethylene or polypropylene microparticle
One or more；Metal material particle is preferably one or more of iron, copper or lead particle.The source of the particle is
Prepared by the commercially available or existing literature method of use, such as glass granules, ceramic particle, quartz particle, iron granules, copper particle use quotient
Purchase obtains, paraffin particle reference literature method self-control (J Biomed Mater Res A, 2007,82A (4): 802-809.),
NaCl particle screens to obtain by grinding and sieve.
4) it post-processes
Round tube mold 2 is removed, demoulds, obtains embedding fine-grained small-caliber artificial blood vessel, particle is completely removed completely, is dried
Dry, finishing obtains the small-caliber artificial blood vessel with microcellular structure.
The method of the particle removal is preferably ultrasonic method or dissolution method.The present invention is for insoluble or be insoluble in organic solvent
Particle, such as glass, ceramics, metal particle etc., using ultrasonic method remove particle, ultrasonic method used medium be preferably distilled water,
One or more of ethyl alcohol, acetone, isopropanol；For soluble easily in water or organic solvent particle, such as NaCl, NH4Cl、KCl、
Paraffin particle etc. removes particle using dissolution method, and dissolution method solvent for use is preferably distilled water, n-hexane, chloroform, ethyl alcohol, third
One or more of ketone or toluene.
The small-caliber artificial blood vessel tube wall with microcellular structure is single or multi-layer structure, wall thickness is preferably 0.02~
1.00mm, length are preferably 20.00~200.00mm, and internal diameter is preferably 2.00~6.00mm, and pore size is preferably 1~1000
μm, according to particulate form and size, the micropore of preparation can be the irregular shapes such as round, rectangular.
Below in conjunction with specific embodiment, the present invention is described in further detail.
Embodiment 1
Step 1: 1) by polyurethane (II 80A, DSM) at 55 DEG C stirring be dissolved in n,N-Dimethylformamide
In, form the polyurethane solutions that concentration is 0.10g/mL；2) at revolving speed 500rpm, with dropper 6 by 0.3mL step 1)
Polyurethane solutions are added on the inner wall of the open end for the glass round tube mold 3 that internal diameter is 5.00mm, form liquid film, then will be turned
Speed is increased to 1500rpm and maintains；The angle of motor 2 and round tube mold 3 is adjusted upward, until the axis of the two axis and fixed link
Angle is 45 °, is evenly applied to polyurethane solutions under centrifugal force and gravity on the inner wall of round tube mold 3, forms liquid
Film, then by the axis trimming of motor 2 and round tube mold 3 to, starting heating device 4, at 60 DEG C vertical with the axis of fixed link
Lower heating 20min makes the organic solvent in liquid film evaporate into liquid film surface in leather hard；3) it repeats step 2) 4 times, and the 4th
Secondary heating time is 5min；
Step 2: 1) remove heating device 4 and dropper 6, micropore preparation facilities is installed, spray canister 10 and round tube mold are made
3 is parallel with fixed bracket axis, and spray canister 10 exports outer end face, and to be vacantly placed in round tube mold 3 intracavitary and away from open end section 1mm；2)
NaCl particle is ground with mortar, it is micro- then to filter out the NaCl that partial size is 150~200 μm with 110 mesh and 75 mesh screens
Grain, is fitted into spare in spray canister；3) starting motor 2 drives round tube mold 3 to rotate with the revolving speed of 100rpm, starts air pump 7, passes through
It is 2.5L/min that flow valve 8, which controls air velocity, and the NaCl particle in spray canister 10 disturbs under airflow function, and with air-flow
It is sprayed from spray canister 10, uniform fold is being in the small-caliber artificial blood vessel inner wall of leather hard；4) micropore preparation facilities is removed, is made
Motor 2 and round tube mold 3 are vertical with fixed bracket axis, start motor 2 and increase its revolving speed to 1000rpm, make particle from
It is embedded in artificial blood vessel's inner surface of leather hard under mental power function, then heating device 4 is installed and starts, until solvent is waved completely
Hair；5) it demoulds, obtains the small-caliber artificial blood vessel embedded with 150~200 μm of partial size NaCl particles, then place it in distilled water
Ultrasonic cleaning 30min is completely dissolved to NaCl particle, is then replaced distilled water repeated washing 3 times, is dried, and finishing is had
The small-caliber artificial blood vessel of microcellular structure.Through detecting, the length is 40.00mm, internal diameter 4.50mm, aperture is 150~200 μ
The SEM of m, photo and microcellular structure such as Fig. 3 (wherein a is lateral schematic diagram, and b is longitudinal schematic diagram) and shown in 4.
Embodiment 2
Step 1: 1) by polyurethane (II 80A, DSM) at 55 DEG C stirring be dissolved in N, N- dimethyl formyl
In amine, the polyurethane solutions that concentration is 0.10g/mL are formed；2) at revolving speed 500rpm, with dropper 6 by 0.3mL step 1)
Polyurethane solutions be added to internal diameter be 5.00mm glass round tube mold 3 open end inner wall on, formed liquid film, then will
Revolving speed is increased to 1500rpm and maintains；The angle of motor 2 and round tube mold 3 is adjusted upward, until the axis of the two axis and fixed link
Wire clamp angle is 45 °, is evenly applied to polyurethane solutions under centrifugal force and gravity on the inner wall of round tube mold 3, is formed
Liquid film, then by the axis trimming of motor 2 and round tube mold 3 to, starting heating device 4,60 vertical with the axis of fixed link
20min is heated at DEG C, and the organic solvent in liquid film is made to evaporate into liquid film surface in leather hard；3) it repeats step 2) 4 times, and the
4 heating times are 5min；
Step 2: 1) remove heating device 4 and dropper 6, micropore preparation facilities is installed, spray canister 10 and round tube mold are made
3 is parallel with fixed bracket axis, and spray canister 10 exports outer end face, and to be vacantly placed in round tube mold 3 intracavitary and away from open end section 1mm；2)
NaCl particle is ground with mortar, it is micro- then to filter out the NaCl that partial size is 20~50 μm with 300 mesh and 900 mesh screens
Grain, is fitted into spare in spray canister；3) starting motor 2 drives round tube mold 3 to rotate with the revolving speed of 100rpm, starts air pump 7, passes through
It is 1L/min that flow valve 8, which controls air velocity, and the NaCl particle in spray canister 10 disturbs under airflow function, and with air-flow from
It is sprayed in spray canister 10, uniform fold is being in the small-caliber artificial blood vessel inner wall of leather hard；4) micropore preparation facilities is removed, electricity is made
Machine 2 and round tube mold 3 are vertical with fixed bracket axis, start motor 2 and increase its revolving speed to 2000rpm, are being centrifuged particle
It is embedded in artificial blood vessel's inner surface of leather hard under power effect, then heating device 4 is installed and starts, until solvent is waved completely
Hair；5) it demoulds, obtains the small-caliber artificial blood vessel embedded with 20~50 μm of partial size NaCl particles, then place it in distilled water and surpass
Sound cleans 30min and is completely dissolved to NaCl particle, then replaces distilled water repeated washing 3 times, dries, and finishing obtains having micro-
The small-caliber artificial blood vessel of pore structure.Through detecting, the length is 40.00mm, internal diameter 4.50mm, aperture is 20~50 μm, is shone
The SEM of piece and microcellular structure such as Fig. 5 (wherein a is lateral schematic diagram, and b is longitudinal schematic diagram) and shown in 6.
Embodiment 3
Step 1: 1) by polyurethane (II 80A, DSM) at 55 DEG C stirring be dissolved in n,N-Dimethylformamide
In, form the polyurethane solutions that concentration is 0.10g/mL；2) at revolving speed 500rpm, with dropper 6 by 0.3mL step 1)
Polyurethane solutions are added on the inner wall of the open end for the glass round tube mold 3 that internal diameter is 5.00mm, form liquid film, then will be turned
Speed is increased to 1500rpm and maintains；The angle of motor 2 and round tube mold 3 is adjusted upward, until the axis of the two axis and fixed link
Angle is 45 °, is evenly applied to polyurethane solutions under centrifugal force and gravity on the inner wall of round tube mold 3, forms liquid
Film, then by the axis trimming of motor 2 and round tube mold 3 to, starting heating device 4, at 60 DEG C vertical with the axis of fixed link
Lower heating 20min makes the organic solvent in liquid film evaporate into liquid film surface in leather hard；3) it repeats step 2) 4 times, and the 4th
Secondary heating time is 5min；
Step 2: 1) remove heating device 4 and dropper 6, micropore preparation facilities is installed, spray canister 10 and round tube mold are made
3 is parallel with fixed bracket axis, and spray canister 10 exports outer end face, and to be vacantly placed in round tube mold 3 intracavitary and away from open end section 1mm；2)
The commercialization glass granules that partial size is 50~100 μm are bought, then its surface is carried out at biofilm with 5% release agent aqueous solution
Reason, is fitted into spare in spray canister after drying；3) starting motor 2 drives round tube mold 3 to rotate with the revolving speed of 500rpm, starts air pump
7, controlling air velocity by flow valve 8 is 2L/min, and the glass granules in spray canister 10 disturb under airflow function, and with
Air-flow is sprayed from spray canister 10, and uniform fold is being in the small-caliber artificial blood vessel inner wall of leather hard；4) micropore preparation dress is removed
It sets, keeps motor 2 and round tube mold 3 vertical with fixed bracket axis, start motor 2 and increase its revolving speed to 1500rpm, make particle
It is embedded in artificial blood vessel's inner surface of leather hard under the action of the centrifugal force, then heating device 4 is installed and starts, until solvent is complete
Full volatilization；5) it demoulds, obtains the small-caliber artificial blood vessel embedded with 50~100 μm of partial size glass granules, then place it in distillation
It is cleaned by ultrasonic 90min in water to completely remove to glass granules, then replaces distilled water repeated washing 5 times, dry, finishing obtains
Small-caliber artificial blood vessel with microcellular structure.Through detecting, the length is 40.00mm, internal diameter 4.50mm, aperture is 50~
100 μm, SEM such as Fig. 7 (wherein a is lateral schematic diagram, and b is longitudinal schematic diagram) of photo and microcellular structure and shown in 8.
Embodiment 4
Step 1: 1) by polyurethane (II 80A, DSM) at 55 DEG C stirring be dissolved in n,N-Dimethylformamide
In, form the polyurethane solutions that concentration is 0.10g/mL；2) at revolving speed 500rpm, with dropper 6 by 0.3mL step 1)
Polyurethane solutions are added on the inner wall of the open end for the glass round tube mold 3 that internal diameter is 5.00mm, form liquid film, then will be turned
Speed is increased to 1500rpm and maintains；The angle of motor 2 and round tube mold 3 is adjusted upward, until the axis of the two axis and fixed link
Angle is 45 °, is evenly applied to polyurethane solutions under centrifugal force and gravity on the inner wall of round tube mold 3, forms liquid
Film, then by the axis trimming of motor 2 and round tube mold 3 to, starting heating device 4, at 60 DEG C vertical with the axis of fixed link
Lower heating 20min makes the organic solvent in liquid film evaporate into liquid film surface in leather hard；3) it repeats step 2) 4 times, and the 4th
Secondary heating time is 5min；
Step 2: 1) remove heating device 4 and dropper 6, micropore preparation facilities is installed, spray canister 10 and round tube mold are made
3 is parallel with fixed bracket axis, and spray canister 10 exports outer end face, and to be vacantly placed in round tube mold 3 intracavitary and away from open end section 1mm；2)
Paraffin particle is made in laboratory by oneself, is poured into 90 DEG C of 250mL of 0.5wt% polyvinyl alcohol water solution after 7g solid paraffin is melted,
It is vigorously stirred until being cooled to room temperature, then filters out the paraffin particle that partial size is 50~150 μm with 300 mesh and 110 mesh screens,
Room temperature is fitted into spare in spray canister after drying；3) starting motor 2 drives round tube mold 3 to rotate with the revolving speed of 100rpm, starts air
Pump 7, controlling air velocity by flow valve 8 is 1.5L/min, and the paraffin particle in spray canister 10 disturbs under airflow function,
And sprayed from spray canister 10 with air-flow, uniform fold is being in the small-caliber artificial blood vessel inner wall of leather hard；4) micropore system is removed
Standby device keeps motor 2 and round tube mold 3 vertical with fixed bracket axis, starts motor 2 and increase its revolving speed to 2500rpm, make
Particle is embedded in artificial blood vessel's inner surface of leather hard under the action of the centrifugal force, then installs heating device 4 and starts, until molten
Agent is volatilized completely；5) it demoulds, obtains the small-caliber artificial blood vessel embedded with 50~150 μm of partial size paraffin particles, then place it in
Ultrasound 120min is completely dissolved to paraffin particle in hexane solution, after then replacing ethyl alcohol repeated washing 3 times, then replaces distillation
It water repeated washing 3 times, dries, finishing obtains the small-caliber artificial blood vessel with microcellular structure.Through detecting, the length is
40.00mm, internal diameter 4.50mm, aperture are 50~150 μm, and (wherein a is laterally signal to SEM such as Fig. 9 of photo and microcellular structure
Figure, b are longitudinal schematic diagram) and shown in 10.
Embodiment 5 has the function of that the small-caliber artificial blood vessel of microcellular structure has and is conducive to vascular endothelial cell proliferation
The small-caliber artificial blood vessel and blank small-caliber vascular sample with microcellular structure that will be prepared in embodiment 2,3,4
Product (pore-free structure) are cut into the disk of Φ=1.20cm after splitting, be respectively placed in 24 porocyte culture plates after sterilizing, then
5 × 10 are cultivated respectively on its surface4A human vascular endothelial (HUVECs) fixes cell after cultivating 72h, then with scanning electricity
Sub- microscope (SEM) is observed and is imaged to material surface and cellular morphology.Experimental result is shown as shown in figure 11, wherein scheming
A represents blank small-caliber vascular sample, and figure b represents the small-caliber artificial blood vessel with microcellular structure of embodiment 4, and figure c is represented
The small-caliber artificial blood vessel with microcellular structure of embodiment 3, figure d represent the small-bore people with microcellular structure of embodiment 2
Work blood vessel, it can be seen from the figure that the microcellular structure of this method preparation can be obviously promoted the proliferation of HUVECs.
Claims (10)
1. a kind of preparation facilities of small-caliber artificial blood vessel microcellular structure, which is characterized in that prepared and filled by small-caliber artificial blood vessel
It sets and micropore preparation facilities forms；
The small-caliber artificial blood vessel preparation facilities include fixed bracket, motor (2), round tube mold (3), heating device (4),
Lifting platform (5) and dropper (6), the fixation bracket include fixed link (1-1), first connecting rod (1-2) and the first folder
Have (1-3), fixed link (1-1) is fixed on stationary plane, and one end of first connecting rod (1-2) is moved up and down along fixed link (1-1)
And it can be fixed on any position of fixed link (1-1), the fixation of the other end and the first fixture (1-3) of first connecting rod (1-2)
End rotation connection, the first fixture (1-3) are pressed from both sides relative to first connecting rod (1-2) pitching movement, the clamping end of the first fixture (1-3)
Hold one end of motor (2)；The axis of motor (2) is mutually perpendicular to support bracket fastened axis, one end of round tube mold (3) and motor
(2) rotary shaft is fixedly connected, and the other end is open end, and round tube mold (3) is under the drive of the rotary shaft of motor (2) along axis
Rotation；Lifting platform (5) is placed on stationary plane, and heating device (4) is placed on lifting platform (5), and is located at round tube mold (3)
Lower section, adjusts height and position under the drive of lifting platform (5), and heating device (4) adds round tube mold (3) by hot-air
Heat, dropper (6) is for containing and Polymer Solution being added dropwise on the inner wall of the open end of round tube mold (3)；
The micropore preparation facilities includes air pump (7), flow valve (8), connecting tube (9), spray canister (10), the second connecting rod
(11) it is placed on stationary plane with the second fixture (12), the air pump (7), one end of air pump (7) passes through connecting tube (9)
It is connect with one end of flow valve (8), the other end of flow valve (8) is connect by connecting tube (9) with one end of spray canister (10), spray canister
(10) it is intracavitary that other end outer end face is vacantly placed in round tube mold (3), and particle is placed in spray canister (10), the second connecting rod (11)
One end moves up and down along fixed link (1-1) and can be fixed on any position of fixed link (1-1), the second connecting rod (11) it is another
The fixing end at end and the second fixture (12) is rotatablely connected, and the clamping end of the second fixture (12) clamps spray canister (10), and spray canister (10) exists
Adjustable position and angle under the drive of second fixture (12).
2. a kind of preparation facilities of small-caliber artificial blood vessel microcellular structure according to claim 1, which is characterized in that described
Round tube mold (3) internal diameter be 3.00~6.00mm, length < 300.00mm.
3. the method that device of any of claims 1 or 2 prepares small-caliber artificial blood vessel microcellular structure characterized by comprising
Step 1: the preparation of small-caliber artificial blood vessel
1) Polymer Solution is prepared
High molecular material is completely dissolved under room temperature or heating in organic solvent of the boiling point lower than 160 DEG C, forming concentration is
The Polymer Solution of 0.01~1.00g/mL；
2) centrifugation coating
It controls motor (2) and round tube mold (3) rotation is first driven with the revolving speed of 10~1000rpm, Polymer Solution is used, dress is added dropwise
On the inner wall for setting the open end that (6) are added drop-wise to round tube mold (3), revolving speed is promoted to 100~3000rpm, passes through the first folder of rotation
The axis angulation of the axis and fixed link (1-1) that have (1-3) adjustment motor (2) and round tube mold (3) is 20~70 °, is made
Polymer Solution is evenly applied on the inner wall of round tube mold (3) under centrifugal force and gravity, forms the liquid of uniformly continuous
Film, then by the axis trimming of motor (2) and round tube mold (3) to, starting heating device vertical with the axis of fixed link (1-1)
(4) it heats, the surface for making the organic solvent in Polymer Solution evaporate into liquid film judges whether thickness reaches in after leather hard
The pipe thickness of required small-caliber artificial blood vessel, reaches, and executes step 3), not up to, repeats step 2)；
3) it selects
If the small-caliber artificial blood vessel tube wall of preparation is single layer structure, step 2 is directly executed；If the small-caliber artificial blood of preparation
Tube wall is multilayered structure, repeats step 1) to step 3), until executing step 2 after the completion of multilayered structure coating, needing
Bright be multilayered structure coating sequence be from outside to inside；
Step 2: the preparation of microcellular structure
1) device is adjusted
Removal heating device (4) and dropper (6), installation micropore preparation facilities, adjustment round tube mold (3) and spray canister (10)
Angle and position make spray canister (10) and round tube mold (3) to be in same axis, and spray canister (10) outlet outer end face is vacantly placed in circle
Pipe mold (3) is intracavitary；
2) particle covers small-caliber artificial blood vessel inner wall
Start motor (2) and round tube mold (3) rotation is driven with the revolving speed of 10~100rpm, starts air pump (7), pass through flow valve
(8) control air velocity is 0.1~4.0L/min, and the particle in spray canister (10) disturbs under airflow function, and with air-flow
It is sprayed from spray canister (10), uniform fold is being in the small-caliber artificial blood vessel inner wall of leather hard；
3) particle is inlayed
Micropore preparation facilities is removed, motor (2) and round tube mold (3) position and angle are adjusted, it is made to hang down with fixed bracket axis
Directly, start motor (2) and increase its revolving speed to 10~3000rpm, particle is made to be embedded in leather hard under the action of the centrifugal force
Then artificial blood vessel's inner surface is installed heating device (4) and is started, until solvent volatilizees completely；
4) it post-processes
It removes round tube mold (3), demoulds, obtain embedding fine-grained small-caliber artificial blood vessel, particle is completely removed completely, is dried
Dry, finishing obtains the small-caliber artificial blood vessel with microcellular structure.
4. the preparation method of small-caliber artificial blood vessel microcellular structure according to claim 3, which is characterized in that the step
High molecular material in one is selected from natural or artificial synthesized one or more of high molecular material；The natural polymer
Material is fibroin albumen or collagen；Artificial synthesized high molecular material is polyurethane, polylactic acid, polycaprolactone or polyolefin.
5. the preparation method of small-caliber artificial blood vessel microcellular structure according to claim 3, which is characterized in that the step
The heating temperature of one heating device (4) is 50~150 DEG C, and heating time is 1~120min.
6. the preparation method of small-caliber artificial blood vessel microcellular structure according to claim 3, which is characterized in that the step
Motor (2) and the axis of spray canister (10) are parallel with fixed bracket axis in two, and spray canister (10) outlet outer end face is away from circular hole mould
(3) open end section 1mm.
7. the preparation method of small-caliber artificial blood vessel microcellular structure according to claim 3, which is characterized in that the step
Two particle is the one or more of particulate inorganic material, organic material particle or metal material particle.
8. the preparation method of small-caliber artificial blood vessel microcellular structure according to claim 7, which is characterized in that the nothing
Machine particles of material is NaCl, NH4One or more of Cl, KCl, glass, quartz or ceramic particle；Organic material particle is stone
One or more of wax, polystyrene, polyethylene or polypropylene microparticle；Metal material particle is in iron, copper or lead particle
It is one or more of.
9. the preparation method of small-caliber artificial blood vessel microcellular structure according to claim 3, which is characterized in that the step
The method that particle removes in two is ultrasonic method or dissolution method.
10. the preparation method of small-caliber artificial blood vessel microcellular structure according to claim 3, which is characterized in that the tool
The small-caliber artificial blood vessel tube wall for having microcellular structure is single or multi-layer structure, and wall thickness is 0.02~1.00mm, length 20.00
~200.00mm, internal diameter are 2.00~6.00mm, and pore size is 1~1000 μm.
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