CN109498839A - A kind of biology composite artificial blood vessel and application - Google Patents
A kind of biology composite artificial blood vessel and application Download PDFInfo
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- CN109498839A CN109498839A CN201811347294.XA CN201811347294A CN109498839A CN 109498839 A CN109498839 A CN 109498839A CN 201811347294 A CN201811347294 A CN 201811347294A CN 109498839 A CN109498839 A CN 109498839A
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- artificial blood
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- 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
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- 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
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- 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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/3633—Extracellular matrix [ECM]
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0005—Use of materials characterised by their function or physical properties
- A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0005—Use of materials characterised by their function or physical properties
- A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
- A61L33/0041—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate characterised by the choice of an antithrombatic agent other than heparin
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
- A61L33/08—Polysaccharides
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- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
- A61L33/12—Polypeptides, proteins or derivatives thereof, e.g. degradation products thereof
- A61L33/128—Other specific proteins or polypeptides not covered by A61L33/122 - A61L33/126
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- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/23—Carbohydrates
- A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
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- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/23—Carbohydrates
- A61L2300/236—Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
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- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
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- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
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- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures
Abstract
The present invention provides a kind of biological composite artificial blood vessels, it is related to bioactive materials technical field, the structure setting of the biology composite artificial blood vessel is internal layer and outer layer, the internal layer is the blood vessel of the new born animal by de- cell processing, the outer layer is macromolecule polymer material, provides mechanical support for internal layer；The outer surface of the cell free blood vessel and the inner surface of macromolecule polymer material are combined closely；The cell free blood vessel passes through anticoagulant modification；The macromolecule polymer material load anticoagulant or anti-proliferative drug.Biological composite artificial blood vessel after transplanting, is had good patency and regeneration effect by the present invention, and no calcification occurs.
Description
Technical field
The present invention relates to bioactive materials technical fields, and in particular to a kind of biology composite artificial blood vessel and application.
Background technique
Cardiovascular disease includes cardiovascular, cranial vascular disease, is referred to due to hyperlipidemia, blood is sticky, artery is athero-
Ischemic or hemorrhagic disease occur for heart caused by hardening, hypertension etc., brain and body tissue.According to " Chinese painstaking effort
Pipe disease report 2017 " point out that current China's cardiovascular patient number is about 2.9 hundred million, cardiovascular disease has become human health
Number one killer.Carrying out vasotransplantation in the angiosomes of lesion is to treat the available strategy of cardiovascular disease.So far, coronal
Artery or the blood vessel of the preferred patient itself of peripheral blood vessel operation, wherein saphena and internal mammary artery are the goldstandards of vasotransplantation.
However, the patient of about one third is since the blood vessel not being suitble to self can use, the source of grafting vessel is just
As a critical issue.In recent years, researcher attempts to prepare artificial blood vessel using synthesis high molecular material, but due to thrombus and
The problems such as endometrial hyperplasia, vascular patency are lower.
Native blood vessels can be used as artificial blood vessel by de- cell processing and be used for clinic.Blood vessel is dynamic mostly from adult at present
Object, but extracellular matrix, after undergoing long-term physiology, pathology reconstruct, function and bioactivity are remarkably decreased, and blood vessel is long-term
Occurs the problems such as calcification after transplanting.
Summary of the invention
The purpose of the present invention is to provide a kind of biological composite artificial blood vessel, biology composite artificial blood vessel provided by the invention
Not only there is good patency, also there is good regeneration effect.
The present invention provides a kind of biological composite artificial blood vessel, the structure setting of the biology composite artificial blood vessel is internal layer
And outer layer, the internal layer are cell free blood vessel, the outer layer is macromolecule polymer material；
The outer surface of the cell free blood vessel and the inner surface of macromolecule polymer material are combined closely；
The cell free blood vessel is modified by anticoagulant；
The macromolecule polymer material load anticoagulant or anti-proliferative drug；
The blood vessel is the blood vessel of birth 1~30d animal.
Preferably, the anticoagulant includes one or more of heparin, hirudin and low-molecular-weight hyaluronic acid；
The anti-proliferative drug includes taxol and/or rapamycin.
Preferably, the blood vessel includes that aorta pectoralis blood vessel, abdominal aorta blood vessel, internal mammary artery blood vessel, the stomach nethike embrane right side are dynamic
Arteries and veins, Artery Vein or arteria epigastrica inferior blood vessel.
Preferably, the macromolecule polymer material includes electrospinning pipe or polymer support.
Preferably, the preparation method of the polymer support, comprising: after mixing raw material with anticoagulant, using melting
Spinning process is prepared, or after raw material is mixed with anti-proliferative drug, is prepared using melt spinning method.
Preferably, the mass ratio of the raw material and anticoagulant is (1000~100000): 1, the raw material and anti-proliferate
The mass ratio of drug is (1000~100000): 1.
Preferably, the preparation method of the electrospinning pipe, comprising: after mixing raw material with anticoagulant, using electrostatic spinning
Method is prepared, or after raw material is mixed with anti-proliferative drug, is prepared using electrospinning process.
Preferably, the mass ratio of the raw material and anticoagulant is (1000~100000): 1, the raw material and anti-proliferate
The mass ratio of drug is (1000~100000): 1.
Preferably, the preparation method of the electrospinning pipe, comprising: after mixing raw material with nitrate, using electrostatic spinning side
Method is prepared.
Preferably, the mass ratio of the raw material and nitrate is (2~1000): 1
Preferably, the raw material include polycaprolactone, polylactide, polyglycolic acid, polylactide-ethanol copolymer,
Poly- (lactide-caprolactone) copolymer, polydioxanone or polyhydroxyalkanoate.
The present invention also provides the biological composite artificial blood vessels described in above-mentioned technical proposal to prepare arteries transplanting material
Application in material.
The present invention provides a kind of biological composite artificial blood vessel, the cell free blood vessel of internal layer remains the extracellular base of native blood vessels
It is viscous to be able to suppress blood platelet by the cell free blood vessel of anticoagulant modification conducive to the adherency and infiltration of host cell for matter ingredient
Attached, to improve the patency of blood vessel, outer layer macromolecule polymer material is not only that cell free blood vessel provides mechanics branch
Support, improves the intensity of cell free blood vessel, after load anticoagulant and anti-proliferative drug, additionally it is possible to improve biological composite vascular
Short-term, long-term patency, therefore biological composite artificial blood vessel has good regeneration effect.
The embodiment of the present invention is as the result is shown: after the present invention transplants biological composite artificial blood vessel, having good
Patency and regeneration effect.
Detailed description of the invention
Fig. 1 is 1 newborn pigs aorta pectoralis of embodiment and abdominal aorta；
Fig. 2 is the frozen section H&E coloration result for the blood vessel that embodiment 1 obtains；
Fig. 3 is the H&E coloration result of the frozen section for the cell free blood vessel that embodiment 3 obtains；
Fig. 4 is the biological composite artificial blood vessel that embodiment 8 obtains；
Fig. 5 is the biological composite artificial blood vessel that embodiment 18 obtains；
Fig. 6 is that biological composite artificial blood vessel is transplanted to rabbit arteria carotis in embodiment 20；
Fig. 7 is that biological composite artificial blood vessel is transplanted to doppler ultrasound result of the rabbit arteria carotis after 3 months in embodiment 20；
H&E coloration result after Fig. 8 is transplanted 3 months for composite artificial blood vessel biological in embodiment 21；
H&E coloration result after Fig. 9 is transplanted 3 months for composite artificial blood vessel biological in embodiment 23.
Von Kossa coloration result after Figure 10 is transplanted 3 months for composite artificial blood vessel biological in embodiment 24.
Specific embodiment
The present invention provides a kind of biological composite artificial blood vessel, the structure setting of the biology composite artificial blood vessel is internal layer
And outer layer, the internal layer are cell free blood vessel, the outer layer is macromolecule polymer material；Outside the cell free blood vessel
The inner surface of surface and macromolecule polymer material is combined closely；The cell free blood vessel is modified by anticoagulant；It is described
Macromolecule polymer material loads anticoagulant and anti-proliferative drug.
In the present invention, the blood vessel is the blood vessel of birth 1~30d animal, the blood vessel for the 7d animal that is preferably born.
In the present invention, the preparation method of the biological composite artificial blood vessel is preferred are as follows: wears the cell free blood vessel
Macromolecule polymer material is crossed, the inner surface of the outer surface and macromolecule polymer material that make cell free blood vessel is combined closely,
Obtain biological composite artificial blood vessel.
In the present invention, the macromolecule polymer material is preferably through preparing biological composite artificial blood vessel again after disinfection,
The present invention is not particularly limited the method for the disinfection reagent used and disinfection, using reagent and the disinfection of routine disinfection
Method.
In the present invention, the biological composite artificial blood vessel of the preparation preferably carries out in an aseptic environment.
The biological composite artificial blood vessel being prepared preferably is stored in the physiological saline containing 1%PS by the present invention, is protected
The temperature deposited is preferably 4 DEG C, and the preservation is preferably kept in dark place.
In the present invention, the cell free blood vessel prepares biological composite artificial blood vessel again after anticoagulant modification, at this
In inventive embodiments, the anticoagulant of the de- cellular vascular is specially heparin, hirudin or low-molecular-weight hyaluronic acid, described
It is preferable to use coupling reagent and acellular matrixes to be covalently attached for anticoagulant, the coupling reagent be n-hydroxysuccinimide and
1- (3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride.In the present invention, the inner surface of the de- cellular vascular is anticoagulant
The amount of drug is preferably 1.0~1000.0U/cm2。
In the present invention, the preparation method of the cell free blood vessel, preferably includes following steps:
1) it carries out first after mixing blood vessel with sodium dodecyl sulfate solution to vibrate, the blood vessel after obtaining the first oscillation,
Blood vessel after first oscillation is subjected to the first cleaning with phosphate buffer, the blood vessel after obtaining the first cleaning；
The quality volume fraction of dodecyl sodium sulfate is 0.05~5w/v% in the sodium dodecyl sulfate solution；
2) blood vessel after obtain the step 1) first is cleaned mixes laggard with Triton X-100 solution
Row second vibrates, the blood vessel after obtaining the second oscillation, and the blood vessel after second oscillation is carried out second with phosphate buffer
Cleaning, the blood vessel after obtaining the second cleaning；
3) blood vessel after the second cleaning for obtaining the step 2) and the phosphate containing disodium ethylene diamine tetraacetate are slow
Third oscillation is carried out after fliud flushing mixing, the blood vessel after obtaining third oscillation delays the blood vessel phosphate after third oscillation
Fliud flushing carries out third cleaning, the blood vessel after obtaining third cleaning；
The phosphate buffer containing disodium ethylene diamine tetraacetate is using phosphate buffer as solvent, further includes: 3-
[3- (gallbladder amido propyl) dimethylamino] propane sulfonic acid inner salt and sodium chloride；
4) blood vessel after cleaning the third that the step 3) obtains is mixed with the DMEM complete medium containing fetal calf serum
The 4th oscillation is carried out afterwards, and the blood vessel after obtaining the 4th oscillation carries out the blood vessel after the 4th oscillation with sulfate buffer
4th cleaning, the blood vessel after obtaining the 4th cleaning；
5) blood vessel after obtain the step 4) the 4th cleans carries out the 5th oscillation after mixing with citric acid solution, obtain
Blood vessel to after de- cell.
In the present invention, the de- cellular vascular is preferably reacted with after anticoagulant, coupling reagent mixing, is resisted
The cell free blood vessel of solidifying drug modification.
The present invention carries out the first oscillation, the blood after obtaining the first oscillation after mixing blood vessel with sodium dodecyl sulfate solution
Blood vessel after first oscillation is carried out the first cleaning with phosphate buffer, the blood vessel after obtaining the first cleaning by pipe；It is described
The quality volume fraction of dodecyl sodium sulfate is 0.05~5w/v% in sodium dodecyl sulfate solution.
In the present invention, the length of the blood vessel and the volume ratio of sodium dodecyl sulfate solution be preferably (1.5~
15.5) cm:(25~35) ml, more preferably (1~15) cm:30ml.
In the present invention, the blood vessel preferably includes aorta pectoralis blood vessel, abdominal aorta blood vessel, internal mammary artery blood vessel, stomach
The right artery of nethike embrane, Artery Vein or arteria epigastrica inferior blood vessel.In the present invention, the source of the blood vessel is preferably newborn moves
Object, the animal are preferably pig and sheep, and the pig age of the pig is preferably 1~2 week, and the present invention is not special to the kind of the pig
It limits, is particularly preferred as Landrace in embodiments of the present invention；The sheep age of the sheep is preferably 1~14 day, and more preferably 7 days,
The present invention is not particularly limited the kind of the sheep, is particularly preferred as sheep in embodiments of the present invention.In the present invention, institute
The preferred source new born animal of blood vessel is stated, makes blood vessel that there is suitable length, bore and wall thickness, so as to safe bearing load arterial blood
It presses and is able to carry out good regeneration.
In the present invention, the separation method of the aorta pectoralis blood vessel and abdominal aorta blood vessel, preferably includes following steps:
Pig or sheep are put to death using the method excessively anaesthetized, pig or sheep are placed on operation table surface in dorsal position, fix four
Limb cleans skin of chest abdomen using Iodophor, extends to midline abdominal along manubrium with scissors, successively cuts off skin and muscle
Layer opens thoracic cavity, exposes heart, and aorta ascendens originates from left ventricle, and aorta pectoralis is the descending aorta of chest, and wears diaphragm
Therefore aorta breach, which migrates, since left ventricle, passes through diaphram for abdominal aorta, gradually separation with caution, until ilium always moves
Arteries and veins, intercostal arteries and subcostal artery are all from aorta pectoralis, must be thin below great care therefore when separation is to aorta pectoralis
Subbranch, and ligatured using degradable suture, it separates in ligation, after isolating blood vessel, is entered with syringe to aorta ascendens
It is slowly injected into the normal saline solution (50U/mL) of test tube of hepari at mouthful, removes residual blood ingredient, blood vessel is stored in containing 1%PS
PBS in, 4 DEG C preservation.According to common knowledge it is found that the front end of aorta pectoralis is aorta ascendens, aorta pectoralis and abdominal aorta
It links together, so together taking out aorta pectoralis blood vessel and abdominal aorta blood vessel when taking blood vessel.
In the present invention, the quality volume fraction of dodecyl sodium sulfate is 0.05 in the sodium dodecyl sulfate solution
~5w/v%, preferably 0.1~5w/v%, more preferably 1~3w/v%.
In the present invention, the condition of first oscillation preferably includes: the time of the oscillation is preferably 3~for 24 hours, it is more excellent
It is selected as 8~16h, most preferably 10~14h；The revolving speed of first oscillation is preferably 60~80rpm, more preferably 65~
75rpm, most preferably 70rpm；The temperature of first oscillation is preferably 15~35 DEG C, and more preferably 20~30 DEG C, most preferably
It is 23~26 DEG C.
In the present invention, the pH value of the phosphate buffer is preferably 7.2~7.4.In the present invention, described first is clear
The step of washing preferably includes: at 4 DEG C, the blood vessel after the first oscillation being mixed 24~96h with phosphate buffer, more every 8h
Change phosphate buffer.
In the present invention, the blood vessel is vibrated after mixing with sodium dodecyl sulfate solution, is cleaned, and can be destroyed thin
After birth.
The present invention carries out second after mixing the blood vessel after the obtain first cleaning with Triton X-100 solution
Blood vessel after second oscillation is carried out the second cleaning with phosphate buffer, obtained by oscillation, the blood vessel after obtaining the second oscillation
Blood vessel to after the second cleaning.
In the present invention, the mass body of Triton X-100 integrates in the Triton X-100 solution
Number is preferably 0.05~5w/v%, more preferably 0.1~4w/v%, most preferably 1~3w/v%.
In the present invention, the condition of second oscillation preferably includes: the time of second oscillation is preferably 4~48h,
More preferably 10~35h, most preferably 15~25h；The speed of second oscillation is preferably 60~70rpm, and more preferably 65
~75rpm, most preferably 70rpm；The temperature of second oscillation is preferably 15~35 DEG C, more preferably 20~30 DEG C, optimal
It is selected as 22~26 DEG C.
In the present invention, the step of the described second cleaning preferably includes: at 4 DEG C, by the blood vessel and phosphorus after the first oscillation
Phthalate buffer mixes 24~96h, replaces phosphate buffer every 8h.
In the present invention, the blood vessel after first cleaning shakes after mixing with Triton X-100 solution
It swings, clean, the connection between lipid and between lipid and protein can be broken.
The present invention mixes the blood vessel after the second cleaning with the phosphate buffer containing disodium ethylene diamine tetraacetate laggard
Blood vessel after third oscillation is carried out third with phosphate buffer by the oscillation of row third, the blood vessel after obtaining third oscillation
Cleaning, the blood vessel after obtaining third cleaning；
The phosphate buffer containing disodium ethylene diamine tetraacetate is using phosphate buffer as solvent, further includes: 3-
[3- (gallbladder amido propyl) dimethylamino] propane sulfonic acid inner salt and sodium chloride.
In the present invention, the phosphate buffer containing disodium ethylene diamine tetraacetate is molten with phosphate buffer
Agent, further includes: 3- [3- (gallbladder amido propyl) dimethylamino] propane sulfonic acid inner salt and sodium chloride.In the present invention, the 3- [3-
(gallbladder amido propyl) dimethylamino] concentration of propane sulfonic acid inner salt is preferably 5~10mM, more preferably 6~9mM, most preferably 7~
8mM；The concentration of the sodium chloride is preferably 0.1~1mM, more preferably 0.3~0.7mM, most preferably 0.4~0.6mM；It is described
The concentration of disodium ethylene diamine tetraacetate is preferably 5~25mM, more preferably 10~20mM, more preferably 13~17mM.
In the present invention, the condition of third oscillation preferably includes: the time of the third oscillation is preferably 3~for 24 hours,
More preferably 10~18h, most preferably 12~14h；The temperature of the third oscillation is preferably 35~42 DEG C, more preferably 37
℃；The speed of the third oscillation is preferably 60~80rpm, more preferably 65~75rpm, most preferably 70rpm.
In the present invention, the step of third is cleaned preferably includes: at 4 DEG C, by the blood vessel and phosphorus after the first oscillation
Phthalate buffer mixes 24~96h, replaces phosphate buffer every 8h.
In the present invention, the blood vessel after second cleaning and the phosphate buffer containing disodium ethylene diamine tetraacetate are mixed
Vibrated, cleaned after conjunction, can interaction between crack protein matter, remove protein component.
The present invention third is cleaned after blood vessel mixed with the DMEM complete medium containing fetal calf serum after carry out the 4th vibration
It swings, the blood vessel after obtaining the 4th oscillation, the blood vessel after the 4th oscillation is subjected to the 4th cleaning with sulfate buffer, is obtained
Blood vessel after 4th cleaning.
In the present invention, the DMEM complete medium containing fetal calf serum is using DMEM complete medium as solvent, preferably
Including fetal calf serum and deoxyribonuclease Ⅰ, the volume fraction of the fetal calf serum is preferably 8~12%, more preferably 9~
11%, most preferably 10%；The concentration of the deoxyribonuclease Ⅰ is preferably 100~300U/mL, more preferably 150~
250U/mL, most preferably 180~220U/mL.
In the present invention, the condition of the 4th oscillation preferably includes: the time of the 4th oscillation is preferably 12~
96h, more preferably 30~80h, most preferably 40~70h；The frequency of 4th oscillation is preferably 60~80rpm, more preferably
For 65~75rpm, most preferably 70rpm；The temperature of 4th oscillation is preferably 35~42 DEG C, and more preferably 37 DEG C.
In the present invention, the step of the described 4th cleaning preferably includes: at 4 DEG C, by the blood vessel and phosphorus after the first oscillation
Phthalate buffer mixes 24~96h, replaces phosphate buffer every 8h.
In the present invention, the blood vessel after the third cleaning carries out after mixing with the DMEM complete medium containing fetal calf serum
Oscillation, cleaning, can digest remaining DNA ingredient in vascular tissue, be removed after cleaning.
The present invention carries out the 5th oscillation after mixing the blood vessel after the 4th cleaning with citric acid solution, obtains de- cell
Blood vessel afterwards.
In the present invention, the quality volume fraction of citric acid is preferably 1~2w/v% in the citric acid solution, more preferably
For 1.47w/v%.In the present invention, the solvent of the citric acid solution is preferably physiological saline.In the present invention, the lemon
The pH value of acid solution is preferably 7.4, it is preferred to use the pH value that concentration is the aqueous citric acid solution of 0.1M to adjust citric acid solution.
In the present invention, the citric acid solution after high-temperature sterilization preferably through reusing, condition of the present invention to the high-temperature sterilization
It is not particularly limited, the condition to be sterilized using conventional high temperature.
In the present invention, the condition of the 5th oscillation preferably includes: the temperature of the 5th oscillation is preferably 4 DEG C；Institute
The time for stating the 5th oscillation is preferably 24~72h, more preferably 30~60h, most preferably 40~50h；5th oscillation
Speed is preferably 60~80rpm, more preferably 65~75rpm, most preferably 70rpm.
In the present invention, the blood vessel after the 4th cleaning carries out the 5th oscillation after mixing with citric acid solution, can be thorough
Remove remaining memebrane protein and DNA residual in bottom.
In the present invention, the cell free blood vessel with the solution containing anticoagulant modified medicaments and coupling reagent after mixing
It is reacted, obtains the blood vessel of anticoagulant modification.
In the present invention, the cell free blood vessel is preferably stored in the phosphate buffer containing penicillin and streptomysin
In, the temperature of preservation is preferably 4 DEG C.In the present invention, in the phosphate buffer penicillin and streptomysin quality percentage
Content is preferably 1%.
In the present invention, the bore of the cell free blood vessel is preferably 2~6mm, more preferably 3~5mm, most preferably
3.5~4.5mm；The length of the cell free blood vessel is preferably 1~15cm, more preferably 3~12cm, most preferably 5~
10cm；The thickness of the cell free blood vessel is preferably 0.1~2.0mm, more preferably 0.2~1.0mm, most preferably 0.4~
0.8mm。
In the present invention, the raw material of the macromolecule polymer material preferably includes polycaprolactone, polylactide, polyethanol
Acid, polylactide-ethanol copolymer, poly- (lactide-caprolactone) copolymer, polydioxanone or poly-hydroxy fatty acid
Ester.
In the present invention, the raw material of the macromolecule polymer material is also preferably nitrate degradative bioactive material
Itrate group be covalently attached degradable polymer terminal hydroxy group formed substance；The terminal hydroxy group degradable polymer preferably wraps
It includes polycaprolactone, polylactide, polyglycolic acid, polylactide-ethanol copolymer, poly- (lactide-caprolactone) copolymer, gather
Lanthanum Isopropoxide or polyhydroxyalkanoate.
In invention, the content of itrate group is preferably 1~20wt% in the nitrate degradative bioactive material,
More preferably 5~15wt%, most preferably 8~12wt%.
In the present invention, biology is prepared again again after the macromolecule polymer material load anticoagulant or anti-proliferative drug
Close artificial blood vessel.The method that the present invention loads anticoagulant or anti-proliferative drug to the macromolecule polymer material is not special
It limits, using routine.In embodiments of the present invention, the anticoagulant is preferably that heparin, hirudin or low molecular weight are saturating
Bright matter acid；The anti-proliferative drug drug is preferably taxol and/or rapamycin.In the present invention, the high molecular polymerization
The amount of anticoagulant or anti-proliferative drug is preferably 0.01~10mg/g in object material.
In the present invention, the macromolecule polymer material preferably includes electrospinning pipe or polymer support.
In the present invention, the electrospinning pipe preferably use the method for electrostatic spinning by the raw material of macromolecule polymer material and
Anticoagulant (or anti-proliferative drug) is prepared, and the present invention is not particularly limited the method for the electrostatic spinning, using normal
Rule method.In the present invention, the mass ratio of the raw material and anticoagulant, anti-proliferative drug is respectively preferably (1000):
(1)~(100000): (1).In the present invention, the mass ratio of the raw material and nitrate is preferably (2:1)~(1000:1).?
In the present invention, the diameter of the electrospinning pipe is preferably 2.5~10mm, more preferably 3.5~7.5mm, most preferably 4.3~
6.5mm；The wall thickness of the electrospinning pipe is preferably 100~300 μm, more preferably 120~200 μm, most preferably 150 μm；It is described
The length of electrospinning pipe is preferably 2~8cm, more preferably 3~6cm, most preferably 3.5~4.5cm.
In the present invention, the polymer support preferably uses the method for melt spinning for macromolecule polymer material and resists
Solidifying drug (or anti-proliferative drug) is prepared, and the present invention is not particularly limited the method for the melt spinning, using routine
Method.In the present invention, the mass ratio of the raw material and anticoagulant (or anti-proliferative drug) is preferably (1000): (1)
~(100000): (1).In the present invention, the diameter of the polymer support is preferably 2.5~10mm, more preferably 3.5~
7.5mm, most preferably 4.3~6.5mm；The wall thickness of the polymer support is preferably 50~200 μm, more preferably 100~160
μm, most preferably 120~140 μm；The length of the polymer support preferably 2~8cm, more preferably 3~6cm,
Most preferably 3.5~4.5cm.
In the present invention, the biological composite artificial blood vessel has good patency and regeneration effect.
The present invention also provides the biological composite artificial blood vessels to prepare the application in arteries graft materials.
A kind of biological composite artificial blood vessel of the present invention and application are done further in detail combined with specific embodiments below
Thin introduction, technical solution of the present invention include but is not limited to following embodiment.
Embodiment 1
The separation of newborn pigs aorta pectoralis and abdominal aorta blood vessel:
The common Landrace cub of be born 7 days, weight 2.5kg is put to death using the method excessively anaesthetized and is placed in dorsal position
On operation table surface, fixing limbs；Skin of chest abdomen is cleaned using Iodophor；Scissors extends to midline abdominal along manubrium, successively
Cut off skin and muscle layer；Thoracic cavity is opened, heart is exposed；Since left ventricle, diaphram is passed through, arrives arteria iliaca communis, gradually sincerely
Careful separation；It is ligatured using 6-0 suture, is separated in ligation；It is slow to aorta ascendens inlet with syringe after isolating blood vessel
The normal saline solution (50U/mL) of slow injection test tube of hepari, removes residual blood ingredient；Blood vessel is stored in the PBS containing 1%PS
In, 4 DEG C of preservations, blood vessel is shown in Fig. 1；
H&E coloration result is as shown in Figure 2.
Embodiment 2
The separation of newborn lamb aorta pectoralis and abdominal aorta blood vessel:
The sheep cub of be born 3 days, weight 3kg is put to death using the method excessively anaesthetized and is placed on operating table in dorsal position
On face, fixing limbs；Chest and skin of abdomen are cleaned using Iodophor；Scissors cuts off thoracic cavity, extends to midline abdominal along manubrium,
Successively cut off skin and muscle layer；Thoracic cavity is opened, heart is exposed；Since left ventricle, diaphram is passed through, arrives arteria iliaca communis, by
Step separation with caution；It is ligatured using 6-0 suture, is separated in ligation；After isolating blood vessel, with syringe to aorta ascendens entrance
Place is slowly injected into the normal saline solution (50U/mL) of test tube of hepari, removes residual blood ingredient；Blood vessel is stored in containing 1%PS's
In PBS, 4 DEG C of preservations；
Embodiment 3
The preparation of the cell free blood vessel of newborn pigs aorta pectoralis:
(1) newborn pigs aorta pectoralis blood vessel (4cm long) is placed in the SDS aqueous solution of 30mL 2w/v%, room temperature condition
Under, shaking table mildly shakes 4 hours, and the speed of concussion is 70rpm；
(2) by treated, vascular grafts are placed in 30mLPBS solution, are cleaned 48 hours, are changed the liquid once for every eight hours, PBS
The pH value of solution is 7.2；
(3) by the TritonX-100 aqueous solution of step (2) treated vascular grafts merging 0.5w/v%, room temperature item
Under part, shaking table mildly shakes 4 hours, and the speed of concussion is 70rpm；
(4) by step (3) treated vascular grafts merging 30mLPBS solution, 48 hours are cleaned under the conditions of 4 DEG C, often
It changes the liquid once within 8 hours；
(5) step (4) treated vascular grafts merging is contained into 5mM CHAPS, the PBS of 0.1MNaCl and 5mM EDTA
In buffer, under the conditions of 37 DEG C, shaking table mildly shakes 24 hours, and the speed of concussion is 70rpm；
(6) by step (5) treated vascular grafts merging 30mLPBS solution, 48 hours are cleaned under the conditions of 4 DEG C, often
It changes the liquid once within 8 hours；
(7) the DMEM complete medium that 30mL contains 10%FBS (fetal calf serum) is prepared, by DNase I with 300U/mL's
Concentration dissolution, by step (6) treated blood vessel merging solution, under the conditions of 37 DEG C, constant-temperature table mildly shakes 24 hours, shake
The speed swung is 70rpm；
(8) step (7) treated blood vessel is placed in 30mL normal saline solution, under the conditions of 4 DEG C, cleans 48 hours, every 8
Hour changes the liquid once；
(9) by step (8), treated that blood vessel is stored in the PBS containing 1%PS, 4 DEG C of preservations；
The frozen section H&E coloration result of de- cell treated blood vessel is as shown in Figure 3.
Embodiment 4
The preparation of the newborn cell free blood vessel of lamb aorta pectoralis:
(1) newborn lamb aorta pectoralis blood vessel (4cm long) is placed in the SDS aqueous solution of 30mL 3w/v%, room temperature condition
Under, shaking table mildly shakes 3 hours, and the speed of concussion is 70rpm；
(2) by treated, vascular grafts are placed in 30mLPBS solution, are cleaned 72 hours, are changed the liquid once for every eight hours, PBS
The pH value of solution is 7.2；
(3) by the TritonX-100 aqueous solution of step (2) treated vascular grafts merging 0.5w/v%, room temperature item
Under part, shaking table mildly shakes 6 hours, and the speed of concussion is 70rpm；
(4) by step (3) treated vascular grafts merging 30mLPBS solution, 48 hours are cleaned under the conditions of 4 DEG C, often
It changes the liquid once within 8 hours；
(5) the DMEM complete medium that 30mL contains 10%FBS (fetal calf serum) is prepared, by DNase I with 300U/mL's
Concentration dissolution, by step (4) treated blood vessel merging solution, under the conditions of 37 DEG C, constant-temperature table mildly shakes 36 hours；
(6) normal saline solution containing 1.47w/v% sodium citrate is prepared, is adjusted to the citric acid solution of 0.1M
PH7.4, after high-temperature sterilization, by step (5) treated blood vessel merging solution, under the conditions of 4 DEG C, it is small that shaking table mildly shakes 36
When, it changes the liquid once within every 12 hours, the speed of concussion is 70rpm；
(7) by step (6), treated that blood vessel is stored in the PBS containing 1%PS, 4 DEG C of preservations；
Embodiment 5
The anticoagulant modification of the cell free blood vessel of newborn pigs aorta pectoralis:
Prepare 30mL 1mg/mL heparin sodium PBS solution, after being completely dissolved, sequentially add 155.37mgNHS and
After 3 minutes, the cell free blood vessel of 4cm long is put into solution by 172.53mg EDC, and under the conditions of 4 DEG C, mild concussion 24 is small
When；Treated, and blood vessel is placed in physiological saline, under the conditions of 4 DEG C, is cleaned 24 hours, is changed the liquid once for every eight hours, will be by anti-
The cell free blood vessel of solidifying modification is stored in the physiological saline containing 1%PS, 4 DEG C of preservations.
Embodiment 6
The anticoagulant modification of the newborn cell free blood vessel of lamb aorta pectoralis:
Prepare 30mL 1mg/mL heparin sodium PBS solution, after being completely dissolved, sequentially add 155.37mgNHS and
After 2 minutes, the cell free blood vessel of 4cm long is put into solution by 172.53mg EDC, and under the conditions of 4 DEG C, mild concussion 24 is small
When；Treated, and blood vessel is placed in physiological saline, under the conditions of 4 DEG C, is cleaned 24 hours, is changed the liquid once for every eight hours, will be by anti-
The cell free blood vessel of solidifying modification is stored in the physiological saline containing 1%PS, 4 DEG C of preservations.
Embodiment 7
Load the preparation of the electrostatic spinning PCL polymer electrospinning pipe of hirudin:
(1) the chloroform/methanol mixed solvent that 9mL volume ratio is 5:1 is prepared, 2.25g PCL particle is weighed, it is molten that mixing is added
Stirring and dissolving is stayed overnight in agent, and the PCL solution of 25w/v% is made；
(2) 0.16g type i collagen is weighed, 2mL hexafluoroisopropanol solution is added, stirring and dissolving is overnight, is made 8w/v%'s
Collagen solution；
(3) 0.005g bovine serum albumin(BSA) powder is weighed, 1mL hexafluoroisopropanol solution is added, the ox of 0.5w/v% is made
Serum albumin solution；
(4) 0.002g hirudin powder is weighed, 2mLPBS solution is added, the hirudin solution of 0.1w/v% is made；
(5) 4:1:1 takes collagen solution, bovine serum albumin solution and hirudin solution to be sufficiently mixed overnight by volume,
Obtain 3mL collagen/hirudin solution；
(6) adjusting indoor humidity 45%, 25 DEG C of temperature.Miniature injection pump is placed on the left of rotating receiver, while will be connect
It receives device and high voltage power supply is connected with ground wire respectively；With specification be 10ml and the syringe of 2.5ml draws prepared 25% respectively
PCL and collagen/hirudin solution.High-pressure electrostatic generator connector is connected with syringe needle, and sets syringe internal diameter and liquid
Flow velocity.PCL electrospinning parameters are as follows: voltage 11kV, flow velocity 8.0ml/h receive distance 25cm；Collagen/hirudin electrospinning parameters: voltage
17kV, flow velocity 0.6ml/h receive distance 15cm.Stainless steel cylinder with diameter for 3.5mm is to receive stick, receives the revolving speed of stick
For 40rpm, the movement speed for receiving stick is 5mm/s；Electrostatic spinning after ten minutes, temperature be 22 DEG C, pressure be -0.075MPa
Under conditions of be dried in vacuo, so that solvent is thoroughly volatilized, obtain load hirudin electrostatic spinning PCL polymer electrospinning pipe；It measures
The wall thickness of electrospinning pipe is 150 μm, diameter 3.8mm, length 8cm.
Embodiment 8
The compound people of biology based on the cell free blood vessel of newborn pigs aorta pectoralis and electrostatic spinning PCL polymer electrospinning pipe
The preparation of work blood vessel:
Select the PCL of the matched load hirudin of cell free external caliber of grafting heparin obtained by internal diameter and embodiment 5
Polymer electrospinning pipe (electrospinning pipe is prepared by embodiment 7)；
Medicinal alcohol immersion PCL polymer electrospinning pipe 30 minutes or more with disinfection；
In sterile super-clean bench, takes out PCL polymer electrospinning pipe and dry；
Tweezers clamp cell free blood vessel and PCL polymer electrospinning pipe respectively, and de- cellular vascular is made to pass through PCL electrostrictive polymer
Pipe is spun, the outer surface of cell free blood vessel and the inner surface of PCL polymer electrospinning pipe is made to combine closely, that is, completes answering for the two
It closes；
Composite vascular is placed in the physiological saline containing 30mL 1%PS, 4 DEG C are kept in dark place for use.
It is as shown in Figure 4 to prepare the biological composite artificial blood vessel completed.
Embodiment 9
The compound people of biology based on the cell free blood vessel of newborn lamb aorta pectoralis and electrostatic spinning PCL polymer electrospinning pipe
The preparation of work blood vessel:
The cell free blood vessel for selecting grafting heparin obtained by internal diameter and embodiment 6 takes off the matched water load of cellular vascular bore
The PCL polymer electrospinning pipe of leech element (electrospinning pipe is prepared by embodiment 7)；
Medicinal alcohol immersion PCL polymer electrospinning pipe 30 minutes or more with disinfection；
In sterile super-clean bench, takes out PCL polymer electrospinning pipe and dry；
Tweezers clamp de- cellular vascular and PCL polymer electrospinning pipe respectively, and de- cellular vascular is made to pass through PCL polymer electrospinning
Pipe, makes the outer surface of cell free blood vessel and the inner surface of PCL polymer electrospinning pipe combine closely, that is, completes the compound of the two；
Composite vascular is placed in the physiological saline containing 30mL 1%PS, 4 DEG C are kept in dark place for use.
Embodiment 10
The preparation of electrostatic spinning nitrate polymer electrospinning pipe:
(1) the chloroform/methanol mixed solvent that 9mL volume ratio is 5:1 is prepared, 2.025g PCL particle and 0.225g nitre are weighed
Acid esters material is added in the mixed solvent stirring and dissolving and stays overnight, the mixed solution of 25w/v% is made, wherein nitric acid ester material and PCL
The mass ratio of material is 1:9；
(2) pass through and adjust indoor humidity 45%, 25 DEG C of temperature.Miniature injection pump is placed on the left of rotating receiver, simultaneously will
Receiver and high voltage power supply are connected with ground wire respectively.The Electrospun solution is fitted into the syringe that diameter is 14.9mm, and
High-voltage DC power supply is connected with syringe needle, adjustment syringe needle alignment cylindrical receivers center, setting syringe needle with
The distance between receiver is 15cm, and solution flow velocity is 8mL/h, DC voltage 13kV；It is the stainless steel circle of 3.5mm with diameter
Column is to receive stick, and the revolving speed for receiving stick is 40rpm, and the movement speed for receiving stick is 5mm/s；Electrostatic spinning after ten minutes, in temperature
Degree is 22 DEG C, pressure is dried in vacuo under conditions of being -0.075MPa, and solvent is made thoroughly to volatilize, and it is poly- to obtain electrostatic spinning nitrate
Close object electrospinning pipe；The wall thickness for measuring electrostatic spinning nitrate polymer electrospinning pipe is 150 μm, diameter 3.8mm, and length is
8.0mm。
Embodiment 11
Biology based on the cell free blood vessel of newborn pigs aorta pectoralis and electrostatic spinning nitrate polymer electrospinning pipe is multiple
Close the preparation of artificial blood vessel:
Select the matched nitrate polymer electrospinning pipe of de- cellular vascular bore that heparin is grafted obtained by internal diameter and embodiment 5
(electrospinning pipe is prepared by embodiment 10)；
Ethylene oxide sterilizing nitrate polymer electrospinning pipe；
In sterile super-clean bench, tweezers clamp de- cellular vascular and nitrate polymer electrospinning pipe respectively, make de- cell blood
Pipe makes the outer surface of cell free blood vessel and the inner surface of electrospinning pipe combine closely across electrospinning pipe, that is, completes the compound of the two；
Composite vascular is placed in the physiological saline containing 30mL 1%PS, 4 DEG C are kept in dark place for use.
Embodiment 12
Biology based on the cell free blood vessel of newborn lamb aorta pectoralis and electrostatic spinning nitrate polymer electrospinning pipe is multiple
Close the preparation of artificial blood vessel:
Select the matched nitrate polymer electrospinning pipe of de- cellular vascular bore that heparin is grafted obtained by internal diameter and embodiment 6
(electrospinning pipe is prepared by embodiment 10)；
Ethylene oxide sterilizing nitrate polymer electrospinning pipe；
In sterile super-clean bench, tweezers clamp de- cellular vascular and nitrate polymer electrospinning pipe respectively, make de- cell blood
Pipe makes the outer surface of cell free blood vessel and the inner surface of electrospinning pipe combine closely across electrospinning pipe, that is, completes the compound of the two；
Composite vascular is placed in the physiological saline containing 30mL 1%PS, 4 DEG C are kept in dark place for use.
Embodiment 13
The preparation method of melt spinning ring-type PCL polymer support:
(1) adjusting indoor humidity 45%, 20 DEG C of temperature；
(2) barrel cleaned up is put into heating mantle, is fixed；
(3) 20g PCL particle is added into barrel, setting heating temperature is 100 DEG C, is kept for heated condition 15 minutes；
(4) install reception stick, by relevant parameter be adjusted to proper states (receive stick revolving speed: 40rpm, hunting frequency:
10Hz, solution flow velocity: 3mL/h) after, spinning can be started, when melt spinning liquid forms two layers of cyclic structure on receiving stick,
Out of service, the wall thickness for measuring melt spinning ring-type PCL polymer support is 200 μm, diameter 4.0mm, length 6.0mm.
Embodiment 14
The preparation method of melt spinning ring-type PLCL polymer support:
(1) adjusting indoor humidity 45%, 20 DEG C of temperature；
(2) barrel cleaned up is put into heating mantle, is arranged 180 DEG C of heating temperature, the poly- L- of 20g is added into barrel
Lactide-caprolactone (PLCL) (Mw=75,000-80,000) is fed herein after being kept for heated condition 15 minutes to nozzle 1cm
Place keeps heating 15 minutes；
(3) suitable high molecular material is added into barrel, setting heating temperature is 150 DEG C, and heated condition 15 is kept to divide
Clock；
(4) install reception stick, by relevant parameter be adjusted to proper states (receive stick revolving speed: 40rpm, hunting frequency:
10Hz, solution flow velocity: 3mL/h) after, spinning can be started, when melt spinning liquid forms two layers of cyclic structure on receiving stick,
Out of service, the wall thickness for measuring melt spinning ring-type PLCL polymer support is 200 μm, diameter 4.0mm, length 6.0mm.
Embodiment 15
The preparation method of melt spinning ring-type PGA polymer support:
(1) adjusting indoor humidity 45%, 20 DEG C of temperature；
(2) barrel cleaned up is put into heating mantle, is arranged 180 DEG C of heating temperature, 20g poly- third is added into barrel
Lactide (PGA) (Mw=30,000) feeds after being kept for heated condition 15 minutes to nozzle 1cm herein, keeps 15 points of heating
Clock；
(3) barrel cleaned up is put into heating mantle, is fixed；
(4) install reception stick, by relevant parameter be adjusted to proper states (receive stick revolving speed: 40rpm, hunting frequency: 8Hz,
Solution flow velocity: 3mL/h) after, spinning can be started, when melt spinning liquid forms two layers of cyclic structure on receiving stick, stopped
Operation, the wall thickness for measuring melt spinning ring-type PGA polymer support is 200 μm, diameter 4.0mm, length 6.0mm.
Embodiment 16
Load the preparation method of the melt spinning ring-type PCL polymer support of heparin:
(1) adjusting indoor humidity 45%, 20 DEG C of temperature；
(2) barrel cleaned up is put into heating mantle, is fixed；
(3) 20g PCL particle and 2mg heparin sodium powder are added into barrel, setting heating temperature is 100 DEG C, keeps adding
Warm status 15 minutes；
(4) install reception stick, by relevant parameter be adjusted to proper states (receive stick revolving speed: 40rpm, hunting frequency:
10Hz, solution flow velocity: 3mL/h) after, spinning can be started, when melt spinning liquid forms two layers of cyclic structure on receiving stick,
Out of service, the wall thickness for measuring the melt spinning ring-type PCL polymer support of load heparin is 200 μm, diameter 4.0mm, long
Degree is 6.0mm.
Embodiment 17
Load the preparation method of the melt spinning ring-type PGA polymer support of rapamycin:
(1) adjusting indoor humidity 45%, 20 DEG C of temperature；
(2) barrel cleaned up is put into heating mantle, is fixed；
(3) 20g PGA particle and 2mg rapamycin powder are added into barrel, setting heating temperature is 100 DEG C, is kept
Heated condition 15 minutes；
(4) install reception stick, by relevant parameter be adjusted to proper states (receive stick revolving speed: 40rpm, hunting frequency:
10Hz, solution flow velocity: 3mL/h) after, spinning can be started, when melt spinning liquid forms two layers of cyclic structure on receiving stick,
Out of service, the wall thickness for measuring the melt spinning ring-type PGA polymer support of load rapamycin is 200 μm, and diameter is
4.0mm, length 6.0mm.
Embodiment 18
Biology based on the cell free blood vessel of newborn pigs aorta pectoralis and melt spinning ring-type PCL polymer support is compound
The preparation of artificial blood vessel:
Select the matched melt spinning ring-type PCL of cell free external caliber that heparin is grafted obtained by internal diameter and embodiment 5
Polymer support (electrospinning pipe is prepared by embodiment 13)；Matched standard is that internal layer takes off cellular vascular and outer layer copolymer branch
Frame is grouped together: firstly, outer layer copolymer bracket will not independently fall off；Secondly, the de- cellular vascular of internal layer will not be because of outer layer
The package of bracket and obvious deformation occurs；
Medicinal alcohol impregnates PCL polymer support 30 minutes with disinfection；
In sterile super-clean bench, takes out PCL polymer support and dry；
Tweezers clamp de- cellular vascular and PCL polymer support respectively, and cell free blood vessel is made to pass through PCL Polymer-supported
Frame makes the outer surface of cell free blood vessel and the inner surface of PCL polymer support combine closely, that is, completes the compound of the two；
Composite vascular is placed in the physiological saline containing 30mL 1%PS, 4 DEG C are kept in dark place for use.
It is as shown in Figure 5 to prepare the biological composite artificial blood vessel completed.
Embodiment 19
Melt spinning ring-type PCL polymer based on the newborn cell free blood vessel of lamb aorta pectoralis and load rapamycin
The preparation of the biological composite artificial blood vessel of bracket:
Select the molten of the matched load rapamycin of cell free external caliber of grafting heparin obtained by internal diameter and embodiment 6
Melt spinning ring-type PCL polymer support (electrospinning pipe is prepared by embodiment 17)；
Medicinal alcohol impregnates PCL polymer support 30 minutes with disinfection；
In sterile super-clean bench, takes out PCL polymer support and dry；
Tweezers clamp de- cellular vascular and PCL polymer support respectively, and de- cellular vascular is made to pass through PCL polymer support,
So that the outer surface of cell free blood vessel and the inner surface of PCL polymer support is combined closely, that is, completes the compound of the two；
Composite vascular is placed in the physiological saline containing 30mL 1%PS, 4 DEG C are kept in dark place for use.
Embodiment 20
Test to rabbit carotid artery transplantation biology composite artificial blood vessel patency:
As follows to 11 gained composite artificial blood vessel of rabbit arteria carotis orthotopic transplantation embodiment:
The biological composite artificial blood vessel that preparation length is 1.5cm passes through end to end anastomosis using rabbit carotid artery transplantation model
It is specific as follows by artificial blood vessel's implantation in rabbit arteria carotis:
(1) new zealand white rabbit, male, weight 2.5kg, fasting 24 hours, leg muscle, which injects 350 lands μ L and sleeps, rather made it
It is of flaccid muscles；
(2) after muscle is fully relaxed, auricular vein successively slowly injects 4mL 30w/v% Ethylurethanm solution, 1mL heparin
Sodium normal saline solution (250U/mL)；
(3) after holonarcosis, animal fixes four limbs in dorsal position；
(4) neck preserved skin, iodophor disinfection, exposure surgical procedure region；
(5) skin of neck is cut off, subcutaneous tissue and fascia are pulled open, pulls open muscle layer, place's carotid artery vascular can be appeared；
(6) it places microvascular and presss from both sides blocking blood flow, the plastic film of one piece of 10mm × 10mm size is placed at rear, to make
Backing；
(7) blood vessel is cut, goes out pipe intracavity blood and clot with 50U/mL heparin sodium physiological saline immediately；
(8) outer membrane is suitably removed；
(9) eight M shapes suture blood vessel (native blood vessels are slightly embedded into material)；
(10) restore blood flow: first removing the blood vessel clip of distal end, then remove the blood vessel clip of proximal part, to restore blood flow；
(11) cotton ball presses blood vessel suitably to stop blooding, and after three minutes, drips a small amount of warm saline on cotton ball to promote
Into vasodilation；
(12) after stopping leakage blood completely, by anatomical layer, layer-by-layer suture；
(13) it is irrigated, and sewed up a wound using the gentamycin solution of 320U/mL, should be avoided leave dead space at this time,
Cause to infect to prevent blood plasma retention.
According to Fig. 6, it can be concluded that, biological composite artificial blood vessel and rabbit native blood vessels coincide well, and there is no blood exudations
The case where.
Postoperative observation in March, using the unobstructed situation of Color doppler ultrasound implantable intravascular, is as a result shown in Fig. 7.
According to Fig. 7, it can be concluded that, doppler ultrasound discovery, after being implanted into March, biological composite artificial blood vessel patency is good,
There is no the bad complication such as oozing of blood and aneurysm.
Embodiment 21
The influence of the regeneration of artificial blood vessel is transplanted to embodiment 20:
It draws materials and analyzes after transplanting:
(1) when rabbit carotid artery transplantation postoperative March, after animal excessively anesthesia, auricular vein injecting heparin carries out whole body blood
Liquid test tube of hepari, neck preserved skin open skin muscular sarcocyte, remove the artificial blood vessel of implantation；
(2) native blood vessels 3-0 suture in artificial blood vessel both ends is ligatured, cuts artificial blood vessel, use 50U/mL liver rapidly
Plain sodium normal saline solution rinses intravascular space, and is soaked in 50U/mL heparin sodium normal saline solution, careful with microscissors
Remove the connective tissue and fat deposit outside blood vessel；
(3) H&E dyeing is carried out after carrying out stereomicroscope observation and frozen section after drawing materials, as a result sees Fig. 8.
Frozen section is carried out with the following method:
1) obtained vascular grafts are immersed in 4% paraformaldehyde solution, 4 DEG C of refrigerators fix 24 hours；
2) vascular grafts for fixing paraformaldehyde are soaked in the sucrose solution equipped with 30%, are sunk down into material molten
When liquid bottom, it can be used for embedded section；
3) it is applied on the freezing stage of freezing-microtome and adds OCT organization embedding glue, it is slightly cooling；
4) liquid for using blotting paper blotting material surface, is quickly placed on cooling OCT glue, and is covered and wrapped with OCT glue
It buries, embedded block is made；
5) freezing-microtome slice thickness is adjusted, is sliced, the thickness of blood vessel frozen section is 7 μm, obtained slice
In -20 DEG C of cryo-conservations.
According to Fig. 8, it can be concluded that, H&E coloration result shows that revascularization is good.
Embodiment 22
Test to sheep carotid artery transplantation biology composite artificial blood vessel patency:
As follows respectively to the biological composite artificial blood vessel of 11 gained of sheep arteria carotis orthotopic transplantation embodiment:
The biological composite artificial blood vessel that preparation length is 4.0cm passes through end to end anastomosis using sheep carotid artery transplantation model
Artificial blood vessel is implanted into sheep arteria carotis, specific as follows:
(1) Small-fat-tail sheep, female, the dormancy of the weight land 15kg, 2mL is peaceful, 0.5mL midazolam is anaesthetized；
(2) it weighs, and records before operating table on；
(3) auricular vein access is established；
(4) the Propofol solution of 10w/v%50mL injects 250mL physiological saline, connects auricular vein；Venous channel retains
One；
(5) ventilator is connected；
(6) neck preserved skin；
(7) skin of neck is cut off, arteria carotis is separated；
(8) alleviate arteriospasm using opium poppy aqueous slkali；
(9) 200UI/kg injecting heparin sodium injection fixes artery clamp after ten minutes, cuts off blood vessel, use 250U/mL immediately
Or higher concentration heparin sodium aqua rinses blood vessel；
(10) 250U/mL heparin solution impregnates vascular grafts and 6-0 suture；
(11) anastomosis of blood vessel, gentamicin repeated flushing wound after skin suture, establish small draining hole；Camera is taken pictures；
(12) stop anesthesia, replace with 5% glucose injection or isotonic glucose；
(13) according to field conditions, respiratory siphon is removed；
Postoperative observation in March, using the unobstructed situation of Color doppler ultrasound implantable intravascular, by stereoscopic aobvious after materials
Micro mirror is to the whole observation of progress inside and outside grafting vessel.
Doppler ultrasound discovery, after being implanted into March, biological composite artificial blood vessel patency is good, there is no oozing of blood and moves
The bad complication such as arteries and veins tumor.
Embodiment 23
The influence of the regeneration of artificial blood vessel is transplanted to embodiment 22:
It draws materials and analyzes after transplanting:
(1) when sheep carotid artery transplantation postoperative March, after animal excessively anesthesia, auricular vein injecting heparin carries out whole body blood
Liquid test tube of hepari, neck preserved skin open skin muscular sarcocyte, remove the artificial blood vessel of implantation；
(2) native blood vessels 3-0 suture in artificial blood vessel both ends is ligatured, cuts artificial blood vessel, use 50U/mL liver rapidly
Plain sodium normal saline solution rinses intravascular space, and is soaked in 50U/mL heparin sodium normal saline solution, careful with microscissors
Remove the connective tissue and fat deposit outside blood vessel；
(3) histologic analysis is carried out after carrying out stereomicroscope observation and frozen section after drawing materials, as a result sees Fig. 9.
Frozen section is carried out with the following method:
1) obtained vascular grafts are immersed in 4% paraformaldehyde solution, 4 DEG C of refrigerators fix 24 hours；
2) vascular grafts for fixing paraformaldehyde are soaked in the sucrose solution equipped with 30%, are sunk down into material molten
When liquid bottom, it can be used for embedded section；
3) it is applied on the freezing stage of freezing-microtome and adds OCT organization embedding glue, it is slightly cooling；
4) liquid for using blotting paper blotting material surface, is quickly placed on cooling OCT glue, and is covered and wrapped with OCT glue
It buries, embedded block is made；
5) freezing-microtome slice thickness is adjusted, is sliced, the thickness of blood vessel frozen section is 5 μm, obtained slice
In -20 DEG C of cryo-conservations.
As can be drawn from Figure 9, H&E coloration result shows that vascular patency is good, and vascular grafts rule is complete.
Embodiment 24
Calcification evaluation is carried out to the biological composite artificial blood vessel that embodiment 23 is implanted into: after 3 months after operation, being taken after putting to death animal
Material, and carry out frozen section and vonKossa dyeing.
It is dyed with the following method:
(1) flowing water rinses 1min；
(2) it is sliced into vonKossa silver nitrate solution, strong illumination 30min；
(3) flowing water rinses 1min；
(4) enter hypo solution processing 2min；
(5) HE dyeing liquor or van Gieson redye nucleus；
(6) conventional to be dehydrated transparent, neutral gum sealing.
Dye whether observation vascular tissue occurs calcification using vonKossa.According to Figure 10, it can be concluded that, embodiment 23 is moved
Calcification situation is not present in vascular wall for blood vessel after plant.
The biological composite artificial blood vessel of 8~9,11~12 and 18~19 gained of embodiment is tested according to the method described above,
As a result similar.
By above embodiments it can be concluded that, it is provided by the invention biology composite artificial blood vessel transplanting after, biological combined artificial
Blood vessel has good patency and regeneration effect.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (12)
1. it is a kind of biology composite artificial blood vessel, which is characterized in that it is described biology composite artificial blood vessel structure setting be internal layer and
Outer layer, the internal layer are cell free blood vessel, and the outer layer is macromolecule polymer material；
The outer surface of the cell free blood vessel and the inner surface of macromolecule polymer material are combined closely；
The cell free blood vessel is modified by anticoagulant；
The macromolecule polymer material load anticoagulant or anti-proliferative drug；
The blood vessel is the blood vessel of birth 1~30d animal.
2. biology composite artificial blood vessel according to claim 1, which is characterized in that the anticoagulant includes heparin, water
One or more of leech element and low-molecular-weight hyaluronic acid；
The anti-proliferative drug includes taxol and/or rapamycin.
3. biology composite artificial blood vessel according to claim 1, which is characterized in that the blood vessel includes aorta pectoralis blood
Pipe, abdominal aorta blood vessel, internal mammary artery blood vessel, right gastroepiploic artery, Artery Vein or arteria epigastrica inferior blood vessel.
4. biology composite artificial blood vessel according to claim 1, which is characterized in that the macromolecule polymer material includes
Electrospinning pipe or polymer support.
5. biology composite artificial blood vessel according to claim 4, which is characterized in that the preparation side of the polymer support
Method, comprising: after mixing raw material with anticoagulant, be prepared using melt spinning method, or by raw material and anti-proliferative drug
After mixing, it is prepared using melt spinning method.
6. biology composite artificial blood vessel according to claim 5, which is characterized in that the quality of the raw material and anticoagulant
Than for (1000~100000): 1, the mass ratio of the raw material and anti-proliferative drug is (1000~100000): 1.
7. biology composite artificial blood vessel according to claim 4, which is characterized in that the preparation method of the electrospinning pipe, packet
It includes: after raw material is mixed with anticoagulant, being prepared using electrospinning process, or raw material is mixed with anti-proliferative drug
Afterwards, it is prepared using electrospinning process.
8. biology composite artificial blood vessel according to claim 7, which is characterized in that the quality of the raw material and anticoagulant
Than for (1000~100000): 1, the mass ratio of the raw material and anti-proliferative drug is (1000~100000): 1.
9. biology composite artificial blood vessel according to claim 4, which is characterized in that the preparation method of the electrospinning pipe, packet
It includes: after raw material is mixed with nitrate, being prepared using electrospinning process.
10. biology composite artificial blood vessel according to claim 9, which is characterized in that the quality of the raw material and nitrate
Than for (2~1000): 1.
11. according to the described in any item biological composite artificial blood vessels of claim 5~10, which is characterized in that the raw material includes
Polycaprolactone, polylactide, polyglycolic acid, polylactide-ethanol copolymer, poly- (lactide-caprolactone) copolymer, poly- pair
Dioxanone or polyhydroxyalkanoate.
12. biological composite artificial blood vessel is in preparing arteries graft materials described in claim 1~11 any one
Using.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110732041A (en) * | 2019-10-12 | 2020-01-31 | 广东省人民医院(广东省医学科学院) | decellularized small-caliber intravascular stent and preparation method thereof |
| CN111700711A (en) * | 2020-05-08 | 2020-09-25 | 南开大学 | Template for preparing low-irritation high-compliance tissue engineering blood vessel and tissue engineering blood vessel |
| CN111961137A (en) * | 2020-08-27 | 2020-11-20 | 南开大学 | Fusion protein for simulating endothelial cell function and application thereof |
| CN112274707A (en) * | 2020-08-11 | 2021-01-29 | 山东朱氏药业集团有限公司 | Medical material and method for preparing anticoagulant coating on surface of medical material |
| WO2023122174A1 (en) * | 2021-12-22 | 2023-06-29 | Axogen Corporation | Drug delivery system and methods of using the same |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2008210523A1 (en) * | 2007-01-30 | 2008-08-07 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Bioerodible wraps and uses therefor |
| CN101496813A (en) * | 2008-02-03 | 2009-08-05 | 吴昊 | Anti-hyperblastosis (vascular restenosis) composition and application method |
| CN105031735A (en) * | 2015-06-24 | 2015-11-11 | 东华大学 | Small-caliber artificial blood vessel with three-layer composite structure, and preparation method of small-caliber artificial blood vessel |
| CN107198793A (en) * | 2016-03-16 | 2017-09-26 | 李温斌 | A kind of intelligent engineering blood vessel |
| CN108478863A (en) * | 2018-04-24 | 2018-09-04 | 重庆大学 | The preparation method and products thereof of compound small-caliber artificial blood vessel |
-
2018
- 2018-11-13 CN CN201811347294.XA patent/CN109498839A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2008210523A1 (en) * | 2007-01-30 | 2008-08-07 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Bioerodible wraps and uses therefor |
| CN101496813A (en) * | 2008-02-03 | 2009-08-05 | 吴昊 | Anti-hyperblastosis (vascular restenosis) composition and application method |
| CN105031735A (en) * | 2015-06-24 | 2015-11-11 | 东华大学 | Small-caliber artificial blood vessel with three-layer composite structure, and preparation method of small-caliber artificial blood vessel |
| CN107198793A (en) * | 2016-03-16 | 2017-09-26 | 李温斌 | A kind of intelligent engineering blood vessel |
| CN108478863A (en) * | 2018-04-24 | 2018-09-04 | 重庆大学 | The preparation method and products thereof of compound small-caliber artificial blood vessel |
Non-Patent Citations (1)
| Title |
|---|
| 殷猛等: "超高压脱细胞组织工程血管支架的实验研究", 《组织工程与重建外科杂志》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110732041A (en) * | 2019-10-12 | 2020-01-31 | 广东省人民医院(广东省医学科学院) | decellularized small-caliber intravascular stent and preparation method thereof |
| CN111700711A (en) * | 2020-05-08 | 2020-09-25 | 南开大学 | Template for preparing low-irritation high-compliance tissue engineering blood vessel and tissue engineering blood vessel |
| CN112274707A (en) * | 2020-08-11 | 2021-01-29 | 山东朱氏药业集团有限公司 | Medical material and method for preparing anticoagulant coating on surface of medical material |
| CN111961137A (en) * | 2020-08-27 | 2020-11-20 | 南开大学 | Fusion protein for simulating endothelial cell function and application thereof |
| CN111961137B (en) * | 2020-08-27 | 2023-09-05 | 南开大学 | Fusion protein with bionic endothelial cell function and application thereof |
| WO2023122174A1 (en) * | 2021-12-22 | 2023-06-29 | Axogen Corporation | Drug delivery system and methods of using the same |
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