CN108938143A - A kind of small-bore bionical blood vessel of three-decker and preparation method thereof - Google Patents
A kind of small-bore bionical blood vessel of three-decker and preparation method thereof Download PDFInfo
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Classifications
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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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
- C08F220/56—Acrylamide; Methacrylamide
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Transplantation (AREA)
- Animal Behavior & Ethology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
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Abstract
The invention discloses small-bore bionical blood vessels of a kind of three-decker and preparation method thereof.Internal layer of the present invention using braiding silk fiber as bionical blood vessel, simulates the structure and performance of human vas collagen, by electrostatic spinning polyurethane fiber as outer layer with the structure and performance of simulated blood vessel elastin laminin.In addition, also further increasing the elasticity of bionical blood vessel as middle layer using polyacrylamide hydrogel, and the burst pressure of bionical blood vessel is improved simultaneously, prevent the infiltration of blood in use process.The present invention can not only simulate the microcosmic three-decker of human vas, and can simulate the special nonlinear mechanical properties of human vas.In addition, the raw material of bionical blood vessel have good cell compatibility and degradable, vascular repair and regeneration suitable for organizational project.Therefore, the small-bore bionical blood vessel of three-decker prepared by the present invention has wide potential practical value.
Description
Technical field
The present invention relates to bionical vascular technique field, more particularly, to a kind of small-bore bionical blood vessel of three-decker and
Preparation method.
Background technique
In recent years, ten hundreds of patients is in the torment by cardiovascular and cerebrovascular disease.The purpose of organizational project be exactly be disease
The tissue or organ of damage provide regenerated resources, provide reliable therapy for various diseases.The target of intravascular tissue engineering is system
It is standby to go out to can plant intracorporal functional blood vessel to replace the blood vessel of lesion, to help the regeneration of new blood vessel.Major diameter
The e-PTFE second of the polyethylene terephthalate (PET) of synthetic vessel such as Dacron company and the production of Gore company
Alkene (ePTFE) is by successfully with such as chest, abdominal aorta on the swiftly flowing aorta of blood.However, making extensively at present
Synthetic vessel is not able to satisfy the demand of small-diameter intravascular.The reason is that, when in the Vascular implantation body of these minor diameters,
It easily forms thrombus and leads to vascellum endometrial hyperplasia.Therefore, functional small-diameter intravascular is prepared urgently at present to meet day
The demand for the cardiovascular disease that benefit increases.
Human vas structure includes three-decker, i.e. inner membrance, middle film and outer membrane.Each layer is by different cell compositions
's.Ideal blood vessel should have the three layer microstructure similar from human vas with promote different cells on blood vessel gradually
Regeneration.In addition, the intravascular tissue engineering bracket of preparation is required to the mechanically performance of bionical human vas, to meet blood normal
The demand of flowing and the demand of transfer operation.Human vas mainly includes two kinds of protein of elastin laminin and collagen, is hit by a bullet
Property albumen have high resiliency, blood pressure can be transmitted and maintain the normal expansion and contraction of blood vessel；Collagenous fibres are a kind of with three
The protein of helical structure, mechanical property with higher.Therefore, the composition of human vas elastase and collagen is imitated
And structure is the important method of bionical blood vessel mechanical performance.
Summary of the invention
The technical problem to be solved by the present invention is to provide for bionical blood vessel structure in the prior art and deficiency functionally
, function similar in a kind of three-decker based on biodegradable material small-bore bionical blood vessel similar with native blood vessels structure and
Preparation method.
The purpose of the present invention is achieved by the following technical programs:
A kind of small-bore bionical blood vessel of three-decker, internal layer are the silk fiber of reticular structure, and middle layer is polyacrylamide
Hydrogel, outer layer are polyurethane nanofiber.
Human vas mainly includes two kinds of protein of elastin laminin and collagen, and elastase has high resiliency, energy
It enough transmitting blood pressure and maintains the normal expansion and contraction of blood vessel, collagenous fibres are a kind of protein with triple-helix structure,
Mechanical property with higher.The intracorporal natural vessel wall of people contains collagenous fibres, elastomer and one layer of elastin laminin group
At film.Fibroin equally has triple-helix structure, and silk fiber shows extremely strong tensile property, can bionical human vas
The structure and performance of interior collagenous fibres.Also, silk fiber is woven as the internal layer of vascular tissue to simulate human collagen in people
Collagenous fibres are consistent in mechanical performance in body blood vessel, fiber and human vas, in the inflated with low pressure stage, weave silk fiber
First to radially extending, intensity is not embodied, when bearing high pressure conditions, then embodies higher-strength.Braiding silk is porous knot
Structure, being conducive to tissue endepidermis precursor can break up in silk hole, grow, and improve silk and tissue
Degrees of fusion.
The outer membrane of human body natural vessel wall is made of connective tissue, and phoirocyte is based on fibroblast, in addition
Containing intensive elastomer and collagenous fibres, there is high resiliency and blood pressure can be transmitted and maintain the normal expansion and receipts of blood vessel
Contracting.Polyurethane has excellent flexibility and biocompatibility and is widely used in bio-medical material.Different from other crystallizations
Type Biodegradable polymer material, polyurethane are generally amorphous state, show good elasticity, being capable of bionical many human bodies
The performance of soft tissue.Polyurethane nanofiber can simulate the structure and performance of elastin laminin as vascular tissue's outer layer, more
Pore structure can simulate human body cell epimatrix micro, and it is raw in the hole of bionical blood vessel to be conducive to human tissue cell
It is long, merge tissue gradually with blood vessel, as polyurethane material is gradually degraded in human body, bionical blood vessel and tissue
Gradually become one.
The middle film of native blood vessels based on elastic membrane and smooth muscle, smooth muscle can produce collagenous fibres, elastomer and
Matrix.The elastomer of middle film has the vascular recoil effect that makes, and collagenous fibres, which rise, maintains tension force effect, has the function of to support.It is poly-
Acrylamide gel is a kind of degradable highly elastic material with good biocompatibility.Polyacrylamide hydrogel is to contain
There is the three-dimensional network polymer of water, with skin-friction coefficient is low, high resiliency, high osmosis, can carry out between external environment
The advantages that mass exchange and good biocompatibility.Good biocompatibility is conducive to cell and grows in hydrogel, raw
Moisture in growth process in hydrogel is gradually substituted by body fluid, can further promote cell proliferation；In addition, the body fluid in hydrogel
Environment is also beneficial to the exchange of oxygen, carbon dioxide and nutriment.The good elasticity of polyacrylamide hydrogel can promote blood
The transmitting of pressure and the reply of bionical blood vessel.It, may under blood pressure effect since silk and polyurethane ectonexine are all porous structure
Accidentality blood loss is caused, can further improve the elasticity of bionical blood vessel as middle layer using polyacrylamide hydrogel, and same
Its burst pressure of Shi Tigao, prevents the infiltration of blood in use process.
The silk fiber, polyurethane and polyacrylamide are nontoxic to the human body, have good biocompatibility and life
Biodegradable performance, and be conducive to the adherency of cell, it is proliferated, promotes revascularization.
The small-bore bionical blood vessel of three-decker according to the present invention, provides preparation method, preparation step are as follows:
S1. the internal layer ring structure of silk fiber woven mesh outside round tube is used；
S2. in the silk external application open column shape die casting polyacrylamide hydrogel precursor liquid of step S1 braiding, crosslinking
Polyacrylamide hydrogel precursor liquid obtains silk fiber/polyacrylamide hydrogel pipe double-layer structure；
S3. outside the silk fiber of the double-layer structure obtained by step S2/polyacrylamide hydrogel pipe, polyurethane nano is prepared
Fibrous outer structure obtains the small-bore bionical blood vessel of three-decker.
Further, the netted silk fiber annular diameter of internal layer described in step S1 is 2~5mm, with a thickness of 100~200 μ
m；Polyacrylamide hydrogel caliber thickness described in step S2 is 400~600 μm；Polyurethane nanofiber diameter described in step S3 is
50~150nm, with a thickness of 50~150 μm.Particularly, the internal diameter and the netted silk fiber thickness of internal layer of tubular blood vessel are prepared,
Polyacrylamide hydrogel thickness and polyurethane nanofiber thickness can be according to required bionical different parts human vas
Basic parameter optimizes.
Further, the preparation step of polyacrylamide hydrogel precursor liquid described in step S2 are as follows: select acrylamide
Monomer, methylene-bisacrylamide accelerate as initiator, tetramethylethylenediamine as crosslinking as crosslinking agent, ammonium persulfate
Agent, phosphate buffer is as solvent.It is made into acrylamide solution with acrylamide and phosphate buffer, in acrylamide solution
Methylene-bisacrylamide and ammonium persulfate is added, tetramethylethylenediamine is added after dissolution, obtains polyacrylamide after being sufficiently stirred
Aqueous amine gel precursor liquid.
Further, the acrylamide solution concentration is 2mol/L, and methylene-bisacrylamide additive amount is acryloyl
The 0.06% of amine quality, ammonium persulfate additive amount are the 0.17% of acrylamide quality, and tetramethylethylenediamine additive amount is propylene
The 0.25% of amide quality.
Further, crosslinking method described in step S2 is ultraviolet-crosslinkable or heat cross-linking.
Further, 30~60min of irradiation time of the ultraviolet-crosslinkable；The heat cross-linking be temperature 40~
60 DEG C, 20~60min of heating time.
Ultraviolet-crosslinkable and heat cross-linking can guarantee that polyacrylamide is crosslinked, and both improve polyacrylamide hydrogel
Mechanical performance in turn ensures the innocuousness to human body of bionical blood vessel.Crosslinking time is too short, the machinery of polyacrylamide hydrogel
Optimal effectiveness is not achieved in performance, and crosslinking time is too long, the flexibility decrease of polyacrylamide hydrogel, and brittleness increases.Polyacrylamide
Aqueous amine gel is excessively crosslinked the mass exchange for influencing blood vessel.It is further preferred that the irradiation time of the ultraviolet-crosslinkable is
40min；The heat cross-linking is that temperature is 50 DEG C, heating time 40min.The polyacrylamide aqueous amine prepared by above method
Gel, elasticity is good, is able to satisfy human vas requirement；The hydrogel network crosslinking of preparation is suitble to, will not when blood vessel bears high pressure
Blood is oozed out, and will not influence mass exchange, and can make human body cell in polyacrylamide hydrogel cross-linked network hole again
Middle growth further blends tissue cell permeable hole and the silk of bionical blood vessel inner layer, makes human tissue cell
It combines together with bionical blood vessel.
Ultraviolet-crosslinkable can preferably control the water content of polyacrylamide hydrogel without heating, and ultraviolet light is handed over
It is high to join the polyacrylamide hydrogel dimensional stability obtained.It is further preferred that the cross-linking method is ultraviolet-crosslinkable.
Further, polyurethane nanofiber layer structure described in step S3 uses electrostatic spinning, step are as follows: with silk
The double-layer structure of fiber/polypropylene amide water-setting sebific duct covers silk fibroin as collection device, by polyurethane solutions direct fabrics
Dimension/polyacrylamide hydrogel pipe double-layer structure surface obtains the small-bore bionical blood vessel of three-decker.
Electrostatic spinning can continuously prepare nano-scale fiber, and the nanofibrous structures of preparation can be outside bionical human body cell
The microstructure of matrix is conducive to the adherency and growth of human body cell.Outside the polyurethane nanofiber prepared by electrostatic spinning
Layer structure can simulate the structure and performance of human vas elastase.
Further, polyurethane solutions concentration is 6~12wt.%；Solvent be dimethylformamide or chloroform, or both
Mixed liquor；Electrostatic spinning voltage is 16~20kV.
The diameter of the solution concentration of electrostatic spinning, voltage influence polyurethane fiber, to keep three-decker of the present invention small
The bionical blood vessel of bore close to native blood vessels performance, it is further preferred that polyurethane solutions concentration be 10wt.%, electrostatic spinning
Voltage is 18kV.
The bore of the small-bore bionical blood vessel of three-decker, each thickness degree and mechanical performance are controllable, are suitable for difference
Artery and vein blood vessel.
Compared with prior art, beneficial effect is:
The internal layer using braiding silk fiber as bionical blood vessel of the invention, weaves silk fiber as blood vessel
For the internal layer of tissue to simulate the structure and performance of human collagen, fiber is consistent with collagenous fibres in human vas, swollen in low pressure
The swollen stage weaves silk fiber first to radially extending, does not embody intensity, when bearing high pressure conditions, then embody more high-strength
Degree.By electrostatic spinning polyurethane fiber as outer layer, polyurethane nanofiber can simulate elasticity as vascular tissue's outer layer
The structure and performance of albumen, porous structure can simulate human body cell epimatrix micro, be conducive to human tissue cell
It is grown in the hole of bionical blood vessel, merges tissue gradually with blood vessel, as polyurethane material gradually drops in human body
Solution, bionical blood vessel and tissue gradually become one.In addition, also being gathered using polyacrylamide aqueous amine elastic gel as middle layer
Acrylamide gel is a kind of degradable highly elastic material with good biocompatibility, and good biocompatibility is advantageous
It is grown in hydrogel in cell, the moisture in growth course in hydrogel is gradually substituted by body fluid, can further promote cell
Breeding；In addition, the fluid environment in hydrogel is also beneficial to the exchange of oxygen, carbon dioxide and nutriment.Silk and poly- ammonia
Ester ectonexine is all porous structure, may cause accidentality blood loss under blood pressure effect, using polyacrylamide hydrogel conduct
Middle layer can further improve the elasticity of bionical blood vessel, and improve the burst pressure of bionical blood vessel simultaneously, prevent blood in use process
The infiltration of liquid.
The present invention weaves silk fiber simulated blood vessel internal layer elastic membrane by the microcosmic three-decker of simulation human vas,
There is polyacrylamide hydrogel cross-linked network to simulate close smooth muscle middle layer, and blood penetration is prevented to hand over without influencing substance
It changes.For polyurethane nanofiber as vascular tissue's outer layer, porous structure can simulate human body cell epimatrix micro, have
It is grown in the hole of bionical blood vessel conducive to human tissue cell.The present invention and the special mechanicalness of human vas can be simulated
Can, silk fiber simulates the tensile property of human vas collagen, and polyurethane simulates elastic proteins retract performance, polyacrylamide aqueous amine
Gel improves the elasticity of bionical blood vessel, and improves the burst pressure of bionical blood vessel simultaneously.
In addition, the material that the present invention selects has good cell compatibility and biodegradable, be conducive to repairing for blood vessel
Multiple and regeneration.Three-dimensional porous structure is presented in the small-bore bionical media of three-decker prepared by the present invention, this porous advantageous
It is grown in the infiltration of vascular endothelial cell.The small-bore bionical blood vessel of the three-decker of preparation be conducive to endepidermis cell adherency and
Growth, using endothelial cell it is Prevascularized after be not easy to form thrombus.The small-bore bionical blood vessel outer surface of the three-decker of preparation is equal
Even to cover polyurethane nanofiber, which is conducive to the growth of blood vessel fibrocyte.Therefore, prepared by the present invention a kind of three
The layer small-bore bionical blood vessel of structure has wide potential practical value.
Detailed description of the invention
Fig. 1 is a kind of preparation process schematic diagram of the small-bore bionical blood vessel of three-decker of the present invention；
Fig. 2 is the scanning electron microscope (SEM) photograph of section after a kind of small-bore bionical blood vessel freeze-drying of three-decker of the present invention；
Fig. 3 is the scanning electron microscope (SEM) photograph of section after a kind of small-bore bionical blood vessel freeze-drying of three-decker of the present invention；
Fig. 4 is the scanning electron microscope (SEM) photograph of inner surface after a kind of small-bore bionical blood vessel freeze-drying of three-decker of the present invention；
Fig. 5 is the scanning electron microscope (SEM) photograph of outer surface after a kind of small-bore bionical blood vessel freeze-drying of three-decker of the present invention；
Fig. 6 is the circumferential cyclic tension performance test figure of the polyurethane tubulose of 1 electrostatic spinning of comparative example preparation；
Fig. 7 is the circumferential cyclic tension performance test figure that comparative example 2 weaves silk and polyacrylamide hydrogel bilayer；
Fig. 8 is a kind of circumferential cyclic tension performance test figure of the small-bore bionical blood vessel of three-decker of the present invention.
Wherein, shown in Fig. 1: 1 round tube, 2 silk fibers, 3 polyacrylamide hydrogel, 4 open column shape molds, 5 poly- ammonia
Ester nanofiber.
Specific embodiment
It is explained further and illustrates below with reference to embodiment, but specific embodiment does not have any type of limit to the present invention
It is fixed.Unless otherwise specified, method and apparatus used in embodiment is ability conventional method and equipment, raw materials used is routine
Marketable material.
The invention discloses a kind of small-bore bionical blood vessels of three-decker, and the present invention is using braiding silk fiber as bionical
The internal layer of blood vessel simulates the structure and performance of human collagen.By electrostatic spinning polyurethane fiber as outer layer to simulate elasticity
The structure and performance of albumen.The elasticity of bionical blood vessel is further increased as middle layer using polyacrylamide hydrogel, and
The burst pressure for improving bionical blood vessel simultaneously, prevents the infiltration of blood in use process.
According to the small-bore bionical blood vessel of three-decker, a kind of preparation method is provided, step includes:
S1. the endothecium structure of silk fiber woven mesh outside round tube is used；
S2. in the silk external application open column shape die casting polyacrylamide hydrogel precursor liquid of step S1 braiding, crosslinking
Polyacrylamide hydrogel precursor liquid obtains silk fiber/polyacrylamide hydrogel pipe double-layer structure；
S3. outside the silk fiber of the double-layer structure obtained by step S2/polyacrylamide hydrogel pipe, polyurethane nano is prepared
Fibrous outer structure obtains the small-bore bionical blood vessel of three-decker.
Further, the netted silk fiber annular diameter of internal layer described in step S1 is 2~5mm, with a thickness of 100~200 μ
m；Polyacrylamide hydrogel caliber thickness described in step S2 is 400~600 μm；Polyurethane nanofiber diameter described in step S3 is
50~150nm, with a thickness of 50~150 μm.Particularly, the internal diameter and the netted silk fiber thickness of internal layer of tubular blood vessel are prepared,
Polyacrylamide hydrogel thickness and polyurethane nanofiber thickness can be according to required bionical different parts human vas
Basic parameter optimizes.
Further, the preparation step of polyacrylamide hydrogel precursor liquid described in step S2 is to select acrylamide list
Body, methylene-bisacrylamide as crosslinking agent, ammonium persulfate as initiator, tetramethylethylenediamine as cross-linking accelerator,
Phosphate buffer is as solvent.It is made into acrylamide solution with acrylamide and phosphate buffer, methylene is added in the solution
Tetramethylethylenediamine is added after dissolution in bisacrylamide and ammonium persulfate, before obtaining polyacrylamide hydrogel after being sufficiently stirred
Drive liquid.
Further, the acrylamide solution concentration is 2mol/L, and methylene-bisacrylamide additive amount is acryloyl
The 0.06% of amine quality, ammonium persulfate additive amount are the 0.17% of acrylamide quality, and tetramethylethylenediamine additive amount is propylene
The 0.25% of amide quality.
Further, crosslinking method described in step S2 is ultraviolet-crosslinkable or heat cross-linking.
Further, the irradiation time of the ultraviolet-crosslinkable is 30~60min；The heat cross-linking is that temperature is 40
~60 DEG C, time heating time is 20~60min.
It is further preferred that the irradiation time of the ultraviolet-crosslinkable is 40min；The heat cross-linking is that temperature is 50
DEG C, heating time is 20~60min.
It is further preferred that the cross-linking method is ultraviolet-crosslinkable.
Further, polyurethane nanofiber layer structure described in step S3 uses electrostatic spinning,
Further, polyurethane solutions concentration is 6~12wt.%；Solvent be dimethylformamide or chloroform, or both
Mixed liquor；Electrostatic spinning voltage is 16~20kV.
It is further preferred that polyurethane solutions concentration is 10wt.%；Electrostatic spinning voltage is 18kV.
Embodiment 1
The present embodiment provides a kind of preparation methods of the small-bore bionical blood vessel of three-decker.
S1. the netted endothecium structure of 100 μ m-thicks is woven outside 2mm round tube with 50 μm of silk fibers of diameter；
S2. it is made into the solution of 2mol/L with acrylamide and phosphate buffer, acrylamide quality is added in the solution
Acrylamide matter is added in 0.06% methylene-bisacrylamide and 0.17% ammonium persulfate of acrylamide quality after dissolution
0.25% tetramethylethylenediamine of amount obtains polyacrylamide hydrogel precursor liquid after being sufficiently stirred.
S3. in the polypropylene of the step S2 preparation of 400 μ m-thick of silk external application open column shape die casting of step S1 braiding
Amide hydrogel precursor liquid irradiates 40min with ultraviolet light, obtains silk fiber/polyacrylamide hydrogel pipe double-layer structure；
S4. polyurethane is dissolved in dimethylformamide and is prepared into the polyurethane solutions that concentration is 10wt.%；
S5. using the resulting silk fiber of step S3/polyacrylamide hydrogel pipe double-layer structure as collection device, use is quiet
The polyurethane solutions of step S4 are prepared the polyurethane nanofiber layer structure of 150 μ m-thicks by Electrospun at 18kV.
Embodiment 2
The present embodiment provides a kind of preparation methods of the small-bore bionical blood vessel of three-decker.
S1. the netted endothecium structure of 100 μ m-thicks is woven outside 2mm round tube with 50 μm of silk fibers of diameter；
S2. it is made into the solution of 2mol/L with acrylamide and phosphate buffer, acrylamide quality is added in the solution
Acrylamide matter is added in 0.06% methylene-bisacrylamide and 0.17% ammonium persulfate of acrylamide quality after dissolution
0.25% tetramethylethylenediamine of amount obtains polyacrylamide hydrogel precursor liquid after being sufficiently stirred.
S3. in the polypropylene of the step S2 preparation of 600 μ m-thick of silk external application open column shape die casting of step S1 braiding
Amide hydrogel precursor liquid obtains silk fiber/polyacrylamide hydrogel pipe double-layer structure with 50 DEG C of heating 40min；
S4. polyurethane is dissolved in dimethylformamide and is prepared into the polyurethane solutions that concentration is 10wt.%；
S5. using the resulting silk fiber of step S3/polyacrylamide hydrogel pipe double-layer structure as collection device, use is quiet
The polyurethane solutions of step S4 are prepared the polyurethane nanofiber layer structure of 50 μ m-thicks by Electrospun at 18kV.
Embodiment 3
S1. the netted endothecium structure of 200 μ m-thicks is woven outside 5mm round tube with 100 μm of silk fibers of diameter；
S2. it is made into the solution of 2mol/L with acrylamide and phosphate buffer, acrylamide quality is added in the solution
Acrylamide matter is added in 0.06% methylene-bisacrylamide and 0.17% ammonium persulfate of acrylamide quality after dissolution
0.25% tetramethylethylenediamine of amount obtains polyacrylamide hydrogel precursor liquid after being sufficiently stirred.
S3. in the polypropylene of the step S2 preparation of 600 μ m-thick of silk external application open column shape die casting of step S1 braiding
Amide hydrogel precursor liquid irradiates 60min with ultraviolet light, obtains silk fiber/polyacrylamide hydrogel pipe double-layer structure；
S4. polyurethane is dissolved in dimethylformamide and is prepared into the polyurethane solutions that concentration is 12wt.%；
S5. using the resulting silk fiber of step S3/polyacrylamide hydrogel pipe double-layer structure as collection device, use is quiet
The polyurethane solutions of step S4 are prepared the polyurethane nanofiber layer structure of 150 μ m-thicks by Electrospun at 20kV.
Embodiment 4
S1. the netted endothecium structure of 100 μ m-thicks is woven outside 5mm round tube with 100 μm of silk fibers of diameter；
S2. it is made into the solution of 2mol/L with acrylamide and phosphate buffer, acrylamide quality is added in the solution
Acrylamide matter is added in 0.06% methylene-bisacrylamide and 0.17% ammonium persulfate of acrylamide quality after dissolution
0.25% tetramethylethylenediamine of amount obtains polyacrylamide hydrogel precursor liquid after being sufficiently stirred.
S3. in the poly- of the step S2 preparation of 600 μ m-thick of silk external application 3mm open column shape die casting of step S1 braiding
Acrylamide gel precursor liquid, 40 DEG C of heating 60min obtain silk fiber/polyacrylamide hydrogel pipe double-layer structure；
S4. polyurethane is dissolved in dimethylformamide and is prepared into the polyurethane solutions that concentration is 12wt.%；
S5. using the resulting silk fiber of step S3/polyacrylamide hydrogel pipe double-layer structure as collection device, use is quiet
The polyurethane solutions of step S4 are prepared the polyurethane nanofiber layer structure of 150 μ m-thicks by Electrospun at 16kV.
Embodiment 5
S1. the netted endothecium structure of 200 μ m-thicks is woven outside 5mm round tube with 100 μm of silk fibers of diameter；
S2. it is made into the solution of 2mol/L with acrylamide and phosphate buffer, acrylamide quality is added in the solution
Acrylamide matter is added in 0.06% methylene-bisacrylamide and 0.17% ammonium persulfate of acrylamide quality after dissolution
0.25% tetramethylethylenediamine of amount obtains polyacrylamide hydrogel precursor liquid after being sufficiently stirred.
S3. in the poly- of the step S2 preparation of 600 μ m-thick of silk external application 3mm open column shape die casting of step S1 braiding
Acrylamide gel precursor liquid, 60 DEG C of heating 20min obtain silk fiber/polyacrylamide hydrogel pipe double-layer structure；
S4. polyurethane is dissolved in dimethylformamide and is prepared into the polyurethane solutions that concentration is 6wt.%；
S5. using the resulting silk fiber of step S3/polyacrylamide hydrogel pipe double-layer structure as collection device, use is quiet
The polyurethane solutions of step S4 are prepared the polyurethane nanofiber layer structure of 150 μ m-thicks by Electrospun at 18kV.
Embodiment 6
S1. the netted endothecium structure of 100 μ m-thicks is woven outside 2mm round tube with 50 μm of silk fibers of diameter；
S2. it is made into the solution of 2mol/L with acrylamide and phosphate buffer, acrylamide quality is added in the solution
Acrylamide matter is added in 0.06% methylene-bisacrylamide and 0.17% ammonium persulfate of acrylamide quality after dissolution
0.25% tetramethylethylenediamine of amount obtains polyacrylamide hydrogel precursor liquid after being sufficiently stirred.
S3. in the polypropylene of the step S2 preparation of 400 μ m-thick of silk external application open column shape die casting of step S1 braiding
Amide hydrogel precursor liquid irradiates 30min with ultraviolet light, obtains silk fiber/polyacrylamide hydrogel pipe double-layer structure；
S4. polyurethane is dissolved in dimethylformamide and is prepared into the polyurethane solutions that concentration is 10wt.%；
S5. using the resulting silk fiber of step S3/polyacrylamide hydrogel pipe double-layer structure as collection device, use is quiet
The polyurethane solutions of step S4 are prepared the polyurethane nanofiber layer structure of 150 μ m-thicks by Electrospun at 18kV.
Comparative example 1
S1. dimethylformamide/chloroformic solution that polyurethane is dissolved in mass ratio 6:4 is prepared into concentration is the poly- of 8wt.%
Urethane solution；
S2. with electrostatic spinning at 15kV by the polyurethane solutions of step S1 prepare internal diameter be 2mm, it is 150 μm thick
The bionical blood vessel of polyurethane nanofiber tubulose.
Comparative example 2
S1. the netted endothecium structure of 100 μ m-thicks is woven outside 2mm round tube with 50 μm of silk fibers of diameter；
S2. it is made into the solution of 2mol/L with acrylamide and phosphate buffer, acrylamide quality is added in the solution
Acrylamide matter is added in 0.06% methylene-bisacrylamide and 0.17% ammonium persulfate of acrylamide quality after dissolution
0.25% tetramethylethylenediamine of amount obtains polyacrylamide hydrogel precursor liquid after being sufficiently stirred.
S3. in the polyacrylamide hydrogel of the silk external application open column shape die casting step S2 preparation of step S1 braiding
Precursor liquid irradiates 40min with ultraviolet light, obtain internal diameter be 2mm, thick 600 μm there is silk fiber/polyacrylamide hydrogel
The bionical blood vessel of the tubulose of double-layer structure.
Comparative example 3
S1. with polyurethane nanofiber, electrostatic spinning goes out the netted endothecium structure of 100 μ m-thicks outside 2mm round tube；
S2. the polyurethane for preparing 600 μm in the structure external crosslinking of step S1 with acrylamide monomer, obtains double-layer hollow
Pipe；
S3. in effective thick 150 μm of the outer layer of silk braiding of the double-layer hollow of step S2, the artificial blood of three-decker is obtained
Pipe.
Embodiment 7
The single layer hollow pipe of the small-bore bionical blood vessel of three-decker and the preparation of comparative examples 1 that prepared to the embodiment of the present invention 1,
Double-layer hollow pipe prepared by comparative example 2 carries out circumferential cyclic tension performance test, and sample is stretched to 30% strain simultaneously in test
It replys, is repeated 10 times.As a result, it has been found that the bionical blood vessel of three-decker has extraordinary cyclic tension performance, in ten circulations
Almost without energy loss, this illustrates that the bionical blood vessel of the three-decker can adapt to the blood pressure work of cyclical-transformation in human vas
With.And energy loss is more obvious in the cycles samples extension test of other single or double layers.
Embodiment 8
The single layer hollow pipe of the small-bore bionical blood vessel of three-decker and the preparation of comparative examples 1 that prepared to the embodiment of the present invention 1,
Double-layer hollow pipe prepared by comparative example 2 carries out surgical thread suture test.As a result, it has been found that the suture strength of polyacrylamide hydrogel
It is extremely low, and the suture strength of the bionical blood vessel of three-decker reaches 11.6N, is higher than thorax artery and vein.
Embodiment 9
The single layer hollow pipe of the small-bore bionical blood vessel of three-decker and the preparation of comparative examples 1 that prepared to the embodiment of the present invention 1,
Double-layer hollow pipe prepared by comparative example 2 carries out the test of phosphate buffer burst pressure.As a result, it has been found that the ectonexine explosion of porous structure
Press lower, and burst pressure is obviously improved after adding polyacrylamide hydrogel layer.The 3600mm mercury column of the bionical blood vessel of three-decker,
Higher than human vein, slightly below thorax artery, but human normal blood pressure range has been much higher than it.
Burst pressure test and surgical thread suture test the result shows that the bionical blood vessel of three-decker has the human vas that matches in excellence or beauty
Performance, be fully able to meet bionical blood vessel in the course of surgery, and in blood of human body environment long-time service requirement.
The small-bore bionical blood vessel of three-decker of the method preparation according to the present invention, is seen by the stereoscan photograph of Fig. 2~5
Out, the small-bore bionical blood vessel of the three-decker is divided into apparent three-decker, comprising: internal layer close to human vas structure
Braiding silk fiber, middle layer polyacrylamide hydrogel it is dry after the porous structure, the outer polyurethane nanofiber that are formed.System
Three-dimensional porous structure, this porous adherency and growth for being conducive to intravascular epidermal cell is presented in standby bionical media.System
Standby bionical vascular inner surface is smooth, is not easy to form thrombus.The regenerative process of blood vessel is three-decker of the present invention from inside to outside
Small-bore bionical blood vessel inner layer silk fiber is conducive to the absorption of endepidermis precursor, differentiation, middle layer polyacrylamide hydrogel
Glue is conducive to the infiltration of endepidermis cell, is differentiated to form blood vessel network, and outer bionical blood vessel outer surface uniform fold polyurethane is received
Rice fiber, the structure are conducive to the growth of blood vessel fibrocyte.Therefore the present invention is conducive to human vas regenerative system.
The small-bore bionical blood vessel of three-decker prepared by according to embodiments of the present invention 1 and comparative example 1 and comparative example 2 are made
Standby small-bore bionical blood vessel is shown, the bionical blood vessel of three-decker of the invention stretches in circumferential cyclic tension by Fig. 6~8
It is essentially coincided with return curve, i.e., energy loss is minimum, and stable machinery can be kept in blood pressure cycle variation by demonstrating it
Performance；Compared with the small-bore bionical blood vessel of the three-decker as prepared by embodiment 1 three layers of blood vessel structure described in the comparative example 3, this
Flexible rebound, the blood pressure transmitting of the bionical blood vessel of the three-decker of invention and native blood vessels keep higher consistency.In addition, this hair
The bionical blood vessel of bright three-decker stress variation under low strain dynamic is small, and the big characteristic of stress variation under Large strain, the characteristic
The bionical well mechanical performance of human vas.
Tensile property test is carried out to the bionical blood vessel of the single layer of material therefor of the present invention preparation, bilayer, three-decker, and
It is compared with native blood vessels, as shown in table 1:
Table 1
It is obtained by table 1, compared to other single or double layer blood vessels, the circumferential tension intensity of the bionical blood vessel of three-decker is broken
Split the requirement of elongation and nonlinear strain closer to human vas, it is thus possible to the knot of good bionical human vas
Structure and performance.
Obviously, the above embodiment of the present invention is only intended to clearly illustrate examples made by the present invention, and is not to this
The restriction of the embodiment of invention.It for those of ordinary skill in the art, on the basis of the above description can be with
It makes other variations or changes in different ways.There is no necessity and possibility to exhaust all the enbodiments.It is all in this hair
Made any modifications, equivalent replacements, and improvements etc., should be included in the claims in the present invention within bright spirit and principle
Within protection scope.
Claims (10)
1. a kind of small-bore bionical blood vessel of three-decker, which is characterized in that internal layer is the silk fiber of reticular structure, and middle layer is poly-
Acrylamide gel, outer layer are polyurethane nanofiber.
2. the small-bore bionical blood vessel of three-decker according to claim 1, which is characterized in that preparation step includes:
S1. the internal layer ring structure of silk fiber woven mesh outside round tube is used；
S2. in the silk external application open column shape die casting polyacrylamide hydrogel precursor liquid of step S1 braiding, crosslinked polypropylene
Acrylamide hydrogel precursor liquid obtains silk fiber/polyacrylamide hydrogel pipe double-layer structure；
S3. outside the silk fiber of the double-layer structure obtained by step S2/polyacrylamide hydrogel pipe, polyurethane nanofiber is prepared
Layer structure obtains the small-bore bionical blood vessel of three-decker.
3. the small-bore bionical blood vessel of three-decker according to claim 2, which is characterized in that netted inner layer ring described in step S1
Shape inside diameter is 2 ~ 5mm, with a thickness of 100 ~ 200 μm；Polyacrylamide hydrogel caliber thickness described in step S2 is 400 ~ 600 μ
m；Polyurethane nanofiber diameter is 50 ~ 100nm in step S3, with a thickness of 50 ~ 150 μm.
4. the small-bore bionical blood vessel of three-decker according to claim 2, which is characterized in that polyacrylamide described in step S2
The preparation step of aqueous amine gel precursor liquid are as follows: acrylamide solution is configured to acrylamide and phosphate buffer, in acryloyl
Methylene-bisacrylamide and ammonium persulfate are added in amine aqueous solution, tetramethylethylenediamine is added after dissolution, is obtained after being sufficiently stirred
Polyacrylamide hydrogel precursor liquid.
5. the preparation method of polyacrylamide hydrogel precursor liquid according to claim 5, which is characterized in that the propylene
Amide solution concentration is 2mol/L, and methylene-bisacrylamide additive amount is the 0.06% of acrylamide quality, ammonium persulfate addition
Amount is the 0.17% of acrylamide quality, and tetramethylethylenediamine additive amount is the 0.25% of acrylamide quality.
6. the small-bore bionical blood vessel of three-decker according to claim 2, which is characterized in that crosslinking method described in step S2
For ultraviolet-crosslinkable or heat cross-linking.
7. the small-bore bionical blood vessel of three-decker according to claim 7, which is characterized in that the photograph of the ultraviolet-crosslinkable
Penetrate 30 ~ 60min of time；40 ~ 60 DEG C of the heating temperature, heat cross-linking time are 20 ~ 60min.
8. the small-bore bionical blood vessel of three-decker according to claim 2, which is characterized in that polyurethane described in step S3 is received
Rice fibrous outer structure uses electrostatic spinning, step are as follows: with silk fiber/polyacrylamide hydrogel pipe double-layer structure and horse
Up to rotating collecting device is connected to, polyurethane solutions direct fabrics are covered into silk fiber/polyacrylamide hydrogel pipe
Double-layer structure surface obtains the small-bore bionical blood vessel of three-decker.
9. the small-bore bionical blood vessel of three-decker according to claim 8, which is characterized in that polyurethane solutions concentration be 6 ~
12wt.%；Solvent be dimethylformamide or chloroform, or both mixed liquor；Electrostatic spinning voltage is 16 ~ 20kV.
10. the small-bore bionical blood vessel of the three-decker of the preparation according to claim 1 ~ 9, which is characterized in that the three-layered node
The small-bore bionical blood vessel of structure is suitable for various arteries and vein blood vessel.
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| CN109675115A (en) * | 2019-01-10 | 2019-04-26 | 上海大学 | A kind of fiber-reinforced composite hydrogel artificial blood vessel structure and its forming method |
| CN112316219A (en) * | 2020-09-29 | 2021-02-05 | 浙江大学 | Anti-adhesion hydrogel-silk scaffold composite membrane and preparation and application thereof |
| CN112316219B (en) * | 2020-09-29 | 2022-05-10 | 浙江大学 | Anti-adhesion hydrogel-silk scaffold composite membrane and preparation and application thereof |
| CN112842618A (en) * | 2021-01-06 | 2021-05-28 | 北京理工大学 | Degradable composite artificial blood vessel and preparation method and application thereof |
| CN113171499A (en) * | 2021-03-17 | 2021-07-27 | 广东粤港澳大湾区国家纳米科技创新研究院 | Anticoagulation material, double-layer hydrogel pipeline, and preparation method and application thereof |
| CN113274165A (en) * | 2021-05-06 | 2021-08-20 | 东华大学 | Integrally-formed micro-nanofiber/hydrogel double-network type artificial blood vessel and preparation method thereof |
| CN113274165B (en) * | 2021-05-06 | 2022-04-15 | 东华大学 | Integrally-formed micro-nanofiber/hydrogel double-network type artificial blood vessel and preparation method thereof |
| CN113576710A (en) * | 2021-08-19 | 2021-11-02 | 遆好伟 | Artificial bionic blood vessel and manufacturing method thereof |
| CN115192768A (en) * | 2022-06-14 | 2022-10-18 | 山东大学齐鲁医院 | Composite material artificial blood vessel and manufacturing process thereof |
| CN115554479A (en) * | 2022-11-02 | 2023-01-03 | 上海市第六人民医院 | Three-layer composite structure tendon sheath anti-adhesion membrane for postoperative bionic tendon |
| CN115554479B (en) * | 2022-11-02 | 2024-05-28 | 上海市第六人民医院 | Three-layer composite structure tendon postoperative bionic tendon sheath anti-adhesion membrane |
| CN115804871A (en) * | 2023-01-30 | 2023-03-17 | 山东百多安医疗器械股份有限公司 | Functionalized degradable drug-loaded artificial bionic blood vessel and preparation method thereof |
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Application publication date: 20181207 |