CN112156229B - Novel small-diameter degradable artificial blood vessel and construction method thereof - Google Patents

Novel small-diameter degradable artificial blood vessel and construction method thereof Download PDF

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CN112156229B
CN112156229B CN202011039552.5A CN202011039552A CN112156229B CN 112156229 B CN112156229 B CN 112156229B CN 202011039552 A CN202011039552 A CN 202011039552A CN 112156229 B CN112156229 B CN 112156229B
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blood vessel
artificial blood
fiber layer
diameter
solution
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CN112156229A (en
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王宪伟
谢超
王祖勇
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06Blood vessels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24Collagen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01DMECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00Formation of filaments, threads, or the like
    • D01D5/0007Electro-spinning
    • D01D5/0015Electro-spinning characterised by the initial state of the material
    • D01D5/003Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01DMECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00Formation of filaments, threads, or the like
    • D01D5/0007Electro-spinning
    • D01D5/0061Electro-spinning characterised by the electro-spinning apparatus
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01DMECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00Formation of filaments, threads, or the like
    • D01D5/0007Electro-spinning
    • D01D5/0061Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0092Electro-spinning characterised by the electro-spinning apparatus characterised by the electrical field, e.g. combined with a magnetic fields, using biased or alternating fields
    • DTEXTILES; PAPER
    • D04BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04HMAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/70Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
    • D04H1/72Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
    • D04H1/728Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning
    • DTEXTILES; PAPER
    • D04BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04HMAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/70Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
    • D04H1/76Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres otherwise than in a plane, e.g. in a tubular way

Abstract

The invention discloses a novel small-diameter degradable artificial blood vessel and a construction method thereof, the novel small-diameter degradable artificial blood vessel comprises an inner surface fiber layer, an outer surface fiber layer and a spiral support structure wound on fibers of the inner surface fiber layer, the preparation method of the artificial blood vessel is simple and convenient, the small-diameter artificial blood vessel formed by double-layer oriented electrostatic spinning fibers can be prepared in one step, single-layer endothelial cells which are oriented and stably adhered can be quickly formed in the artificial blood vessel under the action of geometric pattern signals, smooth muscle cells are induced to grow in a circumferential oriented arrangement, and meanwhile, the novel small-diameter degradable artificial blood vessel has better mechanical properties and helps to regenerate tissues and functions in the artificial blood vessel stably.

Description

Novel small-diameter degradable artificial blood vessel and construction method thereof
Technical Field
The invention relates to a novel small-diameter degradable artificial blood vessel and a construction method thereof, in particular to an improved electrostatic spinning technology and the novel small-diameter degradable artificial blood vessel with a bionic micro-pattern signal, which is constructed by adopting the improved electrostatic spinning technology, and belongs to the technical field of biomedical materials.
Background
Currently, cardiovascular disease (CVD) is the first leading cause of death in the global population, and as reported by the world health organization, about 1790 million people die globally every year from Cardiovascular disease [1]. Vascular occlusion due to atherosclerosis, inflammation, autoimmunity, etc. is a common clinical problem [2]. A commonly used method for coronary artery and peripheral small diameter artery occlusion is to replace or bypass the diseased segment of the blood vessel, where autologous blood vessel transplantation is the "gold standard" for clinical treatment of this disease, but has limited application due to limited sources, the need for additional invasive surgery, patient health, etc. [3]. The artificial vascular graft made of synthetic polymer materials has low preparation cost and convenient use, is widely applied to clinic at present, but the complications such as thrombosis, stenosis, chronic inflammatory reaction and the like are easily caused by the poor mechanical property and the nondegradable property of the synthetic materials, so that the application of the artificial vascular graft in small-diameter artificial blood vessels (< 6 mm) is limited [4]. Therefore, the development of small-diameter artificial blood vessels is urgent.
The human vascular wall consists of three layers of anatomical structures: outer membrane, middle membrane and inner membrane. The intima is composed primarily of vascular endothelial cells, which play an important role in regulating vascular tone, tissue homeostasis, and the transport of nutrients across the vessel wall. In addition, the intima forms a barrier between the circulating blood and the vessel wall with an anticoagulant function. Without a stable adherent monolayer of endothelial cells, the artificial vessel is susceptible to restenosis or blockage by intimal hyperplasia and thrombosis. Thus, an ideal vascular prosthesis should rapidly form a continuous monolayer of endothelial cells under physiological conditions after implantation in humans [5]. Under normal physiological conditions of the human body, the morphology of vascular endothelial cells and the arrangement of cytoskeleton are consistent with the direction of blood flow in blood vessels, and directly influence the function and the adhesive capacity under the shear stress of blood flow [6].
The electrostatic spinning technology is a method for preparing nano-fiber by utilizing high-voltage electric field force. Because the electrostatic spinning equipment is simple and the cost is low, the prepared fiber membrane has higher specific surface area, excellent pore connectivity and controllable fiber diameter. Due to the unstable characteristic of the electrostatic spinning process, the collected fibers are often in a random accumulation form, and the electrostatic spinning nanofibers in such a form have great limitation in the application of artificial blood vessels. If the distribution of the electric spinning fiber is disordered, the fiber tension degree between the nodes is different, and the stress of single fiber in the whole fiber material is uneven, so that the whole fiber cannot exert due mechanical properties.
[1]E.J.Benjamin,P.Muntner,A.Alonso,M.S.Bittencourt,C.W.Callaway,A.P.Carson,A.M.Chamberlain,A.R.Chang,S.Cheng,S.R.Das,F.N.Delling,L.Djousse,M.S.V.Elkind,J.F.Ferguson,M.Fornage,L.C.Jordan,S.S.Khan,B.M.Kissela,K.L.Knutson,T.W.Kwan,D.T.Lackland,T.T.Lewis,J.H.Lichtman,C.T.Longenecker,M.S.Loop,P.L.Lutsey,S.S.Martin,K.Matsushita,A.E.Moran,M.E.Mussolino,M.O'Flaherty,A.Pandey,A.M.Perak,W.D.Rosamond,G.A.Roth,U.K.A.Sampson,G.M.Satou,E.B.Schroeder,S.H.Shah,N.L.Spartano,A.Stokes,D.L.Tirschwell,C.W.Tsao,M.P.Turakhia,L.B.VanWagner,J.T.Wilkins,S.S.Wong,S.S.Virani,E.American Heart Association Council on,C.Prevention Statistics,S.Stroke Statistics,Heart Disease and Stroke Statistics-2019Update:A Report From the American Heart Association,Circulation 139(10)(2019)e56-e66.
[2]A.Timmis,N.Townsend,C.Gale,R.Grobbee,N.Maniadakis,M.Flather,E.Wilkins,L.Wright,R.Vos,J.Bax,M.Blum,F.Pinto,P.Vardas,E.S.C.S.D.Group,European Society of Cardiology:Cardiovascular Disease Statistics2017,Eur Heart J 39(7)(2018)508-579.
[3]A.Goins,A.R.Webb,J.B.Allen,Multi-layer approaches to scaffold-based small diameter vessel engineering:A review,Mater Sci Eng C Mater Biol Appl 97(2019)896-912.
[4]H.Y.Mi,Y.Jiang,X.Jing,E.Enriquez,H.Li,Q.Li,L.S.Turng,Fabrication of triple-layered vascular grafts composed of silk fibers,polyacrylamide hydrogel,and polyurethane nanofibers with biomimetic mechanical properties,Mater Sci Eng C Mater Biol Appl 98(2019)241-249.
[5]D.Radke,W.Jia,D.Sharma,K.Fena,G.Wang,J.Goldman,F.Zhao,Tissue Engineering at the Blood-Contacting Surface:A Review of Challenges and Strategies in Vascular Graft Development,Adv Healthc Mater 7(15)(2018)e1701461.
[6]S.Arora,S.Lin,C.Cheung,E.K.F.Yim,Y.C.Toh,Topography elicits distinct phenotypes and functions in human primary and stem cell derived endothelial cells,Biomaterials 234(2020)119747.
Disclosure of Invention
The invention aims to solve the problems of poor treatment effect and shortage of small-diameter artificial blood vessels in clinical artificial blood vessels in hospitals, and provides a novel small-diameter degradable artificial blood vessel and a construction method thereof.
In order to achieve the technical purpose, the invention adopts the following technical scheme:
a novel small-diameter degradable artificial blood vessel comprises:
inner surface fiber layer: the fiber is composed of loose and porous fibers which are arranged along the long axis direction of the artificial blood vessel in an oriented way and are parallel to each other, and the fiber is a degradable high polymer material and provides geometric pattern signal delivery for the artificial blood vessel;
outer surface fiber layer: the fiber is arranged along the circumferential direction of the artificial blood vessel in an oriented way, connected in a net shape and loose and porous, and provides mechanical support for the artificial blood vessel;
the spiral supporting structure: the fiber is wound on the fiber layer of the inner surface at a fixed interval and width, is a degradable high polymer material and is composed of disordered and compact fibers, and provides mechanical support for the artificial blood vessel.
Preferably, the degradable high molecular material is at least one selected from polycaprolactone and derivatives thereof, polyurethane and derivatives thereof, collagen and derivatives thereof, and silk fibroin and derivatives thereof.
Preferably, the diameter of the fiber in the inner surface fiber layer is 0.2-0.4 μm, the diameter of the fiber in the outer surface fiber layer is 1-5 μm, the diameter of the fiber in the spiral support structure is 1-3 μm, the distance is 2-3 mm, and the width is 0.2-0.6 mm.
Preferably, the average thickness of the inner surface fiber layer is 50 to 1000 μm; the average thickness of the outer surface fiber layer is 1000 to 9000 μm.
The invention also provides a preparation method of the novel small-diameter degradable artificial blood vessel, which comprises the following steps:
(1) Preparing degradable high polymer material into high polymer solution, taking a rotating spring with the rotating speed of 40-100 rpm as a collecting device, enabling electric spinning fibers to be adsorbed on the surface of the spring and gaps among the springs under the action of electrostatic spinning electric field force, and enabling disordered compact fibers adsorbed on the surface of the spring to form a spiral supporting structure so as to provide mechanical support for artificial blood vessels; the fibers which are arranged along the long axis direction of the artificial blood vessel, are parallel to each other and are loose and porous form an inner surface fiber layer at the gaps among the springs so as to deliver geometric pattern signals to the artificial blood vessel;
(2) Placing a conductive solution as an auxiliary electrode under a spring deposited with an inner surface fiber layer and a spiral supporting structure, adjusting the rotating speed of the spring to 1000-5000 rpm, and depositing on the spring under the action of an electric field force and a mechanical tension by adopting an electrostatic spinning process to obtain an outer surface fiber layer which is oriented and arranged along the circumferential direction of the artificial blood vessel and is formed by reticular connection and loose and porous fibers, thereby providing good mechanical properties for the artificial blood vessel;
(3) The artificial blood vessel is taken out by straightening the spring.
Preferably, in the step (1), the mass fraction of the degradable high molecular material in the high molecular polymer solution is 5 to 15%, the solvent is a mixed solvent of at least one of dichloromethane, chloroform and acetic acid and at least one of methanol, ethanol and deionized water, and the volume ratio is 3.
Preferably, in the step (1), the electrostatic spinning process parameters are as follows: the inner diameter of the spray head is 0.06-0.72 mm, the solution flow rate is 1-200 ul/min, the distance between the needle point and the collecting device is 1-14 cm, the voltage is 1-12 KV, and the collecting time is 10-60 min.
Preferably, in the step (2), the electrostatic spinning process parameters are as follows: the conducting solution of the auxiliary electrode is PBS solution or sodium chloride solution, the distance between the needle point and the collecting device is 4-8 cm, the distance between the needle point and the auxiliary electrode is 8-24 cm, the voltage is 8-24 KV, and the collecting time is 1-6 h.
Firstly, preparing inner layer fibers which are highly oriented and arranged along the long axis direction of the artificial blood vessel, have high specific surface area and high porosity by utilizing an electrostatic spinning technology and taking a spring rotating at a relatively low speed as a receiving device; then, a relatively high-speed spring deposited with inner layer fibers is used as a receiving device, and the electrostatic spinning technology is utilized to prepare outer layer fibers which are arranged along the circumferential direction of the artificial blood vessel in an oriented manner, connected in a net shape and loose and porous manner by adding an auxiliary electrode and adjusting preparation parameters, so that mechanical support is provided for the artificial blood vessel; meanwhile, under the action of an electric field force, a spiral supporting structure formed by disordered and compact fibers can be deposited on the spring collecting device, so that mechanical support is further provided for the artificial blood vessel. In the preparation process of the artificial blood vessel, the oriented electrostatic spinning fiber can enable the artificial blood vessel to be stressed more uniformly and not to be broken easily, and meanwhile, the delivered geometric pattern signal clues can promote the cooperative regeneration of blood vessel tissues and functions, so that the applicability of the electrostatic spinning fiber in tissue engineering is improved.
Compared with the existing artificial blood vessel, the invention has the following advantages:
1. in the aspect of the functional design of the artificial blood vessel, the invention adopts a layered design, and the artificial blood vessel is made to simulate the extracellular matrix structure of the natural human blood vessel by a method of geometric pattern signals, thereby playing a key physiological role in the repair and regeneration of the blood vessel. The small-diameter artificial blood vessel provided by the invention adopts a synthetic polymer material, has controllable biodegradability, excellent histocompatibility and mechanical properties, and can improve the integration of the artificial blood vessel with cells and tissues. The geometric pattern signal delivered by the orientation fiber can form an ordered structure similar to the natural vascular tissue by guiding the directional arrangement of vascular endothelial cells and smooth muscle cells so as to maintain the function of the new vascular tissue.
2. In the artificial blood vessel construction method, the invention adopts the electrostatic spinning technology, takes a spring rotating at a relatively low speed as a receiving device, and leads the electric spinning fibers to extend axially, straighten and align to obtain inner layer fibers with large specific area and loose orientation; meanwhile, under the action of an electric field force, the spring collecting device acts to form a spiral supporting structure consisting of disordered and compact fibers in the fibers of the inner layer, so that mechanical support is further provided for the artificial blood vessel; and then, taking a relatively high-speed spring deposited with the inner layer fibers as a receiving device, adding a conductive solution as an auxiliary electrode under the receiving device, adjusting preparation parameters, and aligning the electrospun fibers in the circumferential direction under the action of electric field force and mechanical drawing to obtain the net-shaped connected loose and porous oriented outer layer fibers.
In conclusion, the invention provides a method for preparing a small-diameter degradable artificial blood vessel by applying a spring and an auxiliary electrode based on an electrostatic spinning method, and the obtained artificial blood vessel has the effects of quickly realizing endothelialization of the artificial blood vessel, reducing the risk of thrombus caused by the artificial blood vessel, improving the long-term patency of the artificial blood vessel and the like. The electrostatic spinning fiber artificial blood vessel has simple and convenient manufacturing process, easy operation and controllable components and structure, has the function of simulating the key physiological action of the natural human body blood vessel cytoskeleton, can be used for replacing blood vessels of diseased parts, and has the prospect of industrial mass production.
Drawings
Fig. 1 is a schematic view of an electrospinning artificial blood vessel manufacturing apparatus according to the present invention and a schematic view of an electrospinning fiber artificial blood vessel manufactured in example 1, wherein (a) is a process for manufacturing an inner surface fiber layer and a spiral support structure; (b) an outer surface fiber layer preparation process; (c) The diameter of the prepared small-diameter artificial blood vessel is measured schematically, and the inner diameter is about 3mm; (d) The thickness of the prepared small-diameter artificial blood vessel is measured schematically, and the thickness is about 1mm.
Fig. 2 is a scanning electron microscope image of a small-diameter artificial blood vessel prepared in example 1 of the present invention, wherein (a) is a boundary between a fiber layer on an inner surface of the artificial blood vessel and a spiral support structure; (b) is the surface of the artificial blood vessel spiral supporting structure; (c) is an artificial blood vessel inner surface fiber layer; and (d) is an artificial blood vessel outer surface fiber layer.
FIG. 3 is a scanning electron microscope image of a small-diameter artificial blood vessel prepared in comparative example 1 of the present invention, wherein (a) is an inner surface fibrous layer of the artificial blood vessel; and (b) is an artificial blood vessel outer surface fiber layer.
FIG. 4 is a scanning electron microscope image of a small-diameter artificial blood vessel prepared in comparative example 2 of the present invention, in which (a) is an inner surface fibrous layer of the artificial blood vessel; (b) is the surface of the artificial blood vessel spiral supporting structure; and (c) is an artificial blood vessel outer surface fiber layer.
FIG. 5 is a scanning electron microscope image of a small-diameter artificial blood vessel prepared in comparative example 3 of the present invention, in which (a) is an inner surface fibrous layer of the artificial blood vessel; (b) is the surface of the artificial blood vessel spiral supporting structure; and (c) is an artificial blood vessel outer surface fiber layer.
FIG. 6 is a scanning electron microscope image of a small-diameter artificial blood vessel prepared in comparative example 4 of the present invention, in which (a) is an inner surface fiber layer of the artificial blood vessel; and (b) is an artificial blood vessel outer surface fiber layer.
Detailed Description
The following examples are presented to further illustrate the present invention for better understanding of the present invention, but the present invention is not limited to the following examples.
Example 1
The novel small-diameter degradable artificial blood vessel with the bionic micro-pattern signal, which is constructed by adopting the electrostatic spinning technology, is prepared by the following method:
the first step is as follows: preparation of electrospinning solution
0.5g of Polycaprolactone (PCL) is taken, 200ul of water, 1.3ml of ethanol and 3.5ml of Dichloromethane (DCM) are added, and the solution is shaken and dissolved for 6 hours at room temperature to form a PCL electrostatic spinning solution.
The second step: preparation of inner surface fiber layer (long axis direction orientation fiber layer) and spiral support structure
Transferring the solution prepared in the first step into a 5ml syringe, fixing the syringe on a pressure pump, connecting the syringe with a 25G spray head, setting the distance between the spray head and a rotating shaft to be 8cm, setting the flow rate of the solution to be 12ul/min, connecting the syringe with a high-voltage power supply through a needle head, taking the rotating shaft with the rotating speed of 80rpm and the diameter of 2.8mm as a collecting device, and arranging a stainless steel spring outside the rotating shaft with the outer diameter of 3mm, the length of 15cm and the distance of 3mm outside the rotating shaft. And starting a high-voltage power supply to set a voltage of 10kv, collecting for 30 minutes, and preparing an inner surface fiber layer which is axially stretched and aligned and a spiral supporting structure which is wound on the inner surface orientation fiber at a fixed interval and width, wherein the fiber diameter of the inner surface fiber layer is 0.3 μm, the average thickness is 100 μm, the fiber diameter of the spiral supporting structure is 2 μm, the interval is 3mm, and the width is 0.4mm.
The third step: production of outer surface fiber layer (circumferential direction oriented fiber layer)
PBS solution is placed under the rotating shaft to serve as an auxiliary electrode, the distance between the needle point and the auxiliary electrode is 10cm, the distance between the spray head and the rotating shaft is 4cm, the rotating speed of the rotating shaft is 1000rpm, then 12KV high pressure is applied, after 6 hours of collection, an outer surface fiber layer of a circumferential orientation fiber structure is obtained, the fiber diameter is 3 mu m, the average thickness is 900 mu m, and the spring is straightened and taken out of the artificial blood vessel, so that the small-diameter artificial blood vessel can be finally obtained.
As shown in fig. 2: FIGS. 1a-1c illustrate that the method can successfully produce an inner surface fiber layer having a long axis direction oriented fiber structure and a helical support structure; FIG. 1d illustrates that this method can successfully produce an outer surface fibrous layer of a circumferentially oriented reticulated fibrous structure.
The uniaxial tensile test is performed on the artificial blood vessel in the circumferential direction to obtain a stress-strain mechanical curve, and the Young modulus, yield stress and ultimate stress of the stress-strain mechanical curve are calculated to evaluate the mechanical properties of the artificial blood vessel, and the results are shown in Table 1. The result shows that the artificial blood vessel has excellent mechanical property.
Example 2
The first step is as follows: preparation of electrospinning solution
0.5g of Polycaprolactone (PCL) is taken, 200ul of water, 1.3ml of ethanol and 3.5ml of Dichloromethane (DCM) are added, and the solution is shaken and dissolved for 6 hours at room temperature to form a PCL electrostatic spinning solution.
The second step is that: preparation of inner surface fiber layer (Long-axis orientation fiber layer) and spiral support Structure
Transferring the solution prepared in the first step into a 5ml syringe, fixing the syringe on a pressure pump, connecting the syringe with a 25G spray head, setting the solution flow rate to be 12ul/min, connecting the syringe with a high-voltage power supply through a needle, taking a rotating shaft with the rotating speed of 100rpm and the diameter of 2.8mm as a collecting device, and connecting a stainless steel spring outside the rotating shaft with the outer diameter of 3mm, the length of 15cm and the distance of 3mm with a ground wire through a lead wire. Starting a high-voltage power supply to set a voltage of 11kv, collecting for 30 minutes, and preparing an inner surface fiber layer which is axially stretched and aligned and a spiral supporting structure which is wound on the inner surface orientation fiber at a fixed interval and width, wherein the fiber diameter of the inner surface fiber layer is 0.2 μm, the average thickness is 90 μm, the fiber diameter of the spiral supporting structure is 1 μm, the interval is 2mm, and the width is 0.3mm.
The third step: production of outer surface fiber layer (circumferential direction oriented fiber layer)
PBS solution is placed under the rotating shaft to serve as an auxiliary electrode, the distance between the needle point and the auxiliary electrode is 10cm, the distance between the spray head and the rotating shaft is 4cm, the rotating speed of the rotating shaft is 1100rpm, then 14KV high voltage is applied, after 5.5 hours of collection, an outer surface fiber layer of a circumferential orientation fiber structure is obtained, the fiber diameter is 2 micrometers, the average thickness is 800 micrometers, and the spring is straightened and taken out of the artificial blood vessel, so that the small-diameter artificial blood vessel can be finally obtained.
Example 3
The first step is as follows: preparation of electrostatic spinning solution
0.5g of Polycaprolactone (PCL) is taken, 200ul of water, 1.3ml of ethanol and 3.5ml of Dichloromethane (DCM) are added, and the solution is shaken and dissolved for 6 hours at room temperature to form a PCL electrostatic spinning solution.
The second step is that: preparation of inner surface fiber layer (long axis direction orientation fiber layer) and spiral support structure
Transferring the solution prepared in the first step into a 5ml syringe, fixing the syringe on a pressure pump, connecting the syringe with a 25G spray head, enabling the distance between the spray head and the upper end of a rotating shaft to be 9cm, enabling the solution flow to be 12ul/min, connecting the syringe with a high-voltage power supply through a needle head, enabling the rotating shaft with the rotating speed of 80rpm and the diameter of 2.8mm to serve as a collecting device, and enabling a stainless steel spring outside the rotating shaft to be 3mm in outer diameter, 15cm in length and 3mm in distance. The high voltage power supply was set to a voltage of 9kv, collected for 30 minutes, and an inner surface fiber layer which was axially stretched and aligned in an oriented manner and a spiral support structure which was wound around the inner surface-oriented fibers at a fixed pitch and width were prepared, the fiber diameter of the inner surface fiber layer was 0.3 μm and the average thickness thereof was 100 μm, and the fiber diameter of the spiral support structure was 2 μm, the pitch was 3mm, and the width was 0.4mm.
The third step: production of outer surface fiber layer (circumferential orientation fiber layer)
PBS solution is placed under the rotating shaft to serve as an auxiliary electrode, the distance between the needle point and the auxiliary electrode is 14cm, the distance between the spray head and the rotating shaft is 8cm, the rotating speed of the rotating shaft is 1100rpm, then 14KV high voltage is applied, after 6 hours of collection, an outer surface fiber layer of a circumferential orientation fiber structure is obtained, the fiber diameter is 3 micrometers, the average thickness is 900 micrometers, and the artificial blood vessel is taken out after the spring is straightened, so that the small-diameter artificial blood vessel can be finally obtained.
Comparative example 1
The first step is as follows: preparation of electrospinning solution
0.5g of Polycaprolactone (PCL) is taken, 200ul of water, 1.3ml of ethanol and 3.5ml of Dichloromethane (DCM) are added, and the solution is shaken and dissolved for 6 hours at room temperature to form a PCL electrostatic spinning solution.
The second step: preparation of inner surface fiber layer
Transferring the solution prepared in the first step into a 5ml syringe, fixing the syringe on a pressure pump, connecting the syringe with a 25G spray head, enabling the distance between the spray head and the upper end of a rotating shaft to be 9cm, enabling the solution to flow for 12ul/min, connecting the solution with a high-voltage power supply through a needle head, and taking the rotating shaft with the rotating speed of 80rpm and the diameter of 3mm as a collecting device. The high voltage power supply set a voltage of 9kv, and the inner surface fiber layer was prepared for 30 minutes, and had an average thickness of 100 μm.
The third step: preparation of outer surface fiber layer
PBS solution is placed under the rotating shaft to serve as an auxiliary electrode, the distance between the needle point and the auxiliary electrode is 14cm, the distance between the spray head and the rotating shaft is 8cm, the rotating speed of the rotating shaft is 1100rpm, then 14KV high voltage is applied, after 6 hours of collection, an outer surface fiber layer is obtained, the average thickness of the outer surface fiber layer is 900 micrometers, and the artificial blood vessel is taken out, so that the small-diameter artificial blood vessel can be finally obtained.
As shown in fig. 3: in contrast to fig. 2a-c, fig. 3a shows: the fibers in the inner surface layer are arranged in disorder and do not have a spiral supporting structure; fig. 3b is not significantly different from fig. 2d in specificity, illustrating that the spring plays an important role in the formation of the surface layer structure in the artificial blood vessel, but has no significant effect on the outer surface layer fibers.
The uniaxial tensile test is performed on the artificial blood vessel in the circumferential direction to obtain a stress-strain mechanical curve, and the Young modulus, yield stress and ultimate stress of the stress-strain mechanical curve are calculated to evaluate the mechanical properties of the artificial blood vessel, and the results are shown in Table 1. The Young's modulus, yield stress and ultimate stress of the artificial blood vessel in the circumferential direction are all higher than those of the artificial blood vessel in the embodiment 1, while the yield strain and ultimate strain are obviously reduced because the artificial blood vessel has more fibers arranged along the circumferential direction compared with the embodiment 1, so that the artificial blood vessel has stronger mechanical strength in the circumferential direction, but the elasticity of the artificial blood vessel is reduced, and the artificial blood vessel becomes stiffer.
Comparative example 2
The first step is as follows: preparation of electrospinning solution
0.5g of Polycaprolactone (PCL) is taken, 200ul of water, 1.3ml of ethanol and 3.5ml of Dichloromethane (DCM) are added, and the mixture is shaken and dissolved for 6 hours at room temperature to form a PCL electrostatic spinning solution.
The second step is that: preparation of inner surface fiber layer
Transferring the solution prepared in the first step into a 5ml syringe, fixing the syringe on a pressure pump, connecting the syringe with a 25G spray head, enabling the distance between the spray head and the upper end of a rotating shaft to be 9cm, enabling the solution flow to be 12ul/min, connecting the syringe with a high-voltage power supply through a needle head, enabling the rotating shaft with the rotating speed of 80rpm and the diameter of 2.8mm to serve as a collecting device, and enabling a stainless steel spring outside the rotating shaft to be 3mm in outer diameter, 15cm in length and 3mm in distance. The high voltage power supply was set at a voltage of 9kv and collected for 30 minutes to prepare an inner surface fiber layer having an average thickness of 100 μm.
The third step: preparation of outer surface fiber layer
Adjusting the rotating speed of the rotating shaft to 1100rpm, collecting for 6 hours to obtain an outer surface fiber layer with the average thickness of 900 μm, and taking out the artificial blood vessel.
As shown in fig. 4: FIGS. 4a and 4b illustrate that this method can successfully produce an inner surface fiber layer having a long-axis direction-oriented fiber structure and a spiral support structure; the relatively disordered arrangement of the fibers on the outer surface of the artificial blood vessel and the absence of a distinct network structure in fig. 4c illustrate that the electrolyte auxiliary electrode plays an important role in successfully preparing the outer surface fiber layer of the circumferentially oriented network fiber structure.
The uniaxial tensile test is performed on the artificial blood vessel in the circumferential direction to obtain a stress-strain mechanical curve, and the Young modulus, yield stress and ultimate stress of the stress-strain mechanical curve are calculated to evaluate the mechanical properties of the artificial blood vessel, and the results are shown in Table 1. The young's modulus, yield stress and ultimate stress of the artificial blood vessel are all significantly lower than those of example 1, because the outer layer fibers of the artificial blood vessel are disordered and cannot provide good mechanical support for the circumferential direction of the artificial blood vessel.
Comparative example 3
The first step is as follows: preparation of electrospinning solution
0.5g of Polycaprolactone (PCL) is taken, 200ul of water, 1.3ml of ethanol and 3.5ml of Dichloromethane (DCM) are added, and the solution is shaken and dissolved for 6 hours at room temperature to form a PCL electrostatic spinning solution.
The second step is that: preparation of inner surface fiber layer
Transferring the solution prepared in the first step into a 5ml syringe, fixing the syringe on a pressure pump, connecting the syringe with a 25G spray head, enabling the distance between the spray head and the upper end of a rotating shaft to be 9cm, enabling the solution flow to be 12ul/min, connecting the syringe with a high-voltage power supply through a needle head, enabling the rotating shaft with the rotating speed of 80rpm and the diameter of 2.8mm to serve as a collecting device, and enabling a stainless steel spring outside the rotating shaft to be 3mm in outer diameter, 15cm in length and 3mm in distance. The high voltage power supply set a voltage of 9kv, and the inner surface fiber layer was prepared for 30 minutes, and had an average thickness of 100 μm.
The third step: preparation of outer surface fiber layer
PBS solution is placed under the rotating shaft to serve as an auxiliary electrode, the distance between the needle point and the auxiliary electrode is 14cm, the distance between the spray head and the rotating shaft is 8cm, the rotating speed of the rotating shaft is 80rpm, then 14KV high pressure is applied, after 6 hours of collection, an outer surface fiber layer is obtained, the average thickness of the outer surface fiber layer is 900 micrometers, the spring is straightened, and the artificial blood vessel is taken out, so that the small-diameter artificial blood vessel can be finally obtained.
As shown in fig. 5: FIGS. 5a,5b illustrate that this method successfully produces an inner surface fiber layer having a long axis direction orientation fiber structure and a helical support structure; in FIG. 5c, the fibers on the outer surface of the artificial blood vessel are in a net structure but have no obvious orientation, which shows that the rotation speed of the rotating shaft plays an important role in the formation of the oriented arrangement of the fiber layer on the outer surface in the circumferential direction.
Uniaxial tensile experiments are carried out on the circumference direction of the artificial blood vessel to obtain a stress-strain mechanical curve, and the Young modulus yield stress and the ultimate stress of the stress-strain mechanical curve are calculated to evaluate the mechanical property of the artificial blood vessel, and the results are shown in Table 1. The young's modulus, the yield stress and the ultimate stress of the artificial blood vessel are all obviously lower than those in embodiment 1, and the reason is that the outer layer fibers of the artificial blood vessel are disordered by combining the analysis of an electron microscope picture, so that good mechanical support cannot be provided for the circumferential direction of the artificial blood vessel.
Comparative example 4
The first step is as follows: preparation of electrospinning solution
0.5g of Polycaprolactone (PCL) is taken, 200ul of water, 1.3ml of ethanol and 3.5ml of Dichloromethane (DCM) are added, and the solution is shaken and dissolved for 6 hours at room temperature to form a PCL electrostatic spinning solution.
The second step is that: preparation of inner surface fiber layer
Transferring the solution prepared in the first step into a 5ml syringe, fixing the syringe on a pressure pump, connecting the syringe with a 25G spray head, enabling the distance between the spray head and the upper end of a rotating shaft to be 9cm, enabling the solution to flow for 12ul/min, connecting the solution with a high-voltage power supply through a needle head, using the rotating shaft with the rotating speed of 1000rpm and the diameter of 2.8mm as a collecting device, and enabling a stainless steel spring outside the rotating shaft to have the outer diameter of 3mm, the length of 15cm and the distance of 3mm. The high voltage power supply set a voltage of 9kv, and the inner surface fiber layer was prepared for 30 minutes, and had an average thickness of 100 μm.
The third step: preparation of outer surface fiber layer
PBS solution is placed under the rotating shaft to serve as an auxiliary electrode, the distance between the needle point and the auxiliary electrode is 14cm, the distance between the spray head and the rotating shaft is 8cm, the rotating speed of the rotating shaft is 1000rpm, then 14KV high pressure is applied, after 6 hours of collection, an outer surface fiber layer is obtained, the average thickness of the outer surface fiber layer is 900 micrometers, the spring is straightened, and the artificial blood vessel is taken out, so that the small-diameter artificial blood vessel can be finally obtained.
As shown in fig. 6: FIG. 6a shows the disorderly arrangement of fibers in the inner layer of the artificial blood vessel, illustrating that the formation of the axially oriented fiber structure and the helical framework structure of the fiber layer on the inner surface is influenced by the rotating shaft rotating at a high speed; the artificial blood vessel outer surface fibers in fig. 6b are oriented network fiber structures, illustrating that this method can successfully produce the outer surface fiber layer of the circumferentially oriented network fiber structure.
Uniaxial tensile experiments are carried out on the circumference direction of the artificial blood vessel to obtain a stress-strain mechanical curve, and the Young modulus yield stress and the ultimate stress of the stress-strain mechanical curve are calculated to evaluate the mechanical property of the artificial blood vessel, and the results are shown in Table 1. The Young modulus, yield stress and ultimate stress of the artificial blood vessel in the circumferential direction are all higher than those of the artificial blood vessel in the embodiment 1, while the yield strain and ultimate strain are obviously reduced, and the reason is that the artificial blood vessel has more fibers arranged in the circumferential direction compared with the embodiment 1 by combining the analysis of an electron microscope picture, so that the artificial blood vessel has stronger mechanical strength in the circumferential direction, but also causes the elasticity of the artificial blood vessel to be reduced and becomes stiffer.
TABLE 1 mechanical Properties of Small-diameter vascular prostheses obtained in example 1 and comparative examples 1 to 4
Figure BDA0002706216890000121
Comparative example 5
The first step is as follows: preparation of electrospinning solution
0.5g of Polycaprolactone (PCL) is taken, 200ul of water, 1.3ml of ethanol and 3.5ml of Dichloromethane (DCM) are added, and the solution is shaken and dissolved for 6 hours at room temperature to form a PCL electrostatic spinning solution.
The second step is that: production of outer surface fiber layer (circumferential direction oriented fiber layer)
Transferring the solution prepared in the first step into a 5ml syringe, fixing the syringe on a pressure pump, connecting the syringe with a 25G spray head, enabling the solution flow to be 12ul/min, connecting the syringe with a high-voltage power supply through a needle head, taking a rotating shaft with the rotating speed of 1100rpm and the diameter of 3mm as a collecting device, and enabling the distance between the spray head and the rotating shaft to be 11cm. Setting the voltage of a high-voltage power supply to be 12KV, and collecting for 6 hours to obtain the artificial blood vessel with a single-layer fiber structure, wherein the average thickness of the artificial blood vessel is 800 mu m.
The uniaxial tensile test is performed on the artificial blood vessel in the circumferential direction to obtain a stress-strain mechanical curve, and the Young modulus, yield stress and ultimate stress of the stress-strain mechanical curve are calculated to evaluate the mechanical properties of the artificial blood vessel, and the results are shown in Table 2. The Young modulus, the yield stress and the ultimate stress of the artificial blood vessel are all lower than those of the artificial blood vessel in example 1, and the artificial blood vessel does not form a good oriented fiber net structure by combining the analysis of the previous comparative example, so that the mechanical property of the artificial blood vessel is inferior to that of the artificial blood vessel in example 1.
Comparative example 6
The first step is as follows: preparation of electrostatic spinning solution
0.5g of Polycaprolactone (PCL) is taken, 200ul of water, 1.3ml of ethanol and 3.5ml of Dichloromethane (DCM) are added, and the solution is shaken and dissolved for 6 hours at room temperature to form a PCL electrostatic spinning solution.
The second step is that: preparation of inner surface fiber layer (Long-axis orientation fiber layer)
Transferring the solution prepared in the first step into a 5ml syringe, fixing the syringe on a pressure pump, connecting the syringe with a 25G spray head, enabling the distance between the spray head and the upper end of a rotating shaft to be 9cm, enabling the solution to flow for 12ul/min, connecting the solution with a high-voltage power supply through a needle head, using the rotating shaft with the rotating speed of 80rpm and the diameter of 2.8mm as a collecting device, and enabling a stainless steel spring outside the rotating shaft to have the outer diameter of 3mm, the length of 15cm and the distance of 3mm. The high voltage source was set at a voltage of 9kv and collected for 1 hour to obtain an axially aligned and oriented inner surface fiber layer having an average thickness of 100 μm.
The uniaxial tensile test is performed on the artificial blood vessel in the circumferential direction to obtain a stress-strain mechanical curve, and the Young modulus, yield stress and ultimate stress of the stress-strain mechanical curve are calculated to evaluate the mechanical properties of the artificial blood vessel, and the results are shown in Table 2. The Young modulus, the yield stress and the ultimate stress of the artificial blood vessel are all lower than those of the artificial blood vessel in example 1, and the artificial blood vessel can form a good inner surface layer structure but lack an outer surface circumference orientation structure through the analysis of the previous comparative example, so that the mechanical property of the artificial blood vessel is far lower than that of the artificial blood vessel in example 1.
Comparative example 7
The first step is as follows: preparation of electrospinning solution
0.5g of Polycaprolactone (PCL) is taken, 200ul of water, 1.3ml of ethanol and 3.5ml of Dichloromethane (DCM) are added, and the solution is shaken and dissolved for 6 hours at room temperature to form a PCL electrostatic spinning solution.
The second step is that: production of outer surface fiber layer (circumferential orientation fiber layer)
Transferring the solution prepared in the first step into a 5ml syringe, fixing the syringe on a pressure pump, connecting the syringe with a 25G spray head, enabling the solution flow to be 12ul/min, connecting the syringe with a high-voltage power supply through a needle head, enabling a rotating shaft with the rotating speed of 1100rpm and the diameter of 3mm to serve as a collecting device, placing a PBS solution under the rotating shaft to serve as an auxiliary electrode, enabling the distance between the needle point and the auxiliary electrode to be 14cm, and enabling the distance between the spray head and the rotating shaft to be 8cm. The high voltage power supply is set to have a voltage of 14KV, and the artificial blood vessel with the non-oriented fiber structure is obtained after collection for 6 hours, wherein the average thickness of the artificial blood vessel is 1000 mu m.
The uniaxial tensile test is performed on the artificial blood vessel in the circumferential direction to obtain a stress-strain mechanical curve, and the Young modulus, yield stress and ultimate stress of the stress-strain mechanical curve are calculated to evaluate the mechanical properties of the artificial blood vessel, and the results are shown in Table 2. The Young's modulus, yield stress and ultimate stress of the artificial blood vessel are all higher than those of the artificial blood vessel in the embodiment 1, and the yield strain and the fracture strain are lower than those of the artificial blood vessel in the embodiment 1. According to the analysis of the previous comparative example, the artificial blood vessel can form a good circumferential oriented reticular structure of the outer surface layer, so that the artificial blood vessel has stronger mechanical strength in the circumferential direction, but the elasticity of the artificial blood vessel is reduced, and the artificial blood vessel becomes stiffer.
TABLE 2 mechanical Properties of Small-diameter vascular prostheses obtained in example 1 and comparative examples 5 to 7
Figure BDA0002706216890000141

Claims (8)

1. A method for preparing a small-diameter degradable artificial blood vessel, which comprises the following steps: inner surface fiber layer: the fiber is formed by loose and porous fibers which are arranged along the long axis direction of the artificial blood vessel in an oriented way, are parallel to each other, and provide a geometric pattern signal delivery for the artificial blood vessel; outer surface fiber layer: the fiber is arranged along the circumferential direction of the artificial blood vessel in an oriented way, connected in a net shape and loose and porous, and provides mechanical support for the artificial blood vessel for degradable high polymer materials; the spiral supporting structure comprises: the fiber is wound on the fiber layer of the inner surface at a fixed interval and width, is a degradable high polymer material and is composed of disordered and compact fibers, and provides mechanical support for the artificial blood vessel; preparing degradable high molecular material into high molecular polymer solution, then using a rotating spring with the rotating speed of 40-100 rpm as a collecting device, enabling electric spinning fibers to be adsorbed on the surface of the spring and gaps between the springs under the action of electrostatic spinning electric field force, and enabling disordered compact fibers adsorbed on the surface of the spring to form a spiral supporting structure so as to provide mechanical support for an artificial blood vessel; the fibers which are arranged along the long axis direction of the artificial blood vessel, are parallel to each other and are loose and porous form an inner surface fiber layer at the gaps among the springs so as to deliver geometric pattern signals to the artificial blood vessel; (2) Placing a conductive solution as an auxiliary electrode under a spring deposited with an inner surface fiber layer and a spiral supporting structure, adjusting the rotating speed of the spring to 1000-5000 rpm, and depositing on the spring under the action of an electric field force and a mechanical pulling force by adopting an electrostatic spinning process to obtain an outer surface fiber layer which is oriented and arranged along the circumferential direction of the artificial blood vessel and is formed by reticular connection and loose and porous fibers, thereby providing mechanical support for the artificial blood vessel; and (3) straightening the spring and taking out the artificial blood vessel.
2. The method of claim 1, wherein: in the step (1), the mass fraction of the degradable high molecular material in the high molecular polymer solution is 5-15%, the solvent is a mixed solvent of at least one of dichloromethane, chloroform and acetic acid and at least one of methanol, ethanol and deionized water, and the volume ratio is 3.
3. The method of claim 1, wherein: in the step (1), the electrostatic spinning process parameters are as follows: the inner diameter of the spray head is 0.06-0.72 mm, the solution flow rate is 1-200 ul/min, the distance between the needle point and the collecting device is 1-14 cm, the voltage is 1-12 KV, and the collecting time is 10-60 min.
4. The method of claim 1, wherein: in the step (2), the electrostatic spinning process parameters are as follows: the conducting solution of the auxiliary electrode is PBS solution or sodium chloride solution, the distance between the needle point and the collecting device is 4-8 cm, the distance between the needle point and the auxiliary electrode is 8-24 cm, the voltage is 8-24 KV, and the collecting time is 1-6 h.
5. A small-diameter degradable artificial blood vessel prepared by the method of any one of claims 1 to 4.
6. The small-diameter degradable artificial blood vessel according to claim 5, wherein: the degradable high polymer material is at least one of polycaprolactone and derivatives thereof, polyurethane and derivatives thereof, collagen and derivatives thereof, and silk fibroin and derivatives thereof.
7. The small-diameter degradable artificial blood vessel according to claim 5, wherein: the diameter of the fiber in the inner surface fiber layer is 0.2-0.4 μm, the diameter of the fiber in the outer surface fiber layer is 1-5 μm, the diameter of the fiber of the spiral supporting structure is 1-3 μm, the distance is 2-3 mm, and the width is 0.2-0.6 mm.
8. The small-diameter degradable artificial blood vessel according to claim 5, wherein: the average thickness of the inner surface fiber layer is 50-1000 μm; the average thickness of the outer surface fiber layer is 1000 to 9000 μm.
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WO2006080008A2 (en) * 2005-01-25 2006-08-03 Nicast Ltd. Artificial vascular prosthesis
US20100070020A1 (en) * 2008-06-11 2010-03-18 Nanovasc, Inc. Implantable Medical Device
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