CN105944154A - Composite structure small-caliber tubular porous scaffold and manufacturing method thereof - Google Patents

Composite structure small-caliber tubular porous scaffold and manufacturing method thereof Download PDF

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Publication number
CN105944154A
CN105944154A CN201610396911.XA CN201610396911A CN105944154A CN 105944154 A CN105944154 A CN 105944154A CN 201610396911 A CN201610396911 A CN 201610396911A CN 105944154 A CN105944154 A CN 105944154A
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China
Prior art keywords
small
caliber tubular
caliber
composite construction
layer
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Pending
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CN201610396911.XA
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Chinese (zh)
Inventor
游正伟
王少飞
陈励捷
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Donghua University
National Dong Hwa University
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Donghua University
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Priority to CN201610396911.XA priority Critical patent/CN105944154A/en
Publication of CN105944154A publication Critical patent/CN105944154A/en
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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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/146Porous 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04Macromolecular materials
    • A61L31/048Macromolecular materials obtained 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08Materials for coatings
    • A61L31/10Macromolecular materials
    • 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
    • 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
    • D01D5/0076Electro-spinning characterised by the electro-spinning apparatus characterised by the collecting device, e.g. drum, wheel, endless belt, plate or grid
    • D01D5/0084Coating by electro-spinning, i.e. the electro-spun fibres are not removed from the collecting device but remain integral with it, e.g. coating of prostheses
    • 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
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/12Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • 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
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/18Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
    • 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
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/02Methods for coating medical devices

Abstract

The invention relates to a composite structure small-caliber tubular porous scaffold and a manufacturing method thereof. An inner layer of the small-caliber tubular scaffold is of a porous structure, and an outer layer is an electrostatic spinning nanometer fiber layer. The preparation method comprises the steps that a mold tube material is filled with a pore-forming agent, and a pore-forming agent layer is attached to the inner wall of the tube material; a thermosetting polyester material solution is injected into the pore-forming agent layer, a solvent is volatilized, and crosslinking is performed under the temperature of 120-150 DEG C, the temperature is decreased to the room temperature, then, a supporting bar is moved in, the outer layer mold tube material is removed, and the inner layer structure of the small-caliber tubular scaffold is obtained; electrostatic spinning cladding is performed on the small-caliber tubular scaffold, the pore-forming agent is removed, freezing and drying are performed, the supporting bar is removed, and the small-caliber tubular scaffold on the basis of the composite material and the composite structure is obtained. The preparation method is easy, convenient and efficient to implement; a layer of electrostatic spinning is attached to the outer side of the obtained small-caliber tubular scaffold, errhysis of the inner layer porous structure is avoided, and the mechanical characteristic of the tubular scaffold is enhanced.

Description

A kind of composite construction small-caliber tubular porous support and preparation method thereof
Technical field
The invention belongs to tubular bracket and preparation field thereof, particularly to a kind of composite construction small-caliber tubular porous support and system thereof Preparation Method.
Background technology
At present, clinical medicine needs substantial amounts of blood vessel graft or sub to carry out artificial blood vessel in the operations such as coronary bypass The transplanting of support;Therefore, small-bore artificial blood vessel is more and more paid attention to.And for small-caliber vascular stent, biological Bad being easier to of the compatibility causes thrombosis and restenosis, so the restenosis caused by thrombosis is small-caliber vascular group One significant challenge of weaver's journey.Therefore, in order to meet Treatment need, researchers are devoted to be prepared the side of support by improvement Method.There is loose structure preparation complexity, the problems such as row yielding is low in the research currently for small-caliber tubular support.
Electrostatic spinning technique is the common method preparing support in organizational project, and support specific surface area prepared by this kind of method is big, hole Gap rate is high, and nanofiber diameter is suitable with internal many cell sizes, it is possible to growth factor-loaded inducing cell sticks, breed and Differentiation, has peculiar advantage for Cell culture invitro, analog cell epimatrix structure.Therefore, electrostatic spinning technique gradually becomes The common method of support is prepared for organizational project in applying.
Summary of the invention
The technical problem to be solved is to provide a kind of composite construction small-caliber tubular porous support and preparation method thereof, should Method is easy, efficient, simplifies the preparation method of composite construction internal layer loose structure, improves the preparation of small-caliber tubular support Success rate.
The invention provides a kind of simplicity, the method efficiently preparing the small-caliber tubular support of Material cladding, structure composite.In it Layer loose structure uses salting out method to be processed molding, and material therefor is thermosetting polyester material.Outer layer Static Spinning material therefor is The material of electrostatic spinning can be carried out.Two kinds of different methods, process the small-caliber tubular support of material and structure composite.
A kind of composite construction small-caliber tubular porous support of the present invention, the internal layer of described small-caliber tubular support is loose structure, Outer layer is electrostatic spinning nano fiber layer.
A kind of preparation method of the composite construction small-caliber tubular porous support of the present invention, including:
(1) porogen is filled in the mould tubing of .5mm-10mm, with metal bar, unnecessary porogen is removed outside pipe, Adhere to one layer of closely knit pore oxidant layer at pipe material inner wall, remove metal bar;
(2) thermosetting polyester material solution syringe is injected into the pore oxidant layer in step (1), fully infiltrates, volatilization Solvent, 120-150 DEG C cross-links, and is down to room temperature, then moves into support bar, and removing outer layer mould tubing (will outward with solvent Layer mould tubing dissolves), obtain small-caliber tubular support endothecium structure;
(3) small-caliber tubular support in step (2) is carried out Static Spinning cladding, remove porogen and (use solubilized porogen Solvent soaking support dissolve porogen), lyophilization, remove support bar, obtain based on composite and composite construction little Bore tubular bracket;Wherein, the internal layer of small-caliber tubular support is loose structure, and outer layer is electrostatic spinning nano fiber structure.
In described step (1) porogen be NaCl or other can water-soluble, nontoxic, there is the granule of certain form.
In described step (1), porogen carries out pre-treatment before using, and obtains the porogen having partial miscibility and being bonded together; Described pre-treatment is: by perforating agent through grinding or high-speed stirred, and is filtered out by the screen cloth of certain mesh number and has specific grain The perforating agent of footpath size.Required aperture perforating agent is processed 0.5-5 hour under certain humidity (50-95%), it is ensured that porogen Between have certain bonding force.
Described humidity is 85%.
The pretreatment mode of described NaCl is: NaCl blender is smashed, and sifts out the salt particle of diameter 20~300 μm with screen cloth, It is placed on climatic chamber 0.5-5h, design temperature 25-40 DEG C, humidity 50 95%.
In described step (1), mould tubing is: PMMA pipe (internal diameter 2.0mm) of long 0.5-104cm, outer layer PMMA Effective chloroform dissolves;Described metal bar is: the metal bar (external diameter 1.6~1.7mm) of long 6cm.
In described step (2) thermosetting polyester material be sebacic acid and propyl tri-alcohol ester PGS, other polyprotic acid and polyhydric alcohol thing, Bakelite, epoxy resin, aminoplast, unsaturated polyester (UP) or alkyd plastics etc.;The solvent of thermosetting polyester material solution is THF, acetone, ethyl acetate, methanol, trifluoroethanol or hexafluoroisopropanol etc..
In described step (2), the time of crosslinking is 24-72h.
Supporting bar in described step (2) and step (3) is metal bar.
In described step (3) spinning liquid of Static Spinning be Poly(D,L-lactide-co-glycolide PLGA, polycaprolactone (PCL), poly- The electrostatic spinning solution of lactic acid PLA, gelatin, collagen protein etc..
In described step (3), the condition of Static Spinning is: voltage 5-15KV, feeding speed 0.5-2ml/h, receiving range 5-15cm, The spinning time is 0.5-2h, rotating speed 100-500r/min.
In described step (3), internal diameter based on composite and the small-caliber tubular support of composite construction is 1mm, and wall thickness is 0.5 mm。
The mould that porogen used in the present invention is commercially available, used includes tubing and bar, the Yi Jixiang of available solvent dissolving Answer the metal bar of size.
Beneficial effect
(1) small-caliber tubular support prepared by the present invention simplifies the preparation method of composite construction internal layer loose structure, improves osculum Footpath tubular bracket be prepared as power;
(2) the small-caliber tubular support that prepared by the present invention uses the outer layer tubular die that can be dissolved by the solvent, it is to avoid additive method takes off Damage during mould, finished product caused;
(3) with one layer of electrostatic spinning outside small-caliber tubular support prepared by the present invention, it is to avoid the oozing of blood of internal layer loose structure, Enhance the engineering properties of tubular bracket.
Accompanying drawing explanation
Fig. 1 is the sectional view of the tubular bracket observed under the microscope in embodiment 1;
Fig. 2 is the SEM figure of composite construction small-caliber tubular porous support in embodiment 1;The corresponding diverse location of 2A with 2B.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is expanded on further.Should be understood that these embodiments be merely to illustrate the present invention and not For limiting the scope of the present invention.In addition, it is to be understood that after having read the content that the present invention lectures, those skilled in the art can To make various changes or modifications the present invention, these equivalent form of values fall within the application appended claims limited range equally.
Embodiment 1
NaCl blender is smashed, sifts out the salt particle of diameter 20~300 μ with screen cloth, be placed on climatic chamber 1h, Design temperature 37 DEG C, humidity 85%.
Intercepting PMMA pipe (internal diameter 2.0mm) of long 6cm, the metal bar (external diameter 1.6~1.7mm) of long 6cm, by salt Granule inserts PMMA pipe under said temperature humidity, removes outside pipe with supporting bar by unnecessary salt particle, by true for PMMA pipe Empty drying.
To the THF solution (100mg/ml, 1ml syringe) of salt mold-in injection PGS (prepolymer, self-control), by PMMA Pipe standing is volatilized completely to solvent.Enter vacuum drying oven crosslinking 24h, design temperature 120 DEG C, obtain PGS-salt mold layer.
Effective for outer layer PMMA chloroform is dissolved, the PGS-salt mold layer obtained is stood and volatilizees completely to chloroform, enter oven for drying.
PGS-salt mold layer is carried out Static Spinning cladding, and spinning liquid is PLGA (Mn=60000) hexafluoroisopropanol solution (concentration 150mg/ml, 5ml syringe) Electrospinning parameters is: voltage 10KV, feeding speed 1ml/h, receiving range 15cm, The spinning time is 0.5h, rotating speed 300r/min.
After Static Spinning terminates, salt mould need to be dissolved lyophilization with distilled water immersion 48h by support, removes support bar, must answer Close structure small-caliber tubular porous support.

Claims (10)

1. a composite construction small-caliber tubular porous support, it is characterised in that the internal layer of described small-caliber tubular support is porous knot Structure, outer layer is electrostatic spinning nano fiber layer.
2. a preparation method for composite construction small-caliber tubular porous support, including:
(1) porogen is filled in mould tubing, adheres to one layer of pore oxidant layer at pipe material inner wall;
(2) thermosetting polyester material solution is injected into the pore oxidant layer in step (1), solvent flashing, hands over for 120-150 DEG C Connection, is down to room temperature, then moves into support bar, removes outer layer mould tubing, obtains small-caliber tubular support endothecium structure;
(3) small-caliber tubular support in step (2) is carried out Static Spinning cladding, remove porogen, lyophilization, remove and prop up Support bar, obtains the small-caliber tubular support based on composite and composite construction;Wherein, the internal layer of small-caliber tubular support is Loose structure, outer layer is electrostatic spinning nano fiber structure.
The preparation method of a kind of composite construction small-caliber tubular porous support the most according to claim 2, it is characterised in that institute Stating porogen in step (1) is NaCl.
The preparation method of a kind of composite construction small-caliber tubular porous support the most according to claim 2, it is characterised in that institute State porogen in step (1) and before using, carry out pre-treatment: by porogen through grinding or stirring, and screened by screen cloth, Process 0.5-5 hour under humidity 50-95%.
The preparation method of a kind of composite construction small-caliber tubular porous support the most according to claim 2, it is characterised in that institute State thermosetting polyester material in step (2) be sebacic acid and propyl tri-alcohol ester PGS, bakelite, epoxy plastics, aminoplast, Unsaturated polyester (UP) or alkyd plastics;The solvent of thermosetting polyester material solution is THF, acetone, ethyl acetate, methanol, trifluoro Ethanol or hexafluoroisopropanol.
The preparation method of a kind of composite construction small-caliber tubular porous support the most according to claim 2, it is characterised in that institute The time of crosslinking in step (2) of stating is 24-72h.
The preparation method of a kind of composite construction small-caliber tubular porous support the most according to claim 2, it is characterised in that institute Stating and supporting bar in step (2) and step (3) is metal bar.
The preparation method of a kind of composite construction small-caliber tubular porous support the most according to claim 2, it is characterised in that institute State the composition of the spinning liquid of Static Spinning in step (3) be Poly(D,L-lactide-co-glycolide PLGA, polycaprolactone (PCL), poly- Lactic acid PLA, gelatin or collagen protein.
The preparation method of a kind of composite construction small-caliber tubular porous support the most according to claim 2, it is characterised in that institute The condition of Static Spinning in step (3) of stating is: voltage is 5-15KV, and feeding speed is 0.5-2ml/h, and receiving range is 5-15cm, The spinning time is 0.5-2h, and rotating speed is 100-500r/min.
The preparation method of a kind of composite construction small-caliber tubular porous support the most according to claim 2, it is characterised in that institute Stating internal diameter based on composite and the small-caliber tubular support of composite construction in step (3) is 1mm, and wall thickness is 0.5mm.
CN201610396911.XA 2016-06-06 2016-06-06 Composite structure small-caliber tubular porous scaffold and manufacturing method thereof Pending CN105944154A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112043869A (en) * 2020-08-19 2020-12-08 南方医科大学 Preparation method of elastic and plastic polyester material and elastic and plastic polyester material

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CN105363076A (en) * 2015-09-30 2016-03-02 东华大学 Method for preparing polylactic acid caprolactone-collagen two-layer bionic vascular scaffold
CN105457101A (en) * 2015-12-17 2016-04-06 华南理工大学 Preparation method of small-caliber intravascular stent of three-layer structure

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112043869A (en) * 2020-08-19 2020-12-08 南方医科大学 Preparation method of elastic and plastic polyester material and elastic and plastic polyester material

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