CN1762505A - Catheter stent preparation method for repairing tubular tissue and organ and apparatus thereof - Google Patents
Catheter stent preparation method for repairing tubular tissue and organ and apparatus thereof Download PDFInfo
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- CN1762505A CN1762505A CN 200510060359 CN200510060359A CN1762505A CN 1762505 A CN1762505 A CN 1762505A CN 200510060359 CN200510060359 CN 200510060359 CN 200510060359 A CN200510060359 A CN 200510060359A CN 1762505 A CN1762505 A CN 1762505A
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Abstract
The invention discloses a method for preparing the tube bracket restoring the tubular tissues and organs and its device. The oil soluble and water-soluble medicine or their mixture with two identical or different biological polymer solution through the single layer, inner and outer layer or compartment spinneret form the nanometer or micro fiber under the action of high voltage and static electricity, the fiber accumulates on the core rod to form the tube bracket restoring the tubular tissues and organs. The invention is characterized by the simple equipment, convenient operation and little energy consumption; the prepared tube bracket possesses larger degree of porosity; tubes of different inner diameter and thickness can be prepared by changing the electrical weaving to meet different needs; the medicine can be put into the tube at the time preparing the tubular bracket and can be released slowly in the tube. The tube bracket prepared in this invention can be used for the restoration of tubular tissure such as vessel, nerve, esophagus, tracheal and ureter.
Description
Technical field
The present invention relates to a kind of catheter holder preparation method and device thereof that is used for repairing tubular tissue and organ.
Background technology
Tissue engineering is the principle according to engineering and life sciences, application normally has the active histiocyte of particular organisms and combines with biomaterial, at external or construct in vitro tissue, organ or its biological substitute, to keep, repair, to regenerate or to improve a science of damaged tissue and organ dysfunction.Because of it has profound significance in scientific research and clinical practice field, receive concern more and more widely.Reporting for work about artificial skin, artificial bone's tissue, artificial blood vessel arranged at present a lot.The tubular bracket of the electrospinning method preparation that the present invention relates to mainly is fit to tubular tissue and organ, and for example blood vessel, nerve, esophagus, trachea and ureteral reparation also can be used for osseous tissue.
At present, the preparation method of major diameter catheter holder mainly is the woven or knitting of fiber.The commercialization the earliest of wherein woven catheter holder, the limit but the conduit stiffness of woven support preparation greatly, is easily loose, it is not easy to operate to perform the operation, and sews up difficulty; The catheter holder of knitting preparation has improved the shortcoming of woven conduit to a certain extent, but still needs more subsequent treatment, as densification, rippleization, cleaning, coating, reinforcing etc.And the small diameter catheter support for example the preparation method of nerve conduit stent mainly be solution dip-coating/microgranule leaching process and fibrage method.Consuming time, the complex operation of dip coating wherein; Fibrage method complicated operation is difficult to control the aperture and the microcellular structure of support.
Electrospinning is a kind of simple and convenient, cheap and pollution-free or oligosaprobic spining technology.Just propose electrostatic spinning (electrospinning) notion as far back as American Formhals in 1934, yet up to nearly 10 years, people just carried out theory and experimentation than system to electrospinning.Electricity consumption spin the fiber finer that makes than traditional spin processes of fiber many, generally between tens nanometers were to several microns, electrospinning had been the important method of preparation superfine fibre to diameter at present.Electrospinning is to make macromolecular solution or melt charged, and places the high voltage electric field between spinning nozzle and the receiving screen.On spinning liquid surface, spinning head place with electrostatic repulsion forces overcome its surface tension, thereby make spinning liquid become one charged injection stream, and motion in electric field, traction stretch; Jet solution forms fiber because of the evaporation or the melt cooling curing of solvent simultaneously, is collected at last on the receiving system, becomes the fiber felt of non-woven fabrics shape.Change the device that collection process just can obtain difformity, different fiber accumulations structures.Electrospinning has been widely used in the various aspects of biomedical engineering at present, as medicine sustained release, organizational project, gene transmission and wound dressing etc.
Summary of the invention
The purpose of this invention is to provide a kind of catheter holder preparation method and device thereof that is used for repairing tubular tissue and organ.
The catheter holder preparation method that is used for repairing tubular tissue and organ is: oil-soluble, water soluble drug or their mixture and two kinds of identical or different bioavailable polymer solution are by monolayer, inside and outside two-layer or compartment formula spinneret, under the high-pressure electrostatic effect, form nanometer or micrometer fibers, fiber is piled up on plug, forms the catheter holder of repairing tubular tissue and organ.
Bioavailable polymer is biodegradable aliphatic polyester, poly-anhydride, poe, polyurethane, poly phosphate, poly phosphazene, polyamino acid, polysaccharide, protein or their mixture, nonbiodegradable polyurethane, polyacrylic acid and derivant thereof, polyolefin, polyethers, polysiloxanes or their mixture.Medicine is oil-soluble medicine, water soluble drug, somatomedin, polysaccharide, DNA (deoxyribonucleic acid) or polypeptide.The dissolved solvent of bioavailable polymer is amide-type, sulfone class, organic acid, alcohols, ketone, oxygen heterocycle, nitrogen heterocyclic ring, halogen-containing class, aromatics, water or their mixture.
The device that is used for the catheter holder of repairing tubular tissue and organ has feeder, and the feeder lower end is provided with spinneret, and the spinneret below is axially arranged with plug, be added with high voltage power supply between spinneret and the plug, plug has base, is provided with axial moving device on base, and plug is by driven by motor.
Spinneret is single-layer type spinneret, inside and outside double-deck spinneret or compartment formula spinneret, and its number is at 1～1000.Inside and outside double-deck spinneret is made of the spinning head of two different-diameters, and two spinning heads are arranged in coaxial or approximately axial mode, and identical or different bioavailable polymer solution enters respectively from feeder in the inside and outside spinning head.Compartment formula spinneret is made of a monolayer spinneret, and a plurality of independently compartments are arranged in spinneret inside, and identical or different bioavailable polymer solution enters respectively in the compartment of spinning head from feeder.High voltage power supply is dc source or alternating current power supply, and the voltage of dc high-voltage is 2000V～50000V, and the voltage of AC high voltage is 1000V～50000V.Diameter of mandrel is 1 micron～1 meter, and rotating speed is 1～10000 rev/min, and axially-movable speed is 0～50 meter per second.
Advantage of the present invention:
1) the preparation equipment needed thereby is simple, convenient to operation, one-step shaping, and energy consumption is little;
2) preparation gained support is the non-woven constructions of being piled into by Nano/micron fibers, is imitative extracellular matrix structure, helps histiocytic adhesion, propagation;
3) can be in scaffold fibers by material blend or coaxial blending method with various drug loadings, and can regulate and control the slow release that electrospinning parameter and material degradation are realized medicine, promote tissue reconstruction and functional rehabilitation;
4) pore size of support can be by the electric conductivity control of catcher;
5) internal diameter of catheter holder can be easily by the outside diameter control of plug, and the thickness of catheter holder is by the accumulation time control of fiber.
Description of drawings
Fig. 1 is that spinneret is the schematic representation of apparatus of the catheter holder that is used for repairing tubular tissue and organ of monolayer spinneret;
Fig. 2 is that spinneret is the device sketch map of the catheter holder that is used for repairing tubular tissue and organ of double-deck spinneret;
Fig. 3 is the prepared optical photograph that obtains the large diameter tubular Nano/micron fibers of the present invention;
Fig. 4 is the prepared stereoscan photograph that obtains tubular nanometer/micrometer fibers of the present invention;
Fig. 5 is ibuprofen of the present invention release profiles from tubular nanometer/micrometer fibers.
The specific embodiment
As shown in Figure 1, 2, the device that is used for the catheter holder of repairing tubular tissue and organ has feeder (1), the feeder lower end is provided with spinneret 2, spinneret 2 belows are axially arranged with plug 3, be added with high voltage power supply 4 between spinneret 2 and the plug 3, plug 3 has base 5, is provided with axial moving device 6 on base 5, and plug 3 is driven by motor 7.
The present invention adopt can axially reciprocating plug as gathering-device.Change the shape of diameter, length, velocity of rotation, axially-movable speed and the plug of plug, just can obtain the catheter holder of different-diameter, different length and axial vary in diameter.Change the electrospinning technological parameter,, can control the microstructure and the form of catheter holder as voltage, concentration of dope etc.; Blend by material can change material composition in the catheter holder, to satisfy the different tissues needs; Bioactive substances such as various medicines can be carried in the fiber by co-blended spinning or coaxial electrically spun, can promote tissue reconstruction and functional rehabilitation by the sustained release medicine; The catheter holder that can prepare multiple structure by the multistage spining technology is to satisfy the needs of different situations.
Embodiment 1:
Polycaprolactone (PCL, Mn 42,500, and Aldrich) 2g is dissolved in 10mL dimethyl formamide (DMF)/chloroform mixed solvent (volume ratio 4/6), places feeder shown in Figure 1, by syringe pump control spinning liquid charging rate; Spinning voltage is 10kV; Selecting diameter for use is the plug of 6mm, and the plug rotating speed is 200 rev/mins, and axial velocity is 0～0.15 meter per second.According to above-mentioned condition, change acquisition time, just can obtain internal diameter and be about the thick tubular fiber support of the different ancient piece of jade, round, flat and with a hole in its centres of 6mm.Fibre diameter is about 750nm.
Embodiment 2:
Polycaprolactone (PCL, Mn 42,500, and Aldrich) 2g is dissolved in 10mL dimethyl formamide (DMF)/chloroform mixed solvent (volume ratio 4/6), places feeder shown in Figure 1, by syringe pump control spinning liquid charging rate; Spinning voltage is 10kV; Selecting diameter for use is the plug of 1mm, and the plug rotating speed is 200 rev/mins, and axial velocity is 0～0.15 meter per second.According to above-mentioned condition, change acquisition time, just can obtain internal diameter and be about the thick tubular fiber support of the different ancient piece of jade, round, flat and with a hole in its centres of 1mm.Fibre diameter is about 700nm.
Polycaprolactone (PCL, Mn 42,500, and A1drich) 3g is dissolved in 10ml dimethyl formamide (DMF)/chloroform mixed solvent (volume ratio 3/7), places feeder mistress shown in Figure 1; The 2g dextran (Mn70,000, homemade) be dissolved in the 10ml deionized water with 400mg BSA, place feeder inner room shown in Figure 1; PCL solution nitrogen current extruding spinning head among the mistress, dextran solution is released spinneret with syringe pump in the inner room, and institute's making alive is 14.0kV; Adopting diameter is the plug of 1.5mm, and the plug rotating speed is 300 rev/mins, and axial velocity is 0～0.2 meter per second.Under these conditions, can prepare PCL easily is the tubular bracket that shell, dextran/BSA constitute for the core-shell type nano fiber of examining, and fibre diameter is about 600nm.Fig. 3 is for preparing major diameter catheter holder optical photograph.Fig. 4 is the scanning electron micrograph of this catheter holder.
Embodiment 4:
Poly-(lactide-co-glycolide) (PLGA, Mn 80,000, and is homemade) 2g is dissolved in 10mL dimethyl formamide (DMF)/chloroform mixed solvent (volume ratio 3/7), places feeder mistress shown in Figure 2; 3g polyvinylpyrrolidone (PVP, Mn 55,000, and is homemade) is dissolved in the 10ml deionized water with 400mg BSA, places feeder inner room shown in Figure 2; PLGA solution nitrogen current extruding spinning head among the mistress, PVP solution is released spinneret with syringe pump in the inner room; Institute's making alive is 12.0kV; Adopting diameter is the plug of 8mm, and the plug rotating speed is 500 rev/mins, and axial velocity is 0 meter per second.Under these conditions, can prepare PLGA easily is the tubular bracket that shell, PVP/BSA constitute for the core-shell type nano fiber of examining, and fibre diameter is about 900nm.
Embodiment 5:
Polyurethane (PU, Mw 11,000, and Cardiotech.Intern.) 2.5g is dissolved in 10mL dimethyl formamide/oxolane mixed solvent (volume ratio 9/1), places feeder mistress shown in Figure 2; 2g dextran (Mn 70,000, and is homemade) is dissolved in the 10ml deionized water with the 400mg lysozyme, places feeder inner room shown in Figure 2; Polyurethane solutions nitrogen current extruding spinning head among the mistress, dextran solution is released spinneret with syringe pump in the inner room; Institute's making alive is 20.0kV; Adopting diameter is the plug of 7mm, and rotating speed is 250 rev/mins, and axial velocity is 0～0.3 meter per second.Under these conditions, can prepare polyurethane easily is the support that shell, dextran/lysozyme constitute for the core-shell type nano fiber of examining, and fibre diameter is about 780nm.
Embodiment 6:
Polycaprolactone (PCL, Mn 42,500, and Aldrich) 2.5g and ibuprofen 400mg are dissolved in 10mL dimethyl formamide/chloroform mixed solvent (volume ratio 3/7), place feeder shown in Figure 1; Spinning voltage is 11kV; Adopting diameter is the plug of 6mm, and the plug rotating speed is 200 rev/mins, and axial velocity is 0 meter per second.Under these conditions, the support that constitutes of the PCL nanofiber of ibuprofen that just can obtain load, fibre diameter is about 630nm.Fig. 5 is ibuprofen release profiles from PCL nanofiber catheter holder.
Embodiment 7:
Polylactic acid (PLA, Mn 78,000 is homemade) 2g is dissolved in 10mL dimethyl formamide/chloroform mixed solvent (volume ratio 3/7), places feeder shown in Figure 1; Spinning voltage is 12.5kV; Adopting diameter is the plug of 8mm, 200 rev/mins of plug rotating speeds, and axial velocity is 0～0.2 meter per second.Under these conditions, just can obtain the tubular bracket that the PLA nanofiber constitutes, fibre diameter is about 800nm.This tubular bracket was soaked 20 minutes in the silanization heparin solution, take out nitrogen current and dry up, can obtain the fibrous framework of fiber surface absorption silanization heparin, it has good anticoagulation function.
Embodiment 8:
Polycaprolactone (PCL, Mn 42500, and Aldrich) 2g and poly sebacic polyanhydride (PSA, Mn 12,000) 0.5g is dissolved in 10ml dimethyl formamide (DMF)/chloroform mixed solvent (volume ratio 3/7), places feeder mistress shown in Figure 2; 2g dextran (Mn 70,000, and is homemade) is dissolved in the 10ml deionized water with the 400mg lysozyme, places feeder inner room shown in Figure 2; PCL solution nitrogen current extruding spinning head among the mistress, dextran solution is released spinneret with syringe pump in the inner room, and institute's making alive is 13.6kV; Adopting diameter is the plug of 6mm, and rotating speed is 300 rev/mins, and axial velocity is 0～0.1 meter per second.Under these conditions, can prepare PCL/PSA easily is shell, the core-shell type nano fibrous framework of dextran/lysozyme for examining, and fibre diameter is about 780nm.
Embodiment 9:
Polyurethane (PU, Mw 11,000, and Cardiotech.Intern.) 2.5g is dissolved in 10mL dimethyl formamide/oxolane mixed solvent (volume ratio 9/1), places feeder mistress shown in Figure 2; Polycaprolactone (PCL, Mn 42,500, and Aldrich) 2.5g is dissolved in 10mL dimethyl formamide/chloroform mixed solvent (volume ratio 3/7), places the feeder inner room; Adopting diameter is the plug of 6mm, and rotating speed is 200 rev/mins, and axial velocity is 0～0.15 meter per second; 19.0kV spins the PU nano-fiber tubular scaffold down now, regathers the PCL nanofiber layer at PU fiber pipe skin then under 12kV, promptly obtains the MULTILAYER COMPOSITE support.
Claims (10)
1. catheter holder preparation method that is used for repairing tubular tissue and organ, it is characterized in that, oil-soluble, water soluble drug or their mixture and two kinds of identical or different bioavailable polymer solution are by monolayer, inside and outside two-layer or compartment formula spinneret, under the high-pressure electrostatic effect, form nanometer or micrometer fibers, fiber is piled up on plug, forms the catheter holder of repairing tubular tissue and organ.
2. 1 described a kind of catheter holder preparation method that is used for repairing tubular tissue and organ as requested, it is characterized in that: described bioavailable polymer is biodegradable aliphatic polyester, poly-anhydride, poe, polyurethane, poly phosphate, poly phosphazene, polyamino acid, polysaccharide, protein or their mixture, nonbiodegradable polyurethane, polyacrylic acid and derivant thereof, polyolefin, polyethers, polysiloxanes or their mixture.
3. 1 described a kind of catheter holder preparation method that is used for repairing tubular tissue and organ as requested, it is characterized in that: described medicine is oil-soluble medicine, water soluble drug, somatomedin, polysaccharide, DNA (deoxyribonucleic acid) or polypeptide.
4. 1 described a kind of catheter holder preparation method that is used for repairing tubular tissue and organ as requested, it is characterized in that: the dissolved solvent of described bioavailable polymer is amide-type, sulfone class, organic acid, alcohols, ketone, oxygen heterocycle, nitrogen heterocyclic ring, halogen-containing class, aromatics, water or their mixture.
5. device that is used for the catheter holder of repairing tubular tissue and organ, it is characterized in that it has feeder (1), the feeder lower end is provided with spinneret (2), spinneret (2) below is axially arranged with plug (3), be added with high voltage power supply (4) between spinneret (2) and the plug (3), plug (3) has base (5), is provided with axial moving device (6) on base (5), and plug (3) is driven by motor (7).
6. 5 described a kind of devices that are used for the catheter holder of repairing tubular tissue and organ as requested is characterized in that described spinneret (2) is single-layer type spinneret, inside and outside double-deck spinneret or compartment formula spinneret, and its number is at 1～1000.
7. 6 described a kind of devices that are used for the catheter holder of repairing tubular tissue and organ as requested, it is characterized in that described inside and outside double-deck spinneret is made of the spinning head of two different-diameters, two spinning heads are arranged in coaxial or approximately axial mode, and identical or different bioavailable polymer solution enters respectively from feeder in the inside and outside spinning head.
8. 6 described a kind of devices that are used for the catheter holder of repairing tubular tissue and organ as requested, it is characterized in that described compartment formula spinneret is made of a monolayer spinneret, in spinneret inside a plurality of independently compartments are arranged, identical or different bioavailable polymer solution enters respectively in the compartment of spinning head from feeder.
9. 5 described a kind of devices that are used for the catheter holder of repairing tubular tissue and organ as requested, it is characterized in that described high voltage power supply is dc source or alternating current power supply, the voltage of dc high-voltage is 2000V～50000V, and the voltage of AC high voltage is 1000V～50000V.
10. 5 described a kind of devices that are used for the catheter holder of repairing tubular tissue and organ as requested is characterized in that described diameter of mandrel is 1 micron～1 meter, and rotating speed is 1～10000 rev/min, and axially-movable speed is 0～50 meter per second.
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| CN101579264B (en) * | 2009-06-04 | 2012-06-13 | 宁波大学 | Device for preparing tubular bracket for tissue engineering for simulating in vivo tube-shaped organs |
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| CN105148332A (en) * | 2015-09-21 | 2015-12-16 | 青岛慧生惠众生物科技有限公司 | Degradable blood vessel stent and preparation method and application thereof |
| CN105148329A (en) * | 2015-09-21 | 2015-12-16 | 青岛慧生惠众生物科技有限公司 | Absorbable lumen stent and preparing method and application thereof |
| CN106421921A (en) * | 2015-11-10 | 2017-02-22 | 江苏工程职业技术学院 | Preparation method of double-layer intravascular stent |
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| CN101579264B (en) * | 2009-06-04 | 2012-06-13 | 宁波大学 | Device for preparing tubular bracket for tissue engineering for simulating in vivo tube-shaped organs |
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| CN104287869B (en) * | 2014-09-19 | 2017-03-29 | 上海市肺科医院 | A kind of novel nano tunica fibrosa/yarn count frame for graft of trachea and preparation method thereof |
| CN105148330A (en) * | 2015-09-21 | 2015-12-16 | 青岛慧生惠众生物科技有限公司 | Lumen stent capable of conducting development absorption and preparation method and application thereof |
| CN105148332A (en) * | 2015-09-21 | 2015-12-16 | 青岛慧生惠众生物科技有限公司 | Degradable blood vessel stent and preparation method and application thereof |
| CN105148329A (en) * | 2015-09-21 | 2015-12-16 | 青岛慧生惠众生物科技有限公司 | Absorbable lumen stent and preparing method and application thereof |
| CN105148329B (en) * | 2015-09-21 | 2018-03-30 | 青岛慧生惠众生物科技有限公司 | A kind of absorbable intraluminal stent and its preparation method and application |
| CN106421921A (en) * | 2015-11-10 | 2017-02-22 | 江苏工程职业技术学院 | Preparation method of double-layer intravascular stent |
| CN109602518A (en) * | 2017-09-30 | 2019-04-12 | 厦门大学 | A kind of fluidic gating artificial blood vessel |
| CN110273188A (en) * | 2018-03-15 | 2019-09-24 | 北京普益盛济科技有限公司 | A kind of method of quick Fabrication interventional medicine microtubular tube body |
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