CN104013994A - Preparation method for lovastatin-containing tissue engineering scaffold - Google Patents
Preparation method for lovastatin-containing tissue engineering scaffold Download PDFInfo
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- CN104013994A CN104013994A CN201410211534.9A CN201410211534A CN104013994A CN 104013994 A CN104013994 A CN 104013994A CN 201410211534 A CN201410211534 A CN 201410211534A CN 104013994 A CN104013994 A CN 104013994A
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- lovastatin
- tissue engineering
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- macromolecular material
- engineering scaffold
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Abstract
The invention discloses a preparation method for a lovastatin-containing tissue engineering scaffold, and relates to the field of tissue engineering. The method comprises: together dissolving lovastatin and a high-molecule material in a volatilizable solvent, so as to prepare a homogenous solution, and employing a high-voltage static spinning method to perform spinning, collection and drying, so as to obtain the lovastatin-containing tissue engineering scaffold. The preparation method is simple in operation, low in cost, friendly to environment and suitable for industrialized production. The prepared lovastatin-containing tissue engineering scaffold is controllable in composition fiber diameter and controllable in lovastatin carrying capacity.
Description
Technical field
The present invention relates to field of tissue engineering technology, relate in particular to a kind of preparation method containing lovastatin tissue engineering bracket.
Background technology
Tissue engineering bracket is mainly used in tissue repair and regeneration.The inventive method adopts high-voltage electrostatic spinning legal system standby containing lovastatin skin tissue engineering scaffold, a kind ofly to utilize electric field force that high-voltage electrostatic field provides as driving force, target liq is stretched, after collecting, being dried, obtain the preparation method of fibrous web-like skin tissue engineering scaffold.This method is simple, effectively, can prepare the fibrous web-like skin tissue engineering scaffold of fibre diameter from 1 nm～100 μ m, the lovastatin amount of carrying from 0.1 ‰～50%.
Summary of the invention
The object of this invention is to provide a kind of preparation method containing lovastatin skin tissue engineering scaffold.The method strong adaptability, technique is simple, with low cost, reproducible.What make has the netted structure of three-dimensional fiber containing lovastatin skin tissue engineering scaffold, and, pharmaceutically active high to the envelop rate of lovastatin keeps good.Can be controlled in from 1 nm～100 μ m, the lovastatin amount of carrying from 0.1 ‰～50% scope by the fibre diameter containing lovastatin skin tissue engineering scaffold that regulates preparation parameter to make to make.
The present invention solves its technical problem, and the technical scheme adopting is: a kind of preparation method containing lovastatin skin tissue engineering scaffold, the steps include:
A, the common dissolving of lovastatin and macromolecular material made to homogeneity solution, the mass ratio of lovastatin and macromolecular material is between 1 ︰ 9999～1, and solution A viscosity is 1～10
5between mPas;
B, the solution of A step is carried out to spinning, collection, obtains containing lovastatin skin tissue engineering scaffold after dry with high-voltage electrostatic spinning method, high-voltage electrostatic spinning device nozzle bore between 0.05～5 mm, jet velocity between 1 μ L/min～1 mL/min, voltage between 0.5～30 kV, collect distance between 1～50 cm.
Compared with prior art, the invention has the beneficial effects as follows:
One, the present invention is jointly dissolved in volatile organic solvent by lovastatin and macromolecular material and makes homogeneity solution, adopts the mode of high-voltage electrostatic spinning, prepares the skin tissue engineering scaffold containing lovastatin.Experiment test proves, what the present invention made can significance improves the propagation of vascular endothelial cell containing lovastatin skin tissue engineering scaffold;
What two, prepared by the present invention evenly mixes with macromolecular material containing lovastatin in lovastatin tissue engineering bracket, by regulating kind, molecular weight and the content of macromolecular material to reach, regulate the diameter of the composition fiber that contains lovastatin tissue engineering bracket controlled from 1 nm～100 μ m, the object that reach long-acting, controlled, slowly discharges lovastatin;
Three, the present invention compares and has unique advantage with normal tissue engineering rack technology of preparing: (1) support has the netted structure of three-dimensional fiber, with extracellular matrix structural similarity, is conducive to tissue regeneration and reparation; (2) support can pass through sustained release lovastatin, promotes vascular endothelial cell proliferation, angiogenesis in tissue regeneration and repair process; (3) simple, the strong adaptability of technique, without special installation, with low cost, reproducible; (4) the material range of choice is wide, probably realizes suitability for industrialized production.
Macromolecular material in above-mentioned A step is one or more mixture of starch and derivant, cellulose and derivant thereof, protein, polysaccharide and heteropolysaccharide, acrylic homopolymer and copolymer, vinyl-based homopolymer and copolymer, ethylene oxide homopolymer and copolymer, polyester, polyamino acid, azobenzene polymer, ion exchange resin.
Above macromolecular material is the pharmaceutical polymers of existing maturation, prepares tissue engineering bracket technique simple, with low cost, reproducible, safe with it.
Accompanying drawing explanation
Fig. 1 is the scanning electron microscopic observation figure of lovastatin-polylactic acid bracket of making of the method for the embodiment of the present invention one.
Fig. 2 is the scanning electron microscopic observation figure of lovastatin-polyisobutylene support of making of the method for the embodiment of the present invention three.
Fig. 3 is the scanning electron microscopic observation figure of lovastatin-polyoxyethylene support of making of the method for the embodiment of the present invention four.
Fig. 4 is that lovastatin-polylactic acid bracket of making of the method for the embodiment of the present invention one is for the angiogenesis promoting experimental result of skin repair process.
Fig. 5 does not add lovastatin, but other condition and parameter and the enforcement one just the same polylactic acid bracket making are as the result of the angiogenesis promoting experiment contrast example in skin repair process.
The specific embodiment
Below in conjunction with the drawings and specific embodiments, the present invention is described in further detail.
Embodiment mono-
A, lovastatin and macromolecular material polylactic acid are jointly dissolved in chloroform and form homogeneity solution, lovastatin and polylactic acid ratio are 1:500, and solution viscosity is 100 mPs;
B, the mixed solution A of lovastatin and polylactic acid is sprayed with high-voltage electrostatic spinning method, nozzle diameter is 0.4 mm, jet velocity is 0.05 mL/min, voltage strength is 20 kV, receiving range is 15 cm, and what after collection is dry, obtain is lovastatin-polylactic acid bracket containing lovastatin tissue engineering bracket.
Embodiment bis-
The present embodiment is identical with embodiment mono-, and only, the macromolecular material in steps A is polyisobutylene to difference; High-voltage electrostatic spinning method nozzle diameter in step B is 0.5 mm, and jet velocity is 0.10 mL/min, and voltage strength is 15 kV, and receiving range is 18 cm, and what obtain is lovastatin-polyisobutylene support containing lovastatin tissue engineering bracket.
Embodiment tri-
The present embodiment is identical with embodiment mono-, and only, the macromolecular material in steps A is polyoxyethylene to difference, and solution A viscosity is 500 mPs; High-voltage electrostatic spinning method nozzle diameter in step B is 0.9 mm, and jet velocity is 0.15 mL/min, and voltage strength is 13 kV, and receiving range is 10 cm, and what obtain is lovastatin-polyoxyethylene support containing lovastatin tissue engineering bracket.
Lovastatin in the inventive method and the ratio between macromolecular material, also without specific (special) requirements, produce toxicity as long as the amount of lovastatin is enough to produce curative effect and is unlikely.Its numerical value is determined according to the clinical use amount of existing lovastatin.
Solvent in the inventive method A step is not limited to the solvent using in above embodiment, so long as can dissolve the solvent of selected macromolecular material, all can.
Below experiment showed, and adopt the inventive method to prepare to form fiber from controlled containing lovastatin tissue engineering bracket within the scope of 1 nm～100 μ m, and can in process of tissue reparation, promote angiogenesis containing lovastatin tissue engineering bracket.
One, containing the experiment of lovastatin tissue engineering bracket scanning electron microscopic observation
What the method for use embodiment mono-, two, three made respectively carries out scanning electron microscopic observation experiment containing lovastatin tissue engineering bracket.Experimental technique: 1 mg is sticked to scanning electron microscope special purpose copper target containing lovastatin tissue engineering bracket, contain the composition fibre diameter of lovastatin tissue engineering bracket after metal spraying with scanning electron microscopic observation.
Scanning electron microscopic observation is shown in respectively Fig. 1,2,3 containing the composition fibre diameter result of lovastatin tissue engineering bracket.Wherein Fig. 1,2,3 is respectively the scanning electron microscopic observation composition fibre diameter result of lovastatin-polylactic acid bracket, lovastatin-polyisobutylene support, lovastatin-polyoxyethylene support.
As can be seen from Figure 1: the composition fibre diameter of lovastatin-polylactic acid bracket of embodiment mono-is 469.8 ± 37.8 nm.As can be seen from Figure 2: the composition fibre diameter of lovastatin-polyisobutylene support of embodiment bis-is 185.6 ± 33.8 nm.As can be seen from Figure 3: the composition fibre diameter of lovastatin-polyoxyethylene support of embodiment tri-is 2.85 ± 0.51 μ m.
Two, containing the newborn experiment of the short skin repair process medium vessels of lovastatin tissue engineering bracket
Use lovastatin-polylactic acid bracket that the method in embodiment mono-makes to test for the angiogenesis promoting of skin repair process; Meanwhile, do not add lovastatin, but other condition and parameter and implement a just the same polylactic acid bracket making example in contrast.Experimental technique: respectively 10 mg lovastatin-polylactic acid brackets and polylactic acid bracket are covered in to rat full thickness dermal place, with 3 of surgical threads, sew up fixing, anesthetized rat after 3 days, get skin injury place cambium, after paraformaldehyde is fixing, paraffin embedding, tissue slice, with the expression of the evaluation vascular endothelial cell proliferation marker protein CD105 of cambium place of immunohistochemistry staining method.
Short skin repair process medium vessels new life the results are shown in Figure 3 and Fig. 4, and the brown color position that wherein red circle marks shows vascular endothelial cell proliferation marker protein CD105 positive expression.
As can be seen from Figure 4: lovastatin-polylactic acid bracket of embodiment mono-, when repairing for skin injury, has a large amount of vascular endothelial cell proliferation marker protein CD105 positive expressions in repair tissue, demonstrate obvious angiogenesis promoting effect.As can be seen from Figure 5: do not add the polylactic acid bracket of lovastatin when repairing for skin injury, in repair tissue, there is no vascular endothelial cell proliferation marker protein CD105 positive expression, show not have new vessels to produce.
Claims (2)
1. containing a preparation method for lovastatin tissue engineering bracket, it is characterized in that comprising the steps:
A, lovastatin and macromolecular material are dissolved in to volatilizable solvent jointly, make homogeneity solution, the mass ratio of lovastatin and macromolecular material is between 1 ︰ 9999～1, and solution A viscosity is 1～10
5between mPas;
B, the solution of A step is carried out to spinning, collection, obtains containing lovastatin skin tissue engineering scaffold after dry with high-voltage electrostatic spinning method, high-voltage electrostatic spinning device nozzle bore between 0.05～5 mm, jet velocity between 1 μ L/min～1 mL/min, voltage between 0.5～30 kV, collect distance between 1～50 cm.
2. a kind of preparation method containing lovastatin tissue engineering bracket as claimed in claim 1, is characterized in that: the macromolecular material in described A step is one or more mixture of starch and derivant, cellulose and derivant thereof, protein, polysaccharide and heteropolysaccharide, acrylic homopolymer and copolymer, vinyl-based homopolymer and copolymer, ethylene oxide homopolymer and copolymer, polyester, polyamino acid, azobenzene polymer, ion exchange resin.
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| CN201410211534.9A CN104013994A (en) | 2014-05-19 | 2014-05-19 | Preparation method for lovastatin-containing tissue engineering scaffold |
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Cited By (2)
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|---|---|---|---|---|
| CN105879123A (en) * | 2016-04-12 | 2016-08-24 | 西北工业大学 | PLGA (poly(lactic-co-glycolic acid) fiber-microsphere dual-drug-loaded composite scaffold and preparation method of PLGA fiber-microsphere dual-drug-loaded composite scaffold |
| CN108904888A (en) * | 2018-07-10 | 2018-11-30 | 南方医科大学 | The method that method of electrostatic spinning preparation carries Pravastatin intravascular tissue engineering stent material |
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| US20070048351A1 (en) * | 2005-09-01 | 2007-03-01 | Prescient Medical, Inc. | Drugs coated on a device to treat vulnerable plaque |
| CN1961974A (en) * | 2005-11-09 | 2007-05-16 | 中国科学院化学研究所 | Nano copolymer fibrous membrane material capable of being biodegraded and absorbed and preparation process and use thereof |
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| CN105879123A (en) * | 2016-04-12 | 2016-08-24 | 西北工业大学 | PLGA (poly(lactic-co-glycolic acid) fiber-microsphere dual-drug-loaded composite scaffold and preparation method of PLGA fiber-microsphere dual-drug-loaded composite scaffold |
| CN105879123B (en) * | 2016-04-12 | 2018-10-23 | 西北工业大学 | PLGA fiber-microspheres are double to carry medicine compound rest and preparation method thereof |
| CN108904888A (en) * | 2018-07-10 | 2018-11-30 | 南方医科大学 | The method that method of electrostatic spinning preparation carries Pravastatin intravascular tissue engineering stent material |
| CN108904888B (en) * | 2018-07-10 | 2021-03-23 | 南方医科大学 | Method for preparing pravastatin-loaded vascular tissue engineering scaffold material by electrostatic spinning method |
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Application publication date: 20140903 |