CN102499800B - Blood vessel stent and preparation method thereof - Google Patents
Blood vessel stent and preparation method thereof Download PDFInfo
- Publication number
- CN102499800B CN102499800B CN201110365897.4A CN201110365897A CN102499800B CN 102499800 B CN102499800 B CN 102499800B CN 201110365897 A CN201110365897 A CN 201110365897A CN 102499800 B CN102499800 B CN 102499800B
- Authority
- CN
- China
- Prior art keywords
- internal layer
- middle level
- intravascular stent
- skin
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000002360 preparation method Methods 0.000 title claims description 22
- 210000004204 blood vessel Anatomy 0.000 title abstract description 46
- 108010022355 Fibroins Proteins 0.000 claims abstract description 48
- 238000010041 electrostatic spinning Methods 0.000 claims abstract description 25
- 101000691618 Homo sapiens Inactive phospholipase C-like protein 1 Proteins 0.000 claims abstract description 16
- 102100026207 Inactive phospholipase C-like protein 1 Human genes 0.000 claims abstract description 16
- 229920000848 poly(L-lactide-ε-caprolactone) Polymers 0.000 claims abstract description 16
- 238000009987 spinning Methods 0.000 claims description 24
- 230000003068 static effect Effects 0.000 claims description 24
- 239000007788 liquid Substances 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 239000000463 material Substances 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000008367 deionised water Substances 0.000 claims description 11
- 229910021641 deionized water Inorganic materials 0.000 claims description 11
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 2
- 238000007654 immersion Methods 0.000 claims description 2
- 238000009941 weaving Methods 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 abstract 1
- 230000002792 vascular Effects 0.000 description 13
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 239000002473 artificial blood Substances 0.000 description 10
- 239000000843 powder Substances 0.000 description 9
- 239000012460 protein solution Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 8
- 241000208340 Araliaceae Species 0.000 description 6
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 6
- 235000003140 Panax quinquefolius Nutrition 0.000 description 6
- 239000006227 byproduct Substances 0.000 description 6
- 239000000835 fiber Substances 0.000 description 6
- 235000008434 ginseng Nutrition 0.000 description 6
- 239000011259 mixed solution Substances 0.000 description 6
- 230000001476 alcoholic effect Effects 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 4
- 108010035532 Collagen Proteins 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 229920001436 collagen Polymers 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 230000005489 elastic deformation Effects 0.000 description 4
- 239000004698 Polyethylene Substances 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 230000013011 mating Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- -1 polyethylene Polymers 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 208000005189 Embolism Diseases 0.000 description 2
- 208000001435 Thromboembolism Diseases 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000004177 elastic tissue Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010060872 Transplant failure Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001523 electrospinning Methods 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000007366 host health Effects 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 239000008149 soap solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000007556 vascular defect Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Landscapes
- Prostheses (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a blood vessel stent, which comprises an inner layer, a middle layer and an outer layer. The inner layer is made of an electrostatic spinning screen blended by silk fibroin and PLCL (caprolactone), the middle layer is made of an electrostatic spinning screen blended by silk fibroin and PLCL and is sleeved outside the inner layer, the outer layer is a silk fibroin braided hose and sleeved outside the middle layer, and the inner layer, the middle layer and the outer layer are connected in a stitching manner so that intermittent annular spaces are respectively formed between the inner layer and the middle layer and between the middle layer and the outer layer. The blood vessel stent has fine biological compatibility, can be used for repairing of small-bore blood vessels, and can be matched with blood vessels of hosts due to the compliance thereof.
Description
Technical field
The present invention relates to a kind of intravascular stent, belong to biomedical materials field.
Background technology
Blood vessel kind disease serious harm human body health, there is ten hundreds of people in the whole world because many-sided reasons such as vessel aging, damage, pathological changes suffer from blood vessel kind disease every year.Vascular defects is repaired, and particularly the reparation of small-caliber vascular (6 millimeters of internal diameter <) is one of clinical difficult point always.
Thromboembolism is the main cause of small-caliber vascular post-transplantation failure.The reason that causes thromboembolism is many-sided, and after implanting the compliance of artificial blood vessel and host blood vessel not mate be one of main inducing causing small-caliber artificial blood vessel thrombosis and neointimal hyperplasia.
Compliance (refer generally to radial compliance, can be by formula
characterize intuitively, wherein D
2and D
1represent that respectively pressure is P
2and P
1time blood vessel diameter) refer under fluctuation pressure condition, tube wall is along with pressure changes the ability of continuous enlargement and contraction.After in artificial blood vessel's implantable bioartificial body, link together by mode and the host blood vessel sewed up, play the effect of dredging blood flow.If artificial blood vessel's compliance does not mate with host blood vessel,, in the time bearing the fluctuation pressure of blood flow, artificial blood vessel is different from amount of radial expansion and the amount of contraction of host blood vessel.This difference in the time of enlargement and contraction can cause the two to produce different blood stream pressure ripple spreading rates at suture, causes wave reflection and eddy current, and then causes blood clotting and cell proliferation; This species diversity also can make the two produce stress concentration at suture, and the vascular endothelial cell that bears excessive stresses can discharge a kind of enzyme that promotes smooth muscle cell proliferation, causes sharply thickening and hypertrophy of blood vessel; Meanwhile, compliance does not mate also can upset protein being uniformly distributed in blood vessel, it is formed concentrated at suture.These are not mated by compliance and the consequence that produces can directly cause the failure of blood vessel transplantation above, threaten patient's life security.
As can be seen here, designing, prepare compliance and the akin artificial blood vessel of natural blood vessel is one of key solving current small-caliber artificial blood vessel graft failure.
Summary of the invention
For the deficiencies in the prior art, the technical problem that the present invention solves is to provide a kind of intravascular stent and preparation method thereof, to improve the compliance of intravascular stent.
For solving the problems of the technologies described above, technical scheme of the present invention is achieved in that a kind of intravascular stent, and especially, described intravascular stent comprises:
Internal layer, described internal layer is made up of Static Spinning silk screen, and described Static Spinning silk screen is formed by fibroin albumen and PLCL blend;
Middle level, be made up of Static Spinning silk screen in described middle level, and described Static Spinning silk screen is formed by fibroin albumen and PLCL blend, and described middle level is sheathed on the outside of described internal layer;
Skin, described skin is fibroin albumen braided tube, described skin is sheathed on the outside in described middle level,
Between described internal layer, middle level, skin, sew up and connect, make internal layer and middle level and middle level and the discrete annulus of outer formation.
Preferably, in above-mentioned intravascular stent, described internal layer, middle level and skin are coaxial setting.
Preferably, in above-mentioned intravascular stent, the diameter of described internal layer is 1～6 millimeter, and described intravascular stent length is vertically 2～20 centimetres, the spacing distance in described internal layer and middle level is 0.1～1 millimeter, and described middle level and outer field spacing distance are 0.1～0.5 millimeter.
Preferably, in above-mentioned intravascular stent, the thickness between the inwall of described internal layer and described outer field outer wall is 0.3～2 millimeter.
Preferably, in above-mentioned intravascular stent, the Young's modulus of described internal layer is 1～5 MPa, and the Young's modulus in described middle level is 5～10 MPas, and described outer field Young's modulus is 10～30 MPas.
Technical scheme of the present invention can also realize like this:
A preparation method for intravascular stent, especially, it comprises the following steps:
(1) blend of fibroin albumen and PLCL is dissolved in hexafluoroisopropanol, make electrostatic spinning liquid, adopt Static Spinning technique to process and obtain Static Spinning silk screen described electrostatic spinning liquid, and then made internal layer and the middle level of intravascular stent by described Static Spinning silk screen;
(2) boiled-off silk is woven into tubular material, makes the skin of intravascular stent;
(3) internal layer, middle level and the skin of preparation in step () and (two) are set in together in order, and adopt degradable real silk stitching thread to connect, make internal layer and middle level and middle level and the outer space that forms ring-type.
Preferably, in the preparation method of above-mentioned intravascular stent, described in described step (), the mass ratio of fibroin albumen and PLCL is 1: 9～9: 1
Preferably, in the preparation method of above-mentioned intravascular stent, in described step (), the mass concentration of electrostatic spinning liquid is 4～12%.
Preferably, in the preparation method of above-mentioned intravascular stent, in described step (), also comprise the process that described Static Spinning silk screen is soaked in methanol or ethanol water, the volume accounting of described methanol or ethanol is 70%～90%, soak time is 2 hours, after immersion completes, rinse with deionized water, and then be dried.
Preferably, in the preparation method of above-mentioned intravascular stent, in described step (), also comprise the gathering-device that described electrostatic spinning liquid is gathered into Static Spinning silk screen, the diameter of described gathering-device is 1～7 millimeter, length is 2～20 centimetres, rotating speed is 20～2000 revs/min, and parallel speed is 1～10 cel.
Compared with prior art, the small-caliber vascular stent of coaxial three-decker that what the present invention was prepared have, utilize the cooperation of each layer of different Young's modulus and different bores, make support in the time bearing different blood pressure, embody different compliances, can realize mating of intravascular stent and host blood vessel compliance, thereby be expected to realize the successful transplanting of small-caliber vascular.
Brief description of the drawings
In order to be illustrated more clearly in the embodiment of the present invention or technical scheme of the prior art, to the accompanying drawing of required use in embodiment or description of the Prior Art be briefly described below, apparently, accompanying drawing in the following describes is only some embodiments of the present invention, for those of ordinary skill in the art, do not paying under the prerequisite of creative work, can also obtain according to these accompanying drawings other accompanying drawing.
The stress-strain diagram of the natural blood vessel of Fig. 1;
Fig. 2 is the exploded view of the stress-strain diagram of " J " shape to natural blood vessel;
Figure 3 shows that the structural representation of the embodiment of the present invention one to embodiment tri-medium vessels support;
Figure 4 shows that the electromicroscopic photograph of the internal layer of Fig. 3 medium vessels support;
Figure 5 shows that the electromicroscopic photograph in the middle level of Fig. 3 medium vessels support;
Figure 6 shows that the outer microphotograph of Fig. 3 medium vessels support.
Detailed description of the invention
The object of this invention is to provide a kind of intravascular stent and preparation method thereof, to improve the compliance of intravascular stent.
Improve artificial blood vessel's compliance and fundamentally solve the long-term problem of mating of compliance, artificial blood vessel must have and the akin structure of host health blood vessel and dynamic performance.Natural blood vessel comprises three layers, and innermost layer is blood vessel endothelium, and middle level is made up of several layers of smooth muscle cell, has the three-dimensional net structure being made up of elastic fiber and collagen fiber simultaneously, is the main body of bearing of the normal fluctuation pressure of blood flow; Blood vessel wall skin is the flexing shape collagen fiber that exist with helical structure.
Shown in ginseng Fig. 1, the load-deformation curve of natural blood vessel (caliber with pressure history, i.e. P-D curve) is " J " shape, shows as expansion larger under low fluctuation pressure and contraction, has higher compliance, or less Young's modulus.Now the stressed main body of blood vessel is the good middle elastic fiber of pliability and smooth muscle cell; Under high fluctuation pressure, there is less pliability, and can in the time of excessive expansion, bear tension force, there is lower compliance, or higher Young's modulus.Now the stressed main body of blood vessel is the outer harder flexing collagen fiber that are straightened, and it plays potentiation to blood vessel wall, is used for protecting blood vessel that its unlikely overdistension is even broken.Therefore, prepare the small-caliber artificial blood vessel that compliance and natural blood vessel match, should make material Young's modulus under low pressure less, and under high pressure there is larger Young's modulus.
Shown in ginseng Fig. 2, the present invention has preparation and the small-caliber vascular stent of the akin structure of natural blood vessel and load-deformation curve (caliber with pressure history, i.e. P-D curve), to improve its compliance.The P-D curve separating that natural blood vessel is to " J " shape becomes three crossing straight lines, represents respectively three layers of coaxial pipe of support.When three layers, support is stressed, there is sequencing: when pressure is changed to P by 0
1time, the caliber of internal layer is by D
0be changed to D
1, now internal layer overlaps with middle level, and middle level starts stressed.Along with pressure is increased to P gradually
2, internal layer and middle level caliber are by D
1become D
2, three layers of coincidence of support, the skin that now Young's modulus is higher becomes stressed main body, and the caliber of three layers is expanded simultaneously.Along with pressure reduces gradually, three layers of support are shunk simultaneously, and are returned to gradually initial caliber.
Stress-strain diagram in conjunction with natural blood vessel is known, requires internal layer pliability better, and Young's modulus is lower, and under low pressure distortion is large; Middle level compared with internal layer pliability reduce, Young's modulus slightly increases, and can under low pressure expand and shrink, and has the character identical with arterial elasticity fiber; Skin under high pressure pliability is less, and Young's modulus is higher, can in the time of excessive expansion, bear tension force, has the effect of collagen fiber.
Three layers of support all there is elastic deformation, and its Young's modulus is respectively the slope of three straight lines shown in Fig. 2.A, B point is respectively the turning point that support Young's modulus changes.The P-D curve of support entirety is directly determining the size of its compliance, except being subject to the impact of each layer of Young's modulus, is also subject to the impact of the distance between its three layers.
Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is described in detail, obviously, described embodiment is only the present invention's part embodiment, instead of whole embodiment.Based on the embodiment in the present invention, the every other embodiment that those of ordinary skill in the art obtain under the prerequisite of not making creative work, belongs to the scope of protection of the invention.
Embodiment mono-:
The present embodiment provides a kind of small-caliber vascular stent that improves compliance, and preparation process is as follows:
1) 1 kilogram of cocoon shell is put into the neutral soap solution that 50 mass per liter concentration are 0.5%, in 98～100 DEG C of processing 2 hours, make cocoon case degumming, fully after washing, obtain pure silk element (being fibroin albumen).By the pure silk element after drying, with the lithium bromide water solution of 5 liter of 9.3 mol/L, become fibroin albumen mixed solution 65 ± 2 DEG C of stirring and dissolving.
2) use cellulose membrane as dialysis material, the fibroin albumen mixed solution of gained is dialysed with deionized water, remove the impurity such as lithium bromide, obtain pure silk fibroin protein solution, regulating silk fibroin protein solution mass concentration is 3%.
3) silk fibroin protein solution is poured in polyethylene vessel, room temperature dries, and obtains fibroin protein film, obtains fibroin albumen powder after being pulverized.
4) take 0.3 gram, fibroin albumen powder with electronic balance, take PLCL (LA: CL=50: 50) 2.7 grams, be dissolved in 72 grams of hexafluoroisopropanols, stir and dissolve completely to it for 12 hours, obtain the electrostatic spinning liquid that concentration is 4% (w/w).
5) by step 4) in the electrostatic spinning liquid of 4% (w/w) that prepared pack in the injection device of electrostatic apparatus, select 8 kilovolts of Static Spinning voltages, injection device is injected 0.3 ml/hour of speed, 8 centimetres of pole spans, adopting diameter is that 1 millimeter, length are that the cylindric gathering-device of 2 centimetres is collected, the rotating speed of gathering-device is 20 revs/min, and parallel speed is 1 cel.After certain hour, collection rod by product from gathering-device takes off, in the alcoholic solution of 70% (v/v), soak 2 hours, dry for several times with deionized water rinsing, obtain the internal layer 1 (ginseng Fig. 3) that Young's modulus is about the intravascular stent of 1 MPa.
6) take 0.3 gram, fibroin albumen powder with electronic balance.Take PLCL (LA: CL=70: 30) 0.3 gram, be dissolved in 9.4 grams of hexafluoroisopropanols, stir and dissolve completely to it for 12 hours, obtain the electrostatic spinning liquid that concentration is 6% (w/w).
7) by step 6) in the electrostatic spinning liquid of 6% (w/w) that prepared pack in the injection device of electrostatic apparatus, select 10 kilovolts of Static Spinning voltages, injection device is injected 1.0 mls/hour of speed, 10 centimetres of pole spans, adopting diameter is that 1.1 millimeters, length are that the cylindric gathering-device of 2 centimetres is collected, the rotating speed of gathering-device is 100 revs/min, and parallel speed is 3 cels.After certain hour, collection rod by product from gathering-device takes off, in the alcoholic solution of 75% (v/v), soak 2 hours, dry for several times with deionized water rinsing, obtain the middle level 2 (ginseng Fig. 3) that Young's modulus is about the intravascular stent of 6 MPas.
8) utilize 12 ingot braiders, by specification be 2*2 (by 2 20～22 dawn and twisted filament plying) boiled-off silk to be woven into internal diameter be that 1.2 millimeters, length are the fibroin albumen braided tube that 2 centimetres, Young's modulus are about 15 MPas, make the skin 3 (ginseng Fig. 3) of support.
9) internal layer of support 1, middle level 2, outer 3 are set in together in order, utilize real silk stitching thread to sew up with " Z " type needle tracking.Obtain internal diameter and be 1 millimeter, length and be 2 centimetres, pipe thickness and be the coaxial three-decker intravascular stent of 0.3 millimeter, pipe thickness refers to the thickness between inwall and outer 3 the outer wall of internal layer 1.
Shown in ginseng Fig. 3 to Fig. 6, be respectively the structural representation of intravascular stent, the electromicroscopic photograph of internal layer 1, electromicroscopic photograph and outer 3 microphotographs in middle level 2.
In embodiment mono-, adopt the material preparation of different Young's to there is the small-caliber vascular stent of coaxial three-decker.Support inner layer material has lower Young's modulus, and pliability is better, under low pressure has moderate finite deformation; Middle level slightly increases compared with internal layer Young's modulus; Outer field Young's modulus is higher, in the time of high pressure, can bear tension force, prevents support excessive expansion and breaks.Three layers of support are utilized degradable stitching thread to connect, and three layers elastic deformation all occurs.
Embodiment bis-:
1) 1 kilogram of raw silk is put into the aqueous sodium carbonate that 30 mass per liter concentration are 0.2%, in 98～100 DEG C of processing 2 hours, make stripping, fully after washing, obtain pure silk element (being fibroin albumen).By the pure silk element after drying, the calcium chloride, water, the alcoholic solution that are 1: 8: 2 by 8 liters of mol ratios, at 75 ± 5 DEG C, stirring and dissolving becomes fibroin albumen mixed solution.
2) be dialysis material with cellulose membrane, the fibroin albumen mixed solution of gained is dialysed with deionized water, remove the impurity such as calcium chloride, obtain pure silk fibroin protein solution, regulating silk fibroin protein solution mass concentration is 6%.
3) silk fibroin protein solution is poured in polyethylene vessel, room temperature dries, and obtains fibroin protein film, obtains fibroin albumen powder after being pulverized.
4) take 0.5 gram, fibroin albumen powder with electronic balance, take PLCL (LA: CL=50: 50) 2 grams, be dissolved in 28.75 grams of hexafluoroisopropanols, stir and dissolve completely to it for 12 hours, obtain the electrostatic spinning liquid that concentration is 8% (w/w).
5) by step 4) in the electrostatic spinning liquid of 8% (w/w) that prepared pack in the injection device of electrostatic apparatus, select 12 kilovolts of Static Spinning voltages, injection device is injected 0.5 ml/hour of speed, 10 centimetres of pole spans, adopting diameter is that 3 millimeters, length are that the cylindric gathering-device of 12 centimetres is collected, the rotating speed of gathering-device is 200 revs/min, and parallel speed is 3 cels.After certain hour, the collection rod by product from gathering-device takes off, and soaks 2 hours in the methanol solution of 80% (v/v), dry for several times with deionized water rinsing, obtains the support internal layer 1 that Young's modulus is about 3 MPas.
6) take 1 gram, fibroin albumen powder with electronic balance.Take PLCL (LA: CL=70: 30) 0.25 gram, be dissolved in 11.25 grams of hexafluoroisopropanols, stir and dissolve completely to it for 12 hours, obtain the electrostatic spinning liquid that concentration is 10% (w/w).
7) by step 6) in the electrostatic spinning liquid of 10% (w/w) that prepared pack in the injection device of electrostatic apparatus, select 15 kilovolts of Static Spinning voltages, injection device is injected 1.5 mls/hour of speed, 12 centimetres of pole spans, adopting diameter is that 3.5 millimeters, length are that the cylindric gathering-device of 12 centimetres is collected, the rotating speed of gathering-device is 500 revs/min, and parallel speed is 2 cels.After certain hour, the collection rod by product from gathering-device takes off, and soaks 2 hours in the alcoholic solution of 75% (v/v), dry for several times with deionized water rinsing, obtains the middle level 2 that Young's modulus is about the intravascular stent of 7 MPas.
8) utilize 24 ingot braiders, by specification be 4*2 (by 4 20～22 dawn and twisted filament plying) boiled-off silk to be woven into internal diameter be that 4 millimeters, length are the fibroin albumen braided tube that 12 centimetres, Young's modulus are about 20 MPas, make the skin 3 of intravascular stent.
9) internal layer of support 1, middle level 2, outer 3 are set in together in order, utilize real silk stitching thread to sew up with " Z " type needle tracking.Obtain internal diameter and be 3 millimeters, length and be 12 centimetres, pipe thickness and be the coaxial three-decker intravascular stent of 1.2 millimeters.Pipe thickness refers to the thickness between the inwall of internal layer 1 and the outer wall of skin 3.
In embodiment bis-, adopt the material preparation of different Young's to there is the small-caliber vascular stent of coaxial three-decker.Support inner layer material has lower Young's modulus, and pliability is better, under low pressure has moderate finite deformation; Middle level slightly increases compared with internal layer Young's modulus; Outer field Young's modulus is higher, in the time of high pressure, can bear tension force, prevents support excessive expansion and breaks.Three layers of support are utilized degradable stitching thread to connect, and three layers elastic deformation all occurs.
Embodiment tri-:
1) 200 grams of cocoon shells are put into the aqueous sodium carbonate that 10 mass per liter concentration are 0.3%, in 98～100 DEG C of processing 2 hours, make cocoon case degumming, fully after washing, obtain pure silk element (being fibroin albumen).By the pure silk element after drying, with the lithium bromide water solution of 100 milliliter of 9.3 mol/L, at 65 ± 2 DEG C, stirring and dissolving becomes fibroin albumen mixed solution.
2) be dialysis material with cellulose membrane, the fibroin albumen mixed solution of gained is dialysed with deionized water, remove the impurity such as lithium bromide, obtain pure silk fibroin protein solution, regulating silk fibroin protein solution mass concentration is 9%.
3) silk fibroin protein solution is poured in polyethylene vessel, room temperature dries, and obtains fibroin protein film, obtains fibroin albumen powder after being pulverized.
4) take 0.5 gram, fibroin albumen powder with electronic balance, take PLCL (LA: CL=50: 50) 0.75 gram, be dissolved in 11.25 grams of hexafluoroisopropanols, stir and dissolve completely to it for 12 hours, obtain the electrostatic spinning liquid that concentration is 10% (w/w).
5) by step 4) in the electrostatic spinning liquid of 10% (w/w) that prepared pack in the injection device of electrostatic apparatus, select 15 kilovolts of Static Spinning voltages, injection device is injected 1.0 mls/hour of speed, 12 centimetres of pole spans, adopting diameter is that 6 millimeters, length are that the cylindric gathering-device of 20 centimetres is collected, the rotating speed of gathering-device is 1000 revs/min, and parallel speed is 7 cels.After certain hour, the collection rod by product from gathering-device takes off, and soaks 2 hours in the methanol solution of 90% (v/v), dry for several times with deionized water rinsing, obtains the internal layer 1 that Young's modulus is about the intravascular stent of 5 MPas.
6) take 0.9 gram, fibroin albumen powder with electronic balance.Take PLCL (LA: CL=70: 30) 0.1 gram, be dissolved in 7.3 grams of hexafluoroisopropanols, stir and dissolve completely to it for 12 hours, obtain the electrostatic spinning liquid that concentration is 12% (w/w).
7) by step 6) in the electrostatic spinning liquid of 12% (w/w) that prepared pack in the injection device of electrostatic apparatus, select 15 kilovolts of Static Spinning voltages, injection device is injected 2 mls/hour of speed, 15 centimetres of pole spans, adopting diameter is that 7 millimeters, length are that the cylindric gathering-device of 20 centimetres is collected, the rotating speed of gathering-device is 2000 revs/min, and parallel speed is 10 cels.After certain hour, the collection rod by product from gathering-device takes off, and soaks 2 hours in the alcoholic solution of 85% (v/v), dry for several times with deionized water rinsing, obtains the support middle level 2 that Young's modulus is about 10 MPas.
8) utilize 32 ingot braiders, by specification be 8*2 (by 8 20～22 dawn and twisted filament plying) boiled-off silk to be woven into internal diameter be that 7.5 millimeters, length are the fibroin albumen braided tube that 20 centimetres, Young's modulus are about 30 MPas, make the skin 3 of support.
9) internal layer of support 1, middle level 2, outer 3 are set in together in order, utilize real silk stitching thread to sew up with " Z " type needle tracking.Obtain internal diameter and be 6 millimeters, length and be 20 centimetres, pipe thickness and be the coaxial three-decker intravascular stent of 2 millimeters.Pipe thickness refers to the thickness between the inwall of internal layer 1 and the outer wall of skin 3.
In embodiment tri-, adopt the material preparation of different Young's to there is the small-caliber vascular stent of coaxial three-decker.Support inner layer material has lower Young's modulus, and pliability is better, under low pressure has moderate finite deformation; Middle level slightly increases compared with internal layer Young's modulus; Outer field Young's modulus is higher, in the time of high pressure, can bear tension force, prevents support excessive expansion and breaks.Three layers of support are utilized degradable stitching thread to connect, and three layers elastic deformation all occurs.
In sum, adopt technical scheme provided by the present invention, there is following obvious advantage:
A) small-caliber vascular stent with coaxial three-decker that the present invention is prepared utilizes the cooperation of each layer of different Young's modulus and different bores, make support in the time bearing different blood pressure, embody different compliances, can realize mating of intravascular stent and host blood vessel compliance, thereby be expected to realize the successful transplanting of small-caliber vascular.
B) three of support layers are good, the biodegradable fibroin material of biocompatibility, and the electrospinning adopting and weaving method make structure and the good mechanical performance of support entirety, its pore structure makes the permeability of support good, is conducive to the transhipment of cytotrophy, metabolite.
C) internal layer of support and middle level are electrostatic spinning fiber nets, are conducive to sticking, grow, breed, breaking up of cell; Support skin is fibroin braided tube, and hole is larger, and the cell being conducive in blood vessel surrounding enviroment is grown into.Therefore, this support is applicable to directly substituting and repairing of damaged little blood vessel.
D) each layer of direct preparation of support is shaped to tubular structure, therefore significantly stress defect of each layer of nothing; Utilize sewing method fixing by three layers, avoided the use of organic bond.
The present invention efficiently solve current small-caliber vascular repair materials poor compliance, structural instability, mechanical strength not, the problem such as material bio-toxicity and viral hidden danger, the small-caliber vascular stent for the little blood vessel of the thorough repair deficiency of medical domain and exploitation with China's independent intellectual property right has important scientific meaning and application prospect.
To those skilled in the art, obviously the invention is not restricted to the details of above-mentioned example embodiment, and in the situation that not deviating from spirit of the present invention or basic feature, can realize the present invention with other concrete form.Therefore, no matter from which point, all should regard embodiment as exemplary, and be nonrestrictive, scope of the present invention is limited by claims instead of above-mentioned explanation, is therefore intended to all changes that drop in the implication and the scope that are equal to important document of claim to include in the present invention.Any Reference numeral in claim should be considered as limiting related claim.
In addition, be to be understood that, although this description is described according to embodiment, but be not that each embodiment only comprises an independently technical scheme, this narrating mode of description is only for clarity sake, those skilled in the art should make description as a whole, and the technical scheme in each embodiment also can, through appropriately combined, form other embodiments that it will be appreciated by those skilled in the art that.
Claims (10)
1. an intravascular stent, comprises internal layer and skin, and described internal layer is made up of Static Spinning silk screen, and described skin is braided tube, it is characterized in that,
The Static Spinning silk screen of described internal layer is formed by fibroin albumen and PLCL blend;
Described intravascular stent also comprises middle level, and be made up of Static Spinning silk screen in described middle level, and described Static Spinning silk screen is formed by fibroin albumen and PLCL blend, and described middle level is sheathed on the outside of described internal layer;
Described skin is fibroin albumen braided tube, and described skin is sheathed on the outside in described middle level;
Between described internal layer, middle level, skin, sew up and connect, make internal layer and middle level and middle level and the discrete annulus of outer formation.
2. according to the intravascular stent described in right 1, it is characterized in that: described internal layer, middle level and outer for coaxially arranging.
3. according to the intravascular stent described in right 1, it is characterized in that: the diameter of described internal layer is 1～6 millimeter, described intravascular stent length is vertically 2～20 centimetres, and the spacing distance in described internal layer and middle level is 0.1～1 millimeter, and described middle level and outer field spacing distance are 0.1～0.5 millimeter.
4. according to the intravascular stent described in right 3, it is characterized in that: the thickness between the inwall of described internal layer and described outer field outer wall is 0.3～2 millimeter.
5. according to the intravascular stent described in right 1, it is characterized in that: the Young's modulus of described internal layer is 1～5 MPa, the Young's modulus in described middle level is 5～10 MPas, and described outer field Young's modulus is 10～30 MPas.
6. the preparation method of the intravascular stent as described in claim 1 to 5 any one, comprise the step of preparing internal layer by electrostatic spinning, wherein electrostatic spinning liquid is that polymer is dissolved in hexafluoroisopropanol, and prepare outer field step by weaving method, it is characterized in that, specifically comprise the following steps:
(1) blend of fibroin albumen and PLCL is dissolved in hexafluoroisopropanol, make electrostatic spinning liquid, adopt Static Spinning technique to process and obtain Static Spinning silk screen described electrostatic spinning liquid, and then made internal layer and the middle level of intravascular stent by described Static Spinning silk screen;
(2) boiled-off silk is woven into tubular material, makes the skin of intravascular stent;
(3) internal layer, middle level and the skin of preparation in step () and step (two) are set in together in order, and adopt degradable real silk stitching thread to connect, make internal layer and middle level and middle level and the outer space that forms ring-type.
7. according to the preparation method of the intravascular stent described in right 6, it is characterized in that: described in described step (), the mass ratio of fibroin albumen and PLCL is 1:9～9:1.
8. according to the preparation method of the intravascular stent described in right 7, it is characterized in that: in described step (), the mass concentration of electrostatic spinning liquid is 4～12%.
9. according to the preparation method of the intravascular stent described in right 6, it is characterized in that: in described step (), also comprise the process that described Static Spinning silk screen is soaked in methanol or ethanol water, the volume accounting of described methanol or ethanol is 70%～90%, soak time is 2 hours, after immersion completes, rinse with deionized water, and then be dried.
10. according to the preparation method of the intravascular stent described in right 6, it is characterized in that: in described step (), also comprise the gathering-device that described electrostatic spinning liquid is gathered into Static Spinning silk screen, the diameter of described gathering-device is 1～7 millimeter, length is 2～20 centimetres, rotating speed is 20～2000 revs/min, and parallel speed is 1～10 cel.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110365897.4A CN102499800B (en) | 2011-11-17 | 2011-11-17 | Blood vessel stent and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110365897.4A CN102499800B (en) | 2011-11-17 | 2011-11-17 | Blood vessel stent and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102499800A CN102499800A (en) | 2012-06-20 |
| CN102499800B true CN102499800B (en) | 2014-07-16 |
Family
ID=46211979
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110365897.4A Expired - Fee Related CN102499800B (en) | 2011-11-17 | 2011-11-17 | Blood vessel stent and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102499800B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3315147A1 (en) | 2016-10-28 | 2018-05-02 | Bioengineering Laboratories S.r.l. | Hybrid scaffold suitable for regenerating tissues and production process |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103173931B (en) * | 2013-03-07 | 2016-04-06 | 苏州睿研纳米医学科技有限公司 | Biocompatible fiber composite nonwoven web felt and its preparation method and application |
| CN103173934B (en) * | 2013-04-12 | 2016-05-04 | 东华大学 | A kind of preparation method of galactolipin vinyl acetate/N-isopropylacrylamide copolymer nano tunica fibrosa |
| CN104027851B (en) * | 2014-06-24 | 2016-03-30 | 上海大学 | A kind of manufacturing process of organizational project small-caliber vascular stent and formation system |
| CA2965600C (en) | 2014-10-27 | 2023-03-07 | Silk Biomaterials S.R.L. | Process for the production of a hybrid structure consisting of coupled silk fibroin microfibers and nanofibers, hybrid structure thus obtained and its use as implantable medical device |
| CN104826169B (en) * | 2015-04-21 | 2017-03-29 | 湖南大学 | A kind of novel artificial blood vessel |
| JP6612664B2 (en) * | 2016-03-16 | 2019-11-27 | 株式会社東芝 | Fiber orientation sheet |
| US10801140B2 (en) | 2016-03-16 | 2020-10-13 | Kabushiki Kaisha Toshiba | Fiber sheet and method for manufacturing same |
| CN107446818B (en) * | 2016-09-14 | 2021-05-07 | 四川蓝光英诺生物科技股份有限公司 | Lumen tissue construct printing device, lumen tissue construct printing method and lumen tissue construct |
| CN107456296B (en) * | 2016-09-14 | 2020-07-14 | 四川蓝光英诺生物科技股份有限公司 | Lumen tissue construct, method and device for producing lumen tissue construct |
| CN107411844B (en) * | 2016-09-14 | 2020-06-30 | 四川蓝光英诺生物科技股份有限公司 | Lumen tissue construct, and preparation method and preparation device thereof |
| CN108186162A (en) * | 2017-12-06 | 2018-06-22 | 江苏百优达生命科技有限公司 | A kind of three-decker composite artificial blood vessel |
| CN109172875B (en) * | 2018-09-18 | 2021-04-23 | 武汉纺织大学 | Preparation method of artificial blood vessel with micro-nano composite structure |
| CN109291550B (en) * | 2018-10-15 | 2020-05-01 | 南通纺织丝绸产业技术研究院 | Composite barrier film and preparation method thereof |
| CN109172037B (en) * | 2018-10-22 | 2023-09-12 | 上海交通大学医学院附属上海儿童医学中心 | Design and application of multi-layer tissue engineering tracheal stent based on 3D printing and electrostatic spinning technology |
| CN110115649B (en) * | 2019-05-15 | 2021-05-18 | 四川兴泰普乐医疗科技有限公司 | Self-developing degradable blood vessel stent |
| CN110115650B (en) * | 2019-05-15 | 2021-05-18 | 四川兴泰普乐医疗科技有限公司 | Self-developing electrostatic spinning bracket and preparation method thereof |
| JP6833914B2 (en) * | 2019-06-28 | 2021-02-24 | 株式会社東芝 | Manufacturing method of fiber alignment sheet |
| CN117898867A (en) * | 2022-12-02 | 2024-04-19 | 上海励楷科技有限公司 | Braided stent |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101264349A (en) * | 2008-04-23 | 2008-09-17 | 东华大学 | Method for preparing composite artificial blood vessel stent by combined electro-spinning with knitting technique |
| CN201342120Y (en) * | 2008-12-01 | 2009-11-11 | 无锡市第四人民医院 | Composite artificial small blood vessel support |
| CN101947333A (en) * | 2010-08-27 | 2011-01-19 | 安泰科技股份有限公司 | Biodegradable medicament-loaded polymer scaffold and preparation method thereof |
| CN102212918A (en) * | 2011-05-30 | 2011-10-12 | 东华大学 | Three-layer weaved small-caliber artificial blood vessel and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002537072A (en) * | 1999-02-26 | 2002-11-05 | アドバンスド、カーディオバスキュラー、システムズ、インコーポレーテッド | Composite superelastic / shape memory alloy and malleable alloy stents |
| US20070173787A1 (en) * | 2005-11-01 | 2007-07-26 | Huang Mark C T | Thin-film nitinol based drug eluting stent |
-
2011
- 2011-11-17 CN CN201110365897.4A patent/CN102499800B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101264349A (en) * | 2008-04-23 | 2008-09-17 | 东华大学 | Method for preparing composite artificial blood vessel stent by combined electro-spinning with knitting technique |
| CN201342120Y (en) * | 2008-12-01 | 2009-11-11 | 无锡市第四人民医院 | Composite artificial small blood vessel support |
| CN101947333A (en) * | 2010-08-27 | 2011-01-19 | 安泰科技股份有限公司 | Biodegradable medicament-loaded polymer scaffold and preparation method thereof |
| CN102212918A (en) * | 2011-05-30 | 2011-10-12 | 东华大学 | Three-layer weaved small-caliber artificial blood vessel and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3315147A1 (en) | 2016-10-28 | 2018-05-02 | Bioengineering Laboratories S.r.l. | Hybrid scaffold suitable for regenerating tissues and production process |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102499800A (en) | 2012-06-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102499800B (en) | Blood vessel stent and preparation method thereof | |
| CN101879330B (en) | Small-caliber silk fibroin tubular material and preparation method thereof | |
| EP2741791B1 (en) | Medical device | |
| CN102091349B (en) | High-strength biological scaffold material and preparation method thereof | |
| CN106572906B (en) | The method of manufacture of intraocular valve and the valve obtained using methods described | |
| CN101428155B (en) | Composite artificial minute vessel stent and preparation method thereof | |
| CN103357067B (en) | Fibroin-base artificial ligament repair material and preparation method thereof | |
| CN103006352B (en) | Prosthesis valve and prosthesis valve device | |
| CN105031735A (en) | Small-caliber artificial blood vessel with three-layer composite structure, and preparation method of small-caliber artificial blood vessel | |
| CN105457101A (en) | Preparation method of small-caliber intravascular stent of three-layer structure | |
| CN103083720B (en) | Silk fibroin tube and preparation method thereof | |
| EP3799892B1 (en) | Hybrid scaffold suitable for regenerating animal tissues and process for producing the scaffold | |
| CN108938143A (en) | A kind of small-bore bionical blood vessel of three-decker and preparation method thereof | |
| CN100478037C (en) | A fabric enhanced composite vascular prosthesis | |
| CN101683537B (en) | Tissue engineering tendon compound support material as well as preparation method and application thereof | |
| CN105232184B (en) | A kind of artificial blood vessel and preparation method thereof and ejecting device | |
| CN104689382A (en) | Braiding-reinforced nano-fiber small-caliber intravascular stent, and preparation and application thereof | |
| CN104524641B (en) | Poly-amino acid-based elastic vessel tissue engineering bracket and preparation method thereof | |
| CN106075594A (en) | A kind of Thermal inactive nano-fiber tubular scaffold and preparation method thereof | |
| CN110464881A (en) | Fibroin porous support with hierarchical structure and preparation method thereof | |
| CN109289093A (en) | The PGS/PCL double-layer artificial blood vessel and its construction method of netted sheaths structure | |
| CN104213211B (en) | A kind of method preparing doughnut artificial blood vessel for raw material with polycaprolactone | |
| CN108992711B (en) | Preparation method of double-layer artificial small-caliber blood vessel with modified inner layer | |
| CN103320960A (en) | Method for manufacturing artificial blood vessel | |
| CN102961788B (en) | A kind of heparin load aneurysm treatment overlay film frame and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140716 |