CN101269242A - Transgenic cell overlapped vascular inner rack and manufacture method thereof - Google Patents
Transgenic cell overlapped vascular inner rack and manufacture method thereof Download PDFInfo
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- CN101269242A CN101269242A CNA2008100692524A CN200810069252A CN101269242A CN 101269242 A CN101269242 A CN 101269242A CN A2008100692524 A CNA2008100692524 A CN A2008100692524A CN 200810069252 A CN200810069252 A CN 200810069252A CN 101269242 A CN101269242 A CN 101269242A
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Abstract
The invention provides an intravascular stent covered by transgene cells, which is characterized in that: a low-temperature plasma treatment layer, an adhesive interstitial substance coat and a cell coat are orderly arranged on the surface of the naked metal stent. The adhesive interstitial substance coat is a protein coat or a peptide sequence coat; the cell coat is obtained by stabilizing transfected cells by target gene. Preparing the intravascular stent includes the following steps: obtaining the target gene; constructing and amplifying the eukaryotic expression carrier of the target gene; obtaining cells; modifying the surface of the metal stent; preparing the adhesive interstitial substance coat; rotating, cultivating, and preparing the intravascular stent covered by transgene cells. On the one hand, by expressing the target gene at high-level, the rehabilitating of the injured endovascular endoderm is enhanced and the multiplication of smooth muscle cells is inhibited; one the other hand, by the multiplication of external-source cells, the surface endothelialization of the intravascular stent is accelerated; the coating is close applied on the surface of the stent, the biocompatibility is fine, and the intravascular stent can be inhibited from turning narrower ultimately.
Description
Technical field
The present invention relates to the endovascular stent that a kind of transgenic cell covers, the particularly a kind of transgenic cell of restenosis covers behind percutaneous transluminal coronary angioplasty or the Stent endovascular stent and preparation method thereof that suppresses.
Background technology
Restenosis mainly is because the mechanical injuries that intervene operation causes blood vessel wall (mainly being the endodermis damage) cause that endotheliocyte strips off and dysfunction in the blood vessel, cause the damage location long term exposure in blood environment, bring out autoimmune stress and inflammatory reaction, induce blood monocytes and tunica media smooth muscle cell to inner membrance migration and propagation, finally form restenosis.The restenosis problem has become main challenge and the research focus that vascular interventional treatment faces at present.
Vascular endothelial cell is the cell of a class function complexity, secretes the active substance of multiple adjusting vascular function, and active hematoblastic function adjusting, blood plasma coagulant factor activator, activated clotting factor removing and the fibrinolytic process of participating in is closely related with cardiovascular disease.Vander Giessen etc. has at first carried out the research of endovascular stent endothelialization.Part Study subsequently shows, the metal support surface endothelialization can prevent the formation of acute thrombus, reduce the incidence rate of thrombosis, and by the early stage local endothelium of repairing impaired tremulous pulse, suppress the hypertrophy and the migration of smooth muscle cell, the generation of prevention of restenosis, thereby may be a kind of comparatively ideal method.
Endothelialization research is more again for endovascular stent at present, and has studied support several key technologies of endothelialization more respectively: the source of (1) seed cell; (2) planting technology of cell; (3) screening is applicable to the adhering substrate of cell and endovascular stent.
In vitro study is often taken from bovine aortic with endotheliocyte, but in testing in vivo, for fear of the generation of rejection, carries out the optimum selection of cell seeding beyond doubt from the body endotheliocyte.In the experimentation, vascular endothelial cell is mainly taken from trunk in early days.But collect vascular endothelial cell from trunk certain danger is arranged, clinical practice is limited, collects vascular endothelial cell from superficial vein recently, takes from great saphenous vein or external jugular vein from body, often adopts trypsin or collagenase digesting to separate endotheliocyte.Require the operation of plantation endotheliocyte simple more clinically, the time is short more good more, therefore only depends on the former generation vascular endothelial cell that obtains from vena systemica, still can not satisfy the requirement of plantation.In order to obtain the endotheliocyte of sufficient amount, the vascular endothelial cell culture techniques of having set up fast, increased on a large scale such as nineteen ninety Zilla, its method be take from body superficial vein endotheliocyte carry out former be commissioned to train support after, with 1: ratio (30-40) is do the single cultivation of going down to posterity, about 3 weeks, cell quantity increases sharply surplus in the of 300 times, is enough to satisfy the needs of plantation.Along with to the going deep into of stem-cell research, people begin to separate and cultivate endotheliocyte from bone marrow.Shattacharya etc. utilize CD34
+Medullary cell can be divided into the characteristics of endotheliocyte, earlier with immunomagnetic bead technique enrichment CD34
+Medullary cell is planted on the graft then, with not the plantation compare, the area of endothelialization the former obviously greater than the latter.Because embryonic stem cell has the potential that is divided into any cell in the human body, stem cell especially adult stem cell investigative technique develops rapidly and is ripe, perhaps, the endothelial cell strain that utilizes cell clone technology and embryo stem cell for directional culture technique to set up essentially no immunogenicity can solve endotheliocyte and come source problem and have unrivaled advantage, is worth inquiring into.
The effect of support endothelialization depends on that endotheliocyte number, the adherence rate of cell, the attached cell of plantation are exposed to the retention rate behind the blood flow.Wherein how improving the adherence rate of endotheliocyte, is the problem that needs most solution at present.Cell sticking on material comprises two processes: attaching process and stick process.The attaching process is very fast, is some physics, chemical action between cell and the material, and is caused as Van der Waals force, ionic forces etc., mainly takes the method for rotating and culturing to make cell fully contact, attach with the endovascular stent surface at present.Sticking process and be by interactions such as material and some bioactive molecules such as extracellular matrix protein, epicyte protein, cytoskeletal proteins and cause, is very crucial process.Have only when cell and suitable the sticking of material generation, could on material, sprawl growth, and even break up, breed.Substrate at the short cell adhesion of endovascular stent surface-coated can increase adhesion and the growth of cell at rack surface.
It is that a kind of cell that utilizes is as the new technique that transmits the medicine platform that the endotheliocyte of genetic modification is inoculated on endovascular stent.So-called genetic modification is introduced exogenous gene exactly in target cell, to correct its genetic flaw or to strengthen certain gene and express.Studies show that the endotheliocyte of In vitro culture plantation is not enough to some extent in function aspects than growth endotheliocyte in the body.Developing rapidly of technique for gene engineering makes researcher to carry out genetic modification to endotheliocyte, strengthens its secrete cytokines and tactophily ability and anti-thrombus function.Compare with rack surface absorption or crosslinked growth factor protein or antithrombotic medicine, the sustainable expression destination protein of the exogenous gene that changes over to should have better effect.Mainly consider the selection of genes of interest at present from two aspects, a class is to promote endothelial cell proliferation such as VEGF, this type of somatomedin of FGF; Another kind of is to possess the gene that suppresses the smooth muscle cell proliferation effect, as eNOS, and genes such as wtP53.
Therefore, we can promote endothelial cell proliferation and can suppress smooth muscle cell proliferation gene transfection or common transfection endotheliocyte or stem cell respectively, the adhering substrate coating for preparing the endovascular stent surface again by the ultrasonic atomizatio spraying technology, the rotating and culturing of carrying out endovascular stent and transgenic cell then prepares cell coated, to improve the speed of endothelialization again on Stent after-poppet surface, finally reach the purpose that suppresses restenosis in the blood vessel.
Summary of the invention
Purpose of the present invention is exactly at the deficiencies in the prior art, provide a kind of and prevent and treat restenosis behind percutaneous transluminal coronary angioplasty (PTCA) back or the Stent, finally can reach endovascular stent that the transgenic cell of eliminating the effect of restenosis in the blood vessel covers and preparation method thereof by quickening the endotheliocyte reparation.
For achieving the above object, the present invention adopts following technical scheme:
The endovascular stent that a kind of transgenic cell covers, it has bare metal stent, on described bare metal stent surface processing layer is arranged, and the adhering substrate coating is arranged on processing layer, have cell coatedly on the adhering substrate coating, cell coated is to obtain by the genes of interest stable transfected cells.
Described bare metal stent is stainless steel stent, recalled nitinol alloy stent, cobalt-base alloys support and degradable magnesium alloy bracket.
Described processing layer is the low temperature plasma coating, and its surface roughness is 5～15 μ m.
Described adhering substrate coating is a kind of in protein coating, the sequence peptide coating.
Described albumen is that gelatin, IV collagen type, poly-D-lysine, fibronectin etc. have one or more in the albumen that promotes the cell adhesion function.
Described sequence peptide is to have the sequence peptide that promotes the cell adhesion function, as RGD sequence peptide coating.
Described cell is endotheliocyte or has stem cell to the endotheliocyte differentiation potential.
The preparation method of the endovascular stent that above-mentioned transgenic cell covers may further comprise the steps:
A), obtain genes of interest, adopt extract genome again pcr amplification go out target gene fragment, or a kind of in obtaining by the amplification of RT-PCR method again of the RNA that extracts genes of interest;
B), the structure of the eukaryotic expression vector of genes of interest and amplification; The carrier for expression of eukaryon of described genes of interest is a kind of in adenovirus, the plasmid; Described adenovirus is the AdEasyTM adenovirus system, and described plasmid can be PcD2, PcDNA3.1 plasmid.
C), obtain cell, the cell of employing can be an endotheliocyte, also can be stem cell.Endotheliocyte can be obtained by digestion blood vessel endothelium layer, and stem cell can derive from bone marrow or peripheral blood, has the potential to the endothelium differentiation.
D), bare metal stent surface modification: adopt lower temperature plasma technology to used bare metal stent surface treatment, make the surface form the processing layer of 5～15 μ m roughness, more help the adhesion of adhering substrate coating and cell;
E), preparation adhering substrate coating
The method for preparing the adhering substrate coating is the ultrasonic atomizatio spraying process;
With albumen in the adhering substrate coating or peptide section solvent, be prepared into the solution of respective concentration; The support slewing rate remains on per minute 30-60 changes, and spray time is 0.5-2 minute, will be coated with to be placed in the vacuum drying oven 24-48 hour drying time, baking temperature 30-50 degree; Repeat spraying after the drying, number of repetition 2-3 time, each spray time 0.5-1 minute, the control coating surface roughness was in the 2-5 nanometer, and thickness is about 5～15 microns;
F), rotating and culturing prepares the endovascular stent that transgenic cell covers:
Preparing cell coated method is rotary culturing;
Endovascular stent is fixed in the rotating and culturing pipe, changes with the transgenic cell corotation and cultivate.The transgenic cell inoculum density is 1 * 10
5Individual milliliter, rotary speed is 0.4 rpm, rotational time is 6 hours.After rotating and culturing is finished, take off support, static culture 24-48 hour again, finished product can be used for further research or detects.
The present invention is intended in advance at endovascular stent surface-coated one deck transgenic cell, strengthen the reparation and the inhibition smooth muscle cell proliferation of the blood vessel endothelium layer of damage on the one hand by the high level expression to genes of interest, the propagation by foreign cell reaches the purpose of quickening endovascular stent surface endothelialization on the other hand.The zoopery result is feasible, safe, effective, can effectively suppress the restenosis of metal rack or balloon injured.Apply closely between described metal rack coating and the metal rack, biocompatibility is good, finally reaches the purpose that suppresses the endovascular stent restenosis.
Description of drawings
Fig. 1 is the cross-sectional view that this transgenic endotheliocyte covers endovascular stent;
Fig. 2 is the optical microscope picture (* 400) that the transgenic endotheliocyte covers endovascular stent.
Fig. 3 is the scanning electron microscope picture (* 100) that the transgenic endotheliocyte covers endovascular stent.
Fig. 4 is the immunofluorescence dyeing picture (* 200) that the transgenic endotheliocyte covers endovascular stent.
Fig. 5 is that the transgenic endotheliocyte covers the situation of endothelialization again (* 50) that endovascular stent is implanted one week of rabbit ventral aorta back scanning electron microscopic observation rack surface.
The specific embodiment
The present invention is further illustrated below in conjunction with accompanying drawing, but therefore do not limit the present invention among the described scope of embodiments:
Referring to Fig. 1: the endovascular stent that this transgenic cell covers is to establish processing layer 1 in the metal surface of traditional bare metal stent 4, on processing layer 1, establish adhering substrate coating 2, establishing cell coated 3, cell coated 3 on the adhering substrate coating is to obtain by the genes of interest stable transfected cells.
Wherein, processing layer 1 is the low temperature plasma coating, and its surface roughness is 5～15 μ m.Adhering substrate coating 2 is a kind of in protein coating, the sequence peptide coating.Albumen is that gelatin, IV collagen type, poly-D-lysine, fibronectin etc. have one or more in the albumen that promotes the cell adhesion function.The sequence peptide is to have the sequence peptide that promotes the cell adhesion function, as RGD sequence peptide coating.Cell coated cell is the endotheliocyte of genes of interest stable transfection or has stem cell to the endotheliocyte differentiation potential.
The endovascular stent that above-mentioned transgenic cell covers prepares according to the following steps:
1. obtain genes of interest VEGF
121
Genes of interest VEGF
121Adopt the reverse transcription method to obtain: human leukemia cell (HL-60), with the total RNA of the conventional extraction of TRIZOL, synthetic cDNA carries out the PCR reaction through reverse transcription.Get cDNA reactant liquor 2 μ l, use VEGF
121Forward primer be 5 ' GGGGGATCCGCCTCCGAAACCATGAACTT 3 ', downstream primer is 5 ' CCCGAATTCTCCTGGTGAGAGATCTGGTT3 ', the design BamH I and EcoR I restriction enzyme site are arranged, increase by PCR.The PCR condition is 95 ℃ of pre-degeneration 5 minutes, 94 ℃ 45 seconds, 55 ℃ 40 seconds, 72 ℃ 1 minute, after 36 circulations, 72 ℃ are continued reaction 5 minutes, the PCR product separates through agarose gel electrophoresis, DNA glue reclaims purification kit and reclaims purification, obtains VEGF
121(molecular weight is 550bp) genetic fragment.
2. with the plasmid vector construction eukaryotic expression vector
With PcD2.0 is carrier, reorganization PcD2.0-VEGF
121Eukaryon expression plasmid; Use the genes of interest VEGF of EcoR I, HinDIII double digestion PcD2.0 carrier and purification
121, spend the night with 4 ℃ of connections of T4DNA ligase, connect product and transform DH5 α competent cell respectively, ice bath 30 minutes is put 42 ℃ of water-baths 90 seconds, and ice bath is 1 minute again.Add LB culture fluid 0.8ml then, jolting is 1 hour on 37 ℃ of shaking tables, is inoculated in penbritin after centrifugal and selects in the culture plate, cultivates 16 hours down for 37 ℃.The picking bacterial clone is inoculated in penbritin and selects in the culture fluid, puts 37 ℃ of joltings and cultivates amplification.Get 5ml bacterium liquid, with plasmid DNA a small amount of extraction agent box extracting plasmid, after determined dna sequence and enzyme action were identified, obtaining molecular weight was 5.6kb recombiant plasmid PcD2.0-VEGF after cultivating
121, repeat with aseptic being stored in the nuclease free water behind the test kit extracting plasmid, through UV spectrophotometer measuring, the OD260/OD280 value is 1.8, its purity reaches the transfection requirement, places-20 ℃, and is standby.
3. the cultivation of endotheliocyte, evaluation and stable transfection
The HUVEC (Human umbilical vein endothelial cells system) that cultivates that goes down to posterity carries out VEGF after the evaluation of form, surface antigen and function
121Stable transfection experiment.Carry out transfection with cationic-liposome 2000, experimental result is identified by RT-PCR and immunocytochemistry.
4. metal support surface modification forms low-temperature plasma processing layer 1 on the surface;
Adopt lower temperature plasma technology, plating or other chemical methodes that the used metal support surface of the present invention is handled, be beneficial to the tight coating of coating.The present invention adopts lower temperature plasma technology to carry out the surface modification of metal rack.
The surface modification of support is performed such: the device of employing is the dc source reaction system of a clock-type.Plasma generator is to order about power supply by the MDX-1K magnetron to provide.(25.4 * 25.4 * 0.16cm) constitute two anodes to the corrosion resistant plate of two parallel placements, and magnetron is placed in apart from two plate 15.5cm places.An iron hoop (external diameter 17.5cm, internal diameter 13.8cm, thick 0.16cm) and the coaxial outside of 2 positive plates that is put in of an iron pan (diameter 5cm, thick 0.16cm) are as the magnetic field allotter.Article eight, the equidistant annular of permanent magnet is positioned on iron plate and the iron hoop, the center of south poles iron plate.The magnetic field intensity scope of every block of Magnet is 700-800 Gauss.Rustless steel and nick-eltitanium alloy stent are positioned between two parallel anodes as the negative electrode of plasma reaction system.
Disinfectant metal rack is put in the plasma reactor as its negative electrode.With vacuum pump reative cell is evacuated to earlier and is lower than 1 millitorr.Because the type difference of process, can be a monomer or admixture of gas enters reative cell, the present invention is with TMS (trimethyl silane) and O
2(oxygen) is reacting gas.The MKS flow instrument is used to write down and measure the monomer that enters or the flow velocity of mist, controls the pressure of the gas that enters reative cell with pressure controller.After treating that system pressure is stable at 25 millitorrs, start time (2-5 minute) back acquisition low temperature plasma coating 1 on metal rack that dc source continues to predesignate, behind the EO, remaining gas is discharged from, and system pressure recovers.The vacuum state of reactor disappears, and can take out support to be used for further experiment this moment.
5. prepare adhering substrate coating 2
The method for preparing adhering substrate coating 2 is the ultrasonic atomizatio spraying process.Gelatin, poly-D-lysine and water at room temperature 25-35 ℃, are fully mixed, and the preparation gelatin concentration is the 2-6 mg/ml, and poly-D-lysine is the solution of 10 mcg/ml.The support slewing rate remains on per minute 30-60 changes, and spray time is 0.5-2 minute, will be coated with to be placed in the vacuum drying oven 24-48 hour drying time, baking temperature 30-40 degree.
6. rotating and culturing prepares endovascular stent
Endovascular stent is fixed in the rotating and culturing pipe, changes with transgenic endotheliocyte corotation and cultivate.Transgenic endotheliocyte inoculum density is 1 * 10
5Individual/milliliter, rotary speed is 0.4 rpm, and rotational time is 6 hours.After rotating and culturing is finished, take off support, static culture 24-48 hour again, under optical microscope, to observe, cell adheres to the growth (see figure 2) at rack surface.And detect by scanning electron microscope, the cell quantity of endovascular stent surface adhesion is many and sprawl even (see figure 3) after the rotating and culturing, and immunofluorescence detects finds that the adherent cell of rack surface can well express the vWF factor (see figure 4) of representing the endotheliocyte characteristic.
7. zoopery
Adopt standard ball ductus bursae technology, support of the present invention and crt bracket are implanted the rabbit ventral aorta, endovascular stent group and bare bracket, glutin coating bracket matched group sample size that the transgenic endotheliocyte covers are 10.2 of 1 week back execution, remaining puts to death 4 respectively at the back of performing the operation after 4 weeks, and 4 of remainders are put to death in 12 all backs.Lesion support in the animal body of putting to death is taken out together with blood vessel, make the scanning electron microscopic observation sample, observe the degree of endothelialization again on endovascular stent surface; Make the transmission electron microscope observing sample, determine to be covered in the cell component of rack surface inner membrance; Make pathological section, observe the extent of restenosis of support and the thickness of hypertrophy inner membrance.
The zoopery result proves gene stent safety, effective.The result shows, compare with matched group, cytoskeleton surface endodermis covers complete (see figure 5) once week the time, and bare bracket surface endothelium is torn fully, smooth muscle exposes, and endothelialization again takes place few part, and rack surface has thrombosis, protein coating rack surface endothelialization is imperfect, and a large amount of hemocytees and platelet aggregation are arranged.Illustrate that the endovascular stent that the transgenic endotheliocyte covers can significantly improve endovascular stent surface endothelialization speed, has the effect of antithrombotic and anti-restenosis.
Claims (10)
1, a kind of endovascular stent of transgenic cell covering, it is a matrix with bare metal stent (4), in the metal surface of described bare metal stent (4) processing layer (1) is arranged, adhering substrate coating (2) is arranged on processing layer (1), cell coated (3) are arranged on the adhering substrate coating, cell coated (3) are to obtain by the genes of interest stable transfected cells, it is characterized by:
Described bare metal stent (4) is stainless steel stent, recalled nitinol alloy stent, cobalt-base alloys support or degradable magnesium alloy bracket;
Described processing layer (1) is the low temperature plasma coating, and its surface roughness is 5～15 μ m;
Described adhering substrate coating (2) is a kind of in protein coating, the sequence peptide coating;
Described cell on cell coated is the endotheliocyte of genes of interest stable transfection or has stem cell to the endotheliocyte differentiation potential.
2, the endovascular stent that covers of transgenic cell according to claim 1 is characterized by: the albumen in the described protein coating is to have a kind of in the gelatin that promotes the cell adhesion function, IV collagen type, poly-D-lysine, the fibronectin.
3, the endovascular stent of transgenic cell covering according to claim 1 is characterized by: the peptide section in the described sequence peptide coating is to have the peptide section that promotes the cell adhesion function.
4, the endovascular stent of transgenic cell covering according to claim 3, it is characterized by: described sequence peptide coating is RGD peptide or other sequence peptide coatings.
5, a kind of method for preparing the endovascular stent of the described transgenic cell covering of claim 1 is characterized in that this may further comprise the steps:
1), obtains genes of interest;
2), the structure of the eukaryotic expression vector of genes of interest and amplification;
3), obtain cell: the cell of employing is endotheliocyte or stem cell;
4), bare metal stent (4) is carried out surface modification, acquisition processing layer (1);
5), go up preparation adhering substrate coating (2) at processing layer (1);
6), prepare transgenic cell coating (3), the endovascular stent of covering in adhering substrate coating (2) by rotating and culturing.
6, preparation method according to claim 5 is characterized in that, described genes of interest employing extraction genome pcr amplification again goes out target gene fragment, or the RNA of extraction genes of interest obtains by the amplification of RT-PCR method again; The carrier for expression of eukaryon of genes of interest is a kind of in adenovirus, the plasmid.
7, preparation method according to claim 6 is characterized in that, described adenovirus is the AdEasyTM adenovirus system, and described plasmid is PcD2 or PcDNA3.1 eukaryon expression plasmid.
8, preparation method according to claim 5 is characterized in that, described bare metal stent surface modification adopts lower temperature plasma technology to used bare metal stent surface treatment, makes the surface form the processing layer (1) of 5～15 μ m roughness.
9, preparation method according to claim 5 is characterized in that, adopts the ultrasonic atomizatio spraying process to prepare described adhering substrate coating (2):
Albumen in the adhering substrate coating or sequence peptide are prepared into solution with solvent;
The support slewing rate remains on per minute 30-60 changes, and spray time is 0.5-2 minute, adhering substrate is coated be placed in the vacuum drying oven 24-48 hour drying time, baking temperature 30-40 degree;
Repeat spraying after the drying, number of repetition 2-3 time, each spray time 0.5-1 minute, control adhering substrate coating surface roughness was in the 2-5 nanometer, and thickness is 5～15 microns.
10, preparation method according to claim 5 is characterized in that, prepares cell coated (3) by rotary culturing, and endovascular stent is fixed in the rotating and culturing pipe, changes with the transgenic cell corotation and cultivates; The transgenic cell inoculum density is 1 * 10
5Individual/milliliter, rotary speed is 0.4 rpm, and rotational time is 6 hours; After rotating and culturing is finished, take off support, static culture 24-48 hour again, get finished product.
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| CN102416203A (en) * | 2011-11-29 | 2012-04-18 | 北京中孵友信医药科技股份有限公司 | RNA interference blood vessel stent coating material with local antiplatelet effect and local anticoagulation blood vessel stent prepared therefrom |
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| CN105339017A (en) * | 2013-05-02 | 2016-02-17 | 奥齿泰有限责任公司 | Method for treating surface of implant |
| CN110404121A (en) * | 2019-06-27 | 2019-11-05 | 英诺激光科技股份有限公司 | Innovative method for performing surface modification on degradable support by using laser |
| CN112617949A (en) * | 2020-12-31 | 2021-04-09 | 微创神通医疗科技（上海）有限公司 | Spring ring and preparation method thereof |
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| CN102693817A (en) * | 2011-11-23 | 2012-09-26 | 横店集团东磁股份有限公司 | High-performance bonded magnet processed by low-temperature plasma and preparation method thereof |
| CN102693817B (en) * | 2011-11-23 | 2015-06-17 | 横店集团东磁股份有限公司 | High-performance bonded magnet processed by low-temperature plasma and preparation method thereof |
| CN102416203A (en) * | 2011-11-29 | 2012-04-18 | 北京中孵友信医药科技股份有限公司 | RNA interference blood vessel stent coating material with local antiplatelet effect and local anticoagulation blood vessel stent prepared therefrom |
| CN102416203B (en) * | 2011-11-29 | 2013-10-23 | 北京中孵友信医药科技股份有限公司 | RNA interference blood vessel stent coating material with local antiplatelet effect and local anticoagulation blood vessel stent prepared therefrom |
| CN105339017A (en) * | 2013-05-02 | 2016-02-17 | 奥齿泰有限责任公司 | Method for treating surface of implant |
| CN110404121A (en) * | 2019-06-27 | 2019-11-05 | 英诺激光科技股份有限公司 | Innovative method for performing surface modification on degradable support by using laser |
| CN112617949A (en) * | 2020-12-31 | 2021-04-09 | 微创神通医疗科技（上海）有限公司 | Spring ring and preparation method thereof |
| CN114588320A (en) * | 2022-01-25 | 2022-06-07 | 北京唐颐惠康生物医学技术有限公司 | Composite coating stent and preparation method thereof |
| CN114588320B (en) * | 2022-01-25 | 2023-01-13 | 北京唐颐惠康生物医学技术有限公司 | Composite coating stent and preparation method thereof |
| CN117752859A (en) * | 2023-12-22 | 2024-03-26 | 延边优联农业科技发展有限公司 | Stem cell climbing degradable stent and preparation method and application thereof |
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