CN102895702A - Composite artificial bile duct and preparation method thereof - Google Patents
Composite artificial bile duct and preparation method thereof Download PDFInfo
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- CN102895702A CN102895702A CN2012104476164A CN201210447616A CN102895702A CN 102895702 A CN102895702 A CN 102895702A CN 2012104476164 A CN2012104476164 A CN 2012104476164A CN 201210447616 A CN201210447616 A CN 201210447616A CN 102895702 A CN102895702 A CN 102895702A
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Abstract
The invention discloses a composite artificial bile duct which is a tubular acellular matrix with degradable high-molecular polymer materials coated on the inner and outer surfaces, wherein 2-20 mg of the degradable high-molecular polymer materials are uniformly distributed on each square centimeter of the inner surface of the acellular matrix, and 0-20 mg of the degradable high-molecular polymer materials are uniformly distributed on each square centimeter of the outer surface of the acellular matrix. The artificial bile duct has low immunogenicity, good in-vivo repair effect and good clinical application prospect.
Description
Technical field
The present invention relates to a kind of combined artificial bile duct and preparation method thereof.
Background technology
Extrahepatic bile ducts is the descending unique passage of bile, clinically, in the disease such as tumor of bile duct, bile duct injury, bile duct congenital malformation and the liver transplantation treatment, usually adopts gallbladder intestinal anastomosis operation.This operation can be dredged biliary tract, but operation has changed the normal physiological routes of biliary tract, can make the forfeiture of Oddi sphincter function, and the complication such as retrograde infection, anastomotic stricture easily occur postoperative.Therefore, the R and D that can be used for the artificial choledochus of clinical treatment have very important realistic meaning.
At present, the material category that is used for the manufacturing artificial bile duct is a lot of, according to the degradability of material, can be divided into Nondegradable material and degradable materials two large classes.
Comparatively common non-degradable material is the material of the inanimate object activity of synthetic, and silicone rubber, polyurethane, fluorubber, politef etc. are arranged.Application number: 200810033513.7, denomination of invention: the Patent Application Publication of " plug-in type inside and outside wall dual structure politef artificial choledochus and preparation thereof " a kind of preparation method of plug-in type outer wall dual structure politef artificial choledochus, this artificial choledochus adopts two-layer macromolecular material to be composited, internal layer is teflon hose, and outer is that chemical fibre forms with the knitting braiding.Application number: 200710170515.6, denomination of invention: the Patent Application Publication of " a kind of politef/fluorubber combined artificial bile duct and preparation method thereof " a kind of artificial choledochus, this artificial choledochus is a kind of composite and flexible tube, be followed successively by from inside to outside polytetrafluoroethylene film inner bag basic unit, naphthalene-sodium-tetrahydrofuran solution processing layer and fluorubber cast layer.Non-degradable material non-degradable and mechanical property and normal group are woven with larger difference, can't grow and tissue reconstruction by sustenticular cell, can only use as the bile duct substitute of short-term, can not be used in the body for a long time.
Biodegradable material can be degraded in tissue repair, generates the small-molecule substance of inanimate object toxicity, and excretes with cellular metabolism, for the research and development of artificial choledochus open up a new way.Common degradable material has the macromolecule polymer material of synthetic, as, polycaprolactone also has natural material, such as chitin, chitosan and natural acellular matrix.The degradation material of synthetic has good degradability, but can't grow and tissue reconstruction by sustenticular cell, and repairing effect is good not in the body.Natural acellular matrix material has good degradability and biocompatibility, but and contain the cytokine of Promote cell's growth and tissue repair, its research of using in organizational project has been subject to paying close attention to widely.
The people such as Rosen, " Rosen M; Ponsky J; Petras R; et al.Novel bile duct repairf0rbleed ing biliary anastomatic varices:case report and literature review ", JGastrointest Surg, 2005,9 (2): 832] using the enough biliary tracts of acellular matrix material-submucous layer of small intestine (Small intestinal submucosa, SIS) reparation commonly used succeeds.SIS implants after 5 months degradable, and by the bile duct tissue of regenerating is replaced, the proliferation of fibrous tissue reaction is extremely slight around the bile duct tissue of regeneration.But Gomez etc., " Comez NA; Zapafier JA, Vargas PE.Re: " Smallintestinal submucosa as a bioscafold for biliary tract regeneration ", Surgery; 2004; 135 (4): 460] its result of study is queried, think that SIS is used to repair bile duct wall defects, can produce seepage of bile and cause the tissue adhesion; the inflammation that strong immunoreation causes, and other complicated problems.According to applicant's research, use separately the bile duct acellular matrix to repair bile duct defect, also can produce seepage of bile and cause the tissue adhesion, biliary tract stenosis appears, and the inflammation that has strong immunoreation to cause, cause that finally laboratory animal is dead.
Summary of the invention
In order to address the above problem, the invention provides a kind of new combined artificial bile duct that is formed by synthetic material and natural material and preparation method thereof.
Combined artificial bile duct of the present invention, it is the tubulose acellular matrix that surfaces externally and internally is coated with the degradable high polymer material, wherein, every square centimeter of 2 ~ 20mg degradable high polymer material that evenly distributes on the acellular matrix inner surface, every square centimeter of 0 ~ 20mg degradable high polymer material that evenly distributes on the outer surface.
Described tubulose acellular matrix refers to be shaped as the acellular matrix of tubulose, such as pig, and the acellular matrix of the mammiferous bile duct such as monkey, urethra or blood vessel.
Preferably, every square centimeter of 2 ~ 20mg degradable high polymer material that evenly distributes on the acellular matrix outer surface.
Wherein, described artificial choledochus diameter everywhere is identical, is 4 ~ 13mm.
Preferably, described artificial choledochus is cylindrical, and diameter is 4 ~ 13mm; Perhaps be truncated cone-shaped, handle face diameter is 4 ~ 13mm, and large bottom surface diameter is at most than the large 2mm of handle face diameter.
Wherein, the long 10 ~ 150mm of described artificial choledochus, pipe thickness is 0.5 ~ 2mm.
Preferably, described degradable high polymer material is polyurethane or polyglycolic acid.
Preferably, the molecular weight of described polyurethane is 2 ~ 50,000 g/mol, and the molecular weight of described polyglycolic acid is 3 ~ 50,000 g/mol.
Polyurethane of the present invention is degradability polyurethane, can be according to the patent No.: ZL 200610022715.2, and denomination of invention: the method preparation of the patent record of " method for preparing aqueous nontoxic degradable polyurethane elastomer ".
The preparation method of the artificial bile duct of the present invention, it comprises the steps:
(1) gets tubulose acellular matrix and the degradable high polymer material of aforementioned proportioning;
(2) with the tubulose acellular matrix, be inserted in and be not stained with on the mould lyophilization;
The described grinding tool of not being stained with is cylindrical, and diameter is identical with the acellular matrix diameter; Perhaps be truncated cone-shaped, handle face diameter is identical with the acellular matrix diameter, and large bottom surface diameter is at most than the large 2mm of handle face diameter;
(3) get the degradable high polymer material, make the emulsion that concentration is 5 ~ 20wt%, the tubulose acellular matrix after coating step (2) is processed, 30 ~ 37 ℃ of dryings, sterilization gets final product.
Be not stained with mould, refer to and the NA mould of acellular matrix.
Wherein, the described degradable high polymer material of step (1) is polyurethane or polyglycolic acid.
Wherein, the molecular weight of described polyurethane is 2-5 ten thousand g/mol, and the molecular weight of described polyglycolic acid is 3-5 ten thousand g/mol.
Wherein, the described mould of not being stained with of step (2) adopts the tetrafluoroethene material to be prepared from.
Wherein, in the described step (3), the concentration of polyurethane solutions is 15wt%.
Wherein, in the described step (3), the temperature when dry is 37 ℃.
The immunogenicity of combined artificial bile duct of the present invention is low, and repairing effect is good in the body, can overcome the defective of Traditional Man bile duct, has good potential applicability in clinical practice.
Obviously, according to foregoing of the present invention, according to ordinary skill knowledge and the customary means of this area, not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite, can also make modification, replacement or the change of other various ways.
The specific embodiment of form is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
Description of drawings
Fig. 1 combined artificial biliary tract prosthesis cross sectional representation;
Fig. 2 combined artificial biliary tract prosthesis longitudinal section sketch map;
Fig. 3 is in the structure of 45 ° of C baking oven bakings combined artificial bile duct after 6 hours;
Fig. 4 is in the structure of 20 ° of C baking oven bakings combined artificial bile duct after 6 hours;
Fig. 5 is in the structure of 37 ° of C baking oven bakings combined artificial bile duct of the present invention after 6 hours;
Immunogenicity in the embedding test of Fig. 6 combined artificial biliary tract prosthesis muscle detects.A is the acellular matrix support; B is polyurethane; C is the artificial gallbladder pipe of the present invention;
Fig. 7 matched group is repaired the internal anatomy of bile duct defect;
Fig. 8 combined artificial bile duct of the present invention is implanted into Adult Pig in vivo test result.(A) the normal HE of bile duct tissue dyeing; (B) the combined artificial bile duct is repaired HE dyeing after 90 days.
The specific embodiment
Experiment material:
Polyurethane, according to the patent No.: ZL 200610022715.2, denomination of invention: the method preparation of the patent record of " method for preparing aqueous nontoxic degradable polyurethane elastomer ".
Polyglycolic acid is available from Aldrich.
Embodiment 1 preparation combined artificial bile duct of the present invention
1, the preparation of tubulose acellular matrix:
Get an Adult Pig bile duct, reject bile duct lumen organization fat and connective tissue on every side, cutting into length is the long pipeline of 30mm, diameter 4mm, thick 1mm;
Pipeline stirring and washing 2 hours in PBS liquid, soaking and stirring is 24 hours in 1%SDS solution;
Take out PBS and cleaned after 2 hours in 1%Triton-100 solution soaking and stirring 24 hours;
The support that takes off behind the cell cleaned in PBS 2 hours, and being fixed on outside diameter is that 6mm, end diameter are on the teflon rod of 4mm, obtained dry acellular matrix support after the lyophilization.
2, to apply concentration be the aqueous emulsion of polyurethane of 5wt% at the cytoskeleton inner surface that takes off of drying, and the control valve wall thickness is 0.5mm, 30 ℃ of dry 72h, pack, γ ray sterilization namely obtains combined artificial bile duct of the present invention, can be used for repairing the less pathological changes bile duct of diameter.
Embodiment 2 preparations combined artificial bile duct of the present invention
1, the preparation of tubulose acellular matrix:
Get an Adult Pig bile duct, reject bile duct lumen organization fat and connective tissue on every side, cutting into length is the long pipeline of 10mm, diameter 6mm, thick 2mm;
Pipeline stirring and washing 2 hours in PBS liquid, soaking and stirring is 24 hours in 1%SDS solution;
Take out PBS and cleaned after 2 hours in 1%Triton-100 solution soaking and stirring 24 hours;
The support that takes off behind the cell cleaned in PBS 2 hours, and being fixed on outside diameter is that 8mm, end diameter are on the teflon rod of 6mm, obtained dry acellular matrix support after the lyophilization.
2, to apply concentration be the aqueous emulsion of polyurethane of 15wt% at the cytoskeleton inner surface that takes off of drying, and the control valve wall thickness is 1mm, 37 ℃ of dry 24h, pack, γ ray sterilization namely obtains combined artificial bile duct of the present invention, can be used for substituting the pathological changes bile duct of intermediate diameters.
Embodiment 3 preparations combined artificial bile duct of the present invention
1, the preparation of tubulose acellular matrix:
Get an Adult Pig bile duct, reject bile duct lumen organization fat and connective tissue on every side, cutting into length is the long pipeline of 10mm, diameter 6mm, thick 2mm;
Pipeline stirring and washing 2 hours in PBS liquid, soaking and stirring is 24 hours in 1%SDS solution;
Take out PBS and cleaned after 2 hours in 1%Triton-100 solution soaking and stirring 24 hours;
The support that takes off behind the cell cleaned in PBS 2 hours, and being fixed on diameter is on the cylindrical teflon rod of 6mm, obtained dry acellular matrix support after the lyophilization.
2, to apply concentration be the aqueous emulsion of polyurethane of 15wt% at the cytoskeleton inner surface that takes off of drying, and the control valve wall thickness is 1mm, 37 ℃ of dry 24h, pack, γ ray sterilization namely obtains combined artificial bile duct of the present invention, can be used for substituting the pathological changes bile duct of intermediate diameters.
Embodiment 4 preparations combined artificial bile duct of the present invention
1, the preparation of tubulose acellular matrix:
Get an Adult Pig bile duct, reject bile duct lumen organization fat and connective tissue on every side, cut into the pipeline that length is 150 millimeters long, diameter 13mm, thick 2mm;
Pipeline stirring and washing 2 hours in PBS liquid, soaking and stirring is 24 hours in 1%SDS solution;
Take out PBS and cleaned after 2 hours in 1%Triton-100 solution soaking and stirring 24 hours;
The support that takes off behind the cell cleaned in PBS 2 hours, and being fixed on outside diameter is that 15mm, end diameter are on the teflon rod of 13mm, obtained dry acellular matrix support after the lyophilization.
2, to apply concentration be the polyglycolic acid aqueous emulsion of 20wt% at the cytoskeleton inner surface that takes off of drying, and the control valve wall thickness is 2mm, 35 ℃ of dry 48h, pack, γ ray sterilization namely obtains combined artificial bile duct of the present invention, can be used for substituting larger-diameter pathological changes bile duct.
Embodiment 5 preparations combined artificial bile duct of the present invention
1, the preparation of tubulose acellular matrix:
Get an Adult Pig bile duct, reject bile duct lumen organization fat and connective tissue on every side, cut into the pipeline that length is 100 millimeters long, diameter 8mm, thick 2mm;
Pipeline stirring and washing 2 hours in PBS liquid, soaking and stirring is 24 hours in 1%SDS solution;
Take out PBS and cleaned after 2 hours in 1%Triton-100 solution soaking and stirring 24 hours;
The support that takes off behind the cell cleaned in PBS 2 hours, and being fixed on outside diameter is that 10mm, end diameter are on the teflon rod of 8mm, obtained dry acellular matrix support after the lyophilization.
2, to apply concentration be the aqueous emulsion of polyurethane of 12wt% at take off cytoskeleton inner surface and the outer surface of drying, and the control valve wall thickness is 2mm, 37 ℃ of dry 24h, pack, γ ray sterilization namely obtains combined artificial bile duct of the present invention, can be used for substituting the pathological changes bile duct of intermediate diameters.
Embodiment 6 temperature screening experiment
1, experimental technique
(1) preparation of tubulose acellular matrix:
Get an Adult Pig bile duct, reject bile duct lumen organization fat and connective tissue on every side, cut into the pipeline that length is 100 millimeters long, diameter 6mm, thick 1.5mm;
Pipeline stirring and washing 2 hours in PBS liquid, soaking and stirring is 24 hours in 1%SDS solution;
Take out PBS and cleaned after 2 hours in 1%Triton-100 solution soaking and stirring 24 hours;
The support that takes off behind the cell cleaned in PBS 2 hours, and being fixed on outside diameter is that 8mm, end diameter are on the teflon rod of 6mm, obtained dry acellular matrix support after the lyophilization.
(2) to apply concentration be the aqueous emulsion of polyurethane of 12wt% at the cytoskeleton inner surface that takes off of drying, and the control valve wall thickness is 1mm, at 20 ℃, 37 ℃ and 45 ℃ of dry 48h, packs respectively, and γ ray sterilization namely obtains the combined artificial bile duct.
2, experimental result
Result such as Fig. 3 ~ shown in Figure 5, when temperature is 45 ℃, excess Temperature, supporting structure is destroyed; When temperature was 20 ℃, temperature was excessively low, and the part is thicker, and polyurethane is inhomogeneous at the porous support face coat; When temperature was 37 ℃, temperature was suitable, and polyurethane forms uniform coating at lumen wall, and supporting structure is complete.
Description of test, excess Temperature or the excessively low acellular matrix that all can not obtain to have applied even degradable high polymer material, many experiments is found, only in the scope of 30 ~ 37 ℃ of temperature, just can obtain the artificial bile duct of the present invention---applied the acellular matrix of even degradable high polymer material.
Below in the mode of experimental example beneficial effect of the present invention is described:
The immunogenicity of experimental example 1 combined artificial bile duct of the present invention detects
1, experimental technique
With the diameter 8mm of the embodiment of the invention 2 preparations, thick 2mm acellular matrix support and artificial choledochus, and the polyurethane timbering material is embedded in spinal column both sides, the adult rabbits back latissimus dorsi m. of the about 2.5kg of body weight.Before the operation beginning, every laboratory animal is injected 400,000 unit penicillins, and the chloral hydrate of back part of animal operative site preserved skin pneumoretroperitoneum injection 3ml/kg is anaesthetized.Cut the 8-10cm longitudinal incision at back part of animal, behind spinal column two lateral incision muscle peplos, expose muscle of back, cut off the 1cm osculum in the embedded material position, with smooth the inserting wherein of timbering material.Then, 5-0 absorbable suture interrupted suture is inserted in the rearing-box after animal revives and is raised, and close observation animal state.First, second and third day injected 400,000 unit penicillins for every rabbit after material was implanted.In postoperative the 7th day, laboratory animal lumbar injection pentobarbital sodium inj (100mg/kg) is put to death.Dissect to take out and transplant specimen and perienchyma, specimens paraffin embedding slices is carried out HE dyeing, and specimen is transplanted in observation and rabbit normal structure contact site inflammatory cell is assembled situation.
2, experimental result
Experimental result as shown in Figure 6, acellular matrix material and muscular tissue contact site have a large amount of inflammatory cells to assemble; Can only observe the inflammatory cell of minute quantity on the polyurethane timbering material; The gathering of inflammatory cell is also arranged on the combined artificial biliary tract prosthesis of the present invention, but cell quantity is less.
The immunogenicity of the artificial bile duct of experimental result explanation the present invention is low, and is suitable with the polyurethane porous support, significantly is lower than acellular matrix.
Reparative experiment in the experimental example 2 combined artificial bile duct bodies of the present invention
1, experimental technique
Select the Neijiang Pig of local closed colony, front 2.5% pentobarbital sodium of art (1ml/kg) intravenous anesthesia.Free common bile duct locates to cut about 1cm common bile duct apart from about duodenum upper limb 1cm, insert the combined artificial bile duct of the embodiment of the invention 2 preparations, 5-0 absorbable suture interrupted suture, needle gage 1.5mm, back gauge 1.5mm.Check that anastomotic stoma has or not seepage of bile, infusion 0.9% normal saline 500ml adds gentamycin 160,000 U in the art.The fasting of postoperative animal on the same day, vein replenishes 10% liquid of glucose and 5% sugar-salt-water, and second day after operation begins feed stream juice or semifluid diet, and is transitioned into gradually normal diet.
In 90 days laboratory animal is implemented the anesthesia of intraperitoneal pentobarbital sodium after transplanting, dissect to take out and transplant specimen and perienchyma, fix with 10% formaldehyde, carry out HE dyeing.
Matched group: free common bile duct, apart from about duodenum upper limb 1cm, locate to cut about 1cm common bile duct, insert the acellular matrix support of embodiment 2 preparations of having sterilized, 5-0 absorbable suture interrupted suture, needle gage 1.5mm, back gauge 1.5mm.Check that anastomotic stoma has or not seepage of bile, infusion 0.9% normal saline 500ml adds gentamycin 160,000 U in the art.The fasting of postoperative animal on the same day, vein replenishes 10% liquid of glucose and 5% sugar-salt-water, and second day after operation begins feed stream juice or semifluid diet, and is transitioned into gradually normal diet.
2, experimental result
As shown in Figure 7, seepage of bile appears in matched group, causes the surrounding tissue adhesion, biliary tract stenosis occurs, and is dead after 7 days.
The experimental group animal progressively recovers normally, gallbladder does not occur after the experiment leak, and biliary tract stenosis do not occur, and the injury region bile duct is progressively repaired.After transplanting in the experimental result of HE dyeing in 90 days as shown in Figure 8, with normal bile duct tissue contrast as can be known, the artificial bile duct of the present invention is repaired after the bile duct defect, the artificial choledochus support is degraded, the bile duct cell epimatrix forms, and repairs still and is continuing.
Experimental result explanation, the effect that the artificial bile duct of the present invention is repaired bile duct wall defects is good, the side effect such as tissue adhesion that seepage of bile causes and biliary tract stenosis can not occur.
Combined artificial bile duct immunogenicity of the present invention is low, is used for bile duct defect and the side effect such as seepage of bile and biliary tract stenosis can occur, and the effect of repairing bile duct defect in the body is good, and potential applicability in clinical practice is good.
Claims (12)
1. combined artificial bile duct, it is characterized in that: it is the tubulose acellular matrix that surfaces externally and internally is coated with the degradable high polymer material, wherein, every square centimeter of 2 ~ 20mg degradable high polymer material that evenly distributes on the acellular matrix inner surface, every square centimeter of 0 ~ 20mg degradable high polymer material that evenly distributes on the outer surface.
2. artificial choledochus according to claim 1 is characterized in that: every square centimeter of 2 ~ 20mg degradable high polymer material that evenly distributes on the acellular matrix outer surface.
3. according to claim 1 or 2 described artificial choledochus, it is characterized in that: described artificial choledochus is cylindrical, and diameter is 4 ~ 13mm; Perhaps be truncated cone-shaped, handle face diameter is 4 ~ 13mm, and large bottom surface diameter is at most than the large 2mm of handle face diameter.
4. the described artificial choledochus of any one according to claim 1 ~ 3 is characterized in that: the long 10 ~ 150mm of described artificial choledochus, pipe thickness is 0.5 ~ 2mm.
5. artificial choledochus according to claim 1, it is characterized in that: described degradable high polymer material is polyurethane or polyglycolic acid.
6. artificial choledochus according to claim 5, it is characterized in that: the molecular weight of described polyurethane is 2 ~ 50,000 g/mol, the molecular weight of described polyglycolic acid is 3 ~ 50,000 g/mol.
7. method for preparing the described artificial choledochus of claim 1 ~ 6 any one, it is characterized in that: it comprises the steps:
(1) gets tubulose acellular matrix and degradable high polymer material according to claim 1 or 2 described proportionings;
(2) with the tubulose acellular matrix, be inserted in and be not stained with on the mould lyophilization;
The described grinding tool of not being stained with is cylindrical, and diameter is identical with the acellular matrix diameter; Perhaps be truncated cone-shaped, handle face diameter is identical with the acellular matrix diameter, and large bottom surface diameter is at most than the large 2mm of handle face diameter;
(3) get the degradable high polymer material, make the emulsion that concentration is 5 ~ 20wt%, the tubulose acellular matrix after coating step (2) is processed, 30 ~ 37 ℃ of dryings, sterilization gets final product.
8. method according to claim 7, it is characterized in that: the described degradable high polymer material of step (1) is polyurethane or polyglycolic acid.
9. method according to claim 8, it is characterized in that: the molecular weight of described polyurethane is 2-5 ten thousand g/mol, the molecular weight of described polyglycolic acid is 3-5 ten thousand g/mol.
10. method according to claim 7 is characterized in that: the described mould of not being stained with of step (2) adopts the tetrafluoroethene material to be prepared from.
11. method according to claim 7 is characterized in that: in the described step (3), the concentration of emulsion is 15wt%.
12. method according to claim 7 is characterized in that: in the described step (3), the temperature when dry is 37 ℃.
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| CN104473706A (en) * | 2014-12-09 | 2015-04-01 | 金华市人民医院 | Biodegradable composite type tubular urethral stent and preparation method |
| CN105012050A (en) * | 2015-07-16 | 2015-11-04 | 清华大学 | Method and special mould for preparing tissue and organ precursor with multi-branch channels |
| CN105999405A (en) * | 2016-05-19 | 2016-10-12 | 李世荣 | Absorbable fundal mesh composite and preparation method thereof |
| CN106075582A (en) * | 2016-06-27 | 2016-11-09 | 暨南大学 | A kind of engineering blood vessel support and construction method thereof |
| CN108721697A (en) * | 2018-07-24 | 2018-11-02 | 中国人民解放军总医院 | A kind of modification of surface recombination 3D printing chitosan takes off cellular vascular holder and preparation method thereof |
| CN113144286A (en) * | 2021-04-21 | 2021-07-23 | 四川大学华西医院 | Degradable self-supporting artificial bile duct and preparation method thereof |
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| CN104473706A (en) * | 2014-12-09 | 2015-04-01 | 金华市人民医院 | Biodegradable composite type tubular urethral stent and preparation method |
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| CN106075582A (en) * | 2016-06-27 | 2016-11-09 | 暨南大学 | A kind of engineering blood vessel support and construction method thereof |
| CN108721697A (en) * | 2018-07-24 | 2018-11-02 | 中国人民解放军总医院 | A kind of modification of surface recombination 3D printing chitosan takes off cellular vascular holder and preparation method thereof |
| CN108721697B (en) * | 2018-07-24 | 2020-10-13 | 中国人民解放军总医院 | Modified acellular vascular stent with surface compounded with 3D printed chitosan and preparation method thereof |
| CN113144286A (en) * | 2021-04-21 | 2021-07-23 | 四川大学华西医院 | Degradable self-supporting artificial bile duct and preparation method thereof |
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