CN102641161A - Composite structure artificial blood vessel and dynamic preparation method thereof - Google Patents
Composite structure artificial blood vessel and dynamic preparation method thereof Download PDFInfo
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- CN102641161A CN102641161A CN2012101210915A CN201210121091A CN102641161A CN 102641161 A CN102641161 A CN 102641161A CN 2012101210915 A CN2012101210915 A CN 2012101210915A CN 201210121091 A CN201210121091 A CN 201210121091A CN 102641161 A CN102641161 A CN 102641161A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
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Abstract
The invention relates to a composite structure artificial blood vessel and a dynamic preparation method of the composite structure artificial blood vessel. The artificial blood vessel comprises a woven tube blank (1) and a nano-cellulose coating (9). The preparation method comprises the steps of preparing the tube blank (1) by knitting, weaving, braiding or non-weaving (such as spun-lacing) technology; placing the tube blank in a bacterial cellulose (BC) bio-reactor; passing a stent (2) through the tube blank, with a clearance reserved therebetween; sterilizing at high temperature; adding sterile fermentation culture medium into the reactor; inoculating BC-producing strain seed liquid; and dynamically culturing, coating a layer of nano-cellulose film on inner and outer surfaces of the tube blank. The blood vessel has the advantages of good axial/radial stretching ability, thin wall thickness satisfying requirement of small-caliber blood vessel, good vessel wall sealability, and no need for pre-coagulation. The preparation method provided by invention has the advantages of simple preparation method, and good bio-compatibility and biomechanical performance of the BC nano-coating layer.
Description
Technical field
The invention belongs to artificial blood vessel and preparation field thereof, particularly a kind of composite construction artificial blood vessel and dynamic system Preparation Method thereof.
Background technology
The heavy caliber blood vessel graft has obtained effect preferably in clinical practice at present, but common small-bore artificial blood vessel does not almost have antithrombotic.
The Intellectual Property Right in China system shows; At present existing intellectual property project reduces the formation of thrombosis through the method for blood vessel being carried out finishing; Like number of patent application is to propose the composite vascular prosthesis be made up of anticoagulation layer, fabric enhancement layer and elastic bonding layer in 200610166568.6 " the enhanced composite vascular prosthesis of a kind of fabric ", has improved the artificial blood vessel patency rate to a certain extent; But the elasticity of demand tack coat is connected between fabric enhancement layer and the anticoagulation layer, causes tube wall thicker, is unfavorable for being applied on the small-bore artificial blood vessel, and its complex structure, the preparation difficulty, and the coating amount is uncontrollable.
Common medical artificial vascular grafts is generally hydrophobic material surface free energy height, and material itself is prone to interact with plasma protein, forms mural thrombus.
Summary of the invention
Technical problem to be solved by this invention provides a kind of composite construction artificial blood vessel and preparation method thereof, the internal diameter of this artificial blood vessel can≤6mm, the strength and extension property of blood vessel radial-axial is good, the thinner requirement that more meets small-caliber vascular of tube wall; This method for preparing is simple, and the adhesion between coating and the pipe is good, is difficult for peeling off.
A kind of composite construction artificial blood vessel of the present invention, this artificial blood vessel comprises: the pipe and the nanofiber element coating of weaving base, the internal diameter of said pipe can be less than or equal to 6mm.
The structural pipe wall of said pipe is woven, knitting, braiding or non-woven, the big and Stability Analysis of Structures of its hole.
The material of said pipe is the medical non-degraded macromolecular fibrous material with biocompatibility.
The method for preparing of a kind of composite construction artificial blood vessel of the present invention comprises:
Obtain the pipe of artificial blood vessel through woven, knitting, braiding or nonwoven techniques such as acupuncture, water acupuncture manipulation; Then described pipe is placed the Bacterial cellulose bioreactor, pass pipe, leave the space between support and the pipe with support; Behind the high temperature sterilize; In reaction vessel, pour aseptic fermentation medium into, insert Bacterial cellulose production bacterium seed liquor, dynamically cultivate after 1-7 days and apply one deck nano-cellulose film, promptly get the composite construction artificial blood vessel at the pipe surfaces externally and internally.
In the described Bacterial cellulose bioreactor, pipe rotates along with the rotation of rotating disk, and is as shown in Figure 1.
In the described Bacterial cellulose bioreactor, pipe moves up and down, and is as shown in Figure 2.
Described support is bar-shaped support.
It is acetic acid Pseudomonas (Acetobacter sp.) that described Bacterial cellulose is produced bacterium; Bacterium gluconicum belongs to (Gluconobacter sp.); Gluconic acid Acetobacter sp. (Gluconacetobacter sp.); Glucose oxidation and bacillus (Gluconobacter oxydans); Rhizobium (Rhizobium sp.); Sarcina (Sarcina sp.); Rhodopseudomonas (Pseudomounas sp.); Achromobacter (Achromobacter sp.); Alcaligenes (Alcaligenes sp.); Aerobacter (Aerobacter sp.); Azotobacter (Azotobacter sp.); Agrobacterium (Agrobacterium sp.); Pseudomonas cepacia (Seudomonas cepacia); Campylobacter jejuni (Campylobacter jejuni); Acetobacter xylinum (Acetobacter xylinum) or red tea fungus (kombucha).
Design of the present invention:
1) material
According to instructions for use, the material of pipe uses the medical non-degraded macromolecular fibrous material with biocompatibility.
The nano-cellulose that the nanofiber element coating uses bacterial fermentation to obtain.
2) pipe structural design
That the tube wall of pipe is taked is woven, knitting, braiding or non-woven structure; Through adopting proper yarn arrays and proportioning, adding corresponding with it processing mode, realize having on a kind of artificial blood vessel tube wall than macrovoid but constitutionally stable fabric construction.
3.) nano-cellulose overlay film
The basic fundamental route is following:
Pipe is placed Bacterial cellulose bioreactor (as depicted in figs. 1 and 2); Pass pipe with bar-shaped support; Leave the space between bar-shaped support and the pipe, behind the high temperature sterilize, in reaction vessel, pour aseptic fermentation medium into; Insert Bacterial cellulose and produce the bacterium seed liquor, place under the uniform temperature and dynamically apply one deck nano-cellulose film at the pipe surfaces externally and internally behind the cultivation certain hour.
To the weave pipe of base of the present invention is immersed in the culture fluid, and bacteriogenic nano-cellulose forms cellulosic coating to run through structure growth on weaving parent tube base, finally form the artificial blood vessel of bacterial fibers element coating.
Nanometer bacteria cellulose is direct growth on weaving parent tube base, forms the coating that runs through structure, has overcome the problem of above-mentioned small-caliber vascular complex structure, preparation difficulty; Pipe is a monolayer weaving base, and in order to satisfy the requirement of nanometer bacteria cellulose coating, pipe has macrovoid and constitutionally stable performance, and the little vascular wall that obtains is thinner; The nanometer bacteria cellulose coating is by the antibacterial secretion, adheres on the weaving parent tube base with the form growth that runs through, and can pass through the amount and the direction of its growths of control such as control growing time, growth conditions, so the coating amount is controlled and coating is more even; The nanofiber element coating has higher biocompatibility and excellent biomechanical property; And be that the hydrophilic material surface free energy is low; Material itself is difficult for interacting with plasma protein, prevents that mural thrombus from forming, and improved the patency rate of small-bore artificial blood vessel.
Beneficial effect
(1) pipe of the present invention is a monolayer weaving base, has macrovoid and constitutionally stable performance, and the strength and extension property of the little blood vessel radial-axial that obtains is good, the thinner requirement that more meets small-caliber vascular of tube wall;
(2) nanometer bacteria cellulose direct growth on weaving parent tube base forms the coating that runs through structure, simple in structure, preparation easily, the adhesion between coating and the pipe is good, is difficult for peeling off;
(3) the nanometer bacteria cellulose coating is by the cellulosic bacteria secretion, adheres on the weaving parent tube base with the form growth that runs through, and can pass through the amount and the direction of its growths of control such as control growing time, growth conditions, so coating amount and uniformity are artificially controlled;
(4) the nanometer bacteria cellulose coating has higher biocompatibility and excellent biomechanical property, and is that the hydrophilic material surface free energy is low, and material itself is difficult for interacting with plasma protein, prevents that effectively mural thrombus from forming.
(5) the artificial blood vessel tube wall good leak tightness of nanofiber element coating does not need preparatory blood coagulation, and finishing process can suitably be simplified.
Description of drawings
Fig. 1 is the device sketch map (pipe rotation) of the used Bacterial cellulose bioreactor of the present invention;
Fig. 2 is the device sketch map (pipe moves up and down) of the used Bacterial cellulose bioreactor of the present invention;
Fig. 3 is the cellulosic stereoscan photograph of viscose rayon pipe coated with nano among the embodiment 1;
Fig. 4 is the organization charts of the tubular tissue of lace stitch among the embodiment 1;
Fig. 5 is the tube wall of cellulosic coating among the embodiment 1;
Fig. 6 is the organization charts of latitude plain stitch among the embodiment 2;
1-pipe wherein, 2-support (bar-shaped), 3-rotating disk, 4-culture medium liquid level, 5-water-bath, 6-ground warp, 7-doup end, 8-weft yarn, 9-bacterial fibers element coating.
The specific embodiment
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in the restriction scope of the present invention.Should be understood that in addition those skilled in the art can do various changes or modification to the present invention after the content of having read the present invention's instruction, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
The invention is not restricted to Fig. 1 or rotation shown in Figure 2 or the Bacterial cellulose bioreactor that moves up and down, the Bacterial cellulose bioreactor of dynamically cultivating all can.
The material of pipe adopts the viscose glue bright yarn of 50D/12f; Longitude and latitude knot structure is three strands and compiles in collaboration with; It is the tubular tissue (the as shown in Figure 5 braiding by ground warp 6, doup end 7 and weft yarn 8 forms) of lace stitch that the pipe tissue adopts basic organization.Fabric parameter: (root/10cm) is 400*100, and folding footpath (mm) is 10, and total quantity of warps (root) is 40 in end count * filling density.
Weave figure sees Fig. 4.Select the cellulose of acetobacter xylinum fermentation that pipe is carried out coating.In bioreactor (Fig. 1 and 2) fermentation culture 1-7 days, finally make the small-bore artificial blood vessel of bacterial fibers element coating.
Fermentating culturing process:
(1) spawn culture: with acetobacter xylinum (Acetobacter xylinum) insert the 300mL fluid medium (in every 1L water, mannitol 20g, peptone 3g, yeast extract 5g, pH3.0,121 ℃ of sterilization 20min; Or glucose 200g, yeast extract 5g, tryptone 5g, citric acid 115g, Na
2HPO
42.7g, water 1L, pH7.5,121 ℃ of sterilization 20min) spread cultivation, cultivate or leave standstill after cultivating 12h subsequent use in shaking table under 20 ℃, 100r/min condition;
(2) fermenting process of preparing of Bacterial cellulose composite vascular prosthesis: the fluid medium of producing bacterial strain that contains of step (1) preparation is transferred to and is equipped with in the bioreactor of having fixed blank tube material; Pipe carries out the disturbance cultivation with the rotating speed rotation (Fig. 1) or move up and down (Fig. 2) of 5-60rpm then; In 30 ℃ of water-baths 5, dynamically cultivate after 1-7 days; Get final product at the artificial blood vessel of pipe surfaces externally and internally coated with nano Bacterial cellulose, the SEM photo of material is seen Fig. 3.
Embodiment 2
The material of pipe adopts the viscose glue bright yarn of 50D/12f; Yarn texture is three strands and compiles in collaboration with; It is the knitting tubular tissue of latitude plain stitch that tissue adopts basic organization.Fabric parameter: end count * filling density (individual/5cm) be 35*55, syringe diameter (mm) is 6.
Weave figure sees Fig. 6.Select the cellulose of glucose oxidation and bacillus (Gluconobacter oxydans) fermentation that pipe is carried out coating.In bioreactor (Fig. 1 and 2) fermentation culture 1-7 days, finally make the small-bore artificial blood vessel of bacterial fibers element coating.The cellulosic artificial blood vessel material's of coated with nano electromicroscopic photograph and Fig. 3 result are similar.
Fermentating culturing process:
(1) spawn culture: with glucose oxidation and bacillus (Gluconobacter oxydans) insert the 300mL fluid medium (in every 1L water, mannitol 20g, peptone 3g, yeast extract 5g, pH3.0,121 ℃ of sterilization 20min; Or glucose 200g, yeast extract 5g, tryptone 5g, citric acid 115g, Na
2HPO
42.7g, water 1L, pH7.5,121 ℃ of sterilization 20min) spread cultivation, cultivate or leave standstill after cultivating 12h subsequent use in shaking table under 20 ℃, 100r/min condition;
(2) fermenting process of preparing of Bacterial cellulose composite vascular prosthesis: the fluid medium of producing bacterial strain that contains of step (1) preparation is transferred to and is equipped with in the bioreactor of having fixed blank tube material; Pipe carries out the disturbance cultivation with the rotating speed rotation (Fig. 1) or move up and down (Fig. 2) of 5-60rpm then; In 30 ℃ of water-baths 5, dynamically cultivate after 1-7 days, get final product at the artificial blood vessel of pipe surfaces externally and internally coated with nano Bacterial cellulose.
Embodiment 3
The yarn of pipe adopts the viscose glue bright yarn of 50D/12f; Tissue adopts basic organization to compile tubular tissue for rope.Fabric parameter: the spool number is 32, and core tube diameter (mm) is 6.
Select the cellulose of red tea fungus (kombucha) fermentation that pipe is carried out coating.In bioreactor (Fig. 1 and 2) fermentation culture 1-7 days, finally make the small-bore artificial blood vessel of bacterial fibers element coating.The cellulosic artificial blood vessel material's of coated with nano electromicroscopic photograph and Fig. 3 result are similar.
Fermentating culturing process:
(1) spawn culture: red tea fungus (kombucha) is inserted the 300mL liquid seed culture medium (in every 1L water by the inoculum concentration that 5 diameter 0.5cm disks of access contain bacterium BC film; Green tea 5g; Glucose 10, peptone 3g, yeast extract 5g, pH3.0, pasteurization 30min; In every 1L water, glucose 100g, peptone 3g, yeast extract 5g, pH7.5,121 ℃ of sterilization 20min) spread cultivation, cultivate or leave standstill after cultivating 24h subsequent use in shaking table under 25 ℃, 150r/min condition;
(2) fermenting process of preparing of Bacterial cellulose composite vascular prosthesis: the fluid medium of producing bacterial strain that contains of step (1) preparation is transferred to and is equipped with in the bioreactor of having fixed blank tube material; Pipe carries out the disturbance cultivation with the rotating speed rotation (Fig. 1) or move up and down (Fig. 2) of 5-60rpm then; In 30 ℃ of water-baths 5, dynamically cultivate after 1-7 days, get final product at the artificial blood vessel of pipe surfaces externally and internally coated with nano Bacterial cellulose.
Claims (8)
1. composite construction artificial blood vessel, this artificial blood vessel comprises: the pipe (1) and the nanofiber element coating (9) of weaving base.
2. a kind of composite construction artificial blood vessel according to claim 1 is characterized in that: the structural pipe wall of said pipe (1) is woven, knitting, braiding or non-woven.
3. a kind of composite construction artificial blood vessel according to claim 1 is characterized in that: the material of said pipe (1) is the medical high polymer fibrous material with biocompatibility.
4. the method for preparing of a composite construction artificial blood vessel comprises:
Through woven, knitting, braiding or the non-woven pipe (1) that obtains artificial blood vessel; Then described pipe is placed the Bacterial cellulose bioreactor, pass pipe (1), leave the space between support (2) and the pipe (1) with support (2); Behind the high temperature sterilize; In reaction vessel, pour aseptic fermentation medium into, insert Bacterial cellulose production bacterium seed liquor, dynamically cultivate after 1-7 days and apply one deck nano-cellulose film, promptly get at the pipe surfaces externally and internally.
5. the method for preparing of a kind of composite construction artificial blood vessel according to claim 4 is characterized in that: in the described Bacterial cellulose bioreactor, pipe (1) rotates along with the rotation of rotating disk (3).
6. the method for preparing of the small-bore artificial blood vessel of a kind of composite construction according to claim 4 is characterized in that: in the described Bacterial cellulose bioreactor, pipe (1) moves up and down.
7. the method for preparing of a kind of composite construction artificial blood vessel according to claim 4 is characterized in that: described support (2) is bar-shaped or tubular bracket.
8. the method for preparing of a kind of composite construction artificial blood vessel according to claim 4 is characterized in that: it is that acetic acid Pseudomonas (Acetobacter sp.), Bacterium gluconicum belong to (Gluconobacter sp.), gluconic acid Acetobacter sp. (Gluconacetobacter sp.), glucose oxidation and bacillus (Gluconobacter oxydans), rhizobium (Rhizobium sp.), Sarcina (Sarcina sp.), Rhodopseudomonas (Pseudomounas sp.), achromobacter (Achromobacter sp.), Alcaligenes (Alcaligenes sp.), Aerobacter (Aerobacter sp.), azotobacter (Azotobacter sp.), Agrobacterium (Agrobacterium sp.), Pseudomonas cepacia (Seudomonas cepacia), campylobacter jejuni (Campylobacter jejuni), acetobacter xylinum (Acetobacter xylinum) or red tea fungus (kombucha) that described Bacterial cellulose is produced bacterium.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103341208A (en) * | 2013-07-09 | 2013-10-09 | 钟春燕 | Preparation method of hollow biological cellulose tube |
| CN104689382A (en) * | 2015-03-18 | 2015-06-10 | 东华大学 | Braiding-reinforced nano-fiber small-caliber intravascular stent, and preparation and application thereof |
| CN104963094A (en) * | 2015-07-08 | 2015-10-07 | 江南大学 | Non-woven cloth prepared by composite fibers by means of bacterial cellulose produced by microorganisms and preparation method thereof |
| CN109880140A (en) * | 2019-01-30 | 2019-06-14 | 东华大学 | A kind of alkali contracting Nano bacteria cellulose pipe and its preparation method and application |
| CN111388760A (en) * | 2020-03-25 | 2020-07-10 | 华东交通大学 | Small blood vessel stent with nano fibers oriented along circumferential direction and preparation method |
| CN114159624A (en) * | 2021-11-24 | 2022-03-11 | 山东黄河三角洲纺织科技研究院有限公司 | Coating method of woven artificial blood vessel and artificial blood vessel |
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| CN104963094A (en) * | 2015-07-08 | 2015-10-07 | 江南大学 | Non-woven cloth prepared by composite fibers by means of bacterial cellulose produced by microorganisms and preparation method thereof |
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| CN109880140B (en) * | 2019-01-30 | 2022-09-27 | 东华大学 | Alkali-shrinkable bacteria nano cellulose tube and preparation method and application thereof |
| CN111388760A (en) * | 2020-03-25 | 2020-07-10 | 华东交通大学 | Small blood vessel stent with nano fibers oriented along circumferential direction and preparation method |
| CN114159624A (en) * | 2021-11-24 | 2022-03-11 | 山东黄河三角洲纺织科技研究院有限公司 | Coating method of woven artificial blood vessel and artificial blood vessel |
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