CN110201236A - A kind of novel artificial blood vessel - Google Patents
A kind of novel artificial blood vessel Download PDFInfo
- Publication number
- CN110201236A CN110201236A CN201910633942.6A CN201910633942A CN110201236A CN 110201236 A CN110201236 A CN 110201236A CN 201910633942 A CN201910633942 A CN 201910633942A CN 110201236 A CN110201236 A CN 110201236A
- Authority
- CN
- China
- Prior art keywords
- cell
- blood vessel
- artificial blood
- bacteria cellulose
- vascular
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- 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.)
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Classifications
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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
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- 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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/3633—Extracellular matrix [ECM]
-
- 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
-
- 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
Abstract
The present invention is directed to organizational project and regenerative medicine field, is constructed by macromolecule ordered fiber and bacteria cellulose, and the design for carrying out double-layer artificial blood vessel is modified using specific cell epimatrix.Effect the present invention is based on fiber morphology to cell behavior, the internal layer using ordered fiber as artificial blood vessel provide binding site for vascular endothelial cell and induce its polar growth.Bacteria cellulose is conducive to the infiltration of cell and reserves living space for vascular smooth muscle cells as outer layer.On the basis of structure optimization, Cell culture invitro is carried out to ordered fiber and bacteria cellulose.In short, vascular endothelial cell is cultivated on ordered fiber, bacteria cellulose culture vascular smooth muscle cells.Finally, carrying out the modification of cell-specific extracellular matrix to ordered fiber and bacteria cellulose by de- cell, regulate and control different cells in the behavior of revascularization different phase.
Description
Technical field
The present invention is directed to organizational project and regenerative medicine field, carries out people using macromolecule ordered fiber and bacteria cellulose
The preparation of work blood vessel, and the creative vascular endothelial cell and smooth of cultivating macromolecule ordered fiber and bacteria cellulose respectively
Myocyte probes into the effect that the extracellular matrix of specific cells inoculates itself.Blood vessel endothelium is obtained by de- cell technology
Cell and smooth muscle cell are survived relied on extracellular matrix compound ordered fiber and bacteria cellulose, to structure in vitro
Different vascular cell microenvironments is built, is conducive to vascular cell and permeates and provide specific adhesion bound site for different blood vessel cell
Point promotes vascular cell Phenotypic Change, restores vascular cell function, allows regenerated blood vessel close to the living tissue of receptor itself.
Background technique
Demand of the clinic to safely and effectively vascular repair material is huge.Cardiovascular disease is still to suffer from the world
The main reason for person's morbidity and mortality.In traumatic damage, the reparation of damaged blood vessels during tumor operation or organ transplant
And reconstruction, and usually require for the creation of haemodialysis arteriovenous (AV) conduit using replacement vessels.Undoubtedly certainly
Body artery and vein are the preferred materials of reconstructing blood vessel, however same patient's body harvest and re-use blood vessel usually by
The limitation of patient's pathophysiological condition.Therefore, it in past 40 years, implants in millions of patients and is gathered by varicosity
Tetrafluoroethene (ePTFE) or polyethylene terephthalate (Dacron) are the artificial synthesized vasotransplantation of main material
Object, but their use is along with infection, the risks such as thrombosis.Many biologies of autologous vein and synthetic vessel graft
Substitute, including allogeneic and heterogenous blood vessel and tissue are assessed by food and drug administration and are ratified to be used for people
Class implantation.However, their potentiality are by availability, cost, the limitation of processing technology and clinical effectiveness.Although many substitutes
With matching even more than its mechanical strength with native blood vessels tissue, but to be unfavorable for host thin for the structure and composition of its matrix
Born of the same parents' is suitably proliferated again.Therefore, these allogeneics and heteroplasm never sufficiently remold the living tissue for arriving host itself
In.
As the three dimensional network structure of a kind of protein for possessing complicated threadiness and polysaccharide, extracellular matrix is in human body
Has the function of height adjustment in most of tissues and organ, it is often more important that the ingredient with tissue specificity is simultaneously capable of providing
Dynamic Signal stimulation, adjusts cell behavior.Hot spot of the extracellular matrix (ECM) as research, is not only limited to opening for natural ECM
Hair, researcher are also combined using the unique biological characteristic of ECM with biomaterial, are developed bionical ECM material and are applied to group weaver
Journey and regenerative medicine.
Summary of the invention
In the present invention, we construct double-deck artificial blood vessel using macromolecule ordered fiber and bacteria cellulose.Using thin
Outer layer of the fungin as artificial blood vessel, to enhance the recruitment and infiltration of damage location adjacent side vascular cell.Using orderly
Internal layer of the macromolecular fibre as artificial blood vessel provides attachment sites for vascular endothelial cell and guides its polar growth.Simultaneously
We also pass through Cell culture invitro, by the cell-specific extracellular matrix of deposition to ordered fiber and bacteria cellulose into
Row modification.
Due to design artificial blood vessel not only in structure it is similar to native blood vessels, and modify cell-specific cell
Epimatrix contains a large amount of signaling molecules, plays an active part in the growth of control cell, polarity, form, migration and metabolic activity can enhance
The specific migration of cell and selective attachment regulate and control physiological function of the different blood vessel cell in reconstructing blood vessel various process.
Production method and structure of the present invention:
Outer layer: using acetobacter xylinum production bacteria cellulose as raw material, fibre diameter be less than 100nm, have with it is natural
The similar structure of extracellular matrix.Firstly, the bacteria cellulose aquagel that acetobacter xylinum produces is cleaned with clear water, then
It is boiled with 1%NaOH to solution clarification and is finally dipped to alkalescent or neutrality with ultrapure water.
Internal layer: being to have by biological rapid shaping (3D printing) using high molecular materials such as polycaprolactones (PCL) as raw material
Sequence fiber provides specific adhesion binding site for vascular endothelial cell and induces its polar growth.
Compared with traditional artificial blood vessel, the innovation of the invention consists in that:
1. the present invention uses bacteria cellulose for raw material, it is different from other artificial nano structural materials, bacteria cellulose is not
The infiltration of meeting block cell, and because of its high-biocompatibility, good living environment can be provided for cellular activity.
2. the present invention is multilayered structure, the ordered fiber of internal layer can provide binding site and be induced for vascular endothelial cell
Its polar growth；Outer layer bacteria cellulose is conducive to vascular endothelial cell and infiltrates into internal layer, and provides for vascular smooth muscle cells
Living space.
3. the present invention is modified with cell-specific extracellular matrix, specificity induction and choosing are played to own cells
Selecting property adhesive attraction, regulating cell behavior.
4. internal layer of the present invention is ordered fiber, modeled by computer, can rapid shaping (3D printing) manufacture, and batch is raw
It produces.
5. outer layer of the present invention is bacteria cellulose, obtained by cultivating acetobacter xylinum, method is simply low in cost, can also criticize
Amount production.
Detailed description of the invention
As shown,
Fig. 1 is the double-layer artificial vascular pattern that the present invention designs.Outer layer is bacteria cellulose, and internal layer is that macromolecule is orderly fine
Dimension.
Fig. 2 is the micro-structure diagram of bacteria cellulose, and fibre diameter is less than 100nm.
Fig. 3 is ordered fiber micro-structure diagram.
Specific embodiment
This patent is described further below with reference to implementing regulations.
1) double-layer artificial blood vessel production method
Outer layer: bacteria cellulose.It is obtained by cultivating acetobacter xylinum at acetic acid bacterium culture medium (#350).Bacteria cellulose film
It is first rinsed through clear water, is then boiled by 1%NaOH to solution and clarified, last ultrapure water is dipped to alkalescent or neutrality.75% doctor
10min is impregnated with alcohol, ultraviolet irradiation 1h sterilizes.
Internal layer: ordered fiber silk.7% (v/v) polycaprolactone (PCL) printing solution is prepared, it is fast rapid-result by 3D printing etc.
Type means obtain polycaprolactone ordered fiber.75% medicinal alcohol impregnates 10min, and ultraviolet irradiation 1h sterilizes.
2) Cell culture invitro
It takes ready ordered fiber and bacteria cellulose to cultivate vascular endothelial cell and vascular smooth muscle cells respectively, leads to
The extracellular matrix for crossing deposition modifies two different timbering materials.
3) assembling of double-layer artificial blood vessel
The ordered fiber of extracellular matrix modified and bacteria cellulose are successively wound in the stainless steel tube of diameter 1.6mm
On, 4 DEG C of natural dryings, production internal layer is ordered fiber, and outer layer is the double-layer artificial vascular pattern of bacteria cellulose.
Above-mentioned to disclose this patent with preferred embodiments, so it is not to limit this patent, it is all using equivalent replacement or
Equivalence replacement mode technical solution obtained, all falls within the protection scope of this patent.
Claims (6)
1. a kind of novel artificial blood vessel, which is characterized in that double-layer structure is constructed using bacteria cellulose and orderly macromolecular fibre,
And by Cell culture invitro, modified using cell-specific extracellular matrix, specific regulatory control cell behavior.
2. novel artificial blood vessel according to claim 1, which is characterized in that the influence design based on fiber morphology to cell behavior
Double-layer artificial blood vessel.The ordered fiber of internal layer can induce its polarity raw while providing binding site for vascular endothelial cell
Long, the bacteria cellulose of outer layer is conducive to the infiltration of vascular cell and reserves living space for vascular smooth muscle cells.
3. novel artificial blood vessel according to claim 1, which is characterized in that used and be different from other artificial nanofibrous structures
Material -- bacteria cellulose can be provided because of the infiltration without block cell, and because of its high-biocompatibility for cell good
Good living environment.
4. novel artificial blood vessel according to claim 1, which is characterized in that optimize physical stimulation by structure and fiber morphology and set
It counts and introduces extracellular matrix signal inducing action, rebuild the microenvironment of vascular cell existence in vitro.
5. novel artificial blood vessel according to claim 1, which is characterized in that by Cell culture invitro, utilize cell-specific
Extracellular matrix modifies timbering material, highlights the row that the extracellular matrix of specific cells inoculates own cells
For specific regulatory control effect.
6. novel artificial blood vessel according to claim 1, which is characterized in that cell-specific extracellular matrix is from intravascular
Chrotoplast and smooth muscle cell emphasize recruitment and regulating and controlling effect to surrounding tissue cells, are not originating from sanguimotor thin
Born of the same parents, therefore potentiality are had more to gerontal patient original position vascular replacement.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910633942.6A CN110201236A (en) | 2019-07-15 | 2019-07-15 | A kind of novel artificial blood vessel |
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| CN201910633942.6A CN110201236A (en) | 2019-07-15 | 2019-07-15 | A kind of novel artificial blood vessel |
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| CN110201236A true CN110201236A (en) | 2019-09-06 |
Family
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113694253A (en) * | 2021-09-23 | 2021-11-26 | 北京航空航天大学 | Preparation method of small-caliber artificial blood vessel |
| CN115944786A (en) * | 2023-01-09 | 2023-04-11 | 华东交通大学 | Integrated double-layer small vascular graft and preparation method thereof |
| CN115944786B (en) * | 2023-01-09 | 2024-04-30 | 华东交通大学 | Integrated double-layer small blood vessel graft and preparation method thereof |
Citations (9)
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|---|---|---|---|---|
| EP0275653A1 (en) * | 1987-01-07 | 1988-07-27 | Imperial Chemical Industries Plc | Vascular prosthesis |
| WO2008079034A2 (en) * | 2006-12-24 | 2008-07-03 | Politechnika Lodzka | A biomaterial composed of microbiological cellulose for internal use, a method of producing the biomaterial and the use of the biomaterial composed of microbiological cellulose in soft tissue surgery and bone surgery |
| CN104921841A (en) * | 2015-04-10 | 2015-09-23 | 南开大学 | Method for manufacturing artificial blood vessels with double-layered structures and application of artificial blood vessels |
| JP2016069783A (en) * | 2014-09-30 | 2016-05-09 | 多木化学株式会社 | Collagen fiber |
| CN106075596A (en) * | 2016-07-21 | 2016-11-09 | 南开大学 | A kind of three layers of artificial blood vessel's technology of preparing |
| CN106512087A (en) * | 2016-12-06 | 2017-03-22 | 北京航空航天大学 | Artificial blood vessel stent with aligned fibers and manufacturing method of artificial blood vessel stent |
| US20170081784A1 (en) * | 2014-12-11 | 2017-03-23 | Tepha, Inc. | Methods of orienting multifilament yarn and monofilaments of poly-4-hydroxybutyrate and copolymers thereof |
| CN108245712A (en) * | 2016-12-29 | 2018-07-06 | 国家纳米科学中心 | The preparation method and application of bacteria cellulose minor diameter artificial blood vessel |
| CN108653815A (en) * | 2017-03-31 | 2018-10-16 | 国家纳米科学中心 | Three-dimensional coil structure and its preparation method and application with autonomous adjustment structure function |
-
2019
- 2019-07-15 CN CN201910633942.6A patent/CN110201236A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0275653A1 (en) * | 1987-01-07 | 1988-07-27 | Imperial Chemical Industries Plc | Vascular prosthesis |
| WO2008079034A2 (en) * | 2006-12-24 | 2008-07-03 | Politechnika Lodzka | A biomaterial composed of microbiological cellulose for internal use, a method of producing the biomaterial and the use of the biomaterial composed of microbiological cellulose in soft tissue surgery and bone surgery |
| JP2016069783A (en) * | 2014-09-30 | 2016-05-09 | 多木化学株式会社 | Collagen fiber |
| US20170081784A1 (en) * | 2014-12-11 | 2017-03-23 | Tepha, Inc. | Methods of orienting multifilament yarn and monofilaments of poly-4-hydroxybutyrate and copolymers thereof |
| CN104921841A (en) * | 2015-04-10 | 2015-09-23 | 南开大学 | Method for manufacturing artificial blood vessels with double-layered structures and application of artificial blood vessels |
| CN106075596A (en) * | 2016-07-21 | 2016-11-09 | 南开大学 | A kind of three layers of artificial blood vessel's technology of preparing |
| CN106512087A (en) * | 2016-12-06 | 2017-03-22 | 北京航空航天大学 | Artificial blood vessel stent with aligned fibers and manufacturing method of artificial blood vessel stent |
| CN108245712A (en) * | 2016-12-29 | 2018-07-06 | 国家纳米科学中心 | The preparation method and application of bacteria cellulose minor diameter artificial blood vessel |
| CN108653815A (en) * | 2017-03-31 | 2018-10-16 | 国家纳米科学中心 | Three-dimensional coil structure and its preparation method and application with autonomous adjustment structure function |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113694253A (en) * | 2021-09-23 | 2021-11-26 | 北京航空航天大学 | Preparation method of small-caliber artificial blood vessel |
| CN115944786A (en) * | 2023-01-09 | 2023-04-11 | 华东交通大学 | Integrated double-layer small vascular graft and preparation method thereof |
| CN115944786B (en) * | 2023-01-09 | 2024-04-30 | 华东交通大学 | Integrated double-layer small blood vessel graft and preparation method thereof |
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Application publication date: 20190906 |
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