CN111214703A - iPS-derived myocardial cell composite patch and preparation and application thereof - Google Patents
iPS-derived myocardial cell composite patch and preparation and application thereof Download PDFInfo
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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
- A61L27/20—Polysaccharides
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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
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/222—Gelatin
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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
- A61L27/36—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
- A61L27/38—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 containing added animal cells
- A61L27/3804—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 containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
- A61L27/3826—Muscle cells, e.g. smooth muscle cells
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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
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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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves
Abstract
The invention relates to an iPS (induced pluripotent stem) derived myocardial cell composite patch, which is composed of a basement membrane made of a natural polymer material and a myocardial cell layer which is attached to the surface of one side or two sides of the basement membrane and is generated by iPS cell differentiation, and has the composition, structure and function similar to myocardial tissues. The invention also provides a preparation method of the iPS-derived cardiomyocyte composite patch. The preparation method is simple to operate and low in cost, and the prepared composite patch is high in bioactivity and good in strength, can be attached to a damaged part of a heart and promotes the repair of damaged myocardial tissues. The invention overcomes the defects of the prior art and plays an important role in the field of regenerative medicine.
Description
Technical Field
The invention relates to the field of regenerative medicine, and particularly relates to an iPS (induced pluripotent stem) derived cardiac muscle cell composite patch as well as preparation and application thereof.
Background
Although the existing thrombolytic drugs and interventional surgery can improve the symptoms of patients with myocardial infarction, the existing thrombolytic drugs and interventional surgery cannot reverse necrotic myocardium. For patients with severe myocardial infarction, organ transplantation is the fundamental treatment, but the development of organ transplantation is severely limited due to the lack of transplant donors and the problem of immunological rejection. Although some clinical studies confirm that the conventional cell injection method can improve the cardiac function of patients, there are problems of low cell retention, low cell survival rate, arrhythmia and the like. The myocardial patch is a sheet-shaped engineered heart tissue prepared by a tissue engineering means, has a cell sheet structure, and can improve the survival rate and survival rate of implanted cells, so that more and more attention is paid. Different construction methods can prepare myocardial patches with different characteristics, the functions and the characteristics of the myocardial patches are different, and the myocardial patches have great influence on the treatment effect. At present, the research is widely carried out on a preparation method of a carrier-free cell sheet layer invented by a Japanese Teruo Okano team, namely, by utilizing the principle that a temperature-sensitive material poly (isopropylacrylamide) is hydrophobic at 37 ℃ and is changed into hydrophilic at 20 ℃, the temperature-sensitive material is paved at the bottom of a culture dish and is planted with seed cells, the cells are cultured for a period of time and well connected with each other, and then the temperature is reduced (20 ℃) to gradually separate the cell sheet from the bottom of the culture dish. However, the cell sheets prepared by the method are formed by connecting cells, the culture time is long, the thickness of the cell layers is limited, the mechanical strength is low, the culture time before transplantation is long, the cell sheets are lack of support during transplantation, and the operation is difficult. Compared with a carrier-free cell sheet layer, the carrier-loaded cell sheet layer uses the support material as a substrate layer of the patch, so that the thickness and the mechanical strength of the cell sheet layer can be obviously improved, the operability of the transplantation operation is increased, and the characteristics of the support material can influence the microenvironment of myocardial tissues and the activity and the function of the cell sheet layer. At present, the basal layer of the myocardial patch mainly comprises a basal layer of artificial macromolecules such as polyacrylonitrile, polycaprolactone and the like and a basal layer constructed by one or two natural macromolecules such as collagen, chitosan, fibroin and the like, and the basal layer has large difference from an extracellular matrix in a body in components, structure and functions and lacks sufficient biological activity. In addition, the current myocardial patch is mainly prepared from mature myocardial single cell layers, does not form a micro-tissue, lacks sufficient biological functions and has limited treatment effect. The iPS cell has totipotency, can form a cardiac muscle micro-tissue layer with beating capability through induced differentiation in an approximately in vivo culture environment, and has obviously better function than the cardiac muscle single cell layer.
In order to solve the problems that the difference between the basal layer of the conventional myocardial patch and an in-vivo extracellular matrix is large and the biological function of the myocardial single cell layer is low, the invention combines a bionic substrate and an iPS (induced pluripotent stem), and provides a novel iPS-derived myocardial cell composite patch and a preparation method thereof. The myocardial patch provided by the invention is composed of a basement membrane imitating an extracellular matrix and a myocardial micro-tissue layer generated by iPS cell differentiation on the basement membrane, has higher biological activity and better mechanical strength, is more convenient to implant and operate, and can obviously improve the treatment effect. Therefore, the invention overcomes the defects of the prior art and plays an important role in the field of myocardial repair.
Disclosure of Invention
The invention discloses an iPS (induced pluripotent stem) derived myocardial cell composite patch, which is composed of a basement membrane made of a natural polymer material and a myocardial cell layer which is attached to the surface of one side or two sides of the basement membrane and is generated by iPS cell differentiation, and has the composition, structure and function similar to myocardial tissues.
Base film preparation: preparing a gelling aqueous solution containing chitosan, hyaluronic acid and gelatin, adding a cross-linking agent for cross-linking reaction to obtain a gel film, and neutralizing, cleaning and drying to obtain a basement membrane;
the concentration of the chitosan in the gel-forming water solution is 1-10% (w/v, g/ml), and the preferred concentration is 5% (w/v, g/ml);
the concentration of the hyaluronic acid in the gel-forming aqueous solution is 0.1-1% (w/v, g/ml), and the preferred concentration is 0.5% (w/v, g/ml);
the concentration of the gelatin in the gel-forming water solution is 3-15% (w/v, g/ml), and the preferred concentration is 10% (w/v, g/ml);
the concentration of the cross-linking agent after the cross-linking agent is mixed with the gel-forming aqueous solution is 0.01-3% (w/v, g/ml), and the preferred concentration is 0.5% (w/v, g/ml).
The molecular weight of the chitosan is 30000-200000kDa, and the preferred molecular weight is 110000;
the molecular weight of the hyaluronic acid is 1300000-3000000kDa, and the preferred molecular weight is 2000000 kDa;
the gelatin comprises one or a mixture of alkaline gelatin and acidic gelatin; the gelatin has a jelly strength of greater than 100Bloom g;
the cross-linking agent is one of formaldehyde, glutaraldehyde, genipin and carbodiimide.
The crosslinking condition is that the temperature is 18-25 ℃, and the crosslinking process time is more than or equal to 60 minutes;
the neutralization process is to soak the gel film formed by crosslinking by using 0.05-0.3M glycine solution, the concentration is preferably 0.1M, and the neutralization process time is more than or equal to 10 minutes.
The drying condition is that the temperature is 18-25 ℃ and the humidity is 20-40%.
Sequentially pretreating iPS cells by Activin A and BMP 4;
cells pretreated by Activin A and BMP4 are inoculated on a basement membrane soaked by water, and serum-free induced differentiation is carried out for 1-3 weeks, preferably 2 weeks, so as to obtain the composite patch with beating capability.
The Activin A pretreatment is to treat the iPS cells for 12-36h by using RPMI 1640 culture solution containing 50-200ng/ml Activin A (preferably, the concentration is 100ng/ml) and 1-3% B27 (not containing insulin, preferably, the concentration is 2%), and the treatment time is preferably 24 h.
The BMP4 pretreatment refers to that after Activin A pretreatment, cells are treated for 2-6 days by using RPMI 1640 culture solution containing 5-20ng/ml BMP4 (preferably with the concentration of 10ng/ml) and 1-3% B27 (not containing insulin, preferably with the concentration of 2%) by mass, and the treatment time is preferably 4 days.
Digesting cells pretreated by Activin A and BMP4, and then inoculating the cells on a basement membrane soaked in water, wherein the cell inoculation density is 2-10 multiplied by 104/cm2Preferably 5X 104/cm2；
The serum-free induced differentiation refers to the culture of cells in RPMI 1640 culture medium containing 1-3% by mass of B27 (no insulin, preferably 2% by mass).
The iPS-derived myocardial cell composite patch is applied as a transplant for repairing myocardial damage.
The myocardial patch has similar composition, structure and function to myocardial tissue, and can repair myocardial damage by attaching the iPS-derived myocardial cell composite patch to the surface of the damaged myocardial tissue.
THE ADVANTAGES OF THE PRESENT INVENTION
1. The bionic basement membrane which is similar to the extracellular matrix in vivo in composition and structure is prepared by utilizing various natural polymer materials, so that the biological activity of the basement membrane is obviously improved, a better growth microenvironment is provided for a cell layer, the fusion with host myocardial tissues is facilitated, the mechanical strength and toughness of the patch are also obviously improved, and the implantation operation is facilitated;
2. according to the invention, the myocardial micro-tissue layer generated by iPS cell differentiation is prepared on the bionic basement membrane, so that the patch forms a functional myocardial micro-tissue, the bioactivity of the patch is higher than that of the conventional single-layer myocardial cell, and the in-vivo myocardial repair promotion effect is better.
Detailed Description
Example 1:
preparing a gel-forming aqueous solution containing 1% (w/v, g/ml) of chitosan (30000kDa), 0.1% (w/v, g/ml) of hyaluronic acid (1300000kDa) and 3% (w/v, g/ml) of gelatin (220Bloom g), adding a cross-linking agent genipin for cross-linking reaction, wherein the final concentration of the cross-linking agent is 0.01% (w/v, g/ml), the cross-linking condition is that the temperature is 25 ℃, the humidity is 50%, and the cross-linking process time is 60 minutes, obtaining a gel membrane, neutralizing for 10 minutes by using 0.05M glycine solution, cleaning and drying (18 ℃, the humidity is 20%), and obtaining the simulated extracellular matrix basement membrane. The iPS cells derived from human blood mononuclear cells are treated according to the method 105Cells/cm2Seeded in petri dishes and using mTeSRTM1 culture broth, replacement with 50ng/ml Activin A and 1% B27 (no insulin, Gibco) when cells reached 90% confluenceTMB-27TMSupplement, minisinsulin, cat #: a1895601) for 12 hours. Thereafter, the cells were replaced with RPMI containing 5ng/ml BMP4 and 1% B27 (without insulin)1640 medium to pre-treat cells for 2 days. Then, cells pretreated with Activin A and BMP4 were digested and seeded on the reconstituted basement membrane at a cell seeding density of 2X 104/cm2Cells were cultured for 1 week in RPMI 1640 medium containing 1% B27 (no insulin).
In addition, patches with chitosan molecular weights of 110000, 200000 and 300000 were prepared as control groups (other preparation conditions were the same). The 4 myocardial patches were implanted on the surface of the damaged myocardial tissue of the rat myocardial infarction model, and the area of each myocardial infarction area was evaluated after 4 weeks. The experimental result shows that the myocardial infarction area of the initial animal model is 5cm2The area of the myocardial infarction area of the rat transplanted with the myocardial patch with the chitosan molecular weight of 300000 is the largest and is 4.9cm2And secondly a myocardial patch (4.3 cm) of chitosan molecular weight 2000002) Followed by a myocardial patch (4 cm) of chitosan molecular weight 300002) The patch (3.3 cm) with chitosan molecular weight of 110000 has the smallest infarct size2). These results show that the composite myocardial patch with the iPS-derived myocardial micro-tissue layer can treat damaged myocardial tissues, and the molecular weight of chitosan has an important influence on the repair effect, preferably 110000.
Example 2:
preparing a gelling aqueous solution containing 10% (w/v, g/ml) chitosan (200000kDa), 1% (w/v, g/ml) hyaluronic acid (3000000kDa) and 15% (w/v, g/ml) gelatin (200Bloom g), adding a cross-linking agent glutaraldehyde for cross-linking reaction, wherein the final concentration of the cross-linking agent is 3% (w/v, g/ml), the cross-linking condition is 25 ℃, the humidity is 80%, the cross-linking process time is 5 hours, obtaining a gel membrane, neutralizing with 0.3M glycine solution for 30 minutes, cleaning and drying (25 ℃, the humidity is 40%) to obtain the extracellular matrix-simulated basement membrane. The iPS cells derived from human blood mononuclear cells are treated according to the method 105Cells/cm2Seeded in petri dishes and using mTeSRTM1 culture broth, replacement with 200ng/ml Activin A and 3% B27 (no insulin, Gibco) when cells reached 90% confluenceTMB-27TMSupplement, minus insulin, cat #: a1895601) in RPMI 1640 mediumAnd (4) pretreating nutrient solution for 36 hours. Thereafter, the cells were pre-treated for 6 days with RPMI 1640 medium containing 20ng/ml BMP4 and 3% B27 (no insulin). Then, cells pretreated by Activin A and BMP4 were digested and seeded on the reconstituted basement membrane at a cell seeding density of 105/cm2Cells were cultured for 3 weeks in RPMI 1640 medium with 3% B27 (no insulin).
In addition, patches with gelatin concentrations of 3% (w/v, g/ml), 10% (w/v, g/ml) and 20% (w/v, g/ml) were prepared as controls (other preparation conditions were the same). The 4 myocardial patches were implanted on the surface of the damaged myocardial tissue of the rat myocardial infarction model, and the area of each myocardial infarction area was evaluated after 4 weeks. The experimental result shows that the myocardial infarction area of the initial animal model is 4.8cm2The area of myocardial infarction area of the rat transplanted with the myocardial patch with gelatin concentration of 20% (w/v, g/ml) is the largest and is 4.6cm2And secondly a myocardial patch (4.2 cm) with a gelatin concentration of 3% (w/v, g/ml)2) Followed by a myocardial patch (3.6 cm) with a gelatin concentration of 15% (w/v, g/ml)2) The smallest infarct size was a patch (2.7 cm) of 10% (w/v, g/ml) gelatin concentration2). These results show that the composite myocardial patch with the iPS-derived myocardial microtissue layer prepared by the invention can treat the damaged myocardial tissue, and the gelatin concentration during the preparation of the base membrane has an important influence on the repair effect, preferably 10%.
Example 3:
preparing a gel forming aqueous solution containing 5% (w/v, g/ml) chitosan (110000kDa), 0.5% (w/v, g/ml) hyaluronic acid (2000000kDa) and 10% (w/v, g/ml) gelatin (180Bloom g), adding a crosslinking agent carbodiimide for crosslinking reaction, wherein the final concentration of the crosslinking agent is 0.5% (w/v, g/ml), the crosslinking condition is 25 ℃, the humidity is 60%, the crosslinking process time is 10 hours, obtaining a gel membrane, neutralizing by using 0.1M glycine solution for 20 minutes, cleaning and drying (22 ℃, the humidity is 30%), and obtaining the simulated extracellular matrix basement membrane. The iPS cells derived from human blood mononuclear cells are treated according to the method 105Cells/cm2Seeded in petri dishes and using mTeSRTM1 culture in culture broth, replacement when cells reach 90% confluenceContains 100ng/ml Activin A and 2% B27 (insulin-free, Gibco)TMB-27TMSupplement, minisinsulin, cat #: a1895601) for 24 hours. Thereafter, the cells were pre-treated for 4 days with RPMI 1640 medium containing 10ng/ml BMP4 and 2% B27 (no insulin). Then, cells pretreated with Activin A and BMP4 were digested and seeded on the reconstituted basement membrane at a cell seeding density of 5X 104/cm2Cells were cultured for 2 weeks in RPMI 1640 medium with 2% B27 (no insulin).
In addition, the cell seeding density on the reconstituted basement membrane prepared was 104/cm2、2×104/cm2、105/cm2And 2X 105/cm2The patch of (2) was used as a control group (the other preparation conditions were the same). The 5 myocardial patches were implanted on the surface of the damaged myocardial tissue of a rat myocardial infarction model, and the area of each myocardial infarction area was evaluated after 4 weeks. The experimental result shows that the myocardial infarction area of the initial animal model is 4.9cm2The density of transplanted cells was 104/cm2The area of myocardial infarction region of rat with myocardial patch is 4.5cm2And secondly a cell seeding density of 2X 105/cm2Myocardial patch (4.3 cm)2) Followed by 105/cm2Myocardial patch (3.5 cm)2) Then 2X 104/cm2Myocardial patch (3 cm)2) The minimum infarct size is the cell seeding density of 5X 104/cm2Patch (2.2 cm)2). These results show that the composite myocardial patch with the iPS-derived myocardial micro-tissue layer prepared by the invention can treat the damaged myocardial tissue, and the cell inoculation density on the rehydration basement membrane has an important influence on the repair effect, preferably 5 × 104/cm2。
Claims (10)
1. The iPS-derived myocardial cell composite patch is characterized in that:
consists of a basement membrane made of natural polymer materials and a myocardial cell layer which is attached to one side or two sides of the basement membrane and is generated by iPS cell differentiation.
2. The composite patch of claim 1, wherein:
base film preparation: preparing a gelling aqueous solution containing chitosan, hyaluronic acid and gelatin, adding a cross-linking agent for cross-linking reaction to obtain a gel film, and neutralizing, cleaning and drying to obtain a basement membrane;
the concentration of the chitosan in the gel-forming water solution is 1-10% (w/v, g/ml), and the preferred concentration is 5% (w/v, g/ml);
the concentration of the hyaluronic acid in the gel-forming aqueous solution is 0.1-1% (w/v, g/ml), and the preferred concentration is 0.5% (w/v, g/ml);
the concentration of the gelatin in the gel-forming water solution is 3-15% (w/v, g/ml), and the preferred concentration is 10% (w/v, g/ml);
the concentration of the cross-linking agent after the cross-linking agent is mixed with the gel-forming aqueous solution is 0.01-3% (w/v, g/ml), and the preferred concentration is 0.5% (w/v, g/ml).
3. The composite patch of claim 2, wherein:
the molecular weight of the chitosan is 30000-200000kDa, and the preferred molecular weight is 110000;
the molecular weight of the hyaluronic acid is 1300000-3000000kDa, and the preferred molecular weight is 2000000 kDa;
the gelatin comprises one or a mixture of alkaline gelatin and acidic gelatin; the gelatin has a jelly strength of greater than 100Bloom g;
the cross-linking agent is one of formaldehyde, glutaraldehyde, genipin and carbodiimide.
4. The composite patch of claim 1, wherein:
the crosslinking condition is that the temperature is 18-25 ℃, and the crosslinking process time is more than or equal to 60 minutes;
the neutralization process is to use 0.05-0.3M glycine solution to soak a gel film formed by crosslinking, the preferred concentration is 0.1M, and the time of the neutralization process is more than or equal to 10 minutes; the drying condition is that the temperature is 18-25 ℃ and the humidity is 20-40%.
5. A method of making a composite patch according to any of claims 1-4, characterized by:
1) sequentially pretreating iPS cells by Activin A and BMP 4;
2) cells pretreated by Activin A and BMP4 are inoculated on a basement membrane soaked by water, and serum-free induced differentiation is carried out for 1-3 weeks, preferably 2 weeks, so as to obtain the composite patch with beating capability.
6. The method of claim 5, wherein:
the Activin A pretreatment is to treat the iPS cells for 12-36h by using RPMI 1640 culture solution containing 50-200ng/ml Activin A (preferably, the concentration is 100ng/ml) and 1-3% B27 (not containing insulin, preferably, the concentration is 2%), and the treatment time is preferably 24 h.
7. The method of claim 5, wherein:
the BMP4 pretreatment refers to that after Activin A pretreatment, cells are treated for 2-6 days by using RPMI 1640 culture solution containing 5-20ng/ml BMP4 (preferably with the concentration of 10ng/ml) and 1-3% B27 (not containing insulin, preferably with the concentration of 2%) by mass, and the treatment time is preferably 4 days.
8. The method of claim 5, wherein:
digesting cells pretreated by Activin A and BMP4, and then inoculating the cells on a basement membrane soaked in water, wherein the cell inoculation density is 2-10 multiplied by 104/cm2Preferably 5X 104/cm2；
The serum-free induced differentiation refers to the culture of cells in RPMI 1640 culture medium containing 1-3% by mass of B27 (no insulin, preferably 2% by mass).
9. Use of the iPS-derived cardiomyocyte composite patch according to any one of claims 1 to 4 as a transplant for repairing myocardial injury.
10. Use according to claim 9, characterized in that: the myocardial patch has similar composition, structure and function to myocardial tissue, and the iPS-derived myocardial cell composite patch is attached to the surface of the damaged myocardial tissue, so that myocardial damage can be repaired.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112933299A (en) * | 2021-01-18 | 2021-06-11 | 浙江大学 | Composite structure heart patch for inducing directional arrangement of cells and preparation method thereof |
Citations (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101581010A (en) * | 2009-05-21 | 2009-11-18 | 东华大学 | Preparation of bionic extracellular matrix hyaluronic acid and gelatin compound nanofiber membrane |
| CN104189958A (en) * | 2014-08-25 | 2014-12-10 | 中国人民解放军总医院 | Method for preparing chitosan-silk fibroin composite nano-fiber multifunctional patch for promoting myocardial tissue regeneration and monitoring stem cells |
| EP3013380A1 (en) * | 2013-06-24 | 2016-05-04 | Ramot at Tel-Aviv University Ltd. | Omentum based scaffold and delivery system |
| CN105727378A (en) * | 2014-12-09 | 2016-07-06 | 中国科学院大连化学物理研究所 | Preparation method of bFGF slow-release gelatin-polyethylene glycol composite gel membrane for myocardial repair |
| CN105727365A (en) * | 2016-03-29 | 2016-07-06 | 王嘉显 | Heart band-aid and preparation method thereof |
| CN105749350A (en) * | 2016-04-21 | 2016-07-13 | 四川大学 | Myocardial patch and preparation method thereof |
| CN105849253A (en) * | 2013-09-20 | 2016-08-10 | 修复股份有限公司 | A method to direct differentiation of pluripotent stem cells into functional heart muscle |
| CN106552294A (en) * | 2015-09-25 | 2017-04-05 | 上海市东方医院 | A kind of biology patching material for cardiac repair |
| WO2017073794A1 (en) * | 2015-10-30 | 2017-05-04 | 国立大学法人京都大学 | Method for producing three-dimensional myocardial tissue from pluripotent stem cells |
| CN106693059A (en) * | 2016-12-28 | 2017-05-24 | 广州迈普再生医学科技有限公司 | Composite tissue repair patch and preparation method and application thereof |
| JP2017101015A (en) * | 2015-11-25 | 2017-06-08 | 株式会社サイフューズ | Human heart-like structure and method for producing same |
| CN106806942A (en) * | 2015-12-02 | 2017-06-09 | 中国科学院大连化学物理研究所 | A kind of preparation method of cardiac muscle tissue engineering acellular collagen diaphragm |
| CN107551326A (en) * | 2017-09-30 | 2018-01-09 | 广东泰宝医疗科技股份有限公司 | A kind of bionic heart surgical repair material and preparation method thereof |
| CN108159491A (en) * | 2018-01-02 | 2018-06-15 | 山东百多安医疗器械有限公司 | A kind of Cardiac Stem Cells seed and carrying method |
-
2018
- 2018-11-25 CN CN201811411726.9A patent/CN111214703B/en active Active
Patent Citations (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101581010A (en) * | 2009-05-21 | 2009-11-18 | 东华大学 | Preparation of bionic extracellular matrix hyaluronic acid and gelatin compound nanofiber membrane |
| EP3013380A1 (en) * | 2013-06-24 | 2016-05-04 | Ramot at Tel-Aviv University Ltd. | Omentum based scaffold and delivery system |
| CN105849253A (en) * | 2013-09-20 | 2016-08-10 | 修复股份有限公司 | A method to direct differentiation of pluripotent stem cells into functional heart muscle |
| CN104189958A (en) * | 2014-08-25 | 2014-12-10 | 中国人民解放军总医院 | Method for preparing chitosan-silk fibroin composite nano-fiber multifunctional patch for promoting myocardial tissue regeneration and monitoring stem cells |
| CN105727378A (en) * | 2014-12-09 | 2016-07-06 | 中国科学院大连化学物理研究所 | Preparation method of bFGF slow-release gelatin-polyethylene glycol composite gel membrane for myocardial repair |
| CN106552294A (en) * | 2015-09-25 | 2017-04-05 | 上海市东方医院 | A kind of biology patching material for cardiac repair |
| WO2017073794A1 (en) * | 2015-10-30 | 2017-05-04 | 国立大学法人京都大学 | Method for producing three-dimensional myocardial tissue from pluripotent stem cells |
| JP2017101015A (en) * | 2015-11-25 | 2017-06-08 | 株式会社サイフューズ | Human heart-like structure and method for producing same |
| CN106806942A (en) * | 2015-12-02 | 2017-06-09 | 中国科学院大连化学物理研究所 | A kind of preparation method of cardiac muscle tissue engineering acellular collagen diaphragm |
| CN105727365A (en) * | 2016-03-29 | 2016-07-06 | 王嘉显 | Heart band-aid and preparation method thereof |
| CN105749350A (en) * | 2016-04-21 | 2016-07-13 | 四川大学 | Myocardial patch and preparation method thereof |
| CN106693059A (en) * | 2016-12-28 | 2017-05-24 | 广州迈普再生医学科技有限公司 | Composite tissue repair patch and preparation method and application thereof |
| CN107551326A (en) * | 2017-09-30 | 2018-01-09 | 广东泰宝医疗科技股份有限公司 | A kind of bionic heart surgical repair material and preparation method thereof |
| CN108159491A (en) * | 2018-01-02 | 2018-06-15 | 山东百多安医疗器械有限公司 | A kind of Cardiac Stem Cells seed and carrying method |
Non-Patent Citations (7)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112933299A (en) * | 2021-01-18 | 2021-06-11 | 浙江大学 | Composite structure heart patch for inducing directional arrangement of cells and preparation method thereof |
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