CN110585483A - Novel biological ink capable of being crosslinked by multiple methods and preparation method thereof - Google Patents

Novel biological ink capable of being crosslinked by multiple methods and preparation method thereof Download PDF

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CN110585483A
CN110585483A CN201910915780.5A CN201910915780A CN110585483A CN 110585483 A CN110585483 A CN 110585483A CN 201910915780 A CN201910915780 A CN 201910915780A CN 110585483 A CN110585483 A CN 110585483A
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acellular matrix
methacrylic anhydride
initiator
modified
bio
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莫秀梅
余凡
吴晶磊
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Donghua University
National Dong Hwa University
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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
    • 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
    • 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
    • A61L27/36—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
    • A61L27/3683—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A61L27/3691—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y70/00—Materials specially adapted for additive manufacturing
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F289/00—Macromolecular compounds obtained by polymerising monomers on to macromolecular compounds not provided for in groups C08F251/00 - C08F287/00

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Abstract

The invention relates to novel biological ink capable of being crosslinked by multiple methods and a preparation method thereof. The ink comprises: methacrylic anhydride modified acellular matrix, pepsin, an initiator or other material that can chemically cross-link with methacrylic anhydride modified acellular matrix, and a cell suspension. The method comprises the following steps: adding acellular matrix powder into a solution of pepsin, dropwise adding methacrylic anhydride, performing amidation reaction, dialyzing, freezing, and freeze-drying to obtain an acellular matrix modified by the methacrylic anhydride, and adding an initiator or other materials and cell suspensions capable of chemically crosslinking with the acellular matrix modified by the methacrylic anhydride. The ink has the performances of thermal crosslinking, photo crosslinking and chemical crosslinking, and the biocompatibility is basically unchanged.

Description

Novel biological ink capable of being crosslinked by multiple methods and preparation method thereof
Technical Field
The invention belongs to the field of biological ink and preparation thereof, and particularly relates to novel biological ink capable of being crosslinked by multiple methods and a preparation method thereof.
Background
With the development of aging population and the gradual increase of the incidence of various traumas and diseases, tissue or organ defects become a common phenomenon, such as bone and cartilage defects, heart valve insufficiency, mastectomy, and extensive skin necrosis.
Existing methods of treating tissue or organ defects include filling the defect with degradable natural or synthetic materials, adding cellular material composites, or filling permanent prostheses. The filled material has large mechanical difference with the defect part, the shape can not be completely matched, the difference in chemical composition is very large, and the material lacks of cell recognition sites, and is easy to cause allergy, rejection reaction and the like. Therefore, techniques that can match tissue defects in shape, mechanics, chemical composition, and biological signals are a major development trend in the future.
Three-dimensional printing technology, also known as additive manufacturing technology, is a rapid prototyping technology. It is based on digital model file and uses powder, metal, plastic or hydrogel etc. adhesive material to build the needed shape substance by layer-by-layer printing. At present, the three-dimensional printing technology has been widely researched in the field of tissue engineering. Natural or synthetic biomaterials can be made into bio-ink, and can also be mixed with cells or active drugs, and the technology has great application in the field of tissue engineering by simulating the extracellular matrix of living tissues. At present, the three-dimensional printing technology can be used for preparing tissue and organ and tissue engineering scaffolds for drug tests.
The acellular matrix generally refers to extracellular matrix components and structures without cells prepared by carrying out cell inactivation treatment on heterologous tissues, and the components mainly comprise collagen, structural proteins, glucosamine, elastin and the like. The acellular matrix has the same components of natural extracellular matrix, low immunogenicity, good histocompatibility, and is favorable for cell adhesion, proliferation and differentiation, and is an ideal tissue engineering scaffold material.
At present, the three-dimensional printing of the acellular matrix is mainly mixed with other materials or used as a coating of a synthetic polymer, and due to poor mechanical property and lack of an in-situ crosslinking method, the research on pure acellular matrix biological ink and the acellular matrix as a main raw material is relatively less.
Therefore, the methacrylate functional group is grafted on the decellularized extracellular matrix, so that the decellularized extracellular matrix is endowed with the performances of photocrosslinking and chemical crosslinking on the basis of the original thermal crosslinking, and the biocompatibility is basically unchanged, so that the method has important significance for expanding the application and industrialization of the decellularized extracellular matrix in the three-dimensional printing tissue engineering scaffold.
Disclosure of Invention
The invention aims to solve the technical problem of providing a novel bio-ink capable of being crosslinked by multiple methods and a preparation method thereof, so as to overcome the defects of the prior art that a gelling method for removing extracellular matrix is lacked and the like.
The invention provides a bio-ink capable of being crosslinked by multiple methods, which comprises the following components: methacrylic anhydride modified acellular matrix, pepsin, an initiator or other material that can chemically cross-link with methacrylic anhydride modified acellular matrix, and a cell suspension.
The methacrylic acid modified acellular matrix is obtained by adding methacrylic anhydride into pepsin solution of the acellular matrix for amidation reaction.
The initiator is a photo-crosslinking initiator or a thermal initiator.
The photo-crosslinking initiator includes: 2-hydroxy-2-methyl-1-phenylpropanone, 1-hydroxycyclohexyl phenyl methanone, 2-methyl-2- (4-morpholinyl) -1- [4- (methylthio) phenyl ] -1-propanone, 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropiophenone, 2,4, 6-trimethylbenzoyl-diphenylphosphine oxide or 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone.
The thermal initiator comprises an azo initiator, an organic peroxide initiator or an inorganic peroxide initiator.
The other material chemically crosslinkable with methacrylic acid-modified acellular matrix is a compound that can undergo a michael addition reaction or an addition reaction with methacrylic anhydride-modified acellular matrix.
The compound which has Michael addition reaction or addition reaction with the methacrylic anhydride modified acellular matrix comprises amino acid containing sulfydryl or disulfide bonds, protein or macromolecules containing unsaturated bonds.
The unsaturated bond-containing polymer includes: sulfhydryl terminated polyethylene glycol (4-ARM-PEG-SH, 6-ARM-PEG-SH, or 8-ARM-PEG-SH), sulfhydryl chitosan, sulfhydryl hyaluronic acid, PEG or PEGMA modified by maleic anhydride or its derivatives, proteins involved by one or more of methionine, cysteine, cystine, etc.
The cell comprises: stem cells, cartilage cells, skin cells, IPS cells and cardiac muscle cells.
The biological ink can be used for preparing composite biological ink with natural materials or synthetic materials.
The invention also provides a preparation method of the biological ink capable of being crosslinked by multiple methods, which comprises the following steps:
(1) adding acellular matrix powder into a solution of pepsin, stirring until the acellular matrix powder is dissolved, adjusting the pH value to 7.0-8.0, dropwise adding methacrylic anhydride, performing amidation reaction, dialyzing, freezing, and freeze-drying to obtain an acellular matrix modified by methacrylic acid;
(2) and (2) dissolving the methacrylic anhydride modified acellular matrix in the step (1) in a solution of pepsin, and adding an initiator or other materials capable of chemically crosslinking with the methacrylic anhydride modified acellular matrix and cell suspension to obtain the bio-ink.
The preparation method of the acellular matrix powder in the step (1) comprises the following steps: (1) obtaining fresh animal tissue material, and storing at low temperature of 4 deg.C; (2) decellularizing the animal tissue material to form a decellularized matrix; (3) the acellular matrix was frozen at-80 ℃ and ground, and the above procedure was repeated until acellular matrix powder was obtained.
The acellular matrix is derived from mammals or fishes.
The animal tissue includes skin, cartilage, lung, valve, small intestine, large intestine, ligament, or adipose tissue.
The pH value of the solution of the pepsin in the step (1) is 3.0-4.0.
Stirring until the solution in the step (1) is: slowly stirred at room temperature until completely dissolved.
In the step (1), the amidation reaction temperature is room temperature, and the amidation reaction time is 12-24 h.
The dialysis in the step (1) is as follows: dialyzing in deionized water using 3500 MWCO dialysis bag for three days, and changing water three times per day.
The freezing temperature was-80 ℃.
The gelling mode used by the methacrylic anhydride modified acellular matrix in the step (1) in the biological printing comprises photocrosslinking, thermal crosslinking and chemical crosslinking with other materials.
Advantageous effects
(1) The invention can endow the extracellular matrix with the performances of photo-crosslinking and chemical crosslinking on the basis of the original thermal crosslinking of the extracellular matrix.
(2) The application scenes of the extracellular matrix-free biological ink are enriched.
Drawings
FIG. 1 is a graph of the acellular matrix bio-ink of example 1 before and after photocrosslinking.
FIG. 2 is a diagram of the acellular matrix bio-ink of example 1 before and after thermal crosslinking.
FIG. 3 is the (a) image and (b) scanning electron micrograph of the acellular matrix bio-ink hydrogel of example 1 after freeze-drying.
FIG. 4 is a H-NMR chart of methacrylic anhydride-modified acellular matrix and acellular matrix of example 1.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.
Example 1
A novel biological ink capable of being crosslinked in a multiple method comprises a methacrylic anhydride modified acellular matrix, thiolated chitosan, cells and a solvent, and the preparation method comprises the following steps:
(1) pepsin was weighed out and dissolved in 0.01mol/L HCl solution at a concentration of 1 mg/ml. Weighing acellular matrix, dissolving in the solution at a concentration of 15mg/ml, and stirring at room temperature for 18h at a stirring speed of 300 r/min.
(2) Adjusting the pH of the acellular matrix solution (15mg/ml) to 7.5, and then dropwise adding methacrylic anhydride (the weight ratio of the methacrylic anhydride to the acellular matrix is 0.5 ml/g); reacting at room temperature for 12h, dialyzing in deionized water for three days by using a dialysis bag with the molecular weight cutoff of 3500, and changing water three times per day; the dialyzed solution was frozen at-80 ℃ and then freeze-dried to obtain methacrylic acid-modified acellular matrix powder.
(3) Adding concentrated hydrochloric acid into PBS buffer solution to prepare hydrochloric acid solution with concentration of 0.01mol/L, then adding pepsin into hydrochloric acid solution to make pepsin concentration be 1mg/ml, preparing hydrochloric acid solution of pepsin of methacrylic acid modified acellular matrix powder according to concentration of 15mg/ml, adding sodium hydroxide to regulate pH to be 7.5, digesting cells, centrifuging, pouring out liquid, adding proper amount of culture medium to prepare 5 x 106cell/ml density cell culture medium according to 1.5mg/ml thiolated chitosan, 5 x 105And dissolving the cell/ml L929 cell culture medium in the acellular matrix solution with the adjusted pH value to prepare the biological ink precursor.
(4) Taking 5ml of the biological ink precursor, placing the biological ink precursor in an incubator at 37 ℃ for 2 hours, and then carrying out thermal crosslinking, curing and forming; and (3) adding 25mg of photoinitiator I2959 into 5ml of the biological ink precursor, uniformly stirring, and irradiating for 30s by using an ultraviolet light source with the wavelength of 365nm and the power of 10w to carry out photocrosslinking, curing and molding.
FIG. 3 shows: the solidified hydrogel is frozen at-80 ℃ and then freeze-dried, so that the freeze-dried hydrogel is found to be a loose porous structure, and further scanning electron microscope pictures show that the freeze-dried hydrogel scaffold has a nanofiber structure.
FIG. 4 shows that: by H-NMR nuclear magnetic diagram (solvent D)2O) comparison, methacrylic anhydride modified acellular matrix profile relative to acellular matrix profile, new peaks appear at 6.2ppm (b) and 5.7ppm (a), which are the resulting peaks of methacrylic anhydride binding to collagen in the acellular matrix, indicating successful preparation of methacrylic anhydride modified acellular matrix.
Example 2
A novel biological ink capable of being crosslinked by multiple methods and a preparation method thereof are disclosed, wherein the novel biological ink comprises a methacrylic anhydride modified acellular matrix, methacrylic acid gelatin, a crosslinking initiator, cells and a solvent, and the preparation method comprises the following steps:
(1) preparing hydrochloric acid solution by using PBS buffer solution, preparing pepsin hydrochloric acid solution of methacrylic anhydride modified acellular matrix powder according to the mass fraction of 1.5% of the hydrochloric acid solution, preparing the methacrylic anhydride modified acellular matrix powder and pepsin hydrochloric acid solution according to the same preparation method as the example 1, adding sodium hydroxide to adjust the pH to be 7.5, and taking 2% methacrylic acid acidified gelatin by using the mass fraction of the hydrochloric acid solution, 0.05% photoinitiator I2959 and 5 10 by using the mass fraction of the hydrochloric acid solution5And dissolving the cell/ml L929 cell culture medium in the acellular matrix solution with the adjusted pH value to prepare the biological ink.
(2) 5ml of the biological ink is placed in an incubator at 37 ℃ for 2 hours, and then the thermal crosslinking curing molding is carried out; 5ml of the biological ink is taken, evenly stirred and irradiated for 30s by an ultraviolet light source with the wavelength of 365nm and the power of 10w, and then photocrosslinking, curing and forming are carried out.
The bio-ink manufactured by the prior art comprises 0.01-5 wt% of nano hectorite, 5-40 wt% of methacryloylated gelatin, 0.01-0.5 wt% of photoinitiator and 55-90 wt% of cell culture medium, wherein the photoinitiator is 2-hydroxy-4- (2-hydroxyethoxy) -2-methyl propiophenone.
The invention is different from the prior art in that the hydrogel is made of different main materials, namely, the hydrogel is an acellular matrix modified by methacrylic anhydride, and the prior art is methacrylated gelatin and nano hectorite.

Claims (10)

1. A multi-process crosslinkable bio-ink, comprising: methacrylic anhydride modified acellular matrix, pepsin, an initiator or other material that can chemically cross-link with methacrylic anhydride modified acellular matrix, and a cell suspension.
2. The bio-ink according to claim 1, wherein the methacrylic anhydride modified acellular matrix is obtained by adding methacrylic anhydride to a pepsin solution of the acellular matrix for amidation reaction.
3. The bio-ink according to claim 1, wherein the initiator is a photo-crosslinking initiator or a thermal initiator.
4. The bio-ink according to claim 3, wherein the photo-crosslinking initiator comprises: 2-hydroxy-2-methyl-1-phenylpropanone, 1-hydroxycyclohexylphenylmethanone, 2-methyl-2- (4-morpholinyl) -1- [4- (methylthio) phenyl ] -1-propanone, 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropiophenone, 2,4, 6-trimethylbenzoyl-diphenylphosphine oxide or 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone; the thermal initiator comprises an azo initiator, an organic peroxide initiator or an inorganic peroxide initiator.
5. The bio-ink according to claim 1, wherein the other material chemically crosslinkable with the methacrylic anhydride-modified acellular matrix is a compound capable of undergoing a michael addition reaction or an addition reaction with the methacrylic anhydride-modified acellular matrix.
6. The bio-ink according to claim 5, wherein the compound undergoing Michael addition reaction or addition reaction with methacrylic anhydride-modified acellular matrix comprises amino acids containing thiol or disulfide bonds, proteins, thiol-terminated polyethylene glycol, thiolated chitosan, thiolated hyaluronic acid, PEG or PEGMA modified with maleic anhydride or its derivatives.
7. The bio-ink according to claim 1, wherein the cells comprise: stem cells, cartilage cells, skin cells, IPS cells and cardiac muscle cells.
8. A preparation method of bio-ink capable of being crosslinked by a multiple method comprises the following steps:
(1) adding acellular matrix powder into a solution of pepsin, stirring until the acellular matrix powder is dissolved, adjusting the pH value to 7.0-8.0, dropwise adding methacrylic anhydride, performing amidation reaction, dialyzing, freezing, and freeze-drying to obtain an acellular matrix modified by methacrylic anhydride;
(2) and (2) dissolving the methacrylic anhydride modified acellular matrix in the step (1) in a solution of pepsin, and adding an initiator or other materials capable of chemically crosslinking with the methacrylic anhydride modified acellular matrix and a cell suspension to obtain the bio-ink.
9. The method according to claim 8, wherein the acellular matrix powder of step (1) is prepared by a method comprising: (1) obtaining fresh animal tissue material, and storing at low temperature of 4 deg.C; (2) decellularizing the animal tissue material to form a decellularized matrix; (3) the acellular matrix was frozen at-80 ℃ and ground, and the above procedure was repeated until acellular matrix powder was obtained.
10. The method of claim 8, wherein the amidation reaction temperature in step (1) is room temperature, and the amidation reaction time is 12h-24 h.
CN201910915780.5A 2019-09-26 2019-09-26 Novel biological ink capable of being crosslinked by multiple methods and preparation method thereof Pending CN110585483A (en)

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CN111359011A (en) * 2020-03-31 2020-07-03 东华大学 Method for preparing protein bio-ink by promoting amidation reaction
CN111359017A (en) * 2020-03-31 2020-07-03 东华大学 Preparation method of novel cartilage acellular matrix ink
CN111420121A (en) * 2020-04-03 2020-07-17 苏州大学 Composite biological ink based on methacrylated hydrogel/nanoclay/acellular matrix and preparation method and application thereof
CN111686306A (en) * 2020-07-08 2020-09-22 四川大学 3D printing biological ink based on acellular costal cartilage matrix and preparation method and application thereof
CN111962210A (en) * 2020-06-22 2020-11-20 华南理工大学 Polycaprolactone/methacryloylated elastin nanofiber composite membrane and preparation method and application thereof
CN113304319A (en) * 2021-03-03 2021-08-27 南京市第一医院 Biological material for bladder tissue repair and preparation method thereof
CN113403268A (en) * 2021-08-20 2021-09-17 北京大学第三医院（北京大学第三临床医学院） Biological ink containing stem cell exosomes and manufacturing method thereof
CN113577386A (en) * 2020-04-30 2021-11-02 中国科学院深圳先进技术研究院 Double-network biological ink and preparation method and application thereof
CN115475279A (en) * 2021-05-31 2022-12-16 上海交通大学医学院附属第九人民医院 Photosensitive cartilage acellular matrix hydrogel material and preparation method and application thereof
CN115501376A (en) * 2022-09-16 2022-12-23 常州美杰医疗用品有限公司 Gel type antibacterial medical band-aid and preparation method thereof

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CN111359017A (en) * 2020-03-31 2020-07-03 东华大学 Preparation method of novel cartilage acellular matrix ink
CN111359011A (en) * 2020-03-31 2020-07-03 东华大学 Method for preparing protein bio-ink by promoting amidation reaction
CN111359017B (en) * 2020-03-31 2021-05-11 东华大学 Preparation method of novel cartilage acellular matrix ink
CN111420121A (en) * 2020-04-03 2020-07-17 苏州大学 Composite biological ink based on methacrylated hydrogel/nanoclay/acellular matrix and preparation method and application thereof
CN113577386A (en) * 2020-04-30 2021-11-02 中国科学院深圳先进技术研究院 Double-network biological ink and preparation method and application thereof
CN111962210A (en) * 2020-06-22 2020-11-20 华南理工大学 Polycaprolactone/methacryloylated elastin nanofiber composite membrane and preparation method and application thereof
CN111962210B (en) * 2020-06-22 2022-03-25 华南理工大学 Polycaprolactone/methacryloylated elastin nanofiber composite membrane and preparation method and application thereof
CN111686306A (en) * 2020-07-08 2020-09-22 四川大学 3D printing biological ink based on acellular costal cartilage matrix and preparation method and application thereof
CN113304319A (en) * 2021-03-03 2021-08-27 南京市第一医院 Biological material for bladder tissue repair and preparation method thereof
CN115475279A (en) * 2021-05-31 2022-12-16 上海交通大学医学院附属第九人民医院 Photosensitive cartilage acellular matrix hydrogel material and preparation method and application thereof
CN115475279B (en) * 2021-05-31 2024-05-07 上海交通大学医学院附属第九人民医院 Photosensitive cartilage acellular matrix hydrogel material, and preparation method and application thereof
CN113403268A (en) * 2021-08-20 2021-09-17 北京大学第三医院（北京大学第三临床医学院） Biological ink containing stem cell exosomes and manufacturing method thereof
CN115501376A (en) * 2022-09-16 2022-12-23 常州美杰医疗用品有限公司 Gel type antibacterial medical band-aid and preparation method thereof
CN115501376B (en) * 2022-09-16 2023-09-15 常州美杰医疗用品有限公司 Gel type antibacterial medical band-aid and preparation method thereof

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Application publication date: 20191220