CN104136602B - Cell tissue adhesive - Google Patents
Cell tissue adhesive Download PDFInfo
- Publication number
- CN104136602B CN104136602B CN201180073036.7A CN201180073036A CN104136602B CN 104136602 B CN104136602 B CN 104136602B CN 201180073036 A CN201180073036 A CN 201180073036A CN 104136602 B CN104136602 B CN 104136602B
- Authority
- CN
- China
- Prior art keywords
- growth factor
- factor
- cell
- tissue adhesive
- cell tissue
- Prior art date
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0068—General culture methods using substrates
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- 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
- A61L27/3834—Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
-
- 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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
-
- 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
- A61L27/52—Hydrogels or hydrocolloids
-
- 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
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/64—Animal cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/30—Synthetic polymers
- C12N2533/32—Polylysine, polyornithine
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/50—Proteins
- C12N2533/54—Collagen; Gelatin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2537/00—Supports and/or coatings for cell culture characterised by physical or chemical treatment
- C12N2537/10—Cross-linking
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dermatology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Transplantation (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Botany (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Developmental Biology & Embryology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Composite Materials (AREA)
- Materials Engineering (AREA)
- Materials For Medical Uses (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The present invention provides a kind of cell tissue adhesive of the reaction active groups crosslinking for stopping agent (quenching agent) with crosslinking agent (cross linking agent), resistance.
Description
【Prior art】
Cell tissue adhesive has application miscellaneous because of its adhesion characteristic, and traditional adhesive is to use crosslinking mostly
Agent is to be made material.However, crosslinking agent is toxic to organism.Then in the use of cell tissue adhesive, it is necessary to dropped
The toxicity of low cross-linking agent.
【The content of the invention】
The present invention be based on the unexpected finding that, i.e., one cell tissue gluing can produce friendship by with a crosslinking agent
Connection, and stop agent including a resistance, the functional group that the crosslinking agent is showed can be combined, improve its boundary intensity and reduce toxicity.
Therefore, it is a feature of the present invention that a kind of cell tissue adhesive , Bao Kuo ︰ one or more substrate molecules
(matrix molecule), it produces crosslinking, and a resistance to stop agent with a crosslinking agent (cross-linking agent)
(quenching agent), its functional group for being bonded to the crosslinking agent.
One or more above-mentioned substrate molecules are selected from by collagen (collagen), hyaluronic acid
(hyaluronan), gelatin (gelatin), fiber connect albumen (fibronectin), elastin laminin (elastin), cell adhesion
Plain (tenascin), basement membrane element (laminin), vitronectin (vitronectin), Heparan sulfate (heparan
Sulfate), chondroitin (chondroitin), chondroitin sulfate (chondroitin sulfate), keratan (keratan),
Keratan sulfate (keratan sulfate), dermatan sulfate (dermatan sulfate), carragheen (carrageenan),
Heparin (heparin), chitin (chitin), spherical chitosan (chitosan), alginate (alginate), agar-agar
(agarose), agar (agar), cellulose (cellulose), methylcellulose (methyl cellulose), carboxymethyl are fine
The group that dimension plain (carboxyl methyl cellulose) and glycogen (glycogen) are constituted, but be not limited.One
In embodiment, described substrate molecule including collagen, any one of hyaluronic acid and gelatin.
Crosslinking agent (cross-linking agent) generally has two or more functional response's bases, and the functional group can phase
With or differ.Above-mentioned crosslinking agent is selected from containing epoxides (epoxide), dialdehyde-based (dialdehyde), N- hydroxyls
Base succinimide (N-hydroxysuccinimide ester), carbon imidodicarbonic diamide (carbodiimide), gardenin
(genipin), riboflavin (riboflavin), flavonoids (flavonoid), 6- maleimidocaproic acid active esters (6-
Maleimidohexanoic acid active ester), succinimide suberate (disuccinimidyl
Suberate), sulfosuccinimide base -4- (N- maleimidomehyls) hexamethylene -1- carboxylic acid tert-butyl esters
(sulfosuccinimidyl-4- (N-maleimidomethyl) cyclohexane-1-carboxylate) and double (thio ambers
Amber imide) group that is constituted of suberate (bis (sulfosuccinimidyl) suberate), but be not limited.
It is to be selected to contain diamines (diamine), few amine (oligoamine), polyamines (polyamine), dicarboxylic acids that described resistance stops agent
(dicarboxylic acid), few carboxylic acid (oligo-carboxylic acid), polycarboxylic acids (polycarboxylic
Acid), multi-thioalcohol compound (polysulfhydryl compound), polyol (polyhydroxy
Compound) and base containing isodigeranyl (heterobifunctional) the group that is constituted of compound, but be not limited.
In one embodiment, the crosslinking agent be gardenin and the resistance to stop agent be poly-L-Lysine (poly-L-
lysine).The mean molecule quantity of wherein described polylysine is more than 20kDa, is optimally greater than 99kDa or more than 212kDa.
In another embodiment, the crosslinking agent is ethylene glycol diglycidylether (ethylene glycol diglycidyl
Ether), it is water that the resistance stops agent.In another embodiment, the crosslinking agent is ethylene glycol diglycidylether, and the resistance stops
Agent is polylysine (poly-lysine) or r- polyglutamic acids (r-polyglutamic acid).
Cell of the invention knits adhesive further containing a nutriment (for example, cell culture medium), bioactivator,
And/or cell (for example, stem cell).Described bioactivator can be a growth factor, selected from by EGF
(epidermal growth factor, EGF), fiber mother cell growth factor (fibroblast growth factor,
FGF), VEGF (vascular endothelial growth factor, VEGF), connective tissue growth because
Sub (connective tissue growth factor, CTGF), platelet derived growth factor (platelet-derived
Growth factor, PDGF), insulin-like growth factor (insulin-like growth factor, IGF), nerve growth
The factor (nerve growth factor, NGF), HGF (hepatocyte growth factor, HGF), group
G-CSF (colony-stimulating factor, CSF), stem cell factor (stem cell factor, SCF), angle
Cell plastid growth factor (keratinocyte growth factor, KGF), white blood cell growth factor (granulocyte
Colony-stimulating factor, GCSF), macrophage colony stimulating factor (granulocyte macrophage
Colony-stimulating factor), neuroglia derives nerve and nourishes the factor (glial derived neurotrophic
Factor, GDNF), hairy neurotrophic factor (ciliary neurotrophic factor), endothelial cell monocyte live
Property polypeptide (endothelial-monocyte activating polypeptide), epidermis neutrality ball active peptides
(epithelial neutrophil activating peptide), erythropoietin (erythropoietin), bone modeling
Type albumen (bone morphogenetic protein), brain derived nerve nourish the factor (brain-derived
Neurotrophic factor), conversion growth factor-β (transforming growth factor beta), mammary gland performance
The group that chemotactic factor (CF) (BRAK) and TNF (tumor necrosis factor) are constituted.
The present invention also provides a kind of implantation cell (such as stem cell) and provides a kind of thin in method , Bao Kuo ︰ (i) of an individuality
Born of the same parents' implant (cell implant), the cellular implant includes cell tissue adhesive as described above and a cell source；
And the implant is implanted in the individuality by (ii).Further within the scope of the invention, it is using cell tissue adhesive
In the implant unit that manufacture cell transmission is used.
In following description, further just the details of multiple embodiments is illustrated the present invention, is that can show and know it and send out
Bright feature and advantage.
【Specific embodiment】
Present invention offer is a kind of to can be used for the bio-compatibility small cell tissue adhesive of cell growth.Comprising one or with
On substrate molecule (seeing below), itself and a crosslinking agent produce crosslinking, and a resistance to stop agent, and it is bonded to the one of the crosslinking agent
Functional group.Cell tissue gel of the invention further includes a nutriment (for example, cell culture medium), bioactivator,
And/or cell (for example, stem cell).
Substrate molecule
Substrate molecule (for example, macromolecular compound) helps cell to be maintained at an implant site, is one in extracellular matrix
In extracellular molecules, in this reference person for example:Collagen, hyaluronic acid, gelatin, fiber connect albumen, elastin laminin, carefully
Born of the same parents' conglutnin, basement membrane element, vitronectin, polypeptide, Heparan sulfate, chondroitin, chondroitin sulfate, keratan sulfate, sulfuric acid
Keratan, dermatan sulfate, carrageenan, heparin, chitin, deacetylchitosan, alginates, agarose, agar, methyl is fine
Dimension element, methylcellulose, carboxymethylcellulose calcium, glycogen or derivatives thereof, but not limited to this.Additionally, substrate molecule can also be
Fibrin, fibrinogen, fibrin ferment, and polyglutamic acid, synthetic polymer is (for example, acrylate, PLA, PVOH
Acid, or poly- (lactic-co-glycolic acid), optimal, the high score of the substrate molecule for being applied to tissue gel used in the present invention
Sub- quantity of material, to improve the viscosity of gel.
Any naturally occurring collagen or its its function variant (functional variants), can be used in system
Standby tissue glue of the invention.At present, 28 kinds of collagens of different genes species are at least had found.Collagen can be simple
From the mankind or animal rich in being separated in collagen tissue (such as skin, tendon, ligament and bone tissue), be purified.Separate
Purified collagen method is generally well known in this field.(can refer to Li such as ︰ United States Patent (USP)s 5,512,291, United States Patent (USP)
Application discloses No. 20040138695 publications, Methods in Enzymology, vol.82, pp.33-64,1982, The
Preparation of Highly Purified Insoluble Collagen, Oneson, I., et al,
Am.Leather Chemists Assoc., Vol.LXV, pp.440-450,1970, United States Patent (USP) 6,090,996).Collagen egg
Bai Yineng is prepared using recombinant technique, such as described by Advanced Tissue Sciences (La Jolla, Calif.),
Or buy (such as Fibrogen from different suppliers；South San Francisco,Calif.).The following is an embodiment：Ox
Musculus flexor profundus tendon, washes with water after removing fat and manadesma, freezes, and be cut into 0.5 millimeter of (mm) thin slice with food slicer.First will be appropriate
Section tendon is extracted 24 hours at room temperature with 50 milliliters of water of (mL).Abandon water-soluble portion, the tendon then cut into slices with
Acid solution (such as 0.2N hydrochloric acid) extracts one section of reasonable time at appropriate temperature (such as room temperature), and (such as 12 hours to 24 small
When).Hydrochloric acid solution washes away the acid solution remained on tendon with water after abandoning.Flushed tendon uses alkaline solution (such as
0.75M NaOH) carry out extracting one section of reasonable time (such as 12 hours to 24 hours) in appropriate temperature (such as room temperature).It
Removal of alkaline solution, section tendon is neutralized using acid solution (such as 0.1N hydrochloric acid) until pH value is 4 to 7 (such as pH 5) afterwards,
Then the alkali lye that water remains in tendon to wash away is reused.Tendon is taken off using alcohols (such as isopropanol) in room temperature afterwards
One section of time enough of fat (such as 16 hours).Extract is poured out and tendon is made in room temperature using alcohols (such as isopropanol)
Further extraction a period of time (such as 12 hours to 24 hours), forms the solution containing collagen, and the solution of collagen is dry
Dried in net exhausting cabinet.Therefore the collagen protein powder for being formed can be leached in acid solution (such as 0.5M or 0.25M acetic acid),
In one section of reasonable time of reaction in 4 DEG C in the presence of containing proteolytic enzyme (such as trypsase or pepsin).Use
The stainless steel mesh screen of 100 mesh filters mixture, it is possible to go out soluble collagen Shen Dian, Shen Dian using 5% saline solution
Collagen can be redissolved with above-mentioned acid solution, therefore the solution for being formed can be come using 100 mesh stainless steel mesh screens
Filter, to remove insoluble microparticle.Then this glue protein solution dialyses to remove the acid in solution in pure water.
The hyaluronic acid that the present invention is chatted refers to naturally occurring anionic, the poly- candy of osamine of non sulphate
, including N-acetyl-glucosamine (N-acetylglucosamine) and D- glucuronic acids (D- (glycosaminoglycan)
Glucuronic acid) multiple disaccharide unit, and its derivative.Hyaluronic acid can be separated from natural goods, such as
The vitreum of cryptomere streptococcus, cockscomb, cartilage, synovial joint fluid, umbilical cord, skin histology and eyes, by such as Guillermo
Lago et al.Carbohydrate Polymers 62(4):321-326,2005 and Ichika Amagai et
al.Fisheries Science 75(3):Art methods described in 805-810,2009.Or, can be to the supply of material of business
Business, such as Genzyme Corporation, Lifecore Biomedical, LLC and Hyaluron Contract
Manufacturing buys.The spin-off of natural hyaluronic acid includes but is not limited to following hyaluronic acid ester (hyaluronan
Esters), adipic dihydrazide-modification hyaluronic acid (adipic dihydrazide-modified hyaluronan), thoroughly
Bright matter acid amide products (hyaluronan amide products), cross-linked-hyaluronic acid (crosslinked hyaluronic
Acid), the heavy metal salt of half fat succinic acid (hemiesters of succinic acid) or hyaluronic acid, part or complete
Esterified hyaluronic acid, vulcanization hyaluronic acid (sulphated hyaluronic acid), N- vulcanization hyaluronic acids (N-
Sulphated hyaluronic acid) and amine or diamine modified hyaluronic acid.Derivatives of hyaluronic acids also can by one with
Upper functional group's chemical modification and obtain, wherein the functional group includes, but are not limited to carboxylic acid group (carboxylic acid
Group), hydroxyl (hydroxyl group), reducing end group (reducing end group) and N- acetyl group (N-acetyl
Group) wherein the modification reaction of carboxylic acid group can be by carbon imidodicarbonic diamide (carbodiimide) and bishydrazide
(bishydrazide) catalysis or esterification (esterification) are modified；The wherein modification reaction of hydroxyl, including
But it is not limited to sulphation (sulfation), esterification, isourea coupling (isourea coupling), cyanogen bromide-activated (cyanogen
Bromide activation) and periodate oxidation (periodate oxidation)；Reducing end group can be by reduction amination
(reductive amination) is modifying reducing end group.Hyaluronic acid can also be linked to Phospholipids, dyestuff (such as fluorescent base
Group or chromophore) and it is used to prepare the reagent of nucleophilicity matrix.The derivative of natural hyaluronic acid can also be by using
Crosslinking agent, intramolecular esterification (internal esterification), photo-crosslinking (photocross-linking) or table
Face plasma-based treatment (surface plasma treatment) and obtain, wherein using crosslinking agent include, but are not limited to it is bicyclic
Oxide (bisepoxide), divinyl sulfone (divinylsulfone), dual-carbodiimide (biscarbodiimide), molecule
Less difunctionality base bridging agent, formaldehyde (formaldehyde), NSC 87419 (cyclohexyl isocyanide),
From amino acid ethyl ester (lysine ethyl ester), anionic metal, hydrazides (hydrazide) or above-mentioned combination.
The hyaluronic acid (i.e. more than 5kDa) of hyaluronic acid, particularly HMW has been shown at present, can be effectively facilitated
Blood vessel is new into and then promoting wound healing.Such as U.S.'s Applicatioll 61/390,789, the molecular weight of hyaluronic acid is
(such as 70kDa to 1,500kDa, 200kDa to 1,500kDa, 500kDa to 1,500kDa or 700kDa are extremely for 50kDa to 5,000kDa
1,500kDa)。
Further, show that stem cell shows the improvement of survival rate, collagen and transparent is contained when it is grown in one
Matter acid is in 0.01-100 (collagen)：1 (hyaluronic acid) weight than cell tissue adhesive.Referring to United States Patent (USP) 12/
No. 974535 publications.Cell tissue adhesive described in the invention is being made, the concentration of hyaluronic acid can be every milliliter
0.001 to 100mg/mL is (such as:0.01 to 1mg/mL)；The concentration of collagen can be 0.001 to 100mg/mL.Preferably,
The concentration of collagen is 0.1 to 100mg/mL, and the concentration of hyaluronic acid is 0.01-35mg/mL.More preferably, collagen it
Concentration is 3-75mg/mL (such as 6mg/mL or 9mg/mL), and the concentration of hyaluronic acid is 0.2-20mg/mL.
Crosslinking agent
Crosslinking agent is obtained and reacted with target molecule and crosslinked together with target molecule, and the crosslinking agent generally comprises at least two
The individual functional response's base that can be reacted with the functional group of target molecule, table 1 lists functional response's base and functional group, crosslinking agent and official
Energy base is known.
Crosslinking agent used herein can include, but are not limited to imines ester (imidoester), epoxides
(epoxide) [such as:Ethylene glycol bisglycidyl ethers (ethylene glycol diglycidyl ether)], glutaraldehyde
(glutaraldehyde), N- hydroxysuccinimides ester (N-hydroxysuccinimide ester) is [such as:2,3- dibromos third
Acyl N- hydroxysuccinimides ester (2,3-dibromopropionyl-N-hydroxysuccinimide ester), sulfonic group-
N- hydroxysuccinimides ester (sulfo-N-hydroxysuccinimide ester) and Chlorambucil N- maloyls
Imines ester (chlorambucil-N-hydroxysuccinimide ester)], carbon imidodicarbonic diamide (carbodiimide) [such as:
1- ethyls -3- [3- dimethylaminos] carbon imidodicarbonic diamide (1-ethyl-3- (3-dimethylaminopropyl) carbodiimide
Hydrochloride)], gardenin (genipin), repeatedly maleimide (maleimide), nitrogen (azide), haloacetyl
(haloacetyl), disulfide (pyridyl disulfide), hydrazides (hydrazide), flavine
(riboflavin), bioflavonoid (bioflavonoid), core flavonoids (flavonoid) and its derivative be [such as:Former cyanine
Plain (proanthocyanidin), catechin (catechin), epicatechin (epicatechin), epigallocatechin
(epigallo catechin), L-Epicatechin gallate (epicatechin gallate), nutgall catechin does not have food
Sub- acid (epigallocatechin gallate), Quercetin (quercetin), chalcone element (chalcones), apiolin
(apigenin), luteoiin, a polymethoxylated fiavone, quercitoi, Kaempferol (kaempferol),
Myricetin (myricetin), anthocyanidin (anthocyanin), resveritrol, an isoflavanoid, daidzein
(daidzein), genestiein, Nobiletin (nobiletin), orange peel (tangeretin) and tannic acid (tannic
Acid)], 6- (dimaleoyl imino) caproic acids active ester (6-maleimidohexanoic acid active ester), double ambers
Amber imines acyl suberic acid carbamyl phosphate (disuccinimidyl suberate), double amber imide suberate [bis
(sulfosuccinimidyl) suberate], azide (azide), double ethylene imines (diazirine), 4- (N- Malaysias acyls
Formimino group) hexamethylene -1- carboxylic acid sulfonic group succinimide esters [sulfosuccinimidyl-4- (N-
Maleimidomethyl) cyclohexane-1-carboxylate] and its derivative.The crosslinking agent can also be a polypropylene
Sour sodium includes various identical or different functional response's bases, such as polyepoxides (polyepoxy compound) and poly- (hydroxyl
Acid) (poly (hydroxy acid)).
The reactive group of table 1. and and target functional group
Resistance stops agent
It is the reagent reacted with crosslinking agent reactive group in this reference person that resistance stops agent, when target molecule and cross-linking agents
Afterwards, resistance stops agent and can be reacted with the crosslinking agent reactive group not with target functional response's radical reaction.It is not anti-by " exhausting "
The reactive group answered, resistance stops agent can wholly or in part reduce the toxicity of crosslinking agent.It can be a compound that resistance stops agent, comprising
Amine (amine), sulfydryl (sulfhydryl), carbonyl (carbonyl), ethylene glycol (glycol), repeatedly carboxyl (carboxyl), nitrogen
Compound (azide) or photo-crosslinking group (photo-crosslinking group).In other words, resistance stops agent and includes a functional group
System can react with functional response's base of the crosslinking agent.In one embodiment, when crosslinking agent is to contain the group with amido reaction, resistance
Stop agent and rely ammonia including but not limited to diamine (diamines), few amine (oligoamines) and polyamine (polyamines) such as poly
Sour (polylysine) and poly glutamy acid (polyglutamine).In another embodiment, when crosslinking agent be containing with carboxylic
The group of base reaction, resistance stop agent comprising dicarboxylic acids, few carboxylic acid or polycarboxylic acids such as polyglutamate (polyglutamate or
polyglutamate acid).The resistance of other embodiment stops agent to be included can be used for containing for the sulfydryl reactive group for suppressing
Polysulfhydryl compounds, and can be used for the compound containing polyhydroxy of the hydroxyl reaction base for suppressing.
Nutriment
Nutriment source of nutrition necessary to this reference person is cell growth, it is Amino acid, vitamin, mineral
Matter, carbon source (such as glucose), aliphatic acid or above-mentioned mixture.In one embodiment, described nutriment is cell culture
Base, it includes but is not limited to minimum necessary culture medium (Minimum Essential Medium, MEM), basis according to lattice culture medium
(Basal Medium Eagle, BME), Du Shi improvement Ying Geer culture mediums (Dulbecco's Modified Eagle's
Medium, DMEM), nutrition mixed culture medium (Ham's Nutrient Mixtures F-10 or F-12), culture medium 199
The micro- park research institute culture medium of (Medium 199), Ross (Roswell Park Memorial Institute medium,
RPMI medium), peace Mu Shi culture mediums (Ames'Medium), BGJb Medium (Fitton-Jackson
Modification), Ke Like culture mediums (Click's Medium), CMRL-1066Medium, take snow culture medium
(Fischer's Medium), Glasgow MEM (Glasgow Minimum Essential Medium),
Iscove's Modified Dulbecco's Medium、L-15Medium、McCoy's 5A Modified Medium、
NCTC Medium, Swim's S-77Medium, Waymouth Medium or William's Medium E.
Bioactivator
Any reagent (such as victory peptide, more victory peptide, few candy, polysaccharide or small molecule), can promote cell viability measurement, lift cell
The cell tissue adhesive that Reproductive activity or Cell differentiation inducing activity can all provide the present invention is used.In one embodiment, it is described it
Biochemical activity molecule is growth factor, and it includes that EGF (epidermal growth factor, EGF), fiber are female
Porcine HGF (fibroblast growth factor, FGF), VEGF (vascular
Endothelial growth factor, VEGF), CTGF (connective tissue growth
Factor, CTGF), platelet derived growth factor (platelet-derived growth factor, PDGF), para-insulin
Growth factor (insulin-like growth factor, IGF), nerve growth factor (nerve growth factor,
NGF), HGF (hepatocyte growth factor, HGF), colony stimulating factor (colony-
Stimulating factor, CSF), stem cell factor (stem cell factor, SCF), hydroxytryptamine (serotonin) and
VWF ELISA (von Willebrand factor), TGF (transforming growth
Factor), keratinocyte growth factor (keratinocyte growth factor, KGF), white blood cell growth factor
(granulocyte colony-stimulating factor, GCSF), macrophage colony stimulating factor (granulocyte
Macrophage colony-stimulating factor), granulocyte/macrophage colony stimulatory factor
(granulocyte/macrophage colony stimulating factor), neuroglia derive nerve and nourish the factor
(glial derived neurotrophic factor, GDNF), hairy neurotrophic factor (ciliary
Neurotrophic factor), endothelial cell monocytic activity polypeptide (endothelial-monocyte activating
Polypeptide), epidermis neutrality ball active peptides (epithelial neutrophil activating peptide), red
Blood cell generation plain (erythropoietin), plastotype albumen (bone morphogenetic protein), the brain derived nerve of bone
Nourish the factor (brain-derived neurotrophic factor).In another embodiment, the biochemical activity molecule is one
Cytokine/chemotactic hormone (cytokines/chemokine), it includes but is not limited to IL-2, thymus gland performance chemistry and becomes plain
(breast-expressed chemokine, BRAK), kidney performance chemotactic hormone (kidney-expressed
Chemokine, CXCL14) or above-mentioned substance composition.The biochemical activity molecule is a cell differentiation factor, such as:It is artificial to close
Into corticosteroid (dexamethasone), Sodium Pyruvate (sodium pyruvate), vitamin C phosphate (ascorbic
Acid-2-phosphate), RA (retinoic acid), proline (proline), insulin (insulin), fortune
Ferritin (transferrin), selenous acid (selenous acid), linoleic acid (linoleic acid), bovine serum albumin(BSA)
(bovine Serum Albumin), (the transforming growth factor beta 3, TGF- of conversion growth factor-β 3
β3).In another embodiment, the differentiation factor is that the compound of the Chondrogenesis that can promote mesenchymal stem cell (refers to the U.S.
The disclosed content of the publication of patent 5,908,784), bone newborn [such as dexamethasone (dexamethasone), vitamin C
(ascorbic acid), β-phosphoglycerol (β-glycerol phosphate)], fat generation [such as insulin (insulin),
Isobutyl methylxanthine (isobutylmethylxanthine), dexamethasone (dexamethasone), draw a U.S.A and spill pungent
(indomethacin)], Myocardium Differentiation [such as activin A (activin A), bone morphogenetic protein-4 (bone
Morphogenetic protein-4, BMP-4)], endothelial cell differentiation [such as endothelial cell (EBM-2), dexamethasone
(dexamethasone) and VEGF (VEGF)], SMC differentiation [such as platelet derived growth because
Sub (PDGF)], nerve-inducing [such as basic fibroblast growth factor (basic fibroblast growth factor,
BFGF), EGF (EGF), B27supplement, dimethyl sulfoxide (DMSO) (DMSO), butylhydroxy methoxy benzene
(butylated hydroxyanisole), coleus element (forskolin), valproic acid (valproic acid), potassium chloride,
K252a and N2supplement] and entoderm spectrum be differentiation (endodermal lineage differentiation) [such as
Dexamethasone, HGF (HGF) and fiber mother cell growth factor -4 (FGF-4)].In more preferably embodiment,
Biochemical activity molecule is the active ingredient of Chinese herbal medicine or Chinese herbal medicine.
The preparation of the embedded tissue adhesive of cell
The preparation of tissue adhesive described herein, can be mixed and be maintained by by above-mentioned material with specific weight ratio
Mixture is promoted to form tissue adhesive in suitable condition.And the embedded tissue adhesive of a cell is prepared, cell source can be
Adhesive mixes before being formed with the constituent of adhesive.Cell source can be by mammal (such as:Ox, pig, mouse, horse,
Dog, cat, sheep, monkey and people) stem cell that is obtained.In one embodiment, described cell, it includes but is not limited to placenta source
Stem cell (placenta-derived stem cells), stem cell (bone marrow-derived stem
Cells), stroma cell (stromal cells) is [such as:Adipose stromal cells (dipose-derived stromal
Cells)], mescenchymal stem cell (mesenchymal stem cells), tissue-derived cell (tissue progenitor
Cells), mother cell (blast cells) or fibroblast (fibroblasts)
Foregoing cell tissue adhesive is combined the cellular implant to be formed with cell source and can be implanted into the position of human body
Put, to carry out tissue repair and other therapeutic purposes.
Those skilled in the art can utilize the present invention to greatest extent as described above.System proposes that one has
Body implementation method, only illustrative explanation, the remainder without limiting disclosure.All references cited herein
All it is incorporated herein by reference.
Embodiment:Cell tissue adhesive containing poly-L-Lysine crosslinking agent
(A) materials and methods
Resistance used herein stops agent includes spermine (spermine), fish amine (protamine), 1-6 hexamethylene diamines (1,6-
Hexanediamine), polylysine is then the molecular weight of different groups.The mean molecule quantity of polylysine is respectively
3.4kDa, 20kDa, 99kDa, 212kDa and 225kDa.
The polylysine of equivalent is mixed with the gelatin of 300mg/mL in phosphate buffer, is relied with forming poly- L-
Propylhomoserin-gelatin solution, then by isometric and concentration for the gardenin solution of 20mg/mL mixes with above-mentioned polyamine-gelatin solution
To form cell tissue adhesive, [its size is 10x30x0.7 to 0.9 cubic millimeters of (mm to be then added to pigskin sample3)]
Corium side.Two panels pigskin sample is relative with corium face, and centre is cell tissue adhesive (10x 10mm2), by 50 grammes per square metres
Counterweight is placed on the top 30 minutes of two panels pigskin sample, and with LRX testings of materials be system (Lloyd Instruments Ltd.,
England) so that under the pulling force of 10 centimetres of (mm/min) speed per minute, separation two panels pigskin sample is with test cell tissue gluing
The link strength of agent.
The cell tissue adhesive of 10 μ L is added the culture dish center of 24 porose discs, then is planted into 2x104Individual cells/well
(cell/well) fibroblast, and it is incubated at 5% carbon dioxide (CO2), under 37 DEG C of environment after 38 hours.Survival
Cell quantity is quantified by blood counting chamber, carries out the measurement of toxicity evaluation.
By RheoStress RS 150 (Haake, Germany) it is measurable containing and containing polylysine cell
Organize the rheological equationm of state of adhesive, and real time record elastic storage modulus (elastic storage modulus, G') and reaction
Temperature is that 1 handkerchief (Pa) and frequency are the concussion test-strips of 1 hertz (Hz) in fixed shear stress (fixed shear stress)
Data under part.
(B) link strength test
Result shows that the link that can promote cell tissue adhesive when the molecular weight of polylysine is higher than 20kDa is strong
Degree, from molecular weight for the polylysine of 212kDa makes further research, and the cell tissue gluing containing polylysine
The link strength of agent can strengthen with the rising of polylysine concentration, until polylysine is at concentrations up to 46.8mN.It is right
Carried out in the cell tissue adhesive and the adhesive of unused polylysine being made using 17.5mN polylysines
Research display, the maximum of the link strength of the cell tissue adhesive containing polylysine is more than unused polylysine
Cell tissue adhesive.
No matter the concentration of gardenin, with the rising of polylysine content, the link strength of cell tissue adhesive will
Rise；Additionally, strength of connection strengthens also with the raising of gardenin concentration.
(C) toxicity evaluation
The toxicity of the cell tissue adhesive without polylysine is improved with the rising of gardenin concentration.Add poly- L-
Reduction gardenin that lysine can dramatically poisons effect.When the gardenin using 7.5mg/mL and the polylysine of 46.8mN
When, do not observe significant cytotoxic effect (cytotoxic effect).
(D) rheological equationm of state (rheological properties)
Influence for a further understanding of polylysine to the physics and chemical property of adhesive, elastic storage modulus
The numerical value of (G ') (the elastic storage modulus) is monitored in real-time measure.By fixed shear stress (fixed
Shear stress) (1Pa) and frequency (1Hz) vibration test, result of the test shows, the numerical value of elastic storage modulus (G ') with
Cell tissue adhesive increases from the formation of liquid.The numerical value of elastic storage modulus (G ') is added to polylysine
Significant raising in cell tissue adhesive.The numerical value of elastic storage modulus is detected in the change of differential responses temperature, and
When reaction is carried out at 50 DEG C, the reaction time shows that the numerical value of elastic storage modulus has rising drastically when being 90 minutes.This phase
Transfer phenomena display polylysine take part in the cross-linking reaction of cell tissue adhesive, and increased cell tissue adhesive
Elastic storage modulus.Phase transfer phenomenon is then not observed during without polylysine.
【Other embodiment】
All features for disclosing in the description can be combined by any form.It is disclosed in the description that each is special
Levy and can be used for identical, the alternative features of equivalent or similar purpose are replaced.Therefore, unless otherwise stated, each disclosure
Feature be only general series equivalent or similar characteristics one embodiment.
From the description above, those skilled in the art can readily determine that essential feature of the invention, and not depart from
Spirit and scope of the invention sets out carries out various changes, it is applied to different purposes and condition.Therefore, other embodiments also exist
In claim.
Claims (11)
1. the cell tissue adhesive of a kind of hypotoxicity, it is characterized in that including：
One or more substrate molecules (matrix molecule), it produces friendship with crosslinking agent (cross-linking agent)
Connection；And
Resistance stops agent (quenching agent), and it is bonded with the functional group of the crosslinking agent, wherein：
The crosslinking agent is gardenin (genipin)；
It is poly-L-Lysine (poly-L-lysine) that the resistance stops agent, and its mean molecule quantity is more than 20kDa；Polylysine
Equivalent concentration is more than 17.5mN.
2. cell tissue adhesive as claimed in claim 1, wherein the mean molecule quantity of the polylysine is more than or waits
In 99kDa.
3. cell tissue adhesive as claimed in claim 1, wherein the mean molecule quantity of the polylysine is more than or waits
In 212kDa.
4. cell tissue adhesive as claimed in claim 1, wherein the substrate molecule is selected from collagen
(collagen), hyaluronic acid (hyaluronan), gelatin (gelatin), fiber connect albumen (fibronectin), elastic egg
In vain (elastin), tenascin (tenacin), basement membrane element (laminin), vitronectin (vitronectin), sulfuric acid second
Acyl heparin (heparan sulfate), chondroitin (chondroitin), chondroitin sulfate (chondroitin sulfate),
Keratan (keratan), keratan sulfate (keratan sulfate), dermatan sulfate (dermatan sulfate), OK a karaoke club
Glue (carrageenan), heparin (heparin), chitin (chitin), spherical chitosan (chitosan), alginate
(alginate), agar-agar (agarose), agar (agar), cellulose (cellulose), methylcellulose (methyl
Cellulose one kind), in carboxymethylcellulose calcium (carboxyl methyl cellulose) or glycogen (glycogen) or
It is various.
5. cell tissue adhesive as claimed in claim 1, wherein the substrate molecule is selected from collagen, hyaluronic acid
Or gelatin.
6. cell tissue adhesive as claimed in claim 1, wherein the substrate molecule is collagen and hyaluronic acid.
7. cell tissue adhesive as claimed in claim 1, wherein the substrate molecule includes gelatin.
8. cell tissue adhesive as claimed in claim 1, it also includes nutriment and bioactivator (bioactive
agent)。
9. cell tissue adhesive as claimed in claim 8, wherein the nutriment is cell culture medium.
10. cell tissue adhesive as claimed in claim 8, wherein the bioactivator is growth factor, selected from epidermis
Growth factor (epidermal growth factor, EGF), fiber mother cell growth factor (fibroblast growth
Factor, FGF), VEGF (vascular endothelial growth factor, VEGF), connective group
Knit growth factor (connective tissue growth factor, CTGF), platelet derived growth factor (platelet-
Derived growth factor, PDGF), insulin-like growth factor (insulin-like growth factor, IGF),
Nerve growth factor (nerve growth factor, NGF), HGF (hepatocyte growth
Factor, HGF), colony stimulating factor (colony-stimulating factor, CSF), stem cell factor (stem cell
Factor, SCF), keratinocyte growth factor (keratinocyte growth factor, KGF), white blood cell growth factor
(granulocyte colony-stimulating factor, GCSF), macrophage colony stimulating factor (granulocyte
Macrophage colony-stimulating factor), neuroglia derives nerve and nourishes the factor (glial derived
Neurotrophic factor, GDNF), hairy neurotrophic factor (ciliary neurotrophic factor), endothelium
Cell monocyte cytoactive polypeptide (endothelial-monocyte activating polypeptide), epidermis neutrality ball
Active peptides (epithelial neutrophil activating peptide), erythropoietin
(erythropoietin), bone plastotype albumen (bone morphogenetic protein), brain derived nerve nourish the factor
(brain-derived neurotrophic factor), conversion growth factor-β (transforming growth factor
Beta), mammary gland shows the one kind or many in chemotactic factor (CF) (BRAK) or TNF (tumor necrosis factor)
Kind.
11. cell tissue adhesives as claimed in claim 8, it further includes cell source, and the cell source does not include the mankind
Embryonic stem cell.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2011/041629 WO2012177257A1 (en) | 2011-06-23 | 2011-06-23 | Adhesive cell tissue gels |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104136602A CN104136602A (en) | 2014-11-05 |
| CN104136602B true CN104136602B (en) | 2017-06-09 |
Family
ID=47422853
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201180073036.7A Active CN104136602B (en) | 2011-06-23 | 2011-06-23 | Cell tissue adhesive |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN104136602B (en) |
| WO (1) | WO2012177257A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105087482B (en) * | 2015-08-28 | 2018-10-30 | 广州赛莱拉干细胞科技股份有限公司 | A kind of cell culture substrate and its application and application method |
| CN111163784A (en) * | 2017-09-01 | 2020-05-15 | 黄玲惠 | Pharmaceutical composition for treating crab foot swelling and application thereof |
| CN109439275A (en) * | 2018-09-03 | 2019-03-08 | 捷成实业（深圳）有限公司 | A kind of environmental protection fruit juice gel and preparation method thereof |
| CN109529098A (en) * | 2018-12-03 | 2019-03-29 | 广州润虹医药科技股份有限公司 | A kind of surgery adhesive of medical |
| WO2020140111A1 (en) * | 2018-12-28 | 2020-07-02 | Excel Med, Llc | Biological scaffold and method for fabricating the same |
| CN111969206B (en) * | 2020-08-21 | 2021-11-19 | 华南农业大学 | Water-based binder and application thereof in lithium ion battery |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101111272A (en) * | 2005-01-31 | 2008-01-23 | Bmg株式会社 | Self-degradable two-component reactive adhesive for medical use and resin for medical use |
| CN101854960A (en) * | 2006-12-15 | 2010-10-06 | 生命连结有限公司 | Gelatin-transglutaminase hemostatic dressings and sealants |
| WO2011011658A1 (en) * | 2009-07-23 | 2011-01-27 | University Of Utah Research Fundation | Adhesive complex coacervates and methods of making and using thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0811784A2 (en) * | 2007-05-23 | 2011-05-10 | Allergan Inc | cross-linked collagen and use thereof |
| US8221744B2 (en) * | 2007-09-19 | 2012-07-17 | Abbott Cardiovascular Systems Inc. | Cytocompatible alginate gels |
| US20090305415A1 (en) * | 2008-06-05 | 2009-12-10 | Huang Lynn L H | Method for preserving proliferation and differentiation potential of undifferentiated cells |
| US9393267B2 (en) * | 2009-02-19 | 2016-07-19 | University Of Southern California | Gel delivery system for tissue repair |
-
2011
- 2011-06-23 WO PCT/US2011/041629 patent/WO2012177257A1/en active Application Filing
- 2011-06-23 CN CN201180073036.7A patent/CN104136602B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101111272A (en) * | 2005-01-31 | 2008-01-23 | Bmg株式会社 | Self-degradable two-component reactive adhesive for medical use and resin for medical use |
| CN101854960A (en) * | 2006-12-15 | 2010-10-06 | 生命连结有限公司 | Gelatin-transglutaminase hemostatic dressings and sealants |
| WO2011011658A1 (en) * | 2009-07-23 | 2011-01-27 | University Of Utah Research Fundation | Adhesive complex coacervates and methods of making and using thereof |
Non-Patent Citations (3)
| Title |
|---|
| In situ crosslinkable hyaluronan hydrogels for tissue engineering;SHU,X.Z. et al.;《Biomaterials》;20041231;第25卷;第1339-1348页 * |
| 特种胶粘剂-alpha-氰基丙烯酸酯系医用胶;田霞 等;《化工新型材料》;20070331;第35卷(第3期);第112-115页 * |
| 聚谷氨酸-明胶生物胶的制备及生物性能的研究;王欣;《中国优秀硕士学位论文全文数据库•工程科技I辑》;20051215;全文，尤其是摘要、第18页最后1行、第25页最后1段-26页第1段、第17页图2-1、第26页图2-6、第31页图3.1、第40页4.2.2.1节 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP6120225B2 (en) | 2017-04-26 |
| JP2014519843A (en) | 2014-08-21 |
| CN104136602A (en) | 2014-11-05 |
| WO2012177257A1 (en) | 2012-12-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8790683B2 (en) | Cell tissue gel containing collagen and hyaluronan | |
| CN104136602B (en) | Cell tissue adhesive | |
| US9623146B2 (en) | Bone implant materials comprising cross-linked bioactive hydrogel matrices | |
| US10383981B2 (en) | Structural lattice and method of making same | |
| Zhang et al. | Application of hydrogels in heart valve tissue engineering | |
| KR20110090896A (en) | New biomaterial based on wharton's jelly from the human umbilical cord | |
| CN107001488A (en) | Heparan sulfate | |
| TWI461416B (en) | Cell Tissue Adhesive | |
| Kuo et al. | Effect of bovine pituitary extract on the formation of neocartilage in chitosan/gelatin scaffolds | |
| Hu et al. | Polypeptide resurfacing method improves fibroblast's adhesion to hyaluronan strands | |
| Alizadeh et al. | Sulfated polysaccharide as biomimetic biopolymers for tissue engineering scaffolds fabrication: Challenges and opportunities | |
| US20190060465A1 (en) | Adhesive cell tissue gels | |
| Wei et al. | Injectable natural biomaterials for cartilage tissue engineering | |
| JP6120225B6 (en) | Adhesive cell tissue gel | |
| CN112704768A (en) | Chondroitin sulfate modified collagen/polycaprolactone vascular repair stent and preparation method and application thereof | |
| Kang | Biofabricated platforms for wound healing and skin regeneration | |
| Naranda et al. | Recent Advancements in 3D Printing of Polysaccharide Hydrogels in Cartilage Tissue Engineering. Materials 2021, 14, 3977 | |
| Iordache et al. | Development of scaffolds for vascular tissue engineering: biomaterial mediated neovascularization | |
| ter Horst | A gellan-based fluid gel carrier for spray delivery | |
| Rangel | Cell-laden micropatterns using self-assembled cell-ECM microtissues in soft pectin hydrogels | |
| Behrndtz | Neogenesis of Hyaline Cartilage by Stimulation of Mesenchymal Stem Cells in TGF-β1-Coated 3-D Scaffolds | |
| Tavares Negrete | Development of a GelMA-based bioink enhanced with minimally-processed tissue for the fabrication of skeletal muscle | |
| Granja | Fábio Jorge OliveiraRangel |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |