CN115636960A - Photo-crosslinking silk fibroin hemostatic adhesive and preparation method thereof - Google Patents
Photo-crosslinking silk fibroin hemostatic adhesive and preparation method thereof Download PDFInfo
- Publication number
- CN115636960A CN115636960A CN202211197080.5A CN202211197080A CN115636960A CN 115636960 A CN115636960 A CN 115636960A CN 202211197080 A CN202211197080 A CN 202211197080A CN 115636960 A CN115636960 A CN 115636960A
- Authority
- CN
- China
- Prior art keywords
- silk fibroin
- solution
- hemostatic adhesive
- photo
- preparation
- 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.)
- Granted
Links
- 108010022355 Fibroins Proteins 0.000 title claims abstract description 89
- 239000000853 adhesive Substances 0.000 title claims abstract description 69
- 230000001070 adhesive effect Effects 0.000 title claims abstract description 69
- 230000002439 hemostatic effect Effects 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 238000004132 cross linking Methods 0.000 title claims description 31
- 235000010443 alginic acid Nutrition 0.000 claims abstract description 31
- 239000000783 alginic acid Substances 0.000 claims abstract description 31
- 229960001126 alginic acid Drugs 0.000 claims abstract description 31
- 229920000615 alginic acid Polymers 0.000 claims abstract description 31
- 150000004781 alginic acids Chemical class 0.000 claims abstract description 31
- PASHVRUKOFIRIK-UHFFFAOYSA-L calcium sulfate dihydrate Chemical class O.O.[Ca+2].[O-]S([O-])(=O)=O PASHVRUKOFIRIK-UHFFFAOYSA-L 0.000 claims abstract description 11
- 239000000243 solution Substances 0.000 claims description 91
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 36
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 30
- 239000008367 deionised water Substances 0.000 claims description 28
- 229910021641 deionized water Inorganic materials 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 16
- 229960003638 dopamine Drugs 0.000 claims description 15
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 239000002243 precursor Substances 0.000 claims description 12
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 9
- 229910052751 metal Inorganic materials 0.000 claims description 9
- 239000002184 metal Substances 0.000 claims description 9
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 238000004108 freeze drying Methods 0.000 claims description 6
- 239000000661 sodium alginate Substances 0.000 claims description 6
- 235000010413 sodium alginate Nutrition 0.000 claims description 6
- 229940005550 sodium alginate Drugs 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 5
- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 229960001149 dopamine hydrochloride Drugs 0.000 claims description 5
- 239000011159 matrix material Substances 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 2
- 230000004913 activation Effects 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 230000000379 polymerizing effect Effects 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 abstract description 24
- 238000002156 mixing Methods 0.000 abstract description 10
- 239000000463 material Substances 0.000 abstract description 9
- 210000004204 blood vessel Anatomy 0.000 abstract description 5
- 230000007547 defect Effects 0.000 abstract description 5
- 238000007789 sealing Methods 0.000 abstract description 5
- 230000000740 bleeding effect Effects 0.000 abstract description 4
- 238000011049 filling Methods 0.000 abstract description 4
- 210000003205 muscle Anatomy 0.000 abstract description 4
- 210000003491 skin Anatomy 0.000 abstract description 4
- 239000012620 biological material Substances 0.000 abstract description 3
- 210000000988 bone and bone Anatomy 0.000 abstract description 3
- 210000001508 eye Anatomy 0.000 abstract description 3
- 210000001503 joint Anatomy 0.000 abstract description 3
- 210000004877 mucosa Anatomy 0.000 abstract description 3
- 210000005036 nerve Anatomy 0.000 abstract description 3
- 230000001678 irradiating effect Effects 0.000 abstract description 2
- 210000000056 organ Anatomy 0.000 abstract 1
- 239000000017 hydrogel Substances 0.000 description 19
- 238000000502 dialysis Methods 0.000 description 17
- 239000011230 binding agent Substances 0.000 description 10
- 241000255789 Bombyx mori Species 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 239000003106 tissue adhesive Substances 0.000 description 7
- 206010052428 Wound Diseases 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000023597 hemostasis Effects 0.000 description 6
- 239000003999 initiator Substances 0.000 description 6
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 5
- 208000032843 Hemorrhage Diseases 0.000 description 5
- 239000012711 adhesive precursor Substances 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 210000004872 soft tissue Anatomy 0.000 description 5
- 229940075469 tissue adhesives Drugs 0.000 description 5
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 229910001424 calcium ion Inorganic materials 0.000 description 4
- 210000002216 heart Anatomy 0.000 description 4
- 238000003760 magnetic stirring Methods 0.000 description 4
- 229910021645 metal ion Inorganic materials 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 229920002674 hyaluronan Polymers 0.000 description 3
- 229960003160 hyaluronic acid Drugs 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229920001651 Cyanoacrylate Polymers 0.000 description 2
- MWCLLHOVUTZFKS-UHFFFAOYSA-N Methyl cyanoacrylate Chemical compound COC(=O)C(=C)C#N MWCLLHOVUTZFKS-UHFFFAOYSA-N 0.000 description 2
- 239000004826 Synthetic adhesive Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 230000009920 chelation Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 210000005003 heart tissue Anatomy 0.000 description 2
- 230000009878 intermolecular interaction Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- DCUFMVPCXCSVNP-UHFFFAOYSA-N methacrylic anhydride Chemical compound CC(=C)C(=O)OC(=O)C(C)=C DCUFMVPCXCSVNP-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- 208000012260 Accidental injury Diseases 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 208000005422 Foreign-Body reaction Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004830 Super Glue Substances 0.000 description 1
- 208000031737 Tissue Adhesions Diseases 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 210000004177 elastic tissue Anatomy 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M methacrylate group Chemical group C(C(=C)C)(=O)[O-] CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000021715 photosynthesis, light harvesting Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 238000009991 scouring Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003356 suture material Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
Images
Landscapes
- Materials For Medical Uses (AREA)
- Adhesives Or Adhesive Processes (AREA)
Abstract
The invention discloses a photocrosslinking silk fibroin hemostatic adhesive and a preparation method thereof, belonging to the field of biological materials and biomedical application. The hemostatic adhesive is prepared by uniformly mixing methacrylated silk fibroin, dopamine-modified alginic acid, calcium sulfate dihydrate and a photoinitiator at room temperature in a dark place and irradiating by ultraviolet light. The silk fibroin hemostatic adhesive prepared by the invention has the characteristics of high adhesive strength, high adhesive speed, strong mechanical toughness, good biocompatibility and the like in a wet environment. The operation is simple and easy to master, and secondary operations such as stitch removal and the like are not needed after the operation. The adhesive can be used for almost all wound surfaces, has the functions of adhering tissues, covering the wound surfaces, filling gaps and defects, stopping bleeding, sealing and the like, can be used as a hemostatic adhesive material for tissues such as skin, organs, blood vessels, nerves, muscles, mucosa, bones, joints, eyes and the like, and has wide clinical application prospect.
Description
Technical Field
The invention belongs to the field of biological materials and biomedical application, and particularly relates to a photo-crosslinking silk fibroin hemostatic adhesive and a preparation method thereof.
Background
Massive bleeding due to accidental injury or clinical surgical procedures is one of the leading causes of death in the current world population. At present, the main means for clinically treating tissue hemorrhage is surgical suture, and surgical closure is performed through suture lines, metal wires or closure nails. However, the treatment method is complex to operate, takes longer time, has higher requirements on the level of an operator, forms high stress concentration at the suture part, increases the pain of patients, and leads most patients to have different degrees of suture knot reactions, thereby leaving centipede-like scars after the operation. In addition, in the repair of soft tissues such as heart and liver, the conventional suture material is easy to cause secondary damage to tissues, some parenchyma tissues (such as lung, liver or kidney) are not easy to repair by suture, small tissue damage such as arterial defect is difficult to realize by conventional suture because of insufficient space, and even in the suturable tissues, the hemostatic adhesive biomaterial is required to realize better sealing. With the rapid development of modern medicine, the clinical requirements for surgical methods and auxiliary materials are higher and higher, which not only requires the greatest relief for patients, but also requires the perfect restoration of the appearance while the function is restored, and these requirements make the development of tissue adhesives receive great attention.
As material science has developed, a variety of adhesive materials for tissue adhesion have been developed, and tissue adhesives that have been currently developed mainly include natural tissue adhesives and synthetic tissue adhesives. Common natural tissue adhesives include adhesives based on fibrin, gelatin, collagen, polysaccharides, polypeptides, and the like. The adhesives have good biocompatibility, but generally have the problems of poor mechanical property and flexibility, low adhesion strength (particularly poor adhesion on the surface of wet tissues), slow hemostasis speed, high production cost and the like. Common synthetic adhesives include cyanoacrylate and polyethylene glycol adhesives. The most widely used synthetic adhesive in clinical practice is cyanoacrylate, which has high adhesive strength but poor biocompatibility and biodegradability, and toxic degradation products may cause foreign body reactions and even necrosis. In addition, the high stiffness of cyanoacrylate adhesives can hinder physiological movement of elastic and soft tissues such as lungs, heart and blood vessels, and is detrimental to tissue regeneration and biointegration, and thus such adhesives are limited to repair of external (e.g., skin) lesions. Therefore, it is necessary to develop a tissue adhesive with good biocompatibility and high adhesive strength in a humid environment in vivo.
The photo-crosslinking hydrogel is a solid hydrogel material formed by triggering single-component hydrogel precursor solution or composite hydrogel prepolymer to be gelled by adopting illumination with specific wavelength. The non-physical contact mode of the photo-crosslinking hydrogel can effectively improve the space-time controllability of the application of the adhesive, realize the regulation and control of the whole or local performance of the material, reduce the influence caused by the operation proficiency and have wide application prospect in the aspect of the hemostatic adhesive in the fields of tissue engineering and biomedicine. Silk fibroin is a natural protein derived from silkworms, has biomedical properties such as good biocompatibility and suitable biodegradability, and is approved by the FDA to be applicable to medical devices. Currently, there are patents reporting the preparation of photo-crosslinked silk fibroin hydrogels. In the Chinese patent of CN 114773549A, "a novel methacrylic anhydride modified fibroin preparation method", the silk fibroin hydrogel is prepared by modifying the silk fibroin with glycidyl methacrylate, performing low-temperature treatment with liquid nitrogen, freeze-drying to obtain liquid nitrogen-methacryloylated silk fibroin, and performing photocrosslinking. In the Chinese patent of CN 114524953A, a silk fibroin/hyaluronic acid composite hydrogel, a preparation method and an application thereof, silk fibroin and hyaluronic acid are used as raw materials, the silk fibroin is modified by glycidyl methacrylate, the hyaluronic acid is modified by methacrylic anhydride, the modified products are mixed and dissolved in deionized water, and ultraviolet light is used for driving crosslinking to obtain the hydrogel. However, the methacrylated silk fibroin photo-crosslinked hydrogel is lack of wet adhesion functional groups and multiple intermolecular interactions, so that the adhesive strength of the methacrylated silk fibroin photo-crosslinked hydrogel and the surface of an organism in a wet environment (water, blood and the like) is low, the mechanical toughness is poor, and the methacrylated silk fibroin photo-crosslinked hydrogel cannot adapt to the dynamic adhesion of a tissue interface in a wet physiological environment and the like.
Therefore, the silk fibroin hemostatic adhesive with strong mechanical toughness, high bonding strength in a wet environment, high molding bonding speed and good biocompatibility is obtained by taking the silk fibroin esterified by methacrylic acid as a matrix material, adding the dopamine-grafted alginic acid, calcium ions and a photoinitiator, irradiating by ultraviolet light to ensure that the mixed solution is rapidly cross-linked and polymerized within 1-60 seconds, and under the existence of chemical covalent bond cross-linking and metal ionic bond dynamic cross-linking. At present, relevant research reports are not reported in related patents at home and abroad.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the tissue hemostatic adhesive with good biocompatibility, high bonding strength in a wet environment in vivo, high forming bonding speed and strong mechanical toughness. The invention overcomes the problems of slow forming speed, low bonding strength, poor biocompatibility, poor mechanical toughness and the like of the traditional tissue hemostatic adhesive in the in vivo physiological environment, and the prepared silk fibroin hemostatic adhesive can be used for almost all wound surfaces and has the functions of adhering tissues, covering the wound surfaces, filling tissue defects and gaps, stopping bleeding, sealing and the like.
In order to realize the purpose, the invention adopts the following technical scheme:
a preparation method of a photo-crosslinking silk fibroin hemostatic adhesive comprises the following steps: methacrylic acid esterified silk fibroin is used as a matrix, dopamine-modified alginic acid, calcium sulfate dihydrate and a photoinitiator are added, the mixture is uniformly stirred at room temperature in a dark place, the mixed solution is rapidly crosslinked and polymerized within 60 seconds under the irradiation of ultraviolet light, and the silk fibroin hemostatic adhesive with strong mechanical property and high adhesion property in a wet physiological environment is obtained under the existence of chemical covalent bond crosslinking and metal ionic bond dynamic crosslinking.
Further, a preparation method of the photo-crosslinking silk fibroin hemostatic adhesive specifically comprises the following steps:
(1) Preparation of methacrylated silk fibroin solution: heating deionized water to boil, adding Na 2 CO 3 And silk, degumming the silk; after washing and drying, dissolving the dried degummed silk by using a lithium bromide solution to obtain a silk fibroin solution, then adding glycidyl methacrylate to modify the silk fibroin, and then dialyzing by using deionized water; centrifuging and filtering the dialyzed solution to obtain a methacrylic acid esterified silk fibroin solution; the mass percentage concentration of the silk fibroin solution is 0.1-50% or 0.01 mg/mL-500 mg/mL.
(2) Preparation of dopamine-modified alginic acid: fully dissolving sodium alginate in deionized water, and then adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide and N-hydroxysuccinimide to activate carboxyl; adding dopamine hydrochloride to react overnight after the activation, and controlling the pH value of a reaction system to be less than or equal to 5 in the reaction process; dialyzing the obtained solution, carrying out freeze drying treatment to obtain a white spongy substance, and dissolving the white spongy substance with deionized water to obtain a dopamine-modified alginic acid solution; the mass percentage concentration of the dopamine modified alginic acid solution is 0.1-50% or 0.01 mg/mL-500 mg/mL.
(3) Photo-crosslinked silk fibroin hemostatic adhesive: dissolving the dopamine-modified alginic acid solution prepared in the step (2), calcium sulfate dihydrate and photoinitiator LAP in the methacrylated silk fibroin solution prepared in the step (1) at room temperature in a dark place, and uniformly stirring in the dark place to obtain a precursor solution; the precursor solution is subjected to rapid crosslinking polymerization within 1 minute under the irradiation of ultraviolet light to obtain the silk fibroin hemostatic adhesive with strong mechanical property and high adhesion property in a wet physiological environment. The mass ratio of the added dopamine modified alginic acid to the methacrylic acid esterified silk fibroin is (1-1). The ultraviolet light irradiation wavelength is 200-400 nm.
The photo-crosslinking silk fibroin hemostatic adhesive prepared by the preparation method can be used as a hemostatic adhesive material for tissues such as skin, viscera, blood vessels, nerves, muscles, mucosa, bones, joints, eyes and the like, can realize rapid adhesion in a wet environment (including water, PBS buffer solution and blood environment), and has adhesion time within 60 seconds; has good biocompatibility and strong adhesive force, can be used for almost all wound surfaces, and has the functions of adhering tissues, covering the wound surfaces, filling tissue defects and gaps, stopping bleeding, sealing and the like.
The invention has the following remarkable advantages:
(1) The invention takes silk fibroin with excellent biocompatibility as the main component of an adhesive to prepare methacrylated silk fibroin, and dopamine-modified alginic acid, calcium sulfate dihydrate and a photoinitiator are added. Under the irradiation of ultraviolet light, methacrylated silk fibroin forms chemical covalent bond cross-linking and induces the conformation of silk fibroin molecules to be converted into beta-sheet, alginic acid molecules and metal calcium ions form dynamic metal ion chelation, and alginic acid grafted dopamine groups and polyphenol-metal ion bonds between the metal calcium ions endow the material with excellent mechanical toughness. Compared with the traditional methacrylic acid esterification silk fibroin photo-crosslinking hydrogel, the mechanical toughness of the invention is obviously enhanced. The traditional methacrylic acid esterified silk fibroin photo-crosslinked hydrogel only depends on the methacrylic acid esterified silk fibroin to form chemical covalent bond crosslinking, and no intermolecular interaction such as ionic bond with a dynamic energy dissipation mechanism is introduced, so that the mechanical toughness is poor.
(2) Alginic acid grafted dopamine group can be tightly combined with the surface of moist biological tissue, and based on the synergistic effect of chemical covalent bond crosslinking and metal ionic bond dynamic crosslinking, the adhesive strength of the hemostatic adhesive to the surface of an organism in a wet environment is remarkably improved, and excellent wet adhesion capability is endowed. The invention has the adhesive strength of above 400 kPa to the tissue under the wet environment (including water, PBS buffer solution and blood environment). However, the traditional methacrylated silk fibroin photo-crosslinked hydrogel is poor in adhesive strength (the adhesive strength is below 30 kPa) with the surface of an organism in a wet environment (water, blood and the like) due to the lack of wet adhesion functional groups, and cannot adapt to the dynamic adhesion of a tissue interface. Therefore, the invention is more suitable for the moist environment with massive hemorrhage of the damaged tissue, has good tissue hemostasis adhesive potential, can be used as the hemostasis adhesive material of the tissues of skin, viscera, blood vessels, nerves, muscles, mucosa, bones, joints, eyes and the like,
(3) The light-triggered non-invasive crosslinking mode can realize rapid crosslinking forming within 1-60 seconds under the irradiation of ultraviolet light, and the rapid crosslinking forming principle is attributed to rapid photocrosslinkable reaction of methacrylate groups in the methacrylated silk fibroin, rapid metal ion chelation between alginic acid and metal calcium ions, rapid polyphenol-metal ion bonds between dopamine groups and metal calcium ions and rapid electrostatic interaction between silk fibroin molecules and dopamine groups. The invention effectively avoids environmental hazard caused by long-time ultraviolet irradiation, and improves the space-time controllability of applying the hemostatic adhesive and the adaptability of human tissues. .
(4) The tissue adhesive can be used for adhering wounds with different sizes and shapes according to the needs of patients, and the in-situ curing characteristic provides convenience for clinical application.
(5) The raw materials of the invention are all from natural compounds, thus having good biocompatibility.
(6) The method has the advantages of simple operation, easy batch production and the like, and has good industrialization prospect.
Drawings
Figure 1 is a macroscopic effect diagram of underwater forming and bonding of photo-crosslinked silk fibroin hemostatic adhesive.
Figure 2 is a graph of the hemostatic effect of photocrosslinked silk fibroin hemostatic adhesive on wounded cardiac tissue.
Detailed Description
In order to verify the feasibility of the design, the technical solution of the present invention is further described below with reference to the specific embodiments, but the application of the present invention is not limited thereto.
Example 1
(1) 1L deionized water was heated to boiling and 5.3 g sodium carbonate was added until it was fully dissolved. 40 g silkworm silk is put in the silkworm silk and is degummed for 30 minutes at 100 ℃. Taking out the boiled silk, fully washing the silk with deionized water, and drying the silk in a 60 ℃ oven. Adding the dried degummed silk into 9.3M LiBr solution to dissolve 1 h at 60 ℃ to obtain silk fibroin solution, then adding 12 mL glycidyl methacrylate into the silk fibroin solution to react at 60 ℃ for 3 h, and avoiding light during the whole reaction process. And putting the solution after reaction into a dialysis bag, dialyzing with deionized water for 7 days, and keeping the dialysis process away from light. And filtering and centrifuging the dialyzed solution, and concentrating to obtain a methacrylated silk fibroin solution with the mass fraction of about 25%.
(2) To a round bottom flask was added 400mg sodium alginate and 50ml deionized water and dissolved well with magnetic stirring. 383.4mg of EDC and 230.18 mg of NHS were then added to activate the carboxyl groups and adjust the pH of the reaction solution to 5. 189.62 mg dopamine hydrochloride was added and stirred overnight for 12h. After the reaction is finished, the obtained solution is put into a dialysis bag for dialysis 24 h. And after dialysis, freeze-drying the obtained solution to obtain a white spongy substance, and dissolving the white spongy substance with deionized water to obtain a dopamine-modified alginic acid solution with the mass fraction of about 5%.
(3) Under the condition of room temperature and light protection, 1ml of dopamine modified alginic acid solution and 0.1 ml calcium sulfate dihydrate solution with the concentration of 0.75M are added into 5ml of methacrylated silk fibroin solution, and after uniform mixing, LAP initiator with the final concentration of 0.03wt% is added, and the mixture is stirred and uniformly mixed to obtain the adhesive precursor solution. The binder precursor solution rapidly cross-linked within 5 seconds of ultraviolet light (wavelength 365 nm) to give the binder.
The adhesive is used for hemostasis adhesion of soft tissues such as heart and the like, and has excellent wet adhesion effect. Adhesive inThe adhesive strength under a wet environment (water) is 650 KPa, and the toughness is 80 KJ/m 3 . Fig. 1 is a macroscopic effect diagram of underwater forming and bonding of photo-crosslinked silk fibroin hemostatic adhesive. The invention can realize rapid crosslinking after ultraviolet irradiation. Even if the hydrogel is operated underwater, the hydrogel still shows excellent crosslinking speed and adhesion effect, can be firmly adhered to the surface of a glass substrate underwater and can bear strong water current scouring. Figure 2 is a graph of the hemostatic effect of photocrosslinked silk fibroin hemostatic adhesive on wounded cardiac tissue. The invention can realize the rapid hemostasis of wound tissues on the surface of a beating heart and can resist the violent mechanical movement. The traditional methacrylated silk fibroin photo-crosslinked hydrogel (comparative example 1) has poor adhesion strength with the surface of an organism underwater due to the lack of wet adhesion functional groups, the adhesive strength is 28 KPa, and the toughness is 4.5 KJ/m 3 。
Example 2
(1) After 2L deionized water was heated to boiling, 8.48 g sodium carbonate was added and allowed to dissolve sufficiently. 20 g silkworm silk is put in the silkworm silk and is degummed for 30 minutes at 100 ℃. Taking out the boiled silk, fully washing the silk with deionized water, and drying the silk in a 50 ℃ oven. Adding the dried degummed silk into 9.3M LiBr solution to dissolve 3 h at 60 ℃ to obtain silk fibroin solution, then adding 6 mL glycidyl methacrylate into the silk fibroin solution to react at 60 ℃ to obtain 3 h, and keeping the whole reaction process away from light. And putting the solution after reaction into a dialysis bag, dialyzing with deionized water for 7 days, and keeping the dialysis process away from light. And filtering and centrifuging the dialyzed solution, and concentrating to obtain a methacrylated silk fibroin solution with the mass fraction of about 5%.
(2) To a round bottom flask was added 800 mg sodium alginate and 50ml deionized water and dissolved well with magnetic stirring. Subsequently, 750 mg of EDC and 460 mg of NHS were added to activate the carboxyl group, and the pH of the reaction solution was adjusted to 5. 400mg dopamine hydrochloride is added and stirred overnight for 12h. After the reaction is finished, the obtained solution is put into a dialysis bag for dialysis 24 h. And after the dialysis is finished, freeze-drying the obtained solution to obtain a white spongy substance, and dissolving the white spongy substance with deionized water to obtain a dopamine-modified alginic acid solution with the mass fraction of about 15%.
(3) Adding 7 ml dopamine modified alginic acid solution and 0.3 ml calcium sulfate dihydrate solution with the concentration of 0.75M into 10 ml methacrylated silk fibroin solution under the condition of room temperature and light protection, adding LAP initiator with the final concentration of 0.02wt% after uniform mixing, and stirring and uniformly mixing to obtain an adhesive precursor solution. The binder precursor solution rapidly cross-linked within 20 seconds of ultraviolet light (wavelength 400 nm) to give the binder.
The adhesive is used for sealing and bonding soft tissues such as stomach, intestine and the like, and has excellent wet adhesion effect. The adhesive strength of the adhesive in a wet environment (water) is 410 KPa, and the toughness is 50 KJ/m 3 。
Example 3
(1) After 10L deionized water was heated to boiling, 50 g sodium carbonate was added and allowed to dissolve sufficiently. 400 g silkworm silk is put in the silkworm silk and is degummed for 30 minutes at 100 ℃. Taking out the boiled silk, fully washing the silk with deionized water, and drying the silk in an oven at 70 ℃. Adding the dried degummed silk into 9.3M LiBr solution to dissolve 6 h at 60 ℃ to obtain silk fibroin solution, then adding 150 mL glycidyl methacrylate into the silk fibroin solution to react at 60 ℃ to obtain 6 h, and avoiding light during the whole reaction process. And putting the solution after reaction into a dialysis bag, dialyzing with deionized water for 5 days, and keeping the dialysis process away from light. And filtering and centrifuging the dialyzed solution, and concentrating to obtain a methacrylated silk fibroin solution with the mass fraction of about 50%.
(2) To a round bottom flask was added 2 g sodium alginate and 50ml deionized water and dissolved well with magnetic stirring. Subsequently, 1.5 g of EDC and 1 g of NHS were added to activate the carboxyl group, and the pH of the reaction solution was adjusted to 5. 1.5 g dopamine hydrochloride was added and stirred overnight for 12h reaction. After the reaction is finished, the obtained solution is put into a dialysis bag for dialysis, and 24 h is obtained. And after the dialysis is finished, freeze-drying the obtained solution to obtain a white spongy substance, and dissolving the white spongy substance with deionized water to obtain a dopamine-modified alginic acid solution with the mass fraction of about 50%.
(3) Adding 10 ml dopamine modified alginic acid solution and 3 ml calcium sulfate dihydrate solution with the concentration of 0.75M into 30 ml methacrylated silk fibroin solution under the condition of room temperature and light protection, adding LAP initiator with the final concentration of 0.05wt% after uniform mixing, and stirring and uniformly mixing to obtain an adhesive precursor solution. The binder precursor solution rapidly cross-linked within 50 seconds of ultraviolet light (wavelength 250 nm) to give the binder.
The adhesive is used for hemostasis adhesion of skin, blood vessel, muscle, liver and other soft tissues, and has excellent wet adhesion effect. The adhesive strength of the adhesive under a wet environment (water) is 520 KPa, and the toughness is 70 KJ/m 3 。
Comparative example 1 (traditional methacrylated fibroin photocrosslinked hydrogel)
(1) Same as example 1, step (1);
(2) Under the condition of room temperature and light shielding, adding LAP initiator with final concentration of 0.03wt% into 5ml of methacrylated silk fibroin solution, and stirring and mixing uniformly to obtain precursor solution. The precursor solution is crosslinked by irradiation with ultraviolet light (wavelength 365 nm) to obtain the adhesive.
Comparative example 2 (fibroin not methacrylated)
(1) 1L deionized water was heated to boiling and 5.3 g sodium carbonate was added until it was fully dissolved. 40 g silkworm silk is put in the silkworm silk and is degummed for 30 minutes at 100 ℃. Taking out the boiled silk, fully washing the silk with deionized water, and drying the silk in a 60 ℃ oven. Adding the dried degummed silk into 9.3M LiBr solution, dissolving 1 h at 60 ℃ to obtain silk fibroin solution, filling the reacted solution into a dialysis bag, dialyzing with deionized water for 7 days, and keeping the whole dialysis process away from light. And filtering and centrifuging the dialyzed solution, and concentrating to obtain a silk fibroin solution with the mass fraction of about 25%.
(2) Same as example 1, step (2);
(3) The procedure of example 1, step (3), was followed except that the UV irradiation crosslinking time was varied.
Comparative example 3 (alginic acid without dopamine modification)
(1) Same as example 1, step (1);
(2) Adding 0.1 ml and 0.75M calcium sulfate dihydrate solution into 5ml of methacrylated silk fibroin solution at room temperature in a dark condition, uniformly mixing, adding 0.03wt% of LAP initiator, and stirring and uniformly mixing to obtain an adhesive precursor solution. The binder precursor solution was photocrosslinked under ultraviolet light (wavelength 365 nm) to give a binder.
Comparative example 4 (alginic acid added without dopamine modification)
(1) Same as example 1, step (1);
(2) Adding sodium alginate and deionized water into a round-bottom flask, and fully dissolving under magnetic stirring to obtain a alginic acid solution with the mass fraction of about 5%;
(3) Under the condition of room temperature and light protection, 1ml of alginic acid solution and calcium sulfate dihydrate solution with the concentration of 0.1 ml of 0.75M are added into 5ml of methacrylated silk fibroin solution, and after uniform mixing, LAP initiator with the final concentration of 0.03wt% is added, and the mixture is stirred and uniformly mixed to obtain the adhesive precursor solution. The binder precursor solution was photocrosslinked under ultraviolet light (wavelength 365 nm) to give a binder.
The gel groups of comparative examples 2-4 (alginic acid without methacrylation, dopamine modification, and dopamine modification of added alginic acid) prepared using the single-factor principle had poorer wet adhesion strength and toughness modulus than those of inventive example 1.
The above description is only an example of the present invention, and all the equivalent changes and modifications made according to the claims of the present invention should be covered by the present invention.
Claims (9)
1. A preparation method of a photo-crosslinking silk fibroin hemostatic adhesive is characterized by comprising the following steps: the silk fibroin hemostatic adhesive with strong mechanical property and high adhesion property in a wet physiological environment is obtained by taking methacrylic acid esterified silk fibroin as a matrix, adding dopamine modified alginic acid, calcium sulfate dihydrate and a photoinitiator, uniformly stirring at room temperature in a dark place, quickly crosslinking and polymerizing the mixed solution within 60 seconds under the irradiation of ultraviolet light, and under the existence of chemical covalent bond crosslinking and metal ionic bond dynamic crosslinking.
2. The preparation method of the photo-crosslinked silk fibroin hemostatic adhesive according to claim 1, characterized in that: the method specifically comprises the following steps:
(1) Preparation of methacrylated silk fibroin solution: heating deionized water to boil, adding Na 2 CO 3 And silk, degumming the silk; after washing and drying, dissolving the dried degummed silk by using a lithium bromide solution to obtain a silk fibroin solution, then adding glycidyl methacrylate to modify the silk fibroin, and then dialyzing by using deionized water; centrifuging and filtering the dialyzed solution to obtain a methacrylic acid esterified silk fibroin solution;
(2) Preparation of dopamine-modified alginic acid: fully dissolving sodium alginate in deionized water, and then adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide and N-hydroxysuccinimide to activate carboxyl; after the activation, adding dopamine hydrochloride to react overnight, and controlling the pH value of a reaction system to be less than or equal to 5 in the reaction process; dialyzing the obtained solution, carrying out freeze drying treatment to obtain a white spongy substance, and dissolving the white spongy substance with deionized water to obtain a dopamine-modified alginic acid solution;
(3) Photo-crosslinked silk fibroin hemostatic adhesive: dissolving the dopamine-modified alginic acid solution prepared in the step (2), calcium sulfate dihydrate and a photoinitiator in the methacrylated silk fibroin solution prepared in the step (1) at room temperature in a dark place, and uniformly stirring in the dark place to obtain a precursor solution; the precursor solution is rapidly crosslinked and polymerized within 60 seconds under the irradiation of ultraviolet light to obtain the silk fibroin hemostatic adhesive with strong mechanical property and high adhesion property under a wet physiological environment.
3. The preparation method of the photo-crosslinked silk fibroin hemostatic adhesive according to claim 2, characterized in that: the mass percentage concentration of the methacrylated silk fibroin solution in the step (1) is 0.1-50%.
4. The method for preparing the photo-crosslinking silk fibroin hemostatic adhesive according to claim 2, wherein: the mass percentage concentration of the dopamine modified alginic acid solution in the step (2) is 0.1-50%.
5. The method for preparing the photo-crosslinking silk fibroin hemostatic adhesive according to claim 2, wherein: the mass ratio of the dopamine-modified alginic acid to the methacrylated silk fibroin in the step (3) is 100.
6. The preparation method of the photo-crosslinked silk fibroin hemostatic adhesive according to claim 2, characterized in that: the ultraviolet light irradiated in the step (3) has the wavelength of 200-400 nanometers.
7. The preparation method of the photo-crosslinked silk fibroin hemostatic adhesive according to claim 2, characterized in that: the ultraviolet light irradiation time in the step (3) is 1-60 seconds.
8. The preparation method of the photo-crosslinked silk fibroin hemostatic adhesive according to claim 2, characterized in that: the photoinitiator is photoinitiator LAP.
9. A photocrosslinked silk fibroin hemostatic adhesive made by the method of any one of claims 1~8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211197080.5A CN115636960B (en) | 2022-09-29 | 2022-09-29 | Photo-crosslinking silk fibroin hemostatic adhesive and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211197080.5A CN115636960B (en) | 2022-09-29 | 2022-09-29 | Photo-crosslinking silk fibroin hemostatic adhesive and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115636960A true CN115636960A (en) | 2023-01-24 |
| CN115636960B CN115636960B (en) | 2024-05-31 |
Family
ID=84942533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211197080.5A Active CN115636960B (en) | 2022-09-29 | 2022-09-29 | Photo-crosslinking silk fibroin hemostatic adhesive and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115636960B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117379587A (en) * | 2023-09-15 | 2024-01-12 | 中山大学中山眼科中心 | Tissue adhesive material, and preparation method and application thereof |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103709418A (en) * | 2013-12-13 | 2014-04-09 | 苏州大学 | Silk fibroin/alginate hydrogel material and preparation method thereof |
| CN103877617A (en) * | 2014-02-21 | 2014-06-25 | 广西师范大学 | Injectable silk fibroin-alginate double cross-linking hydrogel and preparation method and use method thereof |
| CN107233626A (en) * | 2017-08-03 | 2017-10-10 | 江南大学 | A kind of preparation method of alginic acid dopamine/nanometer hydroxyapatite compound rest |
| CN108744055A (en) * | 2018-06-15 | 2018-11-06 | 福州大学 | A kind of fibroin albumen bone-cement biological adhesive and preparation method thereof |
| CN108744023A (en) * | 2018-06-15 | 2018-11-06 | 福州大学 | A kind of fibroin albumen medical bio adhesive and preparation method thereof |
| US20200206383A1 (en) * | 2017-09-15 | 2020-07-02 | Haining Zhuluoji Biotechnology Co., Ltd. | Agent for biological damage repair or hemostasis and the method thereof |
| CN111991611A (en) * | 2020-08-12 | 2020-11-27 | 山东百多安医疗器械股份有限公司 | Self-repairing hemostatic sponge capable of being adhered and preparation method thereof |
| CN112043865A (en) * | 2019-06-06 | 2020-12-08 | 天津大学 | Strontium hydroxyapatite and sodium alginate composite injectable hydrogel with adhesion and preparation method and application thereof |
| CN112300418A (en) * | 2020-09-24 | 2021-02-02 | 山东百多安医疗器械股份有限公司 | Adhesive high-efficiency hemostatic microsphere and preparation method thereof |
| CN114524953A (en) * | 2022-03-20 | 2022-05-24 | 山西医科大学 | Silk fibroin/hyaluronic acid composite hydrogel, preparation method and application |
| CN114853965A (en) * | 2022-03-18 | 2022-08-05 | 复旦大学 | Hydrogel material with bioactivity and preparation method and application thereof |
-
2022
- 2022-09-29 CN CN202211197080.5A patent/CN115636960B/en active Active
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103709418A (en) * | 2013-12-13 | 2014-04-09 | 苏州大学 | Silk fibroin/alginate hydrogel material and preparation method thereof |
| CN103877617A (en) * | 2014-02-21 | 2014-06-25 | 广西师范大学 | Injectable silk fibroin-alginate double cross-linking hydrogel and preparation method and use method thereof |
| CN107233626A (en) * | 2017-08-03 | 2017-10-10 | 江南大学 | A kind of preparation method of alginic acid dopamine/nanometer hydroxyapatite compound rest |
| US20200206383A1 (en) * | 2017-09-15 | 2020-07-02 | Haining Zhuluoji Biotechnology Co., Ltd. | Agent for biological damage repair or hemostasis and the method thereof |
| CN108744055A (en) * | 2018-06-15 | 2018-11-06 | 福州大学 | A kind of fibroin albumen bone-cement biological adhesive and preparation method thereof |
| CN108744023A (en) * | 2018-06-15 | 2018-11-06 | 福州大学 | A kind of fibroin albumen medical bio adhesive and preparation method thereof |
| CN112043865A (en) * | 2019-06-06 | 2020-12-08 | 天津大学 | Strontium hydroxyapatite and sodium alginate composite injectable hydrogel with adhesion and preparation method and application thereof |
| CN111991611A (en) * | 2020-08-12 | 2020-11-27 | 山东百多安医疗器械股份有限公司 | Self-repairing hemostatic sponge capable of being adhered and preparation method thereof |
| CN112300418A (en) * | 2020-09-24 | 2021-02-02 | 山东百多安医疗器械股份有限公司 | Adhesive high-efficiency hemostatic microsphere and preparation method thereof |
| CN114853965A (en) * | 2022-03-18 | 2022-08-05 | 复旦大学 | Hydrogel material with bioactivity and preparation method and application thereof |
| CN114524953A (en) * | 2022-03-20 | 2022-05-24 | 山西医科大学 | Silk fibroin/hyaluronic acid composite hydrogel, preparation method and application |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117379587A (en) * | 2023-09-15 | 2024-01-12 | 中山大学中山眼科中心 | Tissue adhesive material, and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115636960B (en) | 2024-05-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108744023B (en) | Silk fibroin medical biological adhesive and preparation method thereof | |
| Bao et al. | The recent progress of tissue adhesives in design strategies, adhesive mechanism and applications | |
| Chen et al. | An injectable anti-microbial and adhesive hydrogel for the effective noncompressible visceral hemostasis and wound repair | |
| CN106310383B (en) | Injectable bone repair hydrogel and preparation method thereof | |
| CN108744055B (en) | Silk fibroin bone cement biological adhesive and preparation method thereof | |
| Zheng et al. | Recent progress in surgical adhesives for biomedical applications | |
| CN114767919B (en) | Hydrogel powder for rapid hemostasis as well as preparation method and application thereof | |
| CN114712550B (en) | Hydrogel adhesive capable of being injected for rapid hemostasis and preparation method and application thereof | |
| WO2009021287A1 (en) | Photoactivated crosslinking of a protein or peptide | |
| CN111057252B (en) | Controllable-removal strong-adhesion hydrogel and preparation method thereof | |
| CN107626002A (en) | A kind of response type medical gel and preparation method and application | |
| CN109453420B (en) | Hemostatic composition, preparation method and application thereof | |
| CN114344556A (en) | Polyphenol-silk fibroin-polyethylene glycol medical tissue adhesive, preparation method and application | |
| WO2022057841A1 (en) | Prosthetic heart valve and preparation method therefor | |
| CN110548171B (en) | Gelatin-based bone tissue adhesive, and preparation method and application thereof | |
| CN115636960A (en) | Photo-crosslinking silk fibroin hemostatic adhesive and preparation method thereof | |
| Kong et al. | Tissue adhesives for wound closure | |
| Yang et al. | Transforming natural silk nonwovens into robust bioadhesives for in vivo tissue amendment | |
| Wang et al. | Functional modification of silk fibroin from silkworms and its application to medical biomaterials: A review | |
| He et al. | Recent advances in photo-crosslinkable methacrylated silk (Sil-MA)-based scaffolds for regenerative medicine: A review | |
| CN115181226B (en) | Micromolecule silk fibroin-based hydrogel and preparation method and application thereof | |
| CN115466410A (en) | Photosensitive silk fibroin flexible gel and preparation method thereof | |
| CN102008740B (en) | Absorbable growth factor composite dressing | |
| CN108619560B (en) | Preparation method of tissue adhesion hemostatic antibacterial nano-film | |
| CN113501981A (en) | Single-component biological hydrogel and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |