CN113999408A - 一种可促进血管生成的光固化水凝胶微球的制备方法 - Google Patents
一种可促进血管生成的光固化水凝胶微球的制备方法 Download PDFInfo
- Publication number
- CN113999408A CN113999408A CN202111178821.0A CN202111178821A CN113999408A CN 113999408 A CN113999408 A CN 113999408A CN 202111178821 A CN202111178821 A CN 202111178821A CN 113999408 A CN113999408 A CN 113999408A
- Authority
- CN
- China
- Prior art keywords
- solution
- microspheres
- gelatin
- proportion
- stirring
- 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.)
- Pending
Links
- 239000004005 microsphere Substances 0.000 title claims abstract description 72
- 239000000017 hydrogel Substances 0.000 title claims abstract description 50
- 230000001737 promoting effect Effects 0.000 title claims abstract description 28
- 230000033115 angiogenesis Effects 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000000016 photochemical curing Methods 0.000 title claims abstract description 11
- 108010010803 Gelatin Proteins 0.000 claims abstract description 31
- 239000008273 gelatin Substances 0.000 claims abstract description 31
- 229920000159 gelatin Polymers 0.000 claims abstract description 31
- 235000019322 gelatine Nutrition 0.000 claims abstract description 31
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 31
- 239000000463 material Substances 0.000 claims abstract description 15
- 125000005395 methacrylic acid group Chemical class 0.000 claims abstract description 15
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims abstract description 13
- DCUFMVPCXCSVNP-UHFFFAOYSA-N methacrylic anhydride Chemical compound CC(=C)C(=O)OC(=O)C(C)=C DCUFMVPCXCSVNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims abstract description 11
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 10
- 239000000243 solution Substances 0.000 claims description 84
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
- 238000003756 stirring Methods 0.000 claims description 35
- 239000008367 deionised water Substances 0.000 claims description 30
- 229910021641 deionized water Inorganic materials 0.000 claims description 30
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 24
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 24
- 238000000502 dialysis Methods 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 238000004108 freeze drying Methods 0.000 claims description 16
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 15
- 239000008055 phosphate buffer solution Substances 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 14
- 108010041308 Endothelial Growth Factors Proteins 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 12
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 10
- 238000010041 electrostatic spinning Methods 0.000 claims description 10
- 229920001184 polypeptide Polymers 0.000 claims description 10
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 10
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 10
- 229940014800 succinic anhydride Drugs 0.000 claims description 10
- 239000000843 powder Substances 0.000 claims description 9
- 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 8
- 229920005615 natural polymer Polymers 0.000 claims description 8
- 235000010413 sodium alginate Nutrition 0.000 claims description 8
- 239000000661 sodium alginate Substances 0.000 claims description 8
- 229940005550 sodium alginate Drugs 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 6
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 5
- 230000004913 activation Effects 0.000 claims description 5
- 229910001424 calcium ion Inorganic materials 0.000 claims description 5
- 238000007865 diluting Methods 0.000 claims description 5
- 238000005516 engineering process Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 230000001678 irradiating effect Effects 0.000 claims description 5
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 5
- 239000012498 ultrapure water Substances 0.000 claims description 5
- 159000000007 calcium salts Chemical class 0.000 claims description 4
- 238000004140 cleaning Methods 0.000 claims description 4
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 3
- 239000001639 calcium acetate Substances 0.000 claims description 3
- 229960005147 calcium acetate Drugs 0.000 claims description 3
- 235000011092 calcium acetate Nutrition 0.000 claims description 3
- NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 claims description 3
- 229910000020 calcium bicarbonate Inorganic materials 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- 238000007710 freezing Methods 0.000 claims 1
- 230000008014 freezing Effects 0.000 claims 1
- -1 lithium-2, 4, 6-trimethylbenzoylphosphonate Chemical compound 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 210000003556 vascular endothelial cell Anatomy 0.000 abstract description 4
- 230000009471 action Effects 0.000 abstract description 3
- 239000012620 biological material Substances 0.000 abstract description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 abstract description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 abstract description 2
- 230000007850 degeneration Effects 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 230000010595 endothelial cell migration Effects 0.000 abstract description 2
- 210000002744 extracellular matrix Anatomy 0.000 abstract description 2
- 238000001727 in vivo Methods 0.000 abstract description 2
- 230000001172 regenerating effect Effects 0.000 abstract description 2
- 230000008728 vascular permeability Effects 0.000 abstract description 2
- 230000021164 cell adhesion Effects 0.000 abstract 2
- 230000005684 electric field Effects 0.000 abstract 1
- 230000035755 proliferation Effects 0.000 abstract 1
- 239000000758 substrate Substances 0.000 abstract 1
- RKCKOWJWQLITLM-UHFFFAOYSA-N P(O)(O)=O.C1(=CC=CC=C1)C=1C(=C(C(=O)[Li])C(=CC1C)C)C Chemical compound P(O)(O)=O.C1(=CC=CC=C1)C=1C(=C(C(=O)[Li])C(=CC1C)C)C RKCKOWJWQLITLM-UHFFFAOYSA-N 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 9
- 210000002969 egg yolk Anatomy 0.000 description 8
- 239000000126 substance Substances 0.000 description 7
- 235000013601 eggs Nutrition 0.000 description 6
- 210000001161 mammalian embryo Anatomy 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 4
- 210000003954 umbilical cord Anatomy 0.000 description 4
- 210000001643 allantois Anatomy 0.000 description 3
- 210000004381 amniotic fluid Anatomy 0.000 description 3
- 210000003837 chick embryo Anatomy 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 210000001325 yolk sac Anatomy 0.000 description 3
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 230000003169 placental effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 210000002993 trophoblast Anatomy 0.000 description 2
- 241000239290 Araneae Species 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004774 atomic orbital Methods 0.000 description 1
- 239000003519 biomedical and dental material Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 210000003278 egg shell Anatomy 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000001808 exosome Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000002220 organoid Anatomy 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/12—Powdering or granulating
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—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
- 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
- A61L27/58—Materials at least partially resorbable by the body
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
- C08J3/246—Intercrosslinking of at least two polymers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/28—Treatment by wave energy or particle radiation
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/04—Alginic acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2389/00—Characterised by the use of proteins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2405/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
- C08J2405/04—Alginic acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2489/00—Characterised by the use of proteins; Derivatives thereof
Abstract
本发明公开一种可促进血管生成的光固化水凝胶微球的制备方法,属于生物材料制备技术领域。该水凝胶微球是一种高度特异性的促进血管生成材料,具有促进细胞黏附、血管通透性增加、细胞外基质变性、血管内皮细胞迁移、增殖和血管形成等作用,可批量制备。该水凝胶微球是以天然来源的高分子材料明胶为基底材料,通过甲基丙烯酸酐对明胶进行改性,并在此基础上采用共价连接方法将具有血管内皮生长因子(VEGF)接枝到甲基丙烯酸酰化明胶的分子骨架上,再在电场的作用下,批量形成微球。由其制备的可控光固化水凝胶微球具有良好的生物相容性,在体内可降解,具有促进血管化的作用,可以主动诱导细胞黏附,在再生医学及临床治疗中应用前景良好。
Description
技术领域
本发明涉及生物材料制备技术领域,尤其是涉及一种可促进血管生成的可控光固化水凝胶微球的制备方法。
技术背景
血管内皮生长因子(vascular endothelial growth factor,VEGF),又称血管通透因子(vascular permeability factor,VPF)是一种高度特异性的促血管内皮细胞生长因子,具有促进血管通透性增加、细胞外基质变性、血管内皮细胞迁移、增殖和血管形成等作用。在人类胎盘滋养细胞及血管内皮细胞上有VEGF及其受体的表达,说明VEGF参与正常妊娠、胎盘血管生成的调节和滋养叶细胞生理性的侵入。但是目前存在的多肽水凝胶无法有效地控制其降解速率。
目前在生物医用材料领域,大部分都是特异性多肽与高分子材料混合,无法达到缓释的作用。共价键(covalent bond)是化学键的一种,两个或多个原子共同使用它们的外层电子,在理想情况下达到电子饱和的状态,由此组成比较稳定的化学结构,像这样由几个相邻原子通过共用电子并与共用电子之间形成的一种强烈作用叫做共价键。其本质是原子轨道重叠后,高概率地出现在两个原子核之间的电子与两个原子核之间的电性作用。采用共价接枝的方法所得到的材料除了能得到稳定的效果外,还可能通过控制反应的条件得到可控力学性能、可控接枝率的生物医用材料。
发明内容
本发明的目的在于提供一种可促进血管生成的光固化水凝胶微球的制备方法,得到的水凝胶兼具有可控的力学性能及良好的生物相容性,具有促进血管化的作用,在再生医学及临床治疗中应用前景良好,具体包括以下步骤:
(1)将碳酸钠加入得到去离子水中,把碳酸钠水溶液稀释调节至pH为 7-10,按50~200g/L的比例将明胶加入碳酸钠溶液中,于35-60°C下搅拌溶解,然后加入甲基丙烯酸酐,甲基丙烯酸酐与明胶体积质量比为1-3:1,反应完成后用去离子水在常温下透析,透析结束后,冷冻干燥后得到甲基丙烯酸酰化明胶,反应化学式如下:
(2)按50~200g/L的比例将甲基丙烯酸酰化明胶溶于去离子水中,然后加入丁二酸酐,丁二酸酐与甲基丙烯酸酰化明胶的体积质量比为1-3:1,在25-55℃下搅拌反应24;反应完成后,用去离子水在常温下透析,透析结束后,冷冻干燥后得到得到甲基丙烯酸酰化明胶-COOH,反应化学式如下:
(3)按50~200g/L的比例将甲基丙烯酸酰化明胶-COOH溶于PBS溶液中,然后按0.1~0.5g/L的比例加入1-(3-二甲基氨基丙基)-3-乙基碳二亚胺(EDC)和0.1~0.5g/L比例的N-羟基琥珀酰亚胺(NHS)的混合物,活化反应0.5-4h,按0.1~0.5g/L的比例加入血管内皮生长因子,活化的材料混合搅拌6-24小时,去离子水在常温下透析,透析结束后,冷冻干燥后得到甲基丙烯酸酰化明胶-血管内皮生长因子,反应化学式如下:
(4)在避光条件下,按0.25~3g/100mL的比例取苯基-2,4,6-三甲基苯甲酰基膦酸锂(LAP),与超纯水混合于35-50℃下磁力搅拌1~8小时配置成苯基-2,4,6-三甲基苯甲酰基膦酸锂(LAP)溶液,按50~200g/L的比例将步骤(3)制备的甲基丙烯酸酰化明胶-血管内皮生长因子溶于基-2,4,6-三甲基苯甲酰基膦酸锂(LAP)溶液中,于50℃下磁力搅拌1~8小时,搅拌均匀制成溶液A;在室温下,按5~20g/L的比例取海藻酸钠粉末搅拌溶解于去离子水中,制成溶液B。
(5)按溶液A与溶液B体积比为1:0.5-1:2的比例将溶液A与溶液B混合后加入到注射器中,采用质量百分比浓度为1%-5%的可溶性钙盐水溶液作为接收溶液,在无菌的环境下,基于静电纺丝技术使注射器中溶液A与溶液B的混合液向接收溶液中射出,用光灯照射制备好的微球,照射时间10-90s,得到双交联的促血管生成的多肽天然高分子水凝胶微球。
(6)将含有水凝胶微球的接收液倒入45-100um的细胞筛网进行过滤,分离得到水凝胶微球;接着,再用无菌的PBS水溶液进行清洗,并进行常温干燥,以去除所述微球表面残留的钙离子,从而得到清洗后的水凝胶微球,即最终可用微球。
优选的,本发明步骤(1)~(3)所述透析的条件为:透析5d,每12h换一次水,透析袋截留分子量为8KDa-14Kda。
优选的,本发明步骤(1)~(3)所述冷冻干燥的条件为:-80℃。
优选的,本发明所述1-(3-二甲基氨基丙基)-3-乙基碳二亚胺与N-羟基琥珀酰亚胺的质量比为1:1-1:3。
优选的,本发明所述静电纺丝的条件为:所采用的正电压为15-30KV,负电压为0。
优选的,本发明所述可溶性钙盐为氯化钙、碳酸氢钙和乙酸钙中的至少一种。
本发明的有益效果:
(1)本发明所述方法制备的微球可用作支架,提供细胞三维培养的微环境,与外界进行物质交换,使细胞在体外培养增殖;在移入动物体内后,还能促进不同器官组织的再生,它是无细胞毒性,与生物体相容,可释放细胞因子,形成类器官。
(2)本发明所述微球也可以包裹不同种类细胞、细胞因子、蛋白质、外泌体等。它在动物体内是缓慢降解的,随着动物体内各种活性酶的作用,降解后的产物可被动物自身作为营养物质吸收消化,无生物毒性。所述微球还具有亲水性和细胞相容性,可渗透营养物质,柔软且富有弹性,使得微球适应流体条件,而不会引起显着的摩擦力或机械刺激。
(3)本发明所述方法以明胶为原料,利用甲基丙烯酸酐对明胶的氨基进行改性引入光交联,采用EDC、NHS将甲基丙烯酸酰化明胶的羧基活化,并使多肽的N端和活化位置结合。本发明采用光交联,对天然高分子水凝胶产生光联网络,避免了合成高分子、有毒交联剂的使用,得到的高强度甲基丙烯酸酰化明胶-血管内皮生长因子水凝胶。水凝胶兼具优异的可调控力学性能及生物相容性,为制备高强度蛋白质基水凝胶提供一种新的思路及方法,有助于蛋白质基水凝胶材料的开发利用,以便其应用在生物材料、组织工程等领域。
(4)本发明所用水凝胶粉为固体,可以长期存放,所占体积小,方便大规模生产和投入市场使用,也可以采用环氧乙烷或辐照灭菌,对生产制备的环境要求低,操作简便,成本低廉,制备得到的光固化凝胶具有良好的光响应性、生物相容性,在体内可降解,具有促进血管化的作用,工业应用前景良好。
附图说明
图1为微球示意图;
图2为鸡胚的发育情况;
图3为包裹细胞微球。
具体实施方式
下面结合附图和具体实施例对本发明作进一步详细说明,但本发明的保护范围并不限于所述内容。
实施例1
一种可促进血管生成的光固化水凝胶微球的制备方法,具体包括以下步骤:
(1)将碳酸钠加入得到去离子水中,稀释调节至pH为 7.4,按100g/L的比例将明胶加入碳酸钠溶液中,于50°C下搅拌溶解,然后加入甲基丙烯酸酐,甲基丙烯酸酐与明胶体积质量比为2:1,反应完成后用去离子水在常温下透析5d,每12h换一次水,透析袋截留分子量为8KDa-14Kda,透析结束后,冷冻干燥后得到甲基丙烯酸酰化明胶。
(2)按100g/L的比例将甲基丙烯酸酰化明胶溶于去离子水中,然后加入丁二酸酐,丁二酸酐与甲基丙烯酸酰化明胶的体积质量比为1:1.6,在50℃下搅拌反应24 h;反应完成后,用去离子水在常温下透析5d,每12h换一次水,透析袋截留分子量为8KDa-14Kda,透析结束后,冷冻干燥后得到得到甲基丙烯酸酰化明胶-COOH。
(3)按100g/L的比例将甲基丙烯酸酰化明胶-COOH溶于PBS溶液中,然后按0.13g/L的比例加入1-(3-二甲基氨基丙基)-3-乙基碳二亚胺(EDC)和0.13g/L比例的N-羟基琥珀酰亚胺(NHS)的混合物,1-(3-二甲基氨基丙基)-3-乙基碳二亚胺与N-羟基琥珀酰亚胺的质量比为1:1,活化反应0.5h,按0.5g/L的比例加入血管内皮生长因子,活化的材料混合搅拌8小时,去离子水在常温下透析5d,每12h换一次水,透析袋截留分子量为8KDa-14Kda,透析结束后,冷冻干燥后得到甲基丙烯酸酰化明胶-血管内皮生长因子。
(4)在避光条件下,按1.5g/100mL的比例取苯基-2,4,6-三甲基苯甲酰基膦酸锂(LAP),与超纯水混合于50℃下磁力搅拌6小时配置成苯基-2,4,6-三甲基苯甲酰基膦酸锂(LAP)溶液,按100g/L的比例将步骤(3)制备的甲基丙烯酸酰化明胶-血管内皮生长因子溶于基-2,4,6-三甲基苯甲酰基膦酸锂(LAP)溶液中,于50℃下磁力搅拌6小时,搅拌均匀制成溶液A;在室温下,按10g/L的比例取海藻酸钠粉末搅拌溶解于去离子水中,制成溶液B。
(5)按溶液A与溶液B体积比为1:1的比例将溶液A与溶液B混合后加入到10ml注射器中,采用质量百分比浓度为3%的CaCl2水溶液作为接收溶液,在无菌的环境下,基于静电纺丝技术使注射器中溶液A与溶液B的混合液向接收溶液中射出,用405um蓝光灯照射制备好的微球,照射时间30s,得到双交联的促血管生成的多肽天然高分子水凝胶微球。所述静电纺丝的条件为:所采用的正电压为15KV,负电压为0。
(6)将含有水凝胶微球的接收液倒入45-100um的细胞筛网进行过滤,分离得到水凝胶微球;接着,再用无菌的PBS水溶液进行清洗,并进行常温干燥,以去除所述微球表面残留的钙离子,从而得到清洗后的水凝胶微球,即最终可用微球(如图1)。
验证实验:
第一步:0日龄受精鸡胚于培养箱温度37.5℃、湿度60%的环境中,进行孵育每日观察现象。
第一天:照蛋时可以发现蛋黄表面有一颗颜色稍深、四周稍亮的圆点。
第二天:可以看到卵黄囊血管区,其形状很像樱桃形。
第三天:卵黄囊血管的形状像静止的蚊子,卵黄颜色稍深的下部像月牙。
第四天:蛋转动时,卵黄不易跟随着转动,胚胎和卵黄囊血管形状像一只小蜘蛛。
第五天:明显看到黑色的眼点。
第六天:胚胎形似“电话筒”,一端是头部,另一端为弯曲增大的躯干部,可以看到羊水。
第七天:羊水增多,胚胎活动尚不强,正面已布满扩大的卵黄和血管。
第八天:胚胎较易看到,像在羊水中浮游一样,卵黄已扩大到背面,蛋转动时两边卵黄不易晃动。
第九天:蛋转动时,两边卵黄容易晃动,接着背面尿囊血管迅速伸展出卵黄。
通过观察鸡胚的发育情况,至9日龄时,开始下一步操作。
第二步:在无菌条件下用牙科锯齿弯镊剥去己标记气室位置的蛋壳部分,取大约1毫升的生理盐水润湿白色蛋膜,用镊子把蛋膜去除,暴露出尿囊膜;放入特氟龙环,将甲基丙烯酸酰化明胶-血管内皮生长因子溶液滴加于特氟龙环内的尿囊膜表面,观察CAM反映情况。当材料置于正在发育的尿囊膜表面,刺激24-48h。
如图2所示材料周围的血管像一个车轮呈放射状,血管密度增加,证明材料有材料有促血管生成的功能。
实施例2
一种可促进血管生成的光固化水凝胶微球的制备方法,具体包括以下步骤:
(1)将碳酸钠加入得到去离子水中,稀释调节至pH为 8,按50g/L的比例将明胶加入碳酸钠溶液中,于35°C下搅拌溶解,然后加入甲基丙烯酸酐,甲基丙烯酸酐与明胶体积质量比为1:1,反应完成后用去离子水在常温下透析5d,每12h换一次水,透析袋截留分子量为8KDa-14Kda,透析结束后,冷冻干燥后得到甲基丙烯酸酰化明胶。
(2)按50g/L的比例将甲基丙烯酸酰化明胶溶于去离子水中,然后加入丁二酸酐,丁二酸酐与甲基丙烯酸酰化明胶的体积质量比为1:1,在25℃下搅拌反应24 h;反应完成后,用去离子水在常温下透析5d,每12h换一次水,透析袋截留分子量为8KDa-14Kda,透析结束后,冷冻干燥后得到得到甲基丙烯酸酰化明胶-COOH。
(3)按50g/L的比例将甲基丙烯酸酰化明胶-COOH溶于PBS溶液中,然后按0.1g/L的比例加入1-(3-二甲基氨基丙基)-3-乙基碳二亚胺(EDC)和0.3g/L比例的N-羟基琥珀酰亚胺(NHS)的混合物,1-(3-二甲基氨基丙基)-3-乙基碳二亚胺与N-羟基琥珀酰亚胺的质量比为1:3,活化反应0.2h,按0.1g/L的比例加入血管内皮生长因子,活化的材料混合搅拌6小时,去离子水在常温下透析5d,每12h换一次水,透析袋截留分子量为8KDa-14Kda,透析结束后,冷冻干燥后得到甲基丙烯酸酰化明胶-血管内皮生长因子。
(4)在避光条件下,按0.25g/100mL的比例取苯基-2,4,6-三甲基苯甲酰基膦酸锂(LAP),与超纯水混合于35℃下磁力搅拌8小时配置成苯基-2,4,6-三甲基苯甲酰基膦酸锂(LAP)溶液,按50g/L的比例将步骤(3)制备的甲基丙烯酸酰化明胶-血管内皮生长因子溶于基-2,4,6-三甲基苯甲酰基膦酸锂(LAP)溶液中,于50℃下磁力搅拌2小时,搅拌均匀制成溶液A;在室温下,按5g/L的比例取海藻酸钠粉末搅拌溶解于去离子水中,制成溶液B。
(5)按溶液A与溶液B体积比为1:0.5的比例将溶液A与溶液B混合后加入到10ml注射器中,采用质量百分比浓度为1%的碳酸氢钙水溶液作为接收溶液,在无菌的环境下,基于静电纺丝技术使注射器中溶液A与溶液B的混合液向接收溶液中射出,用405um蓝光灯照射制备好的微球,照射时间10s,得到双交联的促血管生成的多肽天然高分子水凝胶微球。所述静电纺丝的条件为:所采用的正电压为30KV,负电压为0。
(6)将含有水凝胶微球的接收液倒入45-100um的细胞筛网进行过滤,分离得到水凝胶微球;接着,再用无菌的PBS水溶液进行清洗,并进行常温干燥,以去除所述微球表面残留的钙离子,从而得到清洗后的水凝胶微球,即最终可用微球。
双交联的促血管生成多肽天然高分子水凝胶微球混合脐带间充质干细胞悬浮液培养,由图3a、3b可知,脐带间充质干细胞在水凝胶微球刺激下生长情况良好。
实施例3
一种可促进血管生成的光固化水凝胶微球的制备方法,具体包括以下步骤:
(1)将碳酸钠加入得到去离子水中,稀释调节至pH为 10,按200g/L的比例将明胶加入碳酸钠溶液中,于60°C下搅拌溶解,然后加入甲基丙烯酸酐,甲基丙烯酸酐与明胶体积质量比为3:1,反应完成后用去离子水在常温下透析5d,每12h换一次水,透析袋截留分子量为8KDa-14Kda,透析结束后,冷冻干燥后得到甲基丙烯酸酰化明胶。
(2)按200g/L的比例将甲基丙烯酸酰化明胶溶于去离子水中,然后加入丁二酸酐,丁二酸酐与甲基丙烯酸酰化明胶的体积质量比为1:3,在55℃下搅拌反应24 h;反应完成后,用去离子水在常温下透析5d,每12h换一次水,透析袋截留分子量为8KDa-14Kda,透析结束后,冷冻干燥后得到得到甲基丙烯酸酰化明胶-COOH。
(3)按200g/L的比例将甲基丙烯酸酰化明胶-COOH溶于PBS溶液中,然后按0.5g/L的比例加入1-(3-二甲基氨基丙基)-3-乙基碳二亚胺(EDC)和0.25g/L比例的N-羟基琥珀酰亚胺(NHS)的混合物,1-(3-二甲基氨基丙基)-3-乙基碳二亚胺与N-羟基琥珀酰亚胺的质量比为2:1,活化反应4h,按0.3g/L的比例加入血管内皮生长因子,活化的材料混合搅拌24小时,去离子水在常温下透析5d,每12h换一次水,透析袋截留分子量为8KDa-14Kda,透析结束后,冷冻干燥后得到甲基丙烯酸酰化明胶-血管内皮生长因子。
(4)在避光条件下,按3g/100mL的比例取苯基-2,4,6-三甲基苯甲酰基膦酸锂(LAP),与超纯水混合于40℃下磁力搅拌1小时配置成苯基-2,4,6-三甲基苯甲酰基膦酸锂(LAP)溶液,按200g/L的比例将步骤(3)制备的甲基丙烯酸酰化明胶-血管内皮生长因子溶于基-2,4,6-三甲基苯甲酰基膦酸锂(LAP)溶液中,于50℃下磁力搅拌8小时,搅拌均匀制成溶液A;在室温下,按20g/L的比例取海藻酸钠粉末搅拌溶解于去离子水中,制成溶液B。
(5)按溶液A与溶液B体积比为1:2的比例将溶液A与溶液B混合后加入到10ml注射器中,采用质量百分比浓度为5%的乙酸钙水溶液作为接收溶液,在无菌的环境下,基于静电纺丝技术使注射器中溶液A与溶液B的混合液向接收溶液中射出,用405um蓝光灯照射制备好的微球,照射时间90s,得到双交联的促血管生成的多肽天然高分子水凝胶微球。所述静电纺丝的条件为:所采用的正电压为15KV,负电压为0。
(6)将含有水凝胶微球的接收液倒入45-100um的细胞筛网进行过滤,分离得到水凝胶微球;接着,再用无菌的PBS水溶液进行清洗,并进行常温干燥,以去除所述微球表面残留的钙离子,从而得到清洗后的水凝胶微球,即最终可用微球。
双交联的促血管生成多肽天然高分子水凝胶微球混合脐带间充质干细胞悬浮液培养,脐带间充质干细胞在水凝胶微球刺激下生长情况良好。
Claims (6)
1.一种可促进血管生成的光固化水凝胶微球的制备方法,其特征在于,具体包括以下步骤:
(1)将碳酸钠加入得到去离子水中,把碳酸钠水溶液稀释调节至pH为 7-10,按50~200g/L的比例将明胶加入碳酸钠溶液中,于35-60°C下搅拌溶解,然后加入甲基丙烯酸酐,甲基丙烯酸酐与明胶体积质量比为1-3:1,反应完成后用去离子水在常温下透析,透析结束后,冷冻干燥后得到甲基丙烯酸酰化明胶;
(2)按50~200g/L的比例将甲基丙烯酸酰化明胶溶于去离子水中,然后加入丁二酸酐,丁二酸酐与甲基丙烯酸酰化明胶的体积质量比为1-3:1,在25-55℃下搅拌反应24;反应完成后,用去离子水在常温下透析,透析结束后,冷冻干燥后得到得到甲基丙烯酸酰化明胶-COOH;
(3)按50~200g/L的比例将甲基丙烯酸酰化明胶-COOH溶于PBS溶液中,然后按0.1~0.5g/L的比例加入1-(3-二甲基氨基丙基)-3-乙基碳二亚胺和0.1~0.5g/L比例的N-羟基琥珀酰亚胺的混合物,活化反应0.5-4h,按0.1~0.5g/L的比例加入血管内皮生长因子,活化的材料混合搅拌6-24小时,去离子水在常温下透析,透析结束后,冷冻干燥后得到甲基丙烯酸酰化明胶-血管内皮生长因子;
(4)在避光条件下,按0.25~3g/100mL的比例取苯基-2,4,6-三甲基苯甲酰基膦酸锂,与超纯水混合于35-50℃下磁力搅拌1~8小时配置成苯基-2,4,6-三甲基苯甲酰基膦酸锂溶液,按50~200g/L的比例将步骤(3)制备的甲基丙烯酸酰化明胶-血管内皮生长因子溶于基-2,4,6-三甲基苯甲酰基膦酸锂溶液中,于50℃下磁力搅拌1~8小时,搅拌均匀制成溶液A;在室温下,按5~20g/L的比例取海藻酸钠粉末搅拌溶解于去离子水中,制成溶液B;
(5)按溶液A与溶液B体积比为1:0.5-1:2的比例将溶液A与溶液B混合后加入到注射器中,采用质量百分比浓度为1%-5%的可溶性钙盐水溶液作为接收溶液,在无菌的环境下,基于静电纺丝技术使注射器中溶液A与溶液B的混合液向接收溶液中射出,用光灯照射制备好的微球,照射时间10-90s,得到双交联的促血管生成的多肽天然高分子水凝胶微球;
(6)将含有水凝胶微球的接收液倒入45-100um的细胞筛网进行过滤,分离得到水凝胶微球;接着,再用无菌的PBS水溶液进行清洗,并进行常温干燥,以去除所述微球表面残留的钙离子,从而得到清洗后的水凝胶微球,即最终可用微球。
2.根据权利要求1所述可促进血管生成的光固化水凝胶微球的制备方法,其特征在于:步骤(1)~(3)所述透析的条件为:透析5d,每12h换一次水,透析袋截留分子量为8KDa-14Kda。
3.根据权利要求1所述可促进血管生成的光固化水凝胶微球的制备方法,其特征在于:步骤(1)~(3)所述冷冻干燥的条件为:-80℃。
4.根据权利要求1所述可促进血管生成的光固化水凝胶微球的制备方法,其特征在于:1-(3-二甲基氨基丙基)-3-乙基碳二亚胺与N-羟基琥珀酰亚胺的质量比为1:1-1:3。
5.根据权利要求1所述可促进血管生成的光固化水凝胶微球的制备方法,其特征在于:所述静电纺丝的条件为:所采用的正电压为15-30KV,负电压为0。
6.根据权利要求1所述可促进血管生成的光固化水凝胶微球的制备方法,其特征在于:所述可溶性钙盐为氯化钙、碳酸氢钙和乙酸钙中的至少一种。
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111178821.0A CN113999408A (zh) | 2021-10-09 | 2021-10-09 | 一种可促进血管生成的光固化水凝胶微球的制备方法 |
ZA2022/04463A ZA202204463B (en) | 2021-10-09 | 2022-04-21 | Preparation method for photocuring hydrogel microsphere capable of promoting angiogenesis |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111178821.0A CN113999408A (zh) | 2021-10-09 | 2021-10-09 | 一种可促进血管生成的光固化水凝胶微球的制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113999408A true CN113999408A (zh) | 2022-02-01 |
Family
ID=79922460
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111178821.0A Pending CN113999408A (zh) | 2021-10-09 | 2021-10-09 | 一种可促进血管生成的光固化水凝胶微球的制备方法 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN113999408A (zh) |
ZA (1) | ZA202204463B (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114773629A (zh) * | 2022-05-20 | 2022-07-22 | 昆明理工大学 | 用于创伤性脑损伤的可注射光固化止血水凝胶的制备方法 |
CN115054731A (zh) * | 2022-04-21 | 2022-09-16 | 浙江大学 | 一种可注射功能化异质微球及其制备方法和应用 |
CN115105631A (zh) * | 2022-08-12 | 2022-09-27 | 郑州大学第一附属医院 | 一种冷浇注法制备的光聚合人工外泌体血管、其制备方法及应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105251057A (zh) * | 2015-10-30 | 2016-01-20 | 昆明理工大学 | 一种多孔钛/羟基磷灰石复合材料的制备方法 |
CN109627785A (zh) * | 2018-12-18 | 2019-04-16 | 常州百瑞吉生物医药有限公司 | 改性明胶基复合凝胶制备方法及应用 |
CN110078947A (zh) * | 2019-04-25 | 2019-08-02 | 中国科学院苏州生物医学工程技术研究所 | 一种复合凝胶微球的制备方法、复合凝胶微球及其应用 |
CN110938219A (zh) * | 2019-10-23 | 2020-03-31 | 浙江工业大学 | 一种交联度可调的紫外光固化透明质酸水凝胶的制备方法及其应用 |
CN111228565A (zh) * | 2020-01-21 | 2020-06-05 | 海南卓瑞生物医药有限公司 | 一种载plga微球的透明质酸-明胶复合水凝胶及其制备方法 |
CN111363168A (zh) * | 2020-03-09 | 2020-07-03 | 西南交通大学 | 具有抗凝作用的混合凝胶、其制备方法及应用 |
-
2021
- 2021-10-09 CN CN202111178821.0A patent/CN113999408A/zh active Pending
-
2022
- 2022-04-21 ZA ZA2022/04463A patent/ZA202204463B/en unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105251057A (zh) * | 2015-10-30 | 2016-01-20 | 昆明理工大学 | 一种多孔钛/羟基磷灰石复合材料的制备方法 |
CN109627785A (zh) * | 2018-12-18 | 2019-04-16 | 常州百瑞吉生物医药有限公司 | 改性明胶基复合凝胶制备方法及应用 |
CN110078947A (zh) * | 2019-04-25 | 2019-08-02 | 中国科学院苏州生物医学工程技术研究所 | 一种复合凝胶微球的制备方法、复合凝胶微球及其应用 |
CN110938219A (zh) * | 2019-10-23 | 2020-03-31 | 浙江工业大学 | 一种交联度可调的紫外光固化透明质酸水凝胶的制备方法及其应用 |
CN111228565A (zh) * | 2020-01-21 | 2020-06-05 | 海南卓瑞生物医药有限公司 | 一种载plga微球的透明质酸-明胶复合水凝胶及其制备方法 |
CN111363168A (zh) * | 2020-03-09 | 2020-07-03 | 西南交通大学 | 具有抗凝作用的混合凝胶、其制备方法及应用 |
Non-Patent Citations (3)
Title |
---|
BATZAYA BYAMBAA ET AL.: "Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue", 《ADVANCED HEALTHCARE MATERIALS》, pages 1 - 2 * |
YOUNG HWAN CHOI ET AL.: "Gelatin-based micro-hydrogel carrying genetically engineered human endothelial cells for neovascularization", 《ACTA BIOMATERIALIA》, pages 2 * |
隋继强;郭树忠;吴红;郑岩;易成刚;韩岩;: "血管内皮因子、人表皮生长因子、碱性成纤维细胞生长因子纳米缓释剂对血管内皮细胞影响的比较", 中国美容医学, no. 04 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115054731A (zh) * | 2022-04-21 | 2022-09-16 | 浙江大学 | 一种可注射功能化异质微球及其制备方法和应用 |
CN114773629A (zh) * | 2022-05-20 | 2022-07-22 | 昆明理工大学 | 用于创伤性脑损伤的可注射光固化止血水凝胶的制备方法 |
CN114773629B (zh) * | 2022-05-20 | 2024-04-12 | 昆明理工大学 | 用于创伤性脑损伤的可注射光固化止血水凝胶的制备方法 |
CN115105631A (zh) * | 2022-08-12 | 2022-09-27 | 郑州大学第一附属医院 | 一种冷浇注法制备的光聚合人工外泌体血管、其制备方法及应用 |
Also Published As
Publication number | Publication date |
---|---|
ZA202204463B (en) | 2022-07-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN113999408A (zh) | 一种可促进血管生成的光固化水凝胶微球的制备方法 | |
CN107753421B (zh) | 一种抗生物粘附聚电解质水凝胶及制备方法及应用 | |
US8168215B2 (en) | Alginate coated, collagen matrix cellular device, preparative methods, and uses thereof | |
EP0741550B1 (en) | Multiple layer alginate coatings of biological tissue for transplantation | |
US10434216B2 (en) | Ultra-thin film silk fibroin/collagen composite implant and manufacturing method therefor | |
CA2212300A1 (en) | In vitro or in vivo gelfying chitosan and therapeutic uses thereof | |
CN103877617B (zh) | 可注射蚕丝素蛋白-海藻酸盐双交联水凝胶及其制备方法和使用方法 | |
JPH08508933A (ja) | 水性媒体において膜をゲル化粒子の少なくとも表面に形成するためのエステル化多糖とポリアミンとの間のアシル交換反応の使用、それにより生成した粒子、それらの製造方法及び前記粒子を含有する組成物 | |
CN1897890B (zh) | 用藻酸盐基质控制细胞生长 | |
TWI285100B (en) | Surface modification of polysaccharide, the modified polysaccharide, and method of culturing and recovery cells using the same | |
US20210268151A1 (en) | Pre-Loadable Biological Heart Valve Capable of Rapid Rehydration and Preparation Method Thereof | |
CN103301788A (zh) | Peg接枝改性的海藻酸盐-壳聚糖微胶囊及制备和应用 | |
CN106852914A (zh) | 一种peg原位共价接枝改性海藻酸盐微囊及其制备和应用 | |
JPH08502166A (ja) | カプセル化細胞用キトサンマトリックス | |
US6281341B1 (en) | Hetero-polysaccharide conjugate and methods of making and using the same | |
CN110152055A (zh) | 海藻酸胺化衍生物/细菌纤维素纳米晶复合凝胶构筑的功能性药物缓释医用敷料 | |
CN113813445A (zh) | 一种丝素蛋白复合多孔支架及其制备方法 | |
AU759066B2 (en) | 3D matrix for producing cell transplants | |
US5529913A (en) | Method of removing protein from a water soluble gum and encapsulating cells with the gum | |
CN113941031B (zh) | 一种程序性释放no促血管生成多肽水凝胶的制备方法 | |
US20210196646A1 (en) | Improved formulations for pancreatic islet encapsulation | |
CN111214703B (zh) | 一种iPS来源心肌细胞复合补片及其制备和应用 | |
JP2004533288A (ja) | キトサンおよびヒドロキシカルボン酸をベースとする多孔質および非多孔質マトリクス | |
Huang et al. | Composite of decellular adipose tissue with chitosan-based scaffold for tissue engineering with adipose-derived stem cells | |
JPS6238327B2 (zh) |
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 |