CN118126267A - Application of modified bioactive glass in preparation of multifunctional hydrogel - Google Patents
Application of modified bioactive glass in preparation of multifunctional hydrogel Download PDFInfo
- Publication number
- CN118126267A CN118126267A CN202410342681.3A CN202410342681A CN118126267A CN 118126267 A CN118126267 A CN 118126267A CN 202410342681 A CN202410342681 A CN 202410342681A CN 118126267 A CN118126267 A CN 118126267A
- Authority
- CN
- China
- Prior art keywords
- bioactive glass
- coupling agent
- silane coupling
- hydrogel
- 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
- 239000005313 bioactive glass Substances 0.000 title claims abstract description 108
- 239000000017 hydrogel Substances 0.000 title claims abstract description 90
- 238000002360 preparation method Methods 0.000 title claims description 35
- 239000006087 Silane Coupling Agent Substances 0.000 claims abstract description 61
- 150000003254 radicals Chemical class 0.000 claims abstract description 30
- 239000007864 aqueous solution Substances 0.000 claims abstract description 28
- 108010010803 Gelatin Proteins 0.000 claims abstract description 27
- 229920000159 gelatin Polymers 0.000 claims abstract description 27
- 239000008273 gelatin Substances 0.000 claims abstract description 27
- 235000019322 gelatine Nutrition 0.000 claims abstract description 27
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 27
- 238000007334 copolymerization reaction Methods 0.000 claims abstract description 24
- 239000000178 monomer Substances 0.000 claims abstract description 13
- 239000000463 material Substances 0.000 claims abstract description 10
- 230000004048 modification Effects 0.000 claims abstract description 10
- 238000012986 modification Methods 0.000 claims abstract description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 24
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 20
- 239000008367 deionised water Substances 0.000 claims description 17
- 229910021641 deionized water Inorganic materials 0.000 claims description 17
- 229920001477 hydrophilic polymer Polymers 0.000 claims description 16
- ZPZDIFSPRVHGIF-UHFFFAOYSA-N 3-aminopropylsilicon Chemical compound NCCC[Si] ZPZDIFSPRVHGIF-UHFFFAOYSA-N 0.000 claims description 14
- 238000005580 one pot reaction Methods 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- 229920001661 Chitosan Polymers 0.000 claims description 10
- -1 N-methacrylamidoglycinamide Chemical compound 0.000 claims description 10
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 10
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 8
- 239000004721 Polyphenylene oxide Substances 0.000 claims description 8
- 239000011521 glass Substances 0.000 claims description 8
- 239000003999 initiator Substances 0.000 claims description 8
- 229920000570 polyether Polymers 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 7
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 6
- 239000012065 filter cake Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- DYUWTXWIYMHBQS-UHFFFAOYSA-N n-prop-2-enylprop-2-en-1-amine Chemical compound C=CCNCC=C DYUWTXWIYMHBQS-UHFFFAOYSA-N 0.000 claims description 6
- QRIMLDXJAPZHJE-UHFFFAOYSA-N 2,3-dihydroxypropyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC(O)CO QRIMLDXJAPZHJE-UHFFFAOYSA-N 0.000 claims description 5
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 229910052710 silicon Inorganic materials 0.000 claims description 5
- 239000010703 silicon Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 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 claims description 4
- 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 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 claims description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- UKMBKKFLJMFCSA-UHFFFAOYSA-N [3-hydroxy-2-(2-methylprop-2-enoyloxy)propyl] 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC(CO)OC(=O)C(C)=C UKMBKKFLJMFCSA-UHFFFAOYSA-N 0.000 claims description 4
- 230000002152 alkylating effect Effects 0.000 claims description 4
- 238000005966 aza-Michael addition reaction Methods 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- 229920002674 hyaluronan Polymers 0.000 claims description 4
- 229960003160 hyaluronic acid Drugs 0.000 claims description 4
- 150000002500 ions Chemical class 0.000 claims description 4
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 4
- 235000010413 sodium alginate Nutrition 0.000 claims description 4
- 239000000661 sodium alginate Substances 0.000 claims description 4
- 229940005550 sodium alginate Drugs 0.000 claims description 4
- 238000001291 vacuum drying Methods 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 4
- 229910004298 SiO 2 Inorganic materials 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000005956 quaternization reaction Methods 0.000 claims description 3
- 238000002390 rotary evaporation Methods 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 claims description 2
- 108010022355 Fibroins Proteins 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 229910004742 Na2 O Inorganic materials 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Chemical compound CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- GJKGAPPUXSSCFI-UHFFFAOYSA-N 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone Chemical compound CC(C)(O)C(=O)C1=CC=C(OCCO)C=C1 GJKGAPPUXSSCFI-UHFFFAOYSA-N 0.000 claims 1
- XMLYCEVDHLAQEL-UHFFFAOYSA-N 2-hydroxy-2-methyl-1-phenylpropan-1-one Chemical compound CC(C)(O)C(=O)C1=CC=CC=C1 XMLYCEVDHLAQEL-UHFFFAOYSA-N 0.000 claims 1
- LSWCMUBJZBXTDM-UHFFFAOYSA-M P(=O)(OC1=CC=CC=C1)(OC(C1=C(C=C(C=C1C)C)C)=O)[O-].[Li+] Chemical compound P(=O)(OC1=CC=CC=C1)(OC(C1=C(C=C(C=C1C)C)C)=O)[O-].[Li+] LSWCMUBJZBXTDM-UHFFFAOYSA-M 0.000 claims 1
- 230000002829 reductive effect Effects 0.000 abstract description 14
- 239000002245 particle Substances 0.000 abstract description 9
- 238000003860 storage Methods 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000006185 dispersion Substances 0.000 abstract description 3
- 230000001105 regulatory effect Effects 0.000 abstract description 3
- 229910010272 inorganic material Inorganic materials 0.000 abstract description 2
- 239000011147 inorganic material Substances 0.000 abstract description 2
- 230000016507 interphase Effects 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 description 13
- 210000000988 bone and bone Anatomy 0.000 description 8
- 229920001577 copolymer Polymers 0.000 description 8
- 239000002131 composite material Substances 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- KLGDRWGOXDJNPH-UHFFFAOYSA-N P(=O)(O)(O)O.C1(=CC=CC=C1)C=1C(=C(C(=O)[Li])C(=CC1C)C)C Chemical compound P(=O)(O)(O)O.C1(=CC=CC=C1)C=1C(=C(C(=O)[Li])C(=CC1C)C)C KLGDRWGOXDJNPH-UHFFFAOYSA-N 0.000 description 6
- RFDVZWOFSNTAJH-UHFFFAOYSA-N CC(C(=O)N)=C.[Na] Chemical compound CC(C(=O)N)=C.[Na] RFDVZWOFSNTAJH-UHFFFAOYSA-N 0.000 description 5
- 230000007547 defect Effects 0.000 description 5
- 238000013461 design Methods 0.000 description 5
- 229920000620 organic polymer Polymers 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- BXYHXVIURNMBJM-UHFFFAOYSA-N [P].[Si].[Ca] Chemical compound [P].[Si].[Ca] BXYHXVIURNMBJM-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 150000007942 carboxylates Chemical group 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- 210000004872 soft tissue Anatomy 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 238000005054 agglomeration Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- 239000012496 blank sample Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 125000005395 methacrylic acid group Chemical group 0.000 description 2
- 230000002188 osteogenic effect Effects 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- FZHAPNGMFPVSLP-UHFFFAOYSA-N silanamine Chemical compound [SiH3]N FZHAPNGMFPVSLP-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000009210 therapy by ultrasound Methods 0.000 description 2
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N Na2O Inorganic materials [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical group 0.000 description 1
- 230000003373 anti-fouling effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000000751 azo group Chemical group [*]N=N[*] 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000007849 functional defect Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 125000003055 glycidyl group Chemical group C(C1CO1)* 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000007037 hydroformylation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- DCUFMVPCXCSVNP-UHFFFAOYSA-N methacrylic anhydride Chemical compound CC(=C)C(=O)OC(=O)C(C)=C DCUFMVPCXCSVNP-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229920005613 synthetic organic polymer Polymers 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F292/00—Macromolecular compounds obtained by polymerising monomers on to inorganic materials
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F289/00—Macromolecular compounds obtained by polymerising monomers on to macromolecular compounds not provided for in groups C08F251/00 - C08F287/00
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
The invention provides bioactive glass compound methacryloylated gelatin containing surface modification of a dipropenyl quaternary ammonium cationic silane coupling agent in a molecular structure, and the like, and the multifunctional hydrogel with uniform inter-phase material dispersion, high stability and high strength is obtained through free radical copolymerization reaction in an aqueous solution in the presence of a regulating monomer. The bioactive glass particles are bonded in the gaps of the three-dimensional network of the hydrogel, so that the mechanical property of the hydrogel is not reduced, the storage stability is reduced and the use is limited due to the fact that the hydrogel is doped with inorganic materials. In addition, the raw material proportion for preparing the hydrogel can be adjusted in a large range, and the obtained hydrogel variety is determined by the biomedical application field and the use requirement, so that the application range is wide.
Description
Technical Field
The invention relates to application of modified bioactive glass in preparation of multifunctional hydrogel, wherein the modified bioactive glass is bioactive glass obtained by carrying out surface modification on the modified bioactive glass by adopting a silane coupling agent containing a dipropenyl quaternary ammonium cation in a molecular structure; the multifunctional hydrogel has the functions of resisting and inhibiting bacteria, stimulating soft tissue healing, repairing bone defect and excellent mechanical property, and belongs to the field of biological/medical functional composite materials.
Background
Hydrogels are a class of composite materials comprising a large number of water molecules in a hydrophilic polymer having a three-dimensional network structure. According to the practical application requirement, functional groups can be grafted on the hydrophilic polymer chain structure in the hydrogel to form functional hydrogel; water-soluble functional small molecules or functional macromolecules can be doped into water molecules contained in the hydrogel to obtain the homogeneous functional hydrogel with high storage stability. If water molecules contained in the hydrogel are doped with water-insoluble functional substances, the stability of the prepared heterogeneous functional hydrogel is relatively poor, and even the applicability of the hydrogel is affected. Composite hydrogels such as bioactive glass blended with hydrophilic polymers have been one of the areas of research for fire heat for more than a decade of preparation and application.
The bioactive glass is an inorganic powder material which is mainly composed of quaternary chemical components of SiO2-CaO-P2O5-Na2O, and the bioactive glass has bioactivity mainly because alkali metal ions or alkaline earth metals connected with non-bridging oxygen in a three-dimensional network of the bioactive glass are released in an aqueous medium, na+ or Ca2+ is easily dissolved in water and can be exchanged with organism tissues, so the bioactive glass is called as bioactive glass. Numerous studies over several decades have demonstrated that bioactive glasses have good osteogenic and biocompatible properties, as well as self-degrading properties. When the bioactive glass is used as a bone defect repairing material, the bioactive glass can quickly regenerate bone tissues, and the regenerated bone structure and mechanical property have good matching degree with bone defect parts; meanwhile, the research shows that the bioactive glass can promote the regeneration of soft tissues such as skin and the like, and has the function of obviously promoting the healing of skin wound surfaces. The biologically active glass was cultured with intestinal epithelial cells by a learner and found that the biologically active glass can promote proliferation of intestinal epithelial cells. The above research results all show important uses of bioactive glass in biomedical field. However, the dispersibility of the bioactive glass particles in human tissues or hydrogel is very poor, the bioactive glass particles are very easy to agglomerate, and the bioactive glass is loosely combined with an organic polymer, so that the stability, mechanical properties and the like of the bioactive glass doped hydrogel are greatly reduced, and the service performance of the bioactive glass doped hydrogel is influenced. In order to solve the self-defect of the bioactive glass, related researches of CN201210358478.2, CN201611163396.7, CN201811478997.6, CN201911356221.1 and the like are published at home and abroad, and the surface of the bioactive glass is modified by utilizing a silane coupling agent, so that the interfacial compatibility of the bioactive glass and an organic polymer is improved in a bonding mode, the bonding capability and dispersibility of the bioactive glass and the organic polymer are improved, and the mechanical property of a composite material is enhanced. In view of this, in combination with previous research results such as the subject group ZL201910993648.6、ZL2021107850204、ZL201910994314.0、ZL201811189217、CN2023100519084、CN202310116727.5、CN 202310116725.6, the present inventors have made a re-functionalization design of a commercially available 3-aminopropyl silane coupling agent, creating a multifunctional silane coupling agent with a novel molecular structure for surface modification of bioactive glass. The multifunctional silane coupling agent has a structure shown in a general formula (A):
Wherein R in formula (A) is selected from C 1～C18 hydrocarbyl, preferably CH 3 or C 2H5,R1 is selected from H or methyl, n is selected from natural numbers between 1 and 2000, and Y is selected from C 1～C18 hydrocarbyl or X - is selected from Cl -、Br-、I- or one of p-CH 3C6H4SO3 -; wherein R 2 is selected from C 1～C18 alkyl, and m is selected from natural numbers between 0 and 200.
It is apparent that the hydrolyzable groups in the molecular structure of the multifunctional silane coupling agent are still conventional trialkoxy groups; the amino in the 3-aminopropyl silane coupling agent is firstly subjected to aza-Michael addition reaction with diallylamino polyether acrylate and then subjected to quaternization reaction with an alkylating agent, so that the multifunctional silane coupling agent has a plurality of quaternary ammonium cations in a molecular structure. The multifunctional silane coupling agent with the general formula (A) is applied to the surface modification of the bioactive glass, so that the enhancement effects of antibacterial and bacteriostatic properties, biocompatibility and hydrophilicity of the bioactive glass after the surface modification can be obtained; meanwhile, the diallylammonium which is placed on the surface of the modified bioactive glass has the characteristic of carrying out copolymerization reaction with other olefin monomers or unsaturated organic polymer materials.
The gel-forming substances used for preparing hydrogels are called hydrophilic polymers, also called gel matrices, and are classified into three types according to the hydrophilic polymer source (1) natural organic polymers and their subsequent chemically modified derivatives, such as collagen, gelatin, methacryloylated gelatin, sodium alginate, hydroformylation sodium alginate, hyaluronic acid, methacryloylated hyaluronic acid, hydroxypropylated chitosan, methacryloyl chitosan, modified starch, modified cellulose, etc.; (2) Synthetic organic polymers such as polylactic acid, polyvinyl alcohol, methacryloylated polyvinyl alcohol, polyacrylamide, polyacrylic acid, polyhydroxyethyl acrylate, polybetaine, polyquaternary ammonium salt, cationic polyurethane, zwitterionic polyurethane, and the like; (3) decellularized matrix (decellularized matrix), and the like. Gelatin or chitosan is a natural water-soluble polymer, has low price, no biotoxicity and low price, and has excellent histocompatibility, biodegradability and bioavailability. Gelatin or chitosan and the like are the preferred materials for preparing the hydrogel, and the hydrogel such as gelatin or chitosan and the like can be used as a controlled release carrier of growth factors or medicines and a growth bracket of cells and tissues. However, hydrogels such as gelatin or chitosan have poor mechanical strength, too strong hydrophilicity, too fast degradation rate, and difficult matching with bone tissue regeneration rate, which limits their wide application. And the side chains of the gelatin or chitosan macromolecules have a large number of amino groups and hydroxyl groups, so that the gelatin or chitosan macromolecules can be modified by using some chemical monomers or polymers. For example, methacrylic anhydride is utilized to carry out methacryloylation on amino groups on macromolecular side chains such as gelatin, and the methacryloylated gelatin is subjected to free radical initiation polymerization reaction in aqueous solution, so that the polymethacrylylated gelatin hydrogel is obtained. The degradation performance, stability and mechanical strength of the polymethacrylylated gelatin hydrogel are improved, and the polymethacrylylated gelatin hydrogel is applied to the research of cell culture and bone tissue engineering at present. However, the methacryloylated gelatin hydrogel cannot be applied to the load bearing parts, and has general osteogenic properties and poor repair function for soft tissues or bone defects.
In order to overcome the defects of the existing bioactive glass and the functional defects of the hydrogels such as the methacryloylated gelatin, the invention adopts the bioactive glass compounded with the methacryloylated gelatin and the like with the surface modified by the dipropenyl quaternary ammonium cationic silane coupling agent in the molecular structure, and the multifunctional composite hydrogel with uniform inter-phase material dispersion, high storage stability, controllable bioactivity and high mechanical strength is obtained through the free radical copolymerization reaction in aqueous solution in the presence of a regulating monomer.
Disclosure of Invention
The invention relates to an application of modified bioactive glass in preparing multifunctional hydrogel, which is realized by the following steps: according to the mass percentage of 2-20% of modified bioactive glass, 2-20% of unsaturated hydrophilic polymer, 2-20% of adjustable monomer, 0.1-1.5% of free radical initiator and 40-90% of deionized water, sequentially weighing deionized water, unsaturated hydrophilic polymer, adjustable monomer, modified bioactive glass and free radical initiator, mixing together to prepare an aqueous solution, controlling the temperature to 15-90 ℃ under the protection of N 2, carrying out one-pot free radical copolymerization reaction for 0.4-40 hours, and then reducing the temperature of the copolymer solution to the gel forming temperature to prepare the multifunctional hydrogel;
The application of the modified bioactive glass in preparing the multifunctional hydrogel can be implemented by the following steps: respectively preparing aqueous solutions ① consisting of a regulating monomer, an unsaturated hydrophilic polymer and a free radical initiator according to the mass ratio; and an aqueous solution ② composed of an unsaturated hydrophilic polymer, modified bioactive glass, a tunable monomer, and a radical initiator; the aqueous solution ① is subjected to free radical copolymerization reaction for 0.4 to 40 hours under the protection of N 2 at the temperature of 15 to 90 ℃ to obtain a first-stage copolymer solution; adding the aqueous solution ② into the copolymer solution of the first stage, uniformly mixing, controlling the temperature to be 15-90 ℃ under the protection of N 2, and carrying out free radical copolymerization for 0.4-40 hours to obtain the copolymer solution of the second stage, wherein the temperature of the copolymer solution of the second stage is slowly reduced to the gelling temperature to prepare the multifunctional hydrogel;
The application of the modified bioactive glass in preparing the multifunctional hydrogel is specifically characterized in that: the modified bioactive glass is bioactive glass obtained by modifying the surface of the bioactive glass by adopting a silane coupling agent containing a dipropenyl quaternary ammonium cation in a molecular structure.
Wherein the preparation method of the modified bioactive glass is as follows: sequentially weighing the silane coupling agent containing the dipropenyl quaternary ammonium cation, methanol or ethanol and water according to the mass ratio of the silane coupling agent containing the dipropenyl quaternary ammonium cation to methanol or ethanol/water of 5-50:5-50, mixing the silane coupling agent containing the dipropenyl quaternary ammonium cation, the methanol or ethanol and the water together, preparing a silane coupling agent solution containing the dipropenyl quaternary ammonium cation at room temperature, stirring, adding bioactive glass, and heating to 50-90 ℃ for reacting for 2-20 hours; and (3) ending the reaction process, cooling the temperature of the reaction system to room temperature, filtering, washing the filter cake with ethanol for 1-3 times, conveying the washed filter cake into a vacuum dryer, and vacuum drying at the temperature of 25-65 ℃ to constant weight to obtain the modified bioactive glass. Wherein the molecular structure contains the dipropenyl quaternary ammonium cationic silane coupling agent in an amount which is 5-500% of the mass of the bioactive glass.
The molecular structure of the silane coupling agent containing the dipropenyl quaternary ammonium cation has a structure shown in a general formula (A):
Wherein R in the general formula (A) is selected from C 1～C18 alkyl, R 1 is selected from H or methyl, n is selected from natural numbers between 1 and 200, and Y is selected from C 1～C18 alkyl or X - is selected from one of Cl -、Br-, I-or p-CH 3C6H4SO3 -; wherein R 2 is selected from C 1～C18 alkyl, and m is selected from natural numbers between 0 and 200.
The preparation method of the diallyl quaternary ammonium-containing cationic silane coupling agent in the general formula (A) comprises the steps of dissolving diallylamine polyether acrylate in a solvent, and slowly adding the 3-aminopropyl silane coupling agent by starting stirring under the protection of N 2 at the temperature of 5-35 ℃, wherein the dosage of the diallylamine polyether acrylate is 2.0-2.2 times of the molar quantity of the 3-aminopropyl silane coupling agent; after the 3-aminopropyl silane coupling agent is fed, slowly raising the temperature of the reaction system to 35-90 ℃ for reaction for 2-20 hours, and ending the aza-Michael addition reaction process; adding an alkylating reagent into a reaction system, wherein the dosage of the alkylating reagent is 1.0-3.5 times of the molar quantity of the 3-aminopropyl silane coupling agent, keeping the temperature for continuous reaction for 2-20 hours, and ending the quaternization reaction process; then removing part of solvent by rotary evaporation, cooling to room temperature, separating out a crude product, and purifying the crude product to obtain the dipropenyl quaternary ammonium cationic silane coupling agent with the structure shown in the general formula (A);
Wherein the diallylamine polyether acrylate has a structure shown in a general formula (B):
Wherein R 1 in the general formula (B) is selected from H or methyl, and n is selected from natural numbers between 1 and 200.
The solvent refers to one or more than two of methanol, ethanol, propanol, tetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, dimethyl sulfoxide, N-methylpyrrolidone, N-dimethylformamide, N-diethylformamide or hexamethylphosphoramide; the dosage of the solvent is 1 to 10 times of the mass of the 3-aminopropyl silane coupling agent.
The 3-aminopropyl silane coupling agent has a structure shown in a general formula (C):
wherein R in formula (C) is selected from C 1～C18 hydrocarbyl groups, preferably methyl or ethyl.
The alkylating agent has a structure shown in a general formula (D):
Y-X
general formula (D)
Wherein Y in formula (D) is selected from C 1～C18 hydrocarbon groups orX is selected from Cl, br, I or one of p-CH 3C6H4SO3, wherein R 2 is selected from C 1～C18 alkyl, and m is selected from natural numbers between 0 and 200.
The bioactive glass is a silicon-based glass powder material formed by taking SiO 2-CaO-P2O5-Na2 O as a chemical component, or a silicon-based glass powder material doped with K +、Mg2+、Sr2+、Zn2+、Cu2+、B3+、Al3+、Ti4+ or Zr 4+ ions; according to the mass of each chemical component, the mass percent of SiO 2 is 40-80%, the mass percent of CaO is 10-60%, the mass percent of P 2O5 is 3-20%, the mass percent of Na 2 O is 10-60%, and the doping mass percent of K +、Mg2+、Sr2+、Zn2+、Cu2+、B3+、Al3+、Ti4+ or Zr 4+ ions is 0.25-25% of the mass of the silicon-based glass powder material or is selected according to the requirement.
The unsaturated hydrophilic polymer refers to: one or more of methacryloylated gelatin, methacryloylated chitosan, methacryloylated sodium alginate, methacryloylated hyaluronic acid or silk fibroin methacrylate.
The adjustable monomer refers to: one or more of N-vinyl pyrrolidone, methacrylic acid, 2-hydroxyethyl methacrylate, N-methacrylamidoglycinamide, glycerol methacrylate, glycerol dimethacrylate, polyethylene glycol dimethacrylate or unsaturated quaternary ammonium salt with a structure shown in a general formula (E);
Wherein the unsaturated quaternary ammonium salt has a structure represented by the general formula (E):
Wherein R 1 in formula (E) is selected from H or methyl, R 3 is selected from C 1～C18 hydrocarbyl, Y is selected from C 1～C18 hydrocarbyl or X-is selected from Cl -、Br-、I- or one of p-CH 3C6H4SO3 -; wherein R 2 is selected from C 1～C18 alkyl, and m is selected from natural numbers between 0 and 200.
The free radical initiator is selected from one or more than two of ammonium persulfate, sodium persulfate, potassium persulfate, azo diisobutylamidine hydrochloride, azo diiso Ding Mi-hydrochloride, phenyl (2, 4, 6-trimethyl benzoyl) lithium phosphate, 4-isobutylphenyl-4' -methylphenyl iodohexafluorophosphate, 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-acetone or 2-hydroxy-2-methyl-1-phenyl-1-acetone.
The invention is based on the design concept of chemical principle:
⑴ Existing relevant research results and application test expressions and demonstrations have taught: the structural unit in the multifunctional silane coupling agent can perform some vector optimization selection on Y, R 2 on N + according to actual functions, actions and performances. If the hydrophilic function is emphasized too much for the main modification purpose of the multifunctional silane coupling agent, Y, R 2 can be preferably selected from CH 3 or C 2H5, and n can be 1-3; if the main modification purpose of the multifunctional silane coupling agent is emphasized that the functions of hydrophilicity, antibiosis and sterilization are realized, Y can be preferably dodecyl or benzyl, and n can be 1-3; y may be preferred if hydrophilic, antibacterial, antifouling and biocompatible modifications are the primary objectives R 2 is preferably CH 3 or C 2H5, m and n are optionally 8 to 25.
⑵ The multifunctional silane coupling agent is adopted to modify the bioactive glass, so that the three purposes are realized: firstly, the modified bioactive glass has higher hydrophilicity, good dispersibility in aqueous solution and no sedimentation; the characteristic of easy agglomeration of the modified bioactive glass is eliminated, and the particle size of the modified bioactive glass is stable. Secondly, the diallyl quaternary ammonium cations retained on the surface of the modified bioactive glass participate in the free radical copolymerization reaction of the unsaturated hydrophilic polymer, and the bioactive glass particles are bonded on the hydrogel three-dimensional network, so that the problems of reduced standing storage stability, reduced mechanical property and limited use of the hydrogel caused by doping inorganic materials are avoided. Thirdly, more than two diallyl quaternary ammonium cations can be arranged at one modification point of the modified bioactive glass, and the diallyl quaternary ammonium cations and unsaturated hydrophilic polymers are subjected to free radical copolymerization reaction, so that a cross-linking point between three-dimensional networks of the hydrogel is added, and the modified bioactive glass has remarkable significance for improving the mechanical properties of the hydrogel.
⑶ The invention relates to application of modified bioactive glass in preparing multifunctional hydrogel, which comprises the following raw materials: the unsaturated hydrophilic polymer/adjustable monomer/modified bioactive glass can be prepared in a larger range in the compounding mass percentage; the preparation process of the hydrogel can adopt a one-pot copolymerization process to prepare the functional composite hydrogel with a full-crosslinked structure, and can also adopt a staged copolymerization process to prepare the functional composite hydrogel with interpenetrating network characteristics and a partial crosslinked structure, which is determined by the application field and the use requirement of the hydrogel.
Compared with the prior art, the application of the modified bioactive glass in preparing the multifunctional hydrogel has the beneficial effects that:
① The raw materials for preparing the hydrogel are commercial products, the yield of products in each step of preparation process is high, the preparation and purification technology of the multifunctional silane coupling agent and the modified bio-waveform glass is simple and reliable, and the technological process is simple and easy to implement.
② The surface modified bioactive glass is stable in storage and free from agglomeration; the dispersion in water is good, and sedimentation does not occur.
③ The raw material proportion for preparing the hydrogel can be adjusted in a large range, the obtained hydrogel variety is determined by the biomedical application field and the use requirement, and the application range is wide.
Detailed Description
For a further understanding of the present invention, it is to be understood that the present invention is specifically described by way of examples, and is for the purpose of better understanding of the present invention. Therefore, the use of the surface-modified bioactive glass not listed in the examples for the preparation of the multifunctional hydrogel should not be construed as limiting the scope of the invention.
Example 1 preparation of multifunctional hydrogel (A-1)
Step one, preparation of the multifunctional silane coupling agent of the formula (A-1)
78 G (about 0.202 mol) of diallylamino polyether methacrylate of the formula (B-1) is dissolved in 320 g of methanol to be put into a reaction kettle, stirring is started, 22 g (about 0.1 mol) of commercial brand KH-550 aminosilane coupling agent is slowly added under the protection of N 2 at the temperature of 10-15 ℃, after the KH-550 aminosilane coupling agent is completely added, the reaction temperature is gradually increased to 35-45 ℃ and the reaction is continued for 12 hours, 44 g (about 0.349 mol) of benzyl chloride is added into the reaction kettle after the reaction temperature is increased to 70-90 ℃ and the reaction is carried out for 20 hours, part of methanol is removed by rotary evaporation, the temperature of a reaction product system is reduced to room temperature, light yellow solid matters are separated out, and the multifunctional silane coupling agent of the formula (A-1) is prepared by filtering, washing by dehydrated acetone and vacuum drying.
KH-550 is a commodity abbreviation of 3-aminopropyl triethoxysilane, and the yield of intermediate tertiary amine is about 97.3% and the yield of the multifunctional silane coupling agent of formula (A-1) is about 89.7% through sampling, separating and purifying the aza-Michael addition reaction product of the diallylaminopolyether methacrylate of formula (B-1). The IR spectrogram of the multifunctional silane coupling agent also shows strong absorption peaks near 1726nm and 1108 nm; the elemental analysis results (theoretical value%) of C61.45 (62.00), H8.03 (8.47) and N3.01 (3.10) show that the molecular formula C70H114Cl3N3O14Si is consistent with the design molecular formula of the formula (A-1). The multifunctional silane coupling agent product of the formula (A-1) is subjected to nuclear magnetic resonance and mass spectrometry analysis, and the chemical structure of the product in the preparation process is confirmed to be consistent with the theoretical design.
Step two, preparation of surface modified bioactive glass (A-1)
86 G of ethanol, 14g of a multifunctional silane coupling agent of the formula (A-1) and 100 g of water are weighed, sequentially added into a reaction flask at room temperature, and uniformly stirred to prepare a multifunctional silane coupling agent solution. Then 30 g of calcium phosphorus silicon bioactive glass (purchased from Wohan gram biomedical technology Co., ltd.) with the particle size less than or equal to 10 μm is put into the reaction kettle, after ultrasonic treatment for 0.5 hour, the temperature is raised to 70-80 ℃ and stirred for 6 hours, the reaction process is ended, the temperature is reduced and filtered, the filter cake is washed three times by ethanol, and the temperature is controlled to 50-55 ℃ and vacuum drying is carried out until the constant weight is reached, thus 40.8 g of surface modified bioactive glass (A-1) is obtained.
29.2 G of a blank sample of bioactive glass is prepared by the same method and procedure, and the net weight gain of the surface modified bioactive glass (A-1) can be calculated to be 11.6 g, so that the reaction efficiency of the multifunctional silane coupling agent of the formula (A-1) on the surface of the bioactive glass is estimated to be 91.7%.
In the IR spectrum diagram of the surface modified bioactive glass (A-1) relative to a bioactive glass blank sample, the intermediate and strong absorption peaks are added at 2932nm, 2873nm, 1724nm, 1108nm and the like, and the vibration absorption peaks respectively belong to methyl, methylene, ester carbonyl and C-O-C, so that the surface modified bioactive glass (A-1) has the structural characteristics of carboxylate and ether bonds.
Preparation of multifunctional hydrogel (A-1)
80 G of deionized water, 3.5 g of methacrylic acid acylated gelatin with the substitution degree of 0.3, 10.5 g of methacrylic acid glyceride, 0.5 g of dimethyl acrylic acid glyceride, 0.5 g of ammonium persulfate and 5.0 g of modified bioactive glass (A-1) are sequentially weighed and prepared into an aqueous solution, the temperature is controlled to 60 ℃ under the protection of N 2, the one-pot free radical copolymerization reaction is carried out for 12 hours, and the multifunctional hydrogel (A-1) is prepared after the temperature is reduced.
Comparative example 1
According to the operation method of the first step of example 1, 50g of deionized water, 2.5 g of methacryloylated gelatin with a substitution degree of 0.3, 5.5 g of glycerol methacrylate, 0.25 g of glycerol dimethacrylate, 0.25 g of ammonium persulfate and 5.0 g of modified bioactive glass (A-1) are sequentially weighed and mixed together to prepare an aqueous solution ①; then 30 g of deionized water, 1.0 g of methacrylic acidylated gelatin with the substitution degree of 0.3, 5.0 g of methacrylic acid glyceride, 0.25 g of dimethyl acrylic acid glyceride and 0.25 g of ammonium persulfate are weighed and mixed together to prepare an aqueous solution ②; the aqueous solution ① is subjected to free radical copolymerization reaction for 6 hours under the protection of N 2 at the temperature of 60 ℃ to obtain a first-stage copolymer solution; adding the aqueous solution ② into the copolymer solution of the first stage, uniformly mixing, controlling the temperature to be 60 ℃ under the protection of N 2, carrying out free radical copolymerization reaction for 6 hours to obtain the copolymer solution of the second stage, and cooling to obtain the multifunctional hydrogel (A-1').
Comparative example 2
According to the operation method of the first step of the example 1, 85 g of deionized water, 3.5 g of methacrylic acid gelatin with the substitution degree of 0.3g, 10.5 g of methacrylic acid glyceride, 0.5g of dimethyl acrylic acid glyceride and 0.5g of ammonium persulfate are sequentially weighed and prepared into an aqueous solution, the temperature is controlled to be 60 ℃ under the protection of N 2, the one-pot free radical copolymerization reaction is carried out for 6 hours, and the hydrogel (A-1 ") is prepared after the temperature is reduced.
Example 2 preparation of multifunctional hydrogel (A-2)
According to the procedure of step one of example 1, the diallylaminopolyether methacrylate of the formula (B-1) was changed to 2- (N, N-diallylamino) ethyl methacrylate and benzyl chloride was changed to ω -methoxypolyethylene glycol-400 p-toluenesulfonate to obtain a multifunctional silane coupling agent of the formula (A-2) in a yield of 91.4%. The IR spectrum, 1 H-NMR, mass spectrum analysis and element analysis results (theoretical value%) of the multifunctional silane coupling agent of the formula (A-2) are C53.09 (55.50), H7.93 (8.80) and N1.64 (1.72), which show that the molecular formula C 114H213N3O44S2 Si of the multifunctional silane coupling agent of the formula (A-2) is basically consistent, so that the chemical structure of the multifunctional silane coupling agent product of the formula (A-2) is judged to be consistent with the theoretical design.
70 G of ethanol, 30 g of a multifunctional silane coupling agent of the formula (A-2) and 100 g of water are weighed, sequentially added into a reaction flask at room temperature, and uniformly stirred to prepare a multifunctional silane coupling agent solution. Then 30 g of calcium phosphorus silicon bioactive glass (purchased from Wohang's biological medicine technology Co., ltd.) with particle size less than or equal to 10 μm is put into the reactor, after ultrasonic treatment for 0.5 hour, the temperature is raised to 70-80 ℃ and stirred for 6 hours, the reaction process is ended, the temperature is reduced and filtered, the filter cake is washed three times by ethanol, and the constant weight is dried under vacuum with the temperature controlled between 50 and 55 ℃ to obtain the modified bioactive glass (A-2). By using IR spectrum analysis means, it was confirmed that the modified bioactive glass (A-2) had structural characteristics of carboxylate and ether bond.
80 G of deionized water, 3.5 g of methacrylic acid acylated gelatin with the substitution degree of 0.3, 10.5 g of methacrylic acid glyceride, 0.5 g of dimethyl acrylic acid glyceride, 5.0 g of modified bioactive glass (A-2) and 0.5 g of ammonium persulfate are sequentially weighed, mixed together to prepare an aqueous solution, and the aqueous solution is subjected to one-pot free radical copolymerization reaction for 12 hours under the protection of N 2, and cooled to obtain the multifunctional hydrogel (A-2).
Example 3 preparation of multifunctional hydrogel (A-3)
According to the operation method of the first step of example 1, 75 g of deionized water, 3.5 g of methacrylic acylated gelatin with the substitution degree of 0.3, 10.5 g of methacrylic glyceride, 0.5 g of dimethyl acrylic glyceride, 10.0 g of modified bioactive glass (A-2) and 0.5 g of ammonium persulfate are sequentially weighed, mixed together to prepare an aqueous solution, the temperature is controlled to be 60 ℃ under the protection of N 2, the one-pot free radical copolymerization reaction is carried out for 12 hours, and the multifunctional hydrogel (A-2') is prepared after the temperature is reduced.
EXAMPLE 4 preparation of multifunctional hydrogel (A-4)
According to the method and the operation steps of example 1, the calcium phosphorus silicon bioactive glass powder with the particle size less than or equal to 10 mu m produced by the Wuhank biomedical technology Co., ltd in the second step of example 1 is changed into the bioactive glass with the SiO 2 content of 45%, the CaO 2 content of 24.5%, the Na 2 O content of 24.5% and the P 2O5 content of 6.0% produced by Hebei excellent solid biotechnology Co., ltd, which is powder with the particle size less than or equal to 45 mu m, so as to prepare the surface modified bioactive glass (A-3). And adopting an infrared spectrum analysis means to judge that the surface modified bioactive glass (A-3) has the structural characteristics of carboxylate and ether bond.
80 G of deionized water, 3.5 g of methacrylic acid acylated gelatin with the substitution degree of 0.3 g, 10.5 g of methacrylic acid glyceride, 0.5 g of dimethyl acrylic acid glyceride, 0.5 g of ammonium persulfate and 5.0 g of surface modified bioactive glass (A-3) are sequentially weighed and prepared into an aqueous solution, the temperature is controlled to be 60 ℃ under the protection of N 2, the one-pot free radical copolymerization reaction is carried out for 20 hours, and the multifunctional hydrogel (A-4) is prepared after the temperature is reduced.
Example 5 preparation of multifunctional hydrogel (A-5)
According to the method and the operation procedure of example 1, 14 g of the multifunctional silane coupling agent of formula (A-1) in the second step was changed to 30 g of the multifunctional silane coupling agent of formula (A-1) to prepare a surface-modified bioactive glass (A-4); the procedure of example 1 was repeated except that 0.5 g of ammonium persulfate was changed to 1.0 g of potassium persulfate in the third step to obtain the multifunctional hydrogel (A-5).
Example 6 preparation of multifunctional hydrogel (A-6)
According to the method and the operation procedure of example 1, 79 g of deionized water, 5.0 g of methacryloylated gelatin with a substitution degree of 0.3, 10.5 g of glyceryl methacrylate, 0.5 g of glyceryl dimethacrylate, 1.5 g of phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate and 5.0 g of surface modified bioactive glass (A-1) were weighed in sequence, and formulated into an aqueous solution, and the aqueous solution was subjected to a "one-pot" type radical copolymerization reaction for 30 minutes under N 2 protection and irradiation with ultraviolet light with a wavelength of 365nm at normal temperature to obtain the multifunctional hydrogel (A-6).
Example 7 preparation of multifunctional hydrogel (A-7)
According to the method and the operation procedure of example 1, 70 g of deionized water, 3.5 g of sodium methylacrylamide with the substitution degree of 0.3, 10.5 g of glycerol methacrylate, 0.5 g of glycerol dimethacrylate, 5.0 g of modified bioactive glass (A-1) and 0.5 g of phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate were weighed in sequence, and prepared into an aqueous solution, and under the protection of N 2, the aqueous solution was irradiated with ultraviolet light with the wavelength of 365nm at normal temperature to carry out a one-pot free radical copolymerization reaction for 40 minutes, thus obtaining the multifunctional hydrogel (A-7).
Example 8 preparation of multifunctional hydrogel (A-8)
According to the method and the operation procedure of example 1, 80 g of deionized water, 3.5 g of sodium methylacrylamide with the substitution degree of 0.3, 6.5 g of glycidyl methacrylate, 5.0 g of N-vinyl pyrrolidone, 0.5 g of glycidyl dimethacrylate, 5.0 g of modified bioactive glass (A-4) and 1.5 g of phenyl (2, 4, 6-trimethyl benzoyl) lithium phosphate are sequentially weighed and prepared into an aqueous solution, and under the protection of N 2, ultraviolet irradiation with the wavelength of 365nm is used at normal temperature to carry out one-pot free radical copolymerization reaction for 40 minutes to obtain the multifunctional hydrogel (A-8).
Example 9 preparation of multifunctional hydrogel (A-9)
According to the method and the operation steps of example 1, 83 g of deionized water, 3.5 g of sodium methylacrylamide with the substitution degree of 0.3, 5.5 g of glycidyl methacrylate, 5.0 g of N-vinyl pyrrolidone, 2.5 g of unsaturated quaternary ammonium salt of formula (E-1), 0.5 g of potassium persulfate and 5.0 g of modified bioactive glass (A-4) are weighed in sequence, and are prepared into an aqueous solution, and under the protection of N 2, the temperature is controlled to 60 ℃, the 'one-pot' type free radical copolymerization reaction is carried out for 12 hours, and the multifunctional hydrogel (A-9) is prepared after the temperature is reduced.
Example 10 preparation of multifunctional hydrogel (A-10)
According to the method and the operation procedure of example 1, 81 g of deionized water, 3.5 g of sodium methylacrylamide with the substitution degree of 0.3, 10.5 g of hydroxyethyl methacrylate, 5.0 g of modified bioactive glass (A-4), 5.5 g of unsaturated quaternary ammonium salt of formula (E-1) and 0.5 g of phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate are sequentially weighed, and are prepared into an aqueous solution, and under the protection of N 2, ultraviolet irradiation with the wavelength of 365nm is used for carrying out one-pot free radical copolymerization reaction for 40 minutes at normal temperature to obtain the multifunctional hydrogel (A-10).
EXAMPLE 11 preparation of multifunctional hydrogel (A-11)
According to the method and the operation procedure of example 1, 75 g of deionized water, 3.5 g of sodium methylacrylamide with the substitution degree of 0.3, 8.5 g of hydroxyethyl methacrylate, 5.0g of modified bioactive glass (A-4), 7.5 g of unsaturated quaternary ammonium salt of formula (E-1) and 0.5 g of phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate are sequentially weighed, and are prepared into an aqueous solution, and under the protection of N 2, ultraviolet irradiation with the wavelength of 365nm is used for carrying out one-pot free radical copolymerization reaction for 40 minutes at normal temperature to obtain the multifunctional hydrogel (A-11).
Example 12 Properties of multifunctional hydrogels (A-1 to A-11)
The multifunctional hydrogels of examples a-1 to a-11 were respectively prepared into 50 x 10 x 2mm bars and 10mm diameter cylinders 5mm high, and the respective tensile strength and compressive strength were measured at room temperature using an electronic universal tester, and the specific results are shown in table 1.
TABLE 1 Properties of multifunctional hydrogels of examples A-1 to A-11
Claims (10)
1. The application of the modified bioactive glass in preparing the multifunctional hydrogel is realized through the following steps: according to the mass percentage of 2-20% of modified bioactive glass, 2-20% of unsaturated hydrophilic polymer, 2-20% of adjustable monomer, 0.1-1.5% of free radical initiator and 40-90% of deionized water, sequentially weighing deionized water, unsaturated hydrophilic polymer, adjustable monomer, modified bioactive glass and free radical initiator, mixing to prepare an aqueous solution, under the protection of N 2, controlling the temperature to 15-90 ℃, carrying out free radical copolymerization reaction of a one-pot formula for 0.4-40 hours, and obtaining the multifunctional hydrogel, wherein the modified bioactive glass is the bioactive glass subjected to surface modification by adopting a silane coupling agent containing a dipropenyl quaternary ammonium cation in a molecular structure;
Wherein the silane coupling agent containing the dipropenyl quaternary ammonium cation in the molecular structure has a structure shown in a general formula (A):
Wherein R in the general formula (A) is selected from C 1～C18 alkyl, R 1 is selected from H or methyl, n is selected from natural numbers between 1 and 200, and Y is selected from C 1～C18 alkyl or X - is selected from Cl -、Br-、I- or one of p-CH 3C6H4SO3 -; wherein R 2 is selected from C 1～C18 alkyl, m is selected from natural numbers between 0 and 200;
The bioactive glass is a silicon-based glass powder material formed by taking SiO 2-CaO-P2O5-Na2 O as a chemical component, or a silicon-based glass powder material doped with K +、Mg2+、Sr2+、Zn2+、Cu2+、B3+、Al3+、Ti4+ or Zr 4+ ions; according to the mass of each chemical component, the mass percent of SiO 2 is 40-80%, the mass percent of CaO is 10-60%, the mass percent of P 2O5 is 3-20%, the mass percent of Na 2 O is 10-60%, and the doping mass percent of K+、Mg2+、Sr2 +、Zn2+、Cu2+、B3+、Al3+、Ti4+ or Zr 4+ ions is selected according to the requirement.
2. The use of a modified bioactive glass for the preparation of a multifunctional hydrogel according to claim 1, characterized in that said unsaturated hydrophilic polymer is one or more of methacryloylated gelatin, methacryloylated chitosan, methacryloylated sodium alginate, methacryloylated hyaluronic acid or silk fibroin.
3. Use of a modified bioactive glass in the preparation of a multifunctional hydrogel according to claim 1, characterized in that the modifying monomers refer to: one or more of N-vinyl pyrrolidone, methacrylic acid, 2-hydroxyethyl methacrylate, N-methacrylamidoglycinamide, glycerol methacrylate, glycerol dimethacrylate, polyethylene glycol dimethacrylate or unsaturated quaternary ammonium salt with a structure shown in a general formula (E);
Wherein the unsaturated quaternary ammonium salt has a structure represented by the general formula (E):
Wherein R 1 in formula (E) is selected from H or methyl, R 3 is selected from C 1～C18 hydrocarbyl, Y is selected from C 1～C18 hydrocarbyl or X - is selected from one of Cl -、Br-, I-or p-CH 3C6H4SO3 -; wherein R 2 is selected from C 1～C18 alkyl, and m is selected from natural numbers between 0 and 200.
4. Use of a modified bioactive glass in the preparation of a multifunctional hydrogel according to claim 1, characterized in that the free radical initiator is selected from one or more of ammonium persulfate, sodium persulfate, potassium persulfate, azobisisobutylamidine hydrochloride, phenyl (2, 4, 6-trimethylbenzoyl) phosphate lithium, 4-isobutylphenyl-4' -methylphenyl iodohexafluorophosphate, 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone or 2-hydroxy-2-methyl-1-phenyl-1-propanone.
5. The use of a modified bioactive glass in the preparation of a multifunctional hydrogel according to claim 1, characterized in that the preparation method of the modified bioactive glass is as follows: sequentially weighing the silane coupling agent containing the dipropenyl quaternary ammonium cation, and mixing the methanol or the ethanol with the water according to the mass ratio of the silane coupling agent containing the dipropenyl quaternary ammonium cation to the methanol or the ethanol/the water of 5-50:5-50, preparing a silane coupling agent solution containing the dipropenyl quaternary ammonium cation at room temperature, stirring, adding bioactive glass, and heating to 50-90 ℃ for reacting for 2-20 hours; ending the reaction process, cooling the reaction system to room temperature, filtering, washing the filter cake for 1-3 times by using methanol or ethanol, sending the washed filter cake into a vacuum dryer, and vacuum drying to constant weight at the temperature of 25-65 ℃ to obtain the modified bioactive glass;
Wherein the molecular structure contains the dipropenyl quaternary ammonium cationic silane coupling agent in an amount which is 5-500% of the mass of the bioactive glass.
6. The application of the modified bioactive glass in preparing the multifunctional hydrogel according to claim 1, which is characterized in that the preparation method of the silane coupling agent containing the dipropenyl quaternary ammonium cations in the molecular structure is that diallylamine polyether acrylate is dissolved in a solvent, the temperature is controlled to be 5-35 ℃, under the protection of N 2, 3-aminopropyl silane coupling agent is slowly added by starting stirring, and the dosage of the diallylamine polyether acrylate is 2.0-2.2 times of the molar quantity of the 3-aminopropyl silane coupling agent; after the 3-aminopropyl silane coupling agent is fed, slowly raising the temperature of the reaction system to 35-90 ℃ for reaction for 2-20 hours, and ending the aza-Michael addition reaction process; adding an alkylating reagent into a reaction system, wherein the dosage of the alkylating reagent is 1.0-3.5 times of the molar quantity of the 3-aminopropyl silane coupling agent, keeping the temperature for continuous reaction for 2-20 hours, and ending the quaternization reaction process; and then removing part of the solvent by rotary evaporation, cooling to room temperature, separating out a crude product, and purifying the crude product to obtain the silane coupling agent containing the dipropenyl quaternary ammonium cation in the molecular structure shown in the general formula (A).
7. The use of a modified bioactive glass for the preparation of a multifunctional hydrogel according to claim 6, wherein said diallylamine polyether acrylate has the structure of formula (C):
wherein R 1 in the general formula (C) is selected from H or methyl, and n is selected from natural numbers between 1 and 200.
8. The use of a modified bioactive glass for the preparation of a multifunctional hydrogel according to claim 6, wherein said solvent is one or more of methanol, ethanol, propanol, tetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, dimethyl sulfoxide, N-methylpyrrolidone, N-dimethylformamide, N-diethylformamide, or hexamethylphosphoramide; the dosage of the solvent is 1 to 10 times of the mass of the 3-aminopropyl silane coupling agent.
9. The use of a modified bioactive glass for the preparation of a multifunctional hydrogel according to claim 6, wherein said 3-aminopropyl silane coupling agent has a structure of formula (B):
wherein R in formula (B) is selected from C 1～C18 hydrocarbyl groups.
10. Use of a modified bioactive glass in the preparation of a multifunctional hydrogel according to claim 6, characterized in that said alkylating agent has the structure of general formula (D):
Wherein Y in formula (D) is selected from C 1～C18 hydrocarbon groups or X is selected from Cl, br, I or one of p-CH 3C6H4SO3, wherein R 2 is selected from C 1～C18 alkyl, and m is selected from natural numbers between 0 and 200.
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| CN102886069A (en) * | 2012-09-24 | 2013-01-23 | 华南理工大学 | Method for preparing sol-gel bioglass-high polymer hybrid material |
| KR20210069391A (en) * | 2019-12-03 | 2021-06-11 | 한국산업기술대학교산학협력단 | Bio ink composition, preparing method for 3-dimension scafford and 3-dimension scafford thereby |
| CN117069389A (en) * | 2023-08-16 | 2023-11-17 | 江苏海洋大学 | Application of multifunctional silane coupling agent in surface modification of bioactive glass |
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| CN102886069A (en) * | 2012-09-24 | 2013-01-23 | 华南理工大学 | Method for preparing sol-gel bioglass-high polymer hybrid material |
| KR20210069391A (en) * | 2019-12-03 | 2021-06-11 | 한국산업기술대학교산학협력단 | Bio ink composition, preparing method for 3-dimension scafford and 3-dimension scafford thereby |
| CN117069389A (en) * | 2023-08-16 | 2023-11-17 | 江苏海洋大学 | Application of multifunctional silane coupling agent in surface modification of bioactive glass |
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| 王迎军;赵营刚;卢玲;陈晓峰;吴刚;任力;: "用硅烷偶联剂处理生物玻璃表面及其复合支架的制备", 硅酸盐学报, no. 07, 26 July 2006 (2006-07-26), pages 836 - 841 * |
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