JP5420565B2 - セルロース誘導体からの多孔性スキャフォールドの形成方法 - Google Patents
セルロース誘導体からの多孔性スキャフォールドの形成方法 Download PDFInfo
- Publication number
- JP5420565B2 JP5420565B2 JP2010539393A JP2010539393A JP5420565B2 JP 5420565 B2 JP5420565 B2 JP 5420565B2 JP 2010539393 A JP2010539393 A JP 2010539393A JP 2010539393 A JP2010539393 A JP 2010539393A JP 5420565 B2 JP5420565 B2 JP 5420565B2
- Authority
- JP
- Japan
- Prior art keywords
- scaffold
- polymer
- self
- partially substituted
- partially
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title claims description 53
- 229920002678 cellulose Polymers 0.000 title description 19
- 239000001913 cellulose Substances 0.000 title description 19
- 229920000642 polymer Polymers 0.000 claims description 104
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 72
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 72
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 72
- 239000011148 porous material Substances 0.000 claims description 59
- 239000000839 emulsion Substances 0.000 claims description 36
- 238000004132 cross linking Methods 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 239000012071 phase Substances 0.000 claims description 28
- 238000005191 phase separation Methods 0.000 claims description 22
- HXBPYFMVGFDZFT-UHFFFAOYSA-N allyl isocyanate Chemical group C=CCN=C=O HXBPYFMVGFDZFT-UHFFFAOYSA-N 0.000 claims description 21
- 238000006467 substitution reaction Methods 0.000 claims description 18
- 239000008346 aqueous phase Substances 0.000 claims description 12
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 11
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 11
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 11
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 claims description 11
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 8
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 8
- 230000001939 inductive effect Effects 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 239000000523 sample Substances 0.000 description 79
- 210000004027 cell Anatomy 0.000 description 62
- 125000001424 substituent group Chemical group 0.000 description 34
- 239000002243 precursor Substances 0.000 description 29
- 239000000243 solution Substances 0.000 description 28
- 238000009826 distribution Methods 0.000 description 18
- 239000000499 gel Substances 0.000 description 17
- 238000001878 scanning electron micrograph Methods 0.000 description 17
- 210000003494 hepatocyte Anatomy 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- 239000000017 hydrogel Substances 0.000 description 9
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 8
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 8
- 238000001000 micrograph Methods 0.000 description 7
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 210000002744 extracellular matrix Anatomy 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 5
- 229910052753 mercury Inorganic materials 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 230000001678 irradiating effect Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 210000004872 soft tissue Anatomy 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000000975 bioactive effect Effects 0.000 description 3
- 230000021164 cell adhesion Effects 0.000 description 3
- 230000012292 cell migration Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 239000000084 colloidal system Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 102000012422 Collagen Type I Human genes 0.000 description 2
- 108010022452 Collagen Type I Proteins 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 238000000944 Soxhlet extraction Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 238000001218 confocal laser scanning microscopy Methods 0.000 description 2
- 229920006037 cross link polymer Polymers 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000002073 fluorescence micrograph Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 238000004264 monolayer culture Methods 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- OCAAZRFBJBEVPS-UHFFFAOYSA-N prop-2-enyl carbamate Chemical class NC(=O)OCC=C OCAAZRFBJBEVPS-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000002834 transmittance Methods 0.000 description 2
- 210000003606 umbilical vein Anatomy 0.000 description 2
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 238000012604 3D cell culture Methods 0.000 description 1
- 208000007788 Acute Liver Failure Diseases 0.000 description 1
- 206010000804 Acute hepatic failure Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- ZYFVNVRFVHJEIU-UHFFFAOYSA-N PicoGreen Chemical compound CN(C)CCCN(CCCN(C)C)C1=CC(=CC2=[N+](C3=CC=CC=C3S2)C)C2=CC=CC=C2N1C1=CC=CC=C1 ZYFVNVRFVHJEIU-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- UKLDJPRMSDWDSL-UHFFFAOYSA-L [dibutyl(dodecanoyloxy)stannyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)O[Sn](CCCC)(CCCC)OC(=O)CCCCCCCCCCC UKLDJPRMSDWDSL-UHFFFAOYSA-L 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 231100000836 acute liver failure Toxicity 0.000 description 1
- 238000003349 alamar blue assay Methods 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960002246 beta-d-glucopyranose Drugs 0.000 description 1
- 230000002902 bimodal effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000003592 biomimetic effect Effects 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000008619 cell matrix interaction Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000011557 critical solution Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 239000012975 dibutyltin dilaurate Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000002952 image-based readout Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 238000002459 porosimetry Methods 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000001172 regenerating effect Effects 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
- 230000031070 response to heat Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000013077 target material Substances 0.000 description 1
- 230000008542 thermal sensitivity Effects 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 238000013334 tissue model Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- 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
- A61L27/56—Porous materials, e.g. foams or sponges
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B3/00—Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shape; Layered products comprising a layer having particular features of form
- B32B3/26—Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shape; Layered products comprising a layer having particular features of form characterised by a particular shape of the outline of the cross-section of a continuous layer; characterised by a layer with cavities or internal voids ; characterised by an apertured layer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B11/00—Preparation of cellulose ethers
- C08B11/20—Post-etherification treatments of chemical or physical type, e.g. mixed etherification in two steps, including purification
-
- 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
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
- C08L1/08—Cellulose derivatives
- C08L1/10—Esters of organic acids, i.e. acylates
- C08L1/14—Mixed esters, e.g. cellulose acetate-butyrate
-
- 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
- C08J2201/00—Foams characterised by the foaming process
- C08J2201/02—Foams characterised by the foaming process characterised by mechanical pre- or post-treatments
- C08J2201/024—Preparation or use of a blowing agent concentrate, i.e. masterbatch in a foamable composition
-
- 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
- C08J2201/00—Foams characterised by the foaming process
- C08J2201/02—Foams characterised by the foaming process characterised by mechanical pre- or post-treatments
- C08J2201/026—Crosslinking before of after foaming
-
- 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
- C08J2201/00—Foams characterised by the foaming process
- C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
- C08J2201/048—Elimination of a frozen liquid phase
- C08J2201/0484—Elimination of a frozen liquid phase the liquid phase being aqueous
-
- 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
- C08J2201/00—Foams characterised by the foaming process
- C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
- C08J2201/052—Inducing phase separation by thermal treatment, e.g. cooling a solution
- C08J2201/0524—Inducing phase separation by thermal treatment, e.g. cooling a solution the liquid phase being aqueous
-
- 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
- C08J2205/00—Foams characterised by their properties
- C08J2205/04—Foams characterised by their properties characterised by the foam pores
- C08J2205/044—Micropores, i.e. average diameter being between 0,1 micrometer and 0,1 millimeter
-
- 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
- C08J2207/00—Foams characterised by their intended use
- C08J2207/10—Medical applications, e.g. biocompatible scaffolds
-
- 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
- C08J2301/00—Characterised by the use of cellulose, modified cellulose or cellulose derivatives
- C08J2301/08—Cellulose derivatives
- C08J2301/26—Cellulose ethers
- C08J2301/28—Alkyl ethers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/249921—Web or sheet containing structurally defined element or component
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/249921—Web or sheet containing structurally defined element or component
- Y10T428/249953—Composite having voids in a component [e.g., porous, cellular, etc.]
- Y10T428/249978—Voids specified as micro
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/249921—Web or sheet containing structurally defined element or component
- Y10T428/249953—Composite having voids in a component [e.g., porous, cellular, etc.]
- Y10T428/249978—Voids specified as micro
- Y10T428/249979—Specified thickness of void-containing component [absolute or relative] or numerical cell dimension
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Dermatology (AREA)
- Animal Behavior & Ethology (AREA)
- Transplantation (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Dispersion Chemistry (AREA)
- Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
- Materials For Medical Uses (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
Description
本出願は、2007年12月18日に提出された米国特許仮出願第61/006,090号の恩典を主張し、その全内容が参照により本明細書に組み入れられる。
本発明は、多孔性スキャフォールド、およびそのようなスキャフォールドを形成する方法に関する。
マクロ多孔性スキャフォールドを形成するための技術には、塩浸出、気泡形成、エマルジョン凍結乾燥、繊維状織物の加工、三次元(3D)印刷、等、多くの異なる手法が存在する。大きな孔は、孔内の細胞の移動および成長を促進することが可能であり、十分な養分の到達および代謝物の除去を可能にするため、マクロ多孔性スキャフォールドは、細胞を支えるために有用である。ヒドロキシプロピルセルロース(HPC)を異なる温度で架橋した場合、非多孔性および微小多孔性HPCヒドロゲルの両方を形成できることが報告されている。報告されている微小多孔性HPCヒドロゲルの平均孔径は10マイクロメートル未満である。一般的に、微小孔は、平均孔径が2〜50マイクロメートルの範囲内の孔を指し、マクロ孔は、平均孔径が50マイクロメートルよりも大きい孔を指す。
[本発明1001]
マクロ孔を画定しかつ置換基で部分的に置換されたヒドロキシプロピルセルロースを含むポリマーを含むスキャフォールドであって、
該置換基が自己架橋可能な基を含み、該部分的に置換されたヒドロキシプロピルセルロースが該自己架橋可能な基を介して架橋され、該マクロ孔の平均孔径が50マイクロメートルより大きくかつ少なくとも部分的に相互連結されている、スキャフォールド。
[本発明1002]
前記ポリマーが約50%またはそれ以上の相互連結多孔度を有する、本発明1001のスキャフォールド。
[本発明1003]
前記ポリマーが約80%またはそれ以上の全多孔度を有する、本発明1001または本発明1002のスキャフォールド。
[本発明1004]
前記マクロ孔が、50マイクロメートルよりも大きい値でピークに達する孔径分布を有する、本発明1001〜1003のいずれかのスキャフォールド。
[本発明1005]
前記マクロ孔が、約90マイクロメートルでピークに達する孔径分布を有する、本発明1001〜1003のいずれかのスキャフォールド。
[本発明1006]
前記マクロ孔が、約100マイクロメートルでピークに達する孔径分布を有する、本発明1001〜1003のいずれかのスキャフォールド。
[本発明1007]
前記ポリマーが約85%の平衡含水量を有する、本発明1001〜1006のいずれかのスキャフォールド。
[本発明1008]
前記ポリマーが、水和状態において約10〜約20kPaのヤング率を有する、本発明1001〜1007のいずれかのスキャフォールド。
[本発明1009]
前記自己架橋可能な基が炭素-炭素不飽和二重結合を含む、本発明1001〜1008のいずれかのスキャフォールド。
[本発明1010]
前記置換基がアリルイソシアネートを含む、本発明1001〜1009のいずれかのスキャフォールド。
[本発明1011]
前記置換基が、メタクリル酸、アクリル酸、またはグリシジルメタクリレートを含む、本発明1001〜1009のいずれかのスキャフォールド。
[本発明1012]
前記部分的に置換されたヒドロキシプロピルセルロースが約2.5未満の置換度を有する、本発明1001〜1011のいずれかのスキャフォールド。
[本発明1013]
前記部分的に置換されたヒドロキシプロピルセルロースが約2.1の置換度を有する、本発明1001〜1011のいずれかのスキャフォールド。
[本発明1014]
前記ポリマーがゲルである、本発明1001〜1013のいずれかのスキャフォールド。
[本発明1015]
以下の工程を含む、スキャフォールドを形成する方法:
連続ポリマー相が、置換基で部分的に置換されたヒドロキシプロピルセルロースを含み、該置換基が自己架橋可能な基を含む、連続水相および該連続ポリマー相を含む両連続(bicontinuous)エマルジョンを形成する工程;
少なくとも部分的に相互連結した孔を画定するポリマーを形成するために、該部分的に置換されたヒドロキシプロピルセルロースを該自己架橋可能な基を介して架橋する工程。
[本発明1016]
前記置換基がアリルイソシアネートを含む、本発明1015の方法。
[本発明1017]
前記置換基がメタクリル酸、アクリル酸、またはグリシジルメタクリレートを含む、本発明1015の方法。
[本発明1018]
前記孔がマクロ孔を含む、本発明1015〜1017のいずれかの方法。
[本発明1019]
前記架橋する工程が、前記エマルジョンにγ線を照射する工程を含む、本発明1015〜1018のいずれかの方法。
[本発明1020]
前記架橋する工程が、少なくとも約90重量%の前記部分的に置換されたヒドロキシプロピルセルロースを前記エマルジョン中で架橋する工程を含む、本発明1015〜1019のいずれかの方法。
[本発明1021]
前記ポリマーを凍結乾燥することにより前記孔から水を除去する工程を含む、本発明1015〜1020のいずれかの方法。
[本発明1022]
前記凍結乾燥後、前記ポリマーが約50%またはそれ以上の相互連結多孔度を有し、かつ前記孔が50マイクロメートルよりも大きい平均孔径を有する、本発明1021の方法。
[本発明1023]
前記エマルジョンが、約80〜約90重量%の前記水相および約10〜約20重量%の前記ポリマー相を含む、本発明1015〜1022のいずれかの方法。
[本発明1024]
前記部分的に置換されたヒドロキシプロピルセルロースが、約2.5またはそれ未満の置換度を有する、本発明1015〜1023のいずれかの方法。
[本発明1025]
前記部分的に置換されたヒドロキシプロピルセルロースが、約2.1の置換度を有する、本発明1015〜1024のいずれかの方法。
[本発明1026]
前記ポリマーがゲルである、本発明1015〜1025のいずれかの方法。
[本発明1027]
前記エマルジョンが、水と前記部分的に置換されたヒドロキシプロピルセルロースとを含む溶液を熱処理に供することにより形成される、本発明1015〜1026のいずれかの方法。
[本発明1028]
前記熱処理が、約313Kの温度における約5分間の熱処理を含む、本発明1015〜1027のいずれかの方法。
[本発明1029]
以下の工程を含む、スキャフォールドを形成する方法:
連続ポリマー相および連続水相を含む両連続エマルジョンを形成するために、自己架橋可能な基を含むポリマー前駆体と水とを含む溶液中で相分離を誘導する工程;
少なくとも部分的に相互連結したマクロ孔を画定するポリマーを形成するために、該ポリマー前駆体を該エマルジョン中の該自己架橋可能な基を介して架橋する工程。
[本発明1030]
前記ポリマー前駆体がセルロース誘導体である、本発明1029の方法。
[本発明1031]
前記セルロース誘導体がメチルセルロース誘導体である、本発明1030の方法。
[本発明1032]
前記セルロース誘導体がヒドロキシプロピルセルロース誘導体である、本発明1030の方法。
[本発明1033]
前記ヒドロキシプロピルセルロース誘導体が、アリルイソシアネートにより部分的に置換されたヒドロキシプロピルセルロースである、本発明1032の方法。
[本発明1034]
前記セルロース誘導体が、自己連結可能な基を含む置換基により部分的に置換されている、本発明1030〜1032のいずれかの方法。
[本発明1035]
前記自己架橋可能な基が炭素-炭素不飽和二重結合を含む、本発明1034の方法。
[本発明1036]
前記置換基が、アリルイソシアネート、メタクリル酸、アクリル酸、またはグリシジルメタクリレートを含む、本発明1034の方法。
[本発明1037]
前記ポリマー前駆体が感熱性であり、かつ前記相分離を誘導する工程が前記溶液を加熱する工程を含む、本発明1029〜1036のいずれかの方法。
[本発明1038]
前記ポリマー前駆体がpH感受性であり、かつ前記相分離を誘導する工程が前記溶液のpHを変化させる工程を含む、本発明1029の方法。
[本発明1039]
前記架橋する工程が、前記エマルジョンにγ線を照射する工程を含む、本発明1029〜1038のいずれかの方法。
[本発明1040]
前記ポリマーがゲルである、本発明1029〜1039のいずれかの方法。
本発明の例示的な態様は、アリルイソシアネートにより部分的に置換された架橋ヒドロキシプロピルセルロース(H-A)により形成されたスキャフォールドに関する。スキャフォールドとは、細胞または組織等の何か他の物を支えるための支持骨格を提供するために利用できる、任意の多孔性材料または構造である。H-Aポリマーの孔は、平均孔径が50マイクロメートルよりも大きいマクロ孔である。H-Aポリマーは、水和された際にゲルを形成しうる。
HPC(Mn約10,000;1H NMR測定によると、エーテル化度は約3.4)は、トルエン中で共沸蒸留することにより脱水した。
H-Aの試料溶液および水を用意した。溶液はそれぞれ約10重量%または約20重量%のH-Aを含有した。水は、脱気および脱イオン化してからH-Aと混合した。
比較の目的で、実施例2と同様に調製したH-A溶液も、約273〜約277Kの温度において、相分離無しに、実施例2に記載のとおり照射することにより架橋した。結果として得られた生成物は、均一なゲルであり、実施例2に記載のものと同様の照射後処理に供した。これらのゲルを試料IC(10重量%H-A)および試料IIC(20重量%H-A)と呼んだ。
資料中の架橋度は、スキャフォールドの架橋された分画の重量パーセントとして表した。
細胞培養のために、試料IおよびIIを直径約10mm、厚み約2mmのディスクに切り抜いた。
Claims (9)
- 以下の工程を含む、スキャフォールドを形成する方法:
連続ポリマー相および連続水相を含む両連続(bicontinuous)エマルジョンを形成するために、部分的に置換されたヒドロキシプロピルセルロースと水とを含む溶液中で相分離を誘導する工程であって、該部分的に置換されたヒドロキシプロピルセルロースは自己架橋可能な基を含み、該自己架橋可能な基は炭素-炭素不飽和二重結合を含み、前記部分的に置換されたヒドロキシプロピルセルロースは、2.5またはそれ未満の置換度を有し、前記エマルジョンは、10〜20重量%の前記ポリマー相を含む、工程;および
少なくとも部分的に相互連結したマクロ孔を画定するポリマーを形成するために、前記部分的に置換されたヒドロキシプロピルセルロースを前記エマルジョン中で前記自己架橋可能な基を介して架橋する工程。 - 前記部分的に置換されたヒドロキシプロピルセルロースが、アリルイソシアネートにより部分的に置換されている、請求項1記載の方法。
- 前記部分的に置換されたヒドロキシプロピルセルロースが、前記自己連結可能な基を含む置換基により部分的に置換されている、請求項1記載の方法。
- 前記置換度が2.1である、請求項2記載の方法。
- 前記部分的に置換されたヒドロキシプロピルセルロースが、メタクリル酸、アクリル酸、またはグリシジルメタクリレートにより部分的に置換されている、請求項1記載の方法。
- マクロ孔を画定しかつ置換基で部分的に置換されたヒドロキシプロピルセルロースを含むポリマーを含むスキャフォールドであって、
前記置換基が自己架橋可能な基を含み、該自己架橋可能な基は炭素-炭素不飽和二重結合を含み、前記部分的に置換されたヒドロキシプロピルセルロースは、2.5またはそれ未満の置換度を有し、前記部分的に置換されたヒドロキシプロピルセルロースが該自己架橋可能な基を介して架橋され、前記マクロ孔の平均孔径が50マイクロメートルより大きくかつ該マクロ孔が少なくとも部分的に相互連結されている、スキャフォールド。 - 前記置換度が2.1である、請求項6記載のスキャフォールド。
- 以下の工程を含む、スキャフォールドを形成する方法:
連続水相および連続ポリマー相を含む両連続エマルジョンを形成する工程であって、該連続ポリマー相が、置換基で部分的に置換されたヒドロキシプロピルセルロースを含み、該置換基が自己架橋可能な基を含み、該自己架橋可能な基は炭素-炭素不飽和二重結合を含み、前記部分的に置換されたヒドロキシプロピルセルロースは、2.5またはそれ未満の置換度を有し、前記エマルジョンは、10〜20重量%の前記ポリマー相を含む、工程;および
少なくとも部分的に相互連結した孔を画定するポリマーを形成するために、前記部分的に置換されたヒドロキシプロピルセルロースを前記自己架橋可能な基を介して架橋する工程。 - 前記置換基がアリルイソシアネートを含む、請求項8記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US609007P | 2007-12-18 | 2007-12-18 | |
US61/006,090 | 2007-12-18 | ||
PCT/SG2008/000491 WO2009078819A1 (en) | 2007-12-18 | 2008-12-18 | Forming porous scaffold from cellulose derivatives |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2011505871A JP2011505871A (ja) | 2011-03-03 |
JP2011505871A5 JP2011505871A5 (ja) | 2012-02-02 |
JP5420565B2 true JP5420565B2 (ja) | 2014-02-19 |
Family
ID=40795781
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010539393A Active JP5420565B2 (ja) | 2007-12-18 | 2008-12-18 | セルロース誘導体からの多孔性スキャフォールドの形成方法 |
Country Status (4)
Country | Link |
---|---|
US (3) | US20110201117A1 (ja) |
EP (1) | EP2234655B1 (ja) |
JP (1) | JP5420565B2 (ja) |
WO (1) | WO2009078819A1 (ja) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130142763A1 (en) * | 2010-10-27 | 2013-06-06 | Empire Technology Development Llc | Crosslinked cellulosic polymers |
US11284676B2 (en) | 2012-06-13 | 2022-03-29 | John C. S. Koo | Shoe having a partially coated upper |
MX2015001760A (es) | 2012-08-08 | 2015-06-03 | Smith & Nephew | Aparatos hechos a la medida para el tratamiento de heridas y metodos para su uso en la terapia de heridas con presion negativa. |
US9182420B2 (en) * | 2013-03-15 | 2015-11-10 | Palo Alto Research Center Incorporated | Phase-change enabled flow field visualization |
WO2015017421A2 (en) * | 2013-07-29 | 2015-02-05 | Carnegie Mellon University | Additive manufacturing of embedded materials |
US10179073B2 (en) | 2014-01-21 | 2019-01-15 | Smith & Nephew Plc | Wound treatment apparatuses |
EP3023455A1 (en) | 2014-11-21 | 2016-05-25 | Fundacíon Tecnalia Research & Innovation | Porous cellulosic materials and process for their preparation |
US11220597B2 (en) | 2015-06-01 | 2022-01-11 | The Trustees Of The University Of Pennsylvania | Bijels and methods of making the same |
MX2016013830A (es) * | 2015-10-27 | 2017-05-10 | Shinetsu Chemical Co | Eter de celulosa porosa no ionico soluble en agua que tiene excelente solubilidad y metodo para producir el mismo. |
CN108102129B (zh) * | 2016-11-25 | 2021-01-01 | 山西加乐医疗科技有限责任公司 | 一种纤维素海绵的制备方法 |
US10928383B2 (en) * | 2017-06-03 | 2021-02-23 | Shanxi Pishon Biomedical Technology Co., Ltd | Method for predicting effect of drug |
IT201700087978A1 (it) | 2017-07-31 | 2019-01-31 | Univ Degli Studi Genova | Scaffold di idrogel tridimensionale per colture cellulari e metodo per la sua produzione |
CN110433784A (zh) * | 2019-08-15 | 2019-11-12 | 毛艳艳 | 一种工厂污水用环保处理功能材料的制备方法 |
US11786879B2 (en) | 2019-11-11 | 2023-10-17 | The Trustees Of The University Of Pennsylvania | Three dimensional multiphasic structures via vaporization induced phase separation (VIPS) |
CN111840653B (zh) * | 2020-05-27 | 2021-07-20 | 华南理工大学 | 能包埋亲水性功能因子的甘草酸基缓释多孔泡沫材料及其制备方法与应用 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4964989A (en) * | 1986-12-23 | 1990-10-23 | Pall Corporation | Membranes with low protein adsorbability |
JP2802103B2 (ja) * | 1989-07-03 | 1998-09-24 | アラコ株式会社 | 板状装飾部材の製造方法 |
GB9006726D0 (en) * | 1990-03-26 | 1990-05-23 | Ici Plc | Micro-emulsions |
US5573994A (en) * | 1994-05-13 | 1996-11-12 | University Of Cincinnati | Superabsorbent foams, and method for producing the same |
WO2000078553A1 (en) * | 1999-06-22 | 2000-12-28 | Avecia Limited | Ink receptive substrates |
WO2002074158A2 (en) | 2001-03-20 | 2002-09-26 | Eidgenossische Technische Hochschule Zurich | Two-phase processing of thermosensitive polymers for use as biomaterials |
US20030138490A1 (en) * | 2001-09-08 | 2003-07-24 | Zhibing Hu | Synthesis and uses of polymer gel nanoparticle networks |
-
2008
- 2008-12-18 US US12/809,534 patent/US20110201117A1/en not_active Abandoned
- 2008-12-18 JP JP2010539393A patent/JP5420565B2/ja active Active
- 2008-12-18 WO PCT/SG2008/000491 patent/WO2009078819A1/en active Application Filing
- 2008-12-18 EP EP08863269.0A patent/EP2234655B1/en active Active
-
2010
- 2010-06-25 US US12/824,105 patent/US8283028B2/en active Active
-
2012
- 2012-09-12 US US13/611,339 patent/US8993537B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
EP2234655B1 (en) | 2018-12-12 |
JP2011505871A (ja) | 2011-03-03 |
EP2234655A1 (en) | 2010-10-06 |
EP2234655A4 (en) | 2013-10-16 |
US8283028B2 (en) | 2012-10-09 |
US20110159272A1 (en) | 2011-06-30 |
US8993537B2 (en) | 2015-03-31 |
US20130005945A1 (en) | 2013-01-03 |
US20110201117A1 (en) | 2011-08-18 |
WO2009078819A1 (en) | 2009-06-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5420565B2 (ja) | セルロース誘導体からの多孔性スキャフォールドの形成方法 | |
Badhe et al. | A composite chitosan-gelatin bi-layered, biomimetic macroporous scaffold for blood vessel tissue engineering | |
Rizwan et al. | Sequentially-crosslinked bioactive hydrogels as nano-patterned substrates with customizable stiffness and degradation for corneal tissue engineering applications | |
US11511016B2 (en) | Method for preparing porous scaffold for tissue engineering, cell culture and cell delivery | |
JP6757329B2 (ja) | 自己組み込み型ヒドロゲル及びその製造方法 | |
CN106795225B (zh) | 用于抗纤维化材料的修饰的藻酸盐以及应用 | |
Reverchon et al. | Supercritical fluids in 3-D tissue engineering | |
Salerno et al. | Bio-safe fabrication of PLA scaffolds for bone tissue engineering by combining phase separation, porogen leaching and scCO2 drying | |
Lv et al. | Three-dimensional fibroin/collagen scaffolds derived from aqueous solution and the use for HepG2 culture | |
Yue et al. | Preparation of three-dimensional interconnected macroporous cellulosic hydrogels for soft tissue engineering | |
Fiorica et al. | Hyaluronic acid and beta cyclodextrins films for the release of corneal epithelial cells and dexamethasone | |
US20080131473A1 (en) | Cell-Independent Fabrication of Tissue Equivalents | |
Zhang et al. | A highly transparent, elastic, injectable sericin hydrogel induced by ultrasound | |
Zhao et al. | Chitosan/silk fibroin biomimic scaffolds reinforced by cellulose acetate nanofibers for smooth muscle tissue engineering | |
Zhang et al. | Photopolymerizable chitosan hydrogels with improved strength and 3D printability | |
Pan et al. | One-step cross-linked injectable hydrogels with tunable properties for space-filling scaffolds in tissue engineering | |
Van Vlierberghe et al. | Toward modulating the architecture of hydrogel scaffolds: curtains versus channels | |
Dai et al. | Improved thermostability and cytocompatibility of bacterial cellulose/collagen composite by collagen fibrillogenesis | |
Shi et al. | Activated carbon fibers/poly (lactic-co-glycolic) acid composite scaffolds: preparation and characterizations | |
Zhang et al. | Hybridization of a phospholipid polymer hydrogel with a natural extracellular matrix using active cell immobilization | |
Kafili et al. | Development of bioinspired nanocomposite bioinks based on decellularized amniotic membrane and hydroxyethyl cellulose for skin tissue engineering | |
KR102098134B1 (ko) | 나노 섬유질 콜라겐 3차원 구조체 제조방법 | |
van der Vlies et al. | Dextran acetate-based sponge as cell scaffold for tissue engineering | |
RU2774947C1 (ru) | Биополимерный материал для клеточно-инженерных и/или тканеинженерных конструкций и способ его получения | |
Li | Engineering 3D Collagen Tunable Platforms for Mechanobiology Studies |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111206 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20111206 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130708 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131004 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20131028 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20131120 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5420565 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |