CN107625995A - Multilayer coaxial fiber bone repair membrane material and preparation method thereof - Google Patents
Multilayer coaxial fiber bone repair membrane material and preparation method thereof Download PDFInfo
- Publication number
- CN107625995A CN107625995A CN201710710641.XA CN201710710641A CN107625995A CN 107625995 A CN107625995 A CN 107625995A CN 201710710641 A CN201710710641 A CN 201710710641A CN 107625995 A CN107625995 A CN 107625995A
- Authority
- CN
- China
- Prior art keywords
- solution
- degradable
- room temperature
- magnetic agitation
- added
- 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
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 68
- 239000000835 fiber Substances 0.000 title claims abstract description 61
- 239000000463 material Substances 0.000 title claims abstract description 53
- 239000012528 membrane Substances 0.000 title claims description 18
- 230000008439 repair process Effects 0.000 title abstract description 11
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 229920003232 aliphatic polyester Polymers 0.000 claims abstract description 53
- 238000010041 electrostatic spinning Methods 0.000 claims abstract description 40
- 239000003814 drug Substances 0.000 claims abstract description 35
- 229920002521 macromolecule Polymers 0.000 claims abstract description 28
- 229940079593 drug Drugs 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 13
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 11
- 239000000126 substance Substances 0.000 claims abstract description 8
- 229940124599 anti-inflammatory drug Drugs 0.000 claims abstract description 7
- 238000013019 agitation Methods 0.000 claims description 182
- 238000009987 spinning Methods 0.000 claims description 73
- 229920001661 Chitosan Polymers 0.000 claims description 72
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 71
- 239000002904 solvent Substances 0.000 claims description 65
- 229920001610 polycaprolactone Polymers 0.000 claims description 62
- 239000004632 polycaprolactone Substances 0.000 claims description 62
- 230000007547 defect Effects 0.000 claims description 44
- 102000012422 Collagen Type I Human genes 0.000 claims description 43
- 108010022452 Collagen Type I Proteins 0.000 claims description 43
- 239000011159 matrix material Substances 0.000 claims description 43
- 229920001577 copolymer Polymers 0.000 claims description 41
- 108010022355 Fibroins Proteins 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 21
- 239000007788 liquid Substances 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 19
- 230000005611 electricity Effects 0.000 claims description 18
- 239000003517 fume Substances 0.000 claims description 18
- 229910001220 stainless steel Inorganic materials 0.000 claims description 18
- 239000010935 stainless steel Substances 0.000 claims description 18
- 230000001954 sterilising effect Effects 0.000 claims description 18
- 238000004659 sterilization and disinfection Methods 0.000 claims description 18
- 239000011521 glass Substances 0.000 claims description 16
- 230000000694 effects Effects 0.000 claims description 15
- 239000003102 growth factor Substances 0.000 claims description 10
- 239000010456 wollastonite Substances 0.000 claims description 9
- 229910052882 wollastonite Inorganic materials 0.000 claims description 9
- 125000001931 aliphatic group Chemical group 0.000 claims description 8
- 229940088710 antibiotic agent Drugs 0.000 claims description 8
- 210000004204 blood vessel Anatomy 0.000 claims description 8
- 239000005445 natural material Substances 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 claims description 7
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 claims description 7
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims description 7
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims description 7
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 7
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- TZJALUIVHRYQQB-XFDQAQKOSA-N Icariin Natural products O(C)c1ccc(C2=C(O[C@H]3[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O3)C(=O)c3c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O4)c(C/C=C(\C)/C)c3O2)cc1 TZJALUIVHRYQQB-XFDQAQKOSA-N 0.000 claims description 6
- 102100031372 Thymidine phosphorylase Human genes 0.000 claims description 6
- 229940126864 fibroblast growth factor Drugs 0.000 claims description 6
- 229910021389 graphene Inorganic materials 0.000 claims description 6
- TZJALUIVHRYQQB-XLRXWWTNSA-N icariin Chemical compound C1=CC(OC)=CC=C1C1=C(O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)C(=O)C2=C(O)C=C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-XLRXWWTNSA-N 0.000 claims description 6
- TZJALUIVHRYQQB-UHFFFAOYSA-N icariine Natural products C1=CC(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(C)O2)O)C(=O)C2=C(O)C=C(OC3C(C(O)C(O)C(CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-UHFFFAOYSA-N 0.000 claims description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 5
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 5
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 5
- 230000012010 growth Effects 0.000 claims description 5
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 5
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 5
- 229930182555 Penicillin Natural products 0.000 claims description 4
- 108700023160 Thymidine phosphorylases Proteins 0.000 claims description 4
- 230000002491 angiogenic effect Effects 0.000 claims description 4
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 4
- 239000001506 calcium phosphate Substances 0.000 claims description 4
- 108010083213 heparitinsulfate lyase Proteins 0.000 claims description 4
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 4
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 4
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 3
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 claims description 3
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 claims description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 3
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 3
- 239000003292 glue Substances 0.000 claims description 3
- 229960002009 naproxen Drugs 0.000 claims description 3
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 3
- HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 claims description 3
- OPFTUNCRGUEPRZ-QLFBSQMISA-N (-)-beta-elemene Chemical class CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 claims description 2
- 229930186147 Cephalosporin Chemical class 0.000 claims description 2
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 claims description 2
- 101710132082 Pyrimidine/purine nucleoside phosphorylase Proteins 0.000 claims description 2
- 239000004098 Tetracycline Substances 0.000 claims description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 2
- 229960000590 celecoxib Drugs 0.000 claims description 2
- 229940124587 cephalosporin Drugs 0.000 claims description 2
- 150000001780 cephalosporins Chemical class 0.000 claims description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 claims description 2
- 229940097572 chloromycetin Drugs 0.000 claims description 2
- 229960001259 diclofenac Drugs 0.000 claims description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 2
- 239000004744 fabric Substances 0.000 claims description 2
- 229940124307 fluoroquinolone Drugs 0.000 claims description 2
- -1 fluoroquinolones Chemical class 0.000 claims description 2
- 229960005287 lincomycin Drugs 0.000 claims description 2
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 claims description 2
- 230000000921 morphogenic effect Effects 0.000 claims description 2
- 150000002960 penicillins Chemical class 0.000 claims description 2
- 229920001184 polypeptide Polymers 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 235000019364 tetracycline Nutrition 0.000 claims description 2
- 150000003522 tetracyclines Chemical class 0.000 claims description 2
- 229940040944 tetracyclines Drugs 0.000 claims description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims 2
- LLYXJBROWQDVMI-UHFFFAOYSA-N 2-chloro-4-nitrotoluene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1Cl LLYXJBROWQDVMI-UHFFFAOYSA-N 0.000 claims 1
- 102100022987 Angiogenin Human genes 0.000 claims 1
- 101100277650 Arabidopsis thaliana DFO gene Proteins 0.000 claims 1
- 101150071146 COX2 gene Proteins 0.000 claims 1
- 101100114534 Caenorhabditis elegans ctc-2 gene Proteins 0.000 claims 1
- 101150000187 PTGS2 gene Proteins 0.000 claims 1
- 108010072788 angiogenin Proteins 0.000 claims 1
- 230000003115 biocidal effect Effects 0.000 claims 1
- 229960001680 ibuprofen Drugs 0.000 claims 1
- 229960000905 indomethacin Drugs 0.000 claims 1
- 230000002608 insulinlike Effects 0.000 claims 1
- 239000003120 macrolide antibiotic agent Substances 0.000 claims 1
- 229940041033 macrolides Drugs 0.000 claims 1
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 8
- 239000012620 biological material Substances 0.000 abstract description 6
- 229940124350 antibacterial drug Drugs 0.000 abstract 1
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 230000007774 longterm Effects 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 516
- 239000004626 polylactic acid Substances 0.000 description 71
- 108010010803 Gelatin Proteins 0.000 description 31
- 239000008273 gelatin Substances 0.000 description 31
- 229920000159 gelatin Polymers 0.000 description 31
- 235000019322 gelatine Nutrition 0.000 description 31
- 235000011852 gelatine desserts Nutrition 0.000 description 31
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 28
- 208000034530 PLAA-associated neurodevelopmental disease Diseases 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- 238000003756 stirring Methods 0.000 description 14
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 10
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 9
- 229960000958 deferoxamine Drugs 0.000 description 9
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 8
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 8
- 229920001432 poly(L-lactide) Polymers 0.000 description 8
- 229920000954 Polyglycolide Polymers 0.000 description 7
- 239000002121 nanofiber Substances 0.000 description 7
- 239000004633 polyglycolic acid Substances 0.000 description 7
- 210000000481 breast Anatomy 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- YSMRWXYRXBRSND-UHFFFAOYSA-N TOTP Chemical compound CC1=CC=CC=C1OP(=O)(OC=1C(=CC=CC=1)C)OC1=CC=CC=C1C YSMRWXYRXBRSND-UHFFFAOYSA-N 0.000 description 4
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 3
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 3
- 102000004264 Osteopontin Human genes 0.000 description 3
- 108010081689 Osteopontin Proteins 0.000 description 3
- 229940112869 bone morphogenetic protein Drugs 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 239000004310 lactic acid Substances 0.000 description 3
- 235000014655 lactic acid Nutrition 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 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
- 208000005214 Poroma Diseases 0.000 description 2
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002041 carbon nanotube Substances 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 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 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 238000005553 drilling Methods 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 201000001013 eccrine acrospiroma Diseases 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 150000002596 lactones Chemical class 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000004575 stone Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 208000010392 Bone Fractures Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241001016310 Epimedium grandiflorum Species 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- AGJUUQSLGVCRQA-SWOUQTJZSA-N Fungichromin Chemical compound CCCCC[C@@H](O)[C@@H]1[C@@H](O)C[C@@H](O)C[C@@H](O)C[C@@H](O)C[C@@H](O)C[C@@H](O)[C@@H](O)[C@H](O)\C(C)=C\C=C\C=C\C=C\C=C\[C@H](O)[C@@H](C)OC1=O AGJUUQSLGVCRQA-SWOUQTJZSA-N 0.000 description 1
- 108010022901 Heparin Lyase Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- AGJUUQSLGVCRQA-UHFFFAOYSA-N Pentamycin Natural products CCCCCC(O)C1C(O)CC(O)CC(O)CC(O)CC(O)CC(O)C(O)C(O)C(C)=CC=CC=CC=CC=CC(O)C(C)OC1=O AGJUUQSLGVCRQA-UHFFFAOYSA-N 0.000 description 1
- 208000006735 Periostitis Diseases 0.000 description 1
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 229910052586 apatite Inorganic materials 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- OKBVVJOGVLARMR-QSWIMTSFSA-N cefixime Chemical compound S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QSWIMTSFSA-N 0.000 description 1
- 229960002129 cefixime Drugs 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000011258 core-shell material Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001523 electrospinning Methods 0.000 description 1
- 239000004862 elemi Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000018905 epimedium Nutrition 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 229960003702 moxifloxacin Drugs 0.000 description 1
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 230000004072 osteoblast differentiation Effects 0.000 description 1
- 230000000278 osteoconductive effect Effects 0.000 description 1
- 230000002642 osteogeneic effect Effects 0.000 description 1
- 230000002138 osteoinductive effect Effects 0.000 description 1
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 1
- 229960000339 pentamycin Drugs 0.000 description 1
- 210000003460 periosteum Anatomy 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000002320 radius Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 210000000623 ulna Anatomy 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
Abstract
The invention relates to a multilayer coaxial fibrous bone repair material and a preparation method thereof, belonging to the field of biological materials. The material is prepared by taking biodegradable aliphatic polyester with biocompatibility and natural macromolecules as main raw materials and using four layers of coaxial needles through an electrostatic spinning method. The fiber has a multilayer coaxial structure, and antibacterial and anti-inflammatory drugs and bone-promoting drugs can be added in different layers according to the bone repair process. The material of the invention has excellent biocompatibility and controllable and long-term drug release performance. Meanwhile, along with the progress of the bone repair process, the medicine carried in the fiber is released layer by layer, and corresponding substances required by the process are provided for different stages of the bone repair. The material can realize controllable in vivo degradation according to requirements without taking out the material by a secondary operation.
Description
Technical field
The present invention relates to a kind of preparation method of the coaxial fiber Bone Defect Repari membrane material of multilayer, belong to technical field of biological material, have
Body is related to what a kind of be made up of the fiber with four layers of coaxial configuration, drug release process was adapted with Bone Defect Repari each stage
Bone Defect Repari membrane material and preparation method thereof.
Background technology
Cranial defect is clinically very common wound, and the repair process of bone is very very long, and it mainly includes hemotoncus
With inflammatory phase, initial poroma reaction phase, Subchondral drilling phase and bon e formation and reconstruction phase.Cell secretion is more during Bone Defect Repari
Kind growth factor is played a role with different sequential, ensures the reparation of Cranial defect.
Clinically, when Cranial defect occurs, best bet is to carry out bone collection, mainly including autologous bone transplanting, together
Kind of allogenic bone transplantation and non-tissue repairing's art etc., wherein to bone defect healing effect most preferably autologous bone transplanting.But from
Body bone is taken can excessively bring new wound and complication to patient；Homogeneous allogenic bone transplantation can overcome part autologous bone transplanting
The problem of bringing, but can be limited by organization factorses and immunogenicity etc. when donor source, transplanting；Non- tissue repairing's art
It is generally used for joint replacement surgery, subject matter is exactly can not be with the organizational integration of surrounding and then the focus of formation infection.For
Cranial defect or tissue defect, the problem of preferable solution is sought to overcome in terms of three above.Technical field of biological material is
Solve this problem and provide potential selection.
As a preferable bone renovating bracket material, it is necessary to requirement in terms of meeting following four：
(1) there is biocompatibility, osteoconductive, osteoinductive, support can be provided for normal cellular activity；
(2) biodegradable, can be that neoblastic grow into provides space and gradually substituted by new tissue；
(3) certain mechanical property, the stress during operative process and bone uptake can be born；
(4) link up loose structure, and nutriment and waste are transported for neoblastic generation.
Electrostatic spinning technique is a kind of simple general-purpose method for preparing nanofiber, because its medicine load mode is simply easy
OK, different medicines can be readily loaded into during electrostatic spinning in fiber, in addition, medicine is after being loaded into fiber
Performance change will not occur, remain to keep its performance, the generation that prevention of postoperative infects or promotes bone can be used for.Therefore, electrostatic
Nanofiber medicine carrying membrane prepared by spinning has good potential applicability in clinical practice.Simultaneously at Cranial defect a variety of growth factors lack or
It is that active deficiency is to influence the major reason of osteanagenesis, therefore, research one kind can provide living needed for it for Bone Defect Repari different phase
The biomaterial of sex factor is highly important.
The reparation of Cranial defect mainly includes the following four stage：Hemotoncus and inflammatory phase, initial poroma reaction phase, Subchondral drilling
Phase and bone remodeling phase, in above four-stage, the emphasis that each stage repairs is different, required growth factor and repairs material
Also it is different.Untill present patent application day, have not yet to see can be provide respectively in Bone Defect Repari each stage growth needed for it because
The medicine-carried system of son and nutriment.By the design of four layers of coaxial configuration, this material can adjust the matrix material of each layer of membrane material
For material composition so as to control fiber successively to degrade, realization successively discharges medicine, while passes through the choosing of drug type in different structure layer
Select and the control of content, so as to reach according to the characteristics of fracture healing process, needed for multiple, procedural release skeletonization different phase
Different pharmaceutical and growth factor purpose.After material is loaded into body, fiber outermost layer matrix is first begin to degrade, and releases simultaneously
Antibacterials are put, so as to suppress bacterial infection and the inflammation that hemotoncus and inflammatory phase occur；Then time outer layer matrix will start to release
Put into Angiogenesis, promote at defect into vascular process；Last secondary internal layer and innermost layer matrix then will once degrade and be bone
Whole provide is provided and facilitates bone material with synergy.The drug release process is adapted with the process of Bone Defect Repari.
And the relevant report on artificial periosteum mainly facilitates bone by addition one or more or facilitates the material of blood vessel before, but
Do not mention and discharge anti-infectives and skeletonization or the report into blood vessel inducible factor with the physiology course suitability of Bone Defect Repari.①
Kong Jie, Tu Mei, Zeng Rong, wait a kind of bone growth factor control release type bone renovating materials of and preparation method and application:,CN
102160900 A [P] .2011. 2. Zhou Xiaodong, Zhang Kai, Li little Heng, wait bone renovating materials and preparation method thereof:,CN
102488927 A[P].2012.③Li L,Zhou G,Wang Y,et al.Controlled dual delivery of
BMP-2 and dexamethasone by nanoparticle-embedded electrospun nanofibers for
the efficient repair of critical-sized rat calvarial defect[J].Biomaterials,
2015,37:218.④Lin W H,Yu J,Chen G,et al.Fabrication of multi-biofunctional
gelatin-based electrospun fibrous scaffolds for enhancement of osteogenesis
of mesenchymal stem cells.[J].Colloids&Surfaces B Biointerfaces,2016,138:26-
31.⑤Wang C,Wang M.Electrospun Multicomponent and Multifunctional Nanofibrous
Bone Tissue Engineering Scaffolds[J].Journal of Materials Chemistry B,2017.⑥
Shalumon K T,Lai G J,Chen C H,et al.Modulation of Bone-Specific Tissue
Regeneration by Incorporating Bone Morphogenetic Protein and Controlling the
Shell Thickness of Silk Fibroin/Chitosan/Nanohydroxyapatite Core-Shell
Nanofibrous Membranes[J].Acs Applied Materials&Interfaces,2015,7(38):21170.⑦
Yu D G,Li X Y,Wang X,et al.Nanofibers Fabricated Using Triaxial
Electrospinning as Zero Order Drug Delivery Systems[J].Acs Applied Materials&
Interfaces,2015,7(33).⑧Li L,Zhou G,Wang Y,et al.Controlled dual delivery of
BMP-2 and dexamethasone by nanoparticle-embedded electrospun nanofibers for
the efficient repair of critical-sized rat calvarial defect.[J].Biomaterials,
2015,37:218.⑨Shan D,Long L,Xian L,et al.A nano-micro alternating multilayer
scaffold loading with rBMSCs and BMP-2for bone tissue engineering[J]
.Colloids&Surfaces B Biointerfaces,2015,133:The main innovation of 286. the application is to pass through 4 layers of fiber
The design of structure is so as to the sequencing of Drug controlled release, by the selection of every layer of organism material species so as to control release speed
Degree, by every layer of medicament categories and content so as to reaching the different therapeutic efficiency of different phase.The design has no relevant report.
What is be related in this patent facilitates bone material to refer mainly to hydroxyapatite, graphene oxide, CNT, tricresyl phosphate
Calcium, icariin；Bio-vitric includes 45S5, apatite-wollastonite activity glass, machinable bioactivity glass；Growth
The factor such as bone morphogenetic protein (BMP), fibroblast growth factor (FGF), TGF (TGF- Β), blood platelet
Derivative growth factor (PDGF), vascular endothelial growth factor (VEGF) and IGF (IGF).
The content of the invention
It is an object of the invention to provide a kind of preparation method of the coaxial fiber Bone Defect Repari membrane material of multilayer, antibacterials are realized
With the targeted release for facilitating bone medicine, bone defect healing can be promoted, it is not necessary to second operation, may also suppress after defect occurs and easily send out
Raw bacterial infection and inflammation.
The coaxial fiber Bone Defect Repari membrane material of multilayer, it is characterized in that：
(1) outermost fibers matrix is used as matrix using degradable aliphatic polyester and the high molecular mixture of degradable natural
Material, wherein degradable aliphatic polyester and the high molecular mass ratio of degradable natural are 0/100-20/80, antibacterial-anti-inflammatory drug
Quality and outermost layer matrix material are the ratio between gross mass of degradable aliphatic polyester and the high molecular mixture of degradable natural
For 1/100-30/100；
(2) secondary outer layer fiber matrix is used as matrix using degradable aliphatic polyester and the high molecular mixture of degradable natural
Material, wherein degradable aliphatic polyester and the high molecular mass ratio of degradable natural are 20/80-50/50, facilitate bone medicinal substances
Amount is that the ratio between gross mass of degradable aliphatic polyester and the high molecular mixture of degradable natural is with time outer layer base material
1/100-40/100；
(3) secondary internal layer fibrous matrix is used as matrix using degradable aliphatic polyester and the high molecular mixture of degradable natural
Material, wherein degradable aliphatic polyester and the high molecular mass ratio of degradable natural are 50/50-80/20, facilitate bone medicinal substances
Amount is that the ratio between gross mass of degradable aliphatic polyester and the high molecular mixture of degradable natural is with secondary internal layer matrix material
1/100-40/100；
(4) innermost layer fibrous matrix is used as matrix using degradable aliphatic polyester and the high molecular mixture of degradable natural
Material, wherein degradable aliphatic polyester and the high molecular mass ratio of degradable natural are 80/20-100/0, facilitate bone medicinal substances
Amount is that the ratio between gross mass of degradable aliphatic polyester and the high molecular mixture of degradable natural is with innermost layer matrix material
1/100-40/100；
Degradable aliphatic polyester includes：PLA, polycaprolactone, Poly(D,L-lactide-co-glycolide, PLA-oneself
Lactone copolymers, poly lactic-co-glycolic acid-caprolactone copolymer one or more kinds of mixture therein；Degradable day
Right macromolecule includes：Mixture more than one or both of type i collagen, gelatin, chitosan, fibroin.
The medicine of outermost layer matrix is loaded into comprising in penicillins, cephalosporin class, Tetracyclines, chloromycetin, big ring
Esters, lincomycin, fluoroquinolones, nitro glyoxaline, polypeptide and quaternary ammonium salt antibacterials and aspirin, to Yin
Diindyl U.S. is pungent, naproxen, Diclofenac, brufen, aulin, celecoxib antiinflammatory drugs；It is loaded into time medicine of outer layer matrix
Thing includes VEGF VEGF, thymidine phosphorylase/platelet-derived endothelial cell growth factor PD-ECGF, heparitinase, blood vessel
Generate plain angs, Cycloxygenase COX-2, HIF-1, DFO, hematopoietin Epo, beta-elemene class is into blood
Pipe medicine；The medicine for being loaded into secondary internal layer and innermost layer matrix includes hydroxyapatite, graphene oxide, CNT, tricresyl phosphate
Calcium, icariin, bio-vitric and/or growth factor；Bio-vitric include 45S5, apatite-wollastonite activity glass, can
Cut bioactivity glass；Growth factor for example bone morphogenic protein BMP-2, fibroblast growth factor FGF, conversion growth because
One or more in sub- TGF- Β and insulin-like growth factor I GF.
Described Bone Defect Repari membrane material preparation method for material has the following steps：
(1) degradable aliphatic polyester is dissolved in organic solvent, room temperature magnetic agitation 6-12h, obtains degradable aliphatic
Adoption ester mass concentration is 0.00-0.02g/mL solution A, and when degradable aliphatic polyester content is 0, neat solvent is as molten
Liquid A；
(2) degradable natural macromolecule is added into solution A, room temperature magnetic agitation 6-12h, obtains degradable natural high score
Protonatomic mass concentration is 0.08-0.10g/mL solution B, and degradable aliphatic polyester and degradable natural are high molecular in solution B
Mass ratio is 0/100-20/80；
(3) antibacterials 1 are added into solution B, room temperature magnetic agitation 6-12h, it is 0.1g/mL to obtain matrix material concentration
Solution C, the quality and degradable aliphatic polyester and the ratio of degradable natural macromolecule gross mass of antibacterials 1 in solution C
For 1/100-30/100.
(4) degradable aliphatic polyester is dissolved in organic solvent, room temperature magnetic agitation 6-12h, obtains degradable aliphatic
Adoption ester mass concentration is 0.02-0.05g/mL solution D；
(5) degradable natural macromolecule is added in solution D, room temperature magnetic agitation 6-12h, obtains degradable natural macromolecule
Mass concentration is 0.05-0.08g/mL solution E, degradable aliphatic polyester and the high molecular matter of degradable natural in solution E
It is 20/80-50/50 to measure ratio；
(6) added into solution E and facilitate angiogenic substance 2, room temperature magnetic agitation 6-12h, obtain matrix material mass concentration
For 0.10g/mL solution F, facilitate the quality of angiogenic substance 2 and degradable aliphatic polyester and degradable natural high in solution F
The ratio of molecule gross mass is 1/100-40/100.
(7) degradable aliphatic polyester is dissolved in organic solvent, room temperature magnetic agitation 6-12h, obtains degradable aliphatic
Adoption ester mass concentration is 0.02-0.05g/mL solution G；
(8) degradable natural macromolecule is added in solution G, room temperature magnetic agitation 6-12h, obtains degradable natural macromolecule
Mass concentration is 0.05-0.08g/mL Solution H, degradable aliphatic polyester and the high molecular matter of degradable natural in Solution H
It is 50/50-80/20 to measure ratio；
(9) added into Solution H and facilitate bone material 3, room temperature magnetic agitation 6-12h, it is 0.1g/ to obtain matrix material concentration
ML solution I, facilitate the quality and degradable aliphatic polyester and degradable natural macromolecule gross mass of bone material 3 in solution I
Ratio be 1/100-40/100.
(10) degradable aliphatic polyester is dissolved in organic solvent, room temperature magnetic agitation 6-12h, obtains degradable aliphatic
Adoption ester mass concentration is 0.08-0.10g/mL solution J；
(11) degradable natural macromolecule is added in solution J, room temperature magnetic agitation 6-12h, obtains degradable natural high score
Protonatomic mass concentration is 0.00-0.02g/mL solution K, and degradable aliphatic polyester and degradable natural are high molecular in solution K
Mass ratio is 80/20-100/0, and when degradable natural high molecule mass is 0, step (11) can be omitted, now solution K essence
Upper is solution J；
(12) added into solution K and facilitate bone material 4, room temperature magnetic agitation 6-12h, obtaining matrix material concentration is
Facilitate quality and the degradable aliphatic polyester and degradable natural macromolecule of bone material 4 total in 0.1g/mL solution L, solution L
The ratio of quality is 1/100-40/100.
(13) solution C, solution F, solution I, solution L are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 100-600rpm,
Spinning solution innermost layer flow rate is 0.1-1mL/h, and secondary internal layer flow rate is 0.5-1.5mL/h, and secondary outer flow speed is
0.5-1.5mL/h, outermost layer flow rate are 1-3mL/h, voltage 15-30kV, receive distance 15-30cm, spinning 5-30h, obtain
To electricity spinning fibre film；
(14) after electrostatic spinning terminates, by spinning film, room temperature is placed 2-7 days in fume hood, package sterilization.
The present invention prepares four layers of Coaxial Nanofibers Bone Defect Repari membrane material using the method for electrostatic spinning, but the present invention is not
It is limited to the Bone Defect Repari tunica fibrosa for preparing the structure, is modified on the Bone Defect Repari tunica fibrosa surface with the structure or drug loading
Etc. being suitable for the present invention.
Brief description of the drawings
Fig. 1 is material schematic diagram of the present invention；
According to experimental design, each layer matrix of four layers of coaxial fiber is different, and in use, fiber will be with
The order of first layer-four layers of the second layer-third layer-the is successively degraded, while medicine can be controlled to promote with antibacterial-anti-inflammatory drug 1-
Bone medicine 3- is facilitated to facilitate the release of the order progress of bone medicine 4 successively into blood vessel drug eluting 2-.
Fig. 2 is the electron microscopic picture of embodiment 1-4 membrane material；
It can be seen that, the smooth no bead structure of fiber surface obtained by embodiment 1-4, illustrate medicine very by electron microscopic picture
Well wrapped is in the fibre.
Fig. 3 is TEM (embodiment 5)
By using four layers of coaxial syringe needle it can be seen from the TEM figures of embodiment 5, we have successfully been made with four
The Electrospun nano-fibers of layer coaxial configuration.
Fig. 4 is embodiment 6-8 antibacterial photo (Pseudomonas aeruginosa)
Above-mentioned antibacterial picture is the bacteriostatic experiment experiment photo of the 5th day, it will be seen that at the 5th day, material is still
With preferable bacteriostasis property.It is inflammation and infects the peak period occurred within the 1-3 day in Cranial defect generation, can by above-mentioned experiment
Know, material can help to suppress inflammation or the infection of Cranial defect early period of origination.
Fig. 5 is embodiment 9-12 cell proliferation experiment data
Upper figure is the proliferation experiment picture of MC3T3 cells, it will be seen that at the 7th day of propagation, cell on material
Proliferative amount has exceeded 80% compared with blank sample, illustrate membrane material can effectively help Gegenbaur's cell carry out adhesion and
Propagation, is advantageous to the progress of osteogenetic process.
Fig. 6 is embodiment 13-14 alkaline phosphatase activities data
The generation of alkaline phosphatase is more significant feature at skeletonization initial stage, as seen from the figure, embodiment 13 and embodiment 14
The content of alkaline phosphatase of corresponding experimental group is higher, illustrates that material has preferable facilitation effect to skeletonization.
Fig. 7 is embodiment 15-16 osteopontin contents
Osteopontin is skeletonization middle and later periods more significant mark, from upper figure, embodiment 15 and the institute of embodiment 16
Corresponding experimental group has higher osteopontin content, further illustrates that material has good effect for skeletonization.
Embodiment
With reference to embodiment, the present invention will be further described, but the present invention is not limited to following examples.
Embodiment 1
(1) 1g gelatin is taken, adds in 10mL trifluoroethanol solvents, room temperature magnetic agitation 6h, obtains gelatin mass concentration
For 0.1g/mL solution A；
(2) 0.01g Ciprofloxacins are added into solution A, room temperature magnetic agitation 6h obtains solution B, and solution B middle ring third is husky
The mass ratio of star and gelatin is 1/100；
(3) 0.2g polycaprolactone is taken, is added in 10mL trifluoroethanol solvents, room temperature magnetic agitation 12h, obtains gathering in oneself
Ester mass concentration is 0.02g/mL solution C；
(4) 0.8g gelatin is added into solution C, room temperature magnetic agitation 12h obtains solution D, polycaprolactone in solution D
Mass ratio with gelatin is 20/80；
(5) 0.01gDFO, room temperature magnetic agitation 6h are added into solution D, obtains solution E, in solution E DFO quality with
Polycaprolactone and the ratio of gelatin gross mass are 1/100；
(6) 0.5g polycaprolactone is taken, is added in 10mL trifluoroethanol solvents, room temperature magnetic agitation 6h, obtains gathering in oneself
Ester mass concentration is 0.05g/mL solution F；
(7) 0.5g gelatin is added into solution F, room temperature magnetic agitation 12h obtains solution G, polycaprolactone in solution G
Mass ratio with gelatin is 50/50；
(8) 0.01g hydroxyapatites are added into solution G, room temperature magnetic agitation 6h obtains Solution H, hydroxyl in Solution H
The quality and polycaprolactone of apatite and the ratio of gelatin gross mass are 1/100；
(9) 1g polycaprolactone is taken, adds in 10mL trifluoroethanol solvents, room temperature magnetic agitation 6h, obtains polycaprolactone
Mass concentration is 0.1g/mL solution I；
(10) 0.01g tricalcium phosphates are added into solution I, room temperature magnetic agitation 6h obtains solution J, tricresyl phosphate in solution J
The quality of calcium and the mass ratio of polycaprolactone are 1/100；
(11) solution B, solution E, Solution H, solution J are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 400rpm, spinning
Liquid innermost layer flow rate is 0.1mL/h, and secondary internal layer flow rate is 1mL/h, and secondary outer flow speed is 1mL/h, outermost layer
Flow rate is 2mL/h, voltage 24kV, receives distance 20cm, spinning 16h, obtains electricity spinning fibre film；
(12) after electrostatic spinning terminates, by spinning film, room temperature is placed 3 days in fume hood, package sterilization.
Embodiment 2
(1) 0.2g polycaprolactone is taken, is added in 10mL trifluoroethanol solvents, room temperature magnetic agitation 6h, obtains gathering in oneself
Ester mass concentration is 0.02g/mL solution A；
(2) 0.8g gelatin is added into solution A, room temperature magnetic agitation 12h obtains solution B, polycaprolactone in solution B
Mass ratio with gelatin is 20/80；
(3) 0.3g MOXIFLOXACINs are added into solution B, room temperature magnetic agitation 6h obtains solution C, MOXIFLOXACIN in solution C
Quality and polycaprolactone and the ratio of gross mass of gelatin be 30/100；
(4) 0.5g polycaprolactone is taken, is added in 10mL trifluoroethanol solvents, room temperature magnetic agitation 6h, obtains gathering in oneself
Ester mass concentration is 0.05g/mL solution D；
(5) 0.5g gelatin is added into solution D, room temperature magnetic agitation 12h obtains solution E, polycaprolactone in solution E
Mass ratio with gelatin is 50/50；
(6) 0.10gVEGF, room temperature magnetic agitation 6h are added into solution E, obtains solution F, VEGF quality in solution F
It is 10/100 with polycaprolactone and the ratio of gelatin gross mass；
(7) 0.8g polycaprolactone is taken, is added in 10mL trifluoroethanol solvents, room temperature magnetic agitation 6h, obtains gathering in oneself
Ester mass concentration is 0.08g/mL solution G；
(8) 0.2g gelatin is added into solution G, room temperature magnetic agitation 12h obtains Solution H, polycaprolactone in Solution H
Mass ratio with gelatin is 80/20；
(9) 0.20g icariin is added into Solution H, room temperature magnetic agitation 6h obtains solution I, barrenwort in solution I
The quality and polycaprolactone of glycosides and the ratio of gelatin gross mass are 20/100；
(10) 1g polycaprolactone is taken, adds in 10mL trifluoroethanol solvents, room temperature magnetic agitation 6h, obtains polycaprolactone
Mass concentration is 0.1g/mL solution J；
(11) 0.01g tricalcium phosphates are added into solution J, room temperature magnetic agitation 6h obtains solution K, tricresyl phosphate in solution K
The quality of calcium and the mass ratio of polycaprolactone are 1/100；
(12) solution C, solution F, solution I, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 400rpm, spinning
Liquid innermost layer flow rate is 0.1mL/h, and secondary internal layer flow rate is 0.5mL/h, and secondary outer flow speed is 0.5mL/h, most
Outer flow speed is 3mL/h, voltage 24kV, distance 20cm is received, spinning 16h, obtains electricity spinning fibre film；
(13) after electrostatic spinning terminates, by spinning film, room temperature is placed 3 days in fume hood, package sterilization.
Embodiment 3
(1) take 0.2g PLA, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 9h, obtain
PLA mass concentration is 0.02g/mL solution A；
(2) 0.8g chitosan is added into solution A, room temperature magnetic agitation 10h obtains solution B, PLA in solution B
Mass ratio with chitosan is 20/80；
(3) 0.3g penicillin is added into solution B, room temperature magnetic agitation 6h obtains solution C, the matter of penicillin in solution C
Amount is 30/100 with PLA and the ratio of the gross mass of chitosan；
(4) take 0.4g PLA, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 9h, obtain
PLA mass concentration is 0.04g/mL solution D；
(5) 0.6g chitosan is added into solution D, room temperature magnetic agitation 10h obtains solution E, PLA in solution E
Mass ratio with chitosan is 40/60；
(6) 0.40gPE-ECGF, room temperature magnetic agitation 6h are added into solution E, obtains solution F, PE-ECGF in solution F
Quality and PLA and the ratio of gross mass of chitosan be 40/100；
(7) take 0.6g PLA, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 9h, obtain
PLA mass concentration is 0.06g/mL solution G；
(8) 0.4g chitosan is added into solution G, room temperature magnetic agitation 10h obtains Solution H, PLA in Solution H
Mass ratio with chitosan is 60/40；
(9) 0.4g graphene oxides are added into Solution H, room temperature magnetic agitation 6h, solution I is obtained, stone is aoxidized in solution I
The quality and PLA of black alkene and the ratio of chitosan gross mass are 40/100；
(10) take 0.8g PLA, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 9h, obtain
PLA mass concentration is 0.08g/mL solution J；
(11) 0.2g chitosan is added into solution J, room temperature magnetic agitation 10h obtains solution K, PLA in solution K
Mass ratio with chitosan is 80/20；
(12) 0.01g apatite-wollastonite activity glass is added into solution K, room temperature magnetic agitation 6h, obtains solution L,
The quality of apatite-wollastonite activity glass and PLA and the ratio of the gross mass of chitosan are 1/100 in solution L；
(13) solution C, solution F, solution I, solution L are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 400rpm, spinning
Liquid innermost layer flow rate is 1mL/h, and secondary internal layer flow rate is 1mL/h, and secondary outer flow speed is 1mL/h, outermost laminar flow
Dynamic speed is 1mL/h, voltage 24kV, distance 18cm is received, spinning 12h, obtains electricity spinning fibre film；
(14) after electrostatic spinning terminates, by spinning film, room temperature is placed 4 days in fume hood, package sterilization.
Embodiment 4
(1) take 0.1g PLA, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 6h, obtain
PLA mass concentration is 0.01g/mL solution A；
(2) 0.9g chitosan is added into solution A, room temperature magnetic agitation 10h obtains solution B, PLA in solution B
Mass ratio with chitosan is 10/90；
(3) 0.01g Doxycyclines are added into solution B, room temperature magnetic agitation 6h obtains solution C, how western ring in solution C
The quality of element is 1/100 with PLA and the ratio of the gross mass of chitosan；
(4) take 0.3g PLA, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 6h, obtain
PLA mass concentration is 0.03g/mL solution D；
(5) 0.7g chitosan is added into solution D, room temperature magnetic agitation 10h obtains solution E, PLA in solution E
Mass ratio with chitosan is 30/70；
(6) 0.40g heparitinases are added into solution E, room temperature magnetic agitation 6h obtains solution F, acetyl in solution F
The quality of heparinase is 40/100 with PLA and the ratio of the gross mass of chitosan；
(7) take 0.6g PLA, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 6h, obtain
PLA mass concentration is 0.06g/mL solution G；
(8) 0.4g chitosan is added into solution G, room temperature magnetic agitation 10h obtains Solution H, PLA in Solution H
Mass ratio with chitosan is 60/40；
(9) 0.4g apatite-wollastonite activity glass is added into Solution H, room temperature magnetic agitation 6h, obtains solution I, it is molten
The quality of apatite-wollastonite activity glass and PLA and the ratio of chitosan gross mass are 40/100 in liquid I；
(10) take 0.8g PLA, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 6h, obtain
PLA mass concentration is 0.08g/mL solution J；
(11) 0.2g chitosan is added into solution J, room temperature magnetic agitation 10h obtains solution K, PLA in solution K
Mass ratio with chitosan is 80/20；
(12) 0.4g machinable bioactivity glass is added into solution K, room temperature magnetic agitation 6h, obtains solution L, solution
The quality of machinable bioactivity glass and PLA and the ratio of the gross mass of chitosan are 40/100 in L；
(13) solution C, solution F, solution I, solution L are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 400rpm, spinning
Liquid innermost layer flow rate is 0.1mL/h, and secondary internal layer flow rate is 0.5mL/h, and secondary outer flow speed is 0.5mL/h, most
Outer flow speed is 3mL/h, voltage 24kV, distance 18cm is received, spinning 18h, obtains electricity spinning fibre film；
(14) after electrostatic spinning terminates, by spinning film, room temperature is placed 4 days in fume hood, package sterilization.
Embodiment 5
(1) take 1g chitosan, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 10h, obtain shell
Glycan mass concentration is 0.1g/mL solution A；
(2) 0.3g Cefiximes are added into solution A, room temperature magnetic agitation 6h obtains solution B, Cefixime in solution B
Quality and chitosan mass ratio be 30/100；
(3) take 0.2g PLA, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 10h, obtain
PLA mass concentration is 0.02g/mL solution C；
(4) 0.8g chitosan is added into solution C, room temperature magnetic agitation 10h obtains solution D, PLA in solution D
Mass ratio with chitosan is 20/80；
(5) 0.01g angiogenins are added into solution D, room temperature magnetic agitation 6h, obtain solution E, solution E medium vessels
The quality and PLA and the ratio of the gross mass of chitosan for generating element are 1/100；
(6) take 0.7g PLA, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 10h, obtain
PLA mass concentration is 0.07g/mL solution F；
(7) 0.3g chitosan is added into solution F, room temperature magnetic agitation 10h obtains solution G, PLA in solution G
Mass ratio with chitosan is 70/30；
(8) 0.01g45S5 bio-vitric powder is added into solution G, room temperature magnetic agitation 6h, obtains Solution H, Solution H
The quality and PLA of middle 45S5 bio-vitrics and the ratio of chitosan gross mass are 1/100；
(9) take 0.9g PLA, add 10mLN, in dinethylformamide solvent, room temperature magnetic agitation 10h, obtain
PLA mass concentration is 0.09g/mL solution I；
(10) 0.1g chitosan is added into solution I, room temperature magnetic agitation 10h obtains solution J, PLA in solution J
Mass ratio with chitosan is 90/10；
(11) 0.01gTGF-B, room temperature magnetic agitation 6h are added into solution J, obtains solution K, TGF- Β in solution K
Quality is 1/100 with PLA and the ratio of the gross mass of chitosan；
(12) solution B, solution E, Solution H, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 400rpm, spinning
Liquid innermost layer flow rate is 0.1mL/h, and secondary internal layer flow rate is 1.5mL/h, and secondary outer flow speed is 1.5mL/h, most
Outer flow speed is 2mL/h, voltage 24kV, distance 18cm is received, spinning 5h, obtains electricity spinning fibre film；
(13) after electrostatic spinning terminates, by spinning film, room temperature is placed 4 days in fume hood, package sterilization.
Embodiment 6
(1) 0.1g PLLA is taken, adds in 10mL polyglycolic acid hexafluoroisopropanol solvents, room temperature magnetic agitation 6h, obtains a left side
Revolve the solution A that PLA mass concentration is 0.01g/mL；
(2) 0.9g type i collagen is added into solution C, room temperature magnetic agitation 10h obtains solution B, left-handed poly- in solution B
The mass ratio of lactic acid and type i collagen is 10/90；
(3) 0.01g tacrolimus is added into solution B, room temperature magnetic agitation 6h obtains solution C, Ta Kemo in solution C
The quality of department is 1/100 with PLLA and the ratio of the gross mass of type i collagen；
(4) 0.3g PLLA is taken, adds in 10Ml polyglycolic acid hexafluoroisopropanol solvents, room temperature magnetic agitation 6h, obtains a left side
Revolve the solution D that PLA mass concentration is 0.03g/mL；
(5) 0.7g type i collagen is added into solution D, room temperature magnetic agitation 10h obtains solution E, left-handed poly- in solution E
The mass ratio of lactic acid and type i collagen is 30/70；
(6) 0.40gIGF, room temperature magnetic agitation 6h are added into solution E, obtains solution F, in solution F IGF quality with
The ratio of the gross mass of PLLA and type i collagen is 40/100；
(7) 0.6g PLLA is taken, adds in 10mL polyglycolic acid hexafluoroisopropanol solvents, room temperature magnetic agitation 6h, obtains a left side
Revolve the solution G that PLA mass concentration is 0.06g/mL；
(8) 0.4g type i collagen is added into solution G, room temperature magnetic agitation 10h obtains Solution H, left-handed poly- in Solution H
The mass ratio of lactic acid and type i collagen is 60/40；
(9) 0.4g is added into Solution H and facilitates bone medicine bio-vitric 45S5, room temperature magnetic agitation 6h, obtain solution I,
Bio-vitric 45S5 quality and PLLA and the ratio of type i collagen gross mass are 40/100 in solution I；
(10) 0.8g PLLA is taken, is added in 10mL hexafluoroisopropanols, room temperature magnetic agitation 6h, is obtained left-handed poly-
Lactic acid mass concentration is 0.08g/mL solution J；
(11) 0.2g type i collagen is added into solution J, room temperature magnetic agitation 10h obtains solution K, left-handed in solution K
The mass ratio of PLA and type i collagen is 80/20；
(12) 0.01gBMP-2 and 20mgBSA are dissolved in 500 μ L deionized waters, obtain solution L；
(13) solution L, room temperature magnetic agitation 6h, ultrasonic 5min are added into solution K, obtains solution M, BMP-2 in solution M
Quality and PLLA and the ratio of gross mass of type i collagen be 1/100；
(14) solution C, solution F, solution I, solution M are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 400rpm, spinning
Liquid innermost layer flow rate is 0.1mL/h, and secondary internal layer flow rate is 0.5mL/h, and secondary outer flow speed is 0.5mL/h, most
Outer flow speed is 3mL/h, voltage 24kV, distance 18cm is received, spinning 18h, obtains electricity spinning fibre film；
(15) after electrostatic spinning terminates, by spinning film, room temperature is placed 2 days in fume hood, package sterilization.
Embodiment 7
(1) 1.0g chitosan is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 12h, obtains chitosan
Mass concentration is 0.10g/ml solution A；
(2) 0.02g metronidazoles are added into solution A, room temperature magnetic agitation 12h obtains solution B, metronidazole matter in solution B
The ratio of amount and chitosan mass is 2/100；
(3) 0.25g PLA is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 9h, obtains PLA
Mass concentration is 0.025g/ml solution C；
(4) 0.75g chitosan is added into solution C, room temperature magnetic agitation 6h obtains solution D, PLA in solution D
Mass ratio with chitosan is 25/75；
(5) 0.01g angiogenins are added into solution D, room temperature magnetic agitation 6h, obtain solution E, solution E medium vessels
It is 1/100 to generate the quality of element and the total mass ratio of PLA and chitosan；
(6) 0.5g PLA is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 9h, obtains PLA
Mass concentration is 0.05g/ml solution F；
(7) 0.5g chitosan is added into solution F, room temperature magnetic agitation 6h obtains solution G, in solution G PLA with
The mass ratio of chitosan is 50/50；
(8) 0.05g TGF- α are added into solution G, are stirred, it is 0.10g/ml's to obtain macromolecule total mass concentration
Solution H, the ratio between TGF- α quality and gross mass of PLA and chitosan are 5/100 in Solution H；
(9) 0.75g PLA is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 12h, obtains poly- breast
Sour mass concentration is 0.075g/ml solution I；
(10) 0.25g chitosan is added into solution I, room temperature magnetic agitation 10h, obtains solution J；
(11) 0.4g FGF is added into solution J, is stirred, it is 0.10g/ml's to obtain macromolecule total mass concentration
The ratio between FGF quality and the gross mass of PLA and chitosan are 40/100 in solution K, solution K；
(12) solution B, solution E, Solution H, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 600rpm, spinning
Liquid innermost layer flow rate is 1mL/h, and secondary internal layer flow rate is 1.5mL/h, and secondary outer flow speed is 1.5mL/h, outermost
Laminar flow speed is 3mL/h, voltage 30kV, receives distance 15cm, spinning 5h, obtains electricity spinning fibre film；
(13) after electrostatic spinning terminates, by spinning film, room temperature is placed 5 days in fume hood, package sterilization.
Embodiment 8
(1) 0.1g PLA is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 6h, obtains PLA
Mass concentration is 0.01g/ml solution A；
(2) 0.9g fibroin is added into solution A, room temperature magnetic agitation 6h obtains solution B, PLA and silk in solution B
The mass ratio of element is 10/90；
(3) 0.2g quaternary ammonium salts are added into solution B, room temperature magnetic agitation 6h obtains solution C, quaternary ammonium salt quality in solution C
It is 20/100 with the ratio between the gross mass of PLA and fibroin；
(4) 0.4g PLA is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 12h, obtains PLA
Mass concentration is 0.04g/ml solution C；
(5) 0.6g fibroin is added into solution C, room temperature magnetic agitation 12h obtains solution D, in solution D PLA with
The mass ratio of fibroin is 40/60；
(6) 0.3g beta-elemenes are added into solution D, room temperature magnetic agitation 12h obtains solution E, β-elemi in solution E
The ratio between the quality and PLA of alkene and the gross mass of fibroin are 30/100；
(7) 0.6g PLA is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 9h, obtains PLA
Mass concentration is 0.06g/ml solution F；
(8) 0.4g fibroin is added into solution F, room temperature magnetic agitation 9h obtains solution G, PLA and silk in solution G
The mass ratio of element is 60/40；
(9) 0.2g graphene oxides are added into solution G, are stirred, it is 0.10g/ to obtain macromolecule total mass concentration
Ml Solution H, the ratio between graphene oxide and gross mass of PLA and fibroin are 60/40 in Solution H；
(10) 0.8g PLA is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 9h, obtains PLA
Mass concentration is 0.08g/ml solution I
(11) 0.2g fibroin is added into solution I, room temperature magnetic agitation 10h obtains solution J, in solution J PLA with
The mass ratio of fibroin is 80/20；
(12) 0.2g CNT is added into solution J, stirs, obtains solution K, in solution K CNT with
The ratio between gross mass of PLA and fibroin is 20/100；
(13) solution B, solution E, Solution H, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 200rpm, spinning
Liquid innermost layer flow rate is 0.1mL/h, and secondary internal layer flow rate is 1mL/h, and secondary outer flow speed is 1mL/h, outermost layer
Flow rate is 2mL/h, voltage 28kV, receives distance 15cm, spinning 15h, obtains electricity spinning fibre film；
(14) after electrostatic spinning terminates, by spinning film, room temperature is placed 6 days in fume hood, package sterilization.
Embodiment 9
(1) 0.05g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 7h, is obtained
To the solution A that polycaprolactone mass concentration is 0.005g/ml；
(2) 0.95g chitosan is added into solution A, room temperature magnetic agitation 7h, solution B is obtained, gathers in solution B in oneself
The mass ratio of ester and chitosan is 5/95；
(3) 0.02g aspirin is added into solution B, room temperature magnetic agitation 7h obtains solution C, Ah Si in solution C
The ratio between woods quality and the gross mass of polycaprolactone and chitosan are 2/100；
(4) 0.3g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 9h, is obtained
To the solution C that polycaprolactone mass concentration is 0.03g/ml；
(5) 0.7g chitosan is added into solution C, room temperature magnetic agitation 9h obtains solution D, polycaprolactone in solution D
Mass ratio with chitosan is 30/70；
(6) 0.15gDFO, room temperature magnetic agitation 9h are added into solution D, obtains solution E, in solution E DFO quality with
The ratio between gross mass of polycaprolactone and chitosan is 15/100；
(7) 0.7g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 11h, is obtained
To the solution F that polycaprolactone mass concentration is 0.07g/ml；
(8) 0.3g chitosan is added into solution F, room temperature magnetic agitation 11h, solution G is obtained, gathers in solution G in oneself
The mass ratio of ester and chitosan is 70/30；
(9) 0.11g BMP-2 are added into solution G, are stirred, obtain Solution H, in Solution H BMP-2 quality with it is poly-
The ratio between gross mass of caprolactone and chitosan is 11/100；
(10) 0.95g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 9h,
Obtain the solution I that polycaprolactone mass concentration is 0.095g/ml
(11) 0.05g chitosan is added into solution I, room temperature magnetic agitation 10h, obtains solution J；
(12) 0.24g IGF is added into solution J, stirs, obtains solution K, IGF quality is with gathering oneself in solution K
The ratio between gross mass of lactone and chitosan is 24/100；
(13) solution B, solution E, Solution H, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 400rpm, spinning
Liquid innermost layer flow rate is 0.3mL/h, and secondary internal layer flow rate is 0.6mL/h, and secondary outer flow speed is 0.9mL/h, most
Outer flow speed is 1.2mL/h, voltage 27kV, receives distance 26cm, spinning 10h, obtains electricity spinning fibre film；
(14) after electrostatic spinning terminates, by spinning film, room temperature is placed 2 days in fume hood, package sterilization.
Embodiment 10
(1) 0.05g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 7h, is obtained
To the solution A that polycaprolactone mass concentration is 0.01g/ml；
(2) 0.95g fibroin is added into solution A, room temperature magnetic agitation 7h obtains solution B, polycaprolactone in solution B
Mass ratio with fibroin is 5/95；
(3) 0.1g naproxens are added into solution B, room temperature magnetic agitation 7h obtains solution C, naproxen quality in solution C
It is 10/100 with the ratio between the gross mass of polycaprolactone and fibroin；
(4) 0.3g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 9h, is obtained
To the solution C that polycaprolactone mass concentration is 0.03g/ml；
(5) 0.7g fibroin is added into solution C, room temperature magnetic agitation 9h obtains solution D, in solution D polycaprolactone with
The mass ratio of fibroin is 30/70；
(6) 0.36g DFO, room temperature magnetic agitation 9h are added into solution D, obtains solution E, in solution E DFO quality with
The ratio between gross mass of polycaprolactone and fibroin is 36/100；
(7) 0.7g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 11h, is obtained
To the solution F that polycaprolactone mass concentration is 0.07g/ml；
(8) 0.3g fibroin is added into solution F, room temperature magnetic agitation 11h obtains solution G, polycaprolactone in solution G
Mass ratio with fibroin is 70/30；
(9) 0.08g apatite-wollastonite activity glass is added into solution G to stir, obtain Solution H, in Solution H
The ratio between the quality and polycaprolactone of apatite-wollastonite activity glass and the gross mass of fibroin are 8/100；
(10) 0.95g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 9h,
Obtain the solution I that polycaprolactone mass concentration is 0.095g/ml
(11) 0.05g fibroin is added into solution I, room temperature magnetic agitation 10h, obtains solution J；
(12) 0.19g hydroxyapatite is added into solution J, stirs, obtains solution K, hydroxy-apatite in solution K
The ratio between the quality and polycaprolactone of stone and the gross mass of fibroin are 19/100；
(13) solution B, solution E, Solution H, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 500rpm, spinning
Liquid innermost layer flow rate is 0.4mL/h, and secondary internal layer flow rate is 0.8mL/h, and secondary outer flow speed is 0.8mL/h, most
Outer flow speed is 2mL/h, voltage 30kV, receives distance 22cm, spinning 14h, obtains electricity spinning fibre film；
(14) after electrostatic spinning terminates, by spinning film, room temperature is placed 4 days in fume hood, package sterilization.
Embodiment 11
(1) 1g type i collagen is taken, adds in 10ml trifluoroethanol solvents, room temperature magnetic agitation 9h, obtains type i collagen matter
Measure the solution A that concentration is 0.1g/ml；
(2) 0.02g aulins are added into solution A, room temperature magnetic agitation 3h, it is 0.1g/ to obtain matrix material concentration
Ml solution B, aulin and type i collagen mass ratio are 2/100 in solution B；
(3) 0.75g poly lactic-co-glycolic acid-caprolactone copolymer is taken, is added in 10ml trifluoroethanol solvents, room temperature
Magnetic agitation 10h, obtain the solution C that poly lactic-co-glycolic acid-caprolactone copolymer mass concentration is 0.75g/ml；
(4) 0.25g type i collagen is added into solution C, room temperature magnetic agitation 9h, solution D is obtained, gathers breast in solution D
The mass ratio of acid-hydroxyacetic acid-caprolactone copolymer and type i collagen is 75/25；
(5) 0.02g angiogenins are added into solution D, room temperature magnetic agitation 6h, obtain solution E, solution E medium vessels
It is 2/100 to generate the ratio between quality and gross mass of poly lactic-co-glycolic acid-caprolactone copolymer and type i collagen of element；
(6) 0.5g poly lactic-co-glycolic acid-caprolactone copolymer is taken, is added in 9.5ml trifluoroethanol solvents, room temperature
Magnetic agitation 10h, obtain solution F；
(7) 0.5g type i collagen is added into solution F, room temperature magnetic agitation 9h obtains solution G, PLA in solution G-
The mass ratio of hydroxyacetic acid-caprolactone copolymer and type i collagen is 50/50；
(8) the 0.46ml IGF and BSA aqueous solution (IGF is added into Solution H：0.02g；BSA：80mg), add 40 μ l's
Span80, room temperature magnetic agitation 10min, obtain solution I, and IGF quality and poly lactic-co-glycolic acid-caprolactone are common in solution I
The ratio between gross mass of polymers and type i collagen is 2/100；
(9) 1g poly lactic-co-glycolic acids-caprolactone copolymer is taken, is added in 10ml trifluoroethanol solvents, room temperature magnetic force stirs
10h is mixed, obtains the solution J that poly lactic-co-glycolic acid-caprolactone copolymer mass concentration is 0.10g/ml；
(10) 0.4gFGF, ultrasonic 20min are added into solution J, obtains solution K, FGF quality and poly- breast in solution K
The mass ratio of acid-hydroxyacetic acid-caprolactone copolymer is 40/100；
(11) solution B, solution E, solution I, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 300rpm, spinning
Liquid innermost layer flow rate is 0.1ml/h, and secondary internal layer flow rate is 0.5ml/h, and secondary outer flow speed is 0.8ml/h, most
Outer flow speed is 1.7ml/h, voltage 27kV, receives distance 30cm, spinning 26h, obtains electricity spinning fibre film；
(12) after electrostatic spinning terminates, by spinning film, room temperature is placed 5 days in fume hood, package sterilization.
Embodiment 12
(1) 1g type i collagen is taken, adds in 10ml trifluoroethanol solvents, room temperature magnetic agitation 9h, obtains type i collagen matter
Measure the solution A that concentration is 0.1g/ml；
(2) 0.3g Pentamycins are added into solution A, room temperature magnetic agitation 3h, it is 0.1g/ml to obtain matrix material concentration
Solution B, Pentamycin and type i collagen mass ratio are 30/100 in solution B；
(3) 0.5g poly lactic-co-glycolic acid-caprolactone copolymer is taken, is added in 10ml trifluoroethanol solvents, room temperature magnetic
Power stirs 10h, obtains the solution C that poly lactic-co-glycolic acid-caprolactone copolymer mass concentration is 0.05g/ml；
(4) 0.5g type i collagen is added into solution C, room temperature magnetic agitation 9h, obtaining macromolecule total mass concentration is
0.1g/ml solution D, the mass ratio of poly lactic-co-glycolic acid-caprolactone copolymer and type i collagen is 50/50 in solution D；
(5) add 0.4g into solution D to desferrioxamine (DFO), room temperature magnetic agitation 6h, obtaining macromolecule total mass concentration is
0.10g/ml solution E, desferrioxamine in the solution E quality and poly lactic-co-glycolic acid-caprolactone copolymer and I type glue of (DFO)
The ratio between former gross mass is 40/100；
(6) 0.75g poly lactic-co-glycolic acid-caprolactone copolymer is taken, is added in 9.5ml trifluoroethanol solvents, room temperature
Magnetic agitation 10h, obtain solution F；
(7) 0.25g type i collagen is added into solution F, room temperature magnetic agitation 9h, solution G is obtained, gathers breast in solution G
The mass ratio of acid-hydroxyacetic acid-caprolactone copolymer and type i collagen is 75/25；
(8) 0.46ml TGF-B and the BSA aqueous solution (TGF-B is added into Solution H：0.35g；BSA：80mg), 40 are added
μ l Span80, room temperature magnetic agitation 10min, obtain solution I, and TGF-B quality and poly lactic-co-glycolic acid in solution I-oneself
The ratio between gross mass of lactone copolymers and type i collagen is 35/100；
(9) 1g poly lactic-co-glycolic acids-caprolactone copolymer is taken, is added in 10ml trifluoroethanol solvents, room temperature magnetic force stirs
10h is mixed, obtains the solution J that poly lactic-co-glycolic acid-caprolactone copolymer mass concentration is 0.10g/ml；
(10) 0.07g tricalcium phosphates are added into solution J, ultrasonic 20min obtains solution K, tricalcium phosphate in solution K
Quality and the mass ratio of poly lactic-co-glycolic acid-caprolactone copolymer are 7/100；
(11) solution B, solution E, solution I, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 300rpm, spinning
Liquid innermost layer flow rate is 0.1ml/h, and secondary internal layer flow rate is 0.5ml/h, and secondary outer flow speed is 1.0ml/h, most
Outer flow speed is 3ml/h, voltage 28kV, receives distance 20cm, spinning 18h, obtains electricity spinning fibre film；
(12) after electrostatic spinning terminates, by spinning film, room temperature is placed 3 days in fume hood, package sterilization.
Embodiment 13
(1) 0.2g PLA-caprolactone copolymer is taken, is added in 10ml polyglycolic acid hexafluoroisopropanol solvent, room temperature magnetic force stirs
8h is mixed, obtains the solution A that PLA-caprolactone copolymer mass concentration is 0.04g/ml；
(2) 0.8g chitosan is added into solution A, room temperature magnetic agitation 8h obtains solution B, PLA in solution B-
The mass ratio of caprolactone copolymer and chitosan is 20/80；
(3) 0.3g brufens are added into solution B, room temperature magnetic agitation 10h obtains solution C, brufen in solution C
The ratio between quality and the gross mass of PLA-caprolactone copolymer and chitosan are 30/100；
(4) 0.35g PLA-caprolactone copolymer is taken, is added in 10ml polyglycolic acid hexafluoroisopropanol solvent, room temperature magnetic force stirs
12h is mixed, obtains the solution C that PLA-caprolactone copolymer mass concentration is 0.035g/ml；
(5) 0.65g chitosan is added into solution C, room temperature magnetic agitation 9h obtains solution D, PLA in solution D-
The mass ratio of caprolactone copolymer and chitosan is 35/65；
(6) 0.31g Cycloxygenases are added into solution D, room temperature magnetic agitation 8h obtains solution E, epoxidation in solution E
The ratio between the quality and PLA-caprolactone copolymer of enzyme and the gross mass of chitosan are 31/100；
(7) 0.65g PLA-caprolactone copolymer is taken, is added in 10ml polyglycolic acid hexafluoroisopropanol solvent, room temperature magnetic force stirs
10h is mixed, obtains the solution F that PLA-caprolactone copolymer mass concentration is 0.65g/ml；
(8) 0.35g chitosan is added into solution F, room temperature magnetic agitation 10h, solution G is obtained, gathers breast in solution G
The mass ratio of acid-caprolactone copolymer and chitosan is 65/35；
(9) 0.37g TGF-B are added into solution G, are stirred, obtain Solution H, in Solution H TGF-B quality with it is poly-
The ratio between gross mass of lactic acid-caprol acton copolymer and chitosan is 37/100；
(10) 0.8g PLA-caprolactone copolymer is taken, is added in 10ml polyglycolic acid hexafluoroisopropanol solvent, room temperature magnetic force stirs
9h is mixed, obtains the solution I that PLA-caprolactone copolymer mass concentration is 0.08g/ml
(11) 0.2g chitosan is added into solution I, room temperature magnetic agitation 10h, solution J is obtained, gathers breast in solution J
The mass ratio of acid-caprolactone copolymer and chitosan is 80/20；
(12) 0.18g tricalcium phosphate is added into solution J, stirs, obtains solution K, tricalcium phosphate in solution K
The ratio between quality and the gross mass of PLA-caprolactone copolymer and chitosan are 18/100；
(13) solution B, solution E, Solution H, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 500rpm, spinning
Liquid innermost layer flow rate is 0.2mL/h, and secondary internal layer flow rate is 0.8mL/h, and secondary outer flow speed is 0.8mL/h, most
Outer flow speed is 1mL/h, voltage 21kV, receives distance 24cm, spinning 23h, obtains electricity spinning fibre film；
(14) after electrostatic spinning terminates, by spinning film, room temperature is placed 3 days in fume hood, package sterilization.
Embodiment 14
(1) 0.2g Poly(D,L-lactide-co-glycolide is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature
Magnetic agitation 8h, obtain the solution A that Poly(D,L-lactide-co-glycolide mass concentration is 0.02g/ml；
(2) 0.8g fibroin is added into solution A, room temperature magnetic agitation 8h obtains solution B, polylactic acid-glycolic in solution B
The mass ratio of acetic acid copolymer and fibroin is 20/80；
(3) 0.3g Diclofenacs are added into solution B, room temperature magnetic agitation 10h, obtain solution C, double chlorine are fragrant in solution C
The ratio between the quality and Poly(D,L-lactide-co-glycolide of acid and the gross mass of fibroin are 30/100；
(4) 0.35g Poly(D,L-lactide-co-glycolide is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature
Magnetic agitation 12h, obtain the solution C that Poly(D,L-lactide-co-glycolide mass concentration is 0.035g/ml；
(5) 0.65g fibroin is added into solution C, room temperature magnetic agitation 9h obtains solution D, polylactic acid-glycolic in solution D
The mass ratio of acetic acid copolymer and fibroin is 35/65；
(6) 0.4g heparitinases are added into solution D, room temperature magnetic agitation 8h obtains solution E, acetyl liver in solution E
The ratio between the quality and Poly(D,L-lactide-co-glycolide of plain enzyme and the gross mass of fibroin are 40/100；
(7) 0.65g Poly(D,L-lactide-co-glycolide is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature
Magnetic agitation 10h, obtain the solution F that Poly(D,L-lactide-co-glycolide mass concentration is 0.65g/ml；
(8) 0.35g fibroin is added into solution F, room temperature magnetic agitation 10h obtains solution G, PLA in solution G-
The mass ratio of co-glycolic acid and fibroin is 65/35；
(9) 0.4g TGF-B are added into solution G, are stirred, obtain Solution H, in Solution H TGF-B quality with it is poly-
The ratio between gross mass of poly lactic coglycolic acid and fibroin is 40/100；
(10) 0.8g Poly(D,L-lactide-co-glycolide is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature
Magnetic agitation 9h, obtain the solution I that Poly(D,L-lactide-co-glycolide mass concentration is 0.08g/ml
(11) 0.2g fibroin is added into solution I, room temperature magnetic agitation 10h obtains solution J, PLA in solution J-
The mass ratio of co-glycolic acid and fibroin is 80/20；
(12) 0.4g icariin is added into solution J, stirs, obtains solution K, icariin in solution K
The ratio between quality and the gross mass of Poly(D,L-lactide-co-glycolide and fibroin are 40/100；
(13) solution B, solution E, Solution H, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 500rpm, spinning
Liquid innermost layer flow rate is 0.2mL/h, and secondary internal layer flow rate is 0.6mL/h, and secondary outer flow speed is 0.8mL/h, most
Outer flow speed is 2mL/h, voltage 28kV, receives distance 23cm, spinning 28h, obtains electricity spinning fibre film；
(14) after electrostatic spinning terminates, by spinning film, room temperature is placed 4 days in fume hood, package sterilization.
Embodiment 15
(1) 0.1g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 6h, is obtained
To the solution A that polycaprolactone mass concentration is 0.01g/ml；
(2) 0.9g type i collagen is added into solution A, room temperature magnetic agitation 6h, solution B is obtained, gathers in solution B in oneself
The mass ratio of ester and type i collagen is 10/90；
(3) 0.01g Indomethacins are added into solution B, room temperature magnetic agitation 6h, obtain solution C, indoles is beautiful in solution C
The ratio between pungent quality and the gross mass of polycaprolactone and type i collagen are 1/100；
(4) 0.4g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 12h, is obtained
To the solution C that polycaprolactone mass concentration is 0.04g/ml；
(5) 0.6g type i collagen is added into solution C, room temperature magnetic agitation 12h, solution D is obtained, gathers in solution D in oneself
The mass ratio of ester and type i collagen is 40/60；
(6) 0.01g HIF-1s are added into solution D, room temperature magnetic agitation 12h obtains solution E, in solution E
The ratio between the quality and polycaprolactone of HIF-1 and the gross mass of type i collagen are 1/100；
(7) 0.6g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 9h, is obtained
To the solution F that polycaprolactone mass concentration is 0.06g/ml；
(8) 0.4g type i collagen is added into solution F, room temperature magnetic agitation 9h, solution G is obtained, gathers in solution G in oneself
The mass ratio of ester and type i collagen is 60/40；
(9) 0.01g CNTs are added into solution G, are stirred, it is 0.10g/ml to obtain macromolecule total mass concentration
Solution H, the ratio between the quality of CNT and gross mass of polycaprolactone and type i collagen are 1/100 in Solution H；
(10) 0.95g polycaprolactone is taken, adds 10ml N, in N- dimethylformamide solvents, room temperature magnetic agitation 9h,
Obtain the solution I that polycaprolactone mass concentration is 0.95g/ml；
(11) 0.05g type i collagen is added into solution I, room temperature magnetic agitation 10h, solution J is obtained, gathers oneself in solution J
The mass ratio of lactone and type i collagen is 95/5；
(12) 0.01g machinable bioactivity glass is added into solution J, stirs, obtains solution K, in solution K
The ratio between the quality and polycaprolactone of machinable bioactivity glass and the gross mass of type i collagen are 1/100；
(13) solution B, solution E, Solution H, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 200rpm, spinning
Liquid innermost layer flow rate is 0.2mL/h, and secondary internal layer flow rate is 0.7mL/h, and secondary outer flow speed is 0.9mL/h, most
Outer flow speed is 1.1mL/h, voltage 22kV, receives distance 24cm, spinning 25h, obtains electricity spinning fibre film；
(14) after electrostatic spinning terminates, by spinning film, room temperature is placed 3 days in fume hood, package sterilization.
Embodiment 16
(1) 1.0g gelatin is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 12h, obtains gelatin quality
Concentration is 0.10g/ml solution A；
(2) 0.25g celecoxibs are added into solution A, room temperature magnetic agitation 12h, solution B is obtained, is filled in solution B and carry out former times
The quality of cloth is 25/100 with gelatin mass ratio；
(3) 0.25g PLA is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 9h, obtains PLA
Mass concentration is 0.25g/ml solution C；
(4) 0.75g gelatin is added into solution C, room temperature magnetic agitation 6h obtains solution D, in solution D PLA with
The mass ratio of gelatin is 25/75；
(5) 0.01g PD-ECGF, room temperature magnetic agitation 6h are added into solution D, obtains solution E, PD-ECGF in solution E
Quality and PLA and the ratio between the gross mass of gelatin be 1/100；
(6) 0.5g PLA is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 9h, obtains PLA
Mass concentration is 0.05g/ml solution F；
(7) 0.5g gelatin is added into solution F, room temperature magnetic agitation 6h obtains solution G, in solution G PLA with it is bright
The mass ratio of glue is 50/50；
(8) 0.35g CNTs are added into solution G, are stirred, obtain Solution H, the matter of CNT in Solution H
The ratio between amount and the gross mass of PLA and gelatin are 35/100；
(9) 0.8g PLA is taken, is added in 10ml trifluoroethanol solvent, room temperature magnetic agitation 12h, obtains PLA
Mass concentration is 0.08g/ml solution I
(10) 0.2g gelatin is added into solution I, room temperature magnetic agitation 10h obtains solution J, polycaprolactone in solution J
Mass ratio with gelatin is 80/20；
(11) 0.01g IGF, room temperature magnetic agitation 10min is added into solution J, obtaining macromolecule total mass concentration is
The ratio between IGF quality and the gross mass of PLA and gelatin are 1/100 in 0.10g/ml solution K, solution K；
(12) solution B, solution E, Solution H, solution K are added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer
Electrostatic spinning is carried out in corresponding propeller, using stainless steel drum as reception device, roller slewing rate is 100rpm, spinning
Liquid innermost layer flow rate is 0.1mL/h, and secondary internal layer flow rate is 0.1mL/h, and secondary outer flow speed is 0.1mL/h, most
Outer flow speed is 0.5mL/h, voltage 30kV, receives distance 20cm, spinning 30h, obtains electricity spinning fibre film；
(13) after electrostatic spinning terminates, by spinning film, room temperature is placed 7 days in fume hood, package sterilization.
It is the insoluble drug release table of embodiment below
Application examples
Application site：The light to moderate Cranial defect that the positions such as skull, ulna, radius, femur occur
Application process：Cranial defect position is separated totally with surrounding tissue, the small bone chip at defect is removed, by defect
Defect location is wrapped up with appropriate elasticity using membrane material after place is fixed, avoids tissue from growing into affected part and be scarce to reach
The purpose of nutriment and growth factor needed for defect repair is provided at damage.
Application effect：The 1-3 days after defect generation：Antibacterial-anti-inflammatory drug is discharged first, effectively prevents defect
The inflammation or infection that place may occur；Then discharge and facilitate blood vessel drug eluting, be basically completed in the 3rd day to the 20th day at defect
The reconstruction of blood vessel, blood vessel is played for nutriment needed for transport at defect while discharge the effect of metabolic waste；
After 20 days, facilitate bone medicine to be sustained, inducing cell Osteoblast Differentiation, after 40 days new bone basically form.
Claims (4)
1. the coaxial fiber Bone Defect Repari membrane material of multilayer, it is characterized in that：
(1) outermost fibers matrix is used as matrix material using degradable aliphatic polyester and the high molecular mixture of degradable natural
Material, wherein degradable aliphatic polyester and the high molecular mass ratio of degradable natural are 0/100-20/80, antibiosis anti-inflammatory drug material
Amount is that the ratio between gross mass of degradable aliphatic polyester and the high molecular mixture of degradable natural is with outermost layer matrix material
1/100-30/100；
(2) secondary outer layer fiber matrix is used as matrix material using degradable aliphatic polyester and the high molecular mixture of degradable natural
Material, wherein degradable aliphatic polyester and the high molecular mass ratio of degradable natural are 20/80-50/50, facilitate bone drug quality
It is that the ratio between gross mass of degradable aliphatic polyester and the high molecular mixture of degradable natural is 1/ with secondary outer layer base material
100-40/100；
(3) secondary internal layer fibrous matrix is used as matrix material using degradable aliphatic polyester and the high molecular mixture of degradable natural
Material, wherein degradable aliphatic polyester and the high molecular mass ratio of degradable natural are 50/50-80/20, facilitate bone drug quality
It is that the ratio between gross mass of degradable aliphatic polyester and the high molecular mixture of degradable natural is 1/ with secondary internal layer matrix material
100-40/100；
(4) innermost layer fibrous matrix is used as matrix material using degradable aliphatic polyester and the high molecular mixture of degradable natural
Material, wherein degradable aliphatic polyester and the high molecular mass ratio of degradable natural are 80/20-100/0, facilitate bone drug quality
It is that the ratio between gross mass of degradable aliphatic polyester and the high molecular mixture of degradable natural is 1/ with innermost layer matrix material
100-40/100。
2. the coaxial fiber Bone Defect Repari membrane material of multilayer according to claim 1, it is characterised in that degradable aliphatic polyester
Including：PLA, polycaprolactone, Poly(D,L-lactide-co-glycolide, PLA-caprolactone copolymer, polylactic acid-glycolic base second
Acid-caprolactone copolymer one or more kinds of mixture therein；Degradable natural macromolecule includes：It is type i collagen, bright
Mixture more than one or both of glue, chitosan, fibroin.
3. the coaxial fiber Bone Defect Repari membrane material of multilayer according to claim 1, it is characterised in that be loaded into outermost layer matrix
Medicine include penicillins, cephalosporin class, Tetracyclines, chloromycetin, macrolides, lincomycin, fluoroquinolones,
Nitro glyoxaline, polypeptide and quaternary ammonium salt antibacterials and aspirin, to Indomethacin, naproxen, Diclofenac, cloth
Ibuprofen, aulin, celecoxib antiinflammatory drugs；It is loaded into time medicine of outer layer matrix and includes VEGF
VEGF, thymidine phosphorylase/platelet-derived endothelial cell growth factor PD-ECGF, heparitinase, angiogenin angs, Cycloxygenase COX-
2, HIF-1, DFO, hematopoietin Epo, beta-elemene class is into blood vessel drug eluting；It is loaded into secondary internal layer and most interior
Layer matrix medicine include hydroxyapatite, graphene oxide, CNT, tricalcium phosphate, icariin, bio-vitric and/
Or growth factor；Bio-vitric includes 45S5, apatite-wollastonite activity glass, machinable bioactivity glass；Growth because
Son such as bone morphogenic protein BMP-2, fibroblast growth factor FGF, TGF TGF- Β and insulin-like growth
One or more in factor IGF.
4. prepare the coaxial fiber Bone Defect Repari membrane material of multilayer as described in claim 1-3 any one, method, its feature exists
In having the following steps：
(1) degradable aliphatic polyester is dissolved in organic solvent, room temperature magnetic agitation 6-12h, obtains degradable aliphatic adoption
Ester mass concentration is 0.00-0.02g/mL solution A, and when degradable aliphatic polyester content is 0, neat solvent is solution A；
(2) degradable natural macromolecule is added into solution A, room temperature magnetic agitation 6-12h, obtains degradable natural macromolecule matter
The solution B that concentration is 0.08-0.10g/mL is measured, degradable aliphatic polyester and the high molecular quality of degradable natural in solution B
Than for 0/100-20/80；
(3) antibacterials 1 are added into solution B, room temperature magnetic agitation 6-12h, it is the molten of 0.1g/mL to obtain matrix material concentration
Liquid C, the quality of antibacterials 1 and degradable aliphatic polyester and the ratio of degradable natural macromolecule gross mass are 1/ in solution C
100-30/100。
(4) degradable aliphatic polyester is dissolved in organic solvent, room temperature magnetic agitation 6-12h, obtains degradable aliphatic adoption
Ester mass concentration is 0.02-0.05g/mL solution D；
(5) degradable natural macromolecule is added in solution D, room temperature magnetic agitation 6-12h, obtains degradable natural high molecule mass
Concentration is 0.05-0.08g/mL solution E, degradable aliphatic polyester and the high molecular mass ratio of degradable natural in solution E
For 20/80-50/50；
(6) added into solution E and facilitate angiogenic substance 2, room temperature magnetic agitation 6-12h, obtaining matrix material mass concentration is
Facilitate the quality and degradable aliphatic polyester and degradable natural high score of angiogenic substance 2 in 0.10g/mL solution F, solution F
The ratio of sub- gross mass is 1/100-40/100.
(7) degradable aliphatic polyester is dissolved in organic solvent, room temperature magnetic agitation 6-12h, obtains degradable aliphatic adoption
Ester mass concentration is 0.02-0.05g/mL solution G；
(8) degradable natural macromolecule is added in solution G, room temperature magnetic agitation 6-12h, obtains degradable natural high molecule mass
Concentration is 0.05-0.08g/mL Solution H, degradable aliphatic polyester and the high molecular mass ratio of degradable natural in Solution H
For 50/50-80/20；
(9) added into Solution H and facilitate bone material 3, room temperature magnetic agitation 6-12h, it is 0.1g/mL's to obtain matrix material concentration
Solution I, facilitate the quality and degradable aliphatic polyester and the ratio of degradable natural macromolecule gross mass of bone material 3 in solution I
For 1/100-40/100.
(10) degradable aliphatic polyester is dissolved in organic solvent, room temperature magnetic agitation 6-12h, obtains degradable aliphatic adoption
Ester mass concentration is 0.08-0.10g/mL solution J；
(11) degradable natural macromolecule is added in solution J, room temperature magnetic agitation 6-12h, obtains degradable natural macromolecule matter
Measure degradable aliphatic polyester and the high molecular quality of degradable natural in concentration the solution K for 0.00-0.02g/mL, solution K
Than for 80/20-100/0, when degradable natural high molecule mass is 0, step (11) is omitted, and now solution K is substantially
Solution J；
(12) added into solution K and facilitate bone material 4, room temperature magnetic agitation 6-12h, it is 0.1g/mL to obtain matrix material concentration
Solution L, facilitate the quality of bone material 4 and degradable aliphatic polyester and degradable natural macromolecule gross mass in solution L
Than for 1/100-40/100.
(13) by solution C, solution F, solution I, solution L be added separately to fiber outermost layer, secondary outer layer, secondary internal layer and innermost layer institute it is right
Electrostatic spinning is carried out in the propeller answered, using stainless steel drum as reception device, roller slewing rate is 100-600rpm, spinning
Liquid innermost layer flow rate is 0.1-1mL/h, and secondary internal layer flow rate is 0.5-1.5mL/h, and secondary outer flow speed is 0.5-
1.5mL/h, outermost layer flow rate are 1-3mL/h, voltage 15-30kV, receive distance 15-30cm, spinning 5-30h, obtain electricity
Spinning fibre film；
(14) after electrostatic spinning terminates, by spinning film, room temperature is placed 2-7 days in fume hood, package sterilization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710710641.XA CN107625995B (en) | 2017-08-18 | 2017-08-18 | Multilayer coaxial fiber bone repair membrane material and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710710641.XA CN107625995B (en) | 2017-08-18 | 2017-08-18 | Multilayer coaxial fiber bone repair membrane material and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107625995A true CN107625995A (en) | 2018-01-26 |
| CN107625995B CN107625995B (en) | 2020-07-14 |
Family
ID=61101326
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710710641.XA Active CN107625995B (en) | 2017-08-18 | 2017-08-18 | Multilayer coaxial fiber bone repair membrane material and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107625995B (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108096630A (en) * | 2018-01-29 | 2018-06-01 | 暨南大学 | A kind of polylactic acid base tissue scaffold design and preparation method and application for carrying icariin and Deferoxamine |
| CN108144116A (en) * | 2018-02-26 | 2018-06-12 | 丁文铃 | A kind of novel antibacterial artificial ligament |
| CN108578777A (en) * | 2018-05-06 | 2018-09-28 | 西北工业大学 | A kind of artificial os osseum holder preparation method that growth factor concentration gradient is controllable |
| CN108744061A (en) * | 2018-06-28 | 2018-11-06 | 广州贝奥吉因生物科技有限公司 | A kind of strontium-doped hydroxyapatite/fibroin albumen/heparin compound rest and its preparation method and application of load BMP-2 |
| WO2020186714A1 (en) * | 2019-03-15 | 2020-09-24 | 深圳市光远生物材料有限责任公司 | Drug-loaded nanocomposite fiber membrane system, preparation method therefor and use thereof |
| CN112957347A (en) * | 2021-02-03 | 2021-06-15 | 北京市创伤骨科研究所 | Skin layer-by-layer gradient slow-release nursing film |
| CN113797178A (en) * | 2021-03-29 | 2021-12-17 | 中山大学附属第三医院（中山大学肝脏病医院） | Multifunctional composite material and preparation method and application thereof |
| CN114108177A (en) * | 2020-08-28 | 2022-03-01 | 北京化工大学 | An artificial skin material capable of photothermally triggering the phased release of growth factors and its preparation method and application |
| CN114099759A (en) * | 2020-08-28 | 2022-03-01 | 北京化工大学 | Fiber wound repair scaffold loaded with phase change material particles and its preparation method and application |
| CN114432503A (en) * | 2022-04-12 | 2022-05-06 | 北京大学口腔医学院 | Drug-loaded bone repair material and preparation method and application thereof |
| CN115300669A (en) * | 2022-08-24 | 2022-11-08 | 上海睿植康医疗科技有限公司 | Fiber membrane and preparation method and application thereof |
| CN116212119A (en) * | 2023-03-28 | 2023-06-06 | 汕头大学 | A hydrogel patch for promoting bone repair and preparation method thereof |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101509153A (en) * | 2009-03-23 | 2009-08-19 | 东华大学 | Method for producing shell-core structure medicament nano-fibre with coaxial electrostatic spinning technology |
| US20140186413A1 (en) * | 2012-12-27 | 2014-07-03 | Industry-Academic Cooperation Foundation, Dankook University | Preparation method of core-shell structured fibrous scaffolds |
| CN103948974A (en) * | 2013-12-30 | 2014-07-30 | 北京化工大学 | Drug-loading type guided tissue regeneration membrane and preparation method thereof |
| CN104524643A (en) * | 2014-11-26 | 2015-04-22 | 北京化工大学 | Halloysite-nanotube-containing drug-loaded type guide tissue regeneration membrane and preparation method thereof |
| CN103893819B (en) * | 2014-03-20 | 2015-07-15 | 北京大学第三医院 | Coaxial electrostatic spinning fibrous scaffold and preparation method thereof |
| KR20160059761A (en) * | 2014-11-19 | 2016-05-27 | 단국대학교 천안캠퍼스 산학협력단 | A method of preparing a core-shell structured fibrous scaffold |
| CN106730035A (en) * | 2016-12-30 | 2017-05-31 | 北京化工大学 | A kind of preparation method comprising overloading medicine slow-released system bone renovating material |
| CN106975106A (en) * | 2017-03-31 | 2017-07-25 | 北京化工大学 | A kind of double-deck Bone Defect Repari membrane material and preparation method thereof |
-
2017
- 2017-08-18 CN CN201710710641.XA patent/CN107625995B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101509153A (en) * | 2009-03-23 | 2009-08-19 | 东华大学 | Method for producing shell-core structure medicament nano-fibre with coaxial electrostatic spinning technology |
| US20140186413A1 (en) * | 2012-12-27 | 2014-07-03 | Industry-Academic Cooperation Foundation, Dankook University | Preparation method of core-shell structured fibrous scaffolds |
| CN103948974A (en) * | 2013-12-30 | 2014-07-30 | 北京化工大学 | Drug-loading type guided tissue regeneration membrane and preparation method thereof |
| CN103893819B (en) * | 2014-03-20 | 2015-07-15 | 北京大学第三医院 | Coaxial electrostatic spinning fibrous scaffold and preparation method thereof |
| KR20160059761A (en) * | 2014-11-19 | 2016-05-27 | 단국대학교 천안캠퍼스 산학협력단 | A method of preparing a core-shell structured fibrous scaffold |
| CN104524643A (en) * | 2014-11-26 | 2015-04-22 | 北京化工大学 | Halloysite-nanotube-containing drug-loaded type guide tissue regeneration membrane and preparation method thereof |
| CN106730035A (en) * | 2016-12-30 | 2017-05-31 | 北京化工大学 | A kind of preparation method comprising overloading medicine slow-released system bone renovating material |
| CN106975106A (en) * | 2017-03-31 | 2017-07-25 | 北京化工大学 | A kind of double-deck Bone Defect Repari membrane material and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| YUFEI TANG 等: "Fabrication of PLGA/HA (core)-collagen/amoxicillin (shell) nanofiber membranes through coaxial electrospinning for guided tissue regeneration", 《COMPOSITES SCIENCE AND TECHNOLOGY》 * |
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108096630B (en) * | 2018-01-29 | 2020-09-04 | 暨南大学 | Icariin and deferoxamine-loaded polylactic acid-based bone tissue scaffold and preparation method and application thereof |
| CN108096630A (en) * | 2018-01-29 | 2018-06-01 | 暨南大学 | A kind of polylactic acid base tissue scaffold design and preparation method and application for carrying icariin and Deferoxamine |
| CN108144116A (en) * | 2018-02-26 | 2018-06-12 | 丁文铃 | A kind of novel antibacterial artificial ligament |
| CN108578777A (en) * | 2018-05-06 | 2018-09-28 | 西北工业大学 | A kind of artificial os osseum holder preparation method that growth factor concentration gradient is controllable |
| CN108578777B (en) * | 2018-05-06 | 2021-05-07 | 西北工业大学 | A kind of artificial hard bone scaffold preparation method with controllable growth factor concentration gradient |
| CN108744061A (en) * | 2018-06-28 | 2018-11-06 | 广州贝奥吉因生物科技有限公司 | A kind of strontium-doped hydroxyapatite/fibroin albumen/heparin compound rest and its preparation method and application of load BMP-2 |
| CN108744061B (en) * | 2018-06-28 | 2021-05-11 | 广州贝奥吉因生物科技有限公司 | BMP-2-loaded strontium-doped hydroxyapatite/silk fibroin/heparin composite scaffold and preparation method and application thereof |
| WO2020186714A1 (en) * | 2019-03-15 | 2020-09-24 | 深圳市光远生物材料有限责任公司 | Drug-loaded nanocomposite fiber membrane system, preparation method therefor and use thereof |
| CN114099759B (en) * | 2020-08-28 | 2022-07-12 | 北京化工大学 | Fiber wound repair bracket loaded with phase change material particles and preparation method and application thereof |
| CN114108177B (en) * | 2020-08-28 | 2022-12-27 | 北京化工大学 | Artificial skin material capable of triggering growth factor stage release by photo-thermal, preparation method and application thereof |
| CN114108177A (en) * | 2020-08-28 | 2022-03-01 | 北京化工大学 | An artificial skin material capable of photothermally triggering the phased release of growth factors and its preparation method and application |
| CN114099759A (en) * | 2020-08-28 | 2022-03-01 | 北京化工大学 | Fiber wound repair scaffold loaded with phase change material particles and its preparation method and application |
| CN112957347A (en) * | 2021-02-03 | 2021-06-15 | 北京市创伤骨科研究所 | Skin layer-by-layer gradient slow-release nursing film |
| CN113797178A (en) * | 2021-03-29 | 2021-12-17 | 中山大学附属第三医院（中山大学肝脏病医院） | Multifunctional composite material and preparation method and application thereof |
| CN113797178B (en) * | 2021-03-29 | 2024-03-22 | 中山大学附属第三医院（中山大学肝脏病医院） | Multifunctional composite material and preparation method and application thereof |
| CN114432503A (en) * | 2022-04-12 | 2022-05-06 | 北京大学口腔医学院 | Drug-loaded bone repair material and preparation method and application thereof |
| CN115300669A (en) * | 2022-08-24 | 2022-11-08 | 上海睿植康医疗科技有限公司 | Fiber membrane and preparation method and application thereof |
| CN116212119A (en) * | 2023-03-28 | 2023-06-06 | 汕头大学 | A hydrogel patch for promoting bone repair and preparation method thereof |
| CN116212119B (en) * | 2023-03-28 | 2024-06-11 | 汕头大学 | Hydrogel patch for promoting bone repair and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107625995B (en) | 2020-07-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107625995A (en) | Multilayer coaxial fiber bone repair membrane material and preparation method thereof | |
| CN106975106A (en) | A kind of double-deck Bone Defect Repari membrane material and preparation method thereof | |
| Zhou et al. | Electrospun poly (3-hydroxybutyrate-co-4-hydroxybutyrate)/graphene oxide scaffold: enhanced properties and promoted in vivo bone repair in rats | |
| Wei et al. | 3D printing of silk fibroin-based hybrid scaffold treated with platelet rich plasma for bone tissue engineering | |
| Liu et al. | Biomimetic organic-inorganic hybrid hydrogel electrospinning periosteum for accelerating bone regeneration | |
| Janmohammadi et al. | Electrospun polycaprolactone scaffolds for tissue engineering: a review | |
| Yin et al. | Recent advances in scaffold design and material for vascularized tissue‐engineered bone regeneration | |
| Wu et al. | Enhanced bone regeneration of the silk fibroin electrospun scaffolds through the modification of the graphene oxide functionalized by BMP-2 peptide | |
| Tang et al. | Functional biomaterials for tendon/ligament repair and regeneration | |
| CN106730035B (en) | Preparation method of bone repair material containing multi-drug-loaded slow-release system | |
| Lu et al. | Effects of hydroxyapatite-containing composite nanofibers on osteogenesis of mesenchymal stem cells in vitro and bone regeneration in vivo | |
| Liu et al. | Hydrogel scaffolds in bone regeneration: Their promising roles in angiogenesis | |
| Yin et al. | Physicochemical and biological characteristics of BMP-2/IGF-1-loaded three-dimensional coaxial electrospun fibrous membranes for bone defect repair | |
| CN107397973B (en) | A four-layer coaxial fiber wound dressing and preparation method thereof | |
| Oh et al. | Nanofiber for cardiovascular tissue engineering | |
| Shi et al. | Silk fibroin-based complex particles with bioactive encrustation for bone morphogenetic protein 2 delivery | |
| Chung et al. | Development of an omentum-cultured oesophageal scaffold reinforced by a 3D-printed ring: feasibility of an in vivo bioreactor | |
| Zhang et al. | Poly-ε-caprolactone/Whitlockite electrospun bionic membrane with an osteogenic–angiogenic coupling effect for periosteal regeneration | |
| CN114099759B (en) | Fiber wound repair bracket loaded with phase change material particles and preparation method and application thereof | |
| CN104524643A (en) | Halloysite-nanotube-containing drug-loaded type guide tissue regeneration membrane and preparation method thereof | |
| Allo et al. | Role of bioactive 3D hybrid fibrous scaffolds on mechanical behavior and spatiotemporal osteoblast gene expression | |
| CN113171496B (en) | Porous PCL/collagen artificial periosteum with oriented drug sustained release function and preparation method thereof | |
| WO2021077042A1 (en) | Fiber-based scaffolds for tendon cell migration and regeneration | |
| Wu et al. | The synergetic effect of bioactive molecule–loaded electrospun core‐shell fibres for reconstruction of critical‐sized calvarial bone defect—The effect of synergetic release on bone Formation | |
| Hussain et al. | Biomedical applications of nanofiber scaffolds in tissue engineering |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |