CN1378445B - 药物释放生物可降解纤维植入物 - Google Patents
药物释放生物可降解纤维植入物 Download PDFInfo
- Publication number
- CN1378445B CN1378445B CN008140227A CN00814022A CN1378445B CN 1378445 B CN1378445 B CN 1378445B CN 008140227 A CN008140227 A CN 008140227A CN 00814022 A CN00814022 A CN 00814022A CN 1378445 B CN1378445 B CN 1378445B
- Authority
- CN
- China
- Prior art keywords
- fiber
- compositions
- therapeutic agents
- polymer
- poly
- 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.)
- Expired - Lifetime
Links
- 239000000835 fiber Substances 0.000 title claims abstract description 243
- 239000003814 drug Substances 0.000 title claims abstract description 126
- 229940079593 drug Drugs 0.000 title description 19
- 239000007943 implant Substances 0.000 title description 9
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 79
- 239000000203 mixture Substances 0.000 claims abstract description 71
- 238000000034 method Methods 0.000 claims abstract description 55
- 229920002988 biodegradable polymer Polymers 0.000 claims abstract description 24
- 239000004621 biodegradable polymer Substances 0.000 claims abstract description 24
- 229920000642 polymer Polymers 0.000 claims description 68
- 108090000623 proteins and genes Proteins 0.000 claims description 68
- 229920001661 Chitosan Polymers 0.000 claims description 54
- 239000002904 solvent Substances 0.000 claims description 35
- 230000008859 change Effects 0.000 claims description 33
- 239000003153 chemical reaction reagent Substances 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 19
- 102000004169 proteins and genes Human genes 0.000 claims description 17
- 230000033115 angiogenesis Effects 0.000 claims description 15
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 claims description 14
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 14
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 14
- 229920001432 poly(L-lactide) Polymers 0.000 claims description 14
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 12
- 102000013275 Somatomedins Human genes 0.000 claims description 10
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 10
- 239000004094 surface-active agent Substances 0.000 claims description 10
- 230000006907 apoptotic process Effects 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 229920001577 copolymer Polymers 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 229920001184 polypeptide Polymers 0.000 claims description 7
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 7
- 102000004127 Cytokines Human genes 0.000 claims description 6
- 108090000695 Cytokines Proteins 0.000 claims description 6
- 229920002732 Polyanhydride Polymers 0.000 claims description 6
- 238000009954 braiding Methods 0.000 claims description 6
- 150000004676 glycans Chemical class 0.000 claims description 5
- 229920001282 polysaccharide Polymers 0.000 claims description 5
- 239000005017 polysaccharide Substances 0.000 claims description 5
- 241000463219 Epitheca Species 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003146 anticoagulant agent Substances 0.000 claims description 4
- 229940127219 anticoagulant drug Drugs 0.000 claims description 4
- 230000001965 increasing effect Effects 0.000 claims description 4
- 229960000448 lactic acid Drugs 0.000 claims description 4
- 108091033319 polynucleotide Proteins 0.000 claims description 4
- 102000040430 polynucleotide Human genes 0.000 claims description 4
- 239000002157 polynucleotide Substances 0.000 claims description 4
- 108010035532 Collagen Proteins 0.000 claims description 3
- 102000008186 Collagen Human genes 0.000 claims description 3
- 239000000701 coagulant Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 238000003384 imaging method Methods 0.000 claims description 3
- 229920001610 polycaprolactone Polymers 0.000 claims description 3
- 239000004632 polycaprolactone Substances 0.000 claims description 3
- -1 polydepsipeptides Polymers 0.000 claims description 3
- 238000011160 research Methods 0.000 claims description 3
- 102000004190 Enzymes Human genes 0.000 claims description 2
- 108090000790 Enzymes Proteins 0.000 claims description 2
- 102000009123 Fibrin Human genes 0.000 claims description 2
- 108010073385 Fibrin Proteins 0.000 claims description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 claims description 2
- 239000002975 chemoattractant Substances 0.000 claims description 2
- 239000002872 contrast media Substances 0.000 claims description 2
- 229950003499 fibrin Drugs 0.000 claims description 2
- 239000002955 immunomodulating agent Substances 0.000 claims description 2
- 230000002584 immunomodulator Effects 0.000 claims description 2
- 229940121354 immunomodulator Drugs 0.000 claims description 2
- 239000003226 mitogen Substances 0.000 claims description 2
- 239000013603 viral vector Substances 0.000 claims description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims 2
- 108091005573 modified proteins Chemical class 0.000 claims 2
- 102000035118 modified proteins Human genes 0.000 claims 2
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims 1
- 229920002101 Chitin Polymers 0.000 claims 1
- 229920001287 Chondroitin sulfate Polymers 0.000 claims 1
- 229920001651 Cyanoacrylate Polymers 0.000 claims 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 claims 1
- 229920001503 Glucan Polymers 0.000 claims 1
- 229920002971 Heparan sulfate Polymers 0.000 claims 1
- 239000004677 Nylon Substances 0.000 claims 1
- 229920001710 Polyorthoester Polymers 0.000 claims 1
- 229940072056 alginate Drugs 0.000 claims 1
- 229920000615 alginic acid Polymers 0.000 claims 1
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 229920003232 aliphatic polyester Polymers 0.000 claims 1
- 229920002678 cellulose Polymers 0.000 claims 1
- 239000001913 cellulose Substances 0.000 claims 1
- 229940059329 chondroitin sulfate Drugs 0.000 claims 1
- 229960000633 dextran sulfate Drugs 0.000 claims 1
- 229920000669 heparin Polymers 0.000 claims 1
- 229960002897 heparin Drugs 0.000 claims 1
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims 1
- 229920001778 nylon Polymers 0.000 claims 1
- 229920000747 poly(lactic acid) Polymers 0.000 claims 1
- 229920002627 poly(phosphazenes) Polymers 0.000 claims 1
- 238000009826 distribution Methods 0.000 abstract description 9
- 238000000338 in vitro Methods 0.000 abstract description 2
- 238000001727 in vivo Methods 0.000 abstract 1
- 230000002123 temporal effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 61
- 108020004414 DNA Proteins 0.000 description 35
- 230000001112 coagulating effect Effects 0.000 description 34
- 239000000839 emulsion Substances 0.000 description 25
- 230000014509 gene expression Effects 0.000 description 21
- 239000000758 substrate Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 210000001519 tissue Anatomy 0.000 description 19
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 18
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 18
- 210000002744 extracellular matrix Anatomy 0.000 description 17
- 239000004005 microsphere Substances 0.000 description 15
- 229920005594 polymer fiber Polymers 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 230000006870 function Effects 0.000 description 14
- 239000000463 material Substances 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 230000032258 transport Effects 0.000 description 12
- 210000004204 blood vessel Anatomy 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 11
- 230000001939 inductive effect Effects 0.000 description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000007983 Tris buffer Substances 0.000 description 9
- 239000003513 alkali Substances 0.000 description 9
- 239000011159 matrix material Substances 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 230000029663 wound healing Effects 0.000 description 8
- 230000008901 benefit Effects 0.000 description 7
- 230000012010 growth Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 206010052428 Wound Diseases 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 108010082117 matrigel Proteins 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- 108091026890 Coding region Proteins 0.000 description 5
- 206010040943 Skin Ulcer Diseases 0.000 description 5
- 108091081024 Start codon Proteins 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 230000012292 cell migration Effects 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 230000035876 healing Effects 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 230000001537 neural effect Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- 230000014616 translation Effects 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 241000233803 Nypa Species 0.000 description 4
- 235000005305 Nypa fruticans Nutrition 0.000 description 4
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 4
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 4
- 239000002870 angiogenesis inducing agent Substances 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 210000001508 eye Anatomy 0.000 description 4
- 239000004744 fabric Substances 0.000 description 4
- 238000009940 knitting Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical class 0.000 description 4
- 210000001328 optic nerve Anatomy 0.000 description 4
- 230000008520 organization Effects 0.000 description 4
- 230000008439 repair process Effects 0.000 description 4
- 231100000019 skin ulcer Toxicity 0.000 description 4
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 4
- 231100000397 ulcer Toxicity 0.000 description 4
- 241000701161 unidentified adenovirus Species 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 3
- 102000009027 Albumins Human genes 0.000 description 3
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 3
- 208000010412 Glaucoma Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 108010025020 Nerve Growth Factor Proteins 0.000 description 3
- 102000007072 Nerve Growth Factors Human genes 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 206010072170 Skin wound Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000000975 bioactive effect Effects 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 230000036770 blood supply Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 238000007599 discharging Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 210000003516 pericardium Anatomy 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 210000002027 skeletal muscle Anatomy 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 230000017423 tissue regeneration Effects 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- 108010085895 Laminin Proteins 0.000 description 2
- 108010040897 Microfilament Proteins Proteins 0.000 description 2
- 102000002151 Microfilament Proteins Human genes 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010038934 Retinopathy proliferative Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 102100032889 Sortilin Human genes 0.000 description 2
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 2
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 2
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 2
- 241000700618 Vaccinia virus Species 0.000 description 2
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000027746 artery morphogenesis Effects 0.000 description 2
- 230000028600 axonogenesis Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000013228 contact guidance Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 230000008175 fetal development Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229940096397 interleukin-8 Drugs 0.000 description 2
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 210000003041 ligament Anatomy 0.000 description 2
- 229960000274 lysozyme Drugs 0.000 description 2
- 239000004325 lysozyme Substances 0.000 description 2
- 235000010335 lysozyme Nutrition 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000003632 microfilament Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 210000003497 sciatic nerve Anatomy 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 108010014657 sortilin Proteins 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 210000002435 tendon Anatomy 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000008467 tissue growth Effects 0.000 description 2
- 210000005239 tubule Anatomy 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical class C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- 102000002734 Collagen Type VI Human genes 0.000 description 1
- 108010043741 Collagen Type VI Proteins 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 208000008960 Diabetic foot Diseases 0.000 description 1
- 206010056340 Diabetic ulcer Diseases 0.000 description 1
- 108010001394 Disaccharidases Proteins 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 208000035126 Facies Diseases 0.000 description 1
- 108010003471 Fetal Proteins Proteins 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 229920001499 Heparinoid Polymers 0.000 description 1
- 241001441571 Hiodontidae Species 0.000 description 1
- 101100321817 Human parvovirus B19 (strain HV) 7.5K gene Proteins 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 101150017040 I gene Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 1
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 1
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 229920001872 Spider silk Polymers 0.000 description 1
- 102100031372 Thymidine phosphorylase Human genes 0.000 description 1
- 108700023160 Thymidine phosphorylases Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 208000000558 Varicose Ulcer Diseases 0.000 description 1
- 108091027569 Z-DNA Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 239000003876 biosurfactant Substances 0.000 description 1
- 230000007698 birth defect Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000013601 cosmid vector Substances 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000007646 directional migration Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000010595 endothelial cell migration Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003725 endotheliocyte Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical class C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 239000002554 heparinoid Substances 0.000 description 1
- 210000003701 histiocyte Anatomy 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000008004 immune attack Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 210000001665 muscle stem cell Anatomy 0.000 description 1
- 210000002346 musculoskeletal system Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 108010065781 myosin light chain 2 Proteins 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 230000003448 neutrophilic effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 230000000661 pacemaking effect Effects 0.000 description 1
- 239000012785 packaging film Substances 0.000 description 1
- 229920006280 packaging film Polymers 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 229920013730 reactive polymer Polymers 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 210000002356 skeleton Anatomy 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 210000001604 vasa vasorum Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000009941 weaving Methods 0.000 description 1
Images
Classifications
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F1/00—General methods for the manufacture of artificial filaments or the like
- D01F1/02—Addition of substances to the spinning solution or to the melt
- D01F1/10—Other agents for modifying properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F6/00—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
- D01F6/58—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from homopolycondensation products
- D01F6/62—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from homopolycondensation products from polyesters
- D01F6/625—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from homopolycondensation products from polyesters derived from hydroxy-carboxylic acids, e.g. lactones
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
- D01F8/04—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers
- D01F8/14—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers with at least one polyester as constituent
-
- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
- D06M15/00—Treating fibres, threads, yarns, fabrics, or fibrous goods made from such materials, with macromolecular compounds; Such treatment combined with mechanical treatment
- D06M15/01—Treating fibres, threads, yarns, fabrics, or fibrous goods made from such materials, with macromolecular compounds; Such treatment combined with mechanical treatment with natural macromolecular compounds or derivatives thereof
- D06M15/03—Polysaccharides or derivatives thereof
-
- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
- D06M16/00—Biochemical treatment of fibres, threads, yarns, fabrics, or fibrous goods made from such materials, e.g. enzymatic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/11—Surgical instruments, devices or methods, e.g. tourniquets for performing anastomosis; Buttons for anastomosis
- A61B17/1128—Surgical instruments, devices or methods, e.g. tourniquets for performing anastomosis; Buttons for anastomosis of nerves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
- A61K9/0051—Ocular inserts, ocular implants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/258—Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/426—Immunomodulating agents, i.e. cytokines, interleukins, interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
- A61L2300/604—Biodegradation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/30—Self-sustaining carbon mass or layer with impregnant or other layer
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T442/00—Fabric [woven, knitted, or nonwoven textile or cloth, etc.]
- Y10T442/20—Coated or impregnated woven, knit, or nonwoven fabric which is not [a] associated with another preformed layer or fiber layer or, [b] with respect to woven and knit, characterized, respectively, by a particular or differential weave or knit, wherein the coating or impregnation is neither a foamed material nor a free metal or alloy layer
- Y10T442/2525—Coating or impregnation functions biologically [e.g., insect repellent, antiseptic, insecticide, bactericide, etc.]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Textile Engineering (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Manufacturing & Machinery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明提供了组织工程组合物和方法,其中为体外和体内使用制备了生长细胞的三维基质。此基质包含可以控制运送治疗剂的生物可降解聚合物纤维。所释放的治疗剂的空间和时间分布由在基质中使用规定非均质模式的治疗剂而控制。
Description
发明背景
本发明要求1999年8月6日提交的临时申请60/147,827的优先权。
1.发明背景
本发明涉及医学和组织工程领域,特别是涉及药物释放生物可降解植入物。
2.相关领域描述
组织工程是用活细胞替代动物或人体内由损伤、疾病或先天性缺陷造成的功能缺失的学科。这些替代细胞可以是自体的、同种异体的,或在有限的情况中为异种的。组织工程领域是医学的一项新领域和最佳程序,但仍需进一步阐明。
目前,研究者将一些初级手段用于组织工程。一种是从健康供体获得细胞,优选从同一个体,或至少从同种的适当供体获得细胞,并在体外使这些细胞生长在支架上。该支架一般为三维聚合物网,通常由生物可降解纤维组成。粘附在聚合物网上的细胞一般可以被诱导繁殖。可以将这些由细胞填充的支架植入受损宿主,其目的是这些细胞执行其生理功能并避免受宿主免疫系统破坏。到目前为止,使用纯化细胞系是非常重要的,因为非自体免疫细胞的诱导可以上调强烈的宿主免疫攻击。此方法的难点是支架必需很小,因为没有细胞可以在离氧气和营养物质几毫米远的地方存活。所以,不能用大支架,因为这种支架不能及时充分形成血管以保留内部区域的细胞。
在另一种方法中,直接将空的三维生物可降解聚合物支架植入病人,其目的是诱导宿主中适当类型的细胞迁移到聚合物支架中。优点是血管生成可以与细胞迁移到基质中同时发生。主要问题是目前没有方法可以保证适当的细胞类型迁移到支架,以及维持机械和生物特征以提供病人的生理需要。
在前面的两种方法中,支架是生物可降解的,表示它将随时间进展而被化学和机械破坏。当发生这种破坏时,细胞分泌它们自己的细胞外基质,这在细胞存活和功能中起关键作用。在正常组织中,在组织的构成细胞和细胞外周基质间存在活性和动态互利的交换。细胞外基质提供调节细胞形态学特征和表型性状的化学信号,并可以诱导细胞分裂、分化甚至细胞死亡。另外,细胞也不断重排细胞外基质。细胞降解并重建细胞外基质并分泌化学物质到基质,供它们自己或其它迁移到此区域的细胞使用。也发现细胞外基质是胚胎发育最重要的成分之一。先趋细胞分泌帮助后继细胞分化为适当终表型的化学信号。例如,这种化学信号使神经脊细胞分化为轴突、平滑肌细胞或神经元。
细胞外基质和组织细胞间的综合关系将细胞外基质确立为组织工程的一个重要参数。如果需要细胞表现特定行为,那么细胞外基质必需提供适当的环境和适当的化学/生物信号以诱导该细胞类型的这种行为。目前还不可能如实复制有生物活性的细胞外基质。所以,一些研究者使用生物可降解基质,使细胞可以在外源基质降解时建立自己的细胞外基质。
在前面所描述的组织工程方法中,聚合物支架不仅提供机械支持,而且也提供了新组织或器官需要的三维外形。由于细胞必需接近氧气和营养成分来源以便存活和行使功能,目前主要的限制是供血的限制。目前大多数方法没有提供积极帮助引入血管并使其贯串聚合物基质的特定方法。这就给聚合物基质的物理大小和外形设置了限制。目前广泛应用于临床的唯一组织工程设备为人工皮肤,根据定义有限定的厚度。本发明提供促进适当细胞类型定向迁移到制造的细胞外基质的组合物和方法。通过定向的特异性三维细胞迁移和功能模式,可以诱导定向的血管生成,这克服了目前聚合物植入物外形和大小的限制。它也保证了适当细胞类型将物理位于基质中的特定位置。提供了将表型表达调节为时间和空间的函数的组合物和方法。
发明概述
本发明提供了组织工程组合物和方法,其中为体外和体内使用制备了生长细胞的三维基质。基质包括可以控制运送治疗剂的生物可降解聚合物纤维。所释放治疗剂的空间和时间分布通过使用预定非均质模式的聚合物纤维而控制,可以作为时间的函数释放一种或更多治疗剂。名词“支架”、“支架基质”和“纤维支架”在这里也用于描述本发明的三维基质。在本发明内容中的“规定的非均质模式”表示将特定纤维引入支架基质从而达到所需要的支架基质中一种或更多治疗剂的三维分布。治疗剂在基质纤维中的分布控制试剂从聚合物纤维释放后在基质的胞间基质中的空间分布。以这种方式,可以在三维基质结构和基质紧邻环境中建立所需浓度梯度的空间轮廓。时间分布通过纤维的聚合物组合物以及通过纤维内同轴层的使用而控制。
本发明的一方面是包含生物可降解聚合物纤维支架的生物适合的植入物组合物。在本发明的各种实施方案中,纤维间的距离可以是约50微米,约70微米,约90微米,约100微米,约120微米,约140微米,约160微米,约180微米,约200微米,约220微米,约240微米,约260微米,约280微米,约300微米,约320微米,约340微米,约360微米,约380微米,约400微米,约450微米或约500微米。在各种实施方案中,纤维间的距离可以小于50微米或大于500微米。
此外,在本发明的各种实施方案中,纤维直径将为约20微米,约40微米,约60微米,约80微米,约100微米,约120微米,约140微米,约160微米,约180微米,约200微米,约220微米,约240微米,约260微米,约280微米,约300微米,约320微米,约340微米,约360微米,约380微米,约400微米,约450微米或约500微米(包括中间长度)。在各种实施方案中,纤维直径可以小于20微米或大于500微米。优选地,纤维直径将从约60微米到约80微米。
“约”在本文中意指1-10微米的范围,包括此范围中的中间长度。很容易理解,在本文中的“中间长度”表示在提出范围之间的长度,如21,22,23,24,25,26,27,28,29等;30,31,32等;50,51,52,53等;100,101,102,103等;150,151,152,153等;包括所有200-500之间的所有整数。
发明者也考虑了基质可以是编织的、非编织的、编结的、接合的或者是两种或更多这些制剂的组合。例如,潜在应用如人工动脉可以很好地使用编织的、非编织的和接合的制剂或所有四种制剂的组合。在本发明的某些实施方案中,编结的组合物可以在用于肌腱和韧带时发现特殊应用。这种编结可以提供例如高强度。
在本发明的某些实施方案中,纤维包含一种或更多以规定非均质模式在支架基质中分布的治疗剂。在一种实施方案中,纤维可以包含两种或更多生物可降解聚合物含量不同的纤维亚型。纤维或纤维亚型可以包含多种同轴生物可降解聚合物层。
在本发明的另一种实施方案中,纤维或纤维亚型包含一种或更多治疗剂,使得治疗剂浓度或治疗剂沿纤维或纤维亚型纵轴而改变。活性试剂的浓度可以作为沿纤维纵轴距离的函数,以线性、对数或以任何需要的方式改变。此改变可以是单方向的,即一种或更多治疗剂的含量从纤维或纤维亚型的第一末端到纤维或纤维亚型的第二末端逐渐减小。此含量也可以以双向方式改变,即治疗剂的含量从纤维或纤维亚型的第一末端增加到最大,然后向纤维或纤维亚型的第二末端逐渐减小。
在本发明的某些实施方案中,包含支架的纤维亚型可能不含有治疗剂。对于含有一种或更多治疗剂的纤维,试剂可以包括生长因子、免疫调节剂、促进血管生成的化合物、抑制血管生成的化合物、抗炎化合物、抗生素、细胞因子、抗凝剂、促凝剂、趋化剂、促进凋亡的试剂、抑制凋亡的试剂、促有丝分裂剂、放射性试剂或用于成像研究的造影剂、病毒载体、多核苷酸、治疗基因、DNA、RNA、多肽、粘多糖、糖、糖蛋白。治疗剂也可包括长期维持给予病人的药物如心血管药物、包括血压、起搏、抗心律失常、β阻滞药物和基于钙离子通道的药物。本发明的治疗剂也可包括抗震颤和其它抗癫痫或其它运动疾病的药物。这些试剂也可以包括长期药疗如避孕药和生育药物。它们可以包括神经药物如多巴胺和相关药物以及生理或其它行为药物。治疗剂也可以包括化学清除剂如螯合剂和抗氧化剂。其中治疗剂促进血管生成,此试剂可以是血管内皮生长因子。治疗剂可以是合成或天然药物、蛋白质、DNA、RNA或细胞(有或无遗传改变)。根据长期执行行的专利法,在说明书和权利要求中与“包含”或“包括”结合使用的“一种”表示一种或更多。
总的说来,本发明考虑了使用药物引入到本发明的生物可降解聚合物纤维。这里用到的名词“药物”是定义为可以给予生物体,调节或改变生物体生理的化学物质。这里用到的名词“药物”更优选定义为任何用于治疗或预防疾病的物质。药物包括合成和天然存在的毒素和生物影响物质以及公认的药物,如“The Physicians DeskReference,”471st edition,pages 101-321;“Goodman and Gilman’sThe Pharmacological Basis of Therapeutics”8th Edition(1990),pages 84-1614 and 1655-1715;“The United States Pharmacopeia,The National Formulary”,USPX X II NF X V II(1990)所列出的,在此引入这些参考文献的化合物作为参考。名词“药物”也包括有提示特征而在美国没有发现或无法得到的化合物。名词“药物”包括药物的激活前、激活的和代谢物形式。
生物可降解聚合物可以是单聚合物或共聚合物或聚合物的混合并可以包含聚(L-乳酸)、聚(DL-乳酸)、聚己酸内酯、聚(乙醇酸)、聚酐、脱乙酰壳多糖、或硫酸脱乙酰壳多糖、或天然聚合物或多肽,如重构胶原或蜘蛛丝。
本发明的一方面是包含含有一种或更多治疗剂的生物可降解聚合物纤维的药物运送纤维组合物。在一种实施方案中,纤维中的一种或更多治疗组合物的含量沿纤维纵轴改变,从而使治疗剂的含量从纤维的第一末端到第二末端逐渐减少。在另一种实施方案中,纤维包含多种同轴生物可降解聚合物层。药物运送纤维组合物可以植入身体的许多位点,包括真皮组织、心脏组织、软组织、神经、骨和眼。眼内植入特别用于治疗白内障、糖尿病诱导的增殖性视网膜病变和非增殖性视网膜病变、青光眼、黄斑变性、XXXX色素变性。
本发明的另一方面是控制纤维支架植入物内的一种或更多治疗剂的空间和时间浓度,包含将纤维支架植入宿主的方法。空间浓度可以跨多纤维或通过沿纤维长度加以浓度梯度而提供。纤维支架一般包含含有一种或多种治疗剂的生物可降解聚合物纤维,其中治疗剂以规定的非均质模式分布在纤维支架中。宿主一般是动物,优选为哺乳动物,更优选为人。
而本发明的另一方面是生产制备可以控制一种或更多治疗剂的空间和时间浓度的植入物的纤维支架的方法。这种方法一般包含在三维纤维支架中形成生物可降解聚合物纤维。这种生物可降解聚合物纤维包含一种或更多治疗剂。治疗剂以规定的非均质模式分布在纤维支架中。
进一步预见到本发明的支架可以用于定向和/或组织组织结构,细胞迁移和基质沉积并参与或促进普通伤口愈合。
在本发明的另一种实施方案中,提供了从脱乙酰壳多糖建立药物释放纤维的方法,包含将盐酸作为溶剂和Tris碱作为凝固浴。例如,盐酸浓度可以从约0.25%到约5%,或从约1%到约2%,包括在此范围内的所有浓度。在此方法中,tris碱浓度可以是,例如从约2%到约25%,从约4%到约17%,或从约5%到约15%,包括在此范围内的所有浓度。在本发明的一种实施方案中,此方法可以包含含有不同脱乙酰程度的脱乙酰壳多糖的非均质性混合物。此方法也可以包含建立含有不同脱乙酰程度的脱乙酰壳多糖片段的药物释放纤维。
本发明的药物释放纤维可以从例如脱乙酰壳多糖和细胞外基质建立。在依据本发明建立药物释放纤维的过程中,脱乙酰壳多糖浓度可以是,例如,从约0.5wt.%到约10wt.%,从约1wt.%到约7wt.%,从约2wt.%到约5wt.%,从约3wt.%到约4wt.%,或约3.5wt.%。在本发明的一种实施方案中,细胞外基质浓度可以从约1vol.%到约20vol.%,从约2vol.%到约15vol.%,从约3vol.%到约10vol.%,从约4vol.%到约6vol.%,包括约5vol.%。在此方法中,纤维可以包被于细胞外基质。
本发明使用的脱乙酰壳多糖可以是硫酸化的或非硫酸化的。在本发明的一种实施方案中,当使用硫酸脱乙酰壳多糖时浓度可以从约0.025wt.%到约2wt.%,从约0.05wt.%到约1wt.%,从约0.1wt.%到约0.5wt.%,从约0.15wt.%到约0.3wt.%,包括约0.2wt.%。在此方法中,脱乙酰壳多糖和硫酸脱乙酰壳多糖可以被挤出到纤维。
在本发明的另一种实施方案中,提供了建立药物释放纤维的方法,这种方法包括在酸和凝固浴中添加聚(L-乳酸)微球体到脱乙酰壳多糖。在此方法中,酸可以是例如乙酸或盐酸。当酸为盐酸时,浓度可以是例如从约0.25%到约5%,或从约1%到约2%,包括1.2vol.%以及在此范围内的所有其它浓度。脱乙酰壳多糖浓度可以是例如,从约0.5wt.%到约10wt.%,从约1wt.%到约7wt.%,从约2wt.%到约5wt.%,从约3wt.%到约4wt.%,或约3.5wt.%。凝固浴可以包括氢氧化钠,例如,浓度为从约1vol.%到约20vol.%,从约2vol.%到约15vol.%,从约3vol.%到约10vol.%,从约4vol.%到约6vol.%,包括约5vol.%。在本发明的一种实施方案中,这种方法包括在从约1vol.%盐酸到约2vol.%盐酸中将聚(L-乳酸)微球体添加到约3.5wt.%脱乙酰壳多糖的溶液中,并使用包含从约5vol.%tris碱到约15vol.%tris碱的凝固浴。此方法可以进一步包括将表面活性剂加入溶液,包括白蛋白,例如从约1wt.%到约5wt.%的该白蛋白,包括约3wt.%。而在本发明的另一种实施方案中,脱乙酰壳多糖纤维的组合物包含第二种聚合物的微球体,该微球体包含一种或更多生物分子。此组合物可以包含一种为生物分子的表面活性剂。
而在本发明的另一种实施方案中,组合物包含一种含有脱乙酰壳多糖和细胞外基质的纤维。脱乙酰壳多糖可以是硫酸化的或非硫酸化的。
而在本发明的另一种实施方案中,组合物包含三维支架,该支架包含编织的、非编织的或接合的纤维,其中该纤维包含前面所描述的任何组合物。在一种实施方案中,本发明的组合物可以包含含有脱乙酰壳多糖、细胞外基质和生物分子的纤维。脱乙酰壳多糖可以是硫酸化或非硫酸化的。
而在本发明的另一种实施方案中,组合物包含非均质性纤维支架和前面所描述的生物分子,其中支架的所有纤维中的生物分子并不相同。在组合物中,脱乙酰基的程度可以作为沿纤维距离的函数而不同。组合物可以是细胞外基质。在本发明的某些实施方案中,组合物也可以包括硫酸化或非硫酸化脱乙酰壳多糖。
附图简述
下列附图形成本发明说明书的一部分,包含它们是用于证明本发明的某些方面。通过参考一幅或更多附图并结合这里列出的特定实施方案的详述,可以更好地理解本发明。
图1:表示纤维构型为形成图形的复杂三维编织支架。每条纤维可以加载一种或更多治疗剂。
图2:表示纤维构型为不形成图形的三维非编织支架。每条纤维可以加载一种或更多治疗剂。所有纤维可以含相同治疗剂或同一支架中的其它纤维可以使用许多不同的试剂。
图3A和图3B:纤维可以在如支架的应用中提供给机体短期机械支持。图3A说明了单个聚合物纤维可以维持管状体如动脉、静脉或导管的腔。图3B说明多个聚合物纤维可以维持管状体的腔。
图4:纤维可以被包被而形成同轴纤维。图4表示纤维可以有多种成分的包膜,每种成分加载不同治疗剂。
图5:表示图4所示有包膜纤维的释放动力学,此纤维有两种成分的包膜,每种加载不同的治疗剂。
图6A和图6B:纤维可以沿其长度包含线性梯度。图6A说明了沿长度包含治疗剂线性梯度的纤维。图6B图示了线性梯度。
图7:表示具有沿其长度改变的一种或更多治疗剂浓度的有条带的纤维。条带的分布和频率可以根据需要改变。
图8:描绘了构造含治疗剂的聚合物纤维的设备。
图9A和图9B:通过改变聚合物乳状液注入到凝固浴的速度与车床缠绕速度之比,观察到非常惊人的机械特征改变。图9A图示了缠绕速度与注入速度之比改变时的最终强度[Mpa]。表示了10-wt%,8-wt%和7.5-wt%的聚合物的结果。图9B图示了缠绕速度(Vw)与注入速度(Vi)之比改变时的延伸百分比。
图10A和图10B:纤维的机械特征可以作为聚合物溶剂、凝固浴溶剂、溶剂系统的相互作用、缠绕速度与注入速度之比、凝固浴中的总时间、乳状液中水相与聚合物溶液相之比、以及表面活性剂质量的函数而改变。图10A图示了当缠绕速度与注入速度之比(Vw/Vi)为26.82和23.49时最终强度随聚合物浓度(wt%)的改变。图10B说明了相同比例下弹性随聚合物重量百分比的改变。
图11A,图11B和图11C:产生不同表面质地的纤维。图11A表示有光滑表面质地的纤维。图11B表示有绒面质地的纤维。图11C表示有纵沟表面质地的纤维。
图12:说明纤维直径作为缠绕速度与注入速度之比(Vw/Vi)和重量百分比的改变。
图13:说明在“Y”连接处使用蝶形阀逐渐改变两种溶液之比,从而获得沿纤维长度的浓度梯度。
图14:说明使用独立泵和混合室而建立每厘米长度有已知浓度改变的控制良好的梯度。
图15:说明包装在硅胶或其它适当物质管中并加载了促进轴突生长的神经营养蛋白的平行列纤维。
发明详述
本发明为给组织工程应用中的生长细胞建立非均质的、编织的、接合的、或非编织的或编结的三维基质提供了组合物和方法。这些支架可以体外和体内应用,而且由于它们的非均质性而可以建立治疗剂的空间和时间分布。在本发明中,治疗剂可以包括药物、蛋白质、肽、单和双糖、多糖、糖蛋白、DNA、RNA、病毒或其它感兴趣的分子。本发明的治疗剂也包括用于帮助破坏有害组织如局部区域的肿瘤,或例如在目前支架应用中用于抑制健康组织的生长;或用于成像研究的标记物的放射性物质。
A.三维纤维基质
为建立本发明的非均质性支架,可以这里描述的方法将治疗剂包被于个体纤维中。治疗剂以控制的方式从每个个体纤维缓慢释放。纤维形式作为药物运送平台与其它本领域中公知的缓释试剂如微球体、多孔栓或贴剂相比有许多优点。纤维的主要优点是它们可以在有或没有形成图形的情况下提供复杂的三维编织(图1),或非编织(图2)支架,从而允许细胞附着、扩散、分化和成熟为适当功能的细胞。因为它们可以形成图形,可以编织成“智能织物”而根据释放的特定趋化因子诱导特定类型的细胞迁移到支架的特定区域。支架在胚胎发育和胚后组织中模拟细胞外基质物质的功能。另外,在一种唯一的支架中可以形成微丝,为不是天然记忆的组织修复或重构提供生长底物。
由于编织模式诱导适当细胞类型进入特定区域的能力,可以引入诱导织物中血管形成的链。这可以通过提供释放生长因子如血管内皮生长因子(VEGF)的纤维而实现。通过适当将含VEGF的纤维定位于编织模式中,可以制造大的组织,并且可以给这些组织中的细胞提供充足供血,使它们得到氧气和营养成分并可以清除废物。
纤维也具有在如支架(图3A和3B)的应用中提供给机体短期机械支持的优点,其中聚合物纤维可以保持管状体的腔,如动脉、静脉、导管(如胆管、输尿管、尿道、气管等)、消化道器官如食道、小肠、结肠和结缔组织如肌腱、韧带、肌肉和骨骼。纤维为康复过程中支持机械强度或张力提供了有用的结构。纤维对促进神经再生或神经或脊髓重构也是有用的。
另外,纤维可以被包被,形成图4所示的同轴纤维。每个包膜可以是不同聚合物物质或聚合物的组合,每层可以释放不同治疗剂或治疗剂的组合。包膜也可以被物理分割为多个部分,表示如果需要,可以以各种方向释放不同治疗剂。例如,如图4所描绘,纤维可以有两个成分包膜,每个成分加载不同治疗剂。所以,不仅上述各种治疗剂的空间分布是可能的,而且这些试剂可以有不同的释放动力学,从而产生治疗剂的时间分布。这种包膜纤维的释放动力学如图5所示。例如,如果纤维在核心聚合物外有两层包膜,那么可以释放三种不同的治疗剂或治疗剂的组合。外层包膜将释放它的治疗剂,然后是内层包膜,最后是核心纤维。所以,每种聚合物系统有自己的释放动力学分布图,可以由聚合物类型和该特定包膜层的处理条件而调整。每层包膜由不同聚合物组成并装载不同分子。这提供了每层控释动力学的能力。在不同时间释放不同试剂的能力在组织工程中特别重要,因为迅速分裂的细胞通常不显示同类型非分裂细胞的特定功能。对于本发明,通过释放适当的治疗剂,可以诱导细胞首先迁移到特定位置,然后进入迅速分裂相而填充组织空隙,然后分化为功能形式。
另外,已知细胞遵循浓度梯度。特定因子浓度的改变对细胞迁移的定向是重要的。所以,本发明提供了沿纤维长度获得治疗剂梯度的方法。图6A和6B描绘了线性梯度。通过本发明公开的方法,这种梯度可以是沿纤维长度距离的线性、指数、或其它任何形状的函数。它也可以是双向的,表示例如它可以两端低并在中间达到最高。这诱导细胞迁移并沿纤维的特定方向生长。经过扩展,通过本发明公开的方法,也可以产生有条带的纤维。这些带的分布和频率可以根据需要改变。所以,本发明的治疗剂的运送方面远远超过了微球体或栓的范围,以纤维为基础的“智能支架”超过了一般以纤维为基础的基质,指挥可存活组织的发育,提供三维生物建筑和机械支持。
B.生物可降解聚合物
本发明优选使用的聚合物包括单聚合物、共聚物或聚(L-乳酸)、聚(DL-乳酸)、聚己酸内酯、聚(乙二醇酸)、聚酐、脱乙酰壳多糖或硫酸脱乙酰壳多糖。也可以使用天然存在的聚合物如重构胶原或天然丝。本领域的技术人员会理解这些聚合物只是本发明使用的一类生物可降解聚合物基质的例子。其它生物可降解基质包括聚酐、聚原酸酯和聚(氨基酸)(Peppas and Langer,1994)。可以利用任何这种机制构造本发明使用的有控制特性的生物可降解基质。其它产生非毒性降解产物的生物可降解聚合物见表1。
表1
公认为生物可降解的主要聚合物
摘自Wong and Mooney,1997
C.促进血管生成的试剂
用聚合物纤维包被的一类治疗剂是促进血管生成的治疗剂。成功制造新组织要求建立血管网。血管生成的诱导由许多因子介导,其中的任何一种可以与本发明联合使用(Folkman and Klagsburn,1987,以及这里引用的参考文献,在此引入其全部内容作为参考)。血管生成因子的例子包括,但不限于:血管内皮生长因子(VEGF)或血管通透因子(VPF);成纤维细胞生长因子家族成员,包括酸性成纤维细胞生长因子(aFGF)和碱性成纤维细胞生长因子(bFGF);白介素-8(IL-8);表皮生长因子(EGF);血小板源上皮细胞生长因子(PD-ECGF);转化生长因子α和β(TGF-α,TGF-β);肿瘤坏死因子α(TNF-α);肝细胞生长因子(HGF);粒细胞-巨噬细胞集落刺激因子(GM-CSF);胰岛素生长因子-1(IGF-1);血管生长因子;促血管素;血纤蛋白和烟酰胺(Folkman and Klagsbrun,1987;Nagy et al.,1995)
D.细胞因子
在某些实施方案中考虑了引入本发明聚合物纤维的特定细胞因子的使用。下面的表2是考虑用于本发明的一些细胞因子和相关因子的例子,但不限于这些。
表2
E.多核苷酸
引入本发明的聚合物纤维中的多核苷酸包括全部范围的分子。此核苷酸因此包括基因组DNA,cDNA,单链DNA,双链DNA,三链DNA,寡核苷酸,Z-DNA,mRNA,tRNA和其它RNA。一般优选DNA分子,甚至用DNA表达治疗RNA,如核酶或反义RNA。
编码所选蛋白或RNA的“基因”或DNA节段一般是指含有编码所选蛋白或RNA序列的DNA节段,但是从获得DNA的种属的总基因组DNA中分离出或纯化。DNA节段和这些节段的更小的片段以及重组载体包括,例如,质粒、粘粒、噬菌体、逆转录病毒、腺病毒等都包括在名词“基因”和“DNA节段”的范围内。
为了简便,名词“基因”用于指功能蛋白或肽编码单位。本领域的技术人员将理解,此功能性名词包括基因组序列和cDNA序列。“基本从其它编码序列中分离出”表示感兴趣的基因形成DNA节段编码区的重要部分,且该DNA节段不包括天然存在编码DNA大的部分,如大的染色体片段或其它功能基因或cDNA编码区。当然,这是指原始分离出的DNA节段,且不排除由人工加入到节段中的基因或编码区,如编码前导肽或引导肽的序列。
只要使用的编码节段编码选择的蛋白或RNA并且不包括对靶细胞有严重不良作用的编码和调节序列,则本发明不要求使用高度纯化的DNA或载体。所以,也需要理解有用的核酸序列可以包括附加残基,如附加的编码区5′或3′部分的侧翼非编码序列,或可以包括各种内部序列,即已知在基因内出现的内含子。
可以从现有的,包括商业来源获得许多合适的DNA节段。也可以用一种或更多本领域技术人员公知的分子生物技术获得编码感兴趣蛋白的新DNA节段。例如,可以用具有设计序列的引物或探针筛选cDNA或基因组文库。多聚酶链式反应(PCR)也可以用于产生编码感兴趣蛋白的DNA片段。
在识别适当选择的基因或DNA分子后,可以将其插入本领域中公知的一种或多种载体,使得它可以在掺入靶细胞时指导选择的蛋白的表达和产生。在重组表达载体中,DNA节段的编码部分在启动子/增强子元素的控制下定位。启动子可以以与选定基因天然相关的启动子的形式存在,可以通过使用例如重组克隆和/或PCR技术分离位于编码节段或外显子上游的5′非编码序列而获得。
在另一种实施方案中,考虑了通过在重组或异源启动子的控制下定位编码DNA节段将获得某些优点。这里用到的重组或异源启动子意指正常情况下与其它选定基因在其天然环境中不相关的启动子。这些启动子可以包括正常情况下与其它选定基因和/或从细菌、病毒、真核动物或哺乳动物细胞分离的启动子相关的启动子。在天然情况下,使用有效指导DNA节段在所选靶细胞中表达的启动子是很重要的。
使用重组启动子来获得蛋白表达是分子生物学领域中的技术人员所公知的,例如,见Sanbrool et al.(1989;在此引入作为参考)。使用的启动子可以是构成的或可诱导的,并可以在适当的条件下使用从而指导引入DNA节段的高水平或调节的表达。在构成启动子控制下的基因表达不要求特异性底物的存在而诱导基因表达,并且将在细胞生长的所有条件下出现。相对地,由可诱导启动子控制的基因表达对诱导剂的存在与否是有反应的。
在这里可以使用从在哺乳细胞中生长的病毒基因组中分离的启动子,如RSV,痘苗病毒7.5K,SV40,HSV,腺病毒MLP,MMTV LTR和CMV启动子,以及由重组DNA或合成技术产生的启动子。目前的优选启动子如CMV,RSV LTR,单独的SV40启动子,和与SV40增强子组合的SV40启动子。
显示组织特异性的组织特异性启动子/增强子元素和转录控制区的例子包括,但不限于:在胰腺腺泡细胞中有活性的弹性蛋白酶I基因控制区;在胰腺细胞中有活性的胰岛素基因控制区;在淋巴细胞中有活性的免疫球蛋白基因控制区;在肝中有活性的白蛋白、1-抗胰蛋白酶和胎蛋白基因控制区;在骨髓细胞中有活性的珠蛋白基因控制区;在脑寡突细胞中有活性的髓鞘质碱性蛋白基因控制区;在骨骼肌中有活性的肌凝蛋白轻链-2基因控制区;以及在下丘脑中有活性的促性腺素释放激素基因控制区。为引入对前面所描述元素的进一步描述的参考,在此引入1996年4月12日提出的美国申请No.08/631,334,1997年4月11日提出的PCT申请No.PCT/US97/07301作为参考。
对插入蛋白编码序列足够的翻译也需要特异的起始信号。这些信号包括ATG起始密码子和邻近序列。当整个编码序列,包括起始密码子和邻近序列插入适当表达载体时,不再需要附加的翻译控制信号。然而,当只插入编码序列的一部分时,应该提供外源性翻译控制信号,包括ATG起始密码子。起始密码子必需与蛋白编码序列的读框相协调,以保证整个插入序列的翻译。这些外源性翻译控制信号和起始密码子可以是多种来源的,可以是天然的和合成的。可以通过包含转录衰减序列、增强子元素等增强表达的效率和控制。
可以使用许多载体,包括但不限于,由重组细菌噬菌体DNA、质粒DNA或粘粒DNA衍生的载体。例如,可以使用质粒载体如pBR322,pUC19/18,pUC118,119和M13 mp载体系列。噬菌体载体可以包括gt10,gt11,gt18-23,ZAP/R和EMBR噬菌体载体系列。可以使用的粘粒载体包括,但不限于pJB8,pCV 103,pCV107,pCV108,pTM,pMCS,pNNL,pHSG274,COS202,COS203,pWE15,pWE16和卡隆粒载体系列。允许RNA体外转录的载体,如SP6载体也可以用于产生大量可以掺入基质中的RNA。
选定的基因和DNA节段也可以以DNA插入片段的形式存在于重组病毒,如重组疱疹病毒、逆转录病毒、痘苗病毒、腺病毒、腺病毒相关病毒或牛乳头瘤病毒的基因组中。尽管可以使用整合载体时,通常优选在许多世代中不将基因产物转移到子代细胞的非整合系统。以这种方式,基因产物在确定的生物过程如伤口愈合中表达,当基因癌传代中稀释时,基因产物的表达量减少。
在这些实施方案中,为使基因与靶细胞接触,应该准备重组病毒颗粒,其基因组包括基因插入片段的,并通过从本发明的聚合物纤维释放而接触靶细胞或组织,病毒感染细胞并转移遗传物质。在此引入下面的美国专利作为对病毒基因治疗进一步举例说明的参考:关于腺病毒、逆转录病毒、腺病毒相关病毒、疱疹病毒和巨细胞病毒基因治疗的美国专利5,747,469,关于腺病毒基因治疗的美国专利5,631,236;以及关于疱疹病毒基因治疗的美国专利5,672,344。
本发明也考虑了使用具有不同于文献中描述的序列的基因,只要改变或修饰基因仍然编码以需要(直接或间接)的方式行使功能而影响靶细胞的蛋白。这些序列包括那些由点突变、遗传密码简并或天然存在等位基因变异以及由基因工程即人工引入的进一步修饰导致的序列。
设计在核苷酸序列中引入改变而改变被编码蛋白或多肽的功能特征的技术在本领域中是公知的,如美国专利4,518,584,在此引入作为参考,其技术在这里也有进一步详述。这种修饰包括碱基去除、插入或替换以及由此引起的氨基酸序列改变。也可进行改变而增加蛋白质活性,增加其生物稳定性或半衰期,改变其糖基化模式,赋予温度敏感性或改变蛋白质的表达模式等。所有这些核苷酸序列的修饰都包含在本发明的范围内。
本发明的优点是在基因转移方法和组合物中可以使用一种或一种以上选定的基因。这样核酸运送方法可以要求给予一种、两种、三种或更多选定的基因。可以应用的最大基因数仅仅由实际考虑而限制,如同时制备大量基因构建体需要的努力或甚至引发不良毒性反应的可能性。可以选择基因的特定组合来改变相同的或不同的生化途径。例如,生长因子基因可以与激素基因组合;或第一激素和/或生长因子基因可以与编码能够与第一基因的多肽产物相互作用的细胞表面受体的基因组合。
在使用多种基因的情况下,它们可以在一种或更多启动子的控制下在单基因构建体上结合,或者它们可以作为相同或不同类型的分离构建体而制备。这样,可以使用几乎无限的不同基因和基因构建体的组合。某些基因组合可以设计为,或它们的使用会导致,获得对细胞刺激和组织生长的协同作用,这些组合的任何一种或全部都包含在本发明的范围中。实际上,在科学文献中描述了许多协同作用,所以本领域的常规技术可以很容易识别协同基因组合或甚至基因-蛋白质组合。
也应该理解,如果需要,核酸节段或基因可以与其它试剂如蛋白质或多肽或各种药物活性试剂结合给予。只要遗传物质形成组合物的一部分,假设附加试剂与靶细胞或组织接触时不会导致严重不良反应,则对其它可以包含的成分基本没有限制。这样核酸可以与各种其它试剂一起运送,例如,在某些实施方案中,可以希望给予血管生成因子,如美国专利5,270,300所公开的,在此引入作为参考。
由于基因的化学性质,即作为一串核苷酸是基本不变的,并且因为基因转移和表达的过程是基本相同的,可以理解由本发明的纤维基质转移的基因类型基本是无限的。这一概念从用于DNA接种而转移表述抗原性或免疫原性片段的遗传物质的混合物扩展到细胞功能的刺激,如在创伤修复中;到细胞杀伤方面,如将肿瘤抑制基因、反义癌基因或凋亡诱导基因转移到癌细胞。
仅仅通过实施例,本发明提供的基因包括,但不限于那些编码和表达:激素、生长因子、生长因子受体、干扰素、化学因子、细胞因子、集落刺激因子和趋化因子、转录和延伸因子、细胞循环控制蛋白,包括激酶和磷酸酶、DNA修复蛋白、凋亡诱导基因、凋亡抑制基因、癌基因、反义癌基因、肿瘤抑制基因;血管生成和抗血管生成蛋白;免疫应答刺激和调节蛋白;细胞表面受体、辅助信号分子和运输蛋白;酶和抗细菌和抗病毒蛋白的基因。
F.试剂盒
本发明的备方面需要的基本物质和试剂可以集中在试剂盒中。本发明的试剂盒通常也包括将含有需要成分的小管包含在封闭限制结构中进行商业销售的方法,如保存所需小管的注射或吹气式塑料容器。不考虑容器的数量或类型,本发明的试剂盒一般按使用试剂盒成分的说明书包装。
G.实施例
引入下面的实施例来证明本发明的优选实施方案。本领域的技术人员应该赞同,实施例中公开的按照本发明者发现的代表技术的技术在本发明的执行中有良好作用,这样可以认为是为其实行建立了优选模式。然而,本领域的技术人员按照本公开内容,应该赞同在不离开本发明的精神和范围的前提下,可以在公开的特定实施方案中进行许多改变,仍然获得同样或相似的结果。
实施例1
构造含有治疗剂的聚合物纤维
在本发明的一种实施方案中,用下列程序建立药物释放纤维。此装置如图8所描绘。首先将生物可降解聚合物如聚(L-乳酸)(PLLA)、聚(DL-乳酸)、聚已内酯、聚(乙醇酸)、聚酐、或这些或其它生物可降解聚合物的共聚物或掺合物溶解于根据聚合物类型,浓度从5到30wt%的适当溶剂(A)中,PLLA优选10wt%。在这种实施方案中,溶剂(A)与水有低可混性,与凝固浴溶剂(B高度可混。优选溶解(A)包括氯仿和二氯甲烷。当聚合物溶解后,将含有感兴趣的生物分子和表面活性剂的水溶液加入聚合物溶液。水乳状液的浓度一般为聚合物溶液的1到50%v/v,对于单微丝PLLA纤维,最典型为4-10%。表面活性剂可以是一种或几种本领域技术人员熟悉的物质的结合,如牛血清白蛋白(BSA)、聚(乙烯醇)、环氧乙烷与环氧丙烷的嵌段共聚物、或生物表面活性剂如磷脂族。通过扩展也包括其它在这里没有特别提及,但本领域技术人员已知的表面活性剂。在一种典型的使用中,将BSA以比感兴趣的生物分子高10倍到100倍的浓度用作表面活性剂,一般浓度为水相的10wt%到50wt%。
通过使用一些形式的机械能如超声波、涡流或迫使液体通过小口产生的剪切力,在水和有机相间形成油包水类型的乳状液。乳状液必需在比挤出要求的时间长得多的时间段中保持稳定。分散水相液滴的大小主要取决于表面活性剂的质量和给予系统形成乳状液的机械能的量。水相的大小是纤维释放动力学和机械特征的重要变量。
然后将乳状液挤入含溶剂(B)的凝固浴。然后将聚合物乳状液通过规格从16号到30号的分散头挤出到凝固浴。溶剂(B)必需与溶剂(A)高度可混,必需对于聚合物是非溶剂;异丙醇是最典型的选择,但任何对于聚合物是非溶剂并与溶剂(A)高度可混的溶剂都可以。例如,己烷与二氯甲烷高度可混并且是聚合物的非溶剂,所以,二氯甲烷和己烷产生很好的溶剂和凝固浴组合。因为溶剂(A)与凝固浴溶剂(B)高度可混合,它通过聚合物溶液流自由扩散到凝固浴中。然而,聚合物在溶剂(B)中不可溶,所以开始沉淀,形成纤维外鞘并将乳状液的几乎全部分散水相包入形成的纤维。以这种方式,使纤维加载了感兴趣的药物或蛋白。形成的纤维可以在凝固浴中通过一系列滚柱从而提供了应该需要的通过凝固浴的固定路径长度。以确定的速度将纤维抽出凝固浴。在实验室中,本发明使用了附着于可以精确保持其角速度的改良变速车床的量筒。然后根据所加载的生物分子的推荐储存条件,将抽出和挤出的纤维从量筒中移出并冻干、冷冻或烘干转移并放置于desecrator或冷冻机。
通过改变将聚合物乳状液注入凝固浴的速度与车床线性缠绕速度之比,可以发现纤维机械特征的许多令人惊讶的改变,如图9A和9B所示。纤维的机械特征作为下列变量的函数而改变:聚合物溶剂、凝固浴溶剂、溶剂系统的中间可混性、缠绕速度与注入速度之比、凝固浴中的总时间、乳状液中水相与聚合物溶液相聚合物溶液相之比,以及表面活性剂质量。作为一些变量的函数的机械特征的改变如图10A和10B所示。
另一种令人惊奇的发现是已经完成的纤维的表面质地也可以由溶剂和聚合物系统的适当选择而控制。本发明者制造了表面质地从光滑到绒面到有纵沟的纤维,如图11A-11C所示。这些表面质地的改变对细胞生长有实际应用,绒面质地提供了更大的粘附特征,有纵沟的纤维提供了更好的接触引导。所有这些机械特征和表面质地的改变显著影响了治疗剂的释放动力学。
纤维直径由处理条件控制,如图12所示。因为控制机械特征、表面质地、直径和释放动力学的处理参数是已知的,可以特制有特定特征用于特定用途的纤维。
在构造过程中保持生物活性的生物治疗剂可以用三明治ELISA表示,其中加载到纤维的试剂是鼠IgG的Fab片段。为使ELISA检测Fab的存在,必需保持两个结合表位的生物活性。
在构造过程的另一种实施方案中,将聚合物的不良溶剂加入聚合物溶液如甲苯。不良溶剂的加入改变了纤维的机械特征。
在另一种构造实施方案中,将最多20%v/v的聚合物溶剂加入凝固浴溶剂。聚合物溶剂的加入减小了纤维内到纤维外的浓度梯度。这改变了扩散率并因此改变了形成纤维外鞘的速度。外鞘的形成速度对于纤维表面质地和纤维的机械特性以及生物分子的释放动力学是关键的。
在另一种构造实施方案中,将增稠溶液如甘油加入凝固浴。这增加了凝固浴的粘度并改变了凝固浴的特异性比重。这两个变量都可导致形成加载纤维的能力显著增加。甘油的浓度从8到20%v/v。
另外,可以通过挤出领域的技术人员所公知的方法构造同轴纤维。通过使用这些技术,可以在同轴纤维的每层加入各种聚合物和生物分子。
实施例2
构造含有各种浓度治疗剂的聚合物纤维
在另一种构造实施方案中,过程与实施例1中的描述相似,除沿纤维长度应用了浓度梯度。这是通过采用两种溶液而实现的。一种是含有感兴趣的治疗剂的聚合物乳状液,另一种不含治疗剂或含有不同生物分子。通过在挤出过程中不断改变两种溶液的比例而实现梯度。这可以通过许多途径实现,包括如图13所示在“Y”连接处的蝶形阀或用图14所示的有或无混合室的独立泵。以这种方式,建立了每厘米长度有已知浓度改变的控制良好的梯度。本发明的另一种实施方案是建立了“有条带的纤维”。在有条带的纤维中,有一些可能的构象;在一种实施方案中,两种聚合物溶液都是含不同生物分子的乳状液。这通过与梯度相同的方式实现,梯度是一系列跃阶函数,从乳状液A交替转换为乳状液B。
在第二种实施方案中,从聚合物乳状液得到的一条带含有这里描述的其它实施方案中的一种或更多生物分子。另一条带是作为密封材料的聚合物节段,使得完成的纤维可以被切割为特定长度,而完成的纤维每端的两个末端可以被密封。在每一种实施方案中,带的长度是独立可调整的。这些梯度和有条带的纤维可以在有或无下一实施例中描述的同心包膜的情况下使用。
实施例3
构造有同心包膜的聚合物纤维
而在另一种构造实施方案中,将初步存在的纤维加入喷丝嘴并通过凝固浴。将液体聚合物乳状液加入“T”或“Y”连接并在进入凝固浴前包被纤维。这样将同心包膜应用于纤维,每个包膜具有含有不同治疗剂的能力,如图4所示。包膜聚合物可以与核心聚合物相同或不同。可以有分子附着在核心纤维上而增加包膜聚合物的粘合。例如,一薄层BSA可以改变脱乙酰壳多糖与聚(L-乳酸)的粘合。通过精密的喷丝嘴,可以将含有不同分子的两种或更多乳状液放在包膜内。这是通过将所有的包膜物质放入喷丝嘴,用阀门分开每个包膜聚合物流。这允许纤维以围绕纤维的角度位置的函数释放不同分子。在某些实施方案中,喷丝嘴可能是非圆形的,所以形成任何需要的截面形状。对核心纤维和包膜聚合物都是如此。
另一种构造技术是用特别设计的多腔喷丝嘴建立本领域中公知的标准纤维结构,如核心和鞘、海岛型复合纤维等。
实施例4
构造环境反应性聚合物凝胶纤维
在不同的构造实施方案中,通过聚合或其它方法形成纳球体(nanosphere)大小的环境反应性聚合物水凝胶。然后将这种纳球体掺入纤维。“环境反应性凝胶”表示当凝胶周围的环境进行相对小的改变时物理特征显示出很大改变的聚合物凝胶。发现在本发明中有用的聚合物水凝胶包括聚(N-异丙基丙烯酰胺)(NIPA)和聚(丙烯酸)(PAA)凝胶。例如,NIPA凝胶具有进行反应于小的温度改变(2-3C)而进行100倍的剧烈体积改变的能力。可以通过将这些纳球体浸入生物分予水溶液而给其加载生物分子。然后将这些加载的纳球体干燥并加入聚合物溶液,形成或不形成乳状液。所有其它的构造过程都相同。这一过程建立温度敏感性纤维。NIPA的相变可以由本领域的技术人员控制在38-39C发生。这提供了反应于病人生理状态的纤维。如果病人开始发热,它的释放动力学有剧烈增加,并且由于这是可逆现象,当体温恢复正常时,释放动力学又减慢。
实施例5
基于脱乙酰壳多糖的纤维
在另一种构造实施方案中,不使用前面所述的基于酯的合成聚合物,可以用天然存在的多糖如脱乙酰壳多糖作为聚合物系统。在本领域中熟知可以将脱乙酰壳多糖溶于3%乙酸,并用5%氢氧化钠作为凝固浴来制造脱乙酰壳多糖纤维。本发明者发现可以用1%盐酸溶解脱乙酰壳多糖,脱乙酰壳多糖的浓度可以低至2.5wt%,如果凝固浴由浓度为5到15%的Tris碱组成,可以获得优质纤维(图1)。这是关于在这些条件下挤出的脱乙酰壳多糖纤维的第一次报道。
脱乙酰壳多糖是一种生物可降解聚合物。脱乙酰壳多糖可以被存在于胞浆中、细胞间液和细胞内的溶菌酶酶促降解。由于溶菌酶对脱乙酰壳多糖的作用依赖于聚合物主链上的乙酰基的存在,因此可以在特定环境下以两种其它的方式调节前面所描述的纤维的释放速度:a)从由不同脱乙酰程度的脱乙酰壳多糖聚合物组成的非均质混合物按前面所述挤出纤维。以这种方式,可以维持需要时间段的最优范围内的药物释放水平;b)另一种可能性是挤出脱乙酰壳多糖分段纤维,其中每段由不同脱乙酰程度的脱乙酰壳多糖产生,如图2所示。后一种方法可以通过沿纤维建立时间梯度应用于迁移细胞。
本发明者也将重构基膜提取物(matrigel,Becton Dickinson,Bedford,MA)与溶解在盐酸中的脱乙酰壳多糖混合,并证明了用浓度从10-15%的Tris碱组成的凝固浴挤出优质纤维的能力。在这种情况下,发现轴突伸展比脱乙酰壳多糖单独时有所改进。ELISA证明了matigel的两种主要蛋白(层粘连蛋白和IV型胶原)在纤维中的出现。通过体外神经元附着实验和轴突伸展证明了这些蛋白也保持了生物活性。另一种可能性是用matrigel包被同样的Tris碱挤出的脱乙酰壳多糖纤维。
在一项惊人的发现中,如果本发明者在加入matrigel之前硫酸脱乙酰壳多糖,与matrigel和未处理脱乙酰壳多糖的情况相比,神经元附着和轴突伸展显著改进(图3,图4)。采用同样的化学挤出条件,本发明者可以在有或没有matrigel作为共同挤出物质的情况下挤出由0.2%硫酸脱乙酰壳多糖和3.2%未修饰脱乙酰壳多糖组成的聚合物纤维。
在本领域中熟知,由于相似的化学结构,硫酸脱乙酰壳多糖有类肝素样抗凝特征。可以用硫酸脱乙酰壳多糖或matrigel和硫酸脱乙酰壳多糖包被溶解于盐酸并在Tris碱中挤出的由未修饰脱乙酰壳多糖组成的纤维。这可以产生有固有抗凝特征并可以加载活性药物的纤维。这可以在构造血管支架和其它与血液直接接触并要求机械强度和/或运送药物的能力的医学设备中有大量的临床应用。
按上述方法挤出脱乙酰壳多糖纤维的相对强烈的酸性和碱性环境很大程度将可以掺入纤维的生物分子限制为可以承受很大pH变化的生物分子。所以,为克服这种固有的限制,本发明者开发了一种保持加载到脱乙酰壳多糖纤维的甚至是最敏感生物分子的生物活性的新方法。在这种实施方案中,用溶剂蒸发和其它药物运送文献中熟知的技术将感兴趣的敏感生物分子加载到PLLA微球体。然后将PLLA微球体与3.5wt%的脱乙酰壳多糖溶液混合并按前面所述方法挤出。当用乙酸和氢氧化钠或1.2%盐酸和10-15%Tris碱挤出混合物时将形成加载了PLLA微球体的脱乙酰壳多糖纤维。PLLA微球体可以保护敏感生物分子不受脱乙酰壳多糖纤维的剧烈处理条件的影响。
实施例6
神经组织工程
在本发明的这方面,如图15所示将平行排列的纤维装入硅胶或其它适当物质的管中并加载神经营养蛋白以便轴突生长。将这些纤维束放置于切断的外周或中枢神经。可以将神经生长蛋白以线性或其它一些适当的梯度加载。植入这种设备可以将神经残端之间的缺口连接起来。当纤维释放神经营养蛋白时,轴突迁移到近端之外,跨过纤维束并进入神经远端。当在远端时,由存在的施旺细胞或胶质细胞提供引导线索然后可以进行再连接。以前已经发现轴突通过这些纤维束接收接触引导并且在使用未加载纤维时可以在大鼠坐骨神经切除术中穿过至少1.8cm。管中未加载纤维对于大鼠坐骨神经生长的最优密度为在直径1.5mm的管中约有32条纤维。
实施例7
制备和使用聚合物纤维支架
在另一种实施方案中,可以给纤维加载感兴趣的药物并用于支架或其它需要机械强度的医疗设备。如果需要机械特征,支架可以以将加载纤维与未加载纤维混合的方式编织。
可以将纤维与可买到的支架结合使用从而在放置位点运送药物。在这种情况下,纤维不提供任何机械支持,只作为药物运送储存器。
实施例8
制备和使用伤口敷料
在另一种实施方案中,可以用这些纤维制作纱布或敷料。这种敷料可以有两面,上表面释放用于表皮再生的分子并为这些分子提供培养基。下表面将促进真皮组织再生。这种敷料是为皮肤伤口愈合而设计的,包括烧伤、全皮肤厚度伤口和慢性或不愈合伤口及疼痛。可以包被每条纤维以提供与皮肤伤口愈合的三个阶段相对应的药物或因子的时间释放。
例如,在为创伤病人设计的敷料中,首先释放的化学物质将是止血的促凝因子。下一层然后可以释放帮助募集进行伤口愈合下一阶段的中性粒细胞和巨噬细胞的细胞因子。最后,释放帮助减少多余疤痕组织并抑制尤其对烧伤病人致残的收缩。
实施例9
构造人工动脉
可以用这里描述的技术构建人工血管。可以用非编织技术将一系列中空的、圆柱形切面与加载了各种生物试剂的纤维接合、编织、编结或构造在一起。最内层圆柱体优选紧密编织并含有促进完整内皮细胞层迁移、扩散和起作用的试剂。下一层圆柱体由编织或接合结构组成,其纤维主要在外周缠绕在内层圆柱体周围。这一层将诱导平滑肌纤维的迁移和增生,并促进弹性蛋白的表达从而建立内部弹性介质。下一层圆柱体由接合或非编织纤维组成并将含有促进成纤维细胞、巨噬细胞的内向生长和细胞外基质的建立的药物。最后一层将由促进动脉细胞通过人工滋养血管形成血管的纵向纤维组成,由VEGF释放纤维或其它血管生成的启动子建立。
实施例10
药物运送支架
在另一种实施方案中,这些纤维可以在纤维形式优于微球体的位置用于药物运送支架。例如,对于直接运送到血流的药物,纤维可以附着在血管壁,并被整个包含在血管内。微球体不能流经循环系统,因为它们将在一定水平上被捕捉,潜在危害下游组织。然而,纤维可以释放药物并且只要纤维保持完整不会导致堵塞下游血管分支的问题。其它纤维比微球体更好的位置可以包括眼,在这里微球体可能更容易干扰受试者的视力。纤维可以被朝下粘住而不漂浮到视野中。纤维可以比微球体更好地停留在适当的位置,特别是在纤维可以盘绕的位置中。以这种方式,纤维中的机械张力将使它顶住组织空间的侧面并因此保持适当的位置。
实施例11
原位动脉形成
与实施例9的范围相似的是原位动脉形成。在这种实施方案中,将含VEGF或相似替代物的纤维束放置于体内,纤维束的两端接近或接触存在的血管。当纤维开始释放VEGF或相似替代物时,将诱导存在血管的内皮细胞迁移到存在血管外,遵循与正常血管生成相似的过程。先导上皮细胞将穿过纤维束路径,这样产生沿纤维束路径的新血管。此纤维束可以有几种形式,它可以存在只释放VEGF或它的替代物的单个或几条纤维,或它可以是管状,内部为趋化内皮细胞的VEGF或相似的生长因子,外部为针对平滑肌的不同因子。以这种方式,可以确定建立血管的大小。在这种应用中,细胞被细胞特异性生长因子引导入开始无细胞的支架。
实施例12
骨折愈合
在另一种创伤愈合的实施方案中,将已知促进骨折愈合的蛋白加载到纤维中。然后在骨折位点将纤维包裹在骨周围,释放生长因子并增加骨折修复速度。
这些纤维可以是螺旋结构(单或多螺旋),或它们可以编织为疏松、开放的织物。纤维可以以螺旋或编织形式围绕在骨碎片周围,当释放它们的生长因子时使其保持恰当的位置。
在由于失血或骨折位点供血不足而导致不愈合骨折的情况下,含VEGF或其等同物的一条或一系列纤维可以用于增加骨折区的血供。
在此实施方案中,与未治疗骨折相比,骨折可以以增加的速度愈合,在某些情况下不联合的位点可以愈合。
实施例13
皮肤溃疡愈合
与描述了一种皮肤伤口愈合形式的例8相似,本技术的另一种重要实施例是愈合各种起源的慢性皮肤溃疡,如糖尿病足溃疡,静脉曲张性溃疡和一般的褥疮的潜能。以创建释放抑制加速皮肤愈合的因子,如血小板源生长因子(PDGF)、转化生长因子β(TGF-β)和VEGF或相似蛋白的非编织网眼为基础可以治愈这些状况和其它潜在的相似状况。这种非编织网眼可以插入或直接包裹到溃疡或伤口,在这里生长因子可以帮助加速伤口愈合过程。这些敷料可以设计用于愈合皮肤疮和溃疡。在这种情况下,几乎不需要减少出血;而这些病人,特别是那些有糖尿病溃疡的病人的最大需要之一是缺少到伤口部位的血供。所以,诱导血管生成的因子可以增加循环并帮助疮和溃疡部位的组织再生。
每种敷料可以设计为通过改变释放的生物分子和它们的释放动力学而满足各种伤口和疮类型的特定需要。
实施例14
肌肉移植
在另一种实施方案中,可以将肌肉干细胞加载到平行列的纤维中。这些干细胞可以是心肌、平滑肌或骨骼肌起源。当这些干细胞被种植到纤维列中时,这些纤维可以在体外机械伸展从而帮助这些细胞恰当排列和分化。也可以用很小直径的纤维来完成排列。我们对于轴突的经验提示规格为直径50μm左右的纤维倾向于帮助细胞平行于纤维轴排列。在此束中的其它纤维可以释放血管生成因子从而建立肌肉细胞的血管供应。在骨骼肌或平滑肌组织的情况下,也可包括用于神经生长的纤维以便诱导神经肌肉连接的形成。各种用于收获、分离、繁殖和分化这些干细胞的实验条件是本领域技术人员公知的,不是本发明的一部分。
实施例15
纤维构造程序1的替代程序
为构造规格为100μl聚合物溶液的小量聚合物,开发了下面的方法。按实施例1建立乳状液。将此乳状液加入小容器,如通过在试管底部插入20-30号,最典型为23号的针头而改良的1ml FALCON试管。将此试管放入充满凝固浴溶剂的改良50ml试管。将此试管放入离心机并以500到1200rpm旋转,最典型为700rpm.离心力将推动小量聚合物乳状液通过针头进入凝固浴。通过与实施例1所描述的相似的溶剂交换,形成纤维。此方法使用非常少的聚合物乳状液,浪费很少的乳状液。
实施例16
纤维构造程序2的替代程序
作为替代构造程序,凝固溶剂以规定速度流过长的垂直试管,聚合物溶液被挤出到凝固浴溶剂流中。此液流从试管流出到凝固浴中。纤维经过一个或更多筒管并从凝固浴中取出并盘绕在轴上。溶剂流速、聚合物挤出速度、聚合物溶液/乳状液的组成、凝固浴溶剂的组成、纤维盘绕速度、在连续筒管之间发生的拉伸、以及其它额外的浴或处理将影响纤维的机械和化学特征以及被加载生物物质的释放动力学。
实施例17
青光眼的治疗
与例10所描述的将药物运送到眼,和例6中简要描述的神经支架相似,可以通过将眼内药物运送与应用于视神经的神经治疗相结合而治疗青光眼。视网膜神经节细胞进行凋亡导致视神经轴突的死亡。假设细胞可以在眼内和沿视神经路径得到支持,这些细胞可以存活。释放生长因子如NT-4,BDNF,CNTF的纤维束可以应用于视神经外部。同时,将释放凋亡抑制因子的纤维或支持视网膜神经节细胞的因子植入到眼内。这种结合的努力可以延长或保存青光眼患者的视力。
从前面的实施例中可以看到,当理解了基本生理结构时,可以编织其它组织、器官或结构。这可以扩展到消化系统、肌肉骨骼系统、泌尿系统、循环系统、神经系统的器官。
这里公开和要求的所有组合物和方法可以在没有不适当的实验的条件下根据本公开内容制造和执行。尽管以优选实施方案的形式描述了本发明的组合物和方法,对于本领域技术人员很明显的是,可以在不离开本发明的概念、精神和范围的前提下,对组合物和方法、这里描述的方法的步骤或步骤的顺序进行改变。更具体地说,很明显可以用化学和物理相关的某些试剂替代这里所描述的试剂而达到相同或相似的结果。对于本领域技术人员很明显的是,所有这些由从属权利要求定义的小的替代和修饰认为是在本发明的精神、范围和概念内。
参考文献
下列参考文献,为这里阐述的内容提供了示范程序和其它详细补充,在此特意引入作为参考。
Aigner,Tegeler、 Hutzler,Campoccia,Pavesio,Hammer,Kastenbauer,Naumann,″Cartilage tissue engineering with novel nonwoven structured biomaterial basedon hyaluronic acid benzyl ester,″J.of Biomed Materials Res.,42(2):172-81,1998.
Auerbach and Auerbach,″Angiogenesis inhibition:a review,″Pharmac.Ther.,63:265,1994.
Breitbart,Grande,Kessler,Ryaby,Fitzsimmons,Grant,″Tissue engineered bone repair ofcalvarial defects using cultured periosteal cells,″Plastic & ReconstructiveSurgey,101(3):567-74,1998.
Cao,Rodriguez,Vacanti,Ibarra,Arevalo,Vacanti,″Comparative study of the use ofpoly(glycolic acid),calcium alginate and pluronics in the engineering ofautologous porcine cartilage,″J. of Biomaterials Sci.,Polymer Edition,9(5):475-87,1998.
Dillon,Yu,Sridharan,Ranieri,Bellamkonda,″The influence of physical structure andcharge on neurite extension in a 3D hydrogel scaffold,″J,of Biomaterials Sci.,Polymer Ed,9(10):1049-69,1998.
Elcin,Dixit,Lewin,Gitnick,″Xenotransplantation of fetal porcine hepatocytes in ratsusing a tissue engineering approach,″Artificial Organs,23(2):146-52,1999.
Fauza,Fishman,Mehegan,Atala,″Videofetoscopically assisted fetal tissue engineering:skin replacement,″J. of Pediatric Surgery,33(2):357-61,1998.
Fidler and Ellis″The implications of angiogenesis for the biology and therapy of cancermetastasis,″Cell,79:185,1994.
Folkman and Klagsbrun,″Angiogenic factors,”Science,235:442-447,1987.
Folkman,″How is blood vessel growth regulated in normal and neoplastic tissue,″Cancer Res.,46:467,1986.
Folkman,J.,″Angiogenesis in cancer,vascular,rheumatoid and other disease,″NatureMed.,1:27,1995.
Grande,Halberstadt,Naughton,Schwartz,Manji,″Evaluation of matrix scaffolds fortissue engineering of articular cartilage grafts,″J.of Biomed Mat.Res.,34(2):211-20,1997.
Gutsche,Lo,Zurlo,Yager,Leong″Engineering of a sugar-derivatized porous networkfor hepatocyte culture,″Biomaterials,17(3):387-93,1996.
Hoerstrup,Zund,Lachat,Schoeberlein,Uhlschmid,Vogt,Turina,″Tissue engineering:anew approach in cardiovascular surgery-seeding of human fibroblasts onresorbable mesh,″Swiss Surgery,(Suppl.),2:23-5,1998.
Hoerstrup,Zund,Schoeberlein,Ye,Vogt,Turina,″Fluorescence activated cell sorting:areiable method in tissue engineering of a bioprosthetic heart valve,″Annals ofThoracic Surgery,665(5):1653-7,1998.
Isogai,Landis,Kim,Gerstenfeld,Upton,Vacanti,″Formation of phalanges and smalljoints by tissue-engineering,″J. of Bone & Joint Surgery,American Vol.,81(3):306-16,1999.
Martin,Padera,Vunjak-Novakovic,Freed,″In vitro differentiation of chick embryo bonemarrow stromalcells into cartilaginous and bone-like tissues,″J. of OrthopaedicRes.,16(2):181-9,1998,
Nagy et al.,″Pathogenesis of ascites tumor growth:vascular permeability factor,vascularhyperpermeability,and ascites fluid accumulation,″Cancer Res.,55:360,1995.
Peppas and Langer,″New challenges in biomaterials,″Science 263:1715-1720,1994.
Peter,Miller,Yasko,Yaszemski,Mikos,″Polymer concepts in tissue engineering,″J.ofBiomed. Materials Res.,43(4):422-7,1998.
Sacks,Chuong,Petroll,Kwan,Halberstadt,″Collagen fiber architecture of a cultureddermal tissue,″J. ofBiomed. Engineering,119(1):124-7,1997.
Sambrook et al.,Molecular Cloning:ALaboratory Manual,Coid Spring HarborLaboratory Press,Cold Spring Harbor N.Y.,1989.
Shinoka,Shum-Tim,Ma,Tanel,Isogai,Langer,Vacanti,Mayer,″Creation of viablepulmonary artery autografts through tissue engineering,″J.of Thoracic &Cardiovascular Surgery,115(3):536-45,1998.
Sims,Butler,Cao,Casanova,Randolph,Black,Vacanti,Yaremchuk,″Tissue engineeredneocartilage using plasma derived polymer substrates and chondrocytes,″Plastic&Reconstructive Surgery,101(6):1580-5,1998.
Vunjak-Novakovic,Obradovic,Martin,Bursac,Langer,Freed,″Dynamic cell seeding ofpolymer scaffolds for cartilage tissue engineering,″Biotechnology Progress,14(2):193-202,1998.
Whang,Tsai,Nam,Aitken,Sprague,Patel,Healy,″Ectopic bone formation via rhBMP-2delivery from porous bioabsorbably polymer scaffolds,″J.of Biomed.MaterialsRes.,42(4):491-9,1998.
Wong and Mooney,″Synthesis and properties of biodegradable polymers used in tissueengineering,″In:Synthetic Biodegradable Polymer Scaffolds,(Atala and Mooney,eds.),Birkhauser Press,Boston,MA,pp.51-82,1997.
Yoo and Atala,″A novel gene delivery system using urothelial tissue engineeredneoorgans,″J.of Urology,158(3pt 2):1066-70,1997.
Claims (27)
1.一种组合物,其包含至少一种生物可降解聚合物纤维,其中该纤维是通过以下方法制备的:将5-30wt%的选自聚(L-乳酸)、聚(DL-乳酸)、聚己内酯、聚(乙醇酸)、聚酐或这些聚合物的共聚物或掺合物的生物可降解聚合物溶解于与水有低可混性的溶剂,并且将溶解的聚合物溶液与水溶液混合,其中所述水溶液包含一种或多种治疗剂和表面活性剂,其中所述生物可降解聚合物形成纤维的外鞘,所述水溶液包入纤维内。
2.权利要求1的组合物,其中所述纤维形成一个支架,并且其中所述水溶液被处理以在纤维中形成内部多孔结构。
3.权利要求1的组合物,其中所述纤维与其它纤维一起被编织、编结或接合在一种集合中,并且该集合中至少一种纤维含有一种或多种治疗剂。
4.权利要求1的组合物,其中所述一种或多种所述治疗剂以非均质模式分布在所述水溶液中。
5.权利要求1的组合物,其中所述一种或多种治疗剂的浓度沿纤维纵轴改变。
6.权利要求5的组合物,其中所述一种或多种治疗剂的浓度作为沿纤维纵轴距离的函数以线性、指数或任何所需方式改变。
7.权利要求1的组合物,其中所述一种或多种治疗剂的浓度从纤维的第一端到纤维的第二端逐渐减少。
8.权利要求1的组合物,其中所述一种或多种治疗剂以双向方式改变,所以该一种或多种治疗剂的含量从所述纤维的第一端增加到最大,然后向所述纤维的第二端逐渐减少。
9.权利要求1的组合物,其进一步包含至少一种不含治疗剂的生物可降解聚合物纤维。
10.权利要求1的组合物,其中所述一种或多种治疗剂选自药物和蛋白质。
11.权利要求1的组合物,其中所述一种或多种治疗剂选自酶、生长因子、免疫调节剂、促进血管生成的化合物、抑制血管生成的化合物、抗炎化合物、抗生素、细胞因子、抗凝剂、促凝剂、趋化剂、促进凋亡的试剂、抑制凋亡的试剂和促有丝分裂剂。
12.权利要求1的组合物,其中所述一种或多种治疗剂包括放射性试剂或用于成像研究的造影剂。
13.权利要求1的组合物,其中所述一种或多种治疗剂选自病毒载体、多核苷酸和多肽。
14.权利要求1的组合物,其中所述一种或多种治疗剂包含促进血管生成的试剂。
15.权利要求14的组合物,其中所述促进血管生成的试剂为血管内皮生长因子。
16.权利要求1的组合物,其中所述生物可降解聚合物为单聚合物、共聚物或聚合物的混合物,其中该聚合物选自多肽、polydepsipeptides、尼龙共聚多酰胺、脂族聚酯、聚二氢吡喃、聚磷腈、聚(原酸酯)、聚(氰基丙烯酸酯)、聚酐、经修饰的多糖和经修饰的蛋白质。
17.权利要求16的组合物,其中所述脂族聚合物选自聚(乙醇酸)、聚(乳酸)、聚(亚烷基琥珀酸酯)、聚(羟基丁酸酯)、聚(亚丁基二甘醇酸酯)、聚(ε-己内酯)和其共聚物、掺合物和混合物。
18.权利要求16的组合物,其中所述经修饰的多糖选自纤维素、淀粉-藻酸盐和糖胺聚糖、硫酸软骨素、肝素、葡聚糖、甲壳质和脱乙酰壳多糖。
19.权利要求16的组合物,其中所述经修饰的多糖选自硫酸肝素、硫酸葡聚糖和硫酸脱乙酰壳多糖。
20.权利要求16的组合物,其中所述经修饰的蛋白质选自胶原蛋白和血纤维蛋白。
21.权利要求1的组合物,其中所述纤维包含多层聚合物层,其中一个外层包围一个邻近的内层。
22.权利要求21的组合物,其中所述多层任选包含一种或多种治疗剂。
23.权利要求22的组合物,其中所述一种或多种治疗剂随时间从所述多层中释放。
24.权利要求1的组合物,其中所述纤维沿其长度含有一种以上治疗剂。
25.权利要求24的组合物,其中所述一种以上治疗剂的浓度随所述纤维亚型的长度改变。
26.权利要求24的组合物,其中所述一种以上治疗剂以随时间改变的速度从所述纤维中释放出来。
27.权利要求1的组合物,其中所述一种或多种治疗剂以随时间改变的速度从所述纤维中释放出来。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14782799P | 1999-08-06 | 1999-08-06 | |
US60/147,827 | 1999-08-06 | ||
PCT/US2000/021508 WO2001010421A1 (en) | 1999-08-06 | 2000-08-04 | Drug releasing biodegradable fiber implant |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1378445A CN1378445A (zh) | 2002-11-06 |
CN1378445B true CN1378445B (zh) | 2013-02-06 |
Family
ID=22523056
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN008140227A Expired - Lifetime CN1378445B (zh) | 1999-08-06 | 2000-08-04 | 药物释放生物可降解纤维植入物 |
Country Status (7)
Country | Link |
---|---|
US (3) | US6596296B1 (zh) |
EP (1) | EP1206254A1 (zh) |
JP (2) | JP4859317B2 (zh) |
CN (1) | CN1378445B (zh) |
AU (1) | AU6526100A (zh) |
CA (1) | CA2379909C (zh) |
WO (1) | WO2001010421A1 (zh) |
Families Citing this family (821)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5500013A (en) * | 1991-10-04 | 1996-03-19 | Scimed Life Systems, Inc. | Biodegradable drug delivery vascular stent |
US8795332B2 (en) | 2002-09-30 | 2014-08-05 | Ethicon, Inc. | Barbed sutures |
US6241747B1 (en) | 1993-05-03 | 2001-06-05 | Quill Medical, Inc. | Barbed Bodily tissue connector |
US7070590B1 (en) | 1996-07-02 | 2006-07-04 | Massachusetts Institute Of Technology | Microchip drug delivery devices |
US5931855A (en) | 1997-05-21 | 1999-08-03 | Frank Hoffman | Surgical methods using one-way suture |
US6015433A (en) * | 1998-05-29 | 2000-01-18 | Micro Therapeutics, Inc. | Rolled stent with waveform perforation pattern |
CN1311684A (zh) * | 1998-07-10 | 2001-09-05 | 悉尼大学 | 黄斑变性中新生血管形成的预防治疗 |
US6884427B1 (en) * | 1999-02-08 | 2005-04-26 | Aderans Research Institute, Inc. | Filamentary means for introducing agents into tissue of a living host |
AU6526100A (en) * | 1999-08-06 | 2001-03-05 | Board Of Regents, The University Of Texas System | Drug releasing biodegradable fiber implant |
US7033603B2 (en) * | 1999-08-06 | 2006-04-25 | Board Of Regents The University Of Texas | Drug releasing biodegradable fiber for delivery of therapeutics |
AU770395B2 (en) * | 1999-11-17 | 2004-02-19 | Boston Scientific Limited | Microfabricated devices for the delivery of molecules into a carrier fluid |
US20010053931A1 (en) * | 1999-11-24 | 2001-12-20 | Salvatore J. Abbruzzese | Thin-layered, endovascular silk-covered stent device and method of manufacture thereof |
EP1235560B1 (en) * | 1999-12-10 | 2006-04-19 | Massachusetts Institute Of Technology | Microchip devices for delivery of molecules and methods of fabrication thereof |
AUPQ496500A0 (en) * | 2000-01-06 | 2000-02-03 | University Of Sydney, The | Kit |
US9522217B2 (en) | 2000-03-15 | 2016-12-20 | Orbusneich Medical, Inc. | Medical device with coating for capturing genetically-altered cells and methods for using same |
US8460367B2 (en) | 2000-03-15 | 2013-06-11 | Orbusneich Medical, Inc. | Progenitor endothelial cell capturing with a drug eluting implantable medical device |
US8088060B2 (en) | 2000-03-15 | 2012-01-03 | Orbusneich Medical, Inc. | Progenitor endothelial cell capturing with a drug eluting implantable medical device |
US6638239B1 (en) | 2000-04-14 | 2003-10-28 | Glaukos Corporation | Apparatus and method for treating glaucoma |
AU2001263946A1 (en) * | 2000-05-31 | 2001-12-11 | Mnemoscience Gmbh | Shape memory thermoplastics and polymer networks for tissue engineering |
US8366787B2 (en) * | 2000-08-04 | 2013-02-05 | Depuy Products, Inc. | Hybrid biologic-synthetic bioabsorbable scaffolds |
AU2001279209B2 (en) * | 2000-08-08 | 2006-08-24 | Aderans Research Institute, Inc. | Scaffolds for tissue engineered hair |
SK8222003A3 (en) * | 2000-12-28 | 2003-10-07 | Fidia Advanced Biopolymers Srl | Use of a biological material containing three-dimensional scaffolds of hyaluronic acid derivatives for the preparation of implants in arthroscopy and kit for instruments for implanting said biological material by arthroscopy |
DE10117234A1 (de) * | 2001-04-06 | 2002-10-10 | Alvito Biotechnologie Gmbh | Poröse und nichtporöse Matrices auf Basis von Chitosan und Hydroxycarbonsäuren |
US7431710B2 (en) | 2002-04-08 | 2008-10-07 | Glaukos Corporation | Ocular implants with anchors and methods thereof |
US7488303B1 (en) * | 2002-09-21 | 2009-02-10 | Glaukos Corporation | Ocular implant with anchor and multiple openings |
US6764505B1 (en) * | 2001-04-12 | 2004-07-20 | Advanced Cardiovascular Systems, Inc. | Variable surface area stent |
EP1409647A4 (en) | 2001-04-30 | 2009-09-09 | Yissum Res Dev Co | COMPOSITE SKELETONS AND METHODS OF USE THEREOF FOR GENERATING COMPLEX TISSUE GRAFT |
US7678065B2 (en) | 2001-05-02 | 2010-03-16 | Glaukos Corporation | Implant with intraocular pressure sensor for glaucoma treatment |
AU2002305400A1 (en) | 2001-05-03 | 2002-11-18 | Glaukos Corporation | Medical device and methods of use for glaucoma treatment |
US7862495B2 (en) * | 2001-05-31 | 2011-01-04 | Advanced Cardiovascular Systems, Inc. | Radiation or drug delivery source with activity gradient to minimize edge effects |
GB0113697D0 (en) * | 2001-06-06 | 2001-07-25 | Smith & Nephew | Fixation devices for tissue repair |
US7524513B2 (en) * | 2001-06-15 | 2009-04-28 | Mao Hai-Quan | Biofunctional fibers |
US7056331B2 (en) | 2001-06-29 | 2006-06-06 | Quill Medical, Inc. | Suture method |
AUPR602401A0 (en) * | 2001-06-29 | 2001-07-26 | Smart Drug Systems Inc | Sustained release delivery system |
AUPR602501A0 (en) * | 2001-06-29 | 2001-07-26 | Smart Drug Systems Inc | Sustained release pharmaceutical composition |
US8025896B2 (en) | 2001-07-16 | 2011-09-27 | Depuy Products, Inc. | Porous extracellular matrix scaffold and method |
US7572288B2 (en) | 2001-07-20 | 2009-08-11 | Microvention, Inc. | Aneurysm treatment device and method of use |
US8715312B2 (en) | 2001-07-20 | 2014-05-06 | Microvention, Inc. | Aneurysm treatment device and method of use |
US8252040B2 (en) | 2001-07-20 | 2012-08-28 | Microvention, Inc. | Aneurysm treatment device and method of use |
WO2003009777A2 (en) * | 2001-07-26 | 2003-02-06 | Avantec Vascular Corporation | Delivery of therapeutic capable agents |
US6848152B2 (en) | 2001-08-31 | 2005-02-01 | Quill Medical, Inc. | Method of forming barbs on a suture and apparatus for performing same |
DK1423066T3 (da) | 2001-09-07 | 2008-11-17 | Mardil Inc | Fremgangsmåde og apparat til udvendig hjertestabilisation |
JP2003126125A (ja) * | 2001-10-24 | 2003-05-07 | Katsuko Sakai | 人工血管及びその製造方法 |
GB0126923D0 (en) | 2001-11-09 | 2002-01-02 | Procter & Gamble | Chitosan compositions |
US20040254640A1 (en) * | 2002-03-01 | 2004-12-16 | Children's Medical Center Corporation | Needle punched textile for use in growing anatomical elements |
US7186232B1 (en) * | 2002-03-07 | 2007-03-06 | Glaukoa Corporation | Fluid infusion methods for glaucoma treatment |
US20030180259A1 (en) * | 2002-03-12 | 2003-09-25 | Harold Brem | Method for treating diabetic ulcers |
GB0208418D0 (en) * | 2002-04-11 | 2002-05-22 | Univ Aston | Polymeric fibre |
US8187326B2 (en) * | 2002-05-22 | 2012-05-29 | Advanced Technologies And Regenerative Medicine, Llc. | Attachment of absorbable tissue scaffolds to fixation devices |
US7097850B2 (en) | 2002-06-18 | 2006-08-29 | Surmodics, Inc. | Bioactive agent release coating and controlled humidity method |
US6773450B2 (en) | 2002-08-09 | 2004-08-10 | Quill Medical, Inc. | Suture anchor and method |
US7265097B2 (en) * | 2002-08-20 | 2007-09-04 | Chitogenics, Inc. | Methods of drug delivery using sulphated chitinous polymers |
US20040059409A1 (en) * | 2002-09-24 | 2004-03-25 | Stenzel Eric B. | Method of applying coatings to a medical device |
EP1543860B1 (en) * | 2002-09-25 | 2015-02-18 | Kabushikikaisha Igaki Iryo Sekkei | Thread for vascular stent and vascular stent using the thread |
BR0314743A (pt) * | 2002-09-26 | 2005-07-26 | Angiotech Int Ag | Envoltórios perivasculares |
US20040088003A1 (en) | 2002-09-30 | 2004-05-06 | Leung Jeffrey C. | Barbed suture in combination with surgical needle |
US8100940B2 (en) | 2002-09-30 | 2012-01-24 | Quill Medical, Inc. | Barb configurations for barbed sutures |
US7354574B2 (en) * | 2002-11-07 | 2008-04-08 | Advanced Ocular Systems Limited | Treatment of ocular disease |
US7169178B1 (en) * | 2002-11-12 | 2007-01-30 | Advanced Cardiovascular Systems, Inc. | Stent with drug coating |
US7135040B2 (en) * | 2002-12-23 | 2006-11-14 | Agency For Science, Technology And Research | Medical guide tubes |
ATE531447T1 (de) * | 2003-01-17 | 2011-11-15 | Cornell Res Foundation Inc | Injizierbare hydrogel-microsphären aus wässrigem zwei-phasen-system |
ATE464408T1 (de) * | 2003-02-13 | 2010-04-15 | Teijin Ltd | Poröse faser, poröses fasergebilde und herstellungsverfahren |
US20050198700A1 (en) * | 2003-03-07 | 2005-09-08 | Avigenics, Inc. | Genomic modification |
US20050034186A1 (en) * | 2003-03-07 | 2005-02-10 | Harvey Alex J. | Site specific nucleic acid integration |
US20040255345A1 (en) * | 2003-03-07 | 2004-12-16 | Rapp Jeffrey C. | Production of transgenic avians |
US20050273873A1 (en) * | 2003-03-07 | 2005-12-08 | Avigenics, Inc. | Genomic modification |
EP1610823B1 (en) | 2003-03-28 | 2011-09-28 | Innovational Holdings, LLC | Implantable medical device with continuous agent concentration gradient |
US20040199186A1 (en) * | 2003-04-04 | 2004-10-07 | Kuffler Suzanne Elizabeth | Implant to promote axon regeneration across spinal cord and peripheral nerve gaps |
AU2003902037A0 (en) * | 2003-04-24 | 2003-05-15 | Mclachlan, Craig | Method for tissue growth |
EP2860292B1 (en) | 2003-05-08 | 2020-07-22 | Tepha, Inc. | Polyhydroxyalkanoate medical textiles and fibers |
US7624487B2 (en) | 2003-05-13 | 2009-12-01 | Quill Medical, Inc. | Apparatus and method for forming barbs on a suture |
US9060770B2 (en) | 2003-05-20 | 2015-06-23 | Ethicon Endo-Surgery, Inc. | Robotically-driven surgical instrument with E-beam driver |
US20070084897A1 (en) | 2003-05-20 | 2007-04-19 | Shelton Frederick E Iv | Articulating surgical stapling instrument incorporating a two-piece e-beam firing mechanism |
WO2004108951A1 (en) * | 2003-06-06 | 2004-12-16 | The Board Of Trustees Of The University Of Illinois | Methods for assessing the invasive potential of a cell employing chromatin analysis |
DE10329260A1 (de) * | 2003-06-23 | 2005-01-13 | Biotronik Meß- und Therapiegeräte GmbH & Co. Ingenieurbüro Berlin | Stent mit einem Beschichtungssystem |
US7056332B2 (en) * | 2003-07-24 | 2006-06-06 | Materials Evolution And Development Usa, Inc. | Nucleic acid biomaterials and methods of formation and use |
US7083802B2 (en) * | 2003-07-31 | 2006-08-01 | Advanced Ocular Systems Limited | Treatment of ocular disease |
US7087237B2 (en) | 2003-09-19 | 2006-08-08 | Advanced Ocular Systems Limited | Ocular solutions |
US7083803B2 (en) * | 2003-09-19 | 2006-08-01 | Advanced Ocular Systems Limited | Ocular solutions |
US20050181018A1 (en) * | 2003-09-19 | 2005-08-18 | Peyman Gholam A. | Ocular drug delivery |
US7198675B2 (en) | 2003-09-30 | 2007-04-03 | Advanced Cardiovascular Systems | Stent mandrel fixture and method for selectively coating surfaces of a stent |
US20050079253A1 (en) * | 2003-10-10 | 2005-04-14 | Hiroshi Nakamura | Bilayer edible sheet |
US20050142534A1 (en) * | 2003-10-14 | 2005-06-30 | The Board Of Trustees Of The University Of Illinois | Methods and compositions related to a matrix chip |
JP2007509716A (ja) * | 2003-10-29 | 2007-04-19 | ジェンティス インコーポレイテッド | 組織工学用の重合可能なエマルション |
WO2005046445A2 (en) * | 2003-11-07 | 2005-05-26 | University Of Connecticut | Artificial tissue systems and uses thereof |
US20050148512A1 (en) * | 2003-11-10 | 2005-07-07 | Angiotech International Ag | Medical implants and fibrosis-inducing agents |
EP1682196A2 (en) * | 2003-11-10 | 2006-07-26 | Angiotech International Ag | Medical implants and anti-scarring agents |
US7601285B2 (en) * | 2003-12-31 | 2009-10-13 | Boston Scientific Scimed, Inc. | Medical device with varying physical properties and method for forming same |
WO2005074942A1 (en) * | 2004-02-04 | 2005-08-18 | Retmed Pty Ltd | Slow release steroid composition |
EP1718147B1 (en) * | 2004-02-23 | 2012-03-28 | Loma Linda University Medical Center | Hemostatic agent for topical and internal use |
US20050192257A1 (en) * | 2004-02-26 | 2005-09-01 | Peyman Gholam A. | Predictors for patients at risk for glaucoma from steroid therapy |
CA2557216A1 (en) * | 2004-02-26 | 2005-09-09 | Advanced Ocular Systems Limited | Heparin for the treatment of ocular pathologies |
US20060123504A1 (en) * | 2004-12-07 | 2006-06-08 | Avigenics, Inc. | Methods of producing polyclonal antibodies |
US20060174364A1 (en) * | 2004-03-01 | 2006-08-03 | Avigenics, Inc. | Artificial chromosomes and transchromosomic avians |
FR2867073B1 (fr) * | 2004-03-08 | 2006-05-05 | Europlak | Utilisation cosmetique de chitosane pour le traitement et le comblement des rides |
SI1755616T1 (sl) | 2004-04-08 | 2014-04-30 | Eye Co Pty Ltd. | Zdravljenje eksudativne retinopatije z mineralkortikoidi |
TW200603843A (en) * | 2004-04-20 | 2006-02-01 | Technology Dev Company Ltd | Tissue enhancement implant and method |
EP1740168A2 (en) * | 2004-04-21 | 2007-01-10 | Advanced Ocular Systems Limited | Antiprostaglandins for the treatment of ocular pathologies |
CA2566765C (en) * | 2004-05-11 | 2011-08-23 | Synthasome Inc. | Hybrid tissue scaffolds containing extracellular matrix |
ES2638301T3 (es) | 2004-05-14 | 2017-10-19 | Ethicon Llc | Dispositivos de sutura |
EP1761283A2 (en) * | 2004-06-07 | 2007-03-14 | California Institute Of Technology | Biodegradable drug-polymer delivery system |
US8215531B2 (en) | 2004-07-28 | 2012-07-10 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument having a medical substance dispenser |
US11896225B2 (en) | 2004-07-28 | 2024-02-13 | Cilag Gmbh International | Staple cartridge comprising a pan |
CA2575988C (en) | 2004-08-04 | 2014-02-18 | Brookwood Pharmaceuticals, Inc. | Methods for manufacturing delivery devices and devices thereof |
AR050212A1 (es) * | 2004-08-13 | 2006-10-04 | Aderans Res Inst Inc | Organogenesis a partir de celulas disociadas |
US7351423B2 (en) * | 2004-09-01 | 2008-04-01 | Depuy Spine, Inc. | Musculo-skeletal implant having a bioactive gradient |
US20070190601A1 (en) * | 2004-10-08 | 2007-08-16 | Avigenics, Inc. | Modified integrase and methods of use |
US20060122152A1 (en) * | 2004-12-03 | 2006-06-08 | Peyman Gholam A | Heparin for the treatment of ocular pathologies |
US20060198868A1 (en) * | 2005-01-05 | 2006-09-07 | Dewitt David M | Biodegradable coating compositions comprising blends |
US20060147491A1 (en) * | 2005-01-05 | 2006-07-06 | Dewitt David M | Biodegradable coating compositions including multiple layers |
US7270655B2 (en) * | 2005-01-14 | 2007-09-18 | Haidukewych George J | Autologous material delivery apparatus and method |
US9248015B2 (en) | 2005-03-11 | 2016-02-02 | Wake Forest University Health Services | Production of tissue engineered heart valves |
CA2602029C (en) * | 2005-03-11 | 2014-07-15 | Wake Forest University Health Sciences | Tissue engineered blood vessels |
US20060204539A1 (en) | 2005-03-11 | 2006-09-14 | Anthony Atala | Electrospun cell matrices |
US8728463B2 (en) | 2005-03-11 | 2014-05-20 | Wake Forest University Health Science | Production of tissue engineered digits and limbs |
US20060204445A1 (en) * | 2005-03-11 | 2006-09-14 | Anthony Atala | Cell scaffold matrices with image contrast agents |
US20070020244A1 (en) * | 2005-03-30 | 2007-01-25 | The Johns Hopkins University | Fiber constructs and process of fiber fabrication |
US7311050B2 (en) * | 2005-04-19 | 2007-12-25 | Kamterter Ii, L.L.C. | Systems for the control and use of fluids and particles |
US7536962B2 (en) * | 2005-04-19 | 2009-05-26 | Kamterter Ii, L.L.C. | Systems for the control and use of fluids and particles |
US8308075B2 (en) | 2005-04-19 | 2012-11-13 | Kamterter Products, Llc | Systems for the control and use of fluids and particles |
US8663686B2 (en) * | 2005-05-09 | 2014-03-04 | University Of Washington | Biodegradable chitosan-PEG compositions and methods of use |
US20060257355A1 (en) * | 2005-05-10 | 2006-11-16 | Abiomed, Inc. | Impregnated polymer compositions and devices using them |
FI20055304L (fi) * | 2005-06-13 | 2007-02-20 | Bioretec Oy | Bioabsorboituva implantti, jolla on muuttuva ominaisuus |
US8568761B2 (en) * | 2005-07-15 | 2013-10-29 | Cormatrix Cardiovascular, Inc. | Compositions for regenerating defective or absent myocardium |
US20070014760A1 (en) | 2005-07-18 | 2007-01-18 | Peyman Gholam A | Enhanced recovery following ocular surgery |
PL1904056T3 (pl) * | 2005-07-18 | 2009-09-30 | Minu Llc | Zastosowanie makrolidu do przywracania czucia rogówkowego |
US7604668B2 (en) * | 2005-07-29 | 2009-10-20 | Gore Enterprise Holdings, Inc. | Composite self-cohered web materials |
US20070026039A1 (en) * | 2005-07-29 | 2007-02-01 | Drumheller Paul D | Composite self-cohered web materials |
US7655584B2 (en) * | 2005-07-29 | 2010-02-02 | Gore Enterprise Holdings, Inc. | Highly porous self-cohered web materials |
US8048503B2 (en) * | 2005-07-29 | 2011-11-01 | Gore Enterprise Holdings, Inc. | Highly porous self-cohered web materials |
US20070026040A1 (en) * | 2005-07-29 | 2007-02-01 | Crawley Jerald M | Composite self-cohered web materials |
US7655288B2 (en) * | 2005-07-29 | 2010-02-02 | Gore Enterprise Holdings, Inc. | Composite self-cohered web materials |
US20070027551A1 (en) * | 2005-07-29 | 2007-02-01 | Farnsworth Ted R | Composite self-cohered web materials |
US7850810B2 (en) * | 2005-07-29 | 2010-12-14 | Gore Enterprise Holdings, Inc. | Method of making porous self-cohered web materials |
US9248034B2 (en) | 2005-08-23 | 2016-02-02 | Advanced Cardiovascular Systems, Inc. | Controlled disintegrating implantable medical devices |
US7673781B2 (en) | 2005-08-31 | 2010-03-09 | Ethicon Endo-Surgery, Inc. | Surgical stapling device with staple driver that supports multiple wire diameter staples |
US10159482B2 (en) | 2005-08-31 | 2018-12-25 | Ethicon Llc | Fastener cartridge assembly comprising a fixed anvil and different staple heights |
US9237891B2 (en) | 2005-08-31 | 2016-01-19 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical stapling devices that produce formed staples having different lengths |
US11246590B2 (en) | 2005-08-31 | 2022-02-15 | Cilag Gmbh International | Staple cartridge including staple drivers having different unfired heights |
US11484312B2 (en) | 2005-08-31 | 2022-11-01 | Cilag Gmbh International | Staple cartridge comprising a staple driver arrangement |
US7669746B2 (en) | 2005-08-31 | 2010-03-02 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US7934630B2 (en) | 2005-08-31 | 2011-05-03 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
KR101420988B1 (ko) | 2005-10-13 | 2014-07-17 | 신세스 게엠바하 | 약물-함침 용기 |
GB0522569D0 (en) * | 2005-11-04 | 2005-12-14 | Univ Bath | Biocompatible drug delivery device |
US20070106317A1 (en) | 2005-11-09 | 2007-05-10 | Shelton Frederick E Iv | Hydraulically and electrically actuated articulation joints for surgical instruments |
US20070148138A1 (en) | 2005-11-22 | 2007-06-28 | Aderans Research Institute, Inc. | Hair follicle graft from tissue engineered skin |
WO2007064305A1 (en) * | 2005-12-01 | 2007-06-07 | Agency For Science, Technology And Research | Three-dimensional reconstituted extracellular matrices as scaffolds for tissue engineering |
WO2007066339A1 (en) * | 2005-12-07 | 2007-06-14 | Ramot At Tel Aviv University Ltd. | Drug-delivering composite structures |
AU2015264807A1 (en) * | 2005-12-13 | 2015-12-17 | President And Fellows Of Harvard College | Scaffolds for Cell Transplantation |
EP2347774B1 (en) * | 2005-12-13 | 2017-07-26 | The President and Fellows of Harvard College | Scaffolds for cell transplantation |
US7867547B2 (en) | 2005-12-19 | 2011-01-11 | Advanced Cardiovascular Systems, Inc. | Selectively coating luminal surfaces of stents |
TWI285100B (en) * | 2005-12-27 | 2007-08-11 | Ind Tech Res Inst | Surface modification of polysaccharide, the modified polysaccharide, and method of culturing and recovery cells using the same |
US20070148697A1 (en) * | 2005-12-27 | 2007-06-28 | Boston Scientific Scimed, Inc. | Methods and system for high throughput screening of polymer materials for medical devices |
US7845537B2 (en) | 2006-01-31 | 2010-12-07 | Ethicon Endo-Surgery, Inc. | Surgical instrument having recording capabilities |
US20110290856A1 (en) | 2006-01-31 | 2011-12-01 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical instrument with force-feedback capabilities |
US11278279B2 (en) | 2006-01-31 | 2022-03-22 | Cilag Gmbh International | Surgical instrument assembly |
US9861359B2 (en) | 2006-01-31 | 2018-01-09 | Ethicon Llc | Powered surgical instruments with firing system lockout arrangements |
US11793518B2 (en) | 2006-01-31 | 2023-10-24 | Cilag Gmbh International | Powered surgical instruments with firing system lockout arrangements |
US20110006101A1 (en) | 2009-02-06 | 2011-01-13 | EthiconEndo-Surgery, Inc. | Motor driven surgical fastener device with cutting member lockout arrangements |
US8708213B2 (en) | 2006-01-31 | 2014-04-29 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a feedback system |
US7753904B2 (en) | 2006-01-31 | 2010-07-13 | Ethicon Endo-Surgery, Inc. | Endoscopic surgical instrument with a handle that can articulate with respect to the shaft |
US8186555B2 (en) | 2006-01-31 | 2012-05-29 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting and fastening instrument with mechanical closure system |
US8820603B2 (en) | 2006-01-31 | 2014-09-02 | Ethicon Endo-Surgery, Inc. | Accessing data stored in a memory of a surgical instrument |
US20110024477A1 (en) | 2009-02-06 | 2011-02-03 | Hall Steven G | Driven Surgical Stapler Improvements |
US11224427B2 (en) | 2006-01-31 | 2022-01-18 | Cilag Gmbh International | Surgical stapling system including a console and retraction assembly |
US20120292367A1 (en) | 2006-01-31 | 2012-11-22 | Ethicon Endo-Surgery, Inc. | Robotically-controlled end effector |
US20070208217A1 (en) | 2006-03-03 | 2007-09-06 | Acorn Cardiovascular, Inc. | Self-adjusting attachment structure for a cardiac support device |
CN100375635C (zh) * | 2006-03-07 | 2008-03-19 | 中国药科大学 | 一种水溶性抗癌药物缓释纤维制剂及其制备方法 |
EP2374472B9 (en) | 2006-03-16 | 2019-06-12 | Dyax Corp. | Compositions and methods for treating ophthalmic disorders |
CZ300142B6 (cs) * | 2006-03-22 | 2009-02-25 | Ústav experimentální medicíny AV CR | Zpusob výroby vlákenných biodegradabilních krycích materiálu jako nosicu léciv s rízeným uvolnováním |
US8992422B2 (en) | 2006-03-23 | 2015-03-31 | Ethicon Endo-Surgery, Inc. | Robotically-controlled endoscopic accessory channel |
US8236010B2 (en) | 2006-03-23 | 2012-08-07 | Ethicon Endo-Surgery, Inc. | Surgical fastener and cutter with mimicking end effector |
BRPI0709412A8 (pt) * | 2006-03-28 | 2019-01-02 | Larsen Gustavo | método de produção de uma bandagem hemostática utilizando um objeto rotativo |
US7737060B2 (en) * | 2006-03-31 | 2010-06-15 | Boston Scientific Scimed, Inc. | Medical devices containing multi-component fibers |
JP5538881B2 (ja) * | 2006-04-25 | 2014-07-02 | テレフレックス・メディカル・インコーポレイテッド | リン酸カルシウムポリマー複合材料および方法 |
US20080051335A1 (en) * | 2006-05-02 | 2008-02-28 | Kleiner Lothar W | Methods, compositions and devices for treating lesioned sites using bioabsorbable carriers |
US8003156B2 (en) | 2006-05-04 | 2011-08-23 | Advanced Cardiovascular Systems, Inc. | Rotatable support elements for stents |
US20070275035A1 (en) * | 2006-05-24 | 2007-11-29 | Microchips, Inc. | Minimally Invasive Medical Implant Devices for Controlled Drug Delivery |
CN100447319C (zh) * | 2006-06-08 | 2008-12-31 | 利芳建医药科技咨询(上海)有限公司 | 一种防治乳腺增生的药用蛋白质纤维及其制备和应用 |
US8603530B2 (en) | 2006-06-14 | 2013-12-10 | Abbott Cardiovascular Systems Inc. | Nanoshell therapy |
US8048448B2 (en) | 2006-06-15 | 2011-11-01 | Abbott Cardiovascular Systems Inc. | Nanoshells for drug delivery |
US7458953B2 (en) * | 2006-06-20 | 2008-12-02 | Gholam A. Peyman | Ocular drainage device |
US8017237B2 (en) | 2006-06-23 | 2011-09-13 | Abbott Cardiovascular Systems, Inc. | Nanoshells on polymers |
US8322455B2 (en) | 2006-06-27 | 2012-12-04 | Ethicon Endo-Surgery, Inc. | Manually driven surgical cutting and fastening instrument |
AU2007272224B2 (en) | 2006-07-10 | 2013-05-02 | Novartis Ag | scFv antibodies which pass epithelial and/or endothelial layers |
JP4569543B2 (ja) * | 2006-08-18 | 2010-10-27 | ニプロ株式会社 | 膨潤可能な棒状体を備えた組織再生器具の前駆体 |
WO2008033533A2 (en) * | 2006-09-15 | 2008-03-20 | Angiotech Pharmaceuticals, Inc. | Composite drug delivery system |
US20080097380A1 (en) * | 2006-09-21 | 2008-04-24 | Li Kasey K | Method and apparatus for creating variable stiffness and/or reduction of soft tissue |
US20080078802A1 (en) | 2006-09-29 | 2008-04-03 | Hess Christopher J | Surgical staples and stapling instruments |
US10130359B2 (en) | 2006-09-29 | 2018-11-20 | Ethicon Llc | Method for forming a staple |
US10568652B2 (en) | 2006-09-29 | 2020-02-25 | Ethicon Llc | Surgical staples having attached drivers of different heights and stapling instruments for deploying the same |
US11980366B2 (en) | 2006-10-03 | 2024-05-14 | Cilag Gmbh International | Surgical instrument |
US20090169628A1 (en) * | 2006-10-17 | 2009-07-02 | Armark Authentication Technologies, Llc | Article and method for focused delivery of therapeutic and/or diagnostic materials |
EP1920768A1 (en) * | 2006-11-10 | 2008-05-14 | Abbott GmbH & Co. KG | Solid dosage form with a film containing an active substance, as well as its method of production |
JP5539727B2 (ja) * | 2006-12-11 | 2014-07-02 | チット2ジェル リミテッド | ヒドロゲルを形成する新規な注入可能なキトサン混合物 |
US7871440B2 (en) | 2006-12-11 | 2011-01-18 | Depuy Products, Inc. | Unitary surgical device and method |
US9034348B2 (en) | 2006-12-11 | 2015-05-19 | Chi2Gel Ltd. | Injectable chitosan mixtures forming hydrogels |
US8153612B2 (en) | 2006-12-11 | 2012-04-10 | Chi2Gel Ltd. | Injectable chitosan mixtures forming hydrogels |
US8684253B2 (en) | 2007-01-10 | 2014-04-01 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between a control unit of a robotic system and remote sensor |
US11291441B2 (en) | 2007-01-10 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with wireless communication between control unit and remote sensor |
US8652120B2 (en) | 2007-01-10 | 2014-02-18 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between control unit and sensor transponders |
US11039836B2 (en) | 2007-01-11 | 2021-06-22 | Cilag Gmbh International | Staple cartridge for use with a surgical stapling instrument |
US8701958B2 (en) | 2007-01-11 | 2014-04-22 | Ethicon Endo-Surgery, Inc. | Curved end effector for a surgical stapling device |
DE102007011606A1 (de) * | 2007-03-02 | 2008-09-04 | Carl Freudenberg Kg | Faser-Wirrgelege |
US7604151B2 (en) | 2007-03-15 | 2009-10-20 | Ethicon Endo-Surgery, Inc. | Surgical stapling systems and staple cartridges for deploying surgical staples with tissue compression features |
US8893946B2 (en) | 2007-03-28 | 2014-11-25 | Ethicon Endo-Surgery, Inc. | Laparoscopic tissue thickness and clamp load measuring devices |
WO2008122044A2 (en) * | 2007-04-02 | 2008-10-09 | Georgia Tech Research Corporation | Implantable device for communicating with biological tissue |
US20080255612A1 (en) | 2007-04-13 | 2008-10-16 | Angiotech Pharmaceuticals, Inc. | Self-retaining systems for surgical procedures |
US11564682B2 (en) | 2007-06-04 | 2023-01-31 | Cilag Gmbh International | Surgical stapler device |
US8931682B2 (en) | 2007-06-04 | 2015-01-13 | Ethicon Endo-Surgery, Inc. | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US7985537B2 (en) | 2007-06-12 | 2011-07-26 | Aderans Research Institute, Inc. | Methods for determining the hair follicle inductive properties of a composition |
WO2009002401A2 (en) * | 2007-06-21 | 2008-12-31 | President And Fellows Of Harvard College | Scaffolds for cell collection or elimination |
US8408439B2 (en) | 2007-06-22 | 2013-04-02 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument with an articulatable end effector |
US7753245B2 (en) | 2007-06-22 | 2010-07-13 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments |
WO2009003049A2 (en) | 2007-06-25 | 2008-12-31 | Micro Vention, Inc. | Self-expanding prosthesis |
US8048441B2 (en) | 2007-06-25 | 2011-11-01 | Abbott Cardiovascular Systems, Inc. | Nanobead releasing medical devices |
US11849941B2 (en) | 2007-06-29 | 2023-12-26 | Cilag Gmbh International | Staple cartridge having staple cavities extending at a transverse angle relative to a longitudinal cartridge axis |
KR100932688B1 (ko) * | 2007-07-06 | 2009-12-21 | 한국과학기술연구원 | 인공혈관용 이중막 구조의 튜브형 다공성 스캐폴드 및 그의제조방법 |
US20090036907A1 (en) * | 2007-07-30 | 2009-02-05 | Yves Bayon | Bioresorbable knit |
DE102007039871A1 (de) * | 2007-08-21 | 2009-02-26 | Friedrich-Baur-Gmbh | Weichgewebe-Implantat mit antibakterieller Wirkung |
US8293531B1 (en) | 2007-08-31 | 2012-10-23 | Clemson University Research Foundation | Three-dimensional ex vivo system |
US8092363B2 (en) | 2007-09-05 | 2012-01-10 | Mardil, Inc. | Heart band with fillable chambers to modify heart valve function |
US20090136553A1 (en) * | 2007-09-25 | 2009-05-28 | Gerlach Jorg C | Triggerably dissolvable hollow fibers for controlled delivery |
ES2488406T3 (es) | 2007-09-27 | 2014-08-27 | Ethicon Llc | Suturas de auto-retención que incluyen elementos de retención a tejido con resistencia mejorada |
CN101417121B (zh) * | 2007-10-27 | 2011-09-28 | 董昌金 | 一种治疗皮肤烧烫冻伤的药物 |
US20090130160A1 (en) * | 2007-11-21 | 2009-05-21 | Fiber Innovation Technology, Inc. | Fiber for wound dressing |
WO2009086172A2 (en) | 2007-12-19 | 2009-07-09 | Angiotech Pharmaceuticals, Inc. | Self-retaining sutures with heat-contact mediated retainers |
US8916077B1 (en) | 2007-12-19 | 2014-12-23 | Ethicon, Inc. | Self-retaining sutures with retainers formed from molten material |
US8118834B1 (en) | 2007-12-20 | 2012-02-21 | Angiotech Pharmaceuticals, Inc. | Composite self-retaining sutures and method |
ES2718612T3 (es) | 2007-12-20 | 2019-07-03 | Evonik Corp | Procedimiento para preparar micropartículas que tienen un bajo volumen de disolvente residual |
JP2011509156A (ja) * | 2008-01-08 | 2011-03-24 | イェール ユニバーシティ | 血管移植片の開存性を促進するための組成物および方法 |
US20090192609A1 (en) * | 2008-01-29 | 2009-07-30 | Zimmer, Inc. | Implant device for use in an implant system |
EP2242430B1 (en) | 2008-01-30 | 2016-08-17 | Ethicon, LLC | Apparatus and method for forming self-retaining sutures |
US8615856B1 (en) | 2008-01-30 | 2013-12-31 | Ethicon, Inc. | Apparatus and method for forming self-retaining sutures |
US9782300B2 (en) * | 2008-02-01 | 2017-10-10 | Kci Licensing, Inc. | Fiber-microsphere bioresorbable composite scaffold for wound healing |
US9370558B2 (en) | 2008-02-13 | 2016-06-21 | President And Fellows Of Harvard College | Controlled delivery of TLR agonists in structural polymeric devices |
US8561870B2 (en) | 2008-02-13 | 2013-10-22 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument |
US10328133B2 (en) | 2008-02-13 | 2019-06-25 | President And Fellows Of Harvard College | Continuous cell programming devices |
US8758391B2 (en) | 2008-02-14 | 2014-06-24 | Ethicon Endo-Surgery, Inc. | Interchangeable tools for surgical instruments |
US11986183B2 (en) | 2008-02-14 | 2024-05-21 | Cilag Gmbh International | Surgical cutting and fastening instrument comprising a plurality of sensors to measure an electrical parameter |
US8573465B2 (en) | 2008-02-14 | 2013-11-05 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical end effector system with rotary actuated closure systems |
US8657174B2 (en) | 2008-02-14 | 2014-02-25 | Ethicon Endo-Surgery, Inc. | Motorized surgical cutting and fastening instrument having handle based power source |
US7866527B2 (en) | 2008-02-14 | 2011-01-11 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with interlockable firing system |
RU2493788C2 (ru) | 2008-02-14 | 2013-09-27 | Этикон Эндо-Серджери, Инк. | Хирургический режущий и крепежный инструмент, имеющий радиочастотные электроды |
US9179912B2 (en) | 2008-02-14 | 2015-11-10 | Ethicon Endo-Surgery, Inc. | Robotically-controlled motorized surgical cutting and fastening instrument |
US7819298B2 (en) | 2008-02-14 | 2010-10-26 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with control features operable with one hand |
US8636736B2 (en) | 2008-02-14 | 2014-01-28 | Ethicon Endo-Surgery, Inc. | Motorized surgical cutting and fastening instrument |
US11272927B2 (en) | 2008-02-15 | 2022-03-15 | Cilag Gmbh International | Layer arrangements for surgical staple cartridges |
US9770245B2 (en) | 2008-02-15 | 2017-09-26 | Ethicon Llc | Layer arrangements for surgical staple cartridges |
EP3533399A3 (en) | 2008-02-21 | 2019-10-23 | Ethicon LLC | Method for elevating retainers on self-retaining sutures |
US8216273B1 (en) | 2008-02-25 | 2012-07-10 | Ethicon, Inc. | Self-retainers with supporting structures on a suture |
US8641732B1 (en) | 2008-02-26 | 2014-02-04 | Ethicon, Inc. | Self-retaining suture with variable dimension filament and method |
US7935364B2 (en) * | 2008-03-04 | 2011-05-03 | Wisconsin Alumni Research Foundation | Patterned gradient wound dressing and methods of using same to promote wound healing |
US9233080B2 (en) | 2008-03-27 | 2016-01-12 | Agigma, Inc. | Compositions and methods for the delivery of agents |
CA2720847C (en) | 2008-04-15 | 2016-06-28 | Angiotech Pharmaceuticals, Inc. | Self-retaining sutures with bi-directional retainers or uni-directional retainers |
WO2009135246A1 (en) * | 2008-05-07 | 2009-11-12 | Obj Limited | Method and apparatus for enhanced transdermal diffusion |
US8586086B2 (en) | 2008-05-29 | 2013-11-19 | Politecnico Di Milano | Hydrogel capable of containing and conveying cells |
US9012399B2 (en) * | 2008-05-30 | 2015-04-21 | President And Fellows Of Harvard College | Controlled release of growth factors and signaling molecules for promoting angiogenesis |
AU2009255973B2 (en) | 2008-06-06 | 2013-08-15 | Children's Medical Center Corporation | Promoting axon regeneration in the adult CNS through control of protein translation |
US20110091515A1 (en) * | 2008-06-12 | 2011-04-21 | Ramot At Tel-Aviv University Ltd. | Drug-eluting medical devices |
US20100007059A1 (en) * | 2008-07-08 | 2010-01-14 | Yury Rochev | method in spinning |
CN101628132B (zh) * | 2008-07-17 | 2014-12-03 | 上海交通大学医学院附属瑞金医院 | 一种仿生真皮及其制备方法和用途 |
US20100040660A1 (en) * | 2008-08-12 | 2010-02-18 | Korea Research Institute Of Chemical Technology | Development of a tissue - engineered scaffold for nerve regeneration using a biocompatible and injectable hydrogel |
TWI414328B (zh) * | 2008-09-18 | 2013-11-11 | Nat Health Research Institutes | 可植入性神經再生導管 |
PL3476312T3 (pl) | 2008-09-19 | 2024-03-11 | Ethicon Llc | Stapler chirurgiczny z urządzeniem do dopasowania wysokości zszywek |
US7832612B2 (en) | 2008-09-19 | 2010-11-16 | Ethicon Endo-Surgery, Inc. | Lockout arrangement for a surgical stapler |
US11648005B2 (en) | 2008-09-23 | 2023-05-16 | Cilag Gmbh International | Robotically-controlled motorized surgical instrument with an end effector |
US9005230B2 (en) | 2008-09-23 | 2015-04-14 | Ethicon Endo-Surgery, Inc. | Motorized surgical instrument |
US9386983B2 (en) | 2008-09-23 | 2016-07-12 | Ethicon Endo-Surgery, Llc | Robotically-controlled motorized surgical instrument |
US8210411B2 (en) | 2008-09-23 | 2012-07-03 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting instrument |
WO2010037021A2 (en) * | 2008-09-29 | 2010-04-01 | Armark Authentication Technologies, Llc | Spinneret and method of spinning fiber |
EP2349363B1 (en) | 2008-10-09 | 2018-12-05 | MiMedx Group, Inc. | Methods of making biocomposite medical constructs and related constructs including artificial tissues, vessels and patches |
US8608045B2 (en) | 2008-10-10 | 2013-12-17 | Ethicon Endo-Sugery, Inc. | Powered surgical cutting and stapling apparatus with manually retractable firing system |
US9642658B2 (en) * | 2008-10-15 | 2017-05-09 | Orthoclip Llc | Device and method for delivery of therapeutic agents via internal implants |
EP2346421A1 (en) * | 2008-10-15 | 2011-07-27 | Bioshape Solutions Inc. | Device and method for delivery of therapeutic agents via internal implants |
SG196767A1 (en) | 2008-11-03 | 2014-02-13 | Ethicon Llc | Length of self-retaining suture and method and device for using the same |
CN102281870B (zh) * | 2008-12-10 | 2015-03-04 | 安徽中人科技有限责任公司 | 新型控释组合物 |
GB2466073A (en) * | 2008-12-12 | 2010-06-16 | Univ Manchester | Tissue repair scaffold |
CN101751123B (zh) * | 2008-12-16 | 2011-11-09 | 鸿富锦精密工业(深圳)有限公司 | 方向传感电路及应用该电路的电子装置 |
US20100151114A1 (en) * | 2008-12-17 | 2010-06-17 | Zimmer, Inc. | In-line treatment of yarn prior to creating a fabric |
TWI328565B (en) * | 2008-12-19 | 2010-08-11 | Taiwan Textile Res Inst | Dispersions of conductive carbon materials and methods for preparing the same |
US20100291214A1 (en) * | 2008-12-23 | 2010-11-18 | Armark Authentication Technologies, Llc | Three-dimensional microfiber extrudate structure and process for forming three-dimensional microfiber extrudate structure |
US20100291182A1 (en) * | 2009-01-21 | 2010-11-18 | Arsenal Medical, Inc. | Drug-Loaded Fibers |
US8517239B2 (en) | 2009-02-05 | 2013-08-27 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument comprising a magnetic element driver |
CA2751664A1 (en) | 2009-02-06 | 2010-08-12 | Ethicon Endo-Surgery, Inc. | Driven surgical stapler improvements |
US8444036B2 (en) | 2009-02-06 | 2013-05-21 | Ethicon Endo-Surgery, Inc. | Motor driven surgical fastener device with mechanisms for adjusting a tissue gap within the end effector |
US9345486B2 (en) * | 2009-03-16 | 2016-05-24 | University Of Washington | Nanofibrous conduits for nerve regeneration |
US20100249832A1 (en) * | 2009-03-31 | 2010-09-30 | Joshua Stopek | Multizone Implants |
US9592043B2 (en) * | 2009-03-31 | 2017-03-14 | Covidien Lp | Multizone implants |
US20100249854A1 (en) * | 2009-03-31 | 2010-09-30 | Thomas Jonathan D | Multizone Implants |
US20100249944A1 (en) * | 2009-03-31 | 2010-09-30 | Thomas Jonathan D | Multizone Implants |
WO2010120749A2 (en) | 2009-04-13 | 2010-10-21 | President And Fellow Of Harvard College | Harnessing cell dynamics to engineer materials |
US20120045487A1 (en) * | 2009-04-29 | 2012-02-23 | The Regents Of The University Of Michigan | Multiphasic microfibers for spatially guided cell growth |
US20100291384A1 (en) * | 2009-05-15 | 2010-11-18 | Armark Authentication Technologies, Llc | Fiber having non-uniform composition and method for making same |
US10206813B2 (en) | 2009-05-18 | 2019-02-19 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
WO2010134943A1 (en) * | 2009-05-22 | 2010-11-25 | Soft Tissue Regeneration, Inc. | Mechanically competent scaffold for ligament and tendon regeneration |
JP2012161363A (ja) | 2011-02-03 | 2012-08-30 | Yahashi Kogyo Kk | ケイ素及びカルシウム徐放性綿状物及びその製造方法 |
WO2011014871A1 (en) | 2009-07-31 | 2011-02-03 | President And Fellows Of Harvard College | Programming of cells for tolerogenic therapies |
US9044580B2 (en) | 2009-08-24 | 2015-06-02 | Arsenal Medical, Inc. | In-situ forming foams with outer layer |
US20110202016A1 (en) * | 2009-08-24 | 2011-08-18 | Arsenal Medical, Inc. | Systems and methods relating to polymer foams |
US10420862B2 (en) | 2009-08-24 | 2019-09-24 | Aresenal AAA, LLC. | In-situ forming foams for treatment of aneurysms |
US9173817B2 (en) | 2009-08-24 | 2015-11-03 | Arsenal Medical, Inc. | In situ forming hemostatic foam implants |
CA2775077C (en) * | 2009-09-22 | 2018-05-01 | Evonik Degussa Corporation | Implant devices having varying bioactive agent loading configurations |
WO2011046515A1 (en) | 2009-10-14 | 2011-04-21 | Nanyang Technological University | Antiproliferative agent |
GB2474851A (en) * | 2009-10-27 | 2011-05-04 | Univ Bolton | Wound dressing comprising anti-microbial honey encapsulated within biocompatible and biodegradable fibre, and the fibre's production |
CA2780294C (en) | 2009-11-09 | 2018-01-16 | Spotlight Technology Partners Llc | Polysaccharide based hydrogels |
WO2011057133A1 (en) | 2009-11-09 | 2011-05-12 | Spotlight Technology Partners Llc | Fragmented hydrogels |
WO2011066471A1 (en) | 2009-11-25 | 2011-06-03 | Loma Linda University Medical Center | Chitosan-based hemostatic textile |
EP2338534A2 (de) * | 2009-12-21 | 2011-06-29 | Biotronik VI Patent AG | Medizinisches Implantat, Beschichtungsverfahren sowie Implantationsverfahren |
SG181759A1 (en) | 2009-12-21 | 2012-07-30 | Janssen R & D Ireland | Degradable removable implant for the sustained release of an active compound |
US8851354B2 (en) | 2009-12-24 | 2014-10-07 | Ethicon Endo-Surgery, Inc. | Surgical cutting instrument that analyzes tissue thickness |
US8220688B2 (en) | 2009-12-24 | 2012-07-17 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting instrument with electric actuator directional control assembly |
WO2011090628A2 (en) | 2009-12-29 | 2011-07-28 | Angiotech Pharmaceuticals, Inc. | Bidirectional self-retaining sutures with laser-marked and/or non-laser marked indicia and methods |
US9216240B2 (en) * | 2010-02-03 | 2015-12-22 | Covidien Lp | Differential loading of drug-eluting medical devices |
US20130202672A1 (en) * | 2010-02-19 | 2013-08-08 | Singapore Agency For Science, Technology And Research Act | Fiber-assembled tissue constructs |
US20110218606A1 (en) * | 2010-03-02 | 2011-09-08 | Medtronic Vascular, Inc. | Methods for Stabilizing Femoral Vessels |
US9610328B2 (en) | 2010-03-05 | 2017-04-04 | President And Fellows Of Harvard College | Enhancement of skeletal muscle stem cell engraftment by dual delivery of VEGF and IGF-1 |
WO2011123798A2 (en) * | 2010-04-01 | 2011-10-06 | The Johns Hopkins University | Three-dimensional scaffolds, methods for fabricating the same, and methods of treating a peripheral nerve or spinal or spinal cord injury |
NZ603886A (en) | 2010-05-04 | 2014-12-24 | Ethicon Llc | Self-retaining systems having laser-cut retainers |
JP5569826B2 (ja) * | 2010-05-10 | 2014-08-13 | 独立行政法人物質・材料研究機構 | 高分子ファイバーとその製造方法および製造装置 |
WO2011146978A1 (en) | 2010-05-25 | 2011-12-01 | International Scientific Pty Ltd | Delivery of oral care products |
BR112012031606B1 (pt) | 2010-06-11 | 2020-11-10 | Ethicon Llc | distribuidor de sutura |
JP5718459B2 (ja) | 2010-06-17 | 2015-05-13 | ワシントン・ユニバーシティWashington University | 整列した繊維を有する生物医学的パッチ |
WO2011156869A1 (en) | 2010-06-17 | 2011-12-22 | International Scientific Pty Ltd | Delivery of skin care products |
US9693954B2 (en) | 2010-06-25 | 2017-07-04 | President And Fellows Of Harvard College | Co-delivery of stimulatory and inhibitory factors to create temporally stable and spatially restricted zones |
RU2541949C2 (ru) | 2010-07-02 | 2015-02-20 | Дзе Проктер Энд Гэмбл Компани | Филаменты, содержащие активный агент, нетканые полотна и способы их получения |
CN102971408B (zh) * | 2010-07-02 | 2016-03-02 | 宝洁公司 | 洗涤剂产品 |
CN103025930B (zh) | 2010-07-02 | 2014-11-12 | 宝洁公司 | 递送活性剂的方法 |
US8618200B2 (en) * | 2010-07-22 | 2013-12-31 | Biotronik Se & Co. Kg | Electrode lead for medical use, insulating tube and method for producing the same |
WO2012015623A1 (en) * | 2010-07-27 | 2012-02-02 | Arsenal Medical | Fiber composite structure |
US8783543B2 (en) | 2010-07-30 | 2014-07-22 | Ethicon Endo-Surgery, Inc. | Tissue acquisition arrangements and methods for surgical stapling devices |
CA2807762C (en) | 2010-08-13 | 2023-08-08 | Wake Forest University Health Sciences | Methods for making a tissue engineered muscle repair (temr) construct in vitro for implantation in vivo |
US9629814B2 (en) | 2010-09-30 | 2017-04-25 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator configured to redistribute compressive forces |
US9386988B2 (en) | 2010-09-30 | 2016-07-12 | Ethicon End-Surgery, LLC | Retainer assembly including a tissue thickness compensator |
US9220501B2 (en) | 2010-09-30 | 2015-12-29 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensators |
US10945731B2 (en) | 2010-09-30 | 2021-03-16 | Ethicon Llc | Tissue thickness compensator comprising controlled release and expansion |
US9307989B2 (en) | 2012-03-28 | 2016-04-12 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator incorportating a hydrophobic agent |
RU2013119928A (ru) | 2010-09-30 | 2014-11-10 | Этикон Эндо-Серджери, Инк. | Сшивающая система, содержащая удерживающую матрицу и выравнивающую матрицу |
US11298125B2 (en) | 2010-09-30 | 2022-04-12 | Cilag Gmbh International | Tissue stapler having a thickness compensator |
US9414838B2 (en) | 2012-03-28 | 2016-08-16 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprised of a plurality of materials |
US9301753B2 (en) | 2010-09-30 | 2016-04-05 | Ethicon Endo-Surgery, Llc | Expandable tissue thickness compensator |
US11812965B2 (en) | 2010-09-30 | 2023-11-14 | Cilag Gmbh International | Layer of material for a surgical end effector |
US11849952B2 (en) | 2010-09-30 | 2023-12-26 | Cilag Gmbh International | Staple cartridge comprising staples positioned within a compressible portion thereof |
US9220500B2 (en) | 2010-09-30 | 2015-12-29 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising structure to produce a resilient load |
US9272406B2 (en) | 2010-09-30 | 2016-03-01 | Ethicon Endo-Surgery, Llc | Fastener cartridge comprising a cutting member for releasing a tissue thickness compensator |
US9332974B2 (en) | 2010-09-30 | 2016-05-10 | Ethicon Endo-Surgery, Llc | Layered tissue thickness compensator |
US9241714B2 (en) | 2011-04-29 | 2016-01-26 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator and method for making the same |
US8857694B2 (en) | 2010-09-30 | 2014-10-14 | Ethicon Endo-Surgery, Inc. | Staple cartridge loading assembly |
US9232941B2 (en) | 2010-09-30 | 2016-01-12 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising a reservoir |
US9364233B2 (en) | 2010-09-30 | 2016-06-14 | Ethicon Endo-Surgery, Llc | Tissue thickness compensators for circular surgical staplers |
US9314246B2 (en) | 2010-09-30 | 2016-04-19 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator incorporating an anti-inflammatory agent |
US20120080498A1 (en) | 2010-09-30 | 2012-04-05 | Ethicon Endo-Surgery, Inc. | Curved end effector for a stapling instrument |
US8695866B2 (en) | 2010-10-01 | 2014-04-15 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a power control circuit |
JP6104806B2 (ja) | 2010-10-06 | 2017-03-29 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | 材料に基づく細胞治療のための注射可能孔形成性ハイドロゲル |
WO2012054841A2 (en) | 2010-10-22 | 2012-04-26 | The Regents Of The University Of Michigan | Optical devices with switchable particles |
RU2608237C2 (ru) | 2010-11-03 | 2017-01-17 | ЭТИКОН ЭлЭлСи | Самоудерживающиеся шовные материалы, выделяющие лекарственные средства, и относящиеся к ним методы |
WO2012064697A2 (en) | 2010-11-08 | 2012-05-18 | President And Fellows Of Harvard College | Materials presenting notch signaling molecules to control cell behavior |
NZ704802A (en) | 2010-11-09 | 2015-12-24 | Ethicon Llc | Emergency self-retaining sutures and packaging |
US8360765B2 (en) | 2011-01-07 | 2013-01-29 | Covidien Lp | Systems and method for forming a coaxial implant |
US8968626B2 (en) | 2011-01-31 | 2015-03-03 | Arsenal Medical, Inc. | Electrospinning process for manufacture of multi-layered structures |
US9194058B2 (en) | 2011-01-31 | 2015-11-24 | Arsenal Medical, Inc. | Electrospinning process for manufacture of multi-layered structures |
US9034240B2 (en) | 2011-01-31 | 2015-05-19 | Arsenal Medical, Inc. | Electrospinning process for fiber manufacture |
WO2012118796A1 (en) | 2011-02-28 | 2012-09-07 | The Schepens Eye Research Institute, Inc. | Compositions for controlling neuronal outgrowth |
WO2012121451A1 (ko) * | 2011-03-08 | 2012-09-13 | 연세대학교 산학협력단 | 줄기세포의 인 비보 이동 유도방법 |
AU2012230716B2 (en) | 2011-03-23 | 2016-05-19 | Ethicon Llc | Self-retaining variable loop sutures |
WO2012148684A1 (en) | 2011-04-27 | 2012-11-01 | President And Fellows Of Harvard College | Cell-friendly inverse opal hydrogels for cell encapsulation, drug and protein delivery, and functional nanoparticle encapsulation |
US9675561B2 (en) | 2011-04-28 | 2017-06-13 | President And Fellows Of Harvard College | Injectable cryogel vaccine devices and methods of use thereof |
US10045947B2 (en) | 2011-04-28 | 2018-08-14 | President And Fellows Of Harvard College | Injectable preformed macroscopic 3-dimensional scaffolds for minimally invasive administration |
BR112013027794B1 (pt) | 2011-04-29 | 2020-12-15 | Ethicon Endo-Surgery, Inc | Conjunto de cartucho de grampos |
CA2835427A1 (en) | 2011-05-11 | 2012-11-15 | Microvention, Inc. | Device for occluding a lumen |
US10130654B2 (en) * | 2011-05-24 | 2018-11-20 | Hangli Biosciences Co., Ltd. | Method of inducing osteogensis and promoting osseointegration around an implant |
US11207064B2 (en) | 2011-05-27 | 2021-12-28 | Cilag Gmbh International | Automated end effector component reloading system for use with a robotic system |
US9072535B2 (en) | 2011-05-27 | 2015-07-07 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments with rotatable staple deployment arrangements |
US9486512B2 (en) | 2011-06-03 | 2016-11-08 | President And Fellows Of Harvard College | In situ antigen-generating cancer vaccine |
US20130172931A1 (en) | 2011-06-06 | 2013-07-04 | Jeffrey M. Gross | Methods and devices for soft palate tissue elevation procedures |
US10245178B1 (en) | 2011-06-07 | 2019-04-02 | Glaukos Corporation | Anterior chamber drug-eluting ocular implant |
EP4193907A1 (en) | 2011-09-13 | 2023-06-14 | Glaukos Corporation | Intraocular physiological sensor |
US9050084B2 (en) | 2011-09-23 | 2015-06-09 | Ethicon Endo-Surgery, Inc. | Staple cartridge including collapsible deck arrangement |
US8993831B2 (en) | 2011-11-01 | 2015-03-31 | Arsenal Medical, Inc. | Foam and delivery system for treatment of postpartum hemorrhage |
CN102512707A (zh) * | 2011-11-04 | 2012-06-27 | 无锡中科光远生物材料有限公司 | 一种用于制备肌肉肌腱复合组织的支架及其制备方法 |
CN102397585A (zh) * | 2011-11-04 | 2012-04-04 | 无锡中科光远生物材料有限公司 | 一种含生长因子的纤维支架及其制备方法 |
TWI590843B (zh) | 2011-12-28 | 2017-07-11 | 信迪思有限公司 | 膜及其製造方法 |
US9044230B2 (en) | 2012-02-13 | 2015-06-02 | Ethicon Endo-Surgery, Inc. | Surgical cutting and fastening instrument with apparatus for determining cartridge and firing motion status |
JP6189337B2 (ja) | 2012-02-16 | 2017-08-30 | シンセス・ゲーエムベーハーSynthes GmbH | 植え込み可能本体用薬物溶出挿入部材 |
US9198662B2 (en) | 2012-03-28 | 2015-12-01 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator having improved visibility |
MX353040B (es) | 2012-03-28 | 2017-12-18 | Ethicon Endo Surgery Inc | Unidad retenedora que incluye un compensador de grosor de tejido. |
BR112014024102B1 (pt) | 2012-03-28 | 2022-03-03 | Ethicon Endo-Surgery, Inc | Conjunto de cartucho de prendedores para um instrumento cirúrgico, e conjunto de atuador de extremidade para um instrumento cirúrgico |
CN104334098B (zh) | 2012-03-28 | 2017-03-22 | 伊西康内外科公司 | 包括限定低压强环境的胶囊剂的组织厚度补偿件 |
EP2838515B1 (en) | 2012-04-16 | 2019-11-20 | President and Fellows of Harvard College | Mesoporous silica compositions for modulating immune responses |
US9101358B2 (en) | 2012-06-15 | 2015-08-11 | Ethicon Endo-Surgery, Inc. | Articulatable surgical instrument comprising a firing drive |
US20140017263A1 (en) | 2012-06-28 | 2014-01-16 | Clemson University | Delivery Agents for Targeted Treatment of Elastin Degradation |
US9289256B2 (en) | 2012-06-28 | 2016-03-22 | Ethicon Endo-Surgery, Llc | Surgical end effectors having angled tissue-contacting surfaces |
RU2636861C2 (ru) | 2012-06-28 | 2017-11-28 | Этикон Эндо-Серджери, Инк. | Блокировка пустой кассеты с клипсами |
US9125662B2 (en) | 2012-06-28 | 2015-09-08 | Ethicon Endo-Surgery, Inc. | Multi-axis articulating and rotating surgical tools |
US9282974B2 (en) | 2012-06-28 | 2016-03-15 | Ethicon Endo-Surgery, Llc | Empty clip cartridge lockout |
US9101385B2 (en) | 2012-06-28 | 2015-08-11 | Ethicon Endo-Surgery, Inc. | Electrode connections for rotary driven surgical tools |
US9072536B2 (en) | 2012-06-28 | 2015-07-07 | Ethicon Endo-Surgery, Inc. | Differential locking arrangements for rotary powered surgical instruments |
US20140001234A1 (en) | 2012-06-28 | 2014-01-02 | Ethicon Endo-Surgery, Inc. | Coupling arrangements for attaching surgical end effectors to drive systems therefor |
US11202631B2 (en) | 2012-06-28 | 2021-12-21 | Cilag Gmbh International | Stapling assembly comprising a firing lockout |
BR112014032776B1 (pt) | 2012-06-28 | 2021-09-08 | Ethicon Endo-Surgery, Inc | Sistema de instrumento cirúrgico e kit cirúrgico para uso com um sistema de instrumento cirúrgico |
US9028494B2 (en) | 2012-06-28 | 2015-05-12 | Ethicon Endo-Surgery, Inc. | Interchangeable end effector coupling arrangement |
US20140001231A1 (en) | 2012-06-28 | 2014-01-02 | Ethicon Endo-Surgery, Inc. | Firing system lockout arrangements for surgical instruments |
US9204879B2 (en) | 2012-06-28 | 2015-12-08 | Ethicon Endo-Surgery, Inc. | Flexible drive member |
US9561038B2 (en) | 2012-06-28 | 2017-02-07 | Ethicon Endo-Surgery, Llc | Interchangeable clip applier |
RU2509091C1 (ru) * | 2012-07-05 | 2014-03-10 | Федеральное государственное бюджетное учреждение науки Институт высокомолекулярных соединений Российской академии наук | Биосовместимое биодеградируемое композиционное волокно и способ его получения |
EP2872155A4 (en) | 2012-07-10 | 2016-07-13 | Univ Pennsylvania | BIOMATERIALS TO IMPROVE THE INTEGRATION OF THE IMPLANT WITHIN THE HOST |
SG11201502207WA (en) | 2012-09-21 | 2015-04-29 | Univ Washington | Biomedical patches with spatially arranged fibers |
WO2014059433A2 (en) | 2012-10-12 | 2014-04-17 | Mardil, Inc. | Cardiac treatment system and method |
CN109453433A (zh) * | 2012-11-14 | 2019-03-12 | 整形外科创新中心公司 | 通过添加制造生产的抗微生物物品 |
US20140148506A1 (en) * | 2012-11-26 | 2014-05-29 | Allergan, Inc. | Drug elating silicone gel sheeting for wound healing and scar reduction |
US9386984B2 (en) | 2013-02-08 | 2016-07-12 | Ethicon Endo-Surgery, Llc | Staple cartridge comprising a releasable cover |
CA2901919C (en) * | 2013-02-19 | 2018-05-01 | Board Of Regents, The University Of Texas System | Chemical gradients |
RU2669463C2 (ru) | 2013-03-01 | 2018-10-11 | Этикон Эндо-Серджери, Инк. | Хирургический инструмент с мягким упором |
RU2672520C2 (ru) | 2013-03-01 | 2018-11-15 | Этикон Эндо-Серджери, Инк. | Шарнирно поворачиваемые хирургические инструменты с проводящими путями для передачи сигналов |
US9307986B2 (en) | 2013-03-01 | 2016-04-12 | Ethicon Endo-Surgery, Llc | Surgical instrument soft stop |
US9345481B2 (en) | 2013-03-13 | 2016-05-24 | Ethicon Endo-Surgery, Llc | Staple cartridge tissue thickness sensor system |
US9730638B2 (en) | 2013-03-13 | 2017-08-15 | Glaukos Corporation | Intraocular physiological sensor |
US10405961B2 (en) | 2013-03-14 | 2019-09-10 | Cell and Molecular Tissue Engineering, LLC | Coated surgical mesh, and corresponding systems and methods |
US9629629B2 (en) | 2013-03-14 | 2017-04-25 | Ethicon Endo-Surgey, LLC | Control systems for surgical instruments |
CN105142399B (zh) | 2013-03-14 | 2018-06-12 | 金珂生物医疗公司 | 生物相容的和生物可吸收的衍生的壳聚糖组合物 |
US10130288B2 (en) | 2013-03-14 | 2018-11-20 | Cell and Molecular Tissue Engineering, LLC | Coated sensors, and corresponding systems and methods |
US10470762B2 (en) | 2013-03-14 | 2019-11-12 | Ethicon Llc | Multi-function motor for a surgical instrument |
US9795384B2 (en) | 2013-03-27 | 2017-10-24 | Ethicon Llc | Fastener cartridge comprising a tissue thickness compensator and a gap setting element |
US9332984B2 (en) | 2013-03-27 | 2016-05-10 | Ethicon Endo-Surgery, Llc | Fastener cartridge assemblies |
US9572577B2 (en) | 2013-03-27 | 2017-02-21 | Ethicon Endo-Surgery, Llc | Fastener cartridge comprising a tissue thickness compensator including openings therein |
BR112015026109B1 (pt) | 2013-04-16 | 2022-02-22 | Ethicon Endo-Surgery, Inc | Instrumento cirúrgico |
US9649110B2 (en) | 2013-04-16 | 2017-05-16 | Ethicon Llc | Surgical instrument comprising a closing drive and a firing drive operated from the same rotatable output |
US9574644B2 (en) | 2013-05-30 | 2017-02-21 | Ethicon Endo-Surgery, Llc | Power module for use with a surgical instrument |
WO2014204708A1 (en) | 2013-06-21 | 2014-12-24 | DePuy Synthes Products, LLC | Films and methods of manufacture |
CN106028966B (zh) | 2013-08-23 | 2018-06-22 | 伊西康内外科有限责任公司 | 用于动力外科器械的击发构件回缩装置 |
US20150053737A1 (en) | 2013-08-23 | 2015-02-26 | Ethicon Endo-Surgery, Inc. | End effector detection systems for surgical instruments |
US9795573B2 (en) | 2013-09-24 | 2017-10-24 | Clemson University | Multi-step connective tissue stabilization method and stabilized tissue formed thereby |
USD717954S1 (en) | 2013-10-14 | 2014-11-18 | Mardil, Inc. | Heart treatment device |
US10092679B2 (en) | 2013-10-18 | 2018-10-09 | Wake Forest University Health Sciences | Laminous vascular constructs combining cell sheet engineering and electrospinning technologies |
US9545302B2 (en) | 2013-11-20 | 2017-01-17 | Dermagenesis Llc | Skin printing and auto-grafting |
US20150147379A1 (en) * | 2013-11-26 | 2015-05-28 | Cook Medical Technologies Llc | Medical devices and methods of manufacture thereof |
US11000285B2 (en) | 2013-12-17 | 2021-05-11 | 3Dt Holdings, Llc | Luminal grafts and methods of making and using the same |
US9724092B2 (en) | 2013-12-23 | 2017-08-08 | Ethicon Llc | Modular surgical instruments |
US9839428B2 (en) | 2013-12-23 | 2017-12-12 | Ethicon Llc | Surgical cutting and stapling instruments with independent jaw control features |
US20150173756A1 (en) | 2013-12-23 | 2015-06-25 | Ethicon Endo-Surgery, Inc. | Surgical cutting and stapling methods |
US9763662B2 (en) | 2013-12-23 | 2017-09-19 | Ethicon Llc | Fastener cartridge comprising a firing member configured to directly engage and eject fasteners from the fastener cartridge |
US9962161B2 (en) | 2014-02-12 | 2018-05-08 | Ethicon Llc | Deliverable surgical instrument |
US9884456B2 (en) | 2014-02-24 | 2018-02-06 | Ethicon Llc | Implantable layers and methods for altering one or more properties of implantable layers for use with fastening instruments |
CN106232029B (zh) | 2014-02-24 | 2019-04-12 | 伊西康内外科有限责任公司 | 包括击发构件锁定件的紧固系统 |
BR112016021943B1 (pt) | 2014-03-26 | 2022-06-14 | Ethicon Endo-Surgery, Llc | Instrumento cirúrgico para uso por um operador em um procedimento cirúrgico |
US9913642B2 (en) | 2014-03-26 | 2018-03-13 | Ethicon Llc | Surgical instrument comprising a sensor system |
US9804618B2 (en) | 2014-03-26 | 2017-10-31 | Ethicon Llc | Systems and methods for controlling a segmented circuit |
US10028761B2 (en) | 2014-03-26 | 2018-07-24 | Ethicon Llc | Feedback algorithms for manual bailout systems for surgical instruments |
US10004497B2 (en) | 2014-03-26 | 2018-06-26 | Ethicon Llc | Interface systems for use with surgical instruments |
BR112016023698B1 (pt) | 2014-04-16 | 2022-07-26 | Ethicon Endo-Surgery, Llc | Cartucho de prendedores para uso com um instrumento cirúrgico |
US20150297222A1 (en) | 2014-04-16 | 2015-10-22 | Ethicon Endo-Surgery, Inc. | Fastener cartridges including extensions having different configurations |
US9259357B2 (en) | 2014-04-16 | 2016-02-16 | Loma Linda University | Composition, preparation, and use of chitosan shards for biomedical applications |
CN106456159B (zh) | 2014-04-16 | 2019-03-08 | 伊西康内外科有限责任公司 | 紧固件仓组件和钉保持器盖布置结构 |
US9844369B2 (en) | 2014-04-16 | 2017-12-19 | Ethicon Llc | Surgical end effectors with firing element monitoring arrangements |
US9801627B2 (en) | 2014-09-26 | 2017-10-31 | Ethicon Llc | Fastener cartridge for creating a flexible staple line |
JP6612256B2 (ja) | 2014-04-16 | 2019-11-27 | エシコン エルエルシー | 不均一な締結具を備える締結具カートリッジ |
JP7348708B2 (ja) | 2014-04-30 | 2023-09-21 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | 組み合わせワクチン装置および癌細胞を殺滅する方法 |
EP3677229A1 (en) | 2014-05-29 | 2020-07-08 | Glaukos Corporation | Implants with controlled drug delivery features |
WO2015188223A1 (en) | 2014-06-11 | 2015-12-17 | International Scientific Pty Ltd | Device and method to treat or prevent joint degeneration |
US10045781B2 (en) | 2014-06-13 | 2018-08-14 | Ethicon Llc | Closure lockout systems for surgical instruments |
KR101641299B1 (ko) * | 2014-06-25 | 2016-07-20 | 김동진 | 금속 코팅 가시매선 |
US20160022570A1 (en) | 2014-07-25 | 2016-01-28 | Robert W. Adams | Medical implant |
ES2807178T3 (es) | 2014-08-15 | 2021-02-22 | Tepha Inc | Suturas de autorretención de poli-4-hidroxibutirato y copolímeros del mismo |
BR112017004361B1 (pt) | 2014-09-05 | 2023-04-11 | Ethicon Llc | Sistema eletrônico para um instrumento cirúrgico |
US10111679B2 (en) | 2014-09-05 | 2018-10-30 | Ethicon Llc | Circuitry and sensors for powered medical device |
US11311294B2 (en) | 2014-09-05 | 2022-04-26 | Cilag Gmbh International | Powered medical device including measurement of closure state of jaws |
US10105142B2 (en) | 2014-09-18 | 2018-10-23 | Ethicon Llc | Surgical stapler with plurality of cutting elements |
US11523821B2 (en) | 2014-09-26 | 2022-12-13 | Cilag Gmbh International | Method for creating a flexible staple line |
CN107427300B (zh) | 2014-09-26 | 2020-12-04 | 伊西康有限责任公司 | 外科缝合支撑物和辅助材料 |
US10076325B2 (en) | 2014-10-13 | 2018-09-18 | Ethicon Llc | Surgical stapling apparatus comprising a tissue stop |
US9924944B2 (en) | 2014-10-16 | 2018-03-27 | Ethicon Llc | Staple cartridge comprising an adjunct material |
US10517594B2 (en) | 2014-10-29 | 2019-12-31 | Ethicon Llc | Cartridge assemblies for surgical staplers |
US11141153B2 (en) | 2014-10-29 | 2021-10-12 | Cilag Gmbh International | Staple cartridges comprising driver arrangements |
AU2015339203B2 (en) | 2014-10-30 | 2020-12-24 | Textile-Based Delivery, Inc. | Delivery systems |
US9844376B2 (en) | 2014-11-06 | 2017-12-19 | Ethicon Llc | Staple cartridge comprising a releasable adjunct material |
US10736636B2 (en) | 2014-12-10 | 2020-08-11 | Ethicon Llc | Articulatable surgical instrument system |
CA2969429C (en) | 2014-12-11 | 2020-10-27 | Tepha, Inc. | Methods of orienting multifilament yarn and monofilaments of poly-4-hydroxybutyrate and copolymers thereof |
US10626521B2 (en) | 2014-12-11 | 2020-04-21 | Tepha, Inc. | Methods of manufacturing mesh sutures from poly-4-hydroxybutyrate and copolymers thereof |
US9844375B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Drive arrangements for articulatable surgical instruments |
US9844374B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Surgical instrument systems comprising an articulatable end effector and means for adjusting the firing stroke of a firing member |
US10085748B2 (en) | 2014-12-18 | 2018-10-02 | Ethicon Llc | Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors |
RU2703684C2 (ru) | 2014-12-18 | 2019-10-21 | ЭТИКОН ЭНДО-СЕРДЖЕРИ, ЭлЭлСи | Хирургический инструмент с упором, который выполнен с возможностью избирательного перемещения относительно кассеты со скобами вокруг дискретной неподвижной оси |
US9943309B2 (en) | 2014-12-18 | 2018-04-17 | Ethicon Llc | Surgical instruments with articulatable end effectors and movable firing beam support arrangements |
US10117649B2 (en) | 2014-12-18 | 2018-11-06 | Ethicon Llc | Surgical instrument assembly comprising a lockable articulation system |
US10188385B2 (en) | 2014-12-18 | 2019-01-29 | Ethicon Llc | Surgical instrument system comprising lockable systems |
US9987000B2 (en) | 2014-12-18 | 2018-06-05 | Ethicon Llc | Surgical instrument assembly comprising a flexible articulation system |
WO2016118464A2 (en) | 2015-01-19 | 2016-07-28 | The Regents Of The University Of Michigan | Multiphasic particles fabricated by wettability engendered templated self-assembly (wets) methods |
EP3250250A4 (en) | 2015-01-30 | 2019-05-22 | President and Fellows of Harvard College | PERITUMORAL AND INTRATUMORAL MATERIALS FOR CANCER THERAPY |
US9993258B2 (en) | 2015-02-27 | 2018-06-12 | Ethicon Llc | Adaptable surgical instrument handle |
US11154301B2 (en) | 2015-02-27 | 2021-10-26 | Cilag Gmbh International | Modular stapling assembly |
US10180463B2 (en) | 2015-02-27 | 2019-01-15 | Ethicon Llc | Surgical apparatus configured to assess whether a performance parameter of the surgical apparatus is within an acceptable performance band |
US9931118B2 (en) | 2015-02-27 | 2018-04-03 | Ethicon Endo-Surgery, Llc | Reinforced battery for a surgical instrument |
CN104740681A (zh) * | 2015-03-02 | 2015-07-01 | 吉林大学 | 一种聚乳酸-羟基乙酸/腺病毒复合纳米纤维支架材料、制备方法及其应用 |
US9924961B2 (en) | 2015-03-06 | 2018-03-27 | Ethicon Endo-Surgery, Llc | Interactive feedback system for powered surgical instruments |
JP2020121162A (ja) | 2015-03-06 | 2020-08-13 | エシコン エルエルシーEthicon LLC | 測定の安定性要素、クリープ要素、及び粘弾性要素を決定するためのセンサデータの時間依存性評価 |
US10441279B2 (en) | 2015-03-06 | 2019-10-15 | Ethicon Llc | Multiple level thresholds to modify operation of powered surgical instruments |
US9895148B2 (en) | 2015-03-06 | 2018-02-20 | Ethicon Endo-Surgery, Llc | Monitoring speed control and precision incrementing of motor for powered surgical instruments |
US9901342B2 (en) | 2015-03-06 | 2018-02-27 | Ethicon Endo-Surgery, Llc | Signal and power communication system positioned on a rotatable shaft |
US10052044B2 (en) | 2015-03-06 | 2018-08-21 | Ethicon Llc | Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures |
US10045776B2 (en) | 2015-03-06 | 2018-08-14 | Ethicon Llc | Control techniques and sub-processor contained within modular shaft with select control processing from handle |
US9808246B2 (en) | 2015-03-06 | 2017-11-07 | Ethicon Endo-Surgery, Llc | Method of operating a powered surgical instrument |
US10617412B2 (en) | 2015-03-06 | 2020-04-14 | Ethicon Llc | System for detecting the mis-insertion of a staple cartridge into a surgical stapler |
US9993248B2 (en) | 2015-03-06 | 2018-06-12 | Ethicon Endo-Surgery, Llc | Smart sensors with local signal processing |
US10245033B2 (en) | 2015-03-06 | 2019-04-02 | Ethicon Llc | Surgical instrument comprising a lockable battery housing |
US10687806B2 (en) | 2015-03-06 | 2020-06-23 | Ethicon Llc | Adaptive tissue compression techniques to adjust closure rates for multiple tissue types |
US10433844B2 (en) | 2015-03-31 | 2019-10-08 | Ethicon Llc | Surgical instrument with selectively disengageable threaded drive systems |
JP7094533B2 (ja) | 2015-04-10 | 2022-07-04 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 免疫細胞捕捉デバイスおよびその製造および使用方法 |
US10392612B1 (en) * | 2015-05-26 | 2019-08-27 | Jessica M. Gregory | Method of particulate transport via small-scale morphology materials |
US10182818B2 (en) | 2015-06-18 | 2019-01-22 | Ethicon Llc | Surgical end effectors with positive jaw opening arrangements |
US20180200185A1 (en) | 2015-07-23 | 2018-07-19 | Novaflux, Inc | Implants and constructs including hollow fibers |
CN114949368A (zh) * | 2015-08-17 | 2022-08-30 | 约翰·霍普金斯大学 | 用于组织修复的纤维-水凝胶复合材料外科网片 |
US11058425B2 (en) | 2015-08-17 | 2021-07-13 | Ethicon Llc | Implantable layers for a surgical instrument |
MX2022009705A (es) | 2015-08-26 | 2022-11-07 | Ethicon Llc | Metodo para formar una grapa contra un yunque de un instrumento de engrapado quirurgico. |
US10357251B2 (en) | 2015-08-26 | 2019-07-23 | Ethicon Llc | Surgical staples comprising hardness variations for improved fastening of tissue |
MX2018002388A (es) | 2015-08-26 | 2018-08-01 | Ethicon Llc | Tiras de grapas quirurgicas para permitir propiedades variables de la grapa y facilitar la carga del cartucho. |
US10172619B2 (en) | 2015-09-02 | 2019-01-08 | Ethicon Llc | Surgical staple driver arrays |
MX2022006189A (es) | 2015-09-02 | 2022-06-16 | Ethicon Llc | Configuraciones de grapas quirurgicas con superficies de leva situadas entre porciones que soportan grapas quirurgicas. |
US11925578B2 (en) | 2015-09-02 | 2024-03-12 | Glaukos Corporation | Drug delivery implants with bi-directional delivery capacity |
US10238386B2 (en) | 2015-09-23 | 2019-03-26 | Ethicon Llc | Surgical stapler having motor control based on an electrical parameter related to a motor current |
US10327769B2 (en) | 2015-09-23 | 2019-06-25 | Ethicon Llc | Surgical stapler having motor control based on a drive system component |
US10105139B2 (en) | 2015-09-23 | 2018-10-23 | Ethicon Llc | Surgical stapler having downstream current-based motor control |
US10363036B2 (en) | 2015-09-23 | 2019-07-30 | Ethicon Llc | Surgical stapler having force-based motor control |
US10076326B2 (en) | 2015-09-23 | 2018-09-18 | Ethicon Llc | Surgical stapler having current mirror-based motor control |
US10085751B2 (en) | 2015-09-23 | 2018-10-02 | Ethicon Llc | Surgical stapler having temperature-based motor control |
US11564833B2 (en) | 2015-09-25 | 2023-01-31 | Glaukos Corporation | Punctal implants with controlled drug delivery features and methods of using same |
US10299878B2 (en) | 2015-09-25 | 2019-05-28 | Ethicon Llc | Implantable adjunct systems for determining adjunct skew |
US10980539B2 (en) | 2015-09-30 | 2021-04-20 | Ethicon Llc | Implantable adjunct comprising bonded layers |
US10172620B2 (en) | 2015-09-30 | 2019-01-08 | Ethicon Llc | Compressible adjuncts with bonding nodes |
US20170086829A1 (en) | 2015-09-30 | 2017-03-30 | Ethicon Endo-Surgery, Llc | Compressible adjunct with intermediate supporting structures |
US11890015B2 (en) | 2015-09-30 | 2024-02-06 | Cilag Gmbh International | Compressible adjunct with crossing spacer fibers |
WO2017062757A1 (en) | 2015-10-08 | 2017-04-13 | Massachusetts Institute Of Technology | In situ expansion of engineered devices for regeneration |
CN108601646B (zh) * | 2015-11-12 | 2021-10-12 | 博奥司时代有限责任公司 | 用于产生胃肠道组织的系统和方法 |
CA3007631A1 (en) | 2015-12-11 | 2017-06-15 | Research Institute At Nationwide Children's Hospital | Optimized patient specific non-linear tissue engineered vascular grafts |
US10292704B2 (en) | 2015-12-30 | 2019-05-21 | Ethicon Llc | Mechanisms for compensating for battery pack failure in powered surgical instruments |
US10265068B2 (en) | 2015-12-30 | 2019-04-23 | Ethicon Llc | Surgical instruments with separable motors and motor control circuits |
US10368865B2 (en) | 2015-12-30 | 2019-08-06 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
JP7138864B2 (ja) | 2016-02-06 | 2022-09-20 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 免疫を再構成するための造血ニッチの再現 |
US11213293B2 (en) | 2016-02-09 | 2022-01-04 | Cilag Gmbh International | Articulatable surgical instruments with single articulation link arrangements |
US20170224332A1 (en) | 2016-02-09 | 2017-08-10 | Ethicon Endo-Surgery, Llc | Surgical instruments with non-symmetrical articulation arrangements |
JP6911054B2 (ja) | 2016-02-09 | 2021-07-28 | エシコン エルエルシーEthicon LLC | 非対称の関節構成を備えた外科用器具 |
US10448948B2 (en) | 2016-02-12 | 2019-10-22 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10258331B2 (en) | 2016-02-12 | 2019-04-16 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US11224426B2 (en) | 2016-02-12 | 2022-01-18 | Cilag Gmbh International | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10376263B2 (en) | 2016-04-01 | 2019-08-13 | Ethicon Llc | Anvil modification members for surgical staplers |
US10617413B2 (en) | 2016-04-01 | 2020-04-14 | Ethicon Llc | Closure system arrangements for surgical cutting and stapling devices with separate and distinct firing shafts |
US10456137B2 (en) | 2016-04-15 | 2019-10-29 | Ethicon Llc | Staple formation detection mechanisms |
US10426467B2 (en) | 2016-04-15 | 2019-10-01 | Ethicon Llc | Surgical instrument with detection sensors |
US10492783B2 (en) | 2016-04-15 | 2019-12-03 | Ethicon, Llc | Surgical instrument with improved stop/start control during a firing motion |
US10828028B2 (en) | 2016-04-15 | 2020-11-10 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US11179150B2 (en) | 2016-04-15 | 2021-11-23 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US10357247B2 (en) | 2016-04-15 | 2019-07-23 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US10405859B2 (en) | 2016-04-15 | 2019-09-10 | Ethicon Llc | Surgical instrument with adjustable stop/start control during a firing motion |
US11607239B2 (en) | 2016-04-15 | 2023-03-21 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US10335145B2 (en) | 2016-04-15 | 2019-07-02 | Ethicon Llc | Modular surgical instrument with configurable operating mode |
US20170296173A1 (en) | 2016-04-18 | 2017-10-19 | Ethicon Endo-Surgery, Llc | Method for operating a surgical instrument |
US11317917B2 (en) | 2016-04-18 | 2022-05-03 | Cilag Gmbh International | Surgical stapling system comprising a lockable firing assembly |
US10478181B2 (en) | 2016-04-18 | 2019-11-19 | Ethicon Llc | Cartridge lockout arrangements for rotary powered surgical cutting and stapling instruments |
JP7003110B2 (ja) | 2016-04-20 | 2022-01-20 | ドーズ メディカル コーポレーション | 生体吸収性眼球薬物送達デバイス |
US10632228B2 (en) | 2016-05-12 | 2020-04-28 | Acera Surgical, Inc. | Tissue substitute materials and methods for tissue repair |
US10675024B2 (en) | 2016-06-24 | 2020-06-09 | Ethicon Llc | Staple cartridge comprising overdriven staples |
USD826405S1 (en) | 2016-06-24 | 2018-08-21 | Ethicon Llc | Surgical fastener |
USD850617S1 (en) | 2016-06-24 | 2019-06-04 | Ethicon Llc | Surgical fastener cartridge |
JP6957532B2 (ja) | 2016-06-24 | 2021-11-02 | エシコン エルエルシーEthicon LLC | ワイヤステープル及び打ち抜き加工ステープルを含むステープルカートリッジ |
USD847989S1 (en) | 2016-06-24 | 2019-05-07 | Ethicon Llc | Surgical fastener cartridge |
CN109789092A (zh) | 2016-07-13 | 2019-05-21 | 哈佛学院院长等 | 抗原呈递细胞模拟支架及其制备和使用方法 |
EP3484450A4 (en) * | 2016-07-18 | 2020-04-01 | Tissuegen, Inc. | METHODS AND COMPOSITIONS FOR MAINTAINING THE CONFORMATION AND STRUCTURAL INTEGRITY OF BIOMOLECULES |
WO2018078562A1 (en) * | 2016-10-26 | 2018-05-03 | Association For The Advancement Of Tissue Engineering And Cell Based Technologies & Therapies (A4Tec) | Fibers with segments, their preparation and applications thereof |
CN106620877B (zh) * | 2016-11-02 | 2019-05-10 | 叶川 | 一种毛细血管网及其制备方法 |
US10675026B2 (en) | 2016-12-21 | 2020-06-09 | Ethicon Llc | Methods of stapling tissue |
US10687810B2 (en) | 2016-12-21 | 2020-06-23 | Ethicon Llc | Stepped staple cartridge with tissue retention and gap setting features |
US10835246B2 (en) | 2016-12-21 | 2020-11-17 | Ethicon Llc | Staple cartridges and arrangements of staples and staple cavities therein |
US11684367B2 (en) | 2016-12-21 | 2023-06-27 | Cilag Gmbh International | Stepped assembly having and end-of-life indicator |
US10695055B2 (en) | 2016-12-21 | 2020-06-30 | Ethicon Llc | Firing assembly comprising a lockout |
US11134942B2 (en) | 2016-12-21 | 2021-10-05 | Cilag Gmbh International | Surgical stapling instruments and staple-forming anvils |
US10856868B2 (en) | 2016-12-21 | 2020-12-08 | Ethicon Llc | Firing member pin configurations |
US10426471B2 (en) | 2016-12-21 | 2019-10-01 | Ethicon Llc | Surgical instrument with multiple failure response modes |
US10993715B2 (en) | 2016-12-21 | 2021-05-04 | Ethicon Llc | Staple cartridge comprising staples with different clamping breadths |
US10945727B2 (en) | 2016-12-21 | 2021-03-16 | Ethicon Llc | Staple cartridge with deformable driver retention features |
US20180168625A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Surgical stapling instruments with smart staple cartridges |
US10881401B2 (en) | 2016-12-21 | 2021-01-05 | Ethicon Llc | Staple firing member comprising a missing cartridge and/or spent cartridge lockout |
US10639035B2 (en) | 2016-12-21 | 2020-05-05 | Ethicon Llc | Surgical stapling instruments and replaceable tool assemblies thereof |
JP7010956B2 (ja) | 2016-12-21 | 2022-01-26 | エシコン エルエルシー | 組織をステープル留めする方法 |
US10736629B2 (en) | 2016-12-21 | 2020-08-11 | Ethicon Llc | Surgical tool assemblies with clutching arrangements for shifting between closure systems with closure stroke reduction features and articulation and firing systems |
US11419606B2 (en) | 2016-12-21 | 2022-08-23 | Cilag Gmbh International | Shaft assembly comprising a clutch configured to adapt the output of a rotary firing member to two different systems |
JP6983893B2 (ja) | 2016-12-21 | 2021-12-17 | エシコン エルエルシーEthicon LLC | 外科用エンドエフェクタ及び交換式ツールアセンブリのためのロックアウト構成 |
US10537324B2 (en) | 2016-12-21 | 2020-01-21 | Ethicon Llc | Stepped staple cartridge with asymmetrical staples |
US11191540B2 (en) | 2016-12-21 | 2021-12-07 | Cilag Gmbh International | Protective cover arrangements for a joint interface between a movable jaw and actuator shaft of a surgical instrument |
MX2019007311A (es) | 2016-12-21 | 2019-11-18 | Ethicon Llc | Sistemas de engrapado quirurgico. |
US10448950B2 (en) | 2016-12-21 | 2019-10-22 | Ethicon Llc | Surgical staplers with independently actuatable closing and firing systems |
US10492785B2 (en) | 2016-12-21 | 2019-12-03 | Ethicon Llc | Shaft assembly comprising a lockout |
US10682138B2 (en) | 2016-12-21 | 2020-06-16 | Ethicon Llc | Bilaterally asymmetric staple forming pocket pairs |
US20180168615A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Method of deforming staples from two different types of staple cartridges with the same surgical stapling instrument |
US20180221021A1 (en) * | 2017-02-08 | 2018-08-09 | Ethicon, Inc. | Braided suture with filament containing a medicant |
BR112019022307A2 (pt) | 2017-04-24 | 2020-05-26 | Cocrystal Pharma, Inc. | Derivados da pirrolopirimidina úteis como inibidores de replicação de vírus da influenza. |
MX2019015321A (es) | 2017-06-16 | 2020-07-20 | Avery Therapeutics Inc | Composiciones tridimensionales de tejido y métodos de uso. |
US11090046B2 (en) | 2017-06-20 | 2021-08-17 | Cilag Gmbh International | Systems and methods for controlling displacement member motion of a surgical stapling and cutting instrument |
US10813639B2 (en) | 2017-06-20 | 2020-10-27 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on system conditions |
US10390841B2 (en) | 2017-06-20 | 2019-08-27 | Ethicon Llc | Control of motor velocity of a surgical stapling and cutting instrument based on angle of articulation |
US11382638B2 (en) | 2017-06-20 | 2022-07-12 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified displacement distance |
US10646220B2 (en) | 2017-06-20 | 2020-05-12 | Ethicon Llc | Systems and methods for controlling displacement member velocity for a surgical instrument |
USD879809S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with changeable graphical user interface |
US11071554B2 (en) | 2017-06-20 | 2021-07-27 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on magnitude of velocity error measurements |
US10881399B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Techniques for adaptive control of motor velocity of a surgical stapling and cutting instrument |
US10779820B2 (en) | 2017-06-20 | 2020-09-22 | Ethicon Llc | Systems and methods for controlling motor speed according to user input for a surgical instrument |
USD879808S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with graphical user interface |
US11653914B2 (en) | 2017-06-20 | 2023-05-23 | Cilag Gmbh International | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument according to articulation angle of end effector |
US10888321B2 (en) | 2017-06-20 | 2021-01-12 | Ethicon Llc | Systems and methods for controlling velocity of a displacement member of a surgical stapling and cutting instrument |
USD890784S1 (en) | 2017-06-20 | 2020-07-21 | Ethicon Llc | Display panel with changeable graphical user interface |
US10327767B2 (en) | 2017-06-20 | 2019-06-25 | Ethicon Llc | Control of motor velocity of a surgical stapling and cutting instrument based on angle of articulation |
US11517325B2 (en) | 2017-06-20 | 2022-12-06 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured displacement distance traveled over a specified time interval |
US10307170B2 (en) | 2017-06-20 | 2019-06-04 | Ethicon Llc | Method for closed loop control of motor velocity of a surgical stapling and cutting instrument |
US10881396B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Surgical instrument with variable duration trigger arrangement |
US10624633B2 (en) | 2017-06-20 | 2020-04-21 | Ethicon Llc | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument |
US10368864B2 (en) | 2017-06-20 | 2019-08-06 | Ethicon Llc | Systems and methods for controlling displaying motor velocity for a surgical instrument |
US10980537B2 (en) | 2017-06-20 | 2021-04-20 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified number of shaft rotations |
US11141154B2 (en) | 2017-06-27 | 2021-10-12 | Cilag Gmbh International | Surgical end effectors and anvils |
US11266405B2 (en) | 2017-06-27 | 2022-03-08 | Cilag Gmbh International | Surgical anvil manufacturing methods |
US10772629B2 (en) | 2017-06-27 | 2020-09-15 | Ethicon Llc | Surgical anvil arrangements |
US11324503B2 (en) | 2017-06-27 | 2022-05-10 | Cilag Gmbh International | Surgical firing member arrangements |
US10856869B2 (en) | 2017-06-27 | 2020-12-08 | Ethicon Llc | Surgical anvil arrangements |
US10993716B2 (en) | 2017-06-27 | 2021-05-04 | Ethicon Llc | Surgical anvil arrangements |
USD854151S1 (en) | 2017-06-28 | 2019-07-16 | Ethicon Llc | Surgical instrument shaft |
US11246592B2 (en) | 2017-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical instrument comprising an articulation system lockable to a frame |
US10903685B2 (en) | 2017-06-28 | 2021-01-26 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies forming capacitive channels |
US11478242B2 (en) | 2017-06-28 | 2022-10-25 | Cilag Gmbh International | Jaw retainer arrangement for retaining a pivotable surgical instrument jaw in pivotable retaining engagement with a second surgical instrument jaw |
US11564686B2 (en) | 2017-06-28 | 2023-01-31 | Cilag Gmbh International | Surgical shaft assemblies with flexible interfaces |
EP3420947B1 (en) | 2017-06-28 | 2022-05-25 | Cilag GmbH International | Surgical instrument comprising selectively actuatable rotatable couplers |
US11259805B2 (en) | 2017-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical instrument comprising firing member supports |
US11058424B2 (en) | 2017-06-28 | 2021-07-13 | Cilag Gmbh International | Surgical instrument comprising an offset articulation joint |
US10716614B2 (en) | 2017-06-28 | 2020-07-21 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies with increased contact pressure |
USD869655S1 (en) | 2017-06-28 | 2019-12-10 | Ethicon Llc | Surgical fastener cartridge |
US10765427B2 (en) | 2017-06-28 | 2020-09-08 | Ethicon Llc | Method for articulating a surgical instrument |
USD906355S1 (en) | 2017-06-28 | 2020-12-29 | Ethicon Llc | Display screen or portion thereof with a graphical user interface for a surgical instrument |
USD851762S1 (en) | 2017-06-28 | 2019-06-18 | Ethicon Llc | Anvil |
US10211586B2 (en) | 2017-06-28 | 2019-02-19 | Ethicon Llc | Surgical shaft assemblies with watertight housings |
US10258418B2 (en) | 2017-06-29 | 2019-04-16 | Ethicon Llc | System for controlling articulation forces |
US11007022B2 (en) | 2017-06-29 | 2021-05-18 | Ethicon Llc | Closed loop velocity control techniques based on sensed tissue parameters for robotic surgical instrument |
US10898183B2 (en) | 2017-06-29 | 2021-01-26 | Ethicon Llc | Robotic surgical instrument with closed loop feedback techniques for advancement of closure member during firing |
US10932772B2 (en) | 2017-06-29 | 2021-03-02 | Ethicon Llc | Methods for closed loop velocity control for robotic surgical instrument |
US10398434B2 (en) | 2017-06-29 | 2019-09-03 | Ethicon Llc | Closed loop velocity control of closure member for robotic surgical instrument |
US11944300B2 (en) | 2017-08-03 | 2024-04-02 | Cilag Gmbh International | Method for operating a surgical system bailout |
US11974742B2 (en) | 2017-08-03 | 2024-05-07 | Cilag Gmbh International | Surgical system comprising an articulation bailout |
US11471155B2 (en) | 2017-08-03 | 2022-10-18 | Cilag Gmbh International | Surgical system bailout |
US11304695B2 (en) | 2017-08-03 | 2022-04-19 | Cilag Gmbh International | Surgical system shaft interconnection |
US10765429B2 (en) | 2017-09-29 | 2020-09-08 | Ethicon Llc | Systems and methods for providing alerts according to the operational state of a surgical instrument |
USD907647S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
USD917500S1 (en) | 2017-09-29 | 2021-04-27 | Ethicon Llc | Display screen or portion thereof with graphical user interface |
US10796471B2 (en) | 2017-09-29 | 2020-10-06 | Ethicon Llc | Systems and methods of displaying a knife position for a surgical instrument |
US10729501B2 (en) | 2017-09-29 | 2020-08-04 | Ethicon Llc | Systems and methods for language selection of a surgical instrument |
US11399829B2 (en) | 2017-09-29 | 2022-08-02 | Cilag Gmbh International | Systems and methods of initiating a power shutdown mode for a surgical instrument |
USD907648S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
US10743872B2 (en) | 2017-09-29 | 2020-08-18 | Ethicon Llc | System and methods for controlling a display of a surgical instrument |
US11134944B2 (en) | 2017-10-30 | 2021-10-05 | Cilag Gmbh International | Surgical stapler knife motion controls |
US11090075B2 (en) | 2017-10-30 | 2021-08-17 | Cilag Gmbh International | Articulation features for surgical end effector |
US10779903B2 (en) | 2017-10-31 | 2020-09-22 | Ethicon Llc | Positive shaft rotation lock activated by jaw closure |
US10842490B2 (en) | 2017-10-31 | 2020-11-24 | Ethicon Llc | Cartridge body design with force reduction based on firing completion |
US10743874B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Sealed adapters for use with electromechanical surgical instruments |
US11197670B2 (en) | 2017-12-15 | 2021-12-14 | Cilag Gmbh International | Surgical end effectors with pivotal jaws configured to touch at their respective distal ends when fully closed |
US11071543B2 (en) | 2017-12-15 | 2021-07-27 | Cilag Gmbh International | Surgical end effectors with clamping assemblies configured to increase jaw aperture ranges |
US10828033B2 (en) | 2017-12-15 | 2020-11-10 | Ethicon Llc | Handheld electromechanical surgical instruments with improved motor control arrangements for positioning components of an adapter coupled thereto |
US10779826B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Methods of operating surgical end effectors |
US11033267B2 (en) | 2017-12-15 | 2021-06-15 | Ethicon Llc | Systems and methods of controlling a clamping member firing rate of a surgical instrument |
US10743875B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Surgical end effectors with jaw stiffener arrangements configured to permit monitoring of firing member |
US10966718B2 (en) | 2017-12-15 | 2021-04-06 | Ethicon Llc | Dynamic clamping assemblies with improved wear characteristics for use in connection with electromechanical surgical instruments |
US11006955B2 (en) | 2017-12-15 | 2021-05-18 | Ethicon Llc | End effectors with positive jaw opening features for use with adapters for electromechanical surgical instruments |
US10687813B2 (en) | 2017-12-15 | 2020-06-23 | Ethicon Llc | Adapters with firing stroke sensing arrangements for use in connection with electromechanical surgical instruments |
US10779825B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Adapters with end effector position sensing and control arrangements for use in connection with electromechanical surgical instruments |
US10869666B2 (en) | 2017-12-15 | 2020-12-22 | Ethicon Llc | Adapters with control systems for controlling multiple motors of an electromechanical surgical instrument |
US10835330B2 (en) | 2017-12-19 | 2020-11-17 | Ethicon Llc | Method for determining the position of a rotatable jaw of a surgical instrument attachment assembly |
USD910847S1 (en) | 2017-12-19 | 2021-02-16 | Ethicon Llc | Surgical instrument assembly |
US11045270B2 (en) | 2017-12-19 | 2021-06-29 | Cilag Gmbh International | Robotic attachment comprising exterior drive actuator |
US11020112B2 (en) | 2017-12-19 | 2021-06-01 | Ethicon Llc | Surgical tools configured for interchangeable use with different controller interfaces |
US10716565B2 (en) | 2017-12-19 | 2020-07-21 | Ethicon Llc | Surgical instruments with dual articulation drivers |
US10729509B2 (en) | 2017-12-19 | 2020-08-04 | Ethicon Llc | Surgical instrument comprising closure and firing locking mechanism |
US11311290B2 (en) | 2017-12-21 | 2022-04-26 | Cilag Gmbh International | Surgical instrument comprising an end effector dampener |
US10743868B2 (en) | 2017-12-21 | 2020-08-18 | Ethicon Llc | Surgical instrument comprising a pivotable distal head |
US11129680B2 (en) | 2017-12-21 | 2021-09-28 | Cilag Gmbh International | Surgical instrument comprising a projector |
US11076853B2 (en) | 2017-12-21 | 2021-08-03 | Cilag Gmbh International | Systems and methods of displaying a knife position during transection for a surgical instrument |
AU2019311117A1 (en) | 2018-07-27 | 2021-02-04 | Cocrystal Pharma, Inc. | Pyrrolo(2,3-b)pyridin derivatives as inhibitors of influenza virus replication |
US11253256B2 (en) | 2018-08-20 | 2022-02-22 | Cilag Gmbh International | Articulatable motor powered surgical instruments with dedicated articulation motor arrangements |
US11045192B2 (en) | 2018-08-20 | 2021-06-29 | Cilag Gmbh International | Fabricating techniques for surgical stapler anvils |
US10779821B2 (en) | 2018-08-20 | 2020-09-22 | Ethicon Llc | Surgical stapler anvils with tissue stop features configured to avoid tissue pinch |
US10856870B2 (en) | 2018-08-20 | 2020-12-08 | Ethicon Llc | Switching arrangements for motor powered articulatable surgical instruments |
USD914878S1 (en) | 2018-08-20 | 2021-03-30 | Ethicon Llc | Surgical instrument anvil |
US11324501B2 (en) | 2018-08-20 | 2022-05-10 | Cilag Gmbh International | Surgical stapling devices with improved closure members |
US11039834B2 (en) | 2018-08-20 | 2021-06-22 | Cilag Gmbh International | Surgical stapler anvils with staple directing protrusions and tissue stability features |
US11207065B2 (en) | 2018-08-20 | 2021-12-28 | Cilag Gmbh International | Method for fabricating surgical stapler anvils |
US11291440B2 (en) | 2018-08-20 | 2022-04-05 | Cilag Gmbh International | Method for operating a powered articulatable surgical instrument |
US10842492B2 (en) | 2018-08-20 | 2020-11-24 | Ethicon Llc | Powered articulatable surgical instruments with clutching and locking arrangements for linking an articulation drive system to a firing drive system |
US10912559B2 (en) | 2018-08-20 | 2021-02-09 | Ethicon Llc | Reinforced deformable anvil tip for surgical stapler anvil |
US11083458B2 (en) | 2018-08-20 | 2021-08-10 | Cilag Gmbh International | Powered surgical instruments with clutching arrangements to convert linear drive motions to rotary drive motions |
WO2020055858A1 (en) | 2018-09-10 | 2020-03-19 | Cocrystal Pharma, Inc. | Pyridopyrazine and pyridotriazine inhibitors of influenza virus replication |
AU2019361038A1 (en) | 2018-10-17 | 2021-05-13 | Cocrystal Pharma, Inc. | Combinations of inhibitors of influenza virus replication |
CN109394399A (zh) * | 2018-10-22 | 2019-03-01 | 乐畅医疗器械(上海)有限公司 | 一种药物缓释支架 |
US20220048897A1 (en) | 2018-11-26 | 2022-02-17 | Cocrystal Pharma, Inc. | Inhibitors of influenza virus replication |
CA3121200A1 (en) | 2018-11-30 | 2020-06-04 | Cellphire, Inc. | Platelets as delivery agents |
EP3886879A4 (en) | 2018-11-30 | 2022-12-07 | Cellphire Inc. | PLATES AS DELIVERY AGENTS |
US11147553B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11147551B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11696761B2 (en) | 2019-03-25 | 2023-07-11 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11172929B2 (en) | 2019-03-25 | 2021-11-16 | Cilag Gmbh International | Articulation drive arrangements for surgical systems |
US11903581B2 (en) | 2019-04-30 | 2024-02-20 | Cilag Gmbh International | Methods for stapling tissue using a surgical instrument |
US11432816B2 (en) | 2019-04-30 | 2022-09-06 | Cilag Gmbh International | Articulation pin for a surgical instrument |
US11452528B2 (en) | 2019-04-30 | 2022-09-27 | Cilag Gmbh International | Articulation actuators for a surgical instrument |
US11253254B2 (en) | 2019-04-30 | 2022-02-22 | Cilag Gmbh International | Shaft rotation actuator on a surgical instrument |
US11471157B2 (en) | 2019-04-30 | 2022-10-18 | Cilag Gmbh International | Articulation control mapping for a surgical instrument |
US11648009B2 (en) | 2019-04-30 | 2023-05-16 | Cilag Gmbh International | Rotatable jaw tip for a surgical instrument |
US11426251B2 (en) | 2019-04-30 | 2022-08-30 | Cilag Gmbh International | Articulation directional lights on a surgical instrument |
CN114072159A (zh) | 2019-05-03 | 2022-02-18 | 塞尔菲乐有限公司 | 用于生产血液产品的材料和方法 |
US11627959B2 (en) | 2019-06-28 | 2023-04-18 | Cilag Gmbh International | Surgical instruments including manual and powered system lockouts |
US11553971B2 (en) | 2019-06-28 | 2023-01-17 | Cilag Gmbh International | Surgical RFID assemblies for display and communication |
US11051807B2 (en) | 2019-06-28 | 2021-07-06 | Cilag Gmbh International | Packaging assembly including a particulate trap |
US11771419B2 (en) | 2019-06-28 | 2023-10-03 | Cilag Gmbh International | Packaging for a replaceable component of a surgical stapling system |
US11399837B2 (en) | 2019-06-28 | 2022-08-02 | Cilag Gmbh International | Mechanisms for motor control adjustments of a motorized surgical instrument |
US11298132B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Inlernational | Staple cartridge including a honeycomb extension |
US11259803B2 (en) | 2019-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical stapling system having an information encryption protocol |
US11224497B2 (en) | 2019-06-28 | 2022-01-18 | Cilag Gmbh International | Surgical systems with multiple RFID tags |
US11246678B2 (en) | 2019-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical stapling system having a frangible RFID tag |
US11679066B2 (en) | 2019-06-28 | 2023-06-20 | The Procter & Gamble Company | Dissolvable solid fibrous articles containing anionic surfactants |
US11660163B2 (en) | 2019-06-28 | 2023-05-30 | Cilag Gmbh International | Surgical system with RFID tags for updating motor assembly parameters |
US11497492B2 (en) | 2019-06-28 | 2022-11-15 | Cilag Gmbh International | Surgical instrument including an articulation lock |
US11464601B2 (en) | 2019-06-28 | 2022-10-11 | Cilag Gmbh International | Surgical instrument comprising an RFID system for tracking a movable component |
US11291451B2 (en) | 2019-06-28 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with battery compatibility verification functionality |
US11219455B2 (en) | 2019-06-28 | 2022-01-11 | Cilag Gmbh International | Surgical instrument including a lockout key |
US11298127B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Interational | Surgical stapling system having a lockout mechanism for an incompatible cartridge |
US11684434B2 (en) | 2019-06-28 | 2023-06-27 | Cilag Gmbh International | Surgical RFID assemblies for instrument operational setting control |
US11426167B2 (en) | 2019-06-28 | 2022-08-30 | Cilag Gmbh International | Mechanisms for proper anvil attachment surgical stapling head assembly |
US11638587B2 (en) | 2019-06-28 | 2023-05-02 | Cilag Gmbh International | RFID identification systems for surgical instruments |
US11376098B2 (en) | 2019-06-28 | 2022-07-05 | Cilag Gmbh International | Surgical instrument system comprising an RFID system |
US11478241B2 (en) | 2019-06-28 | 2022-10-25 | Cilag Gmbh International | Staple cartridge including projections |
US11350938B2 (en) | 2019-06-28 | 2022-06-07 | Cilag Gmbh International | Surgical instrument comprising an aligned rfid sensor |
US11523822B2 (en) | 2019-06-28 | 2022-12-13 | Cilag Gmbh International | Battery pack including a circuit interrupter |
US20210299179A1 (en) | 2020-02-04 | 2021-09-30 | Cellphire, Inc. | Methods of treating congenital hemophilia with anti-fibrinolytic loaded platelets |
BR112022002892A2 (pt) | 2019-08-16 | 2022-05-24 | Cellphire Inc | Trombossomos como um agente de reversão de agente antiplaqueta |
US11446029B2 (en) | 2019-12-19 | 2022-09-20 | Cilag Gmbh International | Staple cartridge comprising projections extending from a curved deck surface |
US11607219B2 (en) | 2019-12-19 | 2023-03-21 | Cilag Gmbh International | Staple cartridge comprising a detachable tissue cutting knife |
US11844520B2 (en) | 2019-12-19 | 2023-12-19 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11464512B2 (en) | 2019-12-19 | 2022-10-11 | Cilag Gmbh International | Staple cartridge comprising a curved deck surface |
US11576672B2 (en) | 2019-12-19 | 2023-02-14 | Cilag Gmbh International | Surgical instrument comprising a closure system including a closure member and an opening member driven by a drive screw |
US11234698B2 (en) | 2019-12-19 | 2022-02-01 | Cilag Gmbh International | Stapling system comprising a clamp lockout and a firing lockout |
US11701111B2 (en) | 2019-12-19 | 2023-07-18 | Cilag Gmbh International | Method for operating a surgical stapling instrument |
US11911032B2 (en) | 2019-12-19 | 2024-02-27 | Cilag Gmbh International | Staple cartridge comprising a seating cam |
US11529137B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11504122B2 (en) | 2019-12-19 | 2022-11-22 | Cilag Gmbh International | Surgical instrument comprising a nested firing member |
US11529139B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Motor driven surgical instrument |
US11304696B2 (en) | 2019-12-19 | 2022-04-19 | Cilag Gmbh International | Surgical instrument comprising a powered articulation system |
US11291447B2 (en) | 2019-12-19 | 2022-04-05 | Cilag Gmbh International | Stapling instrument comprising independent jaw closing and staple firing systems |
US11559304B2 (en) | 2019-12-19 | 2023-01-24 | Cilag Gmbh International | Surgical instrument comprising a rapid closure mechanism |
US11931033B2 (en) | 2019-12-19 | 2024-03-19 | Cilag Gmbh International | Staple cartridge comprising a latch lockout |
JP2023515960A (ja) * | 2020-02-28 | 2023-04-17 | ボストン サイエンティフィック サイムド,インコーポレイテッド | 多孔体医療用デバイス及び使用方法 |
WO2021188620A1 (en) | 2020-03-17 | 2021-09-23 | Cocrystal Pharma Inc. | Peptidomimetic n5-methyl-n2-(nonanoyl-l-leucyl)-l-glutaminate derivatives, triazaspiro[4.14]nonadecane derivatives and similar compounds as inhibitors of norovirus and coronavirus replication |
MX2022012714A (es) | 2020-04-10 | 2022-12-15 | Cocrystal Pharma Inc | Inhibidores de la replicacion de norovirus y coronavirus. |
USD975278S1 (en) | 2020-06-02 | 2023-01-10 | Cilag Gmbh International | Staple cartridge |
USD975851S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
USD974560S1 (en) | 2020-06-02 | 2023-01-03 | Cilag Gmbh International | Staple cartridge |
USD966512S1 (en) | 2020-06-02 | 2022-10-11 | Cilag Gmbh International | Staple cartridge |
USD975850S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
USD976401S1 (en) | 2020-06-02 | 2023-01-24 | Cilag Gmbh International | Staple cartridge |
USD967421S1 (en) | 2020-06-02 | 2022-10-18 | Cilag Gmbh International | Staple cartridge |
CN111870732B (zh) * | 2020-07-20 | 2022-06-14 | 卓阮医疗科技(苏州)有限公司 | 一种可诱导组织再生修复的止血颗粒及其制备方法和应用 |
US11737748B2 (en) | 2020-07-28 | 2023-08-29 | Cilag Gmbh International | Surgical instruments with double spherical articulation joints with pivotable links |
JP2023534686A (ja) | 2020-07-31 | 2023-08-10 | ザ プロクター アンド ギャンブル カンパニー | ヘアケア用プリル含有水溶性繊維パウチ |
US11517390B2 (en) | 2020-10-29 | 2022-12-06 | Cilag Gmbh International | Surgical instrument comprising a limited travel switch |
US11844518B2 (en) | 2020-10-29 | 2023-12-19 | Cilag Gmbh International | Method for operating a surgical instrument |
US11617577B2 (en) | 2020-10-29 | 2023-04-04 | Cilag Gmbh International | Surgical instrument comprising a sensor configured to sense whether an articulation drive of the surgical instrument is actuatable |
US11931025B2 (en) | 2020-10-29 | 2024-03-19 | Cilag Gmbh International | Surgical instrument comprising a releasable closure drive lock |
USD980425S1 (en) | 2020-10-29 | 2023-03-07 | Cilag Gmbh International | Surgical instrument assembly |
USD1013170S1 (en) | 2020-10-29 | 2024-01-30 | Cilag Gmbh International | Surgical instrument assembly |
US11779330B2 (en) | 2020-10-29 | 2023-10-10 | Cilag Gmbh International | Surgical instrument comprising a jaw alignment system |
US11534259B2 (en) | 2020-10-29 | 2022-12-27 | Cilag Gmbh International | Surgical instrument comprising an articulation indicator |
US11717289B2 (en) | 2020-10-29 | 2023-08-08 | Cilag Gmbh International | Surgical instrument comprising an indicator which indicates that an articulation drive is actuatable |
US11452526B2 (en) | 2020-10-29 | 2022-09-27 | Cilag Gmbh International | Surgical instrument comprising a staged voltage regulation start-up system |
US11896217B2 (en) | 2020-10-29 | 2024-02-13 | Cilag Gmbh International | Surgical instrument comprising an articulation lock |
US11678882B2 (en) | 2020-12-02 | 2023-06-20 | Cilag Gmbh International | Surgical instruments with interactive features to remedy incidental sled movements |
US11627960B2 (en) | 2020-12-02 | 2023-04-18 | Cilag Gmbh International | Powered surgical instruments with smart reload with separately attachable exteriorly mounted wiring connections |
US11744581B2 (en) | 2020-12-02 | 2023-09-05 | Cilag Gmbh International | Powered surgical instruments with multi-phase tissue treatment |
US11653920B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Powered surgical instruments with communication interfaces through sterile barrier |
US11890010B2 (en) | 2020-12-02 | 2024-02-06 | Cllag GmbH International | Dual-sided reinforced reload for surgical instruments |
US11849943B2 (en) | 2020-12-02 | 2023-12-26 | Cilag Gmbh International | Surgical instrument with cartridge release mechanisms |
US11737751B2 (en) | 2020-12-02 | 2023-08-29 | Cilag Gmbh International | Devices and methods of managing energy dissipated within sterile barriers of surgical instrument housings |
US11653915B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Surgical instruments with sled location detection and adjustment features |
US11944296B2 (en) | 2020-12-02 | 2024-04-02 | Cilag Gmbh International | Powered surgical instruments with external connectors |
US11730473B2 (en) | 2021-02-26 | 2023-08-22 | Cilag Gmbh International | Monitoring of manufacturing life-cycle |
US11751869B2 (en) | 2021-02-26 | 2023-09-12 | Cilag Gmbh International | Monitoring of multiple sensors over time to detect moving characteristics of tissue |
US11950777B2 (en) | 2021-02-26 | 2024-04-09 | Cilag Gmbh International | Staple cartridge comprising an information access control system |
US11925349B2 (en) | 2021-02-26 | 2024-03-12 | Cilag Gmbh International | Adjustment to transfer parameters to improve available power |
US11793514B2 (en) | 2021-02-26 | 2023-10-24 | Cilag Gmbh International | Staple cartridge comprising sensor array which may be embedded in cartridge body |
US11723657B2 (en) | 2021-02-26 | 2023-08-15 | Cilag Gmbh International | Adjustable communication based on available bandwidth and power capacity |
US11980362B2 (en) | 2021-02-26 | 2024-05-14 | Cilag Gmbh International | Surgical instrument system comprising a power transfer coil |
US11701113B2 (en) | 2021-02-26 | 2023-07-18 | Cilag Gmbh International | Stapling instrument comprising a separate power antenna and a data transfer antenna |
US11744583B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Distal communication array to tune frequency of RF systems |
US11749877B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Stapling instrument comprising a signal antenna |
US11696757B2 (en) | 2021-02-26 | 2023-07-11 | Cilag Gmbh International | Monitoring of internal systems to detect and track cartridge motion status |
US11950779B2 (en) | 2021-02-26 | 2024-04-09 | Cilag Gmbh International | Method of powering and communicating with a staple cartridge |
US11812964B2 (en) | 2021-02-26 | 2023-11-14 | Cilag Gmbh International | Staple cartridge comprising a power management circuit |
US11717291B2 (en) | 2021-03-22 | 2023-08-08 | Cilag Gmbh International | Staple cartridge comprising staples configured to apply different tissue compression |
US11723658B2 (en) | 2021-03-22 | 2023-08-15 | Cilag Gmbh International | Staple cartridge comprising a firing lockout |
US11826012B2 (en) | 2021-03-22 | 2023-11-28 | Cilag Gmbh International | Stapling instrument comprising a pulsed motor-driven firing rack |
US11759202B2 (en) | 2021-03-22 | 2023-09-19 | Cilag Gmbh International | Staple cartridge comprising an implantable layer |
US11826042B2 (en) | 2021-03-22 | 2023-11-28 | Cilag Gmbh International | Surgical instrument comprising a firing drive including a selectable leverage mechanism |
US11737749B2 (en) | 2021-03-22 | 2023-08-29 | Cilag Gmbh International | Surgical stapling instrument comprising a retraction system |
US11806011B2 (en) | 2021-03-22 | 2023-11-07 | Cilag Gmbh International | Stapling instrument comprising tissue compression systems |
US11744603B2 (en) | 2021-03-24 | 2023-09-05 | Cilag Gmbh International | Multi-axis pivot joints for surgical instruments and methods for manufacturing same |
US11903582B2 (en) | 2021-03-24 | 2024-02-20 | Cilag Gmbh International | Leveraging surfaces for cartridge installation |
US11786243B2 (en) | 2021-03-24 | 2023-10-17 | Cilag Gmbh International | Firing members having flexible portions for adapting to a load during a surgical firing stroke |
US11793516B2 (en) | 2021-03-24 | 2023-10-24 | Cilag Gmbh International | Surgical staple cartridge comprising longitudinal support beam |
US11832816B2 (en) | 2021-03-24 | 2023-12-05 | Cilag Gmbh International | Surgical stapling assembly comprising nonplanar staples and planar staples |
US11944336B2 (en) | 2021-03-24 | 2024-04-02 | Cilag Gmbh International | Joint arrangements for multi-planar alignment and support of operational drive shafts in articulatable surgical instruments |
US11896219B2 (en) | 2021-03-24 | 2024-02-13 | Cilag Gmbh International | Mating features between drivers and underside of a cartridge deck |
US11849945B2 (en) | 2021-03-24 | 2023-12-26 | Cilag Gmbh International | Rotary-driven surgical stapling assembly comprising eccentrically driven firing member |
US11896218B2 (en) | 2021-03-24 | 2024-02-13 | Cilag Gmbh International | Method of using a powered stapling device |
US11857183B2 (en) | 2021-03-24 | 2024-01-02 | Cilag Gmbh International | Stapling assembly components having metal substrates and plastic bodies |
US11849944B2 (en) | 2021-03-24 | 2023-12-26 | Cilag Gmbh International | Drivers for fastener cartridge assemblies having rotary drive screws |
US11786239B2 (en) | 2021-03-24 | 2023-10-17 | Cilag Gmbh International | Surgical instrument articulation joint arrangements comprising multiple moving linkage features |
US20220378426A1 (en) | 2021-05-28 | 2022-12-01 | Cilag Gmbh International | Stapling instrument comprising a mounted shaft orientation sensor |
IL310394A (en) | 2021-08-03 | 2024-03-01 | Cocrystal Pharma Inc | Corona virus inhibitors |
US11980363B2 (en) | 2021-10-18 | 2024-05-14 | Cilag Gmbh International | Row-to-row staple array variations |
US11957337B2 (en) | 2021-10-18 | 2024-04-16 | Cilag Gmbh International | Surgical stapling assembly with offset ramped drive surfaces |
US11877745B2 (en) | 2021-10-18 | 2024-01-23 | Cilag Gmbh International | Surgical stapling assembly having longitudinally-repeating staple leg clusters |
US11937816B2 (en) | 2021-10-28 | 2024-03-26 | Cilag Gmbh International | Electrical lead arrangements for surgical instruments |
CN116159184A (zh) * | 2023-03-14 | 2023-05-26 | 青岛安融生物健康科技有限公司 | 一种人工血管及其体外制备方法 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1144925B (it) * | 1981-10-08 | 1986-10-29 | Anic Spa | Fibre cave di chitosano e procedimento per il loro ottenimento |
NL8401912A (nl) * | 1984-06-15 | 1986-01-02 | Tno | Met aktieve stof beladen biodegradeerbare polymeersubstraten, geschikt voor het gecontroleerd afgeven van de aktieve stof door middel van een membraan. |
US5567612A (en) | 1986-11-20 | 1996-10-22 | Massachusetts Institute Of Technology | Genitourinary cell-matrix structure for implantation into a human and a method of making |
US4857403A (en) * | 1986-12-16 | 1989-08-15 | E. I. Du Pont De Nemours And Company | High strength fibers from chitin derivatives |
US4861527A (en) | 1986-12-16 | 1989-08-29 | Delucca George V | High strength chitosan fibers and fabrics thereof |
FR2616318A1 (fr) * | 1987-06-15 | 1988-12-16 | Centre Nat Rech Scient | Peau artificielle et son procede de preparation |
US5263984A (en) * | 1987-07-20 | 1993-11-23 | Regen Biologics, Inc. | Prosthetic ligaments |
US5444113A (en) * | 1988-08-08 | 1995-08-22 | Ecopol, Llc | End use applications of biodegradable polymers |
FR2661332B1 (fr) * | 1990-04-25 | 1995-06-16 | Michel Jean Pierre | Prothese ligamentaire et son procede de fabrication. |
US5290271A (en) * | 1990-05-14 | 1994-03-01 | Jernberg Gary R | Surgical implant and method for controlled release of chemotherapeutic agents |
US5270300A (en) | 1991-09-06 | 1993-12-14 | Robert Francis Shaw | Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone |
US5342348A (en) * | 1992-12-04 | 1994-08-30 | Kaplan Aaron V | Method and device for treating and enlarging body lumens |
US6162537A (en) * | 1996-11-12 | 2000-12-19 | Solutia Inc. | Implantable fibers and medical articles |
WO2000049135A2 (en) * | 1999-01-21 | 2000-08-24 | Advanced Medical Solutions Limited | Substrate for cell growth |
AU6526100A (en) * | 1999-08-06 | 2001-03-05 | Board Of Regents, The University Of Texas System | Drug releasing biodegradable fiber implant |
US7033603B2 (en) * | 1999-08-06 | 2006-04-25 | Board Of Regents The University Of Texas | Drug releasing biodegradable fiber for delivery of therapeutics |
-
2000
- 2000-08-04 AU AU65261/00A patent/AU6526100A/en not_active Abandoned
- 2000-08-04 EP EP20000952592 patent/EP1206254A1/en not_active Withdrawn
- 2000-08-04 CA CA 2379909 patent/CA2379909C/en not_active Expired - Lifetime
- 2000-08-04 JP JP2001514941A patent/JP4859317B2/ja not_active Expired - Lifetime
- 2000-08-04 CN CN008140227A patent/CN1378445B/zh not_active Expired - Lifetime
- 2000-08-04 WO PCT/US2000/021508 patent/WO2001010421A1/en active Application Filing
- 2000-08-04 US US09/632,457 patent/US6596296B1/en not_active Expired - Lifetime
-
2003
- 2003-05-02 US US10/428,354 patent/US6858222B2/en not_active Expired - Lifetime
-
2004
- 2004-12-21 US US11/019,801 patent/US7514095B2/en not_active Expired - Lifetime
-
2011
- 2011-08-18 JP JP2011179108A patent/JP5383757B2/ja not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
JP2003506401A (ja) | 2003-02-18 |
US20050106211A1 (en) | 2005-05-19 |
EP1206254A1 (en) | 2002-05-22 |
JP2011255197A (ja) | 2011-12-22 |
US6596296B1 (en) | 2003-07-22 |
JP4859317B2 (ja) | 2012-01-25 |
US20030203003A1 (en) | 2003-10-30 |
US7514095B2 (en) | 2009-04-07 |
JP5383757B2 (ja) | 2014-01-08 |
CA2379909C (en) | 2011-01-04 |
WO2001010421A1 (en) | 2001-02-15 |
AU6526100A (en) | 2001-03-05 |
CA2379909A1 (en) | 2001-02-15 |
CN1378445A (zh) | 2002-11-06 |
US6858222B2 (en) | 2005-02-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1378445B (zh) | 药物释放生物可降解纤维植入物 | |
CN100558319C (zh) | 用于传递治疗剂的药物释放性生物可降解纤维 | |
Barnes et al. | Nanofiber technology: designing the next generation of tissue engineering scaffolds | |
Fu et al. | Electrospun gelatin/PCL and collagen/PLCL scaffolds for vascular tissue engineering | |
Wang et al. | Stem cell-based tissue engineering with silk biomaterials | |
Jiang et al. | Current applications and future perspectives of artificial nerve conduits | |
Saul et al. | Hydrogels in regenerative medicine | |
Mohammadalizadeh et al. | Synthetic-based blended electrospun scaffolds in tissue engineering applications | |
US20050161857A1 (en) | Polymeric fibre and method for making same | |
CN104066459A (zh) | 用于医学应用的链段式、富含ε-己内酯的聚(ε-己内酯-共-对二氧杂环己酮)共聚物和由此的装置 | |
CN1568903A (zh) | 接种哺乳动物细胞的复合支架 | |
Zhang et al. | Systematic review of silk scaffolds in musculoskeletal tissue engineering applications in the recent decade | |
Zha et al. | Electrospun natural polymer and its composite nanofibrous scaffolds for nerve tissue engineering | |
CN109381732A (zh) | 负载生长因子小分子抑制剂的静电纺丝敷料、其制备方法及应用 | |
Yang et al. | Coaxial bioelectrospinning of P34HB/PVA microfibers biomimetic scaffolds with simultaneity cell-laden for improving bone regeneration | |
Zhang et al. | Application of chitosan with different molecular weights in cartilage tissue engineering | |
Mendibil et al. | Bioresorbable and mechanically optimized nerve guidance conduit based on a naturally derived medium chain length polyhydroxyalkanoate and poly (ε-caprolactone) blend | |
CN103933619A (zh) | 神经修复材料及其制备方法 | |
Zhang et al. | Design and characterization of small-diameter tissue-engineered blood vessels constructed by electrospun polyurethane-core and gelatin-shell coaxial fiber |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C12 | Rejection of a patent application after its publication | ||
RJ01 | Rejection of invention patent application after publication |
Open date: 20021106 |
|
CI01 | Publication of corrected invention patent application |
Correction item: Rejection of patent application Correct: Dismiss False: Reject Number: 31 Volume: 26 |
|
ERR | Gazette correction |
Free format text: CORRECT: PATENT APPLICATION REJECTION AFTER PUBLICATION; FROM: REJECTION TO: REJECTION OF REVOCATION |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CX01 | Expiry of patent term |
Granted publication date: 20130206 |
|
CX01 | Expiry of patent term |