CN109172073B - Electrostatic spinning nanofiber membrane for controlling release of growth factors and esophageal tectorial membrane memory stent - Google Patents
Electrostatic spinning nanofiber membrane for controlling release of growth factors and esophageal tectorial membrane memory stent Download PDFInfo
- Publication number
- CN109172073B CN109172073B CN201811019894.3A CN201811019894A CN109172073B CN 109172073 B CN109172073 B CN 109172073B CN 201811019894 A CN201811019894 A CN 201811019894A CN 109172073 B CN109172073 B CN 109172073B
- Authority
- CN
- China
- Prior art keywords
- solution
- layer solution
- esophageal
- core layer
- shell layer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000012528 membrane Substances 0.000 title claims abstract description 63
- 239000002121 nanofiber Substances 0.000 title claims abstract description 54
- 238000010041 electrostatic spinning Methods 0.000 title claims abstract description 32
- 239000003102 growth factor Substances 0.000 title claims abstract description 31
- 210000002489 tectorial membrane Anatomy 0.000 title claims abstract description 21
- 239000010410 layer Substances 0.000 claims abstract description 83
- 239000012792 core layer Substances 0.000 claims abstract description 80
- 238000009987 spinning Methods 0.000 claims abstract description 50
- 239000002904 solvent Substances 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 22
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229920000747 poly(lactic acid) Polymers 0.000 claims abstract description 19
- 239000004626 polylactic acid Substances 0.000 claims abstract description 19
- 229920001577 copolymer Polymers 0.000 claims abstract description 18
- 101710098940 Pro-epidermal growth factor Proteins 0.000 claims abstract description 17
- 208000031481 Pathologic Constriction Diseases 0.000 claims abstract description 10
- 230000036262 stenosis Effects 0.000 claims abstract description 10
- 208000037804 stenosis Diseases 0.000 claims abstract description 10
- 206010058522 Oesophageal injury Diseases 0.000 claims abstract description 7
- 238000001523 electrospinning Methods 0.000 claims description 23
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 17
- 239000012498 ultrapure water Substances 0.000 claims description 17
- 229910052751 metal Inorganic materials 0.000 claims description 12
- 239000002184 metal Substances 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 9
- 238000009954 braiding Methods 0.000 claims description 3
- 230000017423 tissue regeneration Effects 0.000 claims description 3
- 238000009941 weaving Methods 0.000 claims description 3
- 230000001737 promoting effect Effects 0.000 claims description 2
- 239000000243 solution Substances 0.000 abstract description 141
- 230000000694 effects Effects 0.000 abstract description 9
- 230000008439 repair process Effects 0.000 abstract description 5
- 239000007864 aqueous solution Substances 0.000 abstract 1
- 230000004952 protein activity Effects 0.000 abstract 1
- 239000011257 shell material Substances 0.000 description 65
- 210000004379 membrane Anatomy 0.000 description 49
- 239000003814 drug Substances 0.000 description 31
- 229940079593 drug Drugs 0.000 description 26
- 239000000835 fiber Substances 0.000 description 21
- 210000003238 esophagus Anatomy 0.000 description 20
- 210000004877 mucosa Anatomy 0.000 description 18
- 239000000463 material Substances 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 10
- 101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 8
- 230000009471 action Effects 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 230000005684 electric field Effects 0.000 description 8
- 239000012530 fluid Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000005507 spraying Methods 0.000 description 8
- 239000011259 mixed solution Substances 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 229940098773 bovine serum albumin Drugs 0.000 description 6
- 102000012422 Collagen Type I Human genes 0.000 description 5
- 108010022452 Collagen Type I Proteins 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 239000008055 phosphate buffer solution Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 101000691618 Homo sapiens Inactive phospholipase C-like protein 1 Proteins 0.000 description 4
- 102100026207 Inactive phospholipase C-like protein 1 Human genes 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000002674 endoscopic surgery Methods 0.000 description 4
- 229920000848 poly(L-lactide-ε-caprolactone) Polymers 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 208000007217 Esophageal Stenosis Diseases 0.000 description 3
- 206010016717 Fistula Diseases 0.000 description 3
- 206010030178 Oesophageal obstruction Diseases 0.000 description 3
- 206010030194 Oesophageal stenosis Diseases 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000003890 fistula Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- HZEWFHLRYVTOIW-UHFFFAOYSA-N [Ti].[Ni] Chemical compound [Ti].[Ni] HZEWFHLRYVTOIW-UHFFFAOYSA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 108010025899 gelatin film Proteins 0.000 description 2
- 229960004130 itraconazole Drugs 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 229910001000 nickel titanium Inorganic materials 0.000 description 2
- 229920001610 polycaprolactone Polymers 0.000 description 2
- 239000004632 polycaprolactone Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 229910001285 shape-memory alloy Inorganic materials 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 210000003771 C cell Anatomy 0.000 description 1
- JFPVXVDWJQMJEE-QMTHXVAHSA-N Cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)C(=NOC)C1=CC=CO1 JFPVXVDWJQMJEE-QMTHXVAHSA-N 0.000 description 1
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 101100172720 Rattus norvegicus Ces1e gene Proteins 0.000 description 1
- 108010087230 Sincalide Proteins 0.000 description 1
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 1
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 241000190079 Turnera Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000151 anti-reflux effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- XIURVHNZVLADCM-IUODEOHRSA-N cefalotin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CC1=CC=CS1 XIURVHNZVLADCM-IUODEOHRSA-N 0.000 description 1
- 229960000603 cefalotin Drugs 0.000 description 1
- 229960001139 cefazolin Drugs 0.000 description 1
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- XMEVHPAGJVLHIG-FMZCEJRJSA-N chembl454950 Chemical compound [Cl-].C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H]([NH+](C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O XMEVHPAGJVLHIG-FMZCEJRJSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000013013 elastic material Substances 0.000 description 1
- 208000028299 esophageal disease Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- FPCCSQOGAWCVBH-UHFFFAOYSA-N ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 description 1
- 229960005417 ketanserin Drugs 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229940087515 mefoxin Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 230000002138 osteoinductive effect Effects 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960004989 tetracycline hydrochloride Drugs 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
-
- 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
- A61L2300/60—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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Surgery (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Cardiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Anesthesiology (AREA)
- Hematology (AREA)
- Prostheses (AREA)
- Materials For Medical Uses (AREA)
Abstract
The application relates to an electrostatic spinning nanofiber membrane for controlling the release of growth factors and an esophageal tectorial membrane memory stent. The electrostatic spinning nanofiber membrane for controlling the release of growth factors is prepared by adopting a coaxial co-spinning method, wherein a shell layer solution is a polylactic acid caprolactone copolymer solution taking hexafluoroisopropanol as a solvent, and a core layer solution is an EGF protein aqueous solution. The esophageal tectorial membrane memory stent comprises a first fixed end, a second fixed end and a stent main body with the outer diameter of 40-50mm, wherein the second fixed end and the whole outer wall of the stent main body are coated with the electrospun nanofiber membrane for controlling the release of growth factors, and the first fixed end consists of a plurality of membranes with tension. The application provides a novel method for treating esophageal injury without stenosis or obstruction, the esophageal tectorial membrane memory stent can be used for treating esophageal injury without stenosis or obstruction and is not easy to dislocate, the loaded electrostatic spinning nanofiber membrane has excellent slow release effect, the protein activity is maintained well, and the repair of esophageal injury can be obviously promoted.
Description
Technical Field
The application relates to the technical field of medical appliances, in particular to an electrospun nanofiber membrane for controlling the release of growth factors and an esophageal tectorial membrane memory stent.
Background
The esophageal stent is the most commonly used tool in the treatment of various benign and malignant esophageal diseases, the functions of the esophageal stent comprise internal support, can effectively relieve esophageal obstruction, prevent the occurrence of esophageal stenosis, is beneficial to feeding nutrition and is beneficial to physical function recovery. Esophageal stents are routinely left in the patient for a period of time. The general principle of the placement of the esophageal stents is that after the stent is placed, the expanded stent is clamped at a narrow place due to the memory expansion force of the stent, so that the stent is not easy to move.
While some patients with obvious stenosis or obstruction have normal other parts of the esophagus, only have esophageal mucosa interruption, unrepaired esophageal damage caused by endoscopic surgery and the like, often require chest opening surgery, and clinically lack effective esophageal stents to help esophageal mucosa repair.
Generally, the esophageal stents commonly used in clinic are designed to relieve esophageal stenosis and obstruction, and are not suitable for patients with esophageal restenosis or obstruction. For this part of the patients, there is often only surgery, or conservative treatment, due to the lack of a similar stent that can be placed under the endoscope, which greatly affects the disease treatment effect and quality of life of the patient.
Patent document CN201879873U, bulletin day 2011.06.29, in order to overcome the defects of small radial supporting force, easy granulation proliferation at both ends and the like of conventional recoverable anti-reflux esophageal stent, a nickel-titanium memory alloy full-covered super-mouth recoverable esophageal stent is provided, two ends of a stent main body are bulged, the stent main body is a cylinder, the total length of the stent is 40-160 mm, the stent is a reticular structure woven by nickel-titanium shape memory alloy, the whole stent is coated with a silica gel film, the diameter of the section of the stent main body is 10-26 mm, and the silica gel film exceeds the outer mouth of the bulged upper end of the stent main body by 5-10 mm to form a skirt structure. The esophageal stent is not easy to have the problems of stent displacement and falling, restenosis, difficult stent extraction, easy bleeding and the like.
Patent document CN101984940a, publication date 2011.03.16, in order to solve the problem that the traditional esophageal stent does not have the function of preventing and treating cancerous fistula of esophagus, discloses a bag-covered esophageal stent capable of loading medicine, the esophageal stent is composed of an inner supporting tube and a medicine bag, the inner supporting tube is a corrugated tube, two ends of the corrugated tube are respectively extended with a positioning tube with a larger tube diameter, the corrugated tube between the two positioning tubes is an effective part, and the length of the effective part is longer than that of a lesion part; the medicine bag is a cavity formed by sealing the effective part of the corrugated pipe and a layer of elastic material wrapped outside the effective part of the corrugated pipe, and a medicine inlet pipe communicated with the medicine bag is fixed at the pipe wall of the upper end of the effective part of the corrugated pipe. The application has the advantages that: the support has certain axial flexibility, is beneficial to the placement of the support, has good radial strength, can keep a good channel, has better elasticity, flexibility and good adhesion after being charged, can reduce the damage of the support to a lesion part, and can prevent the support from displacement; the stent can also achieve the purpose of preventing and treating esophageal cancerous fistula, thereby relieving the pain of patients. When the stent is selected, the upper and lower openings of the stent are 10-20 mm beyond the narrow section (or lesion part).
Therefore, the two kinds of esophageal stents are still only suitable for the condition that the esophageal stenosis or obstruction exists, so that a new method or device capable of effectively treating the condition that the esophageal has no stenosis or obstruction, but the condition that the esophageal mucosa is interrupted or the esophageal damage caused by endoscopic surgery is not repaired is needed.
In addition, the bag-covered esophageal stent of the patent document CN101984940A can be loaded with a drug, and the drug can be exuded from the bag and gradually released into a human body when in use, so that the purpose of preventing and treating esophageal cancerous fistula is achieved. However, the mode of drug release is not controllable, and the preventive or therapeutic effect cannot be accurately expected.
The polymer electrospinning superfine fiber drug release system is a polymer drug-loaded nanofiber prepared by electrospinning, the diameter of the nanofiber prepared by electrospinning is small, the surface area is large, and the polymer electrospinning superfine fiber drug release system can be used as a drug-loaded material, so that the loaded drug can be slowly decomposed and released, and a better therapeutic effect can be exerted. In the literature report of preparing superfine fiber drug release system by electrospinning, the used drugs include antibiotics, antitumor/anticancer drugs, bioactive factors and other chemical drugs, such as: cephalothin thiophene methoxy cephalosporin sodium (Mefoxin), rifampin, itraconazole (Itraconazole), kel turnera (Ketanserin), tetracycline hydrochloride, cephalosporin V (Cefazolin), taxol, doxorubicin hydrochloride, heparin and the like, and some reports of releasing protein biological drugs have been made. The drug carrier mainly comprises PLA, PGA and block copolymers PLGA with different proportions. Coaxial electrostatic spinning is a new method developed in the traditional electrostatic spinning technology, and continuous shell-core structure nanofibers or hollow nanofibers can be prepared in one step. In the process of coaxial co-spinning, the protein solution and the polymer organic solution are packaged in two containers for simultaneous spinning, so that the contact time of the protein and the organic solution is reduced, and the stability of the protein is improved. The morphology, drug release characteristics and drug activity of the drug-loaded nanofibers are affected by electrostatic spinning parameters such as concentration, molecular weight, conductivity, flow rate, voltage and the like of the solution, but the relationship between each parameter and the structure and performance of the drug-loaded nanofibers is not completely clear at present.
In the repairing process of the esophageal damage, if a polymer electrospinning superfine fiber drug release system is utilized to accelerate the repairing process, the repairing process can be greatly benefited for patients.
Patent document CN107224619a, publication No. 2017.10.03, discloses a method for preparing ICA-SF/PLCL nanofiber membrane by coaxial electrostatic spinning technology, which uses solution formed by SF and PLCL dissolved in hexafluoroisopropanol as shell layer spinning solution, uses ICA solution of 10-5 μmol/L as core layer spinning solution, uses coaxial electrostatic spinning equipment, and controls the optimal technological parameters of electrostatic spinning: spinning solution of the core and the shell at the advancing speed of 0.1mL/h and 1.0mL/h respectively, electrospinning at the room temperature of 25 ℃ and the relative humidity of 50+/-6%, taking glutaraldehyde as a cross-linking agent for 48 hours, and vacuum drying to obtain the ICA-SF/PLCL nanofiber membrane. In vitro osteoinductive differentiation and in vivo application to bone defect experiments indicate that the prepared ICA-SF/PLCL nanofiber membrane can continuously and effectively release ICA to remarkably promote osteogenesis without cytotoxicity.
Patent document CN106730038A, publication date 2017.05.31, discloses a fibrous membrane for tracheal soft tissue repair and a preparation method thereof, the specific preparation method is as follows: (1) preparation of shell material: and dissolving polycaprolactone and type I collagen in hexafluoroisopropanol according to a mass ratio of 4:1, stirring for 12 hours to prepare a polycaprolactone/type I collagen mixed solution with a mass concentration of 12%, and then performing ultrasonic treatment for 30 minutes to remove bubbles generated during stirring to prepare a shell layer material mixed solution. (2) preparation of core layer material: s1: adding recombinant transforming growth factor-beta 3 (rhTGF-beta 3) into phosphate buffer solution, and gently stirring for 1h to prepare rhTGF-beta 3 solution with the concentration of 40 mug/mL; s2: adding Bovine Serum Albumin (BSA) into phosphate buffer solution, and gently stirring for 1h to prepare a BSA solution with the concentration of 200 mug/mL; s3: mixing the rhTGF-beta 3 solution with the concentration of 40 mug/mL prepared by S1 and the BSA solution with the concentration of 200 mug/mL prepared by S2 in equal volume to prepare a mixed solution of rhTGF-beta 3/BSA; s4: dissolving type I collagen in deionized water to prepare type I collagen solution with the mass concentration of 20%; s5: and (3) mixing the type I collagen solution with the mass concentration of 20% prepared in the step (S4) and the mixed solution of rhTGF-beta 3/BSA prepared in the step (S3) in an equal volume to prepare the mixed solution of the nuclear layer material. (3) spinning: s1: respectively adding the shell layer material mixed solution and the core layer material mixed solution into a shell layer material injector and a core layer material injector in coaxial electrostatic spinning equipment, and standing for 30-60min until air of the shell layer material injector and the core layer material injector is exhausted; s2: the distance between the roller receiver and the coaxial spray head is adjusted to 15-20cm, the high-voltage power supply is adjusted to 15-20 kV, the output speed of the microinjection pump carrying the shell layer material injector is adjusted to 1mL/h, the output speed of the microinjection pump carrying the core layer material injector is adjusted to 0.2mL/h, and the rotating speed of the roller receiver is controlled to 200-350 rpm; s4: and after the nuclear layer material is completely output, finishing spinning, and taking down the spinning film from the collecting device to obtain the fiber.
However, no report of successfully applying the drug-loaded nanofiber membrane prepared by the electrostatic spinning technology to esophageal repair is currently available.
Disclosure of Invention
The application aims at solving the problem of poor esophageal injury treatment of no stenosis or obstruction of esophagus in the prior art, and provides an esophageal tectorial membrane memory stent treatment method, an electrospun nanofiber membrane for controlling the release of growth factors and an esophageal tectorial membrane memory stent.
In a first aspect, the present application provides an electrospun nanofiber membrane for controlled release of growth factors, said electrospun nanofiber membrane prepared according to the following method:
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer solution taking hexafluoroisopropanol as a solvent, and the concentration is 0.06-0.10g/mL; the core layer solution takes ultrapure water as a solvent, and the solute is EGF protein;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of a coaxial co-spinning electrostatic spinning device, wherein the spinning voltage is 14-16kV, the distance from a nozzle to a receiving device is 14-16cm, and the stable flow rate of the shell layer and the core layer is controlled to be 0.013-0.017mL/h, namely.
As a preferable example, the core solution uses ultrapure water as a solvent, the solute is EGF protein, and the protein concentration is 15-25ng/ml.
As a preferred example, the electrospun nanofiber membrane is prepared according to the following method:
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer solution taking hexafluoroisopropanol as a solvent, and the concentration is 0.08g/mL; the core layer solution takes ultrapure water as a solvent, and the solute is EGF protein;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of a coaxial co-spinning electrostatic spinning device, wherein the spinning voltage is 15kV, the distance from a nozzle to a receiving device is 15cm, and the stable flow rate of the shell layer and the core layer is controlled to be 0.015mL/h.
In a second aspect, the present application provides a method for preparing an electrospun nanofiber membrane for controlled release of a growth factor, comprising the steps of:
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer solution taking hexafluoroisopropanol as a solvent, and the concentration is 0.06-0.10g/mL; the core layer solution takes ultrapure water as a solvent, and the solute is EGF protein;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of a coaxial co-spinning electrostatic spinning device, wherein the spinning voltage is 14-16kV, the distance from a nozzle to a receiving device is 14-16cm, and the stable flow rate of the shell layer and the core layer is controlled to be 0.013-0.017mL/h.
As a preferred example, the preparation method comprises the following steps:
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer solution taking hexafluoroisopropanol as a solvent, and the concentration is 0.08g/mL; the core layer solution takes ultrapure water as a solvent, and the solute is EGF protein;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of a coaxial co-spinning electrostatic spinning device, wherein the spinning voltage is 15kV, the distance from a nozzle to a receiving device is 15cm, and the stable flow rate of the shell layer and the core layer is controlled to be 0.015mL/h.
In a third aspect, the application provides the use of an electrospun nanofiber membrane as described above in the preparation of a medical device for promoting tissue repair.
As a preferred example, the medical device is an esophageal stent.
In a fourth aspect, the application provides an esophageal tectorial membrane memory stent suitable for treating esophageal injury without stenosis or obstruction, which is characterized in that two ends of the esophageal tectorial membrane memory stent are respectively a first fixed end and a second fixed end, and a stent main body is arranged between the first fixed end and the second fixed end; the bracket main body is formed by braiding memory metal wires and is in a cylindrical tube shape, and the outer diameter of the bracket main body is 40-50mm; the second fixed end is formed by weaving memory metal wires and is in a horn shape; the second fixed end and the whole outer wall of the bracket main body are coated with a growth factor-containing film, and the growth factor-containing film is an electrostatic spinning nanofiber film; the first fixing end consists of a plurality of diaphragms with tension, the lower edges of the diaphragms are connected with the upper edge of the bracket main body, the diaphragms encircle the upper edge of the bracket main body for a circle, and the diaphragms are in a tight shape in a use state.
As a preferable example, the outer diameter of the lower edge of the second fixed end is 52-56mm.
As another preferred example, the membrane is semi-elliptical, semi-circular or trapezoidal.
As another preferable example, the upper edge of the bracket main body is wavy and provided with a plurality of grooves, and the lower end of the diaphragm is connected in the grooves in a positive embedded manner.
The application has the advantages that:
1. based on abundant clinical experience, the inventor provides a novel method for treating the esophageal stent against the situation that the esophagus has no stenosis or obstruction but the esophagus is damaged and is not repaired due to the occurrence of esophageal mucosa interruption or endoscopic surgery, and designs the esophageal tectorial membrane memory stent based on the novel method.
2. The electrostatic spinning nanofiber membrane for controlling the release of the growth factors is arranged on the outer wall of the esophageal tectorial membrane memory support, the growth factors are loaded into the membrane, the growth factors can be slowly released, the repair of mucous membrane is promoted, and the esophagus and external esophageal tissues can be effectively isolated.
3. The upper end of the esophageal tectorial membrane memory bracket consists of a plurality of diaphragms with tension, and the diaphragms are expanded to be in a tight state and are attached to the inner wall of esophageal mucosa in a use state, so that a large friction force is provided, a fixing effect can be achieved, and the bracket is prevented from shifting and falling off; in particular, the tension of the whole diaphragm from bottom to top is gradually reduced, so that the esophageal mucosa at the part has gradually weakened expansion force and plays a good role in protecting the mucosa.
4. The lower end of the esophageal tectorial membrane memory bracket is in a horn shape, and the diameter of the lower end is larger than that of the bracket main body, so that the lower end can support the inner wall of the esophagus and effectively prevent the esophageal bracket from shifting.
5. The application prepares the electrospun nanofiber membrane for controlling the release of the growth factor EGF, adopts hexafluoroisopropanol solution of a polylactic acid caprolactone copolymer as a shell layer, adopts EGF protein water solution as a core layer, strictly controls co-spinning parameters, especially the flow rate, and has excellent slow release effect and better EGF activity. The coating is loaded on the esophageal tectorial memory stent, and can obviously promote the restoration of esophageal injury.
Drawings
FIG. 1 is a front view (in a fully released state) of the esophageal stent graft of example 1.
FIG. 2 is a front view (in a limited state) of the esophageal stent graft of example 1.
FIG. 3 is a front view (in a fully released state) of the esophageal stent graft of example 2.
Detailed Description
The following detailed description of the application provides specific embodiments with reference to the accompanying drawings.
Reference numerals and components referred to in the drawings are as follows:
1. first fixed end 2. Second fixed end
3. Stent body 4. Growth factor-containing Membrane
5. Diaphragm 6. Groove
Example 1 esophageal tectorial memory stent of the application
Referring to fig. 1, fig. 1 is a front view (in a fully released state) of an esophageal stent graft of example 1. The two ends of the esophageal tectorial membrane memory bracket are respectively provided with a first fixed end 1 and a second fixed end 2, and a bracket main body 3 is arranged between the first fixed end 1 and the second fixed end 2. The bracket main body 3 is formed by braiding memory metal wires and is in a cylindrical tube shape, and the outer diameter of the bracket main body is 40-50mm. The second fixed end 2 is also woven by memory metal wires and is in a horn shape, and the outer diameter of the lower edge is 52-56mm. The second fixed end 2 and the memory metal wire of the bracket main body 3 are of an integrated structure. The whole outer wall of the second fixed end 2 and the bracket main body 3 is coated with a growth factor-containing film 4. The first fixed end 1 consists of a plurality of diaphragms 5; the membrane 5 has tension and is semi-elliptic, and the lower edge of the membrane 5 is linear and is connected with the upper edge of the bracket main body 3; these diaphragms 5 are circumferentially wound around the upper edge of the holder body 3.
The application method of the esophageal tectorial membrane memory stent comprises the following steps:
referring first to fig. 2, fig. 2 is a front view (in a limited state) of the esophageal stent graft of example 1. In the unused state, the esophageal tectorial membrane memory stent is limited in a catheter, the memory metal wires of the second fixed end 2 and the stent main body 3 are elongated and radially reduced, the membrane 5 gathers towards the center, and the membrane 4 containing the growth factors is in a wrinkled state.
Referring to fig. 1 again, for the situation that the esophagus is not narrow or obstructed, but the esophagus is broken or damaged due to endoscopic surgery, etc., under the endoscope, the operator places the catheter with the memory stent into the esophagus of the patient, when the part of the esophagus mucosa to be repaired is just located in the section of the stent main body 3, the memory stent is released, at this time, the outer wall of the memory stent containing the growth factors 4 is attached to the inner wall of the esophagus mucosa, the esophagus mucosa to be repaired is contacted with the film containing the growth factors 4, the second fixed end 2 stretches the esophagus, and the film 5 is stretched to be tight due to radial expansion of the memory metal wire. The surgeon then attaches the respective diaphragms 5 to the esophageal mucosa under the endoscope with clips so that the outer wall of the diaphragm 5 is adhered to the inner wall of the esophageal mucosa.
It should be noted that the esophageal tectorial memory stent of the application is suitable for the situation that the esophagus has no stenosis or obstruction but the esophageal damage caused by the esophageal mucosa interruption or endoscopic operation is not repaired, so the outer diameter of the stent main body 3 is 40-50mm, the growth factor-containing film 4 can be ensured to be basically attached to the inner wall of the esophageal mucosa, and the design provides a feasible new method for repairing the esophageal mucosa of a patient with the esophagus having no stenosis or obstruction. The growth factor-containing film 4 is an electrospun nanofiber film prepared according to the method of any one of examples 3-7 of the specification. The growth factor-containing film 4 loads the growth factors into the film, can slowly release the growth factors, promote the repair of mucous membranes, and can effectively isolate esophagus from external esophageal tissues. The growth factor-containing film 4 may be directly attached to the second fixing end 2 and the outer wall of the holder body 3. The first fixing end 1 is composed of a plurality of diaphragms 5 with tension, and the diaphragms 5 are expanded to be in a tight state and are attached to the inner wall of the esophageal mucosa in a use state, so that a large friction force is provided, a fixing effect can be achieved, and the esophageal tectorial memory stent disclosed by the application is prevented from being shifted and falling off. In particular, the tension of the whole diaphragm 5 from bottom to top is gradually reduced, so that the diaphragm has gradually weakened expansion force on the esophageal mucosa of the part, and plays a good role in protecting the mucosa. The thickness of the membrane 5 is preferably 50-200nm, the number of the membrane can be 4-10 sheets, and the membrane can also be semicircular, trapezoid or any curve shape with the lower edge being a straight upper edge. The second fixed end 2 is in a horn shape, and the diameter of the second fixed end is larger than that of the bracket main body 3, so that the inner wall of the esophagus can be supported, and the esophagus bracket is effectively prevented from shifting.
Example 2 esophageal tectorial memory stent (II) of the application
Referring to fig. 3, fig. 3 is a front view (in a fully released state) of the esophageal stent graft according to embodiment 2. The two ends of the esophageal tectorial membrane memory bracket are respectively provided with a first fixed end 1 and a second fixed end 2, and a bracket main body 3 is arranged between the first fixed end 1 and the second fixed end 2. The bracket main body 3 is formed by weaving memory metal wires, is in a cylindrical tube shape, has the outer diameter of 40-50mm, and has a wavy upper edge and a plurality of grooves 6. The second fixed end 2 is also woven by memory metal wires and is in a horn shape, and the outer diameter of the lower edge is 52-56mm. The second fixed end 2 and the memory metal wire of the bracket main body 3 are of an integrated structure. The whole outer wall of the second fixed end 2 and the bracket main body 3 is coated with a growth factor-containing film 4. The first fixed end 1 consists of a plurality of diaphragms 5; the membrane 5 has tension and is oval, the lower end of the membrane 5 is just positioned in the groove 6, and the upper end of the membrane 5 exceeds the upper edge of the bracket main body 3 by a certain height. These diaphragms 5 are circumferentially wound around the upper edge of the holder body 3.
The diaphragm 5 of this embodiment just in time is chimeric connection with recess 6, and under the state of use, the lower extreme of diaphragm 5 just in time by the more powerful stretching expansion of the upper edge of support main part 3, with the inner wall frictional force of esophagus stronger, fixed effect is stronger. The membrane 5 may also be circular, trapezoidal or of other shape.
EXAMPLE 3 electrospun nanofiber membrane of the application (I)
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer (75:25) solution taking hexafluoroisopropanol (purchased from Merck) as a solvent, the concentration is 0.08g/mL, the core layer solution takes ultrapure water as a solvent, the solute is recombinant human EGF protein (purchased from Gibco, product number PHG 0315), and the protein concentration is 20ng/mL;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of coaxial electrostatic spinning equipment (SS-2535, beijing Yongkangle industrial scientific development Co., ltd.), wherein the spinning voltage is 15kV, the distance from a nozzle to a receiving device is 15cm, controlling the stable flow rate of the shell layer and the core layer to be 0.015mL/h, when the voltage exceeds a critical value, spraying the core layer solution and the shell layer solution from inside and outside to the top end of the nozzle, forming superfine solution fluid under the action of an electric field to fly to a receiver and quickly solidifying into superfine fibers with the diameter below micrometers, and receiving the superfine fibers at the receiving device to form a drug-containing nanofiber membrane.
EXAMPLE 4 electrospun nanofiber membrane of the application (II)
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer (75:25) solution taking hexafluoroisopropanol (purchased from Merck) as a solvent, the concentration is 0.10g/mL, the core layer solution takes ultrapure water as a solvent, the solute is recombinant human EGF protein (purchased from Gibco, product number PHG 0315), and the protein concentration is 15ng/mL;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of coaxial electrostatic spinning equipment (SS-2535, beijing Yongkangle industrial scientific development Co., ltd.), wherein the spinning voltage is 14kV, the distance from a nozzle to a receiving device is 14cm, controlling the stable flow rate of the shell layer and the core layer to be 0.017mL/h, when the voltage exceeds a critical value, spraying the core layer solution and the shell layer solution from inside and outside to the top end of the nozzle, forming superfine solution fluid under the action of an electric field to fly to a receiver and quickly solidifying into superfine fibers with the diameter below micrometers, and receiving the superfine fibers with the diameter below micrometers at the receiving device to form a drug-containing nanofiber membrane.
EXAMPLE 5 electrospun nanofiber membrane of the application (III)
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer (75:25) solution taking hexafluoroisopropanol (purchased from Merck) as a solvent, the concentration is 0.06g/mL, the core layer solution takes ultrapure water as a solvent, the solute is recombinant human EGF protein (purchased from Gibco, product number PHG 0315), and the protein concentration is 15ng/mL;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of coaxial electrostatic spinning equipment (SS-2535, beijing Yongkangle industrial scientific development Co., ltd.), wherein the spinning voltage is 16kV, the distance from a nozzle to a receiving device is 14cm, controlling the stable flow rate of the shell layer and the core layer to be 0.015mL/h, when the voltage exceeds a critical value, spraying the core layer solution and the shell layer solution from inside and outside to the top end of the nozzle, forming superfine solution fluid under the action of an electric field to fly to a receiver and quickly solidifying into superfine fibers with the diameter below micrometers, and receiving the superfine fibers at the receiving device to form a drug-containing nanofiber membrane.
EXAMPLE 6 electrospun nanofiber membrane according to the Invention (IV)
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer (75:25) solution taking hexafluoroisopropanol (purchased from Merck) as a solvent, the concentration is 0.10g/mL, the core layer solution takes ultrapure water as a solvent, the solute is recombinant human EGF protein (purchased from Gibco, product number PHG 0315), and the protein concentration is 25ng/mL;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of coaxial electrostatic spinning equipment (SS-2535, beijing Yongkangle industrial scientific development Co., ltd.), wherein the spinning voltage is 16kV, the distance from a nozzle to a receiving device is 16cm, controlling the stable flow rate of the shell layer and the core layer to be 0.013mL/h, when the voltage exceeds a critical value, spraying the core layer solution and the shell layer solution from inside and outside to the top end of the nozzle, forming superfine solution fluid under the action of an electric field to fly to a receiver and quickly solidifying into superfine fibers with the diameter below micrometers, and receiving the superfine fibers at the receiving device to form the drug-containing nanofiber membrane.
EXAMPLE 7 electrospun nanofiber membrane of the application (five)
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer (75:25) solution taking hexafluoroisopropanol (purchased from Merck) as a solvent, the concentration is 0.08g/mL, the core layer solution takes ultrapure water as a solvent, the solute is recombinant human EGF protein (purchased from Gibco, product number PHG 0315), and the protein concentration is 20ng/mL;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of coaxial electrostatic spinning equipment (SS-2535, beijing Yongkangle industrial scientific development Co., ltd.), wherein the spinning voltage is 15kV, the distance from a nozzle to a receiving device is 15cm, controlling the stable flow rate of the shell layer and the core layer to be 0.017mL/h, when the voltage exceeds a critical value, spraying the core layer solution and the shell layer solution from inside and outside to the top end of the nozzle, forming superfine solution fluid under the action of an electric field to fly to a receiver and quickly solidifying into superfine fibers with the diameter below micrometers, and receiving the superfine fibers with the diameter below micrometers at the receiving device to form a drug-containing nanofiber membrane.
Comparative example 1
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer (75:25) solution taking trifluoroethanol (purchased from Merck) as a solvent, the concentration is 0.08g/mL, the core layer solution takes ultrapure water as a solvent, the solute is recombinant human EGF protein (purchased from Gibco, product number PHG 0315), and the protein concentration is 20ng/mL;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of coaxial electrostatic spinning equipment (SS-2535, beijing Yongkangle industrial scientific development Co., ltd.), wherein the spinning voltage is 15kV, the distance from a nozzle to a receiving device is 15cm, controlling the stable flow rate of the shell layer and the core layer to be 0.015mL/h, when the voltage exceeds a critical value, spraying the core layer solution and the shell layer solution from inside and outside to the top end of the nozzle, forming superfine solution fluid under the action of an electric field to fly to a receiver and quickly solidifying into superfine fibers with the diameter below micrometers, and receiving the superfine fibers at the receiving device to form a drug-containing nanofiber membrane.
Comparative example 2
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer (75:25) solution taking hexafluoroisopropanol (purchased from Merck) as a solvent, the concentration is 0.10g/mL, the core layer solution takes ultrapure water as a solvent, the solute is recombinant human EGF protein (purchased from Gibco, product number PHG 0315), and the protein concentration is 15ng/mL;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of coaxial electrostatic spinning equipment (SS-2535, beijing Yongkangle industrial scientific development Co., ltd.), wherein the spinning voltage is 14kV, the distance from a nozzle to a receiving device is 14cm, controlling the stable flow rate of the shell layer and the core layer to be 0.02mL/h, when the voltage exceeds a critical value, spraying the core layer solution and the shell layer solution from inside and outside to the top end of the nozzle, forming superfine solution fluid under the action of an electric field to fly to a receiver and quickly solidifying into superfine fibers with the diameter below micrometers, and receiving the superfine fibers at the receiving device to form a drug-containing nanofiber membrane.
Comparative example 3
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer (75:25) solution taking hexafluoroisopropanol (purchased from Merck) as a solvent, the concentration is 0.10g/mL, the core layer solution takes ultrapure water as a solvent, the solute is recombinant human EGF protein (purchased from Gibco, product number PHG 0315), and the protein concentration is 25ng/mL;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of coaxial electrostatic spinning equipment (SS-2535, beijing Yongkangle industrial scientific development Co., ltd.), wherein the spinning voltage is 16kV, the distance from a nozzle to a receiving device is 16cm, controlling the stable flow rate of the shell layer and the core layer to be 0.01mL/h, when the voltage exceeds a critical value, spraying the core layer solution and the shell layer solution from inside and outside to the top end of the nozzle, forming superfine solution fluid under the action of an electric field to fly to a receiver and quickly solidifying into superfine fibers with the diameter below micrometers, and receiving the superfine fibers at the receiving device to form a drug-containing nanofiber membrane.
Example 8 in vitro Release test
20mg of the electrospun nanofiber membranes prepared in examples 3-7 and comparative examples 1-3 and 5mL of phosphate buffer (pH 7.4) were added to a centrifuge tube, placed in a incubator with constant temperature shaking (100 r/min) at 37 ℃, the supernatant was taken 1 time every 7 days after release, 1 time every 7 days, then sampled 1 time every 2 days until 30 days, 100. Mu.L of freshly prepared phosphate buffer was added to the centrifuge tube after each sampling, the OD value of each well was measured at 450nm by an enzyme-labeled instrument according to the ELISA kit protocol, and the EGF concentration was calculated indirectly. 3 parallel samples are taken, the cumulative release rate (Q) is calculated, and the slow release effect is inspected. The results are shown in Table 1, and it can be seen that the electrospun nanofiber membranes of examples 3-7 were released slowly and the slow release time was maintained long, and the electrospun nanofiber membranes of comparative examples 1-3 showed burst release at the early stage and the EGF release was reduced at the later stage.
TABLE 1 cumulative release rate (Q,%)
EXAMPLE 9 proliferation assay on human gastric mucosal cells
100mg of the electrospun nanofiber membranes prepared in examples 3-7 and comparative examples 1-3 and 5mL of phosphate buffer (pH 7.4) were added to a centrifuge tube, placed in a constant temperature shaking (100 r/min) incubator at 37℃and the supernatant was taken on day 30 after release. CES-1 human gastric mucosal cells (purchased from ATCC) were inoculated in a 96-well plate in an amount of 110. Mu.L per 1ml of 2,000 cells, and cultured in a cell culture incubator at 37℃for 4 hours. After 4h, the electrospun nanofiber membrane was removed, and the in vitro released supernatant and negative control solution (pH 7.4 PBS) were added to 96-well plates, with 3 multiplex wells per dilution well. The 96-well plate is placed in a 37 ℃ cell incubator for culturing for 18 hours, the culture medium is sucked out, 100 mu L of the culture medium and 10 mu L of CCK-8 reagent are added into each well after the culture medium is washed for 1 time by using PBS (phosphate buffer solution), the mixture is placed in the incubator for standing for 4 hours, and the absorbance of each well is measured at 450nm in an enzyme-labeled instrument. The results are shown in Table 2, and it can be seen that EGF released from the electrospun nanofiber membranes of examples 3-7 maintained a high biological activity, and there was a significant difference in biological activity compared to EGF released from the electrospun nanofiber membranes of comparative examples 1-3.
TABLE 2 proliferation of cells
Note that: p <0.05 compared to comparative example 1; p <0.05, compared to comparative example 2; delta, P <0.05 compared to comparative example 3.
The foregoing is merely a preferred embodiment of the present application, and it should be noted that modifications and additions may be made to those skilled in the art without departing from the method of the present application, which modifications and additions are also to be considered as within the scope of the present application.
Claims (10)
1. The electrospun nanofiber membrane for controlling the release of the growth factors is characterized in that the electrospun nanofiber membrane is prepared according to the following method:
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer solution taking hexafluoroisopropanol as a solvent, and the concentration is 0.06-0.10g/mL; the core layer solution takes ultrapure water as a solvent, and the solute is EGF protein;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of a coaxial co-spinning electrostatic spinning device, wherein the spinning voltage is 14-16kV, the distance from a nozzle to a receiving device is 14-16cm, and controlling the stable flow rate of the shell layer and the core layer to be 0.013-0.017mL/h.
2. The electrospun nanofiber membrane according to claim 1, wherein the electrospun nanofiber membrane is prepared according to the following method:
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer solution taking hexafluoroisopropanol as a solvent, and the concentration is 0.08g/mL; the core layer solution takes ultrapure water as a solvent, and the solute is EGF protein;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of a coaxial co-spinning electrostatic spinning device, wherein the spinning voltage is 15kV, the distance from a nozzle to a receiving device is 15cm, and the stable flow rate of the shell layer and the core layer is controlled to be 0.015mL/h.
3. The preparation method of the electrospun nanofiber membrane for controlling the release of the growth factors is characterized by comprising the following steps of:
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer solution taking hexafluoroisopropanol as a solvent, and the concentration is 0.06-0.10g/mL; the core layer solution takes ultrapure water as a solvent, and the solute is EGF protein;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of a coaxial co-spinning electrostatic spinning device, wherein the spinning voltage is 14-16kV, the distance from a nozzle to a receiving device is 14-16cm, and the stable flow rate of the shell layer and the core layer is controlled to be 0.013-0.017mL/h.
4. A method of preparation according to claim 3, comprising the steps of:
(a) Preparing an electrospinning solution: the shell layer solution is a polylactic acid caprolactone copolymer solution taking hexafluoroisopropanol as a solvent, and the concentration is 0.08g/mL; the core layer solution takes ultrapure water as a solvent, and the solute is EGF protein;
(b) Coaxial co-spinning: after the shell layer solution and the core layer solution are completely and uniformly dissolved at the environment temperature of 18-20 ℃ and the humidity of 45-50%, respectively injecting the shell layer solution and the core layer solution into two injectors of a coaxial co-spinning electrostatic spinning device, wherein the spinning voltage is 15kV, the distance from a nozzle to a receiving device is 15cm, and the stable flow rate of the shell layer and the core layer is controlled to be 0.015mL/h.
5. Use of an electrospun nanofiber membrane according to claim 1 or 2 for the preparation of a medical device for promoting tissue repair.
6. The use of claim 5, wherein the medical device is an esophageal stent.
7. The esophageal tectorial membrane memory stent is suitable for treating esophageal injury without stenosis or obstruction, and is characterized in that two ends of the esophageal tectorial membrane memory stent are respectively a first fixed end and a second fixed end, and a stent main body is arranged between the first fixed end and the second fixed end; the bracket main body is formed by braiding memory metal wires and is in a cylindrical tube shape, and the outer diameter of the bracket main body is 40-50mm; the second fixed end is formed by weaving memory metal wires and is in a horn shape; the second fixed end and the whole outer wall of the bracket main body are coated with a growth factor-containing film, and the growth factor-containing film is the electrostatic spinning nanofiber film according to claim 1 or 2; the first fixing end consists of a plurality of diaphragms with tension, the lower edges of the diaphragms are connected with the upper edge of the bracket main body, the diaphragms encircle the upper edge of the bracket main body for a circle, and the diaphragms are in a tight shape in a use state.
8. The esophageal stent graft of claim 7, wherein the second fixed end has a lower edge with an outer diameter of 52-56mm.
9. The esophageal stent graft as defined in claim 7 wherein the membrane is semi-elliptical, semi-circular or trapezoidal.
10. The esophageal tectorial membrane memory stent of claim 7, wherein the upper edge of the stent body is wavy and provided with a plurality of grooves, and the lower end of the membrane is connected in the grooves in a positive fitting way.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811019894.3A CN109172073B (en) | 2018-09-03 | 2018-09-03 | Electrostatic spinning nanofiber membrane for controlling release of growth factors and esophageal tectorial membrane memory stent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811019894.3A CN109172073B (en) | 2018-09-03 | 2018-09-03 | Electrostatic spinning nanofiber membrane for controlling release of growth factors and esophageal tectorial membrane memory stent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109172073A CN109172073A (en) | 2019-01-11 |
| CN109172073B true CN109172073B (en) | 2023-11-21 |
Family
ID=64917870
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811019894.3A Active CN109172073B (en) | 2018-09-03 | 2018-09-03 | Electrostatic spinning nanofiber membrane for controlling release of growth factors and esophageal tectorial membrane memory stent |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109172073B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113183594B (en) * | 2021-04-07 | 2022-07-12 | 广东工业大学 | Preparation method of electrostatic spinning functional nanofiber film for epidermis repair |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007307132A (en) * | 2006-05-18 | 2007-11-29 | Teijin Ltd | Material for revascularization |
| CN101509153A (en) * | 2009-03-23 | 2009-08-19 | 东华大学 | Method for producing shell-core structure medicament nano-fibre with coaxial electrostatic spinning technology |
| CN101984940A (en) * | 2010-11-03 | 2011-03-16 | 华南理工大学 | Sac-covered esophagus scaffold capable of loading medicaments and preparation method thereof |
| CN201879873U (en) * | 2010-11-26 | 2011-06-29 | 江苏省人民医院 | Recyclable esophageal stent of nickel titanium memory alloy full-membrane exceeding opening |
| CN103893819A (en) * | 2014-03-20 | 2014-07-02 | 北京大学第三医院 | Coaxial electrostatic spinning fibrous scaffold and preparation method thereof |
| CN106823011A (en) * | 2017-01-23 | 2017-06-13 | 重庆三峡医药高等专科学校 | The method and product for promoting EGF continuation release nanofiber are prepared using electrostatic spinning technique |
| CN107073169A (en) * | 2014-08-15 | 2017-08-18 | 约翰·霍普金斯大学技术创业公司 | Composite for tissue repair |
| CN107881650A (en) * | 2017-05-10 | 2018-04-06 | 佛山今兰生物科技有限公司 | A kind of coaxial double-layer electrostatic spinning prepares the method and its application of the nano fibrous membrane with core/shell embedding structure |
| CN108324986A (en) * | 2018-05-03 | 2018-07-27 | 东华大学 | A kind of acute injury multi-functional orderly drug release Medical coating film and preparation method thereof |
| CN209474880U (en) * | 2018-09-03 | 2019-10-11 | 上海市第一人民医院 | A kind of oesophagus overlay film memory bracket suitable for treating without narrow or obstruction esophageal injury |
-
2018
- 2018-09-03 CN CN201811019894.3A patent/CN109172073B/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007307132A (en) * | 2006-05-18 | 2007-11-29 | Teijin Ltd | Material for revascularization |
| CN101509153A (en) * | 2009-03-23 | 2009-08-19 | 东华大学 | Method for producing shell-core structure medicament nano-fibre with coaxial electrostatic spinning technology |
| CN101984940A (en) * | 2010-11-03 | 2011-03-16 | 华南理工大学 | Sac-covered esophagus scaffold capable of loading medicaments and preparation method thereof |
| CN201879873U (en) * | 2010-11-26 | 2011-06-29 | 江苏省人民医院 | Recyclable esophageal stent of nickel titanium memory alloy full-membrane exceeding opening |
| CN103893819A (en) * | 2014-03-20 | 2014-07-02 | 北京大学第三医院 | Coaxial electrostatic spinning fibrous scaffold and preparation method thereof |
| CN107073169A (en) * | 2014-08-15 | 2017-08-18 | 约翰·霍普金斯大学技术创业公司 | Composite for tissue repair |
| CN106823011A (en) * | 2017-01-23 | 2017-06-13 | 重庆三峡医药高等专科学校 | The method and product for promoting EGF continuation release nanofiber are prepared using electrostatic spinning technique |
| CN107881650A (en) * | 2017-05-10 | 2018-04-06 | 佛山今兰生物科技有限公司 | A kind of coaxial double-layer electrostatic spinning prepares the method and its application of the nano fibrous membrane with core/shell embedding structure |
| CN108324986A (en) * | 2018-05-03 | 2018-07-27 | 东华大学 | A kind of acute injury multi-functional orderly drug release Medical coating film and preparation method thereof |
| CN209474880U (en) * | 2018-09-03 | 2019-10-11 | 上海市第一人民医院 | A kind of oesophagus overlay film memory bracket suitable for treating without narrow or obstruction esophageal injury |
Non-Patent Citations (1)
| Title |
|---|
| 王建广 ; 刘俊建 ; 范存义 ; 莫秀梅 ; 何创龙 ; 陈峰 ; .同轴静电纺丝法制备神经生长因子纳米纤维缓释载体.中国组织工程研究与临床康复.2008,(23),全文. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109172073A (en) | 2019-01-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9333068B2 (en) | Bioerodible wraps and uses therefor | |
| US11969337B2 (en) | In vivo tissue engineering devices, methods and regenerative and cellular medicine employing scaffolds made of absorbable material | |
| WO2011123798A2 (en) | Three-dimensional scaffolds, methods for fabricating the same, and methods of treating a peripheral nerve or spinal or spinal cord injury | |
| US11759306B2 (en) | In vivo tissue engineering devices, methods and regenerative and cellular medicine employing scaffolds made of absorbable material | |
| EP2174619A1 (en) | Prosthetic material for living organ | |
| US11844685B2 (en) | In vivo tissue engineering devices, methods and regenerative and cellular medicine employing scaffolds made of absorbable material | |
| WO2011150328A1 (en) | Wet-electrospun biodegradable scaffold and uses therefor | |
| US11883275B2 (en) | In vivo tissue engineering devices, methods and regenerative and cellular medicine employing scaffolds made of absorbable material | |
| CN102973339A (en) | Cardia stent with drug coating | |
| CN109172073B (en) | Electrostatic spinning nanofiber membrane for controlling release of growth factors and esophageal tectorial membrane memory stent | |
| CN209474880U (en) | A kind of oesophagus overlay film memory bracket suitable for treating without narrow or obstruction esophageal injury | |
| CN116616953B (en) | Sinus tectorial membrane drug-carrying bracket and preparation method thereof | |
| CN117065096B (en) | Rapid preparation method and application of biological film | |
| CN115154660B (en) | High-strength implant and preparation method thereof | |
| CN113244021A (en) | Support for preventing external auditory canal stenosis through 3D printing acellular matrix and preparation method | |
| Meinel et al. | ELECTROSPUN MATRICES FOR DRUG DELIVERY: REVIEWING TECHNOLOGIES AND BIOMEDICAL APPLICATIONS | |
| WO2003075974A1 (en) | Artificial digestive tract |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |