CN116531560A - 一种温敏性肩袖自锁神经导管及其制备方法 - Google Patents
一种温敏性肩袖自锁神经导管及其制备方法 Download PDFInfo
- Publication number
- CN116531560A CN116531560A CN202310718051.7A CN202310718051A CN116531560A CN 116531560 A CN116531560 A CN 116531560A CN 202310718051 A CN202310718051 A CN 202310718051A CN 116531560 A CN116531560 A CN 116531560A
- Authority
- CN
- China
- Prior art keywords
- nerve
- micro
- temperature
- sensitive
- locking
- 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.)
- Pending
Links
- 210000005036 nerve Anatomy 0.000 title claims abstract description 93
- 210000000513 rotator cuff Anatomy 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000004205 dimethyl polysiloxane Substances 0.000 claims abstract description 40
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims abstract description 40
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 claims abstract description 40
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 claims abstract description 40
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims abstract description 40
- 239000012620 biological material Substances 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 21
- 238000004132 cross linking Methods 0.000 claims abstract description 20
- 239000000017 hydrogel Substances 0.000 claims abstract description 16
- 238000007605 air drying Methods 0.000 claims abstract description 9
- 238000001053 micromoulding Methods 0.000 claims abstract description 7
- 230000001737 promoting effect Effects 0.000 claims abstract description 6
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract 3
- 238000000034 method Methods 0.000 claims description 25
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 claims description 16
- 229940079593 drug Drugs 0.000 claims description 12
- 229920001661 Chitosan Polymers 0.000 claims description 10
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 10
- 229940109262 curcumin Drugs 0.000 claims description 10
- 239000003431 cross linking reagent Substances 0.000 claims description 9
- -1 dimethylsiloxane Chemical class 0.000 claims description 9
- 239000000178 monomer Substances 0.000 claims description 9
- 235000012754 curcumin Nutrition 0.000 claims description 8
- 239000004148 curcumin Substances 0.000 claims description 8
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 claims description 8
- 229920002674 hyaluronan Polymers 0.000 claims description 6
- 229960003160 hyaluronic acid Drugs 0.000 claims description 6
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 5
- 229920003213 poly(N-isopropyl acrylamide) Polymers 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 claims description 4
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 claims description 4
- 108010022355 Fibroins Proteins 0.000 claims description 4
- 102000015336 Nerve Growth Factor Human genes 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 229940053128 nerve growth factor Drugs 0.000 claims description 4
- 229920001977 poly(N,N-diethylacrylamides) Polymers 0.000 claims description 4
- 229920001610 polycaprolactone Polymers 0.000 claims description 4
- 239000004632 polycaprolactone Substances 0.000 claims description 4
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 4
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 4
- 229960002930 sirolimus Drugs 0.000 claims description 4
- 229960002117 triamcinolone acetonide Drugs 0.000 claims description 4
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 claims description 4
- 229940124599 anti-inflammatory drug Drugs 0.000 claims description 3
- 230000008439 repair process Effects 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 102000008186 Collagen Human genes 0.000 claims description 2
- 108010035532 Collagen Proteins 0.000 claims description 2
- 235000010208 anthocyanin Nutrition 0.000 claims description 2
- 239000004410 anthocyanin Substances 0.000 claims description 2
- 229930002877 anthocyanin Natural products 0.000 claims description 2
- 150000004636 anthocyanins Chemical class 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 229920001436 collagen Polymers 0.000 claims description 2
- 229910021389 graphene Inorganic materials 0.000 claims description 2
- 239000004626 polylactic acid Substances 0.000 claims description 2
- 229920002994 synthetic fiber Polymers 0.000 claims description 2
- 238000009827 uniform distribution Methods 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims 1
- 238000005516 engineering process Methods 0.000 abstract description 7
- 230000008929 regeneration Effects 0.000 abstract description 6
- 238000011069 regeneration method Methods 0.000 abstract description 6
- 230000036760 body temperature Effects 0.000 abstract description 5
- 239000012528 membrane Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 40
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 239000012153 distilled water Substances 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 13
- 239000002243 precursor Substances 0.000 description 13
- 238000009849 vacuum degassing Methods 0.000 description 13
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 12
- 239000003999 initiator Substances 0.000 description 12
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 12
- 239000000499 gel Substances 0.000 description 10
- 238000002156 mixing Methods 0.000 description 8
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 102000007072 Nerve Growth Factors Human genes 0.000 description 6
- 239000003900 neurotrophic factor Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 210000004116 schwann cell Anatomy 0.000 description 5
- 208000010886 Peripheral nerve injury Diseases 0.000 description 4
- 210000003050 axon Anatomy 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000006378 damage Effects 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 210000000578 peripheral nerve Anatomy 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 238000010146 3D printing Methods 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 239000011557 critical solution Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010041 electrostatic spinning Methods 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 208000000860 Compassion Fatigue Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 206010017472 Fumbling Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 230000007646 directional migration Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 229910052755 nonmetal Inorganic materials 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000001259 photo etching Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 238000000992 sputter etching Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000013271 transdermal drug delivery Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000001039 wet etching Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/185—Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
-
- 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
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- 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
-
- 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
- A61L27/52—Hydrogels or hydrocolloids
-
- 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
- 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
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
-
- 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
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
-
- 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
-
- 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
-
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction
-
- 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
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0023—Drug applicators using microneedles
-
- 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
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0046—Solid microneedles
-
- 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
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
-
- 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
本发明提供一种温敏性肩袖自锁神经导管及其制备方法,包括如下步骤:制备中间具有微米级各向异性拓扑几何结构,两端具有微针孔洞结构的PDMS模具;在PDMS印章表面的微针孔洞内依次灌注含有促神经生长因子和抗炎因子的天然或合成生物材料,风干或交联固化;将温敏型水凝胶溶液压印到PDMS印章表面,交联后形成生物材料支架;将压印好的生物材料支架剥离PDMS印章,获得温敏性肩袖自锁神经导管。本发明采用微模塑技术和分步浇注技术,得到的生物材料支架易于从PDMS印章上剥离,室温下可保持较大的管径,移植入体内后在体温下可快速收缩实现自锁固定,微针可穿透神经膜在神经内部实现其负载药物的可控释放且其微小结构避免传统手术缝合对神经再生带来负面影响。
Description
技术领域
本发明属于组织工程和再生医学可植入人体中的医用生物材料领域,具体涉及一种内壁具有微针和各向异性拓扑结构的温敏性肩袖自锁神经导管及其制备方法。
背景技术
据研究报道,全世界每年有多达100万人患有周围神经损伤(PNI)。PNI通常发生于外伤、手术切除或局部药物毒害,可能导致严重的感觉运动障碍和慢性神经疼痛,给家庭和社会带来严重的负担。周围神经系统中含有由施万细胞包鞘的平行轴突束,细胞外基质也含有由各种蛋白组成的有序结构,因而具有纵向排列的各向异性拓扑结构的神经导管可以很好地模拟天然神经组织的微环境,有望引导募集施万细胞并促使其沿拓扑方向排列迁移、促进轴突的定向生长延伸来促进周围神经的再生。但,目前人工神经移植物通常直径略大于正常神经,修复缺损时需要通过缝合手术将神经导管与神经缝合起来。尽管已经可吸收性手术缝合线已广泛应用,但缝合处仍有产生瘢痕或增生的风险,且缝合过程中不可避免地会对神经造成一定损害。自锁导管可以随周围环境的变化实现自我收缩,牢靠地固定于断裂神经两端,免除了对神经的穿透和局部过高的拉伸应力,很好地消除了传统手术的危害。因此亟需开发一种制备自锁性神经导管的技术以降低传统手术缝合所带来的风险,并通过载药微针结构进一步提高固定的稳定性和对神经再生的促进作用。
微针(Microneedles,MNs)是近年来一种新兴的系统,由微米级针体组成,常用于经皮给药,但未见在神经导管方面的应用。在目前微针皮肤贴片的研究中,微针既可以穿透表皮层打开药物的递送通道,又可使贴片固定于皮肤表面实现药物的持续释放。因而通过在自锁神经导管两端添加载药微针结构,既可实现药物在神经内部的深层递送,又可完成导管与神经的微创接合,是很有前途的一个方向。目前借助微机电、离子刻蚀、湿法刻蚀、光刻等技术已经可以很好地在各种无机金属和非金属表面实现微米拓扑及微针等精密构造,但有机生物材料的结构加工仍较为困难,常见的方法有静电纺丝、微模塑、3D打印、微流控等。其中,静电纺丝和微流控技术无法制备微针结构,各向异性拓扑结构的取向性也有待提高,且工艺参数复杂,应用过程中需经过多次摸索调试;3D打印精度较低且对材料的限制较多,难以广泛应用;而微模塑技术则可以很好地克服上述缺点,结构多变且易于调整,对材料要求也非常少。
水凝胶(Hydrogel)是一类极为亲水的三维网络结构凝胶,它可以在水中迅速溶胀并保持一定体积但不溶解,通过改变其含水量可实现对体积的可控调节,已广泛应用于组织工程中。温度敏感性水凝胶属于原位凝胶的一种,温度变化时,其分子链上的亲水和疏水基团的作用力及水合能力会受到影响,表现出体积变化或溶胀性能变化。根据溶胶-凝胶相变状态可将水凝胶分为正温度型水凝胶和负温度型水凝胶,正温度型水凝胶有最高临界溶解温度(UCST),该凝胶在高于UCST的温度下吸水溶解,在低于UCST时脱水收缩。负温度型水凝胶具有最低临界溶解温度(LCST),该类水凝胶在LCST之下会保持液态,而在高于LCST时,水凝胶会发生溶胶-凝胶转变,结构收缩,体积缩小。N-异丙基丙烯酰胺(PNIPA)水凝胶分子内具有亲水性的酰胺基和疏水性的异丙基,二者相互作用使凝胶具有良好的温度响应性,其最低临界溶解温度LCST在33℃左右,接近人体生理温度,通过改变亲水/疏水组分的比例(即与亲水单体如丙烯酸(AAc)共聚),还可以在略高于人体温度的情况下进行调节,在生物医学领域研究广泛。
综上,本发明提出了一种内壁具有微针和各向异性拓扑结构的温敏性肩袖自锁神经导管的制备方法。该导管随着温度从储存温度(~4℃)转变为体温(~37℃),体积可以减小30%-50%,实现导管与断裂神经的自锁固定。导管内壁两边的载药微针既可以实现药物的深层缓释,又可强化固定效果,避免因滑动而导致导管的脱落。导管内壁中间部分的各向异性拓扑结构则可以很好地引导施万细胞伸长迁移、引导轴突延伸,加快周围神经再生修复的速度。相较于传统神经移植物,该发明通过各向异性拓扑结构促进了断裂神经的定向伸长,创新性地使用了温敏性生物材料并加入了微针结构,规避了传统手术缝合所带来的负面影响并实现了药物的深层递送。使用方法简便易行,仅需将断裂神经两端塞入导管内部待导管随温度变化实现收缩自锁即可。因此,针对市场相关产品的空缺,本发明是极具应用价值的。
发明内容
本发明的目的是提供一种表面具有微针和微米拓扑几何结构的温敏性肩袖自锁神经导管的制备方法,以消除常规手术缝合可能带来的潜在风险,解决现有技术中难以实现药物深层递送和缓释,难以持续诱导神经长距离定向生长再生的问题。
为解决上述现存问题,本发明采用以下技术方案:
(1)将二甲基硅氧烷单体和交联剂充分混合后,灌注于定制的平面或圆筒状模具中,真空脱气后交联,制备中间具有取向性微米拓扑几何结构、两边具有微针孔洞结构的平面或圆柱状弹性印章即PDMS模具;
(2)在生物材料溶液中预先混好不同药物,采用分步浇注法在PDMS模具表面的微针孔洞内依次灌注混有不同药物的天然或合成生物材料,离心或抽真空确保孔洞填充完全无空气后,风干或交联固化使生物材料成型,得到移植物两侧的针体结构;
(3)将温敏型水凝胶前体溶液与交联剂混合好后,浇注于到PDMS模具表面,交联后形成生物材料支架;
(4)通过降温膨胀使导管自发脱离圆柱状PDMS模具或者将支架剥离平面PDMS模具并将有拓扑结构一侧向内卷曲成管状结构并进行粘接,获得中间具有微米拓扑几何结构两边具有微针结构的温敏性肩袖自锁神经导管。
本发明所述的内表面具有微米拓扑几何结构的温敏性肩袖自锁神经导管中部为微米尺度的拓扑几何结构,而两侧由微米级的微针阵列构成。优选的,所述步骤(1)微米拓扑几何结构为各向异性结构的微米沟脊、微米凹孔、微米凸起等一种或多种阵列组合方式;微针结构为圆锥、棱锥、箭头等多种结构中的一种或几种,微针排列为均匀分布或沿特定方向导向等一种或多种阵列组合方式。进一步优选,所述微米拓扑几何结构选取为微米沟脊,高的部分为脊,低的部分为沟,沟和脊的垂直距离为2-10μm,沟和脊的宽度为10-50μm,沟和脊的连接处为平滑的或者垂直的;所述微针选取为均匀排布,高度为100-1000μm,微针的底部直径为100-200μm,尖端直径为30-50μm。
本发明所述组织工程移植物主体优选为聚(N-异丙基丙烯酰胺)(PNIPA)和聚(N,N-二乙基丙烯酰胺)(PDEAM)等负温度型温敏水凝胶,由储存温度经热敷或红外照射升温至人体温度可实现快速收缩自锁;所述微针材料组成优选为透明质酸(HA)、甲基丙烯酰化透明质酸(HAMA)、壳聚糖(CS)、丝素蛋白(SF)、胶原蛋白(Col)、聚己内酯(PCL)、聚乳酸(PLA)等天然或合成材料中的一种或几种;微针分为针尖和基部两部分,由天然或合成生物材料分别负载不同药物。优选的,针尖负载神经生长因子(NGF)、睫状神经营养因子(CNTF)、雷帕霉素(RAPA)、还原氧化石墨烯(rGO)中的一种或几种促神经生长药物,基部负载曲安奈德(TA)、姜黄素(Cur)、花青素(OPC)中的一种或几种抗炎药物。
优选的,本发明方法制备而成的神经导管,其快速加热方式可以为红外辐射、热敷等。
优选的,本发明方法制备而成的神经导管,其长度可根据实际使用需求,由10-50mm定制;其药物释放可根据优先级将需要优先释放的药物负载于微针尖部,将需要随后释放的药物负载于微针基部,药物释放速度可根据微针所用生物材料的种类和交联度进行控制。
本发明的有益效果:
(1)本发明将微针结构与温敏性水凝胶相结合,可以实现体温下神经导管与受损神经两端的自锁牢靠固定,规避了缝合手术可能带来的二次创伤、瘢痕增生等问题。
(2)本发明制备的温敏自锁神经导管内壁具有微米各向异性拓扑结构,可以有效引导神经再生过程中雪旺细胞的定向迁移、生长及轴突的定向伸长。
(3)本发明微针结构内负载的抗炎药物及促神经生长药物,可以有效抑制损伤后引起的炎症反应,协同促进周围神经损伤的修复,且随着微针结构的缓慢降解具有很好的缓释作用。
(4)本发明制备的温敏性肩袖自锁神经导管具有良好的生物相容性,生物化学性质稳定,柔韧性较好,且可以根据实际需求定制尺寸。
(5)本发明既可制备具有二维微米拓扑及微针图案的生物材料支架,又可制备具有三维微米拓扑及微针图案的人工神经导管。
附图说明
图1内壁具有各向异性拓扑结构导管设计图完整导管结构(左图a)和截面导管结构(右图b)。
图2具肩袖自锁和内壁具有各向异性拓扑结构导管设计图完整导管结构(左图a)和截面导管结构(右图b)。
图3温敏性肩袖自锁神经导管收缩前(左图a)和收缩后(右图b)示意图。
图4为本发明实施例所述利用微模塑技术制备温敏性肩袖自锁神经导管的示意图。
图5为本发明实施例所述的利用微模塑技术制备温敏性肩袖自锁神经导管的内部结构及组成示意图。
图6为本发明实施例所述的平面PDMS模具照片。模具两侧为微型孔洞,中部为取向性拓扑凹槽。该印章可重复利用,适宜大批量稳定生产。
图7为本发明实施例所述的温敏性肩袖自锁神经导管的热收缩照片。图4中所示导管从储存温度(4℃)升温至人体温度(37℃),导管内径减小约50%,可以自锁实现对神经的有效固定。
图8、为本发明实施例所制备的温敏性肩袖自锁神经导管的中部凹槽结构。
图9和两侧微针结构的照片。图5、图6中所制备的凹槽和微针结构高度规整,凹槽具有高度取向性。
具体实施方式
下面结合实例对本发明做进一步阐释。以下实例仅用于说明本发明,但不用于限定本发明的实施范围。此外应理解,在阅读了本发明讲授的内容之后,本领域技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本申请所附权利要求书所限定的范围。
实施例1
一种表面具有微针和微米拓扑几何结构的温敏性肩袖自锁神经导管,具体制备包括如下步骤:
(1)将体积比为10:1的二甲基硅氧烷单体和交联剂充分混合后,灌注于表面具有微针和各向异性微米拓扑结构的筒状高分子模具上,真空脱气1-2h后,于60℃烘箱中交联过夜,充分固化后得到中间具有微米拓扑几何结构、两边具有微针孔洞结构的PDMS柱状模具;
(2)分别将神经营养因子和姜黄素以10-100μg/ml的浓度溶解于3%的壳聚糖溶液中,采用微量注射器依次将两种溶液注射入PDMS的孔洞内,高速离心5min,确保孔洞内填充完全,风干后获得针体结构;
(3)称取48g N-异丙基丙烯酰胺(NIPA)和0.6g N,N’-亚甲基双丙烯酰胺(BIS)于100ml三蒸水中,室温搅拌至完全溶解,得到前体溶液;将1g过硫酸铵(APS)溶于10ml三蒸水中,得到10%的引发剂溶液;
(4)向10ml前体溶液中加入1ml引发剂溶液,在PDMS柱状模具外加一同心圆套筒、将混合溶液迅速浇注于PDMS模具与套筒之间,真空脱气后,于80℃条件下交联1h;
(5)于三蒸水中缓慢降温,待温敏导管降温膨胀后,实现导管从模具上的自主脱除,得到中间具有微米拓扑几何结构两边具有微针结构的温敏性肩袖自锁神经导管;
(6)植入体内时,选择的导管直径略大于神经,将断裂神经两端塞入导管两侧,通过热敷的方法使导管快速受热收缩,达到对神经的有效固定,之后将创口缝合。
实施例2
一种表面具有微针和微米拓扑几何结构的温敏性肩袖自锁神经导管,具体制备包括如下步骤:
(1)将体积比为10:1的二甲基硅氧烷单体和交联剂充分混合后,灌注于表面具有微针和各向异性微米拓扑结构的筒状高分子模具上,真空脱气1-2h后,于60℃烘箱中交联过夜,充分固化后得到中间具有微米拓扑几何结构、两边具有微针孔洞结构的PDMS柱状模具;
(2)分别将神经营养因子和姜黄素以10-100μg/ml的浓度溶解于3%的壳聚糖溶液中,采用微量注射器依次将两种溶液注射入PDMS的孔洞内,高速离心5min,确保孔洞内填充完全,风干后获得针体结构;
(3)称取48g N-异丙基丙烯酰胺(NIPA)和0.6g N,N’-亚甲基双丙烯酰胺(BIS)于100ml三蒸水中,室温搅拌至完全溶解,得到前体溶液;将1g过硫酸铵(APS)溶于10ml三蒸水中,得到10%的引发剂溶液;
(4)向10ml前体溶液中加入2ml引发剂溶液,在PDMS柱状模具外加一同心圆套筒、将混合溶液迅速浇注于PDMS模具与套筒之间,真空脱气后,于80℃条件下交联1h;
(5)于三蒸水中缓慢降温,待温敏导管降温膨胀后,实现导管从模具上的自主脱除,得到中间具有微米拓扑几何结构两边具有微针结构的温敏性肩袖自锁神经导管;
(6)植入体内时,选择的导管直径略大于神经,将断裂神经两端塞入导管两侧,通过热敷的方法使导管快速受热收缩,达到对神经的有效固定,之后将创口缝合。
实施例3
一种表面具有微针和微米拓扑几何结构的温敏性肩袖自锁神经导管,具体制备包括如下步骤:
(1)将体积比为10:1的二甲基硅氧烷单体和交联剂充分混合后,灌注于表面具有微针和各向异性微米拓扑结构的筒状金属模具上,真空脱气1-2h后,于60℃烘箱中交联过夜,充分固化后得到中间具有微米拓扑几何结构、两边具有微针孔洞结构的PDMS柱状模具;
(2)分别将神经营养因子和姜黄素以10-100μg/ml的浓度溶解于3%的壳聚糖溶液中,采用微量注射器依次将两种溶液注射入PDMS的孔洞内,高速离心5min,确保孔洞内填充完全,风干后获得针体结构;
(3)称取48g N-异丙基丙烯酰胺(NIPA)和0.6g N,N’-亚甲基双丙烯酰胺(BIS)于100ml三蒸水中,室温搅拌至完全溶解,得到前体溶液;将1g过硫酸铵(APS)溶于10ml三蒸水中,得到10%的引发剂溶液;
(4)向10ml前体溶液中加入1ml引发剂溶液,在PDMS柱状模具外加一同心圆套筒、将混合溶液迅速浇注于PDMS模具与套筒之间,真空脱气后,于80℃条件下交联1h;
(5)于三蒸水中缓慢降温,待温敏导管降温膨胀后,实现导管从模具上的自主脱除,得到中间具有微米拓扑几何结构两边具有微针结构的温敏性肩袖自锁神经导管;
(6)植入体内时,选择的导管直径略大于神经,将断裂神经两端塞入导管两侧,通过热敷的方法使导管快速受热收缩,达到对神经的有效固定,之后将创口缝合。
实施例4
一种表面具有微针和微米拓扑几何结构的温敏性肩袖自锁神经导管,具体制备包括如下步骤:
(1)将体积比为10:1的二甲基硅氧烷单体和交联剂充分混合后,灌注于表面具有微针和各向异性微米拓扑结构的筒状金属模具上,真空脱气1-2h后,于60℃烘箱中交联过夜,充分固化后得到中间具有微米拓扑几何结构、两边具有微针孔洞结构的PDMS柱状模具;
(2)分别将神经营养因子和姜黄素以10-100μg/ml的浓度溶解于3%的壳聚糖溶液中,采用微量注射器依次将两种溶液注射入PDMS的孔洞内,高速离心5min,确保孔洞内填充完全,风干后获得针体结构;
(3)称取48g N-异丙基丙烯酰胺(NIPA)和0.6g N,N’-亚甲基双丙烯酰胺(BIS)于100ml三蒸水中,室温搅拌至完全溶解,得到前体溶液;将1g过硫酸铵(APS)溶于10ml三蒸水中,得到10%的引发剂溶液;
(4)向10ml前体溶液中加入2ml引发剂溶液,在PDMS柱状模具外加一同心圆套筒、将混合溶液迅速浇注于PDMS模具与套筒之间,真空脱气后,于80℃条件下交联1h;
(5)于三蒸水中缓慢降温,待温敏导管降温膨胀后,实现导管从模具上的自主脱除,得到中间具有微米拓扑几何结构两边具有微针结构的温敏性肩袖自锁神经导管;
(6)植入体内时,选择的导管直径略大于神经,将断裂神经两端塞入导管两侧,通过热敷的方法使导管快速受热收缩,达到对神经的有效固定,之后将创口缝合。
实施例5
一种表面具有微针和微米拓扑几何结构的温敏性肩袖自锁神经导管,具体制备包括如下步骤:
(1)将体积比为10:1的二甲基硅氧烷单体和交联剂充分混合后,灌注于表面具有微针和各向异性微米拓扑结构的金属、高分子或硅片平面模具上,真空脱气1-2h后,于60℃烘箱中交联过夜,充分固化后得到中间具有微米拓扑几何结构、两边具有微针孔洞结构的PDMS平面模具;
(2)分别将神经营养因子和姜黄素以10-100μg/ml的浓度溶解于3%的壳聚糖溶液中,采用微量注射器依次将两种溶液注射入PDMS的孔洞内,高速离心5min,确保孔洞内填充完全,风干后获得针体结构;
(3)称取48g N-异丙基丙烯酰胺(NIPA)和0.6g N,N’-亚甲基双丙烯酰胺(BIS)于100ml三蒸水中,室温搅拌至完全溶解,得到前体溶液;将1g过硫酸铵(APS)溶于10ml三蒸水中,得到10%的引发剂溶液;
(4)向10ml前体溶液中加入1ml引发剂溶液,迅速浇注于PDMS模具表面,真空脱气后,于80℃条件下交联1h;
(5)将支架从模具上剥离,沿平行于拓扑方向卷曲成管,并用胶水固定,得到中间具有微米拓扑几何结构两边具有微针结构的温敏性肩袖自锁神经导管;
(6)植入体内时,选择的导管直径略大于神经,将断裂神经两端塞入导管两侧,通过热敷的方法使导管快速受热收缩,达到对神经的有效固定,之后将创口缝合。
实施例6
一种表面具有微针和微米拓扑几何结构的温敏性肩袖自锁神经导管,具体制备包括如下步骤:
(1)将体积比为10:1的二甲基硅氧烷单体和交联剂充分混合后,灌注于表面具有微针和各向异性微米拓扑结构的金属、高分子或硅片平面模具上,真空脱气1-2h后,于60℃烘箱中交联过夜,充分固化后得到中间具有微米拓扑几何结构、两边具有微针孔洞结构的PDMS平面模具;
(2)分别将神经营养因子和姜黄素以10-100μg/ml的浓度溶解于3%的壳聚糖溶液中,采用微量注射器依次将两种溶液注射入PDMS的孔洞内,高速离心5min,确保孔洞内填充完全,风干后获得针体结构;
(3)称取48g N-异丙基丙烯酰胺(NIPA)和0.6g N,N’-亚甲基双丙烯酰胺(BIS)于100ml三蒸水中,室温搅拌至完全溶解,得到前体溶液;将1g过硫酸铵(APS)溶于10ml三蒸水中,得到10%的引发剂溶液;
(4)向10ml前体溶液中加入2ml引发剂溶液,迅速浇注于PDMS模具表面,真空脱气后,于80℃条件下交联1h;
(5)将支架从模具上剥离,沿平行于拓扑方向卷曲成管,并用胶水固定,得到中间具有微米拓扑几何结构两边具有微针结构的温敏性肩袖自锁神经导管;
(6)植入体内时,选择的导管直径略大于神经,将断裂神经两端塞入导管两侧,通过热敷的方法使导管快速受热收缩,达到对神经的有效固定,之后将创口缝合。
Claims (10)
1.一种温敏性肩袖自锁神经导管,其特征在于,其内部具有微米拓扑几何结构,内壁两边具有微针孔洞结构;微米拓扑几何结构的材质为温敏水凝胶,微针孔洞结构内含有促神经生长和抗炎功能的药物的天然或合成生物材料。
2.一种温敏性肩袖自锁神经导管的制备方法,其特征在于,包括如下步骤:
制备中间具有微米拓扑几何结构、两边具有微针孔洞结构的PDMS模具;
在PDMS模具表面的微针孔洞内依次灌注含有促神经生长和抗炎功能的药物的天然或合成生物材料,风干或交联固化;
将温敏型水凝胶溶液浇注于到PDMS模具表面,交联后形成生物材料支架;
将交联后的生物材料支架从PDMS模具上脱离,获得中间具有微米拓扑几何结构两边具有微针结构的温敏性肩袖自锁神经导管。
3.如权利要求2所述的制备方法,其特征在于,采用微模塑方法制备所述PDMS模具,制备所述PDMS模具的材料由二甲基硅氧烷单体和交联剂以10:1的比例配制而成。
4.如权利要求2所述的制备方法,其特征在于,采用分步浇注法在PDMS模具表面的微针孔洞内依次灌注混有不同药物的天然或合成生物材料。
5.如权利要求2所述的制备方法,其特征在于,所述生物材料支架由微模塑方法制成,管壁厚0.5-5mm,管内径为0.5-5mm。
6.如权利要求2所述的制备方法,其特征在于,微米拓扑几何结构为各向异性结构的微米沟脊、微米凹孔、微米凸起等一种或多种阵列组合方式;微针孔洞结构为圆锥、棱锥、箭头等多种结构中的一种或几种,微针排列为均匀分布或沿特定方向导向等一种或多种阵列组合方式。
7.如权利要求2所述的制备方法,其特征在于,微米拓扑几何结构高的部分为脊,低的部分为沟,沟和脊的垂直距离为2-10μm,沟和脊的宽度为10-50μm,沟和脊的连接处为平滑的或者垂直的;微针的高度为100-1000μm,微针的底部直径为100-200μm,尖端直径为30-50μm。
8.如权利要求2所述的制备方法,其特征在于,微针所用生物材料为透明质酸(HA)、甲基丙烯酰化透明质酸(HAMA)、壳聚糖(CS)、丝素蛋白(SF)、胶原蛋白(Col)、聚己内酯(PCL)、聚乳酸(PLA)等天然或合成材料中的一种或几种;生物材料支架基底所用生物材料为聚(N-异丙基丙烯酰胺)(PNIPA)和聚(N,N-二乙基丙烯酰胺)(PDEAM)等负温度型温敏水凝胶。
9.如权利要求2所述的制备方法,其特征在于,促神经生长因子为神经生长因子(NGF)、睫状神经营养因子(CNTF)、雷帕霉素(RAPA)、还原氧化石墨烯(rGO)中的一种或几种;抗炎药物为曲安奈德(TA)、姜黄素(Cur)、花青素(OPC)中的一种或几种。
10.权利要求1所述温敏性肩袖自锁神经导管在断裂神经修复方面的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310718051.7A CN116531560A (zh) | 2023-06-16 | 2023-06-16 | 一种温敏性肩袖自锁神经导管及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310718051.7A CN116531560A (zh) | 2023-06-16 | 2023-06-16 | 一种温敏性肩袖自锁神经导管及其制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116531560A true CN116531560A (zh) | 2023-08-04 |
Family
ID=87449001
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310718051.7A Pending CN116531560A (zh) | 2023-06-16 | 2023-06-16 | 一种温敏性肩袖自锁神经导管及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116531560A (zh) |
-
2023
- 2023-06-16 CN CN202310718051.7A patent/CN116531560A/zh active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Seong et al. | A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin | |
Houshyar et al. | Peripheral nerve conduit: materials and structures | |
Sarker et al. | Strategic design and fabrication of nerve guidance conduits for peripheral nerve regeneration | |
Chen et al. | Electrospinning: An enabling nanotechnology platform for drug delivery and regenerative medicine | |
Li et al. | Fabrication of gradient porous microneedle array by modified hot embossing for transdermal drug delivery | |
US11344711B2 (en) | Swellable adhesive needles | |
CN103501852B (zh) | 微结构体的制造方法 | |
Lee et al. | Rapid and repeatable fabrication of high A/R silk fibroin microneedles using thermally-drawn micromolds | |
CN103800998B (zh) | 一种丝素蛋白凝胶微针系统及其制备方法 | |
Gao et al. | PEGDA/PVP microneedles with tailorable matrix constitutions for controllable transdermal drug delivery | |
JP2020532643A (ja) | 官能基化および架橋ポリマー | |
BR112018011936B1 (pt) | Microestrutura para absorção transdérmica e método para a fabricação da mesma | |
Sadeqi et al. | Cost-effective fabrication of chitosan microneedles for transdermal drug delivery | |
KR20180018000A (ko) | 주사 가능한 3차원 나노섬유 스캐폴드 및 이의 제조방법 | |
KR101703050B1 (ko) | 경피전달용 미세돌기 구조체 | |
Zennifer et al. | Additive manufacturing of peripheral nerve conduits–fabrication methods, design considerations and clinical challenges | |
Sousa et al. | Anisotropic 3d scaffolds for spinal cord guided repair: current concepts | |
Long et al. | Microneedles for in situ tissue regeneration | |
KR20200037660A (ko) | 전기전도성 마이크로 니들 패치의 제조방법 및 이에 의해 제조된 전기전도성 마이크로 니들 패치 | |
KR102135641B1 (ko) | 주사 가능한 3차원 나노섬유 스캐폴드 및 이의 제조방법 | |
KR101716447B1 (ko) | 진동과 중력을 이용한 마이크로니들 제조방법 | |
CN116531560A (zh) | 一种温敏性肩袖自锁神经导管及其制备方法 | |
KR20160143611A (ko) | 경피전달용 미세돌기 구조체 | |
JP2022500177A (ja) | 微細構造体基盤薬物注入装置およびその製造方法 | |
CN219290254U (zh) | 用于神经修复的导电形状记忆聚合物装置 |
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 |