WO2022113888A1 - 綿形状の骨再生用材料の製造方法 - Google Patents
綿形状の骨再生用材料の製造方法 Download PDFInfo
- Publication number
- WO2022113888A1 WO2022113888A1 PCT/JP2021/042506 JP2021042506W WO2022113888A1 WO 2022113888 A1 WO2022113888 A1 WO 2022113888A1 JP 2021042506 W JP2021042506 W JP 2021042506W WO 2022113888 A1 WO2022113888 A1 WO 2022113888A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- poor solvent
- cotton
- particles
- spinning solution
- bone regeneration
- Prior art date
Links
- 239000000463 material Substances 0.000 title claims abstract description 34
- 230000010478 bone regeneration Effects 0.000 title claims abstract description 28
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 69
- 238000000034 method Methods 0.000 claims abstract description 53
- 239000000835 fiber Substances 0.000 claims abstract description 50
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 48
- 239000002245 particle Substances 0.000 claims abstract description 48
- 238000009987 spinning Methods 0.000 claims abstract description 44
- 238000002166 wet spinning Methods 0.000 claims abstract description 33
- 239000011347 resin Substances 0.000 claims abstract description 28
- 229920005989 resin Polymers 0.000 claims abstract description 28
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 15
- 239000003960 organic solvent Substances 0.000 claims abstract description 14
- 238000003756 stirring Methods 0.000 claims abstract description 8
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 238000003795 desorption Methods 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 52
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 49
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 239000001506 calcium phosphate Substances 0.000 claims description 17
- 229920000742 Cotton Polymers 0.000 claims description 10
- 239000004332 silver Substances 0.000 claims description 9
- 229910052709 silver Inorganic materials 0.000 claims description 9
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 claims description 8
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 8
- 235000011010 calcium phosphates Nutrition 0.000 claims description 8
- -1 silver ions Chemical class 0.000 claims description 7
- 238000009792 diffusion process Methods 0.000 claims description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 4
- 239000011575 calcium Substances 0.000 claims description 4
- 229910052791 calcium Inorganic materials 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 4
- 230000009545 invasion Effects 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims 1
- 239000000243 solution Substances 0.000 abstract description 38
- 238000011049 filling Methods 0.000 abstract 2
- 238000002347 injection Methods 0.000 abstract 1
- 239000007924 injection Substances 0.000 abstract 1
- 230000035515 penetration Effects 0.000 abstract 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 16
- 229920005689 PLLA-PGA Polymers 0.000 description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- 229910052801 chlorine Inorganic materials 0.000 description 12
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 9
- 229940078499 tricalcium phosphate Drugs 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 8
- 239000000945 filler Substances 0.000 description 8
- 239000004310 lactic acid Substances 0.000 description 8
- 235000014655 lactic acid Nutrition 0.000 description 8
- 235000019731 tricalcium phosphate Nutrition 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 238000001125 extrusion Methods 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 6
- 229920001244 Poly(D,L-lactide) Polymers 0.000 description 5
- 230000021164 cell adhesion Effects 0.000 description 5
- 229920001432 poly(L-lactide) Polymers 0.000 description 5
- 229920000747 poly(lactic acid) Polymers 0.000 description 5
- 239000004626 polylactic acid Substances 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 4
- 229910021607 Silver chloride Inorganic materials 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 210000000963 osteoblast Anatomy 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 238000007334 copolymerization reaction Methods 0.000 description 2
- 238000001523 electrospinning Methods 0.000 description 2
- 239000011256 inorganic filler Substances 0.000 description 2
- 229910003475 inorganic filler Inorganic materials 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000003764 ultrasonic spray pyrolysis Methods 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 229920006167 biodegradable resin Polymers 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 239000012094 cell viability reagent Substances 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229920000118 poly(D-lactic acid) Polymers 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Images
Classifications
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/0007—Electro-spinning
- D01D5/0015—Electro-spinning characterised by the initial state of the material
- D01D5/003—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
- D01D5/0046—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion the fibre formed by coagulation, i.e. wet electro-spinning
-
- 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
- A61L27/02—Inorganic materials
- A61L27/04—Metals or alloys
-
- 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
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
-
- 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
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
-
- 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
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F1/00—General methods for the manufacture of artificial filaments or the like
- D01F1/02—Addition of substances to the spinning solution or to the melt
- D01F1/10—Other agents for modifying properties
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F1/00—General methods for the manufacture of artificial filaments or the like
- D01F1/02—Addition of substances to the spinning solution or to the melt
- D01F1/10—Other agents for modifying properties
- D01F1/103—Agents inhibiting growth of microorganisms
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F6/00—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
- D01F6/58—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from homopolycondensation products
- D01F6/62—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from homopolycondensation products from polyesters
- D01F6/625—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from homopolycondensation products from polyesters derived from hydroxy-carboxylic acids, e.g. lactones
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F6/00—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
- D01F6/78—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from copolycondensation products
- D01F6/84—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from copolycondensation products from copolyesters
-
- D—TEXTILES; PAPER
- D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
- D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
- D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
- D04H1/70—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
- D04H1/72—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
- D04H1/728—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning
-
- 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
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
- A61L2300/104—Silver, e.g. silver sulfadiazine
-
- 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
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/112—Phosphorus-containing compounds, e.g. phosphates, phosphonates
-
- 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
- A61L2300/404—Biocides, antimicrobial agents, antiseptic 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
-
- D—TEXTILES; PAPER
- D10—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B2401/00—Physical properties
- D10B2401/06—Load-responsive characteristics
- D10B2401/063—Load-responsive characteristics high strength
-
- D—TEXTILES; PAPER
- D10—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B2509/00—Medical; Hygiene
Definitions
- the present invention relates to a method for producing a cotton-shaped bone regeneration material made of biodegradable fibers containing PLGA resin, and a cotton-shaped bone regeneration material produced by the method.
- bone regeneration materials are used in the form of blocks or granules, but improvements in formability during surgery and concerns about movement / detachment from the target site are also desired. Therefore, polylactic acid having high rigidity is used as a matrix, combined with an inorganic filler ( ⁇ -phase-tricalcium phosphate, silicon-eluting calcium carbonate, etc.) and fiberized by an electrospinning method (ES). ..
- the inventors of the present invention have decided to receive the biodegradable fibers emitted from the nozzles in the ES in a collector container filled with ethanol, and collect and dry the fibers suspended in the ethanol solution to form a cotton shape. It has been successful (US8853298).
- the cotton-shaped bone repair material is a clinically excellent material because it can easily cope with any affected part shape at the time of surgery.
- PLGA has been used instead of polylactic acid as a matrix resin for biodegradable fibers.
- PLGA is an excellent biodegradable resin that is more bioabsorbable than polylactic acid and has been approved by the FDA for safety. Therefore, PLGA is used as a matrix to be combined with an inorganic filler ( ⁇ -phase tricalcium phosphate, calcium carbonate, etc.) and fiberized by an electrospinning method (ES).
- an inorganic filler ⁇ -phase tricalcium phosphate, calcium carbonate, etc.
- PLGA is synthesized by copolymerizing lactic acid and glycolic acid, but it is possible to control biodegradability by adjusting the ratio of lactic acid and glycolic acid.
- PLGA with 85% lactic acid: 15% glycolic acid (85:15) and PLGA with 75% lactic acid: 25% glycolic acid (75:25) is more degradable.
- lactic acid of polylactic acid has a crystalline L-form and an amorphous D-form which is an optical isomer, and PDLLA containing the D-form is more than PLLA which does not contain the D-form and is only the L-form. Is also difficult to crystallize and easily decomposed. Therefore, by copolymerizing PDLLA containing D-form and PGA, it is possible to synthesize PDLLGA having significantly higher degradability than PLGA (PLLGA) not containing D-form.
- PDLLGA is easily soluble in solvents and does not require the use of chlorine-based solvents, and can also be dissolved in non-chlorine-based solvents (eg acetone).
- non-chlorine-based solvents eg acetone
- PDLLGA has a lower molecular weight than PLLGA, and when the ES method in which a high voltage is applied is used, it becomes difficult to maintain the fiber shape, and as a result, a cotton-shaped bone regeneration material is produced using PDLLGA. It was difficult.
- bone regeneration materials to be implanted in the human body are at risk of bacterial infection after implantation surgery. Therefore, it is desirable that the material itself is imparted with antibacterial properties.
- the inventors of the present invention use an improved wet spinning method to produce a cotton-shaped bone regeneration material, which comprises 50-80% by weight of calcium salt particles and 50-20% by weight of PDLLGA resin. Both are put into a mixing container at a ratio, dissolved in acetone and stirred to prepare a spinning solution having a resin concentration of 10 to 20% by weight in which the calcium salt particles are dispersed, and the prepared spinning solution is filled in a syringe. Then, the spinning solution filled in the syringe is extruded from the discharge port of an incident needle having a predetermined diameter and incident on a collector container filled with a poor solvent, and the spinning solution incident on the poor solvent is poor.
- Calcium phosphate particles are preferably used as the calcium salt particles, and ⁇ -TCP particles are more preferably used. ⁇ -TCP containing silver is useful because it has antibacterial properties.
- ethanol is used as the poor solvent.
- water is used as the poor solvent. If water contains chlorine, it may react with silver contained in ⁇ -TCP to form AgCl, so pure water containing no chlorine is preferable.
- the PDLLGA fiber preferably contains 50-80% by weight, more preferably 60-70% by weight of calcium salt particles.
- the spinning solution prepared by mixing the resin and the filler particles and dissolving them in an organic solvent is extruded from a syringe to spin the spinning solution, so that a spinning solution containing a large amount of calcium salt particles can be easily prepared. ..
- ES uses a slurry with low viscosity during spinning, it is necessary to greatly improve the dispersibility of the filler particles in advance, and a special step for uniformly dispersing a large amount of filler particles in the solution ( (Example: kneading) is required, but in the wet spinning method, since a slurry having a viscosity higher than that of ES is used, it is sufficient to disperse the particles in the solution by stirring without taking such a special step. This is because the fluidity of the polymer liquid that fills the spaces between the particles is lowered and aggregation can be prevented.
- Calcium phosphate particles are preferably used as the calcium salt particles, and ⁇ -TCP particles are more preferably used.
- PDLLGA is decomposed in contact with body fluid to elute ⁇ -TCP particles, and further ⁇ -TCP is dissolved to elute calcium ions and phosphorus ions, and bone formation by bone resorption replacement is promoted.
- ⁇ -TCP particles silver ion solid-dissolved ⁇ -TCP particles synthesized by substituting and solid-solving silver ions with calcium in the crystal lattice of ⁇ -TCP are used.
- the ⁇ -TCP particles eluted from the PDLLGA fiber are dissolved, the silver ions dissolved in ⁇ -TCP are eluted and exhibit antibacterial properties.
- the resin concentration of the spinning solution is 10 to 20% by weight.
- the spinning solution is discharged from the nozzle by simply pushing it out, so the resin concentration of the spinning solution can be set relatively freely according to the discharge rate and the thickness of the fiber. ..
- the cotton-shaped bone regeneration material made of PDLLGA fiber produced by the wet spinning method of the present invention has high bioabsorbability and excellent flexibility, and therefore is used for bone regeneration in the dental field in addition to spinal treatment. It can also be suitably used as a material.
- acetone is used instead of chloroform as the organic solvent used for preparing the spinning solution, so that the bone regeneration material produced by the present invention is highly safe.
- the PDLLGA fiber produced by the wet spinning method of the present invention has a smaller number of pores on the fiber surface than the fiber spun by ES, has a fine cross-sectional structure, and is excellent in shape maintenance.
- the wet spinning method of the present invention pushes the spinning solution from the syringe to the discharge port by applying a physical force, so that the content of the filler particles in the spinning solution has a high degree of freedom.
- the particles form an uneven structure on the fiber surface. It is suitable for cell adhesion that the surface of the fiber has an uneven structure.
- the cotton-shaped bone regeneration material made of PDLLGA fiber produced by the wet spinning method of the present invention has PDLLGA dissolved in the body after being implanted in the body, and the pH is locally lowered to create an acidic environment.
- ⁇ -TCP dissolves in an acidic environment, and trace amounts of calcium ions and phosphate ions are eluted and slowly released, contributing to the promotion of bone formation.
- FIG. 1 shows a schematic diagram of a spinning method when ethanol is used as a poor solvent in the wet spinning method of the embodiment of the present invention.
- FIG. 2 shows a sample taken out from the poor solvent and recovered in the wet spinning method (using ethanol as the poor solvent) of the embodiment of the present invention.
- FIG. 3 shows a spinning method when water is used as a poor solvent in the wet spinning method of the embodiment of the present invention.
- FIG. 4 shows a cotton-shaped bone regeneration material produced by using the wet spinning method (using water as a poor solvent) of the embodiment of the present invention.
- FIG. 5 is an SEM photograph showing the surface shape of the biodegradable fiber spun in the wet spinning method (using water as a poor solvent) according to the embodiment of the present invention.
- FIG. 1 shows a schematic diagram of a spinning method when ethanol is used as a poor solvent in the wet spinning method of the embodiment of the present invention.
- FIG. 2 shows a sample taken out from the poor solvent and recovered in the we
- FIG. 6 is an SEM photograph showing the uneven shape of the surface of the biodegradable fiber spun in the wet spinning method (using water as a poor solvent) according to the embodiment of the present invention.
- FIG. 7 shows osteoblasts cultured for 6 hours, 1 day, and 3 days using a cotton-shaped bone regeneration material produced by the wet spinning method (using ethanol as a poor solvent) of the examples of the present invention. As a result, the osteoblasts are attached to the biodegradable fibers.
- FIG. 8 shows, in an experiment using a cotton-shaped bone regeneration material produced by using the wet spinning method (using ethanol as a poor solvent) of the embodiment of the present invention, abruptly one day after cell adhesion. Moreover, it shows how it grows smoothly.
- the PLLGA resin refers to a PLGA resin synthesized by copolymerization of lactic acid containing only L-form and glycolic acid.
- the one with a polymerization ratio of PLLA and PGA of 85:15 is called PLLGA (85:15), and the one with a polymerization ratio of PLLA and PGA of 75:25 is called PLLGA (75:25).
- PLLGA can be more degradable by increasing the proportion of PGA.
- a chlorine-based solvent such as chloroform.
- the PDLLGA resin refers to a PLGA resin synthesized by copolymerization of lactic acid and glycolic acid containing D-form and L-form.
- Lactic acid used for the synthesis of PLGA includes a crystalline L-form and an amorphous D-form which is an optical isomer
- PLA consists of only L-form poly (L-lactic acid) (PLLA) and L.
- PLLA L-lactic acid
- PDLLA poly (D-lactic acid)
- PDLLGA poly (D-lactic acid)
- PDLLGA which is a copolymer of PDLLA and PGA, has particularly high flexibility among PLGAs. PDLLGA can control its degradability by changing the polymerization ratio of PDLLA and PGA.
- the amount of D-form contained in PDLLGA resin is decomposed so that the resin can be dissolved in acetone by containing D-form. It has sex, and that is enough.
- the wet spinning method refers to a method of solidifying into a fiber shape by mutual diffusion of desorption of an organic solvent and invasion of a poor solvent.
- the choice of organic solvent and poor solvent affects the solidification rate of the polymer and the interdiffusion rate of the solvent, and the balance of this interdiffusion rate determines the morphology of the resulting fiber.
- conditions are set and improved for fiberizing a PDLLGA resin containing calcium phosphate particles to form a cotton shape.
- the organic solvent means a solvent used for dissolving a mixture of PDLLGA resin and calcium phosphate particles.
- Chlorine-based organic solvents such as chloroform have excellent solubility but are toxic.
- Acetone is inferior to chloroform in terms of solubility, but does not contain chlorine, so it is excellent in safety to the living body. Since the PDLLGA resin used in the present invention is easily dissolved in a solvent, it is not necessary to use toxicity of a chlorine-based organic solvent such as chloroform, and acetone, which is a highly safe non-chlorine solvent, can be used.
- the poor solvent is used in the coagulation bath solution as a solvent that does not dissolve the PDLLGA resin, and is used for recovering biodegradable fibers in the form of cotton.
- a poor solvent is defined as a solvent when the solute-solvent interaction (free energy) is smaller than the computational average of the solute-solute and solvent-solvent interactions in a specific substance-solvent system.
- the poor solvent used in the method of the present invention is selected in consideration of the balance of mutual diffusion with the organic solvent by using the dissolution parameter as an index.
- ethanol or water in which PDLLGA is insoluble can be preferably used.
- the spinning solution can be fiberized by stirring ethanol in a collector container and stretching the fibers by the flow of the poor solvent generated by the stirring.
- the Hensen solubility parameter of ethanol is 26.5 ⁇ [(MPa) 1/2]
- the Hensen solubility parameter of acetone is 20.0 ⁇ [(MPa) 1/2])
- the degree of divergence between the two is It is 6.5 ⁇ [(MPa) 1/2 ].
- the Hensen solubility parameter of water is 47.8 ⁇ [(MPa) 1/2]
- the Hensen solubility parameter of acetone is 20.0 ⁇ [(MPa) 1/2])
- the degree of divergence between the two is 27. .8 ⁇ [(MPa) 1/2].
- the degree of deviation of the Hensen solubility parameter of water with respect to acetone is considerably larger than the degree of deviation of ethanol with respect to acetone, the rate at which acetone is desorbed from the fiber is much faster than when ethanol is used as a poor solvent.
- the spinning solution extruded from the nozzle is rapidly fiberized in water, so that it is not necessary to stretch the fibers by stirring water in order to fiberize the spinning solution.
- the silver ion solid-dissolved ⁇ -phase tricalcium phosphate is ⁇ -phase tricalcium phosphate in which the calcium sites in the crystal lattice of ⁇ -phase tricalcium phosphate are substituted with Ag + and solid-dissolved.
- the silver ion solid-soluble ⁇ -phase tricalcium phosphate can be prepared by using an ultrasonic spray pyrolysis method.
- the ultrasonic spray pyrolysis method is one of the methods for synthesizing ceramic raw material powder.
- the sample solution is atomized by ultrasonic waves, and the droplets are introduced into a heated electric furnace to instantly droplet the droplets.
- the powder (fine particles) having the desired chemical composition can be obtained by removing the solvent from the water, precipitating the salt, and thermally decomposing the powder. Details are disclosed in Japanese Patent Application Laid-Open No. 2020-130417.
- Reagent special grade purity 99.5 +% -Size of the extrusion port of the incident needle for extrusion of spinning solution 27G (inner diameter 0.2 mm, outer diameter 0.4 mm)
- -Poor solvent container A cylindrical container with a diameter of 15 cm and a height of 7.5 cm was used, and the mixture was stirred with a magnetic stirrer using a stirrer with a length of 5 cm. (refer graph1).
- FIG. 5 shows an SEM photograph of ⁇ -TCP / PDLLGA fiber produced by using water as a poor solvent. It can be seen that the filler particles are exposed on the surface of the fiber to form an uneven shape.
- FIG. 6 shows an SEM photograph of ⁇ -TCP / PDLLGA fiber produced by using water as a poor solvent. It is a flat cross section with a width of 80 to 100 ⁇ m, a thickness of 40 to 50 ⁇ m, and a dent on one side. According to the knowledge of the inventors, the reason why the shape of the fiber is such a shape is considered to be that a flow called "Karman vortex" is generated when the fiber flows out from the syringe, and the center is dented by the flow.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Textile Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Mechanical Engineering (AREA)
- Composite Materials (AREA)
- Materials Engineering (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Manufacturing & Machinery (AREA)
- Artificial Filaments (AREA)
- Materials For Medical Uses (AREA)
- Spinning Methods And Devices For Manufacturing Artificial Fibers (AREA)
Abstract
Description
さらに、人体に埋植する骨再生用材料は、埋植手術の後、細菌感染のリスクに晒される。そこで、材料自体に抗菌性が付与されていることが望ましい。
定義
本発明においてPLLGA樹脂とは、L体のみを含む乳酸とグリコール酸の共重合によって合成されたPLGA樹脂をいう。PLLAとPGAの重合比率が85:15のものをPLLGA(85:15)と称し、PLLAとPGAの重合比率が75:25のものをPLLGA(75:25)と称する。PLLGAはPGAの比率を高めることによって分解性を高めることができる。PLLGAを溶剤で溶かすにはクロロホルム等の塩素系溶剤を用いることが必要である。
本発明においてPDLLGA樹脂とは、D体とL体を含む乳酸とグリコール酸の共重合によって合成されたPLGA樹脂をいう。PLGAの合成に用いられる乳酸には、結晶性のL体と光学異性体であるアモルファス性のD体とが存在し、PLAにはL体のみからなるポリ(L-乳酸)(PLLA)とL体とD体を含むポリ(D―乳酸)(PDLLA)が存在する。このPDLLAとPGAの共重合体であるPDLLGAはPLGAの中でも、特に高い柔軟性を有する。PDLLGAは、PDLLAとPGAとの重合比率を変化させることによって分解性を制御することが可能である。PDLLGAに含まれるD体の量を数値的に特定するのは困難であるが、本発明において、PDLLGA樹脂に含まれるD体の量は、D体を含むことによって樹脂がアセトンで溶解可能な分解性を有し、かつそれで足りる。
本発明において湿式紡糸法とは、有機溶剤の脱離と貧溶媒の侵入の相互拡散によって繊維の形に固化させる方法をいう。有機溶剤と貧溶媒の選択がポリマーの固化速度や溶媒の相互拡散に影響し、この相互拡散の速度のバランスが、得られる繊維の形態を決める。本発明に用いる湿式紡糸法は、リン酸カルシウム粒子を含むPDLLGA樹脂を繊維化して綿形状を形成するための条件設定と改良がなされている。
本発明において有機溶剤とは、PDLLGA樹脂とリン酸カルシウム粒子の混合物を溶解するために用いられる溶剤をいう。クロロホルム等の塩素系の有機溶剤は、溶解性に優れるが、毒性がある。アセトンは、溶解性の点でクロロホルムに劣るが塩素を含まないので、生体に対する安全性に優れる。本発明で用いるPDLLGA樹脂は溶剤に溶解されやすいので、クロロホルム等の塩素系有機溶剤毒性を用いる必要がなく、安全性の高い非塩素系溶剤であるアセトンを用いることができる。
本発明において貧溶媒とは、PDLLGA樹脂を溶かさない溶媒として凝固浴液に用いられ、生分解性繊維を綿形状に回収するために用いられる。
貧溶媒とは、講学上、特定の物質-溶媒系で溶質-溶媒間の相互作用(自由エネルギー)が溶質-溶質間,溶媒-溶媒間の相互作用の算術平均より小さいとき,この溶媒をこの溶質に対して貧溶媒であるというが、本発明の方法に用いる貧溶媒は、溶解パラメータを指標として、有機溶媒との相互拡散のバランスを考慮して選択される。本発明では、PDLLGAが不溶であるエタノール又は水を好適に用いることができる。
本発明の一つの実施例において、銀イオン固溶β相リン酸三カルシウムとは、β相リン酸三カルシウムの結晶格子中のカルシウムサイトがAg+で置換固溶されたβ相リン酸三カルシウムをいう。
銀イオン固溶β相リン酸三カルシウムは、超音波噴霧熱分解法を用いて調製することができる。超音波噴霧熱分解法とは、セラミック原料粉体の合成法の一つであり、試料溶液を超音波により霧状にして、その液滴を加熱した電気炉中に導入して瞬時に液滴からの溶媒の除去・塩の析出・熱分解を起こさせて目的とする化学組成の粉体(微粒子)を得ることができる。詳細は特開2020-130417に開示されている。
以下に示す材料及び装置を使用した。
・β相リン酸三カルシウム(Ca3(PO4)2):太平化学産業株式会社β-TCP-100。
粒径1.7mm以下のものを4μm程度に粉砕したもの(β―TCP粉砕品)を用いた。
・PDLLGA:PLGA (75:25) (PURASORB PDLG7507、Corbion Purac)
・エタノール:キシダ化学一級 純度99.5%
・アセトン:和光純薬 試薬特級純度99.5+%
・紡糸溶液押出用入射針の押出口のサイズ:27G(内径0.2mm、外径0.4mm)
・貧溶媒容器:直径15 cm、高さ7.5 cmの円柱型容器を使用し、長さ5 cmの撹拌子を用いてマグネチックスターラーにて撹拌した。(図1参照)。
β-TCPとPDLLGAを7:3の重量比で混合し、アセトンに溶解させ、一晩混合し、ポリマー濃度17%の紡糸溶液を調製した。
2.紡糸条件
押出速度 0.75ml/h、攪拌速度 200rpm
3.綿形状物の回収
湿式紡糸後、繊維をエタノールにて洗浄し、さらに溶媒を除去するためにエタノールにて一晩保持した。その後、吸水シートにてエタノールを除去し、綿をほぐしながら常温乾燥して綿形状のサンプル1(図2参照)を得た。
以下に示す材料及び装置を使用した。
・β相リン酸三カルシウム(Ca3(PO4)2):太平化学産業株式会社β-TCP-100。
粒径1.7mm以下のものを4μm程度に粉砕したもの(β―TCP粉砕品)を用いた。
・PDLLGA:PLGA (75:25) (PURASORB PDLG7507、Corbion Purac)
・純水
・アセトン:和光純薬 試薬特級純度99.5+%
・紡糸溶液押出用入射針の押出口のサイズ:33G(内径0.07mm、外径0.20mm)
・貧溶媒容器:直径9 cm、高さ25 cmの円柱型容器を使用(図3参照)。
β-TCPとPDLLGAを7:3 重量比で混合し、アセトンに溶解させ、一晩混合し、ポリマー濃度17%の紡糸溶液を調製した。
2.紡糸条件
押出速度 0.6ml/h
3.綿形状物の回収
溶媒のアセトンは水と交換されて出て行くが、その比重が水より小さいので容器の底には溜まらず、上面付近に浮いてくる。その結果、長時間線引きしても繊維同士が再度アセトンによりくっつくなどのことは起こらず、長い一筆書きの繊維ができる(図3参照)。これに対し、貧溶媒にエタノールを用いると、アセトンとエタノールの比重はほとんど同じなので、エタノールに紡糸すると脱けたアセトンが混ざり合ってエタノール中に浮遊する。その結果、湿式紡糸法で長時間紡糸すると、薄められたアセトンによって繊維同士がくっつきやすくなり、乾燥した繊維がゴワゴワした塊になってしまう。
湿式紡糸後、繊維をエタノールにて洗浄し、さらに溶媒を除去するためにエタノール中にて一晩保持した。その後、吸水シートにてエタノールを除去し、綿をほぐしながら常温乾燥して綿形状のサンプル2(図4参照)を得た。
wellに通常培地を1ml入れて、サンプル1を培地になじませた後にマウス由来骨芽細胞様細胞(MC3T3-E1)の懸濁液(2.4x105 cells/ml)0.5mlを入れて、インキュベーター内で6時間、1日間、3日間培養した(CO2濃度5%、37℃)。その後、サンプル1を構成する繊維上への細胞の接着の様子を走査型電子顕微鏡を用いて観察した。その結果、1日までに一部の細胞が繊維表面に接着しはじめ、3日間で表面をほぼ覆うまでに接着・増殖する様子が観察された(図7参照)。
通常培地にAlamarBlue® Cell Viability Reagent (Thermo Fisher Scientific, ここでの略称: ABCVR)を加え、ABCVR溶液 (通常培地 : ABCVR = 10 : 1 wt%)を作製した。培養した各wellから培地を遠沈管へ移した後、ABCVR溶液を2.0 mlずつ加え、インキュベーター内 (CO2濃度: 5 %, 37 °C)で4 h保持し、反応させた。溶液から80 μlずつ取り、測定用の黒底96-well plateに移し替えた。続いて、マルチモードプレートリーダー (Perkin Elmer Life & Analytical Sciences, EnSpire)を用いて蛍光強度を測定した (励起波長: 540 nm 蛍光波長: 590 nm)。これにより6時間の蛍光強度を1とした早退強度を比較して細胞の代謝活性評価とし、即ち増殖性を判断した。
その結果、細胞接着後1日以降に急激に、かつ順調に増殖する様子が明示された(図8参照)。
実験の結果、本発明の湿式紡糸法で紡糸した太いβ-TCP/PDLLGA繊維からなる綿形状の骨再生用材料は、骨芽細胞培養試験で高い増殖性を示すことが確認された。
Claims (10)
- 湿式紡糸法を用いて綿形状の骨再生用材料を製造する方法であって、カルシウム塩粒子50-80重量%とPDLLGA樹脂50-20重量%とを混合容器に投入し、アセトンに溶解させて攪拌することによって、前記カルシウム塩粒子が溶液中に分散した樹脂濃度10~20重量%の紡糸溶液を調製し、前記調製した紡糸溶液をシリンジに充填し、前記シリンジに充填された紡糸溶液を、所定の径を有する入射針の吐出口から押し出して貧溶媒を満たしたコレクター容器中に入射し、前記貧溶媒中に入射された紡糸溶液は、貧溶媒液中で有機溶媒の脱離と貧溶媒の侵入の相互拡散によって固化されて繊維化され、貧溶媒中で固化した繊維は繊維同士が接着することなくコレクター容器に浮遊状態で堆積して、綿形状に回収される、前記湿式紡糸法を用いて綿形状の骨再生用材料を製造する方法。
- 前記貧溶媒はエタノールである、請求項1に記載の方法。
- 前記貧溶媒は水である、請求項1に記載の方法。
- 前記リン酸カルシウム粒子はβ―TCP粒子である、請求項1~3のいずれか一項に記載の方法。
- 前記β―TCP粒子は銀イオンを含有するものである、請求項4に記載の方法。
- 前記β―TCP粒子は、銀イオンをβ-TCPの結晶格子中のカルシウムに置換固溶させることによって合成された銀イオン固溶β-TCPの粒子である、請求項4に記載の方法。
- 湿式紡糸法を用いて製造された綿形状の骨再生用材料であって、前記綿形状の骨再生用材料は、カルシウム塩粒子50-80重量%とPDLLGA樹脂20-50重量%を混合容器に投入し、アセトンに溶解させて攪拌することによって、カルシウム塩粒子が分散した樹脂濃度10~20重量%の紡糸溶液を調製し、前記調製した紡糸溶液をシリンジに充填し、前記シリンジに充填された紡糸溶液を、所定の径を有する入射針の吐出口から押し出して貧溶媒を満たしたコレクター容器中に入射し、前記貧溶媒中に入射された紡糸溶液は、貧溶媒液中で有機溶媒の脱離と貧溶媒の侵入の相互拡散によって固化されて繊維化され、貧溶媒中で固化した繊維は、繊維同士が接着することなくコレクター容器に浮遊して綿形状に回収する、という工程によって製造されたものである、湿式紡糸法を用いて製造された綿形状の骨再生用材料。
- 前記カルシウム塩粒子はリン酸カルシウム粒子である、請求項7に記載の綿形状の骨再生用材料。
- 前記リン酸カルシウム粒子はβ―TCP粒子である、請求項8に記載の綿形状の骨再生用材料。
- 前記β―TCP粒子は、銀イオンをβ-TCPの結晶格子中のカルシウムに置換固溶させることによって合成された銀イオン固溶β-TCPの粒子である、請求項9に記載の綿形状の骨再生用材料。
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2022520496A JP7357308B2 (ja) | 2020-11-24 | 2021-11-18 | 綿形状の骨再生用材料の製造方法 |
US18/038,661 US20240093409A1 (en) | 2020-11-24 | 2021-11-18 | Method for producing bone regeneration material having cotton-wool like structure |
JP2022080238A JP7357306B2 (ja) | 2020-11-24 | 2022-05-16 | 綿形状の骨再生用材料の製造方法 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202063117891P | 2020-11-24 | 2020-11-24 | |
US63/117,891 | 2020-11-24 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2022113888A1 true WO2022113888A1 (ja) | 2022-06-02 |
Family
ID=81754581
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2021/042506 WO2022113888A1 (ja) | 2020-11-24 | 2021-11-18 | 綿形状の骨再生用材料の製造方法 |
Country Status (3)
Country | Link |
---|---|
US (1) | US20240093409A1 (ja) |
JP (2) | JP7357308B2 (ja) |
WO (1) | WO2022113888A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP7460993B2 (ja) | 2022-05-23 | 2024-04-03 | 国立大学法人 名古屋工業大学 | 湿式紡糸法を用いて製造された綿形状の骨再生材料、及び湿式紡糸法を用いて綿形状の骨再生材料を製造する方法 |
JP7474454B1 (ja) | 2022-11-01 | 2024-04-25 | 国立大学法人 名古屋工業大学 | 結晶質リン酸カルシウム粒子を湿式粉砕してアモルファスリン酸カルシウムに改質する方法 |
WO2024095956A1 (ja) * | 2022-11-01 | 2024-05-10 | 国立大学法人 名古屋工業大学 | 結晶質リン酸カルシウム粒子を湿式粉砕してアモルファスリン酸カルシウムに改質する方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010507413A (ja) * | 2006-10-23 | 2010-03-11 | アイトゲネシッシェ テヒニッシェ ホーホシューレ チューリッヒ | インプラント材料 |
CN101716372A (zh) * | 2009-12-30 | 2010-06-02 | 中国科学院长春应用化学研究所 | 一种定向可溶性纤维致孔制备组织工程支架的方法 |
-
2021
- 2021-11-18 JP JP2022520496A patent/JP7357308B2/ja active Active
- 2021-11-18 WO PCT/JP2021/042506 patent/WO2022113888A1/ja active Application Filing
- 2021-11-18 US US18/038,661 patent/US20240093409A1/en active Pending
-
2022
- 2022-05-16 JP JP2022080238A patent/JP7357306B2/ja active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010507413A (ja) * | 2006-10-23 | 2010-03-11 | アイトゲネシッシェ テヒニッシェ ホーホシューレ チューリッヒ | インプラント材料 |
CN101716372A (zh) * | 2009-12-30 | 2010-06-02 | 中国科学院长春应用化学研究所 | 一种定向可溶性纤维致孔制备组织工程支架的方法 |
Non-Patent Citations (1)
Title |
---|
NELSON KEVIN D, ANDRES ROMERO, PAULA WAGGONER, BRENT CROW, ANGELA BORNEMAN, GEORGE M. SMITH: "Technique Paper for Wet-Spinning Poly(L-lactic acid) and Poly(DL-lactide-co-glycolide) Monofilament Fibers", TISSUE ENGINEERING, vol. 9, no. 6, 1 December 2003 (2003-12-01), pages 1323 - 1330, XP055932633, DOI: 10.1089/10763270360728233 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP7460993B2 (ja) | 2022-05-23 | 2024-04-03 | 国立大学法人 名古屋工業大学 | 湿式紡糸法を用いて製造された綿形状の骨再生材料、及び湿式紡糸法を用いて綿形状の骨再生材料を製造する方法 |
JP7481699B2 (ja) | 2022-05-23 | 2024-05-13 | 国立大学法人 名古屋工業大学 | 湿式紡糸法を用いて無機フィラー粒子を含有する生分解性繊維材料を連続的に製造する方法、及びその方法で製造された綿形状の骨再生材料 |
JP7474454B1 (ja) | 2022-11-01 | 2024-04-25 | 国立大学法人 名古屋工業大学 | 結晶質リン酸カルシウム粒子を湿式粉砕してアモルファスリン酸カルシウムに改質する方法 |
WO2024095956A1 (ja) * | 2022-11-01 | 2024-05-10 | 国立大学法人 名古屋工業大学 | 結晶質リン酸カルシウム粒子を湿式粉砕してアモルファスリン酸カルシウムに改質する方法 |
Also Published As
Publication number | Publication date |
---|---|
US20240093409A1 (en) | 2024-03-21 |
JP7357306B2 (ja) | 2023-10-06 |
JP7357308B2 (ja) | 2023-10-06 |
JPWO2022113888A1 (ja) | 2022-06-02 |
JP2022110081A (ja) | 2022-07-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2022113888A1 (ja) | 綿形状の骨再生用材料の製造方法 | |
US11969521B2 (en) | Method for manufacturing bone-regeneration material comprising biodegradable fibers by using electrospinning method | |
US20070112115A1 (en) | Inorganic-organic hybrid micro-/nanofibers | |
Rodenas-Rochina et al. | Effects of hydroxyapatite filler on long-term hydrolytic degradation of PLLA/PCL porous scaffolds | |
KR102316879B1 (ko) | 말뼈 나노세라믹 및 pcl을 포함하는 치주조직 재생용 지지체 및 이의 제조방법 | |
KR20090112760A (ko) | 복합 재료의 제조 방법, 얻어지는 재료 및 그의 용도 | |
Ataie et al. | Carboxymethyl carrageenan immobilized on 3D-printed polycaprolactone scaffold for the adsorption of calcium phosphate/strontium phosphate adapted to bone regeneration | |
Fan et al. | Three-dimensional printed poly (L-lactide) copolymers with nano-hydroxyapatite scaffolds for enhanced osteogenic and regenerative activities in bone tissue engineering | |
Ghafari et al. | Biological evaluation and osteogenic potential of polyhydroxybutyrate-keratin/Al2O3 electrospun nanocomposite scaffold: a novel bone regeneration construct | |
US20120219595A1 (en) | Biodegradable fiber and fiber wadding for filling bone defects and method for producing the same | |
CN101491702A (zh) | 纳米碳磷灰石/壳聚糖-聚乳酸骨组织工程支架材料的制备方法 | |
JP7481699B2 (ja) | 湿式紡糸法を用いて無機フィラー粒子を含有する生分解性繊維材料を連続的に製造する方法、及びその方法で製造された綿形状の骨再生材料 | |
TWI275402B (en) | Biodegradable porous three-dimensional-support and manufacturing method thereof | |
TWI634914B (zh) | 由生物可分解性纖維組成的骨再生用材料,以及用於製造骨再生用材料的方法 | |
Turon et al. | Preparation and applications of hydroxyapatite nanocomposites based on biodegradable and natural polymers | |
Hu et al. | Novel multi-functional microsphere scaffold with shape memory function for bone regeneration | |
WO2003090920A1 (en) | Core-assisted formation of microcapsules | |
Turon et al. | Composites Based on Hydroxyapatite and Biodegradable Polylactide | |
Wang et al. | Preparation of hollow porous HAP microspheres as drug delivery vehicles | |
Aharwar et al. | Preparation of Bacterial 8 Cellulose Composites | |
KR101410536B1 (ko) | 키토산 및 나노생활성유리로 형성된 다공성 로드를 포함하는 이중 기공 구조의 스캐폴드 | |
Peng | Hydroxyapatite/Poly (L-Lactic Acid) Fibrous Composites for Bone Tissue Engineering |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
ENP | Entry into the national phase |
Ref document number: 2022520496 Country of ref document: JP Kind code of ref document: A |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21897862 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 18038661 Country of ref document: US |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 21897862 Country of ref document: EP Kind code of ref document: A1 |