CN117180497A - Composite material with core-shell structure and preparation method and application thereof - Google Patents
Composite material with core-shell structure and preparation method and application thereof Download PDFInfo
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- CN117180497A CN117180497A CN202311052592.7A CN202311052592A CN117180497A CN 117180497 A CN117180497 A CN 117180497A CN 202311052592 A CN202311052592 A CN 202311052592A CN 117180497 A CN117180497 A CN 117180497A
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- bioactive glass
- composite material
- solid
- protein
- lactic acid
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- 239000002131 composite material Substances 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 239000011258 core-shell material Substances 0.000 title claims abstract description 9
- 239000005313 bioactive glass Substances 0.000 claims abstract description 74
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims abstract description 39
- 229920000728 polyester Polymers 0.000 claims abstract description 39
- 239000004005 microsphere Substances 0.000 claims abstract description 37
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 35
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 35
- 239000004310 lactic acid Substances 0.000 claims abstract description 14
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 36
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 33
- 239000004626 polylactic acid Substances 0.000 claims description 33
- 239000007787 solid Substances 0.000 claims description 33
- 229960000448 lactic acid Drugs 0.000 claims description 19
- 239000000155 melt Substances 0.000 claims description 19
- 238000002156 mixing Methods 0.000 claims description 19
- -1 methacryloyl Chemical group 0.000 claims description 17
- 239000007864 aqueous solution Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 16
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 12
- 108010010803 Gelatin Proteins 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 229920000159 gelatin Polymers 0.000 claims description 9
- 239000008273 gelatin Substances 0.000 claims description 9
- 235000019322 gelatine Nutrition 0.000 claims description 9
- 235000011852 gelatine desserts Nutrition 0.000 claims description 9
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- 238000000926 separation method Methods 0.000 claims description 8
- 102000012422 Collagen Type I Human genes 0.000 claims description 7
- 108010022452 Collagen Type I Proteins 0.000 claims description 7
- 108091005647 acylated proteins Proteins 0.000 claims description 7
- 125000005395 methacrylic acid group Chemical group 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 6
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 6
- 238000005507 spraying Methods 0.000 claims description 6
- 102000016942 Elastin Human genes 0.000 claims description 5
- 108010014258 Elastin Proteins 0.000 claims description 5
- 108010022355 Fibroins Proteins 0.000 claims description 5
- 229920002549 elastin Polymers 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 102000008186 Collagen Human genes 0.000 claims description 4
- 108010035532 Collagen Proteins 0.000 claims description 4
- 102000001187 Collagen Type III Human genes 0.000 claims description 4
- 108010069502 Collagen Type III Proteins 0.000 claims description 4
- 229930182843 D-Lactic acid Natural products 0.000 claims description 4
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229920001436 collagen Polymers 0.000 claims description 4
- 229940022769 d- lactic acid Drugs 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 2
- 230000004927 fusion Effects 0.000 abstract description 21
- 239000000463 material Substances 0.000 description 16
- 210000000988 bone and bone Anatomy 0.000 description 12
- 239000005312 bioglass Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 239000008367 deionised water Substances 0.000 description 9
- 229910021641 deionized water Inorganic materials 0.000 description 9
- 230000015556 catabolic process Effects 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 5
- 239000008213 purified water Substances 0.000 description 5
- 230000017423 tissue regeneration Effects 0.000 description 5
- 238000001291 vacuum drying Methods 0.000 description 5
- 150000003863 ammonium salts Chemical class 0.000 description 4
- 150000007942 carboxylates Chemical class 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 229920000193 polymethacrylate Polymers 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000004696 Poly ether ether ketone Substances 0.000 description 3
- 238000006482 condensation reaction Methods 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000011010 flushing procedure Methods 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 229920002530 polyetherether ketone Polymers 0.000 description 3
- 229940057847 polyethylene glycol 600 Drugs 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000010146 3D printing Methods 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 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 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229940085675 polyethylene glycol 800 Drugs 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 238000010526 radical polymerization reaction Methods 0.000 description 2
- 238000010008 shearing Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 241001391944 Commicarpus scandens Species 0.000 description 1
- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000003618 Intervertebral Disc Displacement Diseases 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 229910001069 Ti alloy Inorganic materials 0.000 description 1
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- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
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- 230000001054 cortical effect Effects 0.000 description 1
- 229960001149 dopamine hydrochloride Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010041 electrostatic spinning Methods 0.000 description 1
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 125000003010 ionic group Chemical group 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
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- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
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Abstract
The invention discloses a composite material with a core-shell structure, a preparation method and application thereof, wherein the composite material takes polyester microspheres containing bioactive glass as cores and polymethacrylylated proteins as shells; wherein the polyester microsphere containing the bioactive glass is prepared from the bioactive glass and lactic acid in a mass ratio of 1:8-15. The composite material has higher strength, better toughness and better safety, and can be used for forming an interbody fusion cage.
Description
Technical Field
The invention relates to a composite material and a preparation method and application thereof, in particular to a composite material with a core-shell structure for forming an interbody fusion cage and a preparation method and application thereof.
Background
The intervertebral fusion device is used for the intervertebral bone grafting fusion internal fixation of spine fracture, slippage, instability and disc herniation, can restore the height of the intervertebral space and physiological curvature, provides initial stability for the diseased vertebrae, promotes intervertebral bone fusion and reduces the dosage of autologous bone to a certain extent. Interbody fusion is one of the primary methods of treating degenerative diseases of the spine today.
The polyether-ether-ketone is a thermoplastic polymer, has the characteristics of high strength, high rigidity, corrosion resistance, hydrolysis resistance and the like, has the elastic modulus between cortical bone and cancellous bone, is used as a raw material of an intervertebral fusion device which is clinically used at present and can not be degraded and absorbed, has newer stress shielding effect compared with titanium alloy, can better promote bone healing, can show better fusion rate and lower sinking rate at early implantation stage as the intervertebral fusion device, has lower surface osteogenesis effect due to hydrophobic polyether-ether-ketone surface along with the extension of implantation time, cannot realize bone regeneration between vertebral bodies, and gradually reduces intervertebral fusion rate after long-term implantation.
With the pursuit of high quality life, more and more clinical researchers wish to be able to obtain better cage materials: good biocompatibility and no toxic or side effect; the stability of the intervertebral space can be ensured due to the proper biomechanical characteristics; can synchronously promote the regeneration of the interbody bone, and then the interbody fusion cage is gradually degraded and absorbed, so that the patient really recovers to the normal living state.
Polylactic acid is used as a common absorbable implant material for bone internal fixation, has good biocompatibility and biological force maintenance period matched with bone growth, but has weaker biological mechanical property compared with polyether ether ketone and lacks bone induction activity.
Although the composite of polylactic acid and bioactive glass can provide initial mechanical properties with larger rigidity and strength, the composite is fragile and poor in toughness, so that the composite is easy to break after the material is implanted, and the safe fixation of a patient in the postoperative recovery period cannot be ensured.
CN114870076a discloses a 3D printing composite material for an interbody fusion cage and a preparation method thereof, and the 3D printing composite material comprises the following raw materials in parts by weight: 40-60 parts of 45S bioglass, 40-60 parts of SrO, 1-3 parts of dopamine hydrochloride, 20-60 parts of Tris-HCl buffer solution, 3-6 parts of L-polylactic acid (PLLA), 1-3 parts of absolute ethyl alcohol and 3-5 parts of distilled water; including Sr/Bioglass compounding and modification, mixed powder preparation and Sr/Bioglass/PLLA scaffold/fusion device preparation. The patent document is silent about strength and elongation at break.
CN110564123a discloses a polylactic acid-bioglass composite material, wherein the polylactic acid is modified polylactic acid, and the polylactic acid comprises carboxylate or ammonium salt, wherein one or more of metal ions lithium, sodium and potassium in the carboxylate; the ammonium salt contains one or more of chlorine, bromine and iodine. The bioglass is modified bioglass. The ionic group for modifying the surface of the bioglass comprises sulfonate, carboxylate or ammonium salt. Wherein the sulfonate/carboxylate contains one or more of metal ions lithium, sodium and potassium; the ammonium salt contains one or more of chlorine, bromine and iodine. The composite material of this patent document is less safe for use in an intervertebral fusion device.
CN106983910a discloses a preparation method of polylactic acid composite bioglass tissue repair material, which comprises the following steps: preparing polylactic acid solution, preparing bioglass solution and carrying out electrostatic spinning to obtain the repairing material. Wherein polylactic acid can improve the mechanical property of the material, and bioglass can improve the medical property of the material. The tissue repair material prepared by the patent document has good mechanical property, tissue repair property and medicine adhesiveness.
Disclosure of Invention
Accordingly, it is an object of the present invention to provide a composite material having a core-shell structure, which has high strength, high toughness, and high safety, and can be used to form an intervertebral fusion device. Another object of the present invention is to provide a method for preparing the above composite material. It is a further object of the present invention to provide the use of the above composite material. The invention adopts the following technical scheme to realize the aim.
In one aspect, the invention provides a composite material with a core-shell structure, which takes polyester microspheres containing bioactive glass as a core and polymethacrylylated protein as a shell;
wherein, the polyester microsphere containing bioactive glass is prepared from bioactive glass and lactic acid with the mass ratio of 1:8-15;
wherein the polymethacrylylated protein is polymerized from a methacryloylated protein; the methacryloyl protein is at least one selected from methacryloyl type I collagen, methacryloyl type III collagen, methacryloyl silk fibroin, methacryloyl elastin, methacryloyl recombinant humanized collagen and methacryloyl gelatin.
In another aspect, the present invention also provides a method for preparing the composite material as described above, comprising the steps of:
1) Providing polyester microspheres comprising bioactive glass;
2) Providing an aqueous solution of a methacryloylated protein;
3) Mixing polyester microspheres containing bioactive glass with a methacrylic acylated protein aqueous solution, performing ultrasonic vibration, and performing solid-liquid separation to obtain a solid; and washing and freeze-drying the obtained solid to obtain the composite material.
According to the preparation method of the present invention, preferably, the step 1) includes the following specific steps:
a) Mixing bioactive glass and lactic acid in the mass ratio of 1:8-15, and then reacting at 150-220 ℃ to obtain polylactic acid containing bioactive glass;
b) Melting and blending polylactic acid containing bioactive glass and a high molecular compound in a mass ratio of 10-25:1 to obtain a melt;
c) Dispersing the melt into a good solvent to obtain a solid; and drying the solid to obtain the polyester microsphere containing the bioactive glass.
According to the production method of the present invention, preferably, in the step a), the lactic acid is at least one selected from the group consisting of L-lactic acid, DL-lactic acid and D-lactic acid.
According to the preparation method of the present invention, preferably, in the step b), the polymer compound is one or more selected from polyethylene glycol, polyvinyl alcohol and polyvinylpyrrolidone.
According to the production method of the present invention, preferably, in the step c), the good solvent is one selected from the group consisting of water, dimethyl sulfoxide, and N, N-dimethylformamide.
According to the preparation method of the present invention, preferably, in the step c), the dispersing the melt into the good solvent specifically includes: spraying the melt into a good solvent by adopting a micro-flow extruder; wherein the aperture of the spray nozzle used by the micro-flow extruder is 30-80 mu m.
According to the preparation method of the present invention, preferably, in the step 2), the mass ratio of the methacryloylated protein to water is 1:5 to 10.
According to the preparation method of the present invention, preferably, in the step 3), the solid obtained by solid-liquid separation is washed with water for a plurality of times, and freeze-dried at-30 ℃ or lower to obtain the composite material.
In a further aspect, the invention also provides the use of a composite material according to the above in the formation of an intervertebral fusion.
The composite material of the invention takes polyester microsphere containing bioactive glass as a core and polymethacrylate protein as a shell. The composite material has high strength and good toughness, and can be used as an absorbable interbody fusion cage material which can provide stable fixation required by enough interbody bone fusion time and synchronously induce bone tissue regeneration and finally safely degrade. The preparation method of the composite material can avoid using a catalyst, thereby avoiding the harm of catalyst residues.
Detailed Description
The invention will be further described with reference to specific embodiments, but the scope of the invention is not limited thereto.
< composite Material >
The present invention provides a composite material having a core-shell structure that can be used to form an interbody cage. The composite material is degradable and absorbable, and has good safety and extremely low toxicity.
The composite material of the invention takes polyester microsphere containing bioactive glass as a core and polymethacrylate protein as a shell. Has a core-shell structure. The composite material has high elongation at break and high strength, is degradable, and can be used as a material for forming a degradable and absorbable interbody fusion cage.
Wherein the polyester microsphere containing the bioactive glass is prepared from the bioactive glass and lactic acid in a mass ratio of 1:8-15. The lactic acid is at least one selected from L-lactic acid, DL-lactic acid and D-lactic acid. The bioactive glass is silicate material, and contains SiO as main component 2 、Na 2 O、CaO、P 2 O 5 . The source of the bioactive glass is not particularly limited and is commercially available.
The mass ratio of the bioactive glass to the lactic acid may be 1:8-15, preferably 1:9-14, more preferably 1:10-12.
In the present invention, the polymethacrylylated protein is polymerized from a methacryloylated protein. Specifically, the polymethacrylylated protein is formed by free radical polymerization of the side chain of the methacryloylated protein.
The methacryloylated protein is at least one selected from the group consisting of methacryloylated type I collagen, methacryloylated type III collagen, methacryloylated silk fibroin, methacryloylated elastin, methacryloylated recombinant humanized collagen and methacryloylated gelatin, preferably one selected from the group consisting of methacryloylated type I collagen, methacryloylated silk fibroin, methacryloylated elastin and methacryloylated gelatin, more preferably methacryloylated type I collagen or methacryloylated gelatin.
Compared with a compound formed by polylactic acid and bioactive glass, the composite material has better toughness and higher elongation at break. The strength of the composite material of the present invention is higher than that of a composite formed from polylactic acid and proteins.
< preparation method >
The invention also provides a preparation method of the composite material, which comprises the following steps: 1) Providing polyester microspheres comprising bioactive glass; 2) Providing an aqueous solution of a methacryloylated protein; 3) Forming a composite material.
In the step (1) of the process,
step 1) comprises the following specific steps:
a) Mixing bioactive glass and lactic acid in the mass ratio of 1:8-15, and then reacting at 150-220 ℃ to obtain polylactic acid containing bioactive glass;
b) Melting and blending polylactic acid containing bioactive glass and a high molecular compound at 190-220 ℃ according to the mass ratio of 10-25:1 to obtain a melt;
c) Dispersing the melt into a good solvent to obtain a solid, and drying the solid to obtain the polyester microsphere containing bioactive glass.
Wherein in step a), the lactic acid is at least one selected from the group consisting of L-lactic acid, DL-lactic acid and D-lactic acid. The bioactive glass is silicate material, and contains SiO as main component 2 、Na 2 O、CaO、P 2 O 5 . The mass ratio of the bioactive glass to the lactic acid may be 1:8-15, preferably 1:9-14, more preferably 1:10-12.
Mixing bioactive glass and lactic acid, and dewatering condensation reaction at 150-220 deg.c. The reaction temperature of the dehydration condensation reaction may be 150 to 220 ℃, preferably 160 to 210 ℃, more preferably 170 to 200 ℃. The reaction time may be 5 to 10 hours, preferably 6 to 9 hours, more preferably 6 to 8 hours.
In step b), the molecular weight of the polymer compound is 400 to 2000. The polymer compound is selected from one or more of polyethylene glycol, polyvinyl alcohol and polyvinylpyrrolidone, preferably from one of polyethylene glycol and polyvinyl alcohol.
The mass ratio of polylactic acid and polymer compound containing bioactive glass may be 10-25:1, preferably 13-20:1, more preferably 15-17:1.
The temperature of the melt blending may be 190 to 220 ℃, preferably 200 to 220 ℃, more preferably 205 to 210 ℃. The time for melt blending may be 10 to 40 minutes, preferably 15 to 30 minutes, more preferably 18 to 20 minutes.
In the present invention, melt blending can be performed using a rheometer known in the art.
In the step c), the good solvent is selected from one of water, dimethyl sulfoxide and N, N-dimethylformamide. The water is purified water, such as deionized water, purified water or distilled water.
The dispersing of the melt into the good solvent specifically comprises: spraying the melt into a good solvent by adopting a micro-flow extruder; wherein the aperture of the nozzle used in the micro-flow extruder is 30-80 μm, preferably 40-70 μm.
And (3) drying the solid in vacuum to obtain the polyester microsphere containing the bioactive glass. The temperature of the vacuum drying may be 40 to 60 ℃, preferably 50 to 60 ℃, and the time of the vacuum drying may be 4 to 8 hours, preferably 5 to 7 hours.
In the step 2) of the process, the process is carried out,
the mass ratio of the methacryloyl protein to water is 1:5 to 10, preferably 1:7 to 10, more preferably 1:9 to 10. The water herein is purified water, preferably deionized water, purified water or distilled water. The methacryloylated protein is at least one selected from the group consisting of methacryloylated type I collagen, methacryloylated type III collagen, methacryloylated silk fibroin, methacryloylated elastin, methacryloylated recombinant humanized collagen and methacryloylated gelatin.
In the step 3) of the method,
mixing polyester microspheres containing bioactive glass with a methacrylic acylated protein aqueous solution, performing ultrasonic vibration, and performing solid-liquid separation to obtain a solid; the obtained solid was washed and freeze-dried to obtain a composite material. The composite material with the polyester microsphere containing bioactive glass as a core and the polymethacrylate protein as a shell is obtained.
The mass ratio of the polyester microsphere containing the bioactive glass to the methacryloyl protein is 4-12:1, preferably 7-12:1, more preferably 8-10:1, and even more preferably 9-10:1.
The mass volume ratio of the polyester microsphere containing the bioactive glass to the methacrylic acid protein aqueous solution is 1 g:15-35 mL, preferably 1 g:20-30 mL, and more preferably 1 g:20-25 mL.
The ultrasonic vibration time is 10 to 25 minutes, preferably 15 to 25 minutes, more preferably 15 to 20 minutes. The ultrasonic frequency is 50 to 300kHz, preferably 150 to 300kHz, more preferably 240 to 300kHz. The invention speculates that the porous surface of the polyester microsphere containing bioactive glass reacts with water and air under the action of ultrasonic vibration to generate a large amount of free radicals (the free radicals can comprise hydroxyl free radicals OH and superoxide anion free radicals O 2 - ) Thereby catalyzing the carbon-carbon double bond existing on the side chain of the methacrylic acylated protein to generate free radical polymerization, and forming the composite material with the polyester microsphere containing bioactive glass as a core and the polymethacrylylated protein as a shell.
The washing adopts water, and the water is purified water, such as deionized water. The washing may be performed three or more times, for example, preferably four or more times. The temperature of freeze-drying may be-30℃or lower, preferably-40℃or lower.
In the preparation method, no catalyst is required to be additionally added, and the obtained composite material has no catalyst residue, so that the composite material has no toxicity of the catalyst residue and is safer.
< use >
The present invention also provides the use of a composite material as described above for forming an intervertebral cage. The composite material has high strength, good toughness, degradability, and can promote bone tissue regeneration and absorption. Can be used as a material for forming an intervertebral fusion device.
< analytical methods >
Elongation at break test: firstly, according to YY/T1806.1-2021, part 1 of an in vitro degradation Performance evaluation method of biomedical materials: the requirement of degradable polyesters is that in vitro accelerated degradation tests are carried out at 70 ℃. Samples were taken at 0 day, 1 week, 2 weeks, 4 weeks, 6 weeks of degradation, respectively, according to GB/T1040.2-2006 part 2 of determination of Plastic tensile Properties: the elongation at break test is carried out as required by the test conditions for molding and extrusion of plastics.
Shear strength test: firstly, a sample plate with the diameter of 50mm, the thickness of 1mm and a circular hole with the diameter of 11mm is prepared by injection molding according to the requirement of 6 samples in HG/T3839 perforation method of plastic shearing strength test, and then the part 1 of the in vitro degradation performance evaluation method of biomedical materials is carried out according to YY/T1806.1-2021: the requirement of degradable polyesters is that in vitro accelerated degradation tests are carried out at 70 ℃. Samples were taken at 0 day, 1 week, 2 weeks, 4 weeks, and 6 weeks of degradation, respectively, and shear strength testing was performed according to the 7 test procedures in HG/T3839-2006, perforation method for Plastic shear Strength test.
Sources of part of the raw materials in the following examples:
bioactive glass: purchased from wuhank biomedical technologies limited.
Methacryloylated gelatin: purchased from Jiangyin Set Biotechnology Co.
Preparation example 1
Mixing bioactive glass and L-lactic acid in the mass ratio of 1:10, and then dehydrating and condensing at 160 ℃ for 6 hours to obtain the polylactic acid containing bioactive glass.
Polylactic acid and polyethylene glycol 800 containing bioactive glass with the mass ratio of 15:1 are added into a rheometer and are melt-blended for 18min at 205 ℃ to obtain a melt.
Spraying the melt into deionized water through a micro-flow extruder with the nozzle diameter of 10 mu m to obtain precipitated solid, flushing the precipitated solid with deionized water for 5 times to remove polyethylene glycol 800 to obtain solid, and vacuum drying the solid at 50 ℃ for 6 hours to obtain the polyester microsphere containing bioactive glass.
Example 1
2g of the polyester microspheres containing bioactive glass prepared in preparation example 1 were prepared.
The methacryloylated gelatin with the mass ratio of 1:10 is mixed with water at 37 ℃ to form a viscous aqueous solution, namely the methacryloylated protein aqueous solution.
Adding 2g of polyester microspheres containing bioactive glass into 50mL of methacrylic acylated protein aqueous solution, mixing, ultrasonically vibrating for 10min, and carrying out solid-liquid separation to obtain a solid; the obtained solid was washed 3 times with water and freeze-dried at-40 ℃ to obtain a composite material with the bioactive glass-containing polyester microspheres as the core and the polymethacrylylated protein as the shell.
Preparation example 2
Mixing bioactive glass and L-lactic acid in the mass ratio of 1:12, and then dehydrating and condensing at 170 ℃ for 6 hours to obtain the polylactic acid containing bioactive glass.
The polylactic acid and the polyvinyl alcohol containing the bioactive glass with the mass ratio of 15:1 are added into a rheometer and are melt-blended for 18min at 205 ℃ to obtain a melt.
Spraying the melt into deionized water through a micro-flow extruder with the nozzle diameter of 10 mu m to obtain precipitated solid, flushing the precipitated solid with deionized water for 5 times to remove polyvinyl alcohol to obtain solid, and vacuum drying the solid at 50 ℃ for 6 hours to obtain the polyester microsphere containing bioactive glass.
Example 2
2g of the polyester microspheres containing bioactive glass prepared in preparation example 2 were prepared.
The methacryloylated type I collagen with the mass ratio of 1:9 is mixed with water at 37 ℃ to form a viscous aqueous solution, namely the methacryloylated protein aqueous solution.
Adding 2g of polyester microspheres containing bioactive glass into 50mL of methacrylic acylated protein aqueous solution, mixing, ultrasonically vibrating for 15min, and carrying out solid-liquid separation to obtain a solid; the obtained solid was washed 3 times with water and freeze-dried at-40 ℃ to obtain a composite material with the bioactive glass-containing polyester microspheres as the core and the polymethacrylylated protein as the shell.
Preparation example 3
Mixing bioactive glass with DL lactic acid and L-lactic acid in a mass ratio of 1:6:6, and performing dehydration condensation reaction at 170 ℃ for 8 hours to obtain polylactic acid containing bioactive glass (specifically, a polylactic acid and poly DL lactic acid compound containing bioactive glass).
Polylactic acid and polyethylene glycol 600 (PEG) containing bioactive glass with mass ratio of 15:1 600 ) Added into a rheometer and melt blended at 205 ℃ for 18min to obtain a melt.
Spraying the melt into deionized water through a micro-flow extruder with the nozzle diameter of 10 mu m to obtain precipitated solid, flushing the precipitated solid with deionized water for 5 times to remove polyethylene glycol 600 to obtain solid, and vacuum drying the solid at 50 ℃ for 6 hours to obtain the polyester microsphere containing bioactive glass.
Example 3
2g of the polyester microspheres containing bioactive glass prepared in preparation example 3 were prepared.
The methacryloylated gelatin with the mass ratio of 1:10 is mixed with water at 37 ℃ to form a viscous aqueous solution, namely the methacryloylated protein aqueous solution.
Adding 2g of polyester microspheres containing bioactive glass into 50mL of methacrylic acylated protein aqueous solution, mixing, ultrasonically vibrating for 15min, and carrying out solid-liquid separation to obtain a solid; the obtained solid was washed 3 times with water and freeze-dried at-40 ℃ to obtain a composite material with the bioactive glass-containing polyester microspheres as the core and the polymethacrylylated protein as the shell.
The composites of example 1, example 2, example 3, polylactic acid of molecular weight 120000 and blends of polylactic acid of molecular weight 120000 with bioactive glass materials were each subjected to performance testing. The results of elongation at break are shown in Table 1 and the results of shear strength are shown in Table 2.
TABLE 1
As can be seen from Table 1, the elongation at break of the composites prepared in examples 1, 2 and 3 were significantly higher than that of the blend of polylactic acid having a molecular weight of 120000, polylactic acid having a molecular weight of 120000 and bioactive glass.
TABLE 2
As can be seen from Table 2, the shear strength of the composites prepared in example 1, example 2 and example 3 were significantly higher than the blend of polylactic acid having a molecular weight of 120000, polylactic acid having a molecular weight of 120000 and bioactive glass.
In summary, the invention uses the polyester microsphere containing bioactive glass as a core and uses the polymethacrylate protein as a shell, compared with the pure polylactic acid or the blend of the polylactic acid and the bioactive glass, the invention can effectively improve the elongation at break and the shearing strength of the composite material and prolong the effective mechanical property maintenance period of the composite material. The composite material prepared by the invention can be used for preparing renewable interbody fusion cage.
Any modifications, improvements, substitutions that may occur to one of ordinary skill in the art without departing from the spirit of the invention are within the scope of the invention.
Claims (10)
1. A composite material with a core-shell structure is characterized in that polyester microspheres containing bioactive glass are taken as cores, and polymethacrylylated proteins are taken as shells;
wherein, the polyester microsphere containing bioactive glass is prepared from bioactive glass and lactic acid with the mass ratio of 1:8-15;
wherein the polymethacrylylated protein is polymerized from a methacryloylated protein; the methacryloyl protein is at least one selected from methacryloyl type I collagen, methacryloyl type III collagen, methacryloyl silk fibroin, methacryloyl elastin, methacryloyl recombinant humanized collagen and methacryloyl gelatin.
2. The method of preparing a composite material according to claim 1, comprising the steps of:
1) Providing polyester microspheres comprising bioactive glass;
2) Providing an aqueous solution of a methacryloylated protein;
3) Mixing polyester microspheres containing bioactive glass with a methacrylic acylated protein aqueous solution, performing ultrasonic vibration, and performing solid-liquid separation to obtain a solid; and washing and freeze-drying the obtained solid to obtain the composite material.
3. The preparation method according to claim 2, wherein step 1) comprises the following specific steps:
a) Mixing bioactive glass and lactic acid in the mass ratio of 1:8-15, and then reacting at 150-220 ℃ to obtain polylactic acid containing bioactive glass;
b) Melting and blending polylactic acid containing bioactive glass and a high molecular compound in a mass ratio of 10-25:1 to obtain a melt;
c) Dispersing the melt into a good solvent to obtain a solid; and drying the solid to obtain the polyester microsphere containing the bioactive glass.
4. The method according to claim 3, wherein in the step a), the lactic acid is at least one selected from the group consisting of L-lactic acid, DL-lactic acid and D-lactic acid.
5. The method according to claim 3, wherein in the step b), the polymer compound is one or more selected from the group consisting of polyethylene glycol, polyvinyl alcohol and polyvinylpyrrolidone.
6. The method according to claim 3, wherein in the step c), the good solvent is one selected from the group consisting of water, dimethyl sulfoxide, and N, N-dimethylformamide.
7. The method of claim 3, wherein in step c), the dispersing the melt into the good solvent comprises: spraying the melt into a good solvent by adopting a micro-flow extruder; wherein the aperture of the spray nozzle used by the micro-flow extruder is 30-80 mu m.
8. The process according to claim 3, wherein in the step 2), the mass ratio of the methacryloylated protein to water is 1:5 to 10.
9. The process according to claim 3, wherein in step 3), the solid obtained by the solid-liquid separation is washed with water a plurality of times and freeze-dried at a temperature of-30 ℃ or lower to obtain the composite material.
10. Use of the composite material of claim 1 for forming an intersomatic cage.
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