CN116474164A - Bone repair stent with functional ion microcapsule and preparation method thereof - Google Patents
Bone repair stent with functional ion microcapsule and preparation method thereof Download PDFInfo
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- CN116474164A CN116474164A CN202310604762.1A CN202310604762A CN116474164A CN 116474164 A CN116474164 A CN 116474164A CN 202310604762 A CN202310604762 A CN 202310604762A CN 116474164 A CN116474164 A CN 116474164A
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- bone repair
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- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 45
- 239000003094 microcapsule Substances 0.000 title claims abstract description 42
- 230000008439 repair process Effects 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 150000002500 ions Chemical class 0.000 claims abstract description 43
- 239000011777 magnesium Substances 0.000 claims abstract description 7
- -1 iron ions Chemical class 0.000 claims abstract description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 3
- 239000011575 calcium Substances 0.000 claims abstract description 3
- 229910052802 copper Inorganic materials 0.000 claims abstract description 3
- 239000010949 copper Substances 0.000 claims abstract description 3
- 229910052742 iron Inorganic materials 0.000 claims abstract description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 3
- 229910052712 strontium Inorganic materials 0.000 claims abstract description 3
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000011701 zinc Substances 0.000 claims abstract description 3
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 3
- 238000002347 injection Methods 0.000 claims description 16
- 239000007924 injection Substances 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 15
- 239000000919 ceramic Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 229920001296 polysiloxane Polymers 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000004005 microsphere Substances 0.000 claims description 8
- 239000011148 porous material Substances 0.000 claims description 7
- 239000005662 Paraffin oil Substances 0.000 claims description 6
- 239000002270 dispersing agent Substances 0.000 claims description 6
- 239000011347 resin Substances 0.000 claims description 6
- 229920005989 resin Polymers 0.000 claims description 6
- 239000002002 slurry Substances 0.000 claims description 6
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 238000007639 printing Methods 0.000 claims description 4
- 238000005086 pumping Methods 0.000 claims description 4
- 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 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000004132 cross linking Methods 0.000 claims description 3
- 238000005238 degreasing Methods 0.000 claims description 3
- 239000012153 distilled water Substances 0.000 claims description 3
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 238000005245 sintering Methods 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 238000004506 ultrasonic cleaning Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 2
- 239000003462 bioceramic Substances 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- 239000000378 calcium silicate Substances 0.000 claims description 2
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 2
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000000017 hydrogel Substances 0.000 abstract description 11
- 230000004071 biological effect Effects 0.000 abstract description 4
- 239000012567 medical material Substances 0.000 abstract description 2
- 230000002138 osteoinductive effect Effects 0.000 abstract description 2
- 239000000463 material Substances 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 3
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 229910001425 magnesium ion Inorganic materials 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 238000000016 photochemical curing Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 229910010293 ceramic material Inorganic materials 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 150000008040 ionic compounds Chemical class 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
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- 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
-
- 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
- A61L27/10—Ceramics or glasses
-
- 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
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/222—Gelatin
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
- A61L27/56—Porous materials, e.g. foams or sponges
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y10/00—Processes of additive manufacturing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y70/00—Materials specially adapted for additive manufacturing
- B33Y70/10—Composites of different types of material, e.g. mixtures of ceramics and polymers or mixtures of metals and biomaterials
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y80/00—Products made by additive manufacturing
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- 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
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- 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
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/622—Microcapsules
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- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
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Abstract
The invention discloses a bone repair stent carrying functional ion microcapsules and a preparation method thereof, and relates to the technical field of medical materials. Aiming at the problems of single performance of the bone scaffold and insufficient osteoinductive performance of the scaffold in a short period after operation, microcapsules carrying functional ions are injected into the bone repair scaffold, wherein the functional ions comprise one or more of calcium, magnesium, zinc, copper, strontium and iron ions. According to the invention, the hydrogel microcapsule coated with functional ions is injected on the porous bracket, so that on one hand, the toughness of the bracket is improved; on the other hand, the biological activity of the scaffold is improved by the ion slow release of the microcapsules in the surface and the aperture of the scaffold.
Description
Technical Field
The invention relates to the technical field of medical materials, in particular to a bone repair stent with functional ion microcapsules and a preparation method thereof.
Background
Today, bone problems are endlessly formed, the market of bone repair materials is urgent, and currently, the main stream of artificial bone repair materials are made of metal materials, biological ceramic materials, high polymer materials and the like. However, bone scaffolds of the sole component tend to be single in nature, with a number of drawbacks. The development of artificial bones is an infinite bionic process, and is supposed to be closer to the relevant characteristics of natural bones in both materials and structures. It is well known that natural bone consists of hydroxyapatite and collagen and has a three-dimensional porous structure.
The photo-curing printing technology is rapidly developed in the field of ceramic manufacturing by virtue of the personalized design and excellent forming speed. In addition, the technology has high forming precision and can accurately form the related structural dimension. In this regard, the technique is widely used in the field of shaping porous bone scaffolds.
The polymer coating material is widely applied to modification of the surface of the stent, so that the biological property and the mechanical property of the stent are improved. However, the direct coating method causes internal porous blockage, cells cannot grow in, air permeability is poor, and finally bone ingrowth fails. In this respect, there is an urgent need for a cell-like structure having a large specific surface area and good air permeability.
In addition, the artificial bone is often not obvious enough in cell induction due to wound inflammation and other problems at the early stage of implantation. In this regard, the addition of functional ions such as mg2+, ag+, cu2+, sr+ may enhance the osteoinductive properties of the scaffold, for which reason injection is often used in medical practice to deliver these functional ions to the wound site. However, these ions are in the free state in the body, on the one hand, in inaccurate positions of action and, on the other hand, often prematurely decomposed. Thus, how to accurately and slowly release ions becomes a difficult problem for researchers.
Disclosure of Invention
Aiming at the problems, the invention provides a bone repair stent with functional ion microcapsules and a preparation method thereof, aiming at the problems of single performance of the bone repair stent and insufficient bone induction performance of the stent in a short period after operation, the bone repair stent with functional ion microcapsules is formed by a photocuring technology, then microspheres with functional ions are injected into holes of the stent by a disposable injector, and freeze drying is carried out, so that a bionic natural bone structure with mutually staggered polymer and biological ceramic is formed, and the bone repair stent with the functional ion microcapsules is obtained.
The technical scheme of the invention is as follows: microcapsules carrying functional ions including one or more of calcium, magnesium, zinc, copper, strontium and iron ions are injected into the bone repair stent.
The microcapsule consists of hydrogel with good biocompatibility, has a three-dimensional network structure, has a similar extracellular matrix structure due to a spherical state, has a large specific surface area, good air permeability and excellent cell adhesion.
The preparation method comprises the following steps:
step 1: mixing ceramic powder, photosensitive resin and a dispersing agent, and stirring for 15 minutes at a rotating speed of 900rpm and a vacuum degree of 0.08mpa to obtain uniformly mixed ceramic slurry;
step 2: introducing the bracket model into a 3D printer, pouring the ceramic slurry into the printer for printing and forming to obtain a ceramic blank body with a three-dimensional porous structure, and degreasing and sintering the blank body after ultrasonic cleaning to obtain the porous bone bracket;
step 3: dissolving a certain amount of anhydrous functional ion compound in PBS to obtain PBS solution containing functional ions;
step 4: placing a certain amount of GelMA solid into a light-resistant centrifuge tube, adding the PBS solution containing the functional ions, preserving heat in a water bath at 50 ℃ for 15 minutes to melt the PBS solution, then adding 0.25wt% of LAP photoinitiator, and fully dissolving the LAP photoinitiator in the water bath at 50 ℃ for 15 minutes to obtain a 3wt% GelMA solution serving as a disperse phase;
step 5: pumping paraffin oil as a continuous phase at one end of a capillary silicone tube by using an injection pump at a certain speed, inserting a disposable injection needle at a position 30-40mm away from the injection end, injecting the disperse phase in the step 4 by using the injection pump at a certain speed, exposing the injected silicone tube to an ultraviolet lamp, crosslinking the microspheres, and finally inserting the other end of the silicone tube into a culture dish filled with the paraffin oil to collect the generated microspheres;
step 6: washing the microcapsule with distilled water for three times, collecting with a syringe, and injecting the microcapsule into the bracket obtained in the step 2;
step 7: and freeze-drying the injected scaffold to obtain the bone repair scaffold carrying the functional ion microcapsules.
Further, the bioceramic powder in the step 1 is one or more of hydroxyapatite, calcium silicate, alumina, zirconia and calcium phosphate.
Further, the mass ratio of the photosensitive resin and the dispersing agent in the step 1 in the mixture is 30% -60% and 2% -3% respectively.
Further, the porosity of the stent model in the step 2 is 65-75%, and the pore diameter is 400-500 nm.
Further, the concentration of the functional ion in the step 3 is 5mM-10mM.
Further, the continuous phase is pumped at a rate of 4ul/min to 6ul/min and the dispersed phase is pumped at a rate of 1ul/min to 3ul/min in step 5.
Further, in the step 5, the inner diameter of the capillary silica gel tube is 0.2-0.6mm, the diameter of the disposable injection needle is smaller than the inner diameter of the capillary tube and is 0.1-0.3mm, and the needle is a needle with a conical inclined opening so as to generate larger shearing force.
Further, the conical opening of the needle faces the outside of the silicone tube when the needle is inserted in step 5.
Further, the diameter of the syringe needle in the step 6 is 0.4-0.8mm larger than the diameter of the capillary silicone tube.
According to the invention, the hydrogel microcapsule coated with functional ions is injected on the porous bracket, so that on one hand, the toughness of the bracket is improved; on the other hand, the biological activity of the scaffold is improved by the ion slow release of the microcapsules in the surface and the aperture of the scaffold.
Compared with the prior art, the invention has the following benefits:
1. according to the invention, the material characteristics of the natural bone are simulated through the combination of the biological ceramic and the polymer hydrogel, so that the toughness and the bioactivity of the bracket are further improved, and the defect of single material performance is overcome.
2. According to the invention, the hydrogel microsphere capable of carrying functional ions is manufactured by a microfluidic technology, so that the effect of ion slow release is achieved, and the biological performance of the scaffold is further improved.
3. The hydrogel microsphere disclosed by the invention has a three-dimensional reticular structure, is large in specific surface area and good in air permeability, and avoids the problem that the coated hydrogel blocks the pores.
4. The microcapsule hydrogel has a cell-like structure, and can promote cell adhesion.
Drawings
FIG. 1 is a schematic diagram of a process for preparing hydrogel microcapsules of the present invention;
FIG. 2 is a photomicrograph of a hydrogel microcapsule of the invention;
FIG. 3 is a view of the aperture and surface microcapsule adhesion mirror of the bone repair stent of the present invention;
FIG. 4 is a fluorescent image of surface cell staining of scaffolds 4 days after co-culture with MC3T3-E1 cells.
Detailed Description
In order to clearly illustrate the technical features of the present patent, the following detailed description will make reference to the accompanying drawings.
As shown in fig. 1, the preparation flow chart of the bone repair stent carrying the functional ion microcapsule comprises the following specific steps:
step 1: mixing hydroxyapatite powder, photosensitive resin and dispersing agent, and stirring in a stirrer at a rotation speed of 800-1000r for 15 minutes to obtain uniform ceramic slurry.
Step 2: and (3) introducing the bracket model into a 3D printer, pouring the ceramic slurry, printing and forming to obtain a ceramic blank with a three-dimensional porous structure, and degreasing and sintering the blank after ultrasonic cleaning to obtain the porous bone bracket.
Step 3: a quantity of anhydrous functional ionic compound was dissolved in PBS to give a PBS solution containing 6mM magnesium ions.
Step 4: placing 300mg of GelMA solid into a light-resistant centrifuge tube, adding 10ml of the PBS solution containing 6mM magnesium ions, preserving heat in a water bath at 50 ℃ for 15 minutes to melt the PBS solution, adding LAP photoinitiator with the mass fraction of 0.25%, and fully dissolving the LAP photoinitiator in the water bath at 50 ℃ for 15 minutes to obtain GelMA solution;
step 5: injecting paraffin oil into one end of a capillary silicone tube with an inner diameter of 0.6mm at a speed of 5ul/min by using an injection pump, inserting a disposable injection needle with a distance of 30mm from the injection end, respectively injecting the PBS solution containing functional ions and the GelMA solution at a speed of 2ul/min by using the injection pump, exposing the silica gel tube after passing through the injection end to an ultraviolet lamp, crosslinking the GelMA solution, and finally inserting the other end into a culture dish filled with paraffin oil to collect the generated microcapsules.
Step 6: washing the microcapsule with distilled water for three times, collecting with a syringe with a needle of 0.8mm, and injecting into the stent obtained in the step 2;
step 7: and freeze-drying the injected scaffold to obtain the bone repair scaffold carrying the functional ion microcapsule.
Further, in the step 1, the mass ratio of the hydroxyapatite powder to the photosensitive resin to the dispersing agent is 47:50:3 respectively.
Further, in the step 2, the porosity of the stent model is 60%, and the pore diameter is 450nm.
Further, in the step 5, the tapered opening of the needle faces the outside of the silicone tube when the needle is inserted.
As shown in FIG. 2, the Mg-containing material prepared by the method 2+ Photomicrographs of microcapsules from which the hydrogel was completely encapsulated with Mg-containing 2+ Is a microsphere of (a). FIG. 3 is a view of a Mg-bearing 2+ The microscopic image of the pore diameter of the bone repair stent of the microcapsule shows that the microcapsule is firmly adhered to the surface of the stent and in the pore diameter.
Carrying Mg obtained by the steps 2+ Sterilizing the microcapsule bone repair stent, placing into 24-hole cell culture plate, and adding MC3T3-E1 cells with concentration of 10 into each hole 4 1mL of cell culture medium with the concentration of 1mL, putting a 24-pore plate into a cell culture box with the temperature of 37 ℃ and the CO2 content of 5% for culture for 4 days, cleaning with PBS every two days in the process, and replacing the culture medium, wherein the culture medium is observed by a confocal microscope, and the surface cells of the bracket show good growth state and adhesion effect, namely, the bracket has good biological activity and bone growth inducibility.
While there have been described what are believed to be the preferred embodiments of the present invention, it will be apparent to those skilled in the art that many more modifications are possible without departing from the principles of the invention.
Claims (10)
1. A bone repair stent carrying functional ion microcapsules, wherein the bone repair stent is injected with the functional ion microcapsules, and the functional ions comprise one or more of calcium, magnesium, zinc, copper, strontium and iron ions.
2. A method of preparing a functional ion microcapsule-carrying bone repair scaffold according to claim 1, comprising the steps of:
step 1: mixing ceramic powder, photosensitive resin and a dispersing agent to obtain uniformly mixed ceramic slurry;
step 2: introducing the bracket model into a 3D printer, pouring the ceramic slurry into the printer for printing and forming to obtain a ceramic blank body with a three-dimensional porous structure, and degreasing and sintering the blank body after ultrasonic cleaning to obtain the porous bone bracket;
step 3: dissolving a certain amount of anhydrous functional ion compound in PBS to obtain PBS solution containing functional ions;
step 4: placing a certain amount of GelMA solid into a light-resistant centrifuge tube, adding the PBS solution containing the functional ions, preserving heat in a water bath at 50 ℃ for 15 minutes to melt the PBS solution, then adding 0.25wt% of LAP photoinitiator, and fully dissolving the LAP photoinitiator in the water bath at 50 ℃ for 15 minutes to obtain a 3wt% GelMA solution serving as a disperse phase;
step 5: pumping paraffin oil as a continuous phase at one end of a capillary silicone tube by using an injection pump at a certain speed, inserting a disposable injection needle at a position 30-40mm away from the injection end, injecting the disperse phase in the step 4 by using the injection pump at a certain speed, exposing the injected silicone tube to an ultraviolet lamp, crosslinking the microspheres, and finally inserting the other end of the silicone tube into a culture dish filled with the paraffin oil to collect the generated microspheres;
step 6: washing the microcapsule with distilled water for three times, collecting with a syringe, and injecting the microcapsule into the bracket obtained in the step 2;
step 7: and freeze-drying the injected scaffold to obtain the bone repair scaffold carrying the functional ion microcapsules.
3. The method for preparing a bone repair scaffold carrying functional ion microcapsules according to claim 2, wherein the bioceramic powder in step 1 is one or more of hydroxyapatite, calcium silicate, alumina, zirconia, and calcium phosphate.
4. The method for preparing a bone repair stent carrying functional ion microcapsules according to claim 2, wherein the photosensitive resin and the dispersing agent in the step 1 account for 30% -60% and 2% -3% of the mixture by mass, respectively.
5. The method for preparing a bone repair stent carrying functional ion microcapsules according to claim 2, wherein the porosity of the stent model in the step 2 is 65% -75%, and the pore size is 400nm-500nm.
6. The method for preparing a bone repair stent carrying functional ion microcapsules according to claim 2, wherein the functional ion concentration in the step 3 is 5mM-10mM.
7. The method of preparing a bone repair stent with functional ion microcapsules according to claim 2, wherein the pumping speed of the continuous phase in the step 5 is 4ul/min-6ul/min, and the pumping speed of the disperse phase is 1ul/min-3ul/min.
8. The method for preparing a bone repair stent carrying functional ion microcapsules according to claim 2, wherein in the step 5, the inner diameter of the capillary silica gel tube is 0.2-0.6mm, the diameter of the disposable injection needle is smaller than the inner diameter of the capillary tube and is 0.1-0.3mm, and the needle is a conical inclined opening needle.
9. The method for preparing a bone repair stent carrying functional ion microcapsules according to claim 2, wherein the tapered opening of the needle faces the outside of the silicone tube when the needle is inserted in step 5.
10. The method for preparing a bone repair stent carrying functional ion microcapsules according to claim 2, wherein the diameter of the syringe needle in the step 6 is 0.4-0.8mm larger than the diameter of the capillary silicone tube.
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