CN112773944A - Bone repair stent with microelement-loaded coating and preparation method thereof - Google Patents
Bone repair stent with microelement-loaded coating and preparation method thereof Download PDFInfo
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- CN112773944A CN112773944A CN202011332592.9A CN202011332592A CN112773944A CN 112773944 A CN112773944 A CN 112773944A CN 202011332592 A CN202011332592 A CN 202011332592A CN 112773944 A CN112773944 A CN 112773944A
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- gelatin
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- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 41
- 230000008439 repair process Effects 0.000 title claims abstract description 41
- 239000011248 coating agent Substances 0.000 title claims abstract description 38
- 238000000576 coating method Methods 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 108010010803 Gelatin Proteins 0.000 claims abstract description 98
- 229920000159 gelatin Polymers 0.000 claims abstract description 98
- 239000008273 gelatin Substances 0.000 claims abstract description 98
- 235000019322 gelatine Nutrition 0.000 claims abstract description 98
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 98
- 239000011573 trace mineral Substances 0.000 claims abstract description 42
- 235000013619 trace mineral Nutrition 0.000 claims abstract description 41
- 239000000919 ceramic Substances 0.000 claims abstract description 25
- 238000004132 cross linking Methods 0.000 claims abstract description 16
- 239000011777 magnesium Substances 0.000 claims abstract description 11
- 229910052710 silicon Inorganic materials 0.000 claims abstract description 11
- 239000010703 silicon Substances 0.000 claims abstract description 11
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 10
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 9
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910052802 copper Inorganic materials 0.000 claims abstract description 9
- 239000010949 copper Substances 0.000 claims abstract description 9
- 229910052712 strontium Inorganic materials 0.000 claims abstract description 9
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000011701 zinc Substances 0.000 claims abstract description 9
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 9
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 8
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 8
- 239000011575 calcium Substances 0.000 claims abstract description 8
- 230000015556 catabolic process Effects 0.000 claims abstract description 6
- 238000006731 degradation reaction Methods 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 65
- 238000001035 drying Methods 0.000 claims description 36
- 239000007864 aqueous solution Substances 0.000 claims description 12
- AZKVWQKMDGGDSV-BCMRRPTOSA-N Genipin Chemical compound COC(=O)C1=CO[C@@H](O)[C@@H]2C(CO)=CC[C@H]12 AZKVWQKMDGGDSV-BCMRRPTOSA-N 0.000 claims description 11
- AZKVWQKMDGGDSV-UHFFFAOYSA-N genipin Natural products COC(=O)C1=COC(O)C2C(CO)=CCC12 AZKVWQKMDGGDSV-UHFFFAOYSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- 238000004108 freeze drying Methods 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 238000001291 vacuum drying Methods 0.000 claims description 7
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 claims description 6
- 229910001425 magnesium ion Inorganic materials 0.000 claims description 6
- 230000008595 infiltration Effects 0.000 claims description 5
- 238000001764 infiltration Methods 0.000 claims description 5
- 239000010410 layer Substances 0.000 claims description 5
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 4
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 229910001431 copper ion Inorganic materials 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 229910001427 strontium ion Inorganic materials 0.000 claims description 4
- 238000012546 transfer Methods 0.000 claims description 4
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 3
- 229910001424 calcium ion Inorganic materials 0.000 claims description 3
- 238000001727 in vivo Methods 0.000 claims description 3
- -1 silicon ions Chemical class 0.000 claims description 3
- 239000002344 surface layer Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000011164 ossification Effects 0.000 abstract description 4
- 239000003431 cross linking reagent Substances 0.000 abstract description 3
- 239000012567 medical material Substances 0.000 abstract description 2
- 230000007998 vessel formation Effects 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 238000005303 weighing Methods 0.000 description 4
- 230000007547 defect Effects 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 description 3
- 229940061634 magnesium sulfate heptahydrate Drugs 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000031877 prophase Effects 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001768 cations Chemical group 0.000 description 1
- 229910010293 ceramic material Inorganic materials 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000005470 impregnation Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000001089 mineralizing effect Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 229940047908 strontium chloride hexahydrate Drugs 0.000 description 1
- AMGRXJSJSONEEG-UHFFFAOYSA-L strontium dichloride hexahydrate Chemical compound O.O.O.O.O.O.Cl[Sr]Cl AMGRXJSJSONEEG-UHFFFAOYSA-L 0.000 description 1
- PWYYWQHXAPXYMF-UHFFFAOYSA-N strontium(2+) Chemical compound [Sr+2] PWYYWQHXAPXYMF-UHFFFAOYSA-N 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
Classifications
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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
-
- 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
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
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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
- A61L27/54—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
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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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
- 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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- Oral & Maxillofacial Surgery (AREA)
- Dermatology (AREA)
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Abstract
The invention relates to the technical field of medical materials, and particularly discloses a bone repair support with a microelement-loaded coating and a preparation method thereof. The bone repair scaffold comprises a porous ceramic scaffold body and a gelatin coating on the surface of the porous ceramic scaffold body, wherein the gelatin coating contains trace elements, and the trace elements are selected from one or more of magnesium, copper, calcium, zinc, strontium and silicon. According to the invention, the microelement gelatin coating is loaded on the porous ceramic support, so that the strength and toughness of the porous ceramic bone repair support are improved, the degradation rate of the gelatin can be controlled by controlling the crosslinking degree of the gelatin and the crosslinking agent, the release rate of the microelement is further controlled, the bone formation and the blood vessel formation are facilitated, and the bone repair is further promoted. Furthermore, different trace elements are distributed at different positions of the gelatin coating, so that the sequential release of the trace elements at different times is realized, and the repair capability of bone repair at each time stage is promoted more specifically.
Description
Technical Field
The invention relates to the technical field of medical materials, in particular to a bone repair support with a microelement-loaded coating.
Background
The problem of bone defect repair is always a difficult problem to be solved urgently in clinic. The appearance of the bioactive ceramic provides a new solution for bone defect repair, and the bioactive ceramic has good biocompatibility and osteoconductivity and can effectively promote the formation of new bones at bone defect positions. But the biological ceramic porous bone repair scaffold has the problems of low strength and poor toughness.
Gelatin is a product of collagen heat deformation or partial hydrolysis, and has good biocompatibility and biodegradability. The gelatin coating porous ceramic bone repair bracket prepared by the vacuum impregnation technology can improve the strength and toughness of the porous bone repair bracket.
If microelements which are beneficial to osteogenesis and angiogenesis can be loaded in the gelatin coating, the degradation rate of the gelatin is controlled by controlling the crosslinking degree of the gelatin and the crosslinking agent, and the release of the microelements is controlled according to different requirements in different periods, the repairing effect of bone repair can be effectively promoted.
Disclosure of Invention
In order to solve the problems in the prior art, the invention aims to provide a bone repair scaffold with a microelement-loaded coating and a preparation method thereof.
In order to realize the purpose of the invention, the technical scheme of the invention is as follows:
in a first aspect, the invention provides a bone repair scaffold with a trace element loaded coating, which comprises a porous ceramic scaffold body and a gelatin coating on the surface of the porous ceramic scaffold body, wherein the gelatin coating contains trace elements.
Wherein the trace elements are selected from one or more of magnesium, copper, calcium, zinc, strontium and silicon.
Furthermore, the gelatin coating is subjected to crosslinking treatment and aims to delay the dissolution of gelatin and further control the release rate of trace elements in the coating, and the time for complete degradation of the crosslinked gelatin coating in vivo is about 14-60 days.
Preferably, the gelatin coating is divided into two layers, the surface layer contains one or more trace elements selected from magnesium and copper, and the subsurface layer contains one or more trace elements selected from calcium, zinc, strontium and silicon. The staged release during application is realized through different distribution positions of the trace elements in the gelatin coating.
For example, magnesium, copper and other elements are placed in the surface layer of the coating, and can promote the proliferation and migration of prophase endothelial cells through early release, so as to enhance prophase neovascularization; and calcium, zinc, strontium, silicon and other elements are placed in the subsurface layer of the coating to delay the release of the elements, and the release of the elements in a relatively later period is utilized to realize the purposes of promoting the proliferation and differentiation of osteoblasts and mineralizing extracellular matrix.
In a second aspect, the invention provides a preparation method of the bone repair scaffold, which comprises the following steps:
(1) preparing a gelatin aqueous solution with the mass concentration of 2.5-10%, and dissolving the trace elements in the solution to obtain a trace element-loaded gelatin solution;
immersing the porous ceramic support into the gelatin solution, carrying out infiltration treatment for 5-15 min in a vacuum drying oven with the temperature of 60 ℃ and the pressure of 0.08MPa, then taking out a sample, and drying for 8-12 h in a drying oven with the temperature of 50 ℃;
(2) preparing 1-20 mg/mL genipin solution by using absolute ethyl alcohol as a solvent, and immersing the sample dried in the step (1) into the genipin solution for 1-24 h at room temperature to perform a crosslinking reaction; and (3) taking out the sample after crosslinking is finished, drying the sample in a drying oven at the temperature of 50 ℃ for 8-12 h, and then freeze-drying the sample at the temperature of-20 ℃ to obtain the bone repair scaffold.
Further, the concentration of the trace elements in the gelatin solution is 5 mu mol/L-10 mmol/L; wherein, the preferable concentration of magnesium ions is 2.5-7.5 mmol/L, the preferable concentration of copper ions is 20-30 mu mol/L, the preferable concentration of calcium ions is 2-8 mmol/L, the preferable concentration of zinc ions is 10-20 mu mol/L, the preferable concentration of strontium ions is 0.1-1 mmol/L, and the preferable concentration of silicon ions is 5-20 mu mol/L.
The trace elements are added in a cation form, and anions can be selected from chloride ions or sulfate ions.
Furthermore, the mass concentration of the gelatin aqueous solution is preferably 7.5%, and the mass concentration can avoid the blockage of the porous ceramic material caused by overhigh concentration, and can effectively delay the dissolution time of the gelatin coating, thereby achieving the optimal slow release effect on trace elements.
In view of the foregoing preferred embodiment, the preparation method of the bone repair scaffold specifically includes the following steps:
(1) preparing a gelatin aqueous solution with the mass concentration of 2.5-10%, and dissolving first trace elements in the solution to obtain a gelatin solution A;
immersing the porous ceramic support into gelatin solution A, carrying out infiltration treatment for 5-15 min in a vacuum drying oven with the temperature of 60 ℃ and the pressure of 0.08MPa, then taking out a sample, and drying for 8-12 h in a drying oven with the temperature of 50 ℃;
(2) preparing a gelatin aqueous solution with the mass concentration of 2.5-10%, and dissolving a second type of trace elements in the solution to obtain a gelatin solution B;
dripping a gelatin solution B on the dried sample obtained in the step (1) by using a liquid transfer gun to uniformly cover the surface of the sample with the gelatin solution B, and then drying the sample in a drying oven at the temperature of 50 ℃ for 8-12 h;
(3) preparing 1-20 mg/mL genipin solution by using absolute ethyl alcohol as a solvent, and immersing the sample dried in the step (2) into the genipin solution for 1-24 h at room temperature to perform a crosslinking reaction; and (3) taking out the sample after crosslinking is finished, drying the sample in a drying oven at the temperature of 50 ℃ for 8-12 h, and then freeze-drying the sample at the temperature of-20 ℃ to obtain the bone repair scaffold.
Further preferably, the first type of trace elements are selected from one or more of calcium, zinc, strontium and silicon, wherein the preferable concentration of calcium ions in the gelatin solution A is 2-8 mmol/L, the preferable concentration of zinc ions in the gelatin solution A is 10-20 μmol/L, the preferable concentration of strontium ions in the gelatin solution A is 0.1-1 mmol/L, and the preferable concentration of silicon ions in the gelatin solution A is 5-20 μmol/L.
Further preferably, the second type of trace element is selected from one or more of magnesium and copper, wherein the preferred concentration of magnesium ions in the gelatin solution B is 2.5-7.5 mmol/L, and the preferred concentration of copper ions in the gelatin solution B is 20-30 μmol/L.
The porous ceramic support of the present invention may be made of conventional materials or by conventional methods, which is not limited in the present invention.
The raw materials or reagents involved in the invention are all common commercial products, and the operations involved are all routine operations in the field unless otherwise specified.
The above-described preferred conditions may be combined with each other to obtain a specific embodiment, in accordance with common knowledge in the art.
The invention has the beneficial effects that:
according to the invention, the microelement gelatin coating is loaded on the porous ceramic support, so that the strength and toughness of the porous ceramic bone repair support are improved, the degradation rate of the gelatin can be controlled by controlling the crosslinking degree of the gelatin and the crosslinking agent, the release rate of the microelement is further controlled, the bone formation and the blood vessel formation are facilitated, and the bone repair is further promoted.
Furthermore, different trace elements are distributed at different positions of the gelatin coating, so that the sequential release of the trace elements at different times is realized, and the repair capability of bone repair at each time stage is promoted more specifically.
Detailed Description
In order that the above objects, features and advantages of the present invention may be more clearly understood, a solution of the present invention will be further described below. It should be noted that the embodiments of the present invention and features of the embodiments may be combined with each other without conflict.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those described herein; it is to be understood that the embodiments described in this specification are only some embodiments of the invention, and not all embodiments.
Preferred embodiments of the present invention will be described in detail with reference to the following examples. It is to be understood that the following examples are given for illustrative purposes only and are not intended to limit the scope of the present invention. Various modifications and alterations of this invention will become apparent to those skilled in the art without departing from the spirit and scope of this invention.
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
Example 1
This example is used to illustrate a method for preparing a bone repair scaffold with a single trace element (Mg) loading coating according to the present invention, and specifically includes the following steps:
(1) 2.25g of gelatin particles and 27.75g of deionized water were weighed to prepare a 7.5% gelatin aqueous solution, and magnesium sulfate heptahydrate was added thereto to prepare a gelatin solution having a magnesium ion concentration of 5 mmol/L. Immersing the sintered biological ceramic bracket into the solution, performing infiltration treatment in a vacuum drying oven with the temperature of 60 ℃ and the pressure of-0.08 MPa for 10min, taking out a sample, and drying in the drying oven with the temperature of 50 ℃ for 12 h;
(2) and (3) preparing a genipin solution with the concentration of 20mg/mL by using absolute ethyl alcohol as a solvent. The dried sample was immersed in the solution at room temperature for 12h to crosslink the gelatin. And (3) taking out a sample after crosslinking is finished, drying the sample in a drying oven at the temperature of 50 ℃ for 12h, taking out the sample, freezing the sample in a refrigerator at the temperature of-20 ℃, and freeze-drying the sample to prepare the metal ion loaded gelatin coated porous ceramic bone repair scaffold.
Example 2
This example is used to illustrate a method for preparing a bone repair scaffold with a two-trace-element (magnesium, zinc) load coating according to the present invention, and specifically includes the following steps:
(1) weighing 7.5g of gelatin particles and 92.5g of deionized water, preparing a gelatin aqueous solution with the mass concentration of 7.5%, adding zinc sulfate into the gelatin aqueous solution to prepare a gelatin solution A with the zinc ion concentration of 10 mu mol/L;
immersing the sintered biological ceramic bracket into gelatin solution A, performing osmosis treatment for 10min in a vacuum drying oven with the temperature of 60 ℃ and the pressure of-0.08 MPa, taking out a sample, and drying for 12h in a drying oven with the temperature of 50 ℃;
(2) weighing 7.5g of gelatin particles and 92.5g of deionized water, preparing a 7.5% gelatin aqueous solution, adding magnesium sulfate heptahydrate, and preparing a gelatin solution B with a magnesium ion concentration of 5 mmol/L;
dripping a gelatin solution B on the sample dried in the step (1) by using a liquid transfer gun to uniformly cover the surface of the sample with the gelatin solution B, and drying for 12 hours in a drying oven at the temperature of 50 ℃;
(3) and preparing 20mg/ml genipin solution by using absolute ethyl alcohol as a solvent. The dried sample was immersed in the solution for 24h at room temperature to crosslink the gelatin. And (3) taking out a sample after crosslinking is finished, drying the sample in a drying oven at the temperature of 50 ℃ for 12h, taking out the sample, freezing the sample in a refrigerator at the temperature of-20 ℃, and freeze-drying the sample to prepare the metal ion-loaded gelatin-coated porous ceramic bone repair scaffold.
Example 3
This example is used to illustrate a method for preparing a bone repair scaffold with a loading coating of three trace elements (magnesium, copper, strontium) according to the present invention, which specifically includes the following steps:
(1) weighing 7.5g of gelatin particles and 92.5g of deionized water, preparing a 7.5% gelatin aqueous solution, adding strontium chloride hexahydrate, and preparing a gelatin solution A with a strontium ion concentration of 0.1 mmol/L;
immersing the sintered biological ceramic bracket into gelatin solution A, performing osmosis treatment for 10min in a vacuum drying oven with the temperature of 60 ℃ and the pressure of-0.08 MPa, taking out a sample, and drying for 12h in a drying oven with the temperature of 50 ℃;
(2) weighing 7.5g of gelatin particles and 92.5g of deionized water, preparing a gelatin water solution with the mass concentration of 7.5%, adding magnesium sulfate heptahydrate and copper sulfate pentahydrate into the gelatin water solution, and preparing a gelatin solution B with the magnesium ion concentration of 5mmol/L and the copper ion concentration of 20 mu mol/L;
dripping a gelatin solution B on the sample dried in the step (1) by using a liquid transfer gun to uniformly cover the surface of the sample with the gelatin solution B, and drying for 12 hours in a drying oven at the temperature of 50 ℃;
(3) and preparing 20mg/ml genipin solution by using absolute ethyl alcohol as a solvent. The dried sample was immersed in the solution for 24h at room temperature to crosslink the gelatin. And (3) taking out a sample after crosslinking is finished, drying the sample in a drying oven at the temperature of 50 ℃ for 12h, taking out the sample, freezing the sample in a refrigerator at the temperature of-20 ℃, and freeze-drying the sample to prepare the metal ion-loaded gelatin-coated porous ceramic bone repair scaffold.
Experimental example 1
In vivo environment simulation experiments prove that the gelatin coating on the bone repair scaffold prepared in the embodiment 1-3 can be slowly degraded in a simulated environment, so that trace elements in the gelatin coating are slowly released. When the gelatin coating contains various trace elements, the sequence of release of different trace elements can be controlled by the degradation speed, and the angiogenesis and osteogenesis are promoted, so that the aim of promoting bone repair is fulfilled.
In practical application, the types and concentrations of the trace elements in the gelatin coating can be adjusted according to different requirements, and the crosslinking degree of the gelatin coating can be adjusted within the process range of the method according to the required acting concentration so as to increase or reduce the release rate of the trace elements.
The foregoing are merely exemplary embodiments of the present invention, which enable those skilled in the art to understand or practice the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (10)
1. The bone repair support with the trace element loaded coating is characterized by comprising a porous ceramic support body and a gelatin coating on the surface of the porous ceramic support body, wherein the gelatin coating contains trace elements.
2. The bone repair scaffold according to claim 1, wherein the trace elements are selected from one or more of magnesium, copper, calcium, zinc, strontium, silicon.
3. The bone repair scaffold according to claim 2, wherein the gelatin coating is a cross-linked gelatin coating, and the time for complete degradation in vivo is 14-60 days.
4. The bone repair scaffold according to claim 3, wherein the gelatin coating is divided into two layers, the surface layer contains one or more trace elements selected from magnesium and copper, and the subsurface layer contains one or more trace elements selected from calcium, zinc, strontium and silicon.
5. A method of preparing a bone repair scaffold according to any of claims 1 to 3, comprising the steps of:
(1) preparing a gelatin aqueous solution with the mass concentration of 2.5-10%, and dissolving the trace elements in the solution to obtain a trace element-loaded gelatin solution;
immersing the porous ceramic support into the gelatin solution, carrying out infiltration treatment for 5-15 min in a vacuum drying oven with the temperature of 60 ℃ and the pressure of 0.08MPa, then taking out a sample, and drying for 8-12 h in a drying oven with the temperature of 50 ℃;
(2) preparing 1-20 mg/mL genipin solution by using absolute ethyl alcohol as a solvent, and immersing the sample dried in the step (1) into the genipin solution for 1-24 h at room temperature to perform a crosslinking reaction; and (3) taking out the sample after crosslinking is finished, drying the sample in a drying oven at the temperature of 50 ℃ for 8-12 h, and then freeze-drying the sample at the temperature of-20 ℃ to obtain the bone repair scaffold.
6. The method according to claim 5, wherein the concentration of the trace element in the gelatin solution is 5 μmol/L to 10 mmol/L.
7. The production method according to claim 6, wherein the mass concentration of the aqueous gelatin solution is 7.5%.
8. The method for preparing a bone repair scaffold according to claim 4, comprising the steps of:
(1) preparing a gelatin aqueous solution with the mass concentration of 2.5-10%, and dissolving first trace elements in the solution to obtain a gelatin solution A;
immersing the porous ceramic support into gelatin solution A, carrying out infiltration treatment for 5-15 min in a vacuum drying oven with the temperature of 60 ℃ and the pressure of 0.08MPa, then taking out a sample, and drying for 8-12 h in a drying oven with the temperature of 50 ℃;
(2) preparing a gelatin aqueous solution with the mass concentration of 2.5-10%, and dissolving a second type of trace elements in the solution to obtain a gelatin solution B;
dripping a gelatin solution B on the dried sample obtained in the step (1) by using a liquid transfer gun, uniformly covering the surface of the sample with the gelatin solution B, and drying for 8-12 h in a drying oven at the temperature of 50 ℃;
(3) preparing 1-20 mg/mL genipin solution by using absolute ethyl alcohol as a solvent, and immersing the sample dried in the step (2) into the genipin solution for 1-24 h at room temperature to perform a crosslinking reaction; and (3) taking out the sample after crosslinking is finished, drying the sample in a drying oven at the temperature of 50 ℃ for 8-12 h, and then freeze-drying the sample at the temperature of-20 ℃ to obtain the bone repair scaffold.
9. The preparation method according to claim 8, wherein the first type of trace elements are selected from one or more of calcium, zinc, strontium and silicon, wherein the concentration of calcium ions in the gelatin solution A is 2-8 mmol/L, the concentration of zinc ions in the gelatin solution A is 10-20 μmol/L, the concentration of strontium ions in the gelatin solution A is 0.1-1 mmol/L, and the concentration of silicon ions in the gelatin solution A is 5-20 μmol/L.
10. The preparation method according to claim 8, wherein the second type of trace element is one or more selected from magnesium and copper, wherein the concentration of magnesium ions in the gelatin solution B is 2.5-7.5 mmol/L, and the concentration of copper ions in the gelatin solution B is 20-30 μmol/L.
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