CN117338993A - Modified nano hydroxyapatite/citric acid/gelatin/calcined dolomite bone binder and preparation method thereof - Google Patents
Modified nano hydroxyapatite/citric acid/gelatin/calcined dolomite bone binder and preparation method thereof Download PDFInfo
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- CN117338993A CN117338993A CN202311509220.2A CN202311509220A CN117338993A CN 117338993 A CN117338993 A CN 117338993A CN 202311509220 A CN202311509220 A CN 202311509220A CN 117338993 A CN117338993 A CN 117338993A
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- citric acid
- gelatin
- calcined dolomite
- bone
- hydroxyapatite
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 title claims abstract description 245
- 239000010459 dolomite Substances 0.000 title claims abstract description 101
- 229910000514 dolomite Inorganic materials 0.000 title claims abstract description 101
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 84
- 108010010803 Gelatin Proteins 0.000 title claims abstract description 64
- 239000008273 gelatin Substances 0.000 title claims abstract description 64
- 229920000159 gelatin Polymers 0.000 title claims abstract description 64
- 235000019322 gelatine Nutrition 0.000 title claims abstract description 64
- 235000011852 gelatine desserts Nutrition 0.000 title claims abstract description 64
- 229910052588 hydroxylapatite Inorganic materials 0.000 title claims abstract description 61
- 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 title claims abstract description 47
- 239000011230 binding agent Substances 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title abstract description 10
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 title 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 90
- 239000008367 deionised water Substances 0.000 claims abstract description 75
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 75
- 230000001070 adhesive effect Effects 0.000 claims abstract description 71
- 239000000853 adhesive Substances 0.000 claims abstract description 70
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims abstract description 64
- 239000007791 liquid phase Substances 0.000 claims abstract description 50
- 239000001361 adipic acid Substances 0.000 claims abstract description 32
- 235000011037 adipic acid Nutrition 0.000 claims abstract description 32
- 238000002156 mixing Methods 0.000 claims abstract description 25
- 239000007790 solid phase Substances 0.000 claims abstract description 24
- 238000003756 stirring Methods 0.000 claims description 76
- 238000000227 grinding Methods 0.000 claims description 45
- 239000002639 bone cement Substances 0.000 claims description 31
- 238000010438 heat treatment Methods 0.000 claims description 29
- 239000002244 precipitate Substances 0.000 claims description 28
- 238000001035 drying Methods 0.000 claims description 15
- 230000007935 neutral effect Effects 0.000 claims description 15
- 238000007873 sieving Methods 0.000 claims description 15
- 239000006228 supernatant Substances 0.000 claims description 15
- 238000005406 washing Methods 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 239000000126 substance Substances 0.000 abstract description 28
- 239000011575 calcium Substances 0.000 abstract description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 7
- 229910052751 metal Inorganic materials 0.000 abstract description 6
- 239000002184 metal Substances 0.000 abstract description 6
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 abstract description 4
- 229910001425 magnesium ion Inorganic materials 0.000 abstract description 4
- 230000006911 nucleation Effects 0.000 abstract description 4
- 238000010899 nucleation Methods 0.000 abstract description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 3
- 238000007112 amidation reaction Methods 0.000 abstract description 3
- 210000002449 bone cell Anatomy 0.000 abstract description 3
- 230000009920 chelation Effects 0.000 abstract description 3
- 229910052739 hydrogen Chemical group 0.000 abstract description 3
- 239000001257 hydrogen Chemical group 0.000 abstract description 3
- 231100000252 nontoxic Toxicity 0.000 abstract description 3
- 230000003000 nontoxic effect Effects 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000006664 bond formation reaction Methods 0.000 abstract description 2
- 229910001424 calcium ion Inorganic materials 0.000 abstract description 2
- 230000010261 cell growth Effects 0.000 abstract description 2
- 235000015097 nutrients Nutrition 0.000 abstract description 2
- 239000000843 powder Substances 0.000 description 41
- 239000000243 solution Substances 0.000 description 33
- 239000007787 solid Substances 0.000 description 26
- 238000005303 weighing Methods 0.000 description 24
- 238000002791 soaking Methods 0.000 description 23
- 239000000203 mixture Substances 0.000 description 14
- 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 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- 239000011259 mixed solution Substances 0.000 description 13
- 239000004570 mortar (masonry) Substances 0.000 description 13
- 239000002245 particle Substances 0.000 description 13
- 238000003825 pressing Methods 0.000 description 13
- 238000003892 spreading Methods 0.000 description 13
- 230000007480 spreading Effects 0.000 description 13
- 238000009210 therapy by ultrasound Methods 0.000 description 13
- 239000011777 magnesium Substances 0.000 description 7
- 239000007943 implant Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000008439 repair process Effects 0.000 description 4
- 208000010392 Bone Fractures Diseases 0.000 description 3
- 206010017076 Fracture Diseases 0.000 description 3
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 3
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 3
- 239000000395 magnesium oxide Substances 0.000 description 3
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 3
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000000467 phytic acid Substances 0.000 description 3
- 229940068041 phytic acid Drugs 0.000 description 3
- 235000002949 phytic acid Nutrition 0.000 description 3
- ODINCKMPIJJUCX-UHFFFAOYSA-N Calcium oxide Chemical compound [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 108010022355 Fibroins Proteins 0.000 description 2
- 239000000316 bone substitute Substances 0.000 description 2
- 125000002843 carboxylic acid group Chemical group 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 208000024779 Comminuted Fractures Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000006670 Multiple fractures Diseases 0.000 description 1
- 208000001164 Osteoporotic Fractures Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010061363 Skeletal injury Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 238000011882 arthroplasty Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003106 tissue adhesive Substances 0.000 description 1
- 229940075469 tissue adhesives Drugs 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/0047—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L24/0073—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix
- A61L24/0084—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix containing fillers of phosphorus-containing inorganic compounds, e.g. apatite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0042—Materials resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/112—Phosphorus-containing compounds, e.g. phosphates, phosphonates
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
- A61L2300/604—Biodegradation
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- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- Composite Materials (AREA)
- Inorganic Chemistry (AREA)
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Abstract
The invention discloses a modified nano hydroxyapatite/citric acid/gelatin/calcined dolomite bone adhesive and a preparation method thereof, wherein the bone adhesive is prepared by mixing solid phase obtained by blending adipic acid modified nano hydroxyapatite and calcined dolomite, and liquid phase obtained by dissolving gelatin and citric acid in deionized water; according to the invention, by utilizing the principle that magnesium ions in nano hydroxyapatite can be chelated with carboxyl in adipic acid, the number of nucleation centers of the nano hydroxyapatite is increased, metal chelation of calcium and magnesium ions in calcined dolomite with citric acid and gelatin, amidation reaction of gelatin with carboxyl of the citric acid and hydrogen bond formation are carried out, the obtained bone adhesive can achieve stronger bonding strength and excellent compressive strength and tensile strength; because the raw materials are nontoxic, and the bone adhesive can absorb nutrient substances by organisms and promote bone cell growth, the bone adhesive has good biocompatibility and biodegradability.
Description
Technical Field
The invention relates to a bone adhesive and a preparation method thereof, in particular to a modified nano hydroxyapatite/citric acid/gelatin/calcined dolomite bone adhesive and a preparation method thereof
Background
Bone is a dynamic structure with a hierarchical structure and precise inorganic-organic interfaces that can be constantly self-repaired to maintain its load-bearing properties. However, the bone remodeling process does not adequately compensate for damage caused in some cases, such as large fractures and defects (e.g., comminuted fractures), requiring additionalSurgical intervention to fix the broken tissue and promote healing. The metal implant internal fixation method is a method of suturing with metal wires or metal forceps (plates, needles and screws) in bone surgery to help adhesion of bone tissue, is simple and effective, and is widely used in fracture surgery due to its good mechanical properties (any of the general areas, zhang Zhiliang, han Pengfei, chen Taoyu, li Pengcui, wei Xiaochun. Meta analysis of clinical effect of nonmetallic and metallic materials on patellar fracture internal fixation [ J]Chinese bone injury 2018,31 (10): 927-932. However, the internal fixation method of the metal implant also has certain limitations, such as stress shielding effect, growth interference and fixture dislocation after the screw is implanted, and the implant is placed in the body for a long time, so that the direct contact of the implant and the human body can lead to poor integration and the need for secondary operation to take out the screw. Therefore, the bone cement having high adhesive strength is introduced, not only the crushed bone can be fixed, but also the effective components (such as Ca 2+ 、Mg 2+ ) But also can accelerate bone formation.
Synthetic bone adhesives such as polymethyl methacrylate (Chu Jianjun, fu Yao, li Chuang, guo Jing. Bio-based antibacterial composite adhesive materials and methods for preparing the same: chinese patent No. CN114225095a, 2022.) are characterized by good biocompatibility, low cost, easy operation, sufficient strength and in situ formability, etc., and are bone substitutes widely used in arthroplasty, vertebroplasty and osteoporotic fracture, however, a large amount of heat is released during the preparation of polymethyl methacrylate, which may cause thermal necrosis of surrounding bone tissue, thus limiting their application in the field of bone repair. Natural bone adhesives such as fibrin adhesives (ever peaked Chen Yi. Function of fibrin adhesives and effect on repair of skin soft tissue [ J ]. Bonding 2023,50 (03): 25-29.) can achieve adhesion by covalent bond formation of the amino groups themselves with carboxylic acid groups in the collagen matrix of bone tissue, but their bond strength to bone is far inferior to synthetic bone adhesives.
Bone adhesives of inorganic mineral and organic compound such as phytic acid/silk fibroin/calcined dolomite bone adhesive (Zhou Chunhui, zhou Shuqing. Preparation method of phytic acid/silk fibroin/calcined dolomite bone adhesive [ P ]]Zhejiang province: CN112516378B, 2022-02-11.) has the advantages of good biocompatibility, low cost, easy operation, short curing time, good biodegradability, etc., but the method is simple by using phytic acid and Mg in calcined dolomite 2+ 、Ca 2+ Chelating is performed, the bonding performance is too low, and strong bonding of the bone adhesive to broken bones cannot be realized. nano-Hydroxyapatite (n-HAp, ca) 10 (PO 4 ) 6 (OH) 2 ) Is the main inorganic component for forming organism bone tissue and teeth, and because of the characteristics of good biocompatibility, bioactivity, bone conductivity, osteogenesis and no cytotoxicity, the n-HAp has been widely applied to bone repair scaffolds, implant materials for orthopaedics and dentistry and bone substitute materials. Adipic acid is a nontoxic and biocompatible compound having two carboxyl functional groups which are bound by Mg in n-HAp 2+ Chelation can increase the number of nucleation centers of n-HAp and improve the mechanical strength and adhesive property of the matrix.
The dolomite is thoroughly calcined in a muffle furnace at high temperature to completely convert the dolomite into a mixture of calcium oxide (CaO) and magnesium oxide (MgO) for providing Ca required for physiological bone metabolism 2+ And Mg (magnesium) 2+ Therefore, the calcined dolomite can be applied to the field of bone repair to promote the regeneration and proliferation of bone cells. Gelatin is a natural polymer product produced by the hydrolysis of collagen, which consists of polypeptides and proteins rich in amine and carboxylic acid groups, and its degradability, biocompatibility, cheapness and high availability make it one of the most popular choices for tissue adhesives. Citric acid is extracted from starch and saccharides, and the biological material using citric acid as a cross-linking agent has excellent biocompatibility and biodegradability, and excellent physical and mechanical properties which can be adjusted and adapt to specific application requirements, and is widely applied to the biomedical field.
At present, there are few reports of novel bone adhesives, which modify inorganic minerals, combine them with organic materials, and achieve high bonding strength in a short time and have high biocompatibility.
Disclosure of Invention
Aiming at the defects of small bonding performance and low mechanical strength of the existing bone adhesive, the invention provides a modified nano hydroxyapatite/citric acid/gelatin/calcined dolomite bone adhesive with high bonding performance and a preparation method thereof.
The technical scheme of the invention is as follows:
a modified nano-hydroxyapatite/citric acid/gelatin/calcined dolomite bone adhesive is prepared by mixing solid phase obtained by blending adipic acid modified nano-hydroxyapatite and calcined dolomite, and liquid phase obtained by dissolving gelatin and citric acid in deionized water;
the mass ratio of the solid phase to the liquid phase is 0.5-1: 20, a step of;
in the solid phase, the mass ratio of the calcined dolomite is 2-22%, and the balance is adipic acid modified nano hydroxyapatite;
the mass fraction of the citric acid in the liquid phase is 10-30%, the mass fraction of the gelatin is 9-25%, and the balance is deionized water.
The preparation method of the modified nano hydroxyapatite/citric acid/gelatin/calcined dolomite bone binder comprises the following steps:
(1) Mixing adipic acid, nano hydroxyapatite and deionized water, regulating the pH value of the solution to be 4.0-4.5, treating at 70-80 ℃ for 80-100 min, centrifuging to remove supernatant, washing precipitate until the pH value is neutral, drying, and grinding to obtain adipic acid modified nano hydroxyapatite for later use;
preferably, the mass ratio of adipic acid to nano hydroxyapatite is 0.1:1, a step of;
(2) Grinding and sieving natural dolomite, then placing the natural dolomite into a muffle furnace, heating to 800-900 ℃ and keeping for 3-5 h to obtain calcined dolomite for later use;
preferably, the heating rate is 5-10 ℃/min;
the obtained calcined dolomite powder mainly contains MgO and CaO;
(3) Mixing the adipic acid modified nano hydroxyapatite obtained in the step (1) with the calcined dolomite obtained in the step (2), and grinding to obtain a solid phase;
(4) Dissolving citric acid in deionized water to prepare a citric acid solution; adding gelatin into citric acid solution, and dissolving to obtain liquid phase;
(5) Placing the liquid phase obtained in the step (4) in a water bath at 35-40 ℃, adding the solid phase obtained in the step (3) while stirring, and then carrying out ultrasonic full mixing reaction to obtain the bone adhesive;
preferably, the time of the ultrasound is 2 minutes.
The technical principle of the invention is as follows:
the invention innovatively uses a direct adding method to carry out adipic acid modification on the nano-hydroxyapatite, and utilizes two carboxyl functional groups of adipic acid and Mg in the nano-hydroxyapatite 2+ Chelating can increase the number of nucleation centers of nano hydroxyapatite and improve the mechanical strength and the bonding performance of the matrix. Meanwhile, the metal chelation of calcium and magnesium ions, citric acid and gelatin in the calcined dolomite and the principle that the gelatin and carboxyl of the citric acid are subjected to amidation reaction and form hydrogen bonds, so that the obtained bone adhesive can achieve stronger bonding strength and excellent compressive strength and tensile strength. Because the raw materials are nontoxic, and the bone adhesive can absorb nutrient substances by organisms and promote bone cell growth, the bone adhesive has good biocompatibility and biodegradability.
Compared with the existing bone adhesive, the invention has the following beneficial effects:
in the invention, phosphate radical in nano-hydroxyapatite can be tightly chelated with calcium in bone, magnesium ion in nano-hydroxyapatite can be chelated with carboxyl in adipic acid, the number of nucleation centers of nano-hydroxyapatite is increased, and Ca in dolomite is calcined 2+ 、Mg 2+ The bone adhesive prepared by the amidation reaction of carboxyl and amino and the tight combination of hydrogen bond of citric acid and gelatin can reach very strong bonding strength, very excellent compressive strength and tensile strength, and has good biocompatibility and biodegradability, simple preparation method and low cost.
Drawings
Fig. 1 is a bone bonded according to example 1.
Detailed Description
The invention will be further described with reference to specific embodiments, and advantages and features of the invention will become apparent from the description. These examples are merely exemplary and do not limit the scope of the invention in any way. It will be understood by those skilled in the art that various changes and substitutions can be made in the details and form of the technical solution of the present invention without departing from the spirit and scope of the invention as described above, but these changes and substitutions fall within the scope of the present invention.
In the following examples, natural dolomite is from Qingyang county, anhui province.
The nano hydroxyapatite is from Shanghai Ala Biochemical technology Co., ltd.
Example 1
Weighing 4g of citric acid, 1.8g of gelatin and 14.2g of deionized water, adding the citric acid into the deionized water, stirring by a magnetic stirrer to completely dissolve the citric acid into the deionized water, pouring the weighed gelatin particles into a citric acid solution, and stirring by the magnetic stirrer again to completely dissolve the gelatin to obtain a liquid phase substance. And (3) placing 0.096g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.070g of adipic acid powder, 0.704g of nano hydroxyapatite powder and 69.626ml of deionized water by an electronic balance, mixing and stirring to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging in a centrifuge at 4000rpm/min for 5min after soaking, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 7.016MPa and the compressive strength is 7.971MPa measured by a digital display pointer push-pull tension meter.
Example 2
Weighing 4g of citric acid, 2.6g of gelatin and 13.4g of deionized water, adding the citric acid into the deionized water, stirring by a magnetic stirrer to ensure that the citric acid is completely dissolved in the deionized water, pouring the weighed gelatin particles into a citric acid solution, and stirring by the magnetic stirrer again to ensure that the gelatin is completely dissolved to obtain a liquid phase substance. And (3) placing 0.096g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.070g of adipic acid powder, 0.704g of nano hydroxyapatite powder and 69.626ml of deionized water by an electronic balance, mixing and stirring to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging in a centrifuge at 4000rpm/min for 5min after soaking, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 9.006MPa and the compressive strength is 8.967MPa measured by a digital display pointer push-pull tension meter.
Example 3
Weighing 4g of citric acid, 4.2g of gelatin and 11.8g of deionized water, adding the citric acid into the deionized water, stirring by a magnetic stirrer to ensure that the citric acid is completely dissolved in the deionized water, pouring the weighed gelatin particles into a citric acid solution, and stirring by the magnetic stirrer again to ensure that the gelatin is completely dissolved to obtain a liquid phase substance. And (3) placing 0.096g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.070g of adipic acid powder, 0.704g of nano hydroxyapatite powder and 69.626ml of deionized water by an electronic balance, mixing and stirring to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging in a centrifuge at 4000rpm/min for 5min after soaking, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 10.658MPa and the compressive strength is 11.156MPa as measured by a digital display pointer push-pull tension meter.
Example 4
Weighing 4g of citric acid, 5g of gelatin and 11g of deionized water, adding the citric acid into the deionized water, stirring by using a magnetic stirrer to completely dissolve the citric acid into the deionized water, pouring the weighed gelatin particles into a citric acid solution, and stirring again by using the magnetic stirrer to completely dissolve the gelatin to obtain a liquid phase substance. And (3) placing 0.096g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.070g of adipic acid powder, 0.704g of nano hydroxyapatite powder and 69.626ml of deionized water by an electronic balance, mixing and stirring to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging in a centrifuge at 4000rpm/min for 5min after soaking, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 8.389MPa and the compressive strength is 8.568MPa as measured by a digital display pointer push-pull tension meter.
Example 5
Weighing 4g of citric acid, 3.4g of gelatin and 12.6g of deionized water, adding the citric acid into the deionized water, stirring by a magnetic stirrer to ensure that the citric acid is completely dissolved in the deionized water, pouring the weighed gelatin particles into a citric acid solution, and stirring by the magnetic stirrer again to ensure that the gelatin is completely dissolved to obtain a liquid phase substance. And (3) placing 0.016g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.078g of adipic acid powder, 0.784g of nano hydroxyapatite powder and 77.538ml of deionized water by using an electronic balance, mixing and stirring the materials to eliminate solid components, adjusting the pH value of the solution to be 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging the soaked solution in a centrifuge at 4000rpm/min for 5min, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 10.857MPa and the compressive strength is 8.967MPa as measured by a digital display pointer push-pull tension meter.
Example 6
Weighing 4g of citric acid, 3.4g of gelatin and 12.6g of deionized water, adding the citric acid into the deionized water, stirring by a magnetic stirrer to ensure that the citric acid is completely dissolved in the deionized water, pouring the weighed gelatin particles into a citric acid solution, and stirring by the magnetic stirrer again to ensure that the gelatin is completely dissolved to obtain a liquid phase substance. And (3) placing 0.056g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.074g of adipic acid powder, 0.744g of nano hydroxyapatite powder and 73.582ml of deionized water by an electronic balance, mixing and stirring to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging in a centrifuge at 4000rpm/min for 5min after soaking, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 11.853MPa and the compressive strength is 9.365MPa as measured by a digital display pointer push-pull tension meter.
Example 7
Weighing 4g of citric acid, 3.4g of gelatin and 12.6g of deionized water, adding the citric acid into the deionized water, stirring by a magnetic stirrer to ensure that the citric acid is completely dissolved in the deionized water, pouring the weighed gelatin particles into a citric acid solution, and stirring by the magnetic stirrer again to ensure that the gelatin is completely dissolved to obtain a liquid phase substance. And (3) placing 0.136g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.066g of adipic acid powder, 0.664g of nano hydroxyapatite powder and 65.670ml of deionized water by an electronic balance, mixing and stirring the materials to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging the soaked solution in a centrifuge at 4000rpm/min for 5min, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 12.808MPa and the compressive strength is 8.310MPa as measured by a digital display pointer push-pull tension meter.
Example 8
Weighing 4g of citric acid, 3.4g of gelatin and 12.6g of deionized water, adding the citric acid into the deionized water, stirring by a magnetic stirrer to ensure that the citric acid is completely dissolved in the deionized water, pouring the weighed gelatin particles into a citric acid solution, and stirring by the magnetic stirrer again to ensure that the gelatin is completely dissolved to obtain a liquid phase substance. And (3) placing 0.176g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.062g of adipic acid powder, 0.624g of nano hydroxyapatite powder and 61.714ml of deionized water by using an electronic balance, mixing and stirring the adipic acid powder, the nano hydroxyapatite powder and the 61.714ml of deionized water to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging the soaked solution in a centrifuge at 4000rpm/min for 5min, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 9.962MPa and the compressive strength is 6.479MPa as measured by a digital display pointer push-pull tension meter.
Example 9
2g of citric acid, 3.4g of gelatin and 14.6g of deionized water are weighed, the citric acid is added into the deionized water and stirred by a magnetic stirrer, so that the citric acid is completely dissolved in the deionized water, then the weighed gelatin particles are poured into a citric acid solution and stirred by the magnetic stirrer again, and the gelatin is fully dissolved, thus obtaining a liquid phase substance. And (3) placing 0.096g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.070g of adipic acid powder, 0.704g of nano hydroxyapatite powder and 69.626ml of deionized water by an electronic balance, mixing and stirring to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging in a centrifuge at 4000rpm/min for 5min after soaking, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 4.408MPa and the compressive strength is 5.483MPa as measured by a digital display pointer push-pull tension meter.
Example 10
3g of citric acid, 3.4g of gelatin and 13.6g of deionized water are weighed, the citric acid is added into the deionized water and stirred by a magnetic stirrer, so that the citric acid is completely dissolved in the deionized water, then the weighed gelatin particles are poured into a citric acid solution and stirred by the magnetic stirrer again, and the gelatin is fully dissolved, thus obtaining a liquid phase substance. And (3) placing 0.096g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.070g of adipic acid powder, 0.704g of nano hydroxyapatite powder and 69.626ml of deionized water by an electronic balance, mixing and stirring to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging in a centrifuge at 4000rpm/min for 5min after soaking, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 5.145MPa and the compressive strength is 6.877MPa as measured by a digital display pointer push-pull tension meter.
Example 11
Weighing 5g of citric acid, 3.4g of gelatin and 11.6g of deionized water, adding the citric acid into the deionized water, stirring by a magnetic stirrer to ensure that the citric acid is completely dissolved in the deionized water, pouring the weighed gelatin particles into a citric acid solution, and stirring by the magnetic stirrer again to ensure that the gelatin is completely dissolved to obtain a liquid phase substance. And (3) placing 0.096g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.070g of adipic acid powder, 0.704g of nano hydroxyapatite powder and 69.626ml of deionized water by an electronic balance, mixing and stirring to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging in a centrifuge at 4000rpm/min for 5min after soaking, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 4.488MPa and the compressive strength is 8.469MPa as measured by a digital display pointer push-pull tension meter.
Example 12
Weighing 6g of citric acid, 3.4g of gelatin and 10.6g of deionized water, adding the citric acid into the deionized water, stirring by a magnetic stirrer to completely dissolve the citric acid into the deionized water, pouring the weighed gelatin particles into a citric acid solution, and stirring by the magnetic stirrer again to completely dissolve the gelatin to obtain a liquid phase substance. And (3) placing 0.096g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.070g of adipic acid powder, 0.704g of nano hydroxyapatite powder and 69.626ml of deionized water by an electronic balance, mixing and stirring to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging in a centrifuge at 4000rpm/min for 5min after soaking, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 4.189MPa and the compressive strength is 8.588MPa as measured by a digital display pointer push-pull tension meter.
Example 13
Weighing 4g of citric acid, 3.4g of gelatin and 12.6g of deionized water, adding the citric acid into the deionized water, stirring by a magnetic stirrer to ensure that the citric acid is completely dissolved in the deionized water, pouring the weighed gelatin particles into a citric acid solution, and stirring by the magnetic stirrer again to ensure that the gelatin is completely dissolved to obtain a liquid phase substance. And (3) placing 0.096g of natural dolomite into a muffle furnace, heating to 850 ℃ at a heating rate of 5 ℃/min, preserving heat for 4 hours, and cooling to room temperature to obtain the calcined dolomite. Grinding the calcined dolomite into powder by an agate mortar, fully grinding, and sieving with a 200-mesh sieve to obtain the calcined dolomite powder.
Weighing 0.070g of adipic acid powder, 0.704g of nano hydroxyapatite powder and 69.626ml of deionized water by an electronic balance, mixing and stirring to eliminate solid components, adjusting the pH value of the solution to 4.3+/-0.1, soaking the mixed solution at 75 ℃ for 90min, centrifuging in a centrifuge at 4000rpm/min for 5min after soaking, discarding supernatant, washing precipitate with deionized water for multiple times until the pH value is neutral, taking the precipitate, drying, and grinding to obtain the modified nano hydroxyapatite. Continuously stirring the liquid phase substances in a water bath at 37 ℃, adding the calcined dolomite/modified nano hydroxyapatite mixed solid while stirring, uniformly stirring, and then placing the mixture into an ultrasonic cleaner for ultrasonic treatment for 2min to enable the solid phase and the liquid phase to fully and uniformly react, thus obtaining the bone adhesive.
Spreading bone adhesive on fresh pig rib section, and continuously pressing pig rib along axis for 1min to obtain bonded pig rib. The bone cement is pressed into a cylindrical mold with a bottom x height=10 mm x 5mm, and after the mold is formed, the cured bone cement is obtained after demolding. The bond strength of the bone adhesive is 14.102MPa and the compressive strength is 14.888MPa as measured by a digital display pointer push-pull tension meter.
Table 1 detailed data on raw materials and bond strength and compressive strength of the resulting bone cement for each example
Claims (8)
1. The modified nano hydroxyapatite/citric acid/gelatin/calcined dolomite bone adhesive is characterized in that the bone adhesive is prepared by mixing solid phase obtained by blending adipic acid modified nano hydroxyapatite and calcined dolomite, and liquid phase obtained by dissolving gelatin and citric acid in deionized water.
2. The modified nano-hydroxyapatite/citric acid/gelatin/calcined dolomite bone cement according to claim 1, wherein the mass ratio of the solid phase to the liquid phase is 0.5 to 1:20.
3. the modified nano-hydroxyapatite/citric acid/gelatin/calcined dolomite bone cement according to claim 1, wherein the mass ratio of the calcined dolomite in the solid phase is 2 to 22%, and the balance is adipic acid modified nano-hydroxyapatite.
4. The modified nano-hydroxyapatite/citric acid/gelatin/calcined dolomite bone binder according to claim 1, wherein the mass fraction of citric acid in the liquid phase is 10 to 30%, the mass fraction of gelatin is 9 to 25%, and the balance is deionized water.
5. The method for preparing the modified nano-hydroxyapatite/citric acid/gelatin/calcined dolomite bone cement according to claim 1, comprising the steps of:
(1) Mixing adipic acid, nano hydroxyapatite and deionized water, regulating the pH value of the solution to be 4.0-4.5, treating at 70-80 ℃ for 80-100 min, centrifuging to remove supernatant, washing precipitate until the pH value is neutral, drying, and grinding to obtain adipic acid modified nano hydroxyapatite for later use;
(2) Grinding and sieving natural dolomite, then placing the natural dolomite into a muffle furnace, heating to 800-900 ℃ and keeping for 3-5 h to obtain calcined dolomite for later use;
(3) Mixing the adipic acid modified nano hydroxyapatite obtained in the step (1) with the calcined dolomite obtained in the step (2), and grinding to obtain a solid phase;
(4) Dissolving citric acid in deionized water to prepare a citric acid solution; adding gelatin into citric acid solution, and dissolving to obtain liquid phase;
(5) Placing the liquid phase obtained in the step (4) in a water bath at 35-40 ℃, adding the solid phase obtained in the step (3) while stirring, and then carrying out ultrasonic full mixing reaction to obtain the bone adhesive.
6. The method according to claim 5, wherein in the step (1), the mass ratio of adipic acid to nano-hydroxyapatite is 0.1:1.
7. the method according to claim 5, wherein in the step (2), the temperature rise rate is 5 to 10 ℃/min.
8. The method of claim 5, wherein in step (5), the time of the ultrasonic wave is 2 minutes.
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