LU504657B1 - Grafting process of chlorogenic acid-chitosan complexes on zirconia surface for enhancing osteogenic activity - Google Patents
Grafting process of chlorogenic acid-chitosan complexes on zirconia surface for enhancing osteogenic activity Download PDFInfo
- Publication number
- LU504657B1 LU504657B1 LU504657A LU504657A LU504657B1 LU 504657 B1 LU504657 B1 LU 504657B1 LU 504657 A LU504657 A LU 504657A LU 504657 A LU504657 A LU 504657A LU 504657 B1 LU504657 B1 LU 504657B1
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- Luxembourg
- Prior art keywords
- zirconia
- chlorogenic acid
- solution
- polyethyleneimine
- chitosan
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- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 title claims abstract description 157
- 229920001661 Chitosan Polymers 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title abstract description 14
- 230000002188 osteogenic effect Effects 0.000 title abstract description 7
- 230000002708 enhancing effect Effects 0.000 title description 3
- 230000008569 process Effects 0.000 title description 2
- 239000007943 implant Substances 0.000 claims abstract description 46
- 229940074393 chlorogenic acid Drugs 0.000 claims abstract description 43
- CWVRJTMFETXNAD-FWCWNIRPSA-N 3-O-Caffeoylquinic acid Natural products O[C@H]1[C@@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-FWCWNIRPSA-N 0.000 claims abstract description 41
- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 claims abstract description 41
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 claims abstract description 41
- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical group O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 claims abstract description 41
- FFQSDFBBSXGVKF-KHSQJDLVSA-N chlorogenic acid Natural products O[C@@H]1C[C@](O)(C[C@@H](CC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O FFQSDFBBSXGVKF-KHSQJDLVSA-N 0.000 claims abstract description 41
- 235000001368 chlorogenic acid Nutrition 0.000 claims abstract description 41
- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 claims abstract description 41
- 229920002873 Polyethylenimine Polymers 0.000 claims abstract description 32
- 238000000576 coating method Methods 0.000 claims abstract description 20
- 239000011248 coating agent Substances 0.000 claims abstract description 18
- 239000000919 ceramic Substances 0.000 claims abstract description 14
- 239000000758 substrate Substances 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000002791 soaking Methods 0.000 claims description 7
- 238000004140 cleaning Methods 0.000 claims description 2
- 238000007865 diluting Methods 0.000 claims description 2
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- 230000001737 promoting effect Effects 0.000 abstract description 7
- 210000000988 bone and bone Anatomy 0.000 abstract description 5
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
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- 238000011282 treatment Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
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- 238000010609 cell counting kit-8 assay Methods 0.000 description 3
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- 238000001262 western blot Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 2
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- 231100000053 low toxicity Toxicity 0.000 description 2
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- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000005488 sandblasting Methods 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 235000003913 Coccoloba uvifera Nutrition 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 108010009711 Phalloidine Proteins 0.000 description 1
- 240000008976 Pterocarpus marsupium Species 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
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- 229920004890 Triton X-100 Polymers 0.000 description 1
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- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
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- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
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- 210000004877 mucosa Anatomy 0.000 description 1
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- 230000003287 optical effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 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 description 1
- 150000007965 phenolic acids Chemical class 0.000 description 1
- 235000009048 phenolic acids Nutrition 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- GUGNSJAORJLKGP-UHFFFAOYSA-K sodium 8-methoxypyrene-1,3,6-trisulfonate Chemical compound [Na+].[Na+].[Na+].C1=C2C(OC)=CC(S([O-])(=O)=O)=C(C=C3)C2=C2C3=C(S([O-])(=O)=O)C=C(S([O-])(=O)=O)C2=C1 GUGNSJAORJLKGP-UHFFFAOYSA-K 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
- A61C8/0012—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy
- A61C8/0013—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy with a surface layer, coating
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/3094—Designing or manufacturing processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/04—Metals or alloys
- A61L27/047—Other specific metals or alloys not covered by A61L27/042 - A61L27/045 or A61L27/06
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00179—Ceramics or ceramic-like structures
- A61F2310/00185—Ceramics or ceramic-like structures based on metal oxides
- A61F2310/00239—Ceramics or ceramic-like structures based on metal oxides containing zirconia or zirconium oxide ZrO2
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Ceramic Engineering (AREA)
- Inorganic Chemistry (AREA)
- Dentistry (AREA)
- Manufacturing & Machinery (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a method for promoting bone activation on zirconia implant surfaces, the zirconia implant comprise a substrate, a coating and an active molecule, where the substrate is zirconia ceramics, the coating is a polyethyleneimine/chitosan coat attached to the surface of the substrate, and the active molecule is chlorogenic acid grafted onto the coating. After grafting active molecule on the surface of zirconia implant by the method of the invention, it can effectively promote cell adhesion and osteogenic differentiation, that is, it has good osteogenic activity promoting ability and good clinical application prospect.
Description
DESCRIPTION LU504657
GRAFTING PROCESS OF CHLOROGENIC ACID-CHITOSAN COMPLEXES ON
ZIRCONIA SURFACE FOR ENHANCING OSTEOGENIC ACTIVITY
The invention relate to that field of medical materials, in particular to a method for promoting bone activation on zirconia implant surfaces.
The application of traditional titanium implants in patients with insufficient thickness of mucosa around the anterior teeth and some implants is limited by the dark gray color of the metal. With the deepening of the concept of "metal-free planting”, zirconia is considered as an ideal substitute for titanium because of its good biocompatibility, aesthetic effect and mechanical properties such as high fracture toughness and high bending strength. A large number of experiments were carried out in vivo and in vitro to evaluate the feasibility of zirconia as implant material, but it was found that the osteogenic induction performance of zirconia material was not good compared with pure titanium implant. Zirconia is biologically inert and has few organic functional groups on its surface, which is not conducive to the adsorption of protein components and osteoblasts in blood, which has become the main problem limiting the wide application of zirconia implants.
Tissue reaction and osseointegration on the surface of implants are the key to successful implantation. The research on how to effectively improve the surface bioactivity and promote osseointegration of zirconia implants has been going on. Physical methods (sandblasting, laser treatment and ultraviolet treatment, etc.), chemical methods (acid etching), physical and chemical methods (sandblasting acid etching and selective osmotic acid etching, etc.) and surface coating or chemical modification are the common means to improve the early osseointegration of zirconia. Among them, the surface coating or chemical modification does not damage the essence of the implant, which has l&J504657 remarkable effect of improving the biological activity and has a good application prospect.
Bioactive coatings on zirconia surfaces offer the advantage of bioactivity as they are able to induce the formation of hydroxyapatite in the biological environment, which is essential for subsequent bone proliferation. Various studies have attempted to load biologically active drugs onto the implant surface to obtain the corresponding antibacterial and anti- inflammatory effects and thus better promote wound healing, for instance. In order to enhance the osteogenic induction properties of zirconia implant surfaces, the search for an active molecule with osteogenic activity to be loaded on the surface of zirconia implants is the subject of this invention.
Chlorogenic acid is one of the active acids found naturally in the phenolic compounds found in coffee extracts and green tea and has antioxidant, antibacterial, anti- inflammatory, antiviral, anti-microbial, anti-hypertensive, free radical scavenger and central nervous system stimulant activities. Chlorogenic acid regulates lipid metabolism and blood glucose in hereditary and health-related metabolic diseases. Applicant hypothesizes that chlorogenic acid plays an important role in regulating lipid metabolism and glucose metabolism, thus contributing to the prevention of diseases such as osteoporosis. This invention namely employs chlorogenic acid for the coating treatment of zirconia surfaces with a view to enhancing bioactivity and achieving the goal of promoting osseointegration.
SUMMARY LU504657
The purpose of the invention is to provide a method for promoting bone activation on zirconia implant surfaces, to solve the problems existing in the prior art. By impregnating the surface of zirconia with a polyethyleneimine/chitosan coating by using a conjugate adsorption method and grafting an active molecule chlorogenic acid, the purpose of promoting early osteogenic differentiation and achieving good bone bonding is achieved.
To achieve the above objectives, the present invention provides the following scheme: the invention provides a zirconia implant, comprising a substrate, a coating and an active molecule, where the substrate is zirconia ceramics, the coating is a polyethyleneimine/chlorogenic acid-chitosan coating attached to the surface of the substrate
Further, the polyethyleneimine/chlorogenic acid-chitosan coating comprises a polyethyleneimine film attached to the surface of the substrate and chlorogenic acid- chitosan complex grafted on the polyethyleneimine film.
The invention also provides a preparation method of the zirconia implant, comprising the following steps: cleaning and drying the zirconia ceramics, first soaking in a polyethyleneimine solution to form a polyethyleneimine film, then soaking in a chlorogenic acid -chitosan solution to form a polyethyleneimine/ chlorogenic acid-chitosan coating.
Further, the concentration of the polyethyleneimine solution is 5 mg/mL, and the pH is 9.0.
Further, the concentration of the chitosan solution is 1 g/mL, and the viscosity is 100-200
P.
Further, that concentration of the chlorogenic acid solution is 0.025-0.1 mg/mL.
Further, the chlorogenic acid solution is obtained by diluting chlorogenic acid pre-solution; the chlorogenic acid pre-solution is a chlorogenic acid dimethyl sulfoxide solution with a concentration of 100 mg/mL, and the pre-solution is dissolved in a chitosan solution with a final concentration of 0.1 mg/mL.
Further, the immersion time of the zirconia ceramics in the polyethyleneimine solution is 4h.
Further, the soaking time of the zirconia ceramics in the chitosan-chlorogenic acid solutidrv504657 is 24 h.
The invention discloses the following technical effects: in the invention, firstly, zirconia ceramics are placed in polyethyleneimine solution for treatment; cationic polymer polyethyleneimine can promote the adsorption of cells and other molecules because of its polar group (amino group) and hydrophobic group (vinyl group) structure; the tertiary amine group of secondary amine can be protonated in neutral environment, which makes the surface of zirconia implant with high positive charge density; chitosan has the advantages of low toxicity, biodegradability and biocompatibility; by grafting chitosan onto the surface of polyethyleneimine film, the low toxicity of polyethyleneimine is reduced and more positive charges are added to the surface of the material; chlorogenic acid is one of the most effective phenolic acids naturally found in coffee extract and green tea; it can promote the proliferation and adhesion of osteoblasts, and the grafting on the surface of zirconia implants is stable and effective; after grafting active molecules on the surface of zirconia implant by the method of the invention, it can effectively promote cell adhesion and osteogenic differentiation, that is, it has good osteogenic activity promoting ability and good clinical application prospect.
BRIEF DESCRIPTION OF THE FIGURES LU504657
In order to explain the embodiments of the present invention or the technical scheme in the prior art more clearly, the figures needed in the embodiments will be briefly introduced below. Obviously, the figures described below are only some embodiments of the present invention, and other figures can be obtained according to these figures without creative work for ordinary people in the field.
Fig. 1 is a flow chart of surface treatment of zirconia implant of the present invention.
Fig. 2 is the surface spectrogram of zirconia implant treated by single grafting PEI and chlorogenic acid with different concentrations in effect verification 1 of the present invention; Figs. 2A and 2B are XPS carbon spectra and oxygen spectra of untreated zirconia; Figs. 2C and 2D are XPS carbon spectra and oxygen spectra of zirconia bonded with PEI; Figs. 2E and 2F are XPS carbon spectra and oxygen spectra of 0.025 mg/mL chlorogenic acid grafted zirconia; Figs. 2G and 2H are XPS carbon spectra and oxygen spectra of 0.05 mg/mL chlorogenic acid grafted zirconia; Figs. 21 and 2J are XPS carbon spectra and oxygen spectra of chlorogenic acid grafted zirconia with a concentration of 0.1 mg/mL.
Fig. 3 is the contact angle test chart of zirconia implant in the effect verification 1 of the present invention, in which, Fig. 3A is the blank group, Fig. 3B is the PEI group, Fig. 3C is the 0.025 mg/mL chlorogenic acid grafted zirconia group, Fig. 3D is the 0.1 mg/mL chlorogenic acid grafted zirconia group, and Fig. 3E is the 0.025 mg/mL chlorogenic acid grafted zirconia group.
Fig. 4 is a morphological diagram of MC3T3-E1 cells observed under a laser confocal microscope in the effect verification 2 of the present invention, which are cultured on the surface of zirconia with single grafting of PET/CS and different concentrations of chlorogenic acid for 6 h; Figs. 4A- 4C show untreated zirconia; Figs. 4D- 4F show single- bonded PEI/CS zirconia; Figs. 4G- 41 show 0.025 mg/mL chlorogenic acid grafted zirconia;
Figs. 4J- 4L show 0.05 mg/mL chlorogenic acid grafted zirconia; Figs. 4M- 40 show chlorogenic acid grafted zirconia (green: actin; blue: nucleus).
Fig. 5 is a graph showing the expression levels of COL-1, RUNX2 and OCN proteins dru504657 the 7th day of MC3T3-E1 cells on the surface of zirconia implants which are not treated or grafted with chlorogenic acid with different concentrations by western blotting in the effect verification 2 of the present invention.
Fig. 6 shows the effects of different coatings and different active factors on osteoblast proliferation in effect verification 2 of the present invention.
Fig. 7 is a graph showing the relative growth rate of cells of zirconia implants which are not treated or grafted with different concentrations of chlorogenic acid in the effect verification 2 of the present invention, where Fig. 7A is the first day and Fig. 7B is the fourth day.
A number of exemplary embodiments of the present invention will now be described in detail, and this detailed description should not be considered as a limitation of the present invention but should be understood as a more detailed description of certain aspects, characteristics and embodiments of the present invention.
It should be understood that the terminology described in the present invention is only for describing specific embodiments and is not used to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper limit and the lower limit of the range is also specifically disclosed. The intermediate value within any stated value or stated range and every smaller range between any other stated value or intermediate value within the stated range are also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded from the range.
Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention relates. Although the present invention only describes the preferred methods and materials, any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention.
All documents mentioned in this specification are incorporated by reference to disclogéJ504657 and describe methods and/or materials related to the documents. In case of conflict with any incorporated document, the contents of this specification shall prevail.
It is obvious to those skilled in the art that many improvements and changes can be made to the specific embodiments of the present invention without departing from the scope or spirit of the present invention. Other embodiments will be apparent to the skilled person from the description of the invention. The description and example of that present invention are exemplary only.
The terms "including", "comprising", "having" and "containing" used in this description are all open terms, which means including but not limited to.
Embodiment 1
A preparation method of zirconia implant, the flow of which is shown in Fig. 1, including the following steps:
Three zirconia ceramic tiles (5% Y2O3, 95% ZrO», Zhuhai Yuebojia New Materials Co.,
Ltd., China) with a diameter of 5 mm and a thickness of 1 mm are ultrasonically cleaned with ethanol and pure water for three times and then dried; immerse the cleaned and dried ceramic tiles in polyethyleneimine solution (5 mg/mL with deionized water, pH 9.0) for 4 h, then air-dry them in a ventilated environment at room temperature for 4 h; 1 mg/mL chitosan solution is prepared by dissolving 1 g chitosan in 100 mL of 1% (v/v) glacial acetic acid solution with a magnetic stirrer; prepare 100 mg/mL chlorogenic acid dimethyl sulfoxide solution, dilute the chlorogenic acid dimethyl sulfoxide solution with chitosan solution according to the concentrations of 0.025 mg/mL, 0.05 mg/mL and 0.1 mg/mL, respectively, soak the above ceramic tiles in the solution for 24 h, rinse and dry with pure water, and store them under aseptic condition at 37°C for later use.
Effect verification 1
Three zirconia implants prepared in Embodiment 1 are used as the experimental group, and zirconia implants grafted with polyethyleneimine alone and zirconia implants without grafting treatment are used as the control.
(1) XPS LU504657
XPS (Escalab 250xi, Thermo Fisher Scientific, UK) is used to detect the combination of silane and zirconia at the end of different zirconia implants. Specifically, it is measured by monochromatic AlKa irradiation (1486.7 eV) at 225 W, and the incident angle is 90°. The carbon spectrum and oxygen spectrum of XPS are analyzed by CasaXPS software, and the binding energy of each spectrum is calibrated by C1 (285.0 eV). The results are shown in Fig. 2. (2) Contact angle
The surface hydrophilicity of zirconia implants in each group is tested. Using a contact angle meter (SL200, Kino Industry, Boston, MA, USA), the hydrophilicity of zirconia implants is detected by the contact angle of 1 uL water drops. Select one zirconia implant from each group, measure the contact angles at three places to get the average value, and evaluate the wettability of each group. The results are shown in Fig. 3. As can be seen from Fig. 3, compared with pure zirconia ceramic tiles, the water contact angle of zirconia surface coated with PEI is significantly reduced from 79.39° to 45.86°, and the hydrophilicity is increased. The decrease of contact angle and the increase of hydrophilicity can be attributed to the existence of amino functional groups with positive charges in CS molecules. After grafting chlorogenic acid, the contact angle further decreased to 36.18°, because the phenolic hydroxyl and carboxyl groups of chlorogenic acid increased its hydrophilic effect.
Effect verification 2 (1) Immunofluorescence
MC3T3-E1 cells (Shanghai Cell Bank of China Academy of Sciences) are cultured on zirconia implants prepared in Embodiment 1 for 6 h, washed with 1xPBS for three times to remove the culture medium and floating cells, fixed with 4% paraformaldehyde for 30 min, and then permeabilized with 0.1% Triton X-100. The nucleus and cytoskeleton are stained by DAPI (ApexBio, USA) and phalloidin, respectively, and the samples are observed by laser confocal scanning microscope (ZEISS LSM710, CarlZeiss, Germany).
The results are shown in Fig. 4. As can be seen from Fig. 4, the cells cultured on the surface of chlorogenic acid grafted zirconia show flat polygonal morphology and obvious actin stress fibers, and with the increase of concentration, the polygonal morphology and)504657 fibers become more obvious, indicating that the cells have strong adhesion at the interface. (2) Western blot method
The protein on the 7th day of culture is extracted with RIPA lysis buffer (Beyotime
Biotechnology, China). After protein is separated on 10% SDS-PAGE gel (BioFroxx,
Germany), the sample is transferred to PVDF membrane (Millibo, Germany). After blocking with quick blocking solution, the primary antibody is incubated overnight at 4°C.
After TBST washed PVDF membrane for three times, the secondary antibody is labeled for 1 h. All antibodies are used at 1:1000 dilution, and GAPDH is used as internal reference. Observe the expression of COL-1, RUNX2, OCN proteins in MC3T3-E1 cells on the surface of zirconia before and after chlorogenic acid grafting by western blot, and the results are shown in Fig. 5. It can be concluded from Fig. 5 that the expression of
COL-1, RUNX2 and OCN proteins in MC3T3-E1 cells on the surface of chlorogenic acid grafted zirconia increased. (3) cell proliferation
The number of cells on the 1st and 4th day is estimated by the cell counting kit-8 (Dojindo
Molecular Technologies, Kumamoto, Japan). 0.9 mL medium and 0.1 mL CCK-8 are used to replace the medium for 2 h. Then, 100 uL of the above culture medium is transferred to a 96-well plate for detection. The medium with CCK-8 solution but no cells is used as the control group. The absorption of the medium at 450 nm is measured using a micro flat-panel reader (PerkinElmer, Waltham, MA, USA). Subtract the absorbance of cell-free culture medium (blank group) from the sample value. Each group has 5 holes, and the optical density (OD) is expressed by the average absorbance. The effect of cell proliferation iis evaluated according to the relative growth rate (RGR) of cells, and the relative growth rate of cells is calculated by the following formula: RGR of experimental group = (OD- blank group OD/ control group OD-blank group OD) x 100%. It can be seen from Fig. 6 that chlorogenic acid has a good proliferation effect on osteoblasts in the surface coating treatment of polyethyleneimine/chitosan, dopamine and MPTS. It can be seen from Fig. 7 that with the increase of drug concentration, the relative growth rates of cells on the first day and the fourth day show an increasing trend compared with the blarik)504657 group, indicating that chlorogenic acid promotes the growth of osteoblasts in the early stage. Among them, the relative growth rate of cells in PEI group decreases on the first day because PEI has certain cytotoxicity.
The above-mentioned embodiments only describe the preferred mode of the invention, and do not limit the scope of the invention. Under the premise of not departing from the design spirit of the invention, various modifications and improvements made by ordinary technicians in the field to the technical scheme of the invention shall fall within the protection scope determined by the claims of the invention.
Claims (10)
1. A zirconia implant, characterized by comprising a substrate, a coating and an active molecule, wherein the substrate is zirconia ceramics, the coating is a polyethyleneimine/chlorogenic acid-chitosan coating attached to the surface of the substrate.
2. The zirconia implant according to claim 1, characterized in that the polyethyleneimine/chlorogenic acid-chitosan coating comprises a polyethyleneimine film attached to the surface of the substrate and chlorogenic acid-chitosan complex grafted onto the polyethyleneimine film.
3. A preparation method of the zirconia implant according to claim 1 or 2, characterized by comprising: cleaning and drying the zirconia ceramics, first soaking in a polyethyleneimine solution to form a polyethyleneimine film, then soaking in a chlorogenic acid-chitosan solution to form a polyethyleneimine/chlorogenic acid-chitosan coating to obtain the zirconia implant.
4. The preparation method of the zirconia implant according to claim 3, characterized in that the concentration of the polyethyleneimine solution is 5 mg/mL, and the pH is 9.0.
5. The preparation method of the zirconia implant according to claim 3, characterized in that the concentration of the chitosan solution is 1 g/mL and the viscosity is 100-200 P.
6. The preparation method of the zirconia implant according to claim 3, characterized in that the concentration of chlorogenic acid solution is 0.025-0.1 mg/mL.
7. The preparation method of the zirconia implant according to claim 6, characterized 504657 that the chlorogenic acid solution is obtained by diluting chlorogenic acid pre-solution; the chlorogenic acid pre-solution is a chlorogenic acid dimethyl sulfoxide solution of 100 mg/mL.
8. The preparation method of the zirconia implant according to claim 3, characterized in that the soaking time of the zirconia ceramic in the polyethyleneimine solution is 4 h.
9. The preparation method of the zirconia implant according to claim 3, characterized in that the chlorogenic acid solution is dissolved in chitosan solution, and the final concentration is 0.1 mg/mL.
10. The preparation method of the zirconia implant according to claim 3, characterized in that the soaking time of the zirconia ceramic in the chitosan-chlorogenic acid solution is 24 h.
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