CN106539627A - A kind of tooth implant of the bioactivity surface containing RGD - Google Patents
A kind of tooth implant of the bioactivity surface containing RGD Download PDFInfo
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- CN106539627A CN106539627A CN201611208563.5A CN201611208563A CN106539627A CN 106539627 A CN106539627 A CN 106539627A CN 201611208563 A CN201611208563 A CN 201611208563A CN 106539627 A CN106539627 A CN 106539627A
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- 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
- A61C8/0018—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 shape
- A61C8/0022—Self-screwing
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- 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
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- 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
- A61C8/0016—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 polymeric material
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- 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
- A61C8/0018—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 shape
- A61C8/0037—Details of the shape
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/30—Inorganic materials
- A61L27/306—Other specific inorganic materials not covered by A61L27/303 - A61L27/32
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- 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
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/25—Peptides having up to 20 amino acids in a defined sequence
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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
- A61L2300/404—Biocides, antimicrobial agents, antiseptic 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
- A61L2300/606—Coatings
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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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/04—Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
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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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/08—Coatings comprising two or more layers
Abstract
The present invention discloses a kind of tooth implant of the bioactivity surface containing RGD, is specifically improving tooth implant structure simultaneously, outer surface is improved, the tooth implant with different number of plies coatings is constructed.Its coating relies primarily on cation and anion electrostatic attraction each other, forms the molecular coatings of ordered arrangement in the planting body surface of solids, because shitosan RGD and AMP compound is the biomaterial with good biodegradability properties and biocompatibility.Due to the presence of top layer chondroitin sulfate layer antibacterial peptide layer lamination layer structure, with lasting, efficient sterilized, anti-infection ability, its antibacterial, anti-apoptotic activities, adhesion, survival, growth and the differentiation of various kinds of cell (such as Gegenbaur's cell, cartilage cell) can be supported, is had broad application prospects.
Description
Technical field
The invention belongs to tooth implant technical field, and in particular to a kind of tooth implant of the bioactivity surface containing RGD.
Background technology
With the continuous development of tooth implant technology, and widely approved by doctor patient, and sent out in dentistry in recent years
Open up most fast one professional, constantly make a breakthrough, specialty help is provided for more tooth disease patients.However, not
Obtaining another present situation not recognized is, existing intervention device is easy to infection after implanting.Main infection mechanism is
Material surface is sticked to first into internal bacterium, and due to nutrient environment abundant in vivo, bacterium occurs breeding, defines one
The biomembrane of layer protectiveness.It is biomembranous to exist so that the infection of medical apparatus initiation is particularly refractory.
Roos.Jansaker etc. carries out follow-up for many years to plantation postoperative patient, examines bleeding while not occurring there is spy
Deossification carries out clinical case statistics for diagnostic criteria, as a result shows, the incidence of disease of peri-implant mucositis is about 79%；Very
To there are some researches show, about have more than 90% planting body and spy occurred and examine bleeding.And peri-implantitiss can cause peri-implant
The defect of bone tissue, forfeiture, such as treatment can cause the loose or dislocation of planting body not in time.
As the main component of dental implant surface is generally processed as negatively charged state.And will be poly- containing electropositive groups
Compound such as shitosan has preferable adhesion with dental implant surface.In addition containing with hydroxyl hydrogen-bond donor/acceptor each other
The polymer of group, such as sodium alginate, hydroxypropyl cellulose etc. are likely to have certain adhesion with dental implant surface.
Biologically active peptide be in protein 20 natural amino acids with different compositions and arrangement mode constituted from dipeptides to
The general name of complicated linear, loop configuration different peptides, is derived from the multi-functional compounds of protein.Active peptide has various
Body metabolism and physiological regulation function, absorption easy to digest have promotion immunity, hormone control, antibacterial, antiviral, hypotensive, drop blood
Fat etc. is acted on.
RGD is made up of arginine, glycine and aspartic acid, is present in various kinds of cell epimatrix, can be integrated with 11 kinds
Element specific binding, can be effectively facilitated adhesion of the cell to biomaterial.RGD sequence is fixed on into titanium or titanium alloy implant
Surface, can promote adhesion of the Gegenbaur's cell to titanium or titanium alloy surface, further promote implant osseointegration, improve plantation justice
The success rate of tooth.The space structure of RGD sequence, modification density, around sequence pair its activity have certain impact.
In a word, tooth implant requires very high to the surface nature of material.Therefore, explore new dental implant surface to change
Property method has been increasingly becoming the direction of scientific rersearch of field of planting.
The content of the invention
By solving the technical scheme that adopts of above-mentioned technical problem it is：A kind of tooth of the bioactivity surface containing RGD is disclosed
Planting body, manual tooth planting's external surface are provided with screw thread, and the implanting body of artificial tooth two ends are respectively neck and head,
Characterized in that, helical form self tapping groove is provided with the outer surface of the head, the hand of spiral of the helical form self tapping groove with
Hand of thread spiral is identical, and the lead angle of the helical form self tapping groove is different from the lead angle of screw thread, the antibacterial peptide layer
To be covered in thread surface, basic unit's implant surface is sequentially coated with titanium dioxide layer, positive charge chitosan layer and negative electrical charge
RGD peptide layer or the alternatively stacked slow release layer of AMP composite layers, outer layer load chondroitin sulfate layer-antibacterial peptide layer.
For above-mentioned technical proposal, it is preferred in the case of, preparation method includes following operating procedure：
(1) 100mg RGD peptides are first weighed add to the concentration of 10ml and be 1% Acetic acid-sodium acetate buffer solution；It is slowly stirred
To after dissolving, EDCHCl 500mg are added, NHS 250mg are added, 12h is activated through magnetic stirring apparatus；It is put into ddH2In O
Dialysis, it is overnight under magnetic stirrer state；Obtain RGD peptide solution；
(2) implant surface is polished, cleans, drying；With 50～100 μm of TiO2Particulate carries out sandblasting to implant surface
Process；Being placed in the mixing etching agent that hydrofluoric acid is constituted with hydrochloric acid again carries out surface etching treatment, takes out planting body and is cleaned by ultrasonic,
It is dried；Planting body is placed in into 60 DEG C, 5mol/L NaOH solutions incubation 24-48h again, is cleaned by ultrasonic with water standby；
(3) tooth implant described in step (2) is immersed in into 10～20min in the chitosan solution of 0.5～5mg/ml, with
Dental implant surface is made to become positively charged lotus；Deionized water is fully cleaned again；
(4) tooth implant described in step (3) is immersed in into more than 3h in the RGD peptide solution described in step (1)；Or submergence
5～10min in AMP complex solution of the concentration for lmg/ml, so that negative electrical charge on dental implant surface band；Deionization is used again
Water is fully cleaned；
The number of plies for assembling as needed, repeat step (3), (4) and (3) can obtain the tooth kind with different number of plies coatings
Implant；
(5) tooth implant described in step (4) is soaked in chondroitin sulfate sodium sulfate salt solution of the concentration for 2mg/mL
5～15min of bubble, solution system control ph are 6, then are spontaneously dried after deionized water is fully cleaned；Sulfuric acid is coated with again
It is 7 that the tooth implant of chondroitin is soaked in pH value, and concentration is 5～15min in the antibacterial peptide solution of 0.5mg/mL, then uses deionization
Water is spontaneously dried after fully cleaning, and acquisition is coated with the material of chondroitin sulfate layer-antibacterial peptide layer composite bed.
In above-mentioned technical proposal, the RGD is the short peptide sequence of Arg-Gly-Asp, by arginine, glycine and asparagus fern ammonia
Acid composition；
The EDCHCl be 1- ethyls-(3- dimethylaminopropyls) phosphinylidyne diimmonium salt hydrochlorate, English name：1-
(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride；
The NHS be N-hydroxy-succinamide, English name:N-Hydroxysuccinimide；
The AMP be cationic antimicrobial small peptide, English name:cationic antimicrobial peptides.For
Above-mentioned technical proposal, it is preferred in the case of, a kind of tooth implant of described bioactivity surface containing RGD, wherein, it is described
Cleaning refers to that deionized water, ethanol and acetone are cleaned by ultrasonic, and after being dried up with nitrogen, is put in vacuum drying chamber, in 60 DEG C of bar
It is dried 24 hours under part.
For above-mentioned technical proposal, it is preferred in the case of, a kind of Dental implantion of described bioactivity surface containing RGD
Body, wherein, the deacetylation of described shitosan is that 50～98%, Mw is 100～1500kDa.
For above-mentioned technical proposal, it is preferred in the case of, a kind of Dental implantion of described bioactivity surface containing RGD
Body, wherein, during described chitosan solution is the acetic acid solution for dissolve chitosan in 0.3～3%, it is made into 0.5～5mg/ml
Chitosan solution, resulting solution is mixed with atoleine, volume ratio is 0.1～0.4, and add volumetric concentration for 0.5～
1% sorbester p17, while adding dispersant magnesium stearate, sorbester p17 is 2～4: 1 with the mass ratio of magnesium stearate, stirring gained
Water-in-oil emulsion, is added thereto to the crosslinking agent vanillic aldehyde 1ml of 5～10mg/ml, and 4～6 are reacted under 40 DEG C～60 DEG C stirrings
After hour；Standing takes supernatant；The chitosan particle of gained is added into a small amount of glacial acetic acid solution with aqueous suspension again, magnetic force is stirred
Mix under device stirring condition, add NaCl so as to which final concentration reaches 0.15M；The solution is positively charged.
For above-mentioned technical proposal, it is preferred in the case of, a kind of Dental implantion of described bioactivity surface containing RGD
Body, wherein, the standing takes supernatant and refers to, stands more than 12 hours oil-water separation phases, takes lower aqueous solution, adjusts pH value and is
8～9, sediment is centrifuged off, supernatant is taken and is obtained chitosan particle suspension.
For above-mentioned technical proposal, it is preferred in the case of, a kind of Dental implantion of described bioactivity surface containing RGD
Body, wherein, the concentration for the collocation method of the AMP complex solutions of lmg/ml is：The concentration is combined for the AMP of lmg/ml
The collocation method of thing solution is：Weigh 50mg AMP composite powders to add to after the sterilizing of 50ml in deionized water, stirring is abundant
To being completely dissolved, it is 5.0 that acetic acid on the rocks adjusts pH, and this solution carries positive charge.
For above-mentioned technical proposal, it is preferred in the case of, the self tapping groove is made up of two arc surfaces, two arc surfaces
Binding site is tangent connection；The self tapping groove number is two or more, described two above self tapping grooves be distributed on head outward
Surface；The head is frustum, and near neck, the head is circular arc away from one end of neck to the bigger diameter end of the head frustum
Face；The neck is frustum, and the bigger diameter end of the neck frustum is near head；The depth of the self tapping groove is from the little of head frustum
Footpath end is gradually become shallower as to the bigger diameter end of head frustum.
For above-mentioned technical proposal, it is preferred in the case of, the blind hole is coaxial with planting body, and the blind hole includes coaxially suitable
The conical bore of secondary connection, quincunx hole, cylindrical hole and screwed hole, the conical bore near blind hole openend, the conical bore is
Meet the conical bore in Morse's cone face；It is quincunx through hole that the quincunx hole is cross section.
The present invention character of innovation be：
The tooth implant with different number of plies coatings prepared by the present invention.Its coating relies primarily on cation and anion
Electrostatic attraction each other, the planting body surface of solids formed ordered arrangement molecular coatings because shitosan and RGD layers or
AMP composite layers are the biomaterials with good biodegradability properties and biocompatibility.Due to top layer chondroitin sulfate layer-anti-
The presence of bacterium peptide layer lamination layer structure, with lasting, efficient sterilized, anti-infection ability, its antibacterial, anti-apoptotic activities can
Adhesion, survival, growth and the differentiation of various kinds of cell (such as Gegenbaur's cell, cartilage cell) are supported, is had broad application prospects.
Description of the drawings
Fig. 1 is the front view of planting body of the present invention；
Specific embodiment
Following non-limiting examples can make one of ordinary skill in the art be more fully understood the present invention, but not with
Any mode limits the present invention.Any those familiar with the art in the technical scope of present disclosure, according to
Technical scheme and its inventive concept carry out equivalent or change belongs to protection category of the present invention.
AMP complex solution of the configuration concentration for lmg/ml；
Weigh 50mg AMP composite powders to add to after the sterilizing of 50ml in deionized water, stirring fully to being completely dissolved,
It is 5.0 that acetic acid on the rocks adjusts pH, and this solution carries positive charge.
Configuration concentration is 0.5mg/mL antibacterial peptide solutions
5mg antibacterial peptides are weighed, is dissolved in 10mL deionized waters, it is 7 to be prepared into pH value, and concentration is anti-for 0.5mg/mL
Bacterium peptide solution.
Configuration RGD peptide solution
Weigh 100mg RGD peptides and add to the concentration of 10ml and be 1% Acetic acid-sodium acetate buffer solution；It is slowly stirred to molten
Xie Hou, adds EDCHCl 500mg, adds NHS 250mg, activates 12h through magnetic stirring apparatus；It is put into ddH2In O thoroughly
Analysis, the acquisition RGD peptide solution overnight under magnetic stirrer state；
In following embodiments, implanting body of artificial tooth used has following architectural feature：
Manual tooth planting's external surface is provided with screw thread, as shown in figure 1, the plantation external surface is provided with screw thread,
Planting body two ends are respectively neck 6 and head 5, and helical form self tapping groove 2, helical form self tapping groove 2 are provided with the outer surface of head 5
The hand of spiral of the hand of spiral and screw thread be dextrorotation, the lead angle of the lead angle of helical form self tapping groove 2 more than screw thread.
Self tapping groove 2 is made up of the first arc surface 3 and the second arc surface 4, and the binding site of the first arc surface 3 and the second arc surface 4 is phase
Connection is cut, angle fluting stress concentration around the corner can be avoided, planting body intensity is improved.The present embodiment head 5 is frustum,
About 80 ° of the taper conical surface of head frustum and the angle of horizontal plane, the bigger diameter end of 5 frustum of head near neck 6, head 5 away from
One end of neck 6 is arc surface 1；Neck 6 is frustum, and the bigger diameter end of 6 frustum of neck is near head 5.The depth of self tapping groove 2 is from head
The miner diameter end of 5 frustum of portion is gradually become shallower as to the bigger diameter end of 5 frustum of head, with bone tissue after the volume of self tapping groove 2 and screw thread extruding
Volume is consistent.The antibacterial peptide layer is to be covered in thread surface, and basic unit is titanium dioxide nanotube array layer, then by positive charge
Chitosan layer and negative electrical charge Sodium Hyaluronate layer are alternately assembled, the knot of outer layer load chondroitin sulfate layer and antibacterial peptide layer composition
Structure.
Embodiment 1
(1) by the tooth implant that surface is titanium dioxide layer, deionized water, ethanol and acetone ultrasonic cleaning, use successively
After nitrogen is dried up, it is put in vacuum drying chamber, is dried 24 hours under conditions of 60 DEG C, places standby；
(2) dissolve chitosan in 0.3% acetic acid solution, be made into the chitosan solution of 0.5mg/ml, described shell
The deacetylation of glycan is 1000kDa for 50%, Mw.
(3) step (2) resulting solution is mixed with atoleine, volume ratio is 0.1, and adds volumetric concentration to be 0.5%
Sorbester p17, while adding dispersant magnesium stearate, the mass ratio of sorbester p17 and magnesium stearate is 2: 1, is stirred 1 hour under room temperature
More than, form uniform water-in-oil emulsion；
(4) in the crosslinking agent vanillic aldehyde 1ml by 5mg/ml is added in water-in-oil emulsion obtained by step (3), 40 DEG C of stirring shapes
React 4 hours under state, obtain chitosan particle；
(5) step (4) products therefrom is stood into more than 12 hours oil-water separation phases, takes lower aqueous solution, adjusting pH value is
8, sediment is centrifuged off, supernatant is taken and is obtained chitosan particle suspension
(6) the chitosan particle suspension in deionized water obtained by addition step (5), adds the glacial acetic acid solution of lml,
Under the conditions of magnetic stirrer, NaCl is added so as to which final concentration reaches 0.15M；The solution is positively charged；
Embodiment 2
(1) by the tooth implant that surface is titanium dioxide layer, deionized water, ethanol and acetone ultrasonic cleaning, use successively
After nitrogen is dried up, it is put in vacuum drying chamber, is dried 24 hours under conditions of 60 DEG C, places standby；
(2) dissolve chitosan in 3% acetic acid solution, be made into the chitosan solution of 5mg/ml, described shitosan
Deacetylation be 1500kDa for 98%, Mw.
(3) step (2) resulting solution is mixed with atoleine, volume ratio is 0.4, and adds volumetric concentration to be 1%
Sorbester p17, while adding dispersant magnesium stearate, the mass ratio of sorbester p17 and magnesium stearate is 4: 1, stir under room temperature 1 hour with
On, form uniform water-in-oil emulsion；
(4) in the crosslinking agent vanillic aldehyde 1ml by 10mg/ml is added in water-in-oil emulsion obtained by step (3), 60 DEG C of stirring shapes
React 6 hours under state, obtain chitosan particle；
(5) step (4) products therefrom is stood into more than 12 hours oil-water separation phases, takes lower aqueous solution, adjusting pH value is
9, sediment is centrifuged off, supernatant is taken and is obtained chitosan particle suspension
(6) the chitosan particle suspension in deionized water obtained by addition step (5), adds the glacial acetic acid solution of lml,
Under the conditions of magnetic stirrer, NaCl is added so as to which final concentration reaches 0.15M；The solution is positively charged；
Embodiment 3
Implant surface is polished, is cleaned, drying；With 100 μm of TiO2Particulate carries out blasting treatment to implant surface；Again
Being placed in the mixing etching agent that hydrofluoric acid is constituted with hydrochloric acid carries out surface etching treatment, takes out planting body and is cleaned by ultrasonic, is dried；Again
Planting body is placed in into 60 DEG C, 5mol/L NaOH solutions incubation 48h, is cleaned by ultrasonic with water standby.
Embodiment 4
(1) tooth implant that the process of embodiment 3 is obtained is immersed in the chitosan solution described in example 2 above
20min, the lotus so that dental implant surface becomes positively charged；Deionized water is fully cleaned again；
(2) tooth implant described in step (1) is immersed in into more than 3h in RGD peptide solution；Or concentration is immersed in for lmg/
10min in the AMP complex solutions of ml, so that negative electrical charge on dental implant surface band；Deionized water is fully cleaned again；
(3) number of plies for assembling as needed, repeat step (1), (2) and (1) can be obtained with different number of plies coatings
Tooth implant；
(4) tooth implant described in step (3) is soaked in chondroitin sulfate sodium sulfate salt solution of the concentration for 2mg/mL
Bubble 15min, solution system control ph are 6, then are spontaneously dried after deionized water is fully cleaned；Chondroitin sulfate is coated with again
It is 7 that the tooth implant of element is soaked in pH value, and concentration is abundant for 15min in the antibacterial peptide solution of 0.5mg/mL, then deionized water
Spontaneously dry after cleaning.
Embodiment 5
The tooth implant of different number of plies coatings is assembled in embodiment 4 as needed will, it is soft for the sulfuric acid of 2mg/mL in concentration
Immersion 20min in ossein sodium sulfate salt solution (polysaccharide solution with negative electrical charge), solution system control ph is 6, then is spent
Ionized water is spontaneously dried after fully cleaning；
It is 7 that the material for having chondroitin sulfate will be coated and be soaked in pH value, and concentration is in the antibacterial peptide solution of 0.5mg/mL
15min, then spontaneously dry after deionized water is fully cleaned, acquisition is coated with chondroitin sulfate layer-antibacterial peptide layer composite bed
Material.
For the tooth implant that said method is prepared, surface contact angle analysis is carried out, its result is from hydrophily and profit
The presence of coating is also demonstrate that on moist.
Understood according to analysis, the tooth implant with different number of plies coatings prepared by the present invention.Its coating is relied primarily on
Cation and anion electrostatic attraction each other, form the molecular coatings of ordered arrangement in the planting body surface of solids, because
Shitosan and RGD or AMP compounds are the biomaterials with good biodegradability properties and biocompatibility.Along with top layer sulphur
The presence of aching and limp ossein layer-antibacterial peptide layer lamination layer structure, it is lasting, efficient sterilized, anti-infective that the tooth implant must have
Ability, its antibacterial, anti-apoptotic activities, it would be preferable to support the adhesion of various kinds of cell (such as Gegenbaur's cell, cartilage cell), survival, growth
With differentiation, have broad application prospects.In planting body clinical practice, promote planting body. osseous tissue interface's healing, raising bone
Integration rate and the benefit for improving planting body primary stability are obvious.
Claims (9)
1. a kind of tooth implant of the bioactivity surface containing RGD, it is characterised in that：Manual tooth planting's external surface is arranged
There is screw thread, the implanting body of artificial tooth two ends are respectively neck and head, it is characterised in that arrange on the outer surface of the head
There is helical form self tapping groove, the hand of spiral of the helical form self tapping groove is identical with hand of thread spiral, the helical form self tapping groove
Lead angle it is different from the lead angle of screw thread, the antibacterial peptide layer is to be covered in thread surface, basic unit's implant surface
Titanium dioxide layer, positive charge chitosan layer and negative electrical charge RGD peptide layer or the alternatively stacked sustained release of AMP composite layers are coated with sequentially
Layer, outer layer load chondroitin sulfate layer-antibacterial peptide layer.
2. the tooth implant of a kind of bioactivity surface containing RGD according to claim 1, it is characterised in that：Its preparation
Method includes following operating procedure：
(1) 100mg RGD are first weighed add to the concentration of 10ml and be 1% Acetic acid-sodium acetate buffer solution；It is slowly stirred to dissolving
Afterwards, EDCHCl 500mg are added, add NHS 250mg, 12h is activated through magnetic stirring apparatus；It is put into ddH2Dialyse in O,
It is overnight under magnetic stirrer state；Obtain RGD peptide solution；
(2) implant surface is polished, cleans, drying；With 50～100 μm of TiO2Particulate carries out blasting treatment to implant surface；
Being placed in the mixing etching agent that hydrofluoric acid is constituted with hydrochloric acid again carries out surface etching treatment, takes out planting body and is cleaned by ultrasonic, is dried；
Planting body is placed in into 60 DEG C, 5mol/L NaOH solutions incubation 24-48h again, is cleaned by ultrasonic with water standby；
(3) tooth implant described in step (2) is immersed in into 10～20min in the chitosan solution of 0.5～5mg/ml, so that tooth
Implant surface becomes positively charged lotus；Deionized water is fully cleaned again；
(4) tooth implant described in step (3) is immersed in into more than 3h in the RGD peptide solution described in step (1)；Or be immersed in dense
5～10min in the AMP complex solutions for lmg/ml is spent, so that negative electrical charge on dental implant surface band；Deionized water is filled again
Distinguish and wash；
The number of plies for assembling as needed, repeat step (3), (4) and (3) can obtain the Dental implantion with different number of plies coatings
Body；
(5) by the tooth implant described in step (4) concentration for 2mg/mL chondroitin sulfate sodium sulfate salt solution in immersion 5～
15min, solution system control ph are 6, then are spontaneously dried after deionized water is fully cleaned；Chondroitin sulfate is coated with again
Tooth implant be soaked in pH value for 7, concentration is abundant for 5～15min in the antibacterial peptide solution of 0.5mg/mL, then deionized water
Spontaneously dry after cleaning, acquisition is coated with the material of chondroitin sulfate layer-antibacterial peptide layer composite bed.
3. the tooth implant of a kind of bioactivity surface containing RGD according to claim 1, it is characterised in that：Described
Cleaning refers to that deionized water, ethanol and acetone are cleaned by ultrasonic, and after being dried up with nitrogen, is put in vacuum drying chamber, in 60 DEG C of bar
It is dried 24 hours under part.
4. the tooth implant of a kind of bioactivity surface containing RGD according to claim 1, it is characterised in that：Described
It is 100～1500kDa that the deacetylation of shitosan is 50～98%, Mw.
5. the tooth implant of a kind of bioactivity surface containing RGD according to claim 1, it is characterised in that：Described
During chitosan solution is the acetic acid solution for dissolve chitosan in 0.3～3%, the chitosan solution of 0.5～5mg/ml is made into, will
Resulting solution is mixed with atoleine, and volume ratio is 0.1～0.4, and adds the sorbester p17 that volumetric concentration is 0.5～1%, while
Dispersant magnesium stearate is added, sorbester p17 is 2～4: 1 with the mass ratio of magnesium stearate, stirring gained water-in-oil emulsion, thereto
The crosslinking agent vanillic aldehyde 1ml of 5～10mg/ml is added, after reacting 4～6 hours under 40 DEG C～60 DEG C stirrings；Standing takes supernatant
Liquid；The chitosan particle of gained is added into a small amount of glacial acetic acid solution with aqueous suspension again, under the conditions of magnetic stirrer, then
Add NaCl so as to which final concentration reaches 0.15M；The solution is positively charged.
6. the tooth implant of a kind of bioactivity surface containing RGD according to claim 5, it is characterised in that：It is described quiet
Put and take supernatant and refer to, stand more than 12 hours oil-water separation phases, take lower aqueous solution, it is 8～9 to adjust pH value, is centrifuged off
Sediment, takes supernatant and obtains chitosan particle suspension.
7. the tooth implant of a kind of bioactivity surface containing RGD according to claim 1, it is characterised in that：It is described dense
The collocation method for spending the AMP complex solutions for lmg/ml is：Weigh after 50mg AMP composite powders add to the sterilizing of 50ml
In deionized water, fully to being completely dissolved, it is 5.0 that acetic acid on the rocks adjusts pH, and this solution carries positive charge for stirring.
8. according to claim 1 comprising the dentistry implant for being coated with antibacterial peptide layer, it is characterised in that：The self tapping groove
It is made up of two arc surfaces, the binding site of two arc surfaces is tangent connection；The self tapping groove number is two or more, described
Two or more self tapping groove is distributed on the outer surface of head；The head be frustum, the bigger diameter end of the head frustum near neck,
The head is arc surface away from one end of neck；The neck is frustum, and the bigger diameter end of the neck frustum is near head；Institute
The depth for stating self tapping groove is gradually become shallower as from the miner diameter end of head frustum to the bigger diameter end of head frustum.
9. according to claim 1 comprising the dentistry implant for being coated with antibacterial peptide layer, it is characterised in that：The blind hole with
Planting body is coaxial, and the blind hole includes conical bore, quincunx hole, cylindrical hole and the screwed hole being coaxially sequentially connected with, the circular cone
Near blind hole openend, the conical bore is the conical bore for meeting Morse's cone face in hole；It is plum that the quincunx hole is cross section
Flower-shape through hole.
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Cited By (1)
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| CN110893121A (en) * | 2018-09-13 | 2020-03-20 | 光弘生医科技股份有限公司 | Implant structure and preparation method thereof |
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