CN106539627B - A kind of dental implant of the bioactivity surface containing RGD - Google Patents
A kind of dental implant of the bioactivity surface containing RGD Download PDFInfo
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- CN106539627B CN106539627B CN201611208563.5A CN201611208563A CN106539627B CN 106539627 B CN106539627 B CN 106539627B CN 201611208563 A CN201611208563 A CN 201611208563A CN 106539627 B CN106539627 B CN 106539627B
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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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- 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
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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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- 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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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Abstract
The present invention discloses a kind of dental implant of bioactivity surface containing RGD, is specifically improving dental implant structure simultaneously, is improving to outer surface, construct the dental implant with different number of plies coatings.Its coating relies primarily on cation and the mutual electrostatic attraction of anion, the molecular coatings of ordered arrangement is formed in the planting body surface of solids, because chitosan RGD and AMP compound is the biomaterial with good biodegradability properties and biocompatibility.Due to the presence of surface layer chondroitin sulfate layer-antibacterial peptide layer lamination layer structure, there is lasting, efficient sterilization, anti-infection ability, antibacterial, anti-apoptotic activities can support adherency, survival, growth and the differentiation of various kinds of cell, have broad application prospects.
Description
Technical field
The invention belongs to dental implant technical fields, and in particular to a kind of dental implant of the bioactivity surface containing RGD.
Background technique
Widely approve with the continuous development of dental implant technology, and by doctor patient, and sends out in dentistry in recent years
A most fast profession is opened up, constantly makes a breakthrough, provides professional help for more tooth disease patients.However, not
Obtaining another status not recognized is that existing intervention device is easy to infect after implanting.Main infection mechanism is
It is adhered to first on the surface of the material into intracorporal bacterium, due to internal nutrient environment abundant, bacterium is bred, and forms one
The protective biomembrane of layer.The infection that the presence of biomembrane causes medical apparatus is especially refractory.
Roos.Jansaker etc. carries out the follow-up of many years to plantation postoperative patient, to examine bleeding in the presence of spy while not occur
Deossification is that diagnostic criteria carries out clinical case statistics, the results show that the disease incidence of peri-implant mucositis is about 79%;Very
To some researches show that, about have more than 90% planting body occurred visit examine bleeding.And peri-implantitiss can lead to peri-implant
The defect of bone tissue is lost, and the loose or dislocation that can lead to planting body is such as not treated in time.
Since the main component of dental implant surface is usually handled as negatively charged state.And it will be poly- containing electropositive groups
Closing object such as chitosan and dental implant surface has preferable adhesion.In addition containing with hydroxyl hydrogen-bond donor/receptor each other
The polymer of group, such as sodium alginate, hydroxypropyl cellulose may also have certain adhesion with dental implant surface.
Biologically active peptide be in protein 20 natural amino acids with it is different form and arrangement mode constituted slave dipeptides to
The general name of complicated linear, ring structure different peptides, is derived from the multi-functional compounds of protein.Active peptide has a variety of
Body metabolism and physiological regulation function, absorption easy to digest have immune promotion, hormone control, antibacterial, antiviral, blood pressure lowering, drop blood
The effects of rouge.
RGD is made 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 adherency of the cell to biomaterial.RGD sequence is fixed on titanium or titanium alloy implant
Surface can promote osteoblast to the adherency of 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, surrounding sequence have certain influence to its activity.
In short, dental implant is very high to the surface nature requirement of material.Therefore, novel dental implant surface is explored to change
Property method has been increasingly becoming the direction of scientific rersearch of field of planting.
Summary of the invention
Used technical solution is to solve above-mentioned technical problem: disclosing a kind of tooth of bioactivity surface containing RGD
Planting body, manual tooth planting's external surface are provided with screw thread, and the implanting body of artificial tooth both ends are respectively neck and head,
It is characterized in that, be provided with helical form self tapping slot on the outer surface on the head, the hand of spiral of the helical form self tapping slot with
Hand of thread spiral is identical, and the lead angle of the helical form self tapping slot is different from the lead angle of screw thread, the antibacterial peptide layer
To be covered in thread surface, base'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 layer, outer layer load chondroitin sulfate layer-antibacterial peptide layer.
For above-mentioned technical proposal, in preferred situation, preparation method includes following operating procedure:
(1) 100mg RGD peptide is first weighed to add in the Acetic acid-sodium acetate buffer that the concentration of 10ml is 1%;It is slowly stirred
To dissolution, EDCHCl 500mg is added, adds NHS 250mg, activates 12h by 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, is cleaned, drying;With 50~100 μm of TiO2Particle carries out sandblasting to implant surface
Processing;It is placed in the mixing etching agent of hydrofluoric acid and hydrochloric acid composition again and carries out surface etching treatment, take out planting body ultrasonic cleaning,
It is dry;Planting body is placed in 60 DEG C, 5mol/L NaOH solution incubation 24-48h again, is cleaned by ultrasonic with water spare;
(3) dental implant described in step (2) is immersed in 10~20min in the chitosan solution of 0.5~5mg/ml, with
Dental implant surface is set to become positively charged lotus;It is sufficiently cleaned with deionized water again;
(4) dental implant described in step (3) is immersed in 3h or more in RGD peptide solution described in step (1);Or submergence
5~10min in the AMP complex solution that concentration is lmg/ml, so that negative electrical charge on dental implant surface band;Deionization is used again
Water sufficiently cleans;
The number of plies assembled as needed, repeating step (3), (4) and (3) can be obtained the tooth kind with different number of plies coatings
Implant;
(5) dental implant described in step (4) is soaked in the chondroitin sulfate sodium sulfate salt solution that concentration is 2mg/mL
5~15min is steeped, it is 6 that solution system, which controls pH value, then is spontaneously dried after sufficiently being cleaned with deionized water;It is coated with sulfuric acid again
It is 7 that the dental implant of chondroitin, which is soaked in pH value, and concentration is 5~15min in the antibacterial peptide solution of 0.5mg/mL, then uses deionization
Water spontaneously dries after sufficiently cleaning, and obtains and is coated with chondroitin sulfate layer-antibacterial peptide layer composite layer material.
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 is 1- ethyl-(3- dimethylaminopropyl) phosphinylidyne diimmonium salt hydrochlorate, English name: 1-
(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride;
The NHS is n-hydroxysuccinimide, English name: N-Hydroxysuccinimide;
The AMP is cationic antimicrobial small peptide, English name: cationic antimicrobial peptides.For
Above-mentioned technical proposal, in preferred situation, the dental implant of a kind of bioactivity surface containing RGD, wherein described
Cleaning refers to deionized water, ethyl alcohol and acetone ultrasonic cleaning, after being dried with nitrogen, puts in a vacuum drying oven, in 60 DEG C of item
It is 24 hours dry under part.
For above-mentioned technical proposal, in preferred situation, a kind of Dental implantion of bioactivity surface containing RGD
Body, wherein the deacetylation of the chitosan is that 50~98%, Mw is 100~1500kDa.
For above-mentioned technical proposal, in preferred situation, a kind of Dental implantion of bioactivity surface containing RGD
Body, wherein the chitosan solution is to be made into 0.5~5mg/ml in the acetic acid solution for dissolve chitosan in 0.3~3%
Chitosan solution, acquired solution is mixed with atoleine, volume ratio be 0.1~0.4, and be added volumetric concentration be 0.5~
1% sorbester p17, while dispersing agent magnesium stearate is added, the mass ratio of sorbester p17 and magnesium stearate is 2~4: 1, stirring gained
The crosslinking agent vanillic aldehyde 1ml of 5~10mg/ml is added thereto, reacts 4~6 under 40 DEG C~60 DEG C stirrings for water-in-oil emulsion
After hour;Standing takes supernatant;Resulting chitosan particle is added into a small amount of glacial acetic acid solution with aqueous suspension again, magnetic force stirs
It mixes under device stirring condition, adds NaCl, its final concentration is made to reach 0.15M;The solution is positively charged.
For above-mentioned technical proposal, in preferred situation, a kind of Dental implantion of bioactivity surface containing RGD
Body, wherein the standing takes supernatant to refer to, standing 12 hours or more oil-water separation phases take lower aqueous solution, and adjusting pH value is
8~9, it is centrifuged off sediment, supernatant is taken to obtain chitosan particle suspension.
For above-mentioned technical proposal, in preferred situation, a kind of Dental implantion of bioactivity surface containing RGD
Body, wherein the concentration is the configuration method of the AMP complex solution of lmg/ml are as follows: the concentration is that the AMP of lmg/ml is compound
The configuration method of object solution are as follows: weigh 50mg AMP composite powder and add to after the sterilizing of 50ml in deionized water, stirring is abundant
To being completely dissolved, acetic acid tune pH on the rocks is 5.0, this solution has positive charge.
For above-mentioned technical proposal, in preferred situation, the self tapping slot is made of two arc surfaces, two arc surfaces
Binding site is tangent connection;The self tapping slot number is two or more, and described two above self tapping slots are evenly arranged on the outer of head
Surface;The head is frustum, and for the bigger diameter end of the head frustum close to neck, the one end of the head far from neck is circular arc
Face;The neck is frustum, and the bigger diameter end of the neck frustum is close to head;The depth of the self tapping slot is from the small of head frustum
Diameter end gradually becomes shallower as to the bigger diameter end of head frustum.
For above-mentioned technical proposal, in preferred situation, the blind hole and planting body are coaxial, and the blind hole includes coaxial suitable
The conical bore of secondary connection, quincunx hole, cylindrical hole and threaded hole, the conical bore are close to blind hole open end, the conical bore
Meet the conical bore in Morse's cone face;The quincunx hole is that cross section is quincunx through-hole.
Character of innovation of the invention is:
The dental implant of different number of plies coatings is had prepared by the present invention.Its coating relies primarily on cation and anion
Mutual electrostatic attraction, the planting body surface of solids formed ordered arrangement molecular coatings because chitosan and RGD layers or
AMP composite layer is the biomaterial with good biodegradability properties and biocompatibility.Since surface layer chondroitin sulfate layer-is anti-
The presence of bacterium peptide layer lamination layer structure has lasting, efficient sterilization, anti-infection ability, and antibacterial, anti-apoptotic activities can
Adherency, survival, growth and the differentiation for supporting various kinds of cell (such as osteoblast, cartilage cell), have broad application prospects.
Detailed description of the invention
Fig. 1 is the main view of planting body of the present invention;
Specific embodiment
Following non-limiting embodiments can with a person of ordinary skill in the art will more fully understand the present invention, but not with
Any mode limits the present invention.Anyone skilled in the art within the technical scope of the present disclosure, according to
Technical solution of the present invention and its inventive concept, which are equivalently replaced or change, belongs to protection category of the present invention.
Configuration concentration is the AMP complex solution of lmg/ml;
50mg AMP composite powder is weighed to add to after the sterilizing of 50ml in deionized water, stirring sufficiently to being completely dissolved,
Acetic acid tune pH on the rocks is 5.0, this solution has positive charge.
Configuration concentration is 0.5mg/mL antibacterial peptide solution
5mg antibacterial peptide is weighed, is dissolved in 10mL deionized water, being prepared into pH value is 7, and concentration is anti-for 0.5mg/mL
Bacterium peptide solution.
Configure RGD peptide solution
100mg RGD peptide is weighed to add in the Acetic acid-sodium acetate buffer that the concentration of 10ml is 1%;It is slowly stirred to molten
Xie Hou is added EDCHCl 500mg, adds NHS 250mg, activates 12h by 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 structure 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 both ends are respectively neck 6 and head 5, and helical form self tapping slot 2, helical form self tapping slot 2 are provided on the outer surface on head 5
The hand of spiral and the hand of spiral of screw thread be dextrorotation, the lead angle of helical form self tapping slot 2 is greater than the lead angle of screw thread.
Self tapping slot 2 is made 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, the stress concentration that angle is recessed at corner is can be avoided, improves planting body intensity.The present embodiment head 5 is frustum,
The taper conical surface of head frustum and the angle of horizontal plane are about 80 °, and for the bigger diameter end of 5 frustum of head close to neck 6, head 5 is separate
One end of neck 6 is arc surface 1;Neck 6 is frustum, and the bigger diameter end of 6 frustum of neck is close to head 5.The depth of self tapping slot 2 is from head
The miner diameter end of 5 frustum of portion gradually becomes shallower as to the bigger diameter end of 5 frustum of head, the volume and screw thread of self tapping slot 2 squeeze after with bone tissue
Volume is consistent.The antibacterial peptide layer is to be covered in thread surface, and base is titanium dioxide nanotube array layer, then by positive charge
Chitosan layer and negative electrical charge Sodium Hyaluronate layer alternately assemble, and outer layer loads the knot of chondroitin sulfate layer and antibacterial peptide layer composition
Structure.
Embodiment 1
(1) it is the dental implant of titanium dioxide layer by surface, successively uses deionized water, ethyl alcohol and acetone ultrasonic cleaning, use
After being dried with nitrogen, put in a vacuum drying oven, it is 24 hours dry under conditions of 60 DEG C, it places spare;
(2) it dissolves chitosan in 0.3% acetic acid solution, is made into the chitosan solution of 0.5mg/ml, the shell
The deacetylation of glycan is 50%, Mw 1000kDa.
(3) step (2) acquired solution is mixed with atoleine, volume ratio 0.1, and it is 0.5% that volumetric concentration, which is added,
Sorbester p17, while dispersing agent magnesium stearate is added, the mass ratio of sorbester p17 and magnesium stearate is 2: 1, is stirred 1 hour at room temperature
More than, form uniform water-in-oil emulsion;
(4) the crosslinking agent vanillic aldehyde 1ml of 5mg/ml, 40 DEG C of stirring shapes will be added in water-in-oil emulsion obtained by step (3)
It is reacted 4 hours under state, obtains chitosan particle;
(5) by step (4) products therefrom standing 12 hours or more oil-water separation phases, lower aqueous solution is taken, adjusting pH value is
8, it is centrifuged off sediment, supernatant is taken to obtain chitosan particle suspension
(6) step (5) resulting chitosan particle suspension is added into deionized water, adds the glacial acetic acid solution of lml,
Under the conditions of magnetic stirrer, NaCl is added, its final concentration is made to reach 0.15M;The solution is positively charged;
Embodiment 2
(1) it is the dental implant of titanium dioxide layer by surface, successively uses deionized water, ethyl alcohol and acetone ultrasonic cleaning, use
After being dried with nitrogen, put in a vacuum drying oven, it is 24 hours dry under conditions of 60 DEG C, it places spare;
(2) it dissolves chitosan in 3% acetic acid solution, is made into the chitosan solution of 5mg/ml, the chitosan
Deacetylation be 98%, Mw 1500kDa.
(3) step (2) acquired solution is mixed with atoleine, volume ratio 0.4, and it is 1% that volumetric concentration, which is added,
Sorbester p17, while dispersing agent magnesium stearate is added, the mass ratio of sorbester p17 and magnesium stearate are 4: 1, stir at room temperature 1 hour with
On, form uniform water-in-oil emulsion;
(4) the crosslinking agent vanillic aldehyde 1ml of 10mg/ml, 60 DEG C of stirring shapes will be added in water-in-oil emulsion obtained by step (3)
It is reacted 6 hours under state, obtains chitosan particle;
(5) by step (4) products therefrom standing 12 hours or more oil-water separation phases, lower aqueous solution is taken, adjusting pH value is
9, it is centrifuged off sediment, supernatant is taken to obtain chitosan particle suspension
(6) step (5) resulting chitosan particle suspension is added into deionized water, adds the glacial acetic acid solution of lml,
Under the conditions of magnetic stirrer, NaCl is added, its final concentration is made to reach 0.15M;The solution is positively charged;
Embodiment 3
Implant surface is polished, is cleaned, drying;With 100 μm of TiO2Particle carries out blasting treatment to implant surface;Again
It is placed in the mixing etching agent of hydrofluoric acid and hydrochloric acid composition and carries out surface etching treatment, take out planting body ultrasonic cleaning, it is dry;Again
Planting body is placed in 60 DEG C, 5mol/L NaOH solution incubation 48h, is cleaned by ultrasonic with water spare.
Embodiment 4
(1) dental implant that the processing of embodiment 3 obtains is immersed in chitosan solution described in example 2 above
20min, the lotus so that dental implant surface becomes positively charged;It is sufficiently cleaned with deionized water again;
(2) dental implant described in step (1) is immersed in 3h or more in RGD peptide solution;Or being immersed in concentration is lmg/
10min in the AMP complex solution of ml, so that negative electrical charge on dental implant surface band;It is sufficiently cleaned with deionized water again;
(3) number of plies assembled as needed, repeating step (1), (2) and (1) can be obtained with different number of plies coatings
Dental implant;
(4) dental implant described in step (3) is soaked in the chondroitin sulfate sodium sulfate salt solution that concentration is 2mg/mL
15min is steeped, it is 6 that solution system, which controls pH value, then is spontaneously dried after sufficiently being cleaned with deionized water;It is coated with chondroitin sulfate again
It is 7 that the dental implant of element, which is soaked in pH value, and concentration is 15min in the antibacterial peptide solution of 0.5mg/mL, then abundant with deionized water
It is spontaneously dried after cleaning.
Embodiment 5
The dental implant of different number of plies coatings will be assembled as needed in embodiment 4, it is soft in the sulfuric acid that concentration is 2mg/mL
20min is impregnated in ossein sodium sulfate salt solution (polysaccharide solution with negative electrical charge), it is 6 that solution system, which controls pH value, then is spent
Ionized water spontaneously dries after sufficiently cleaning;
It is 7 that this, which will be coated, to have the material of chondroitin sulfate to be soaked in pH value, and concentration is in the antibacterial peptide solution of 0.5mg/mL
15min, then spontaneously dried after sufficiently being cleaned with deionized water, it obtains and is coated with chondroitin sulfate layer-antibacterial peptide layer composite layer
Material.
For the dental implant that the above method prepares, surface contact angle analysis is carried out, result is from hydrophily and profit
The presence of coating is also demonstrated on moist.
According to analysis it is found that having the dental implant of different number of plies coatings prepared by the present invention.Its coating relies primarily on
Cation and the mutual electrostatic attraction of anion form the molecular coatings of ordered arrangement in the planting body surface of solids, because
Chitosan and RGD or AMP compound are the biomaterials with good biodegradability properties and biocompatibility.Along with surface layer sulphur
The presence of aching and limp ossein layer-antibacterial peptide layer lamination layer structure, which must have is lasting, efficient sterilization, anti-infective
Ability, antibacterial, anti-apoptotic activities can support adherency, the survival, growth of various kinds of cell (such as osteoblast, cartilage cell)
With differentiation, have broad application prospects.In planting body clinical application, promotes the healing of planting body osseous tissue interface, improves bone
Integration rate and the benefit for improving planting body primary stability are obvious.
Claims (7)
1. a kind of dental implant of the bioactivity surface containing RGD, it is characterised in that: the dental implant outer surface is provided with spiral shell
Line, the dental implant both ends are respectively neck and head, and helical form self tapping slot is provided on the outer surface on the head, described
The hand of spiral of helical form self tapping slot is identical as hand of thread spiral, the lead angle of the helical form self tapping slot and the spiral shell of screw thread
Line lift angle is different, and antibacterial peptide layer is to be covered in thread surface, and base's implant surface is sequentially coated with titanium dioxide layer, positive electricity
Lotus chitosan layer and negative electrical charge RGD peptide layer or the alternatively stacked slow release layer of AMP composite layer, outer layer load chondroitin sulfate layer-
Antibacterial peptide layer;
The dental implant preparation method includes following operating procedure:
(1) 100mg RGD is first weighed to add in the Acetic acid-sodium acetate buffer that the concentration of 10ml is 1%;It is slowly stirred to dissolution
Afterwards, EDCHCl 500mg is added, adds NHS 250mg, activates 12h by magnetic stirring apparatus;It is put into ddH2It dialyses in O,
It is overnight under magnetic stirrer state;Obtain RGD peptide solution;
(2) implant surface is polished, is cleaned, drying;With 50~100 μm of TiO2Particle carries out blasting treatment to implant surface;
It is placed in the mixing etching agent of hydrofluoric acid and hydrochloric acid composition again and carries out surface etching treatment, take out planting body ultrasonic cleaning, it is dry;
Planting body is placed in 60 DEG C, 5mol/L NaOH solution incubation 24-48h again, is cleaned by ultrasonic with water spare;
(3) dental implant described in step (2) is immersed in 10~20min in the chitosan solution of 0.5~5mg/ml, so that tooth
Implant surface becomes positively charged lotus;It is sufficiently cleaned with deionized water again;
(4) dental implant described in step (3) is immersed in 3h or more in RGD peptide solution described in step (1);Or it is immersed in dense
Degree is 5~10min in the AMP complex solution of lmg/ml, so that negative electrical charge on dental implant surface band;It is filled again with deionized water
It distinguishes and washes;
(5) number of plies assembled as needed, repeating step (3), (4) and (3) can be obtained the tooth kind with different number of plies coatings
Implant;
(6) by dental implant described in step (5) concentration be 2mg/mL chondroitin sulfate sodium sulfate salt solution in impregnate 5~
15min, it is 6 that solution system, which controls pH value, then is spontaneously dried after sufficiently being cleaned with deionized water;It is coated with chondroitin sulfate again
Dental implant to be soaked in pH value be 7, concentration is 5~15min in the antibacterial peptide solution of 0.5mg/mL, then abundant with deionized water
It is spontaneously dried after cleaning, obtains and be coated with chondroitin sulfate layer-antibacterial peptide layer composite layer material.
2. a kind of dental implant of bioactivity surface containing RGD according to claim 1, it is characterised in that: described
Cleaning refers to deionized water, ethyl alcohol and acetone ultrasonic cleaning, after being dried with nitrogen, puts in a vacuum drying oven, in 60 DEG C of item
It is 24 hours dry under part.
3. a kind of dental implant of bioactivity surface containing RGD according to claim 1, it is characterised in that: described
The deacetylation of chitosan is that 50~98%, Mw is 100~1500kDa.
4. a kind of dental implant of bioactivity surface containing RGD according to claim 1, it is characterised in that: described
Chitosan solution is to be made into the chitosan solution of 0.5~5mg/ml in the acetic acid solution for dissolve chitosan in 0.3~3%, will
Acquired solution is mixed with atoleine, and volume ratio is 0.1~0.4, and the sorbester p17 that volumetric concentration is 0.5~1% is added, simultaneously
The mass ratio of addition dispersing agent magnesium stearate, sorbester p17 and magnesium stearate is 2~4: 1, 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;Again by resulting chitosan particle with aqueous suspension, a small amount of glacial acetic acid solution is added, under the conditions of magnetic stirrer, then
NaCl is added, its final concentration is made to reach 0.15M;Solution is positively charged.
5. a kind of dental implant of bioactivity surface containing RGD according to claim 4, it is characterised in that: described quiet
It sets and supernatant is taken to refer to, standing 12 hours or more oil-water separation phases take lower aqueous solution, and adjusting pH value is 8~9, is centrifuged off
Sediment takes supernatant to obtain chitosan particle suspension.
6. a kind of dental implant of bioactivity surface containing RGD according to claim 1, it is characterised in that: described dense
Degree is the configuration method of the AMP complex solution of lmg/ml are as follows: is weighed after 50mg AMP composite powder adds to the sterilizing of 50ml
In deionized water, stirring is sufficiently to being completely dissolved, and acetic acid tune pH on the rocks is 5.0, and solution has positive charge.
7. a kind of dental implant of bioactivity surface containing RGD according to claim 1, it is characterised in that: it is described from
It attacks slot to be made of two arc surfaces, the binding site of two arc surfaces is tangent connection;The self tapping slot number is two or more,
Described two above self tapping slots are evenly arranged on the outer surface on head;The head is frustum, and the bigger diameter end of the head frustum is close
Neck, the one end of the head far from neck is arc surface;The neck is frustum, and the bigger diameter end of the neck frustum is close to head
Portion;The depth of the self tapping slot gradually becomes shallower as from the miner diameter end of head frustum to the bigger diameter end of head frustum.
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CN100594947C (en) * | 2004-03-19 | 2010-03-24 | 首尔国立大学工业基金会 | Bone graft and scaffolding materials immobilized with osteogenesis enhancing peptides on the surface |
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CN103550004A (en) * | 2013-11-18 | 2014-02-05 | 大连三生科技发展有限公司 | Artificial dental implant, artificial dental implanting system and implanting method |
CN105126165A (en) * | 2015-01-21 | 2015-12-09 | 中国人民解放军第三〇七医院 | Titanium dental implant material and preparing method and application of titanium dental implant material |
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KR101278204B1 (en) * | 2011-12-22 | 2013-06-27 | 경북대학교 산학협력단 | Method for preparing biomedical metal/alloy material with multi-drug delivery system |
SE537633C2 (en) * | 2012-09-18 | 2015-08-25 | Corticalis As | Hydrogel coated titanium dioxide scaffold and method of making this scaffold |
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CN100594947C (en) * | 2004-03-19 | 2010-03-24 | 首尔国立大学工业基金会 | Bone graft and scaffolding materials immobilized with osteogenesis enhancing peptides on the surface |
KR20130007857A (en) * | 2011-07-11 | 2013-01-21 | 조선대학교산학협력단 | Method of preparing biomedical ceramic materials comprising multi-drug delivery system |
CN102327645A (en) * | 2011-09-26 | 2012-01-25 | 浙江大学 | Preparation method of bionic coating carrying bioactive factors |
CN103550004A (en) * | 2013-11-18 | 2014-02-05 | 大连三生科技发展有限公司 | Artificial dental implant, artificial dental implanting system and implanting method |
CN105126165A (en) * | 2015-01-21 | 2015-12-09 | 中国人民解放军第三〇七医院 | Titanium dental implant material and preparing method and application of titanium dental implant material |
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