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 PDF

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Publication number
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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dental implant
solution
layer
chitosan
head
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CN106539627A (en
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史亮
张久文
蔡俊江
彭鹏
李闪
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Dalian Sansheng Science & Technology Development Co Ltd
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Dalian Sansheng Science & Technology Development Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61CDENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0018Means 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
    • A61C8/0022Self-screwing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61CDENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0012Means 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
    • A61C8/0013Means 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61CDENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0012Means 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
    • A61C8/0016Means 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61CDENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0018Means 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
    • A61C8/0037Details of the shape
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28Materials for coating prostheses
    • A61L27/30Inorganic materials
    • A61L27/306Other specific inorganic materials not covered by A61L27/303 - A61L27/32
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28Materials for coating prostheses
    • A61L27/34Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/25Peptides having up to 20 amino acids in a defined sequence
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606Coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/04Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/08Coatings comprising two or more layers

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  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Dentistry (AREA)
  • Dermatology (AREA)
  • Transplantation (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Ceramic Engineering (AREA)
  • Inorganic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Materials For Medical Uses (AREA)
  • Dental Preparations (AREA)

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

A kind of dental implant of the bioactivity surface containing RGD
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.
CN201611208563.5A 2016-12-23 2016-12-23 A kind of dental implant of the bioactivity surface containing RGD Expired - Fee Related CN106539627B (en)

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KR20130007857A (en) * 2011-07-11 2013-01-21 조선대학교산학협력단 Method of preparing biomedical ceramic materials comprising multi-drug delivery system
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