CN108404222A - A kind of POROUS TITANIUM based nano composite material for hard tissue material and preparation method thereof, application - Google Patents

A kind of POROUS TITANIUM based nano composite material for hard tissue material and preparation method thereof, application Download PDF

Info

Publication number
CN108404222A
CN108404222A CN201810512957.2A CN201810512957A CN108404222A CN 108404222 A CN108404222 A CN 108404222A CN 201810512957 A CN201810512957 A CN 201810512957A CN 108404222 A CN108404222 A CN 108404222A
Authority
CN
China
Prior art keywords
chitosan
deposition
base material
present
porous titanium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201810512957.2A
Other languages
Chinese (zh)
Other versions
CN108404222B (en
Inventor
皮立波
孙若为
温景成
孙绮
孙一绮
杨志
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hunan Morning Nano Robot Co Ltd
Original Assignee
Hunan Morning Nano Robot Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hunan Morning Nano Robot Co Ltd filed Critical Hunan Morning Nano Robot Co Ltd
Priority to CN201810512957.2A priority Critical patent/CN108404222B/en
Publication of CN108404222A publication Critical patent/CN108404222A/en
Application granted granted Critical
Publication of CN108404222B publication Critical patent/CN108404222B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • 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
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
    • A61L27/06—Titanium or titanium alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/20—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A61L27/32—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
    • C25D11/02—Anodisation
    • C25D11/26—Anodisation of refractory metals or alloys based thereon
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D15/00—Electrolytic or electrophoretic production of coatings containing embedded materials, e.g. particles, whiskers, wires
    • 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
    • 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
    • A61L2300/406—Antibiotics
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Abstract

The present invention provides a kind of porous titanium matrix composite, including porous titanium base material, the hydroxyapatite layer that is compounded on the porous titanium base material, and the chitosan vancomycin that is compounded on the hydroxyapatite layer.The present invention reduces or eliminates " stress shielding " effect, and have stronger binding force by porous titanium base material.Porous titanium matrix composite provided by the invention has more the chitosan vancomycin for being compounded in outer surface, the two combination significantly solves skeletonization post-transplantation at this stage and is easy to be infected, lead to transplant inflammation or functional deterioration, graft failure is caused, and there are problems that binding force and medicament slow release time short problem.Porous titanium matrix composite provided by the invention can be good at combining HAp, chitosan functional drug and the composite coating formed using porous structure, and dispersibility is more preferable, and binding force is stronger, and slow-release time significantly improves, and plays the effect of long-term antibacterial.

Description

It is a kind of for the POROUS TITANIUM based nano composite material of hard tissue material and its preparation side Method, application
Technical field
The present invention relates to biomedical material technology, be related to a kind of porous titanium matrix composite and preparation method thereof, Using a kind of, and in particular to POROUS TITANIUM based nano composite material for hard tissue material and preparation method thereof, in bio-medical Application in terms of material.
Background technology
With the quickening of aging of population degree and sharply increasing for various unexpected injuries, lead to sclerous tissues' defect Patient populations increasingly increase, according to the Organization of Economy and Cooperation Development of the United Nations, it is expected that arriving the year two thousand twenty, the hard tissue repair thus caused The market value of product is up to 800,000,000,000 dollars.
As the important component of bio-medical material, human body hard tissue (bone, pass of the hard tissue material to repair deficiency Section etc.) and the physiological function etc. lost of reconstruction have important role.Bone defect healing is mainly by autologous bone transplanting, different Body bone collection and artificial material substitute.However, no matter autologous bone transplanting or allogenic bone transplantation all existing defects, autologous bone transplanting The mode of " cutting the flesh to cure a boil " is not preferably to select, and source is also very limited；There is immune rows again for allogenic bone transplantation The risk that reprimand reaction and donor source are infected；So being the important side of current bone defect healing using hard tissue repair artificial material Method.Special use environment based on bone alternate material, the requirement for the medical alternative materials of human body hard tissue be it is extremely stringent, There should be good comprehensive mechanical mechanical property, there is excellent bioactivity again；Titanium alloy has excellent synthesis mechanics Performance and excellent wear-corrosion resistance, but relative to bone tissue, its elasticity modulus is higher, easy tos produce " stress shielding ", makes At the degeneration of bone tissue, while although its good biocompatibility, bio-inert material is still fallen within, lacks bioactivity, It is difficult to directly form chemical bonding with bone tissue after implantation, thus causes bond strength relatively low, loosening is easy to happen, to cause Tissue reconstruction repairing failure.
Hydroxyapatite [Ca10(PO4)6(OH)2] (Hydroxyapatite, HAp) be a kind of important biomedical material Material, while there is good biocompatibility and bioactivity, the mineral phosphor ash in chemical composition and crystal and bone tissue Stone is similar, is the important inanimate matter ingredient for constituting body bone tissue, interfacial reaction can occur with bone tissue, form chemical bond Close, but HAp brittleness is big, and fracture toughness is only the 1/70~1/40 of titanium alloy, but mechanical property is poor, strongly limit it The application of biomedical materials field.
So at this stage in technology, in the hard tissue repair technique that artificial material replaces, hydroxyapatite combination metal structure It is good to make up hydroxyapatite bioactive at composite coating, it may advantageously facilitate Osteogenesis.As patent CN103014801A is public A kind of electro-deposition preparation method of titanium-based hydroxylapatite biology medical composite material is opened, by pretreated titanium or titanium alloy Substrate prepares one layer of hydroxyapatite coating layer by the method for constant current or constant pressure electro-deposition in titanium-based surface, improves the parent with body With property and biocompatibility, promote the growth of new bone, preparation process is simple, and reaction avoids high temperature, but still there are resultant forces The problems such as performance is poor, and metal base comprehensive mechanical property is considerable, and bioactivity is not satisfactory is learned, elasticity modulus is larger, just Property it is high, the adverse effect of " stress shielding " effect can not be reduced.
Therefore, a kind of composite material can be used in sclerous tissues how is obtained, above-mentioned challenge is solved and is lacked It falls into, is preferably applied to biomedical materials field, it has also become field Nei Ge production firms and a line researcher are urgently to be resolved hurrily The problem of.
Invention content
In view of this, the technical problem to be solved in the present invention is to provide a kind of porous titanium matrix composite and its preparation side Method, application, are a kind of porous titanium matrix composites for hard tissue material, porous titanium matrix composite provided by the invention, " stress shielding " effect can be effectively reduced or be eliminated, and there is good compatibility and bioactivity, with more lasting The effect of antibacterial plays the role of cooperateing with repairing and treating, the success rate of bone tissue reparation is improved, to reach good medicine controlled releasing Effect.
The present invention provides a kind of porous titanium matrix composite, including porous titanium base material, be compounded in it is described porous Hydroxyapatite layer on titanium base material, and chitosan-vancomycin for being compounded on the hydroxyapatite layer.
Preferably, the titanium base material includes titanium or titanium alloy；
The aperture of the titanium base material is 30~60nm；
The porosity of the titanium base material is 90~98.6%；
The size of the titanium base material is (40~60) × (20~40) × (0.5~2mm).
Preferably, the mass ratio of the titanium base material and hydroxyapatite is (10~20)：1；
The mass ratio of the titanium base material and the chitosan-vancomycin is (40~70)：1；
The hydroxyapatite layer has fine acicular surface texture；
Chitosan-the vancomycin has one in flocculent structure, petal-like structures, ellipsoid structure and block structure Kind is a variety of.
Preferably, the thickness of the hydroxyapatite layer is 6~15 μm；
A diameter of 1~4 μm of the fine needle；
Chitosan-the vancomycin is entrained in the needle cluster of the hydroxyapatite layer surface and/or is covered in described Apatite layer surface.
The present invention also provides a kind of preparation methods of porous titanium matrix composite, include the following steps：
1) it will be obtained with porous structure by pretreated titanium base material after anode oxidation process and annealing The titanium base material on surface；
After chitosan and vancomycin mixed liquor, calcium salt, microcosmic salt and water are mixed, pH value is adjusted, the first mixed liquor is obtained；
2) titanium base material with porous structure surface and the first mixed liquor obtained above-mentioned steps after electro-deposition, Obtain semi-finished product；
3) semi-finished product for obtaining above-mentioned steps obtain porous titanium matrix composite after alkali immersion treatment.
Preferably, the pretreated process includes one or more in polishing, cleaning, dry and polishing；
The anode oxidation process is constant-voltage method anode oxidation process；
The oxidation voltage of the anodic oxidation is 10~20V；
The time of the anodic oxidation is 1~3h；
The oxidizing temperature of the anodic oxidation is 20~30 DEG C；
The electrolyte of the anodic oxidation includes hydrofluoric acid solution, ammonium fluoride ethylene glycol organic electrolysis plastidome and hydrogen fluorine It is one or more in acid/sulfuric acid/water system；
The temperature of the annealing is 350~550 DEG C；
The time of the annealing is 2~3h；
The heating rate of the annealing is 3~5 DEG C/min.
Preferably, the mixing the specific steps are：
After calcium salt, microcosmic salt and water are mixed, calcium microcosmic salt mixed solution is obtained；
Chitosan piece is dissolved in acid solution, after dilution, chitosan solution is obtained, supernatant liquor is taken after stirring, then to Vancomycin is added in supernatant liquor, after mixing again, obtains suspension；
After suspension and calcium microcosmic salt mixed solution that above-mentioned steps obtain are continued mixing, pH value is adjusted, it is mixed to obtain first Close liquid.
Preferably, the calcium salt includes Ca (NO3)2、CaCl2、Ca(NO3)2·4H2It is one or more in O；
The microcosmic salt includes (NH4)2HPO4、K2HPO4、KH2PO4And NaH2PO4In it is one or more；
Calcium phosphorus molar ratio in the calcium microcosmic salt mixed solution is 5：3；
The mass ratio of the calcium salt and water is 7：(200~250)；
The weight average molecular weight of the chitosan is 50~100KDa；
The deacetylation of the chitosan is more than or equal to 95%；
The acid solution includes glacial acetic acid solution；
The mass concentration of the acid solution is 1wt%~2wt%；
A concentration of 1~3mg/mL of the chitosan solution；
The mass ratio of chitosan and vancomycin is 1 in the suspension：(5~10)；
The pH value is 4~6.2.
Preferably, the temperature of the electro-deposition is 30~40 DEG C；
The electro-deposition is specially to rise current method using ladder to carry out electro-deposition；
The deposition current of first ladder of the electro-deposition is 0.5~1.0A；The deposition of first ladder of the electro-deposition Time is 5~10min；
The deposition current of second ladder of the electro-deposition is 1.0~1.5A；The deposition of second ladder of the electro-deposition Time is 5~10min；
The deposition current of the third ladder of the electro-deposition is 1.5~3.0A；The deposition of the third ladder of the electro-deposition Time is 20~40min；
The time of the alkali immersion treatment is 2~3h；
A concentration of 1.0~1.5mol/L of the alkali immersion treatment lye；
The alkali immersion treatment lye includes sodium hydroxide solution and/or ammonium hydroxide.
Described in porous titanium matrix composite or above-mentioned technical proposal any one described in above-mentioned technical proposal any one Preparation method prepared by application of the porous titanium matrix composite in terms of bio-medical material.
The present invention provides a kind of porous titanium matrix composite, including porous titanium base material, be compounded in it is described porous Hydroxyapatite layer on titanium base material, and chitosan-vancomycin for being compounded on the hydroxyapatite layer.With it is existing Technology is compared, and the present invention is directed to existing hard tissue material, there is " stress shielding ", causes the degeneration of bone tissue, is lacked Bioactivity, the defects of being difficult to directly form chemical bonding with bone tissue after implantation.It is considered herein that long time without surface modification treatment Test button usually possess higher elasticity modulus, rigidity is high, and relative to bone tissue, its elasticity modulus is higher, easy tos produce " stress shielding " causes the degeneration of bone tissue, and then by porous titanium base material, height is prepared on titanium base material surface Specific surface, more regular TiO2Nano-porous structure utilizes density, the intensity of Porosity Rate Influence titanium alloy implant entirety And elasticity modulus, to reduce or eliminate " stress shielding " effect.And TiO2The high specific surface area of nano-porous structure and thick Rough surface has good compatibility and bioactivity, then deposits one layer of fine and close hydroxyapatite on porous structure surface (HAp), there is stronger binding force, the existing composite coating bond strength of effective solution is low, is easy to happen loosenings, thus Cause the defect of tissue reconstruction repairing failure.
The present invention is more directed to planting body and infects, one of the complication of most serious in this orthopaedics and trauma operation, due to hand Microorganism can be caused to be adhered in biomedical material surface after art transplanting, occurred so as to cause infection, this kind of infection is known as " biology The relevant infection (Biomaterial-centered infection, BCI) of material ", not only reduces the success of tissue repair Rate is also possible to the critical issue for causing hypofunction, plantation failure, chronic osteomyelitis even dead when serious.The present invention provides Porous titanium matrix composite have more and be compounded in chitosan-vancomycin of outer surface, chitosan is unique in nature Natural cationic macromolecule has good nontoxic, biocompatibility, biodegradability, bioadhesive, antibacterial and promotees solidifying The performances such as blood, and there is PH responses, it is in cationic in PH ＜ 6.3；Vancomycin is a kind of glycopeptide antibiotics, Bacterium is killed by inhibiting growth and the breeding of bacterium, has been widely used for the work(for treating and preventing osteomyelitis and deep infection Energy property antibacterials play the role of cooperateing with repairing and treating, the success rate of bone tissue reparation are improved, to reach good drug control Effect is released, the two combination significantly solves skeletonization post-transplantation at this stage and is easy to be infected, and leads to transplant inflammation or function The composite coating degenerated, cause graft failure, and be made of functional drug is not there is only binding force problem, and medicament slow release Time is mostly one month or so the problem of.
Porous titanium matrix composite provided by the invention can be good at combining HAp, chitosan-work(using porous structure Energy property drug and the composite coating formed, dispersibility is more preferable, and binding force is stronger, and slow-release time significantly improves, and plays permanent anti- The effect of bacterium.
The experimental results showed that porous titanium matrix composite prepared by the present invention, matrix has cellular structures, possesses Higher specific surface area, aperture are 30~60nm, and porosity reaches 90~98.6%, multifunctional composite coating with it is cellular porous Structure combine it is compact, preferable in conjunction with effect, composite material is only 0.23g or so in initial burst release amount, and burst release rate is about 28.75%, accumulative release can extend to one month or more, can preferably achieve the effect that durable antibiotic.
Description of the drawings
Fig. 1 is the titanium base material surface SEM shape appearance figures with porous structure surface prepared by the embodiment of the present invention 1；
Fig. 2 is that the titanium base material surface SEM shape appearance figures with porous structure surface prepared by the embodiment of the present invention 1 are locally put Big figure；
Fig. 3 is the electro-deposition experimental provision used in the embodiment of the present invention；
Fig. 4 is the SEM shape appearance figures of the compound functional medicine carrying material of multicoat prepared by the embodiment of the present invention 1；
Fig. 5 is the SEM shape appearance figures of the semi-finished product without alkaline bath processing after electro-deposition in the embodiment of the present invention 3；
Fig. 6 is electro-deposition and to carry out alkaline bath treated the SEM patterns of porous titanium matrix composite in the embodiment of the present invention 3 Figure；
Fig. 7 is that the vancomycin drug of porous titanium matrix composite prepared by the embodiment of the present invention 3 adds up release rate curve.
Specific implementation mode
In order to further appreciate that the present invention, the preferred embodiments of the invention are described with reference to embodiment, but It is it should be appreciated that these descriptions are only the feature and advantage further illustrated the present invention rather than to patent requirements of the present invention Limitation.
All raw materials of the present invention, are not particularly limited its source, buying on the market or according to people in the art It is prepared by conventional method known to member.
All raw materials of the present invention, are not particularly limited its purity, and present invention preferably employs drug is pure or field of medicaments Conventional purity.
The expression of all nouns of the present invention and referred to as belong to this field routine noun expression and referred to as, each noun expression and Referred to as it is explicit in its related application field, those skilled in the art are expressed according to noun and abbreviation, Neng Gouqing Chu is accurately uniquely understood.
The present invention provides a kind of porous titanium matrix composite, including porous titanium base material, be compounded in it is described porous Hydroxyapatite layer on titanium base material, and chitosan-vancomycin for being compounded on the hydroxyapatite layer.
The titanium base material is not particularly limited in the present invention, with titanium base material well known to those skilled in the art, Those skilled in the art can select and adjust according to practical situations, product requirement and properties of product, the present invention The titanium base material preferably includes titanium or titanium alloy, more preferably titanium alloy, and the titanium alloy can specifically include Ti-6Al- It is one or more in 4V, Ti-3Al-2.5V, Ti-6Al-7Nb and Ti-5Al-2.5Fe, more preferably Ti-6Al-4V, Ti- 3Al-2.5V, Ti-6Al-7Nb or Ti-5Al-2.5Fe.
The design parameter of the porous titanium base material is not particularly limited in the present invention, with known to those skilled in the art This conventional polyporous materials parameter, those skilled in the art can according to practical situations, product requirement and Properties of product are selected and are adjusted, and the aperture of porous titanium base material of the present invention is preferably 30~60nm, more preferably 35~55nm, more preferably 40~50nm.The porosity of porous titanium base material of the present invention is preferably 90~98.6%, more Preferably 91~97%, more preferably 93~95%.Titanium base material of the present invention be preferably dimensioned to be (40~60) × (20~ 40) × (0.5~2mm), more preferably (43~58) × (22~38) × (0.8~1.8mm), more preferably (45~55) × (25~35) × (1.0~1.5mm), more preferably (47~52) × (27~32) × (1.1~1.4mm).
The combined state of the hydroxyapatite layer is not particularly limited in the present invention, with well known to those skilled in the art Composite definitions, the present invention preferably coats, half coats, is laminated or generates, more preferably cladding or half cladding, most preferably Cladding.The cladding is not particularly limited in the present invention, is defined with cladding well known to those skilled in the art, and the present invention is excellent It is selected as coating entirely.Hydroxyapatite of the present invention also fills up not only in titanium base material surface stratification in titanium base material table In the hole in face.
The thickness of the hydroxyapatite layer is not particularly limited in the present invention, with routine well known to those skilled in the art The thickness of this polyporous materials, those skilled in the art can be according to practical situations, product requirement and products It can be selected and be adjusted, the thickness of hydroxyapatite layer of the present invention is preferably 6~15 μm, more preferably 8~13 μm, more Preferably 10~11 μm.The addition of the hydroxyapatite is not particularly limited in the present invention, and those skilled in the art can be with It is selected according to practical situations, product requirement and properties of product, titanium base material and hydroxyapatite of the present invention Mass ratio be preferably (10~20)：1, more preferably (12~18)：1, more preferably (14~16)：1.
The configuration of surface of the hydroxyapatite layer is not particularly limited in the present invention, and those skilled in the art can basis Practical situations, product requirement and properties of product are selected and are adjusted, and hydroxyapatite layer of the present invention is especially excellent Select the surface texture with fine acicular, the surface texture of more preferably specific multiple needle tufted.The diameter of fine needle of the present invention is excellent It is selected as 1~4 μm, more preferably 1.5~3.5 μm, more preferably 2~3 μm.
The combined state of the chitosan-vancomycin is not particularly limited in the present invention, ripe with those skilled in the art The composite definitions known, the present invention are preferably doping, cladding, partly coat, is in stacking and insertion one or more, more preferably It is a variety of in doping, stacking and insertion.
The parameter of the chitosan-vancomycin is not particularly limited in the present invention, with well known to those skilled in the art Conventional parameter, those skilled in the art can select according to practical situations, product requirement and properties of product And adjustment.The addition of the hydroxyapatite is not particularly limited in the present invention, and those skilled in the art can be according to reality Applicable cases, product requirement and properties of product are selected, the matter of titanium base material of the present invention and chitosan-vancomycin Amount is than being preferably (40~70)：1, more preferably (45~65)：1, more preferably (50~60)：1.
The form of the chitosan-vancomycin is not particularly limited in the present invention, and those skilled in the art can basis Practical situations, product requirement and properties of product are selected and are adjusted, and chitosan-vancomycin of the present invention is not only In the fine needle cluster for being entrained in hydroxyapatite surface, it can also stack and be covered in hydroxyapatite surface.Shell of the present invention is poly- Sugar-vancomycin is preferably with one or more in flocculent structure, petal-like structures, ellipsoid structure and block structure, more It is preferred that with a variety of in flocculent structure, petal-like structures, ellipsoid structure and block structure, more preferably there is cotton-shaped and petal Shape structure.The present invention can control the pattern of chitosan-vancomycin by conditions such as the time of alkali process and temperature so that Ellipsoid structure blooms to form more cotton-shaped and petal-shapeds.
The present invention also provides a kind of preparation methods of porous titanium matrix composite, include the following steps：
1) it will be obtained with porous structure by pretreated titanium base material after anode oxidation process and annealing The titanium base material on surface；
After chitosan and vancomycin mixed liquor, calcium salt, microcosmic salt and water are mixed, pH value is adjusted, the first mixed liquor is obtained；
2) titanium base material with porous structure surface and the first mixed liquor obtained above-mentioned steps after electro-deposition, Obtain semi-finished product；
3) semi-finished product for obtaining above-mentioned steps obtain porous titanium matrix composite after alkali immersion treatment.
The present invention is to the selection of raw material, ratio and its corresponding optimum principle in the preparation method, with previous porous titanium The selection of the material of based composites, ratio and its corresponding optimum principle are consistent, and this is no longer going to repeat them.
The present invention will be had first by pretreated titanium base material after anode oxidation process and annealing The titanium base material on porous structure surface.
The pretreating process of the titanium base material is not particularly limited in the present invention, with well known to those skilled in the art normal The pretreating process of such material is advised, those skilled in the art can be according to practical condition, product requirement and production Moral character can be selected and be adjusted, and pretreated process of the present invention preferably includes one in polishing, cleaning, dry and polishing Kind is a variety of, more preferably polishes, cleans, is in dry and polishing a variety of, more preferably polished, cleaned successively, dried, Polishing, cleaning and drying.Polishing of the present invention is preferably electrochemical polish.
The present invention is to further increase the performance of final products, complete and refinement preparation process, the pretreating process tool Body can be following steps：
1) by size be 40 × 20 × 1mm titanium alloy successively use 220#, 400#, 600#, 800#, 1000# sand paper into Row polishing, is then respectively put into acetone, absolute ethyl alcohol, deionized water and is respectively cleaned by ultrasonic 10~15min, after to be cleaned Cold wind drying is spare；
2) by above-mentioned gained sample in phosphoric acid：Sulfuric acid：Water=1:3:Electrochemistry throwing is carried out in the polishing fluid of 10 (volume ratios) Light, electrochemical polish carry out in 80~90 DEG C of oil bath devices, are carried out at the same time magnetic agitation, and mixing speed is 800~1200r/ Min, it is 25~50A/dm that polishing, which uses constant flow method, current density,2, polishing time is 10~20s, and the sample after polishing is spent Ionized water is cleaned by ultrasonic 10~15min, after takes out and rinses well, cold wind dries up.Then 20 × 20mm is pressed with adhesive tape It is spare to not participating in being packaged on one side for reaction, to control reaction zone and prevent edge from polarizing.
The anode oxidation process is not particularly limited in the present invention, with the such material of routine well known to those skilled in the art The anode oxidation process of material, those skilled in the art can be according to practical condition, product requirement and properties of product It is selected and is adjusted, anode oxidation process of the present invention is preferably constant-voltage method anode oxidation process.The present invention is to the sun The design parameter of pole oxidation technology is not particularly limited, with the parameter of conventional anodes oxidation technology well known to those skilled in the art , those skilled in the art can select and adjust according to practical condition, product requirement and properties of product, this The oxidation voltage for inventing the anodic oxidation is preferably 10~20V, more preferably 12~18V, more preferably 14~16V.This hair The time of the bright anodic oxidation is preferably 1~3h, more preferably 1.2~2.8h, more preferably 1.5~2.5h.Institute of the present invention The oxidizing temperature for stating anodic oxidation is preferably 20~30 DEG C, more preferably 22~28 DEG C, more preferably 24~26 DEG C.Institute of the present invention The mixing speed for stating anode oxidation process is preferably 800~1200r/min, more preferably 850~1150r/min, more preferably 900~1100r/min.It is organic that the electrolyte of anodic oxidation of the present invention preferably includes hydrofluoric acid solution, ammonium fluoride ethylene glycol It is one or more in electrolyte system and hydrofluoric acid/sulfuric acid/water system, more preferably hydrofluoric acid solution, ammonium fluoride ethylene glycol Organic electrolysis plastidome or hydrofluoric acid/sulfuric acid/water system, most preferably hydrofluoric acid solution.
The design parameter of the hydrofluoric acid solution is not particularly limited in the present invention, and those skilled in the art can be according to reality The border condition of production, product requirement and properties of product are selected and are adjusted, and the concentration of hydrofluoric acid solution of the present invention is preferred For 0.3wt%~0.7wt%, more preferably 0.35wt%~0.65wt%, more preferably 0.4wt%~0.6wt%, more preferably For 0.45wt%~0.55wt%.
Anode oxidation process of the present invention preferably uses bipolar electrode system, and pretreated titanium base material is preferably made sun Pole is more preferably used as using graphite electrode to electrode, be particularly preferred as taking out after anodic oxidation sample and rapidly with largely go from Sub- water rinses, and dries at room temperature.
The present invention is then made annealing treatment again, and the present invention does not limit the design parameter of the annealing especially System, with the parameter that conventional annealing well known to those skilled in the art is handled, those skilled in the art can be according to practical life Production situation, product requirement and properties of product are selected and are adjusted, and the temperature of annealing of the present invention is preferably 350~ 550 DEG C, more preferably 375~525 DEG C, more preferably 400~500 DEG C, more preferably 425~575 DEG C.Annealing of the present invention Time be preferably 2~3h, more preferably 2.2~2.8h, more preferably 2.4~2.6h.The heating speed of annealing of the present invention Rate is preferably 3~5 DEG C/min, more preferably 3.2~4.8 DEG C/min, more preferably 3.5~4.5 DEG C/min.It is of the present invention to move back Is carried out in the specific tubular annealing stove preferably under air atmosphere of fire processing, after cool to after room temperature that take out material standby with the furnace With.
The present invention mixes chitosan and vancomycin mixed liquor, calcium salt, microcosmic salt and water again after, pH value is adjusted, obtains the One mixed liquor.
The specific choice of the calcium salt is not particularly limited in the present invention, with common calcium salt well known to those skilled in the art , those skilled in the art can select and adjust according to practical condition, product requirement and properties of product, this It invents the calcium salt and preferably includes Ca (NO3)2、CaCl2、Ca(NO3)2·4H2It is one or more in O, more preferably Ca (NO3)2、CaCl2Or Ca (NO3)2·4H2O.The specific choice of the microcosmic salt is not particularly limited in the present invention, with this field skill Microcosmic salt is commonly used known to art personnel, those skilled in the art can be according to practical condition, product requirement and product Performance is selected and is adjusted, and microcosmic salt of the present invention preferably includes (NH4)2HPO4、K2HPO4、KH2PO4And NaH2PO4In one Kind or a variety of, more preferably (NH4)2HPO4、K2HPO4、KH2PO4Or NaH2PO4。
The specific choice of the chitosan is not particularly limited in the present invention, with common shell well known to those skilled in the art Glycan, those skilled in the art can select and adjust according to practical condition, product requirement and properties of product Whole, the weight average molecular weight of chitosan of the present invention is preferably 50~100KDa, more preferably 60~90KDa, more preferably 70 ~80KDa.The deacetylation of chitosan of the present invention is preferably greater than or equal to 95%, is more preferably greater than equal to 96%, more preferably More than or equal to 98%.
The specific steps and parameter of the mixing are not particularly limited in the present invention, with well known to those skilled in the art normal Advise the mixing step and parameter of such raw material, those skilled in the art can according to practical condition, product requirement with And properties of product are selected and are adjusted, the present invention is to ensure the performance of final products, and complete and process for refining flow is described mixed The specific steps of conjunction, i.e. above-mentioned steps are preferably：
After calcium salt, microcosmic salt and water are mixed, calcium microcosmic salt mixed solution is obtained；
Chitosan piece is dissolved in acid solution, after dilution, chitosan solution is obtained, supernatant liquor is taken after stirring, then to Vancomycin is added in supernatant liquor, after mixing again, obtains suspension；
After suspension and calcium microcosmic salt mixed solution that above-mentioned steps obtain are continued mixing, pH value is adjusted, it is mixed to obtain first Close liquid.
The dosage of the calcium salt and microcosmic salt is not particularly limited in the present invention, with conventional use well known to those skilled in the art Amount, those skilled in the art can select and adjust according to practical condition, product requirement and properties of product, The present invention is to ensure that hydroxyapatite is preferably formed, and be more advantageous to the Hap to be formed and be deposited on titanium-based porous surface, this hair Calcium phosphorus molar ratio in the bright calcium microcosmic salt mixed solution is preferably 5：3.
The dosage of the water is not particularly limited in the present invention, with conventional amount used well known to those skilled in the art, Those skilled in the art can select and adjust according to practical condition, product requirement and properties of product, the present invention The mass ratio of the calcium salt and water is preferably 7：(200~250), more preferably 7：(210~240), more preferably 7：(220~ 230)。
The specific choice and parameter of the acid solution is not particularly limited in the present invention, with well known to those skilled in the art normal With acid solution and parameter, those skilled in the art can carry out according to practical condition, product requirement and properties of product Selection and adjustment, acid solution of the present invention preferably include glacial acetic acid solution.The mass concentration of acid solution of the present invention is preferably 1wt%~2wt%, more preferably 1.2wt%~1.8wt%, more preferably 1.4wt%~1.6wt%.
The concentration of chitosan solution of the present invention is preferably 1~3mg/mL, more preferably 1.2~2.8mg/mL, more excellent It is selected as 1.5~2.5mg/mL, more preferably 1.8~2.2mg/mL.The present invention does not have the dosage of the chitosan and vancomycin There is special limitation, with conventional amount used well known to those skilled in the art, those skilled in the art can be according to actual production Situation, product requirement and properties of product are selected and are adjusted, and the present invention is preferably to ensure the effect of final products, balance The time of sustained release and concentration, the mass ratio of chitosan and vancomycin, i.e., chitosan and ten thousand in final products in the suspension The mass ratio of ancient mycin, preferably 1：(5~10), more preferably 1：(6~9), more preferably 1：(7~8).
The specific choice of the pH value is not particularly limited in the present invention, and those skilled in the art can be according to actual production Situation, product requirement and properties of product are selected and are adjusted, and the present invention is preferably to ensure the effect of final products, is ensured The pH responses of chitosan, the pH value are preferably 4~6.2, and more preferably 4.2~6.0, more preferably 4.5~5.7 are more excellent 5~5.5 are selected as, is specifically as follows 4.5~5.
The present invention is to ensure the performance of final products, complete and process for refining flow, the specific steps of the mixing, i.e., on Step is stated to be specifically as follows：
Ca (NO are accurately weighed at room temperature3)2·4H2O and (NH4)2HPO4It is respectively placed in 150ml beakers, then adds respectively Enter deionized water, after uniform stirring dissolving, is poured into 500ml beakers and mixes, make its Ca：P=5:3 (molar ratios), so Chitosan piece (Mw=50~100KDa, DD >=95%) is dissolved in glacial acetic acid afterwards, the shell that deionized water is made into is added Glycan solution, and centrifugal mixer (50ml centrifuge tubes), take supernatant liquor, a certain amount of vancomycin powder are added into supernatant liquor To prepare polymer suspension liquid so that the mass ratio of vancomycin and chitosan is 5~10 in suspension, then will be prepared Polymer suspension liquid is added in water-soluble calcium microcosmic salt solution, and adjustment liquid level is 250ml, finally adjusts solution PH=4.5 ~5.
The titanium base material and the first mixed liquor process with porous structure surface that the present invention then obtains above-mentioned steps After electro-deposition, semi-finished product are obtained.
The specific steps and parameter of the electro-deposition are not particularly limited in the present invention, with well known to those skilled in the art The electrodeposition step and parameter of conventional such raw material, those skilled in the art can want according to practical condition, product It asks and properties of product is selected and adjusted, electro-deposition of the present invention is particularly preferred as rising current method progress electricity using ladder Deposition.The temperature of electro-deposition of the present invention is preferably 30~40 DEG C, more preferably 32~38 DEG C, more preferably 34~36 DEG C. The deposition current of electro-deposition of the present invention is preferably 0.5~3.0A, more preferably 1~2.5A, more preferably 1.5~2.0A. The sedimentation time of electro-deposition of the present invention is preferably 30~60min, more preferably 35~55min, more preferably 40~ 50min。
Ladder of the present invention rises current method and carries out electro-deposition, can specifically be divided into 2~5 sections, be either 3~4 sections or It is 3 sections.
The detailed process and parameter of electro-deposition of the present invention can be：
The deposition current of first ladder of the electro-deposition be preferably 0.5~1.0A, more preferably 0.6~0.9A, it is more excellent It is selected as 0.7~0.8A.The sedimentation time of first ladder of the electro-deposition is preferably 5~10min, more preferably 6~9min, more It is preferred that 7~8min.The deposition current of second ladder of the electro-deposition is preferably 1.0~1.5A, more preferably 1.1~1.4A, More preferably 1.2~1.3A.The sedimentation time of second ladder of the electro-deposition is preferably 5~10min, more preferably 6~ 9min, more preferable 7~8min.The deposition current of the third ladder of the electro-deposition is preferably 1.5~3.0A, and more preferably 1.7 ~2.8A, more preferably 2.0~2.5A.The sedimentation time of the third ladder of the electro-deposition is preferably 20~40min, more preferably For 22~38min, more preferable 25~35min.
The present invention is to ensure deposition effect, and complete and process for refining flow, the specific steps of the electro-deposition can be：
500ml beakers are put into constant-temperature heating magnetic stirring apparatus, anode connects graphite electrode, and cathode connects sample and makees work electricity Working electrode is first placed in deposition liquid before depositing and stablizes 1~2min by pole, electrode spacing 3cm, and electrodeposition temperature is 30~40 DEG C, mixing speed be 800~1200r/min, while using ladder rise current method, first with 0.5~1.0A current deposits 5~ 10min, then by current boost to 1.0~1.5A, 5~10min of redeposition, finally rise to 1.5~3.0A stably depositings 20~ 40min, after sample has deposited taking-up cleaned with deionized water, natural air drying.
The semi-finished product that the present invention finally obtains above-mentioned steps obtain porous titanium-based composite wood after alkali immersion treatment The compound functional medicine carrying material of material, i.e. multicoat.
The specific steps and parameter of the alkali immersion treatment are not particularly limited in the present invention, ripe with those skilled in the art The step of routine known such alkali immersion treatment and parameter, those skilled in the art can be according to practical condition, productions Product require and properties of product are selected and adjusted, and the time of alkali immersion treatment of the present invention is preferably 2~3h, more preferably For 2.2~2.8h, more preferably 2.4~2.6h.The temperature that alkali of the present invention impregnates is preferably 36.5~37.5 DEG C, more preferably It is 36.7~37.3 DEG C, more preferably 36.9~37.1 DEG C.The concentration of alkali immersion treatment lye of the present invention is preferably 1.0 ~1.5mol/L, more preferably 1.1~1.4mol/L, more preferably 1.2~1.3mol/L.Alkali immersion treatment of the present invention is used Lye preferably includes sodium hydroxide solution and/or ammonium hydroxide, more preferably sodium hydroxide solution or ammonium hydroxide, more preferably sodium hydroxide Solution.
The present invention is to ensure that alkaline bath impregnates the effect of the hydrolysis biologically active HAp coatings of fabricated in situ, and then improve The performance of product, complete and process for refining flow, the specific steps of the alkali immersion treatment can be：
Sample (semi-finished product) after air-drying is subjected to alkaline bath 2~3h of immersion treatment in NaOH solution, obtains base extraction Sample, surface is rinsed after taking-up with deionized water, and natural air drying obtains the compound functional medicine carrying material of coating.
Above-mentioned steps of the present invention provide a kind of porous titanium matrix composite and preparation method thereof for hard tissue material, The present invention for " stress shielding " this technology can not be eliminated at this stage the problem of, start with from its essence, it is believed that change without surface Property processing test button usually possess higher elasticity modulus, rigidity is high, and relative to bone tissue, its elasticity modulus is higher, is easy It generates " stress shielding ", causes the degeneration of bone tissue.Thus, the present invention, can be with by controlling anode oxidation process parameter More regular nano-pore or nanotube are prepared, " stress shielding " can be reduced or eliminated as far as possible according to actual conditions and be produced Raw influence.
The present invention is directed to the existing method using hydrothermal synthesis and prepares HAp again, although effect is preferable, really higher It is carried out under warm high pressure, and time-consuming, and mostly deposits HAp on the surface of non-modified processing, however bond strength is relatively modified Composite coating for want low, loosening is easy to happen, the problem of to cause tissue reconstruction repairing failure.The present invention utilizes TiO2 The high specific surface area of nano-porous structure, along with modified coarse porous structure surface has good compatibility and biology Activity first deposits one layer of fine and close, stronger CaHPO of binding force by the method for electro-deposition on porous structure surface4·2H2O calcium Then phosphorous layer carries out alkaline bath and impregnates hydrolysis fabricated in situ biologically active HAp coatings, the existing combination of effective solution The low problem of intensity.
It is the one of the major reasons for leading to skeletonization graft failure that the present invention is directed to bone tissue transplant infection again, using silver ion As antiseptic, it is understood that there may be security risk, using functional drug auxiliary treatment, although fine curative effect can be played, It is the medicine controlled releasing time generally to continue only one or two week, and asked present in these relatively long practical applications of clinical slow-release time Topic.Composite coating prepared by the present invention, using porous structure can be good at combine HAp, chitosan-functional drug and The composite coating formed, dispersibility is more preferable, and binding force is stronger, and slow-release time significantly improves, and plays the effect of long-term antibacterial, greatly Big solve at this stage that skeletonization post-transplantation is easy to be infected, and leads to transplant inflammation or functional deterioration, causes graft failure, And there is only binding force problems for the composite coating being made of functional drug, and the medicament slow release time is mostly on a month left side The right side, time short problem.
The present invention also provides described in above-mentioned technical proposal any one porous titanium matrix composite or above-mentioned technical side Application of the porous titanium matrix composite in terms of bio-medical material prepared by preparation method described in case any one.
Bio-medical material of the present invention is more preferably hard tissue material, to the human body hard tissue of repair deficiency (bone, Joint etc.) and rebuild the physiological function etc. lost and have important role, porous titanium matrix composite of the present invention It is mainly used for the artificial material of bone defect healing.
It is cured the present invention provides a kind of porous titanium matrix composite for hard tissue material and preparation method thereof, in biology With the application in terms of material.The present invention using anodizing titanium or titanium alloy surface prepare high-ratio surface, more advise TiO then2Nano-porous structure is passed through using density, intensity and the elasticity modulus of Porosity Rate Influence titanium alloy implant entirety Anode oxidation process parameter adjustment pore size and porosity are adjusted to make the mechanical property of itself and host bone tissue match, from And reduce or eliminate " stress shielding " effect.Due to TiO2The high specific surface area of nano-porous structure, along with modified coarse Porous structure surface there is good compatibility and bioactivity, first deposited on porous structure surface by the method for electro-deposition One layer of fine and close, stronger CaHPO of binding force4·2H2Then O calcium-phosphate layers carry out alkaline bath and impregnate hydrolysis fabricated in situ with biology Active HAp coatings.In order to solve the problems, such as that bone tissue post-transplantation infects, it is added that be mixed with shell poly- in electro-deposition must deposit liquid Sugar-vancomycin, wherein chitosan are unique natural cationic macromolecules in nature, have good nontoxic, biofacies The performances such as capacitive, biodegradability, bioadhesive, antibacterial and rush blood coagulation, and there is PH responses, in PH ＜ 6.3, In cationic；Vancomycin is a kind of glycopeptide antibiotics, and bacterium is killed by the growth and breeding that inhibit bacterium, by Be widely used in and treat and prevent osteomyelitis and deep infection) functional antibiosis drug, play the role of cooperateing with repairing and treating, carry The success rate of high bone tissue reparation, to reach good medicine controlled releasing effect.
The present invention can make it according to actual demand to change anode oxidation process parameter adjustment pore size and porosity Match with the mechanical property of host bone tissue, to reduce or eliminate stress-shielding effect, and using the nanometer of small-bore Porous structure (about 30~60nm) can deposit hydroxyapatite antimicrobial medicine composite coating well, and dispersibility is more preferable, binding force Stronger, the medicament slow release time is long, can play the effect of durable antibiotic.Of the invention simultaneously prepares the simple for process of composite coating, Cost is relatively low, and each component is very safe to the equal nonhazardous of human body or absorbable and degradable in composite coating, is suitable for large-scale promotion And application.
The experimental results showed that porous titanium matrix composite prepared by the present invention, matrix has cellular structures, possesses Higher specific surface area, aperture are 30~60nm, and porosity reaches 90~98.6%, multifunctional composite coating with it is cellular porous Structure combine it is compact, preferable in conjunction with effect, composite material is only 0.23g or so in initial burst release amount, and burst release rate is about 28.75%, accumulative release can extend to one month or more, can preferably achieve the effect that durable antibiotic.
In order to further illustrate the present invention, with reference to embodiments to a kind of porous titanium matrix composite provided by the invention And preparation method thereof, using being described in detail, but it is to be understood that these embodiments are before being with technical solution of the present invention It puts and is implemented, give detailed embodiment and specific operating process, only the spy to further illustrate the present invention It seeks peace advantage, rather than limiting to the claimed invention, protection scope of the present invention are also not necessarily limited to following embodiments.
Detecting step：
Porous titanium matrix composite after alkaline bath immersion treatment carries medicine is placed in equipped with 3ml human body simulations body fluid (SBF) In centrifuge tube in, drug release studies, 37 DEG C of cultivation temperature, substep release time interval are then carried out in constant incubator It, need to will be former when replacing the new PBS solution of equivalent every time for 1h, 3h, 9h, 15h, 30h, 60h, 100h, 150h, 300h and 600h The PBS solution come in centrifuge tube retains to detect, and detection is completed by ultraviolet specrophotometer (UV), the compound work(of multicoat Energy property medicine carrying material observes specimen surface pattern using field emission scanning electron microscope (Hitachi SU8010).
Embodiment 1
The titanium alloy that size is 40 × 20 × 1mm is first polished with sand paper successively, is then respectively put into acetone, anhydrous Respectively be cleaned by ultrasonic 10min in ethyl alcohol, deionized water, it is to be cleaned after cold wind drying it is spare；By above-mentioned gained sample in phosphorus Acid：Sulfuric acid：Water=1:3:Electrochemical polish is carried out in the polishing fluid of 10 (volume ratios), electrochemical polish is in 85 DEG C of oil bath devices It carries out, mixing speed 800r/min, polishing uses constant flow method, current density 25A/dm2, polishing time 10s will polish Sample afterwards is cleaned by ultrasonic 10min with deionized water, after takes out and rinses well, cold wind dries up, and is then pressed with adhesive tape 20 × 20mm is spare to not participating in being packaged on one side for reaction, to control reaction zone and prevent edge from polarizing.
Anodic oxidation uses constant-voltage method, and hydrofluoric acid solution is as electrolyte, wherein hydrofluoric acid concentration 0.5wt%, oxidation electricity Pressure is 10V, and oxidization time 1h, oxidizing temperature is 25 DEG C, mixing speed 1000r/min, and sample and fast is taken out after anodic oxidation Speed is rinsed with a large amount of deionized waters, is dried at room temperature.It is made annealing treatment after drying, annealing temperature is 350 DEG C, soaking time 2h, 5 DEG C/min of heating rate cool to the furnace after room temperature and take out spare, obtain the titanium base material with porous structure surface.
The titanium base material with porous structure surface prepared to the embodiment of the present invention 1 characterizes.
It is the titanium base material surface SEM patterns with porous structure surface prepared by the embodiment of the present invention 1 referring to Fig. 1, Fig. 1 Figure.
It is the titanium base material surface SEM patterns with porous structure surface prepared by the embodiment of the present invention 1 referring to Fig. 2, Fig. 2 Figure partial enlarged view.
By Fig. 1 and Fig. 2 it is found that cellular porous structure arranges compact, high porosity, high-specific surface area, pore size About 30~60nm can be used as the good carrier of hydroxyapatite.
7.0845g Ca (NO are accurately weighed at room temperature3)2·4H2O and 2.3772g (NH4)2HPO4It is respectively placed in 150ml burnings In cup, 100ml deionized waters are then respectively adding, after uniform stirring dissolving, is poured into 500ml beakers and mixes, make it Ca：P=5:3 (molar ratios) then carry out chitosan piece (Mw=50~100KDa, DD >=95%) in 2wt% glacial acetic acid Dissolving is added the chitosan solution that appropriate amount of deionized water is made into 2.0mg/ml, and centrifugal mixer (50ml centrifuge tubes), takes upper layer clear Liquid a certain amount of vancomycin powder is added into supernatant liquor to prepare polymer suspension liquid so that vancomycin in suspension Mass ratio with chitosan is 6, and then prepared polymer suspension liquid is added in water-soluble calcium microcosmic salt solution, adjusts liquid Face height is 250ml, finally adjusts solution PH=4.7.
It is the electro-deposition experimental provision used in the embodiment of the present invention referring to Fig. 3, Fig. 3.
Using electro-deposition experimental provision shown in Fig. 3,500ml beakers are put into constant-temperature heating magnetic stirring apparatus, anode connects Graphite electrode, cathode connect sample and make working electrode, and working electrode is first placed in steady in deposition liquid by electrode spacing 3cm before depositing Determine 2min, electrodeposition temperature is 37 DEG C, mixing speed 900r/min, while rising current method using ladder, first uses 0.7A electric currents 5min is deposited, then by current boost to 1.3A, redeposited 5min finally rises to 2.0A stably depositing 20min, waits for that sample deposits Complete rear taking-up is cleaned with deionized water, natural air drying, the alkaline bath at 0.1mol/L NaOH solutions, 37 DEG C of the sample after air-drying Immersion treatment 2h obtains base extraction sample, and surface is rinsed with deionized water after taking-up, and it is multiple to obtain porous titanium-based for natural air drying The compound functional medicine carrying material of condensation material, i.e. multicoat.
Process product and final product to the embodiment of the present invention 4 are characterized using scanning electron microscope.
Referring to Fig. 4, Fig. 4 is the SEM patterns of the compound functional medicine carrying material of multicoat prepared by the embodiment of the present invention 1 Figure.
As shown in Figure 4, the hydroxyapatite layer for the porous titanium matrix composite that prepared by the present invention is filled in titanium base material table The hole in face and it is coated on porous titanium base material surface.Chitosan-vancomycin stacking is covered in hydroxyapatite surface, With ellipsoid structure and block structure.The little particle of many American football shapes on the surface, size is at 3~7 μm or so, throughout whole A specimen surface, little particle bottom calcium-phosphate layer are tightly combined, and the hydroxyapatite of no apparent fine needle tufted is observed.
The compound functional medicine carrying material of multicoat prepared by the embodiment of the present invention 1 is detected.
The burst release amount of the compound functional medicine carrying material of multicoat prepared by the embodiment of the present invention 1 in for 24 hours initially is only 0.33g or so, burst release rate are about 41.25%, and accumulative release can extend to one month or more, can preferably reach durable antibiotic Effect.
Embodiment 2
The titanium alloy that size is 40 × 20 × 1mm is first polished with sand paper successively, is then respectively put into acetone, anhydrous Respectively be cleaned by ultrasonic 15min in ethyl alcohol, deionized water, it is to be cleaned after cold wind drying it is spare；By above-mentioned gained sample in phosphorus Acid：Sulfuric acid：Water=1:3:Electrochemical polish is carried out in the polishing fluid of 10 (volume ratios), electrochemical polish is in 87 DEG C of oil bath devices It carries out, mixing speed 1000r/min, polishing uses constant flow method, current density 35A/dm2, polishing time 15s will throw Sample after light is cleaned by ultrasonic 13min with deionized water, after takes out and rinses well, cold wind dries up, and then uses adhesive tape It is spare to not participating in being packaged on one side for reaction by 20 × 20mm, to control reaction zone and prevent edge from polarizing.
Anodic oxidation uses constant-voltage method, and hydrofluoric acid solution is as electrolyte, wherein hydrofluoric acid concentration 0.5wt%, oxidation electricity Pressure is 20V, and oxidization time 1h, oxidizing temperature is 25 DEG C, mixing speed 800r/min, and sample and rapid is taken out after anodic oxidation It is rinsed with a large amount of deionized waters, is dried at room temperature.It being made annealing treatment after drying, annealing temperature is 350 DEG C, soaking time 2h, 5 DEG C/min of heating rate cools to the furnace after room temperature and takes out spare, obtains the titanium base material with porous structure surface.
7.0845g Ca (NO are accurately weighed at room temperature3)2·4H2O and 2.3772g (NH4)2HPO4It is respectively placed in 150ml burnings In cup, 100ml deionized waters are then respectively adding, after uniform stirring dissolving, is poured into 500ml beakers and mixes, make it Ca：P=5:3 (molar ratios) then carry out chitosan piece (Mw=50~100KDa, DD >=95%) in 2wt% glacial acetic acid Dissolving is added the chitosan solution that 40ml deionized waters are made into 2.0mg/ml, and centrifugal mixer (50ml centrifuge tubes), takes upper layer clear Liquid a certain amount of vancomycin powder is added into supernatant liquor to prepare polymer suspension liquid so that vancomycin in suspension Mass ratio with chitosan is 8, and then prepared polymer suspension liquid is added in water-soluble calcium microcosmic salt solution, adjusts liquid Face height is 250ml, finally adjusts solution PH=4.5.
Using electro-deposition experimental provision shown in Fig. 3,500ml beakers are put into constant-temperature heating magnetic stirring apparatus, anode connects Graphite electrode, cathode connect sample and make working electrode, and working electrode is first placed in steady in deposition liquid by electrode spacing 3cm before depositing Determine 2min, electrodeposition temperature is 35 DEG C, mixing speed 1200r/min, while rising current method using ladder, first uses 0.5A electric currents 5min is deposited, then by current boost to 1.0A, redeposited 5min finally rises to 1.5A stably depositing 20min, waits for that sample deposits Complete rear taking-up is cleaned with deionized water, natural air drying, the alkaline bath at 0.1mol/L NaOH solutions, 37 DEG C of the sample after air-drying Immersion treatment 3h obtains base extraction sample, and surface is rinsed with deionized water after taking-up, and it is multiple to obtain porous titanium-based for natural air drying The compound functional medicine carrying material of condensation material, i.e. multicoat.
The compound functional medicine carrying material of multicoat prepared by the embodiment of the present invention 2 is detected.
The burst release amount of the compound functional medicine carrying material of multicoat prepared by the embodiment of the present invention 2 in for 24 hours initially is only 0.31g or so, burst release rate are about 38.75%, and accumulative release can extend to one month or more, can preferably reach durable antibiotic Effect.
Embodiment 3
The titanium alloy that size is 40 × 20 × 1mm is first polished with sand paper successively, is then respectively put into acetone, anhydrous Respectively be cleaned by ultrasonic 12min in ethyl alcohol, deionized water, it is to be cleaned after cold wind drying it is spare；By above-mentioned gained sample in phosphorus Acid：Sulfuric acid：Water=1:3:Electrochemical polish is carried out in the polishing fluid of 10 (volume ratios), electrochemical polish is in 82 DEG C of oil bath devices It carries out, mixing speed 900r/min, polishing uses constant flow method, current density 50A/dm2, polishing time 15s will polish Sample afterwards is cleaned by ultrasonic 15min with deionized water, after takes out and rinses well, cold wind dries up, and is then pressed with adhesive tape 20 × 20mm is spare to not participating in being packaged on one side for reaction, to control reaction zone and prevent edge from polarizing.
Anodic oxidation uses constant-voltage method, and hydrofluoric acid solution is as electrolyte, wherein hydrofluoric acid concentration 0.7wt%, oxidation electricity Pressure is 15V, and oxidization time 2h, oxidizing temperature is 30 DEG C, mixing speed 1200r/min, and sample and fast is taken out after anodic oxidation Speed is rinsed with a large amount of deionized waters, is dried at room temperature.It is made annealing treatment after drying, annealing temperature is 550 DEG C, soaking time 3h, 5 DEG C/min of heating rate cool to the furnace after room temperature and take out spare, obtain the titanium base material with porous structure surface.
7.0845g Ca (NO are accurately weighed at room temperature3)2·4H2O and 2.3772g (NH4)2HPO4It is respectively placed in 150ml burnings In cup, 100ml deionized waters are then respectively adding, after uniform stirring dissolving, is poured into 500ml beakers and mixes, make it Ca：P=5:3 (molar ratios) then carry out chitosan piece (Mw=50~100KDa, DD >=95%) in 2wt% glacial acetic acid Dissolving is added the chitosan solution that 40ml deionized waters are made into 2.0mg/ml, and centrifugal mixer (50ml centrifuge tubes), takes upper layer clear Liquid a certain amount of vancomycin powder is added into supernatant liquor to prepare polymer suspension liquid so that vancomycin in suspension Mass ratio with chitosan is 10, and then prepared polymer suspension liquid is added in water-soluble calcium microcosmic salt solution, is adjusted Liquid level is 250ml, finally adjusts solution PH=5.
Two electrode spacings are 3cm in electro-deposition experimental provision, and first working electrode is placed in deposition liquid before deposition and is stablized 1.5min, electrodeposition temperature is 40 DEG C, mixing speed 800r/min, while rising current method using ladder, first uses 1.0A electric currents 5min is deposited, then by current boost to 1.5A, redeposited 5min finally rises to 3.0A stably depositing 20min, waits for that sample deposits Complete rear taking-up is cleaned with deionized water, natural air drying, the alkaline bath at 0.1mol/L NaOH solutions, 37 DEG C of the sample after air-drying Immersion treatment 2.5h obtains base extraction sample, and surface is rinsed with deionized water after taking-up, and natural air drying obtains porous titanium-based The compound functional medicine carrying material of composite material, i.e. multicoat.
Process product and final product to the embodiment of the present invention 4 are characterized using scanning electron microscope.
Referring to the SEM shape appearance figures that Fig. 5, Fig. 5 are the semi-finished product in the embodiment of the present invention 3 without alkaline bath processing after electro-deposition.
Referring to Fig. 6, Fig. 6 is electro-deposition and to carry out alkaline bath treated porous titanium matrix composite in the embodiment of the present invention 3 SEM shape appearance figures.
By Fig. 5 and Fig. 6 it is found that the hydroxyapatite layer of porous titanium matrix composite prepared by the present invention is filled in titanium-based material Expect the hole on surface and is coated on porous titanium base material surface.The configuration of surface of hydroxyapatite layer has the surface of fine acicular Structure more forms the surface texture of multiple needle tufted；And chitosan-vancomycin is not only entrained in the thin of hydroxyapatite surface In needle cluster, it can also stack and be covered in hydroxyapatite surface.There is cotton-shaped structure, stacking to have on the surface in needle cluster for it Petal-like structures and ellipsoid structure.
The compound functional medicine carrying material of multicoat prepared by the embodiment of the present invention 3 is detected.
Referring to Fig. 7, Fig. 7, which is that the vancomycin drug of porous titanium matrix composite prepared by the embodiment of the present invention 3 is accumulative, to be released Put rate curve.
As shown in Figure 7, the compound functional medicine carrying material of multicoat that prepared by the embodiment of the present invention 3 is in for 24 hours initially Burst release amount is only 0.30g or so, and burst release rate is about 37.50%, and accumulative release can extend to one month or more, can preferably be reached To the effect of durable antibiotic.
Embodiment 4
The titanium alloy that size is 40 × 20 × 1mm is first polished with sand paper successively, is then respectively put into acetone, anhydrous Respectively be cleaned by ultrasonic 12min in ethyl alcohol, deionized water, it is to be cleaned after cold wind drying it is spare；By above-mentioned gained sample in phosphorus Acid：Sulfuric acid：Water=1:3:Electrochemical polish is carried out in the polishing fluid of 10 (volume ratios), electrochemical polish is in 80 DEG C of oil bath devices It carries out, mixing speed 1200r/min, polishing uses constant flow method, current density 45A/dm2, polishing time 13s will throw Sample after light is cleaned by ultrasonic 10min with deionized water, after takes out and rinses well, cold wind dries up, and then uses adhesive tape It is spare to not participating in being packaged on one side for reaction by 20 × 20mm, to control reaction zone and prevent edge from polarizing.
Anodic oxidation uses constant-voltage method, and hydrofluoric acid solution is as electrolyte, wherein hydrofluoric acid concentration 0.3wt%, oxidation electricity Pressure is 20V, and oxidization time 3h, oxidizing temperature is 27 DEG C, mixing speed 1000r/min, and sample and fast is taken out after anodic oxidation Speed is rinsed with a large amount of deionized waters, is dried at room temperature.It is made annealing treatment after drying, annealing temperature is 450 DEG C, soaking time 2h, 5 DEG C/min of heating rate cool to the furnace after room temperature and take out spare, obtain the titanium base material with porous structure surface.
7.0845g Ca (NO are accurately weighed at room temperature3)2·4H2O and 2.3772g (NH4)2HPO4It is respectively placed in 150ml burnings In cup, 100ml deionized waters are then respectively adding, after uniform stirring dissolving, is poured into 500ml beakers and mixes, make it Ca：P=5:3 (molar ratios) then carry out chitosan piece (Mw=50~100KDa, DD >=95%) in 2wt% glacial acetic acid Dissolving is added the chitosan solution that 40ml deionized waters are made into 2.0mg/ml, and centrifugal mixer (50ml centrifuge tubes), takes upper layer clear Liquid a certain amount of vancomycin powder is added into supernatant liquor to prepare polymer suspension liquid so that vancomycin in suspension Mass ratio with chitosan is 5, and then prepared polymer suspension liquid is added in water-soluble calcium microcosmic salt solution, adjusts liquid Face height is 250ml, finally adjusts solution PH=4.6.
Two electrode spacings are 3cm in electro-deposition experimental provision, and first working electrode is placed in deposition liquid before deposition and is stablized 2min, electrodeposition temperature are 30 DEG C, mixing speed 1000r/min, while rising current method using ladder, first use 1.0A electric currents heavy Product 5min, then by current boost to 1.5A, redeposited 5min finally rises to 2.5A stably depositing 20min, waits for that sample has deposited Taking-up is cleaned with deionized water afterwards, natural air drying, and by the sample after air-drying, alkaline bath soaks at 0.1mol/L NaOH solutions, 37 DEG C Bubble processing 3h, obtains base extraction sample, surface is rinsed with deionized water after taking-up, it is compound to obtain porous titanium-based for natural air drying The compound functional medicine carrying material of material, i.e. multicoat.
The compound functional medicine carrying material of multicoat prepared by the embodiment of the present invention 4 is detected.
The burst release amount of the compound functional medicine carrying material of multicoat prepared by the embodiment of the present invention 4 in for 24 hours initially is only 0.34g or so, burst release rate are about 42.50%, and accumulative release can extend to one month or more, can preferably reach durable antibiotic Effect.
Above to provided by the invention a kind of for the POROUS TITANIUM based nano composite material of hard tissue material and its preparation side Method, the application in terms of bio-medical material are described in detail, original of the specific case used herein to the present invention Reason and embodiment are expounded, and the explanation of above example is only intended to help to understand that the method for the present invention and its core are thought Think, including best mode, and but also any person skilled in the art can put into practice the present invention, including manufactures and use Any device or system, and implement the method for any combination.It should be pointed out that coming for those skilled in the art It says, without departing from the principle of the present invention, can be with several improvements and modifications are made to the present invention, these improvement and modification It also falls within the protection scope of the claims of the present invention.The range of patent protection of the present invention is defined by the claims, and can Including those skilled in the art it is conceivable that other embodiment.It is not different from right if these other embodiments have and wants The structural element of character express is sought, or if they include and equivalent structure of the character express of claim without essence difference Element, then these other embodiments should also be included in the scope of the claims.

Claims (10)

1. a kind of porous titanium matrix composite, which is characterized in that including porous titanium base material, be compounded in the porous titanium-based Hydroxyapatite layer on material, and chitosan-vancomycin for being compounded on the hydroxyapatite layer.
2. porous titanium matrix composite according to claim 1, which is characterized in that the titanium base material includes that titanium or titanium close Gold；
The aperture of the titanium base material is 30~60nm；
The porosity of the titanium base material is 90~98.6%；
The size of the titanium base material is (40~60) × (20~40) × (0.5~2mm).
3. porous titanium matrix composite according to claim 1 or 2, which is characterized in that the titanium base material and hydroxyl phosphorus The mass ratio of lime stone is (10~20)：1；
The mass ratio of the titanium base material and the chitosan-vancomycin is (40~70)：1；
The hydroxyapatite layer has fine acicular surface texture；
Chitosan-the vancomycin have flocculent structure, petal-like structures, ellipsoid structure and one kind in block structure or It is a variety of.
4. porous titanium matrix composite according to claim 3, which is characterized in that the thickness of the hydroxyapatite layer is 6~15 μm；
A diameter of 1~4 μm of the fine needle；
Chitosan-the vancomycin is entrained in the needle cluster of the hydroxyapatite layer surface and/or is covered in the phosphorus ash Rock layers surface.
5. a kind of preparation method of porous titanium matrix composite, which is characterized in that include the following steps：
1) it will be obtained with porous structure surface by pretreated titanium base material after anode oxidation process and annealing Titanium base material；
After chitosan and vancomycin mixed liquor, calcium salt, microcosmic salt and water are mixed, pH value is adjusted, the first mixed liquor is obtained；
2) titanium base material with porous structure surface and the first mixed liquor obtained above-mentioned steps obtains after electro-deposition Semi-finished product；
3) semi-finished product for obtaining above-mentioned steps obtain porous titanium matrix composite after alkali immersion treatment.
6. preparation method according to claim 5, which is characterized in that the pretreated process includes polishing, cleaning, does It is one or more in dry and polishing；
The anode oxidation process is constant-voltage method anode oxidation process；
The oxidation voltage of the anodic oxidation is 10~20V；
The time of the anodic oxidation is 1~3h；
The oxidizing temperature of the anodic oxidation is 20~30 DEG C；
The electrolyte of the anodic oxidation includes hydrofluoric acid solution, ammonium fluoride ethylene glycol organic electrolysis plastidome and hydrofluoric acid/sulphur It is one or more in acid/aqueous systems；
The temperature of the annealing is 350~550 DEG C；
The time of the annealing is 2~3h；
The heating rate of the annealing is 3~5 DEG C/min.
7. preparation method according to claim 5, which is characterized in that the mixing the specific steps are：
After calcium salt, microcosmic salt and water are mixed, calcium microcosmic salt mixed solution is obtained；
Chitosan piece is dissolved in acid solution, after dilution, chitosan solution is obtained, supernatant liquor is taken after stirring, then up layer Vancomycin is added in clear liquid, after mixing again, obtains suspension；
After suspension and calcium microcosmic salt mixed solution that above-mentioned steps obtain are continued mixing, pH value is adjusted, the first mixed liquor is obtained.
8. preparation method according to claim 7, which is characterized in that the calcium salt includes Ca (NO3)2、CaCl2、Ca (NO3)2·4H2It is one or more in O；
The microcosmic salt includes (NH4)2HPO4、K2HPO4、KH2PO4And NaH2PO4In it is one or more；
Calcium phosphorus molar ratio in the calcium microcosmic salt mixed solution is 5：3；
The mass ratio of the calcium salt and water is 7：(200~250)；
The weight average molecular weight of the chitosan is 50~100KDa；
The deacetylation of the chitosan is more than or equal to 95%；
The acid solution includes glacial acetic acid solution；
The mass concentration of the acid solution is 1wt%~2wt%；
A concentration of 1~3mg/mL of the chitosan solution；
The mass ratio of chitosan and vancomycin is 1 in the suspension：(5~10)；
The pH value is 4~6.2.
9. according to the preparation method described in claim 5~8 any one, which is characterized in that the temperature of the electro-deposition is 30 ~40 DEG C；
The electro-deposition is specially to rise current method using ladder to carry out electro-deposition；
The deposition current of first ladder of the electro-deposition is 0.5~1.0A；The sedimentation time of first ladder of the electro-deposition For 5~10min；
The deposition current of second ladder of the electro-deposition is 1.0~1.5A；The sedimentation time of second ladder of the electro-deposition For 5~10min；
The deposition current of the third ladder of the electro-deposition is 1.5~3.0A；The sedimentation time of the third ladder of the electro-deposition For 20~40min；
The time of the alkali immersion treatment is 2~3h；
A concentration of 1.0~1.5mol/L of the alkali immersion treatment lye；
The alkali immersion treatment lye includes sodium hydroxide solution and/or ammonium hydroxide.
10. described in the porous titanium matrix composite or claim 5~9 any one described in Claims 1 to 4 any one Application of the porous titanium matrix composite in terms of bio-medical material prepared by preparation method.
CN201810512957.2A 2018-05-25 2018-05-25 Porous titanium-based nano composite material for hard tissue material and preparation method and application thereof Active CN108404222B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810512957.2A CN108404222B (en) 2018-05-25 2018-05-25 Porous titanium-based nano composite material for hard tissue material and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810512957.2A CN108404222B (en) 2018-05-25 2018-05-25 Porous titanium-based nano composite material for hard tissue material and preparation method and application thereof

Publications (2)

Publication Number Publication Date
CN108404222A true CN108404222A (en) 2018-08-17
CN108404222B CN108404222B (en) 2021-09-21

Family

ID=63140669

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810512957.2A Active CN108404222B (en) 2018-05-25 2018-05-25 Porous titanium-based nano composite material for hard tissue material and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN108404222B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109621006A (en) * 2019-02-21 2019-04-16 刘昕 A kind of 3D printing POROUS TITANIUM rack surface anti-infection bio active coating preparation method
CN112386748A (en) * 2019-08-12 2021-02-23 湖南早晨纳米机器人有限公司 Magnesium alloy nano robot and preparation method thereof
CN112438962A (en) * 2019-08-12 2021-03-05 湖南早晨纳米机器人有限公司 Magnetic drug-loaded nano robot and preparation method thereof

Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002098307A1 (en) * 2001-06-07 2002-12-12 The Royal Alexandra Hospital For Children A device for the delivery of a drug to a fractured bone
US20050170070A1 (en) * 2001-01-30 2005-08-04 Isotis S.A. Method for applying a bioactive coating on a medical device
CN101381881A (en) * 2007-09-05 2009-03-11 西南交通大学 Method for preparing hydroxylapatite/chitosan composite coating by pulse electrochemical deposition
CN101411892A (en) * 2007-10-19 2009-04-22 中国科学院金属研究所 Method for preparing hydroxylapatite/polylactic acid composite biological coating on surface of magnesium alloy
CN101507832A (en) * 2009-03-31 2009-08-19 扬州大学 Method for preparing rod-shaped hydroxyapatite capable of controlling nano size
CN101636186A (en) * 2006-11-10 2010-01-27 山特维克知识产权股份有限公司 Surgical implant composite materials and kits and methods of manufacture
CN101791436A (en) * 2010-04-15 2010-08-04 四川大学 Biomedical material with porous calcium phosphate-chitosan composite coating
CN102028969A (en) * 2010-12-07 2011-04-27 浙江大学 Heterogeneous layered mineralized coating on surface of medical implant and preparation method thereof
CN103405809A (en) * 2013-07-23 2013-11-27 东华大学 Method used for preparing microcarrier/polymer composite scaffold by electro-deposition
CN103805987A (en) * 2014-01-23 2014-05-21 南京纳创新材料技术有限公司 Preparation method of patterned titanium coating hard tissue substitute material
CN103908357A (en) * 2014-04-09 2014-07-09 飞而康快速制造科技有限责任公司 Artificial skeletal structure
CN104353121A (en) * 2014-11-24 2015-02-18 吴志宏 BMP microsphere loaded 3D printing porous metal stent and preparation method thereof
CN105442022A (en) * 2015-11-24 2016-03-30 哈尔滨医科大学 Method for preparing gentamicin-loaded magnesium-based calcium phosphate/chitosan/nanotube medicine carrying film layer through electrophoresis method
CN105624762A (en) * 2016-01-15 2016-06-01 厦门大学 Method for preparing bioactive composite coating on surface of titanium or titanium alloy
CN105862095A (en) * 2016-06-02 2016-08-17 中南大学 Bioactive coating and preparation method thereof
CN107456610A (en) * 2016-06-02 2017-12-12 北京大学 A kind of Zn-Ag systems kirsite and preparation method and application

Patent Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050170070A1 (en) * 2001-01-30 2005-08-04 Isotis S.A. Method for applying a bioactive coating on a medical device
WO2002098307A1 (en) * 2001-06-07 2002-12-12 The Royal Alexandra Hospital For Children A device for the delivery of a drug to a fractured bone
CN101636186A (en) * 2006-11-10 2010-01-27 山特维克知识产权股份有限公司 Surgical implant composite materials and kits and methods of manufacture
CN101381881A (en) * 2007-09-05 2009-03-11 西南交通大学 Method for preparing hydroxylapatite/chitosan composite coating by pulse electrochemical deposition
CN101411892A (en) * 2007-10-19 2009-04-22 中国科学院金属研究所 Method for preparing hydroxylapatite/polylactic acid composite biological coating on surface of magnesium alloy
CN101507832A (en) * 2009-03-31 2009-08-19 扬州大学 Method for preparing rod-shaped hydroxyapatite capable of controlling nano size
CN101791436A (en) * 2010-04-15 2010-08-04 四川大学 Biomedical material with porous calcium phosphate-chitosan composite coating
CN102028969A (en) * 2010-12-07 2011-04-27 浙江大学 Heterogeneous layered mineralized coating on surface of medical implant and preparation method thereof
CN103405809A (en) * 2013-07-23 2013-11-27 东华大学 Method used for preparing microcarrier/polymer composite scaffold by electro-deposition
CN103805987A (en) * 2014-01-23 2014-05-21 南京纳创新材料技术有限公司 Preparation method of patterned titanium coating hard tissue substitute material
CN103908357A (en) * 2014-04-09 2014-07-09 飞而康快速制造科技有限责任公司 Artificial skeletal structure
CN104353121A (en) * 2014-11-24 2015-02-18 吴志宏 BMP microsphere loaded 3D printing porous metal stent and preparation method thereof
CN105442022A (en) * 2015-11-24 2016-03-30 哈尔滨医科大学 Method for preparing gentamicin-loaded magnesium-based calcium phosphate/chitosan/nanotube medicine carrying film layer through electrophoresis method
CN105624762A (en) * 2016-01-15 2016-06-01 厦门大学 Method for preparing bioactive composite coating on surface of titanium or titanium alloy
CN105862095A (en) * 2016-06-02 2016-08-17 中南大学 Bioactive coating and preparation method thereof
CN107456610A (en) * 2016-06-02 2017-12-12 北京大学 A kind of Zn-Ag systems kirsite and preparation method and application

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
F. ORDIKHANIA ET AL.: "Long-term antibiotic delivery by chitosan-based composite coatingswith bone regenerative potential", 《APPLIED SURFACE SCIENCE》 *
JODY REDEPENNING ET AL.: "Electrochemical preparation of chitosan/hydroxyapatite composite coatings on titanium substrates", 《JOURNAL OF BIOMEDICAL MATERIALS RESEARCH》 *
周加贝: "可载药生物高分子/磷酸钙多孔复合涂层的制备、表征及生物学评价", 《中国博士学位论文全文库工程科技Ι辑》 *
张杭州等: "万古霉素/羟基磷灰石/二氧化钛纳米管的抗菌性能", 《中国组织工程研究》 *
张珍容等: "纯钛表面立方介孔SiO2薄膜诱导沉积碳磷灰石层", 《无机材料学报》 *
李贵臻等: "《计算机信息技术与生物医学工程》", 31 March 2018, 天津科学技术出版社 *
王杏等: "《纳米二氧化钛的生产与应用》", 31 July 2014, 贵州科技出版社 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109621006A (en) * 2019-02-21 2019-04-16 刘昕 A kind of 3D printing POROUS TITANIUM rack surface anti-infection bio active coating preparation method
CN112386748A (en) * 2019-08-12 2021-02-23 湖南早晨纳米机器人有限公司 Magnesium alloy nano robot and preparation method thereof
CN112438962A (en) * 2019-08-12 2021-03-05 湖南早晨纳米机器人有限公司 Magnetic drug-loaded nano robot and preparation method thereof

Also Published As

Publication number Publication date
CN108404222B (en) 2021-09-21

Similar Documents

Publication Publication Date Title
EP1385449B1 (en) Biologically-functionalised, metabolically-inductive implant surfaces
EP1381402B1 (en) Method for improvement of soft tissue attachment and implants making use of said method
Ma et al. Biomimetic processing of nanocrystallite bioactive apatite coating on titanium
CN103272269B (en) Hydroxyapatite/chitosan composite coating and preparation method thereof
CN102743789B (en) Artificial tooth root with micro-nano hierarchical topologic surface structure and preparation method of artificial tooth root
CN108404222A (en) A kind of POROUS TITANIUM based nano composite material for hard tissue material and preparation method thereof, application
WO2016202100A1 (en) Polyether ether ketone/nano hydroxyapatite dental implant and manufacturing method thereof
CN108434517A (en) Antibacterial dental implant and preparation method thereof
CN102113918B (en) Method for preparing porous structure on surface of pure titanium dental implant
CN103566411B (en) Mesoporous bioactive glass-modified porous ceramic ball prosthetic eye holder and preparation method thereof
CN108042846B (en) Preparation method of strontium-doped tantalum oxide nanorod structure bioactive coating
CN106267342A (en) A kind of dentistry implant and preparation method thereof
CN109385658A (en) Hydroxyapatite nano stick array configuration coating of titanium-based surface multiple element codope and its preparation method and application
CN108348637A (en) Large size 3D porous supports and its acquisition technique made of the activity hydroxy apatite obtained the biomorph transformation through natural structure
CN110338921B (en) Dental implant and preparation method thereof
CN106435690B (en) A kind of microarc oxidation solution of titanium alloy biological coating containing strontium and its application
CN105497990B (en) A kind of three-dimensional porous titanium-based magnesium doping coating and preparation method thereof
CN108004527A (en) A kind of preparation method of zinc doping hydroxyapatite coating layer for magnesium alloy materials
Zhao et al. Promotion of bone formation and antibacterial properties of titanium coated with porous Si/Ag-doped titanium dioxide
CN108144125A (en) A kind of planting body with surface active coating
CN111407923A (en) Drug release controlled magnesium or magnesium alloy bionic bone and preparation method thereof
Zhou et al. Bioactive ceramics and metals for regenerative engineering
CN208243822U (en) A kind of 3D printing composite magnetic metallic support
CN112190762A (en) Injection type magnesium-based composite fiber reinforced calcium phosphate biological bone adhesive and preparation method and application thereof
Baino et al. Ceramics for oculo-orbital surgery

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant