CN110403736A - A kind of super porous titanium alloy of 3D printing facilitates bone surface method of modifying - Google Patents
A kind of super porous titanium alloy of 3D printing facilitates bone surface method of modifying Download PDFInfo
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- CN110403736A CN110403736A CN201910732441.3A CN201910732441A CN110403736A CN 110403736 A CN110403736 A CN 110403736A CN 201910732441 A CN201910732441 A CN 201910732441A CN 110403736 A CN110403736 A CN 110403736A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
- A61F2/30771—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
- A61F2002/30772—Apertures or holes, e.g. of circular cross section
- A61F2002/30784—Plurality of holes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
- A61F2002/3093—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth for promoting ingrowth of bone tissue
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/3094—Designing or manufacturing processes
- A61F2002/30985—Designing or manufacturing processes using three dimensional printing [3DP]
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- Health & Medical Sciences (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
The invention belongs to bioactivity coatings processing technology field, discloses a kind of super porous titanium alloy of 3D printing and facilitate bone surface method of modifying, the Ti6Al4V experimental member with most suitable microcellular structure is made in conjunction with accuracy controlling Arcam 3D printer；Reliably bone active is facilitated to combine RGD excellent adhesion characteristics and BMP II, proposes the method that compound RGD-BMP II sustained-release micro-spheres carry out porous titanium alloy structure to facilitate bone surface modified；And it is detected by experiment, and analyze it and promote Osteogenic Mechanism.The present invention facilitates bone surface activity processing method to the super porous titanium alloy of 3D printing is simplified, orthopaedics personalization bone defect healing efficiency, expanded metal 3D printing porous titanium alloy technology are improved in the application in Bone Ingrowth, Bone Defect Repari field, there is important theory significance and clinical value.
Description
Technical field
The invention belongs to bioactivity coatings processing technology fields more particularly to a kind of super porous titanium alloy of 3D printing to facilitate
Bone surface method of modifying.
Background technique
Currently, the immediate prior art: as digital orthopaedic technique development especially 3D printing technique is dashed forward in recent years
Fly the progress to push ahead vigorously, the newest fruits of bond material process for modifying surface, for solve clinical orthopaedics large segmental bone defect reparation and
The research and development at personalized implants Bone Ingrowth interface (micro cavity layer structures) provide unprecedented opportunity.3D printing is according to object
Three-dimensional digital model carries out discrete dynamics models by successively increasing material, has the fabrication schedule of simplified product, shortens and develop week
Phase, the advantages of improving efficiency and reducing cost, it is considered as the one of the important signs that of the fourth industrial revolution.With 3D printing technique
Development, equipment cost reduction, be applied to the fields such as aerospace, industrial manufacture, biomedicine at present.3D printing is special
It is suitably applied this kind of skeleton with complicated surface and space structure, for orthopedics diagnosis treatment, medical apparatus industry
Development brings unprecedented new opportunities.Application of the 3D printing technique in orthopedic treatment is mainly reflected in surgery planning at present
With simulation, establish operation guide plate, personalized three levels of orthopaedics implant, and the latter undoubtedly belongs to the high level in clinical orthopaedics
Secondary application.
(1) metal 3D printing personalization orthopaedics implant
Due to the individual sex differernce of skeleton, the standardization orthopaedics implantation of the different sequences, model of produced in conventional processes
Object tends not to and the bone of different patients all matches.Doctor selects the implants model closest to specific subjects bones, then
Burr is carried out to corresponding bone during operation or bending moulding is carried out to implantation material, with realize between implants and bone as far as possible
Match.But this method will lead to the complication such as operating time length, more, the Yi Yinfa implantation material surrounding fracture of bleeding；And adjustment modeling
Shape changes the mechanical mechanics property of implantation material, increases the risk that its postoperative implants is loosened, is broken.Metal 3D printing is rapid-result fastly
Shape (Rapid Prototyping, RP) technology is a kind of novel forming technique based on discrete dynamics models forming thought, it uses material
The cumulative manufacturing theory of material quickly produces 3D solid interplantation by 3D printing by computer aided processing (CAD) data
Object prosthese.The rapid processing manufacture of implant complex appearance not only may be implemented in this technology, but also can accurately control plant
Inside and the appearance pore structure for entering body, size, porosity, shape, space trend, connectivity including micropore etc..
With the fast development of increases material manufacturing technology, metal 3D printing technique is designed and is manufactured to orthopaedics implant and brings
Unprecedented good opportunity.According to the skeleton model of patient, designs and 3D printing goes out personalized titanium alloy orthopedic implantation material, directly
It realizes the matching between good prosthese and bone or the substitution of neoplastic bone, so as to shorten operating time, reduces postoperative complication,
And improve surgical quality.In addition, comparing with traditional formula manufacture that subtracts, metal 3D printing, which is more suitable for processing, has complex surface shape
The personalized orthopaedics implant of shape is compared with conventional custom, substantially reduces manufacturing time and monetary cost.The following figure is author's early period
Designed and manufacture personalized Modular femoral prosthesis.
(2) metal 3D printing porous titanium alloy (Ti6Al4V) structure
Due to the unique mechanism of metal 3D printing technique, using Ti6Al4V powder as raw material, using EBM (high-power electron beam
Melting) or SLM (laser melting) metal 3D printing technique, bullet is prepared by adjusting the pore size and porosity of printed material
The property lower porous titanium alloy bracket of modulus.Porous titanium alloy can promote Bone Ingrowth microcellular structure to make implants and bone because of it
Firm Integrated implant is obtained between bone and is considered in the dentistry implant, filling and repairing of bone defect, spinal interbody fusion, artificial
The medical domains such as articular prosthesis Bone Ingrowth interface have immeasurable application prospect, and have obtained Preliminary Applications, and prospect is gratifying.
Such as be applied to artificial field, need and around sclerotin generation Integrated implant position such as artificial femur handle prosthese proximal end face, people
Extension rod surface in work acetabular cup outer surface, acetabular bone defect filling block and Biotype artificial knee joint tibia support or marrow,
Printable titanium alloy surface micro cavity layer structures, to promote Bone Ingrowth and Integrated implant.Because being the metal micro-holes painting of integration printing
Layer, if completely eliminating using the possibility that falls off existing for the coatings such as hydroxyapatite, calcium phosphate, bioactivity glass.Therefore,
Metal 3D printing porous titanium alloy technology is undoubtedly brought to medical domains such as orthopaedics, the department of stomatology, decorative sursery and Plastic renovations
Completely new treatment means and far-reaching influence.
(3) significance that metal 3D printing titanium alloy (Ti6Al4V) porous structure facilitates bone surface modified
Metal 3D printing porous titanium alloy structure repairs in bone defect, the Integrated implant at implants Bone Ingrowth interface, or even makees
There is huge application potential for tissue engineering bracket etc..But because titanium alloy belongs to biologically inert metal, surface
Inactive, being chronically implanted may cause " titanium alloy-bone tissue " in vivo interface Integrated implant is bad, and implantation material is caused to loosen,
It falls off.Therefore, surface biological inertia be porous titanium alloy become the problem that must overcome of ideal orthopedic implanting material it
One.Over several years, scholars have been devoted to the study on the modification of porous metals surface texture, and pass through deposition various types coating
It improves its Integrated implant ability, using the chemical modification of material surface to reach the biocompatibility for improving material, promotes cell
Sticking and grow on its surface, finally constructing bionical bone alternate material is always that bone material and field of tissue engineering technology are ground
The emphasis studied carefully.A Duan Xulie of the arginine-glycine-aspartic acid (RGD) as fibronectin on extracellular matrix be
The minmal sequence that integrin can identify on extracellular matrix on cell membrane.It is most effective at present applied to rush cell-specific
The polypeptide sequence sticked, the surface bioactive modification for being widely used in multiple material promote cell on the surface of the material to reach
Specific adhesion, but do not there is relevant application experience to report the porous titanium alloy structure of 3D printing.At current
Property customization, rapid shaping, precision, intelligent Osteological and prosthesis trend under, it is necessary to explore more effective
Ground promote porous surface metal implant cell adhesion technology, the research be rich in prospect, benefit from it is wide it is wealthy, demand is huge
Multidisciplinary application market.
Domestic and international present Research analysis
(1) its osteogenic ability is improved by the nano modification of porous titanium alloy structure, using anode oxidation process to pure
After titanium carries out anodized, specimen surface generates the anatase-phase nano pipe array oxide layer of marshalling.There is research will
Strontium is constructed in POROUS TITANIUM implant in conjunction with titanium nanotube, using anodizing technology carries strontium nanoscale pipe array spline structure, leads to
It crosses the modification of hydro-thermal process mode surface and greatly improves the hydrophily of porous material.And pass through SD rat BMSCs cells in vitro
Experiment discovery nanotube group and carry strontium nanotube group and inhibit the proliferation of cell, but carry strontium nanotube group be obviously promoted cell to
The differentiation in skeletonization direction；The zoopery discovery of porous Ti6Al4V bracket is implanted by the femoral lateral condyle in new zealand white rabbit,
The load porous Ti6Al4V bracket of strontium nanotube coatings is grown into preferably rush bone tissue and bone regeneration capability.
(2) metal coatings such as porous titanium alloy body structure surface spraying tantalum, magnesium improve Integrated implant ability, and tantalum metal is a kind of reason
The medical metal material thought can be integrated with bone tissue, and porous tantalum is made into a variety of implants for repairing bone defect, quilt
Clinical application proves that surface osteogenic ability is strong, is a kind of ideal bone substitution repair materials, but expensive, the fusing point of tantalum compared with
Titanium alloy (Ti6Al4V) is much higher, and manufacturing process is complicated.Li Xiang utilizes chemical vapor deposition method, in controllable porous structure
Ti6Al4V alloy bracket surface deposition tantalum metal coating, makes it be provided simultaneously with ideal three dimensional pore structures and mechanics phase
Capacitive and the excellent biology performance of tantalum metal.The porous tantalum girder metal implant phase produced with Zimmer company, the U.S.
Than tantalum coated porous titanium alloy bracket has the elasticity modulus and compression strength more like with human Cortex's bone.But the technology is wanted
It asks high, carries out the complexity and consuming that tantalum coating considerably increases technique in titanium alloy surface.Have research using magnesium metal as
Biodegradable coating is used to prepare the surface texture in titanium alloy material, considers magnesium alloy due to degradability and multiple
Bioactivity, it is considered to be a kind of revolutionary medical implants metal material.But there is also obvious disadvantages for magnesium coating: magnesium
It degrades after implanting too fast, causes its mechanical property will receive and seriously affect.Therefore, magnesium alloy is implanted into as orthopaedics metal
The application of object is somewhat limited.
(3) physical mechanical stimulation can be used as a kind of supplementary means to promote the Bone Ingrowth of bone grafting rack surface, both at home and abroad
Multinomial research confirms ultrasonic wave and pulse electromagnetic field (PEMF) is used as a kind of alternative non-intrusion type physiotherapy means, right
Knitting, bone nonunion and osteoarthritis etc. can generate satisfactory therapeutic effect.Qin Limei by mouse MC3T3-E1 cell with
The porous titanium alloy timbering material compound criteria modified through differential arc oxidation studies varying strength ultrasonic wave to through differential arc oxidization surface
On the porous titanium alloy bracket of modification osteoblastic proliferation and biological behaviour from skeletonization to differentiation influence, find 30mW/cm2
The ultrasonic wave of intensity influences osteoblastic proliferation on porous titanium alloy bracket and skeletonization to the biological behaviour of differentiation best.Have
Research finds that low intensity pulsed ultrasound (low-intensity pulsed ultrasound stimulation, LIPUS) is right
Mass exchange has facilitation in three-dimensional porous material, to promote knitting, and suggest using LIPUS as supplementary means and
Artificial bone joint, is used for bone defect healing, provides a new thinking for the reparation of large area bone defect.But for big section
Bone defect, only manages mechanical stimulus with artificial bone implant combination, and mechanical strength is troubling.Therefore, physical method includes super
Sound wave and electromagnetic stimulation only can be used as a kind of supplementary means and combine with bone alternate material, the reparation for bone defect.
(4) skeletonization is lacked due to the biologically inert of titanium alloy material in the porous titanium alloy surface recombination osteogenic activity factor
Induced activity, cannot effectively induce bone tissue reparation, even porous titanium alloy in vivo, and surface Bone Ingrowth effect is also big
It gives a discount.Fan Xiangli prepares gelatine microsphere and the gelatin slow-released system of compound rhBMP-2 using modified form emulsification condensation collection method, with
In porous titanium alloy hole gelatin slowly degrade release rhBMP-2, adherency, proliferation and the Osteoblast Differentiation of composite material MSCs refers to
(ALP, OC) is marked obviously higher than non-complex group.Although the gelatine microsphere of compound rhBMP-2 has good sustained release performance, biology
Safety and osteogenic activity, but do not make us between the gelatine microsphere of compound rhBMP-2 and porous titanium alloy surface texture full
The bonding effect of meaning.Therefore, the adhesive capacity for facilitating the bone active factor Yu porous titanium alloy surface texture is improved, is to be promoted
An important ring for Oesteoblast growth, proliferation and mineralising.
(5) become new direction in the customization multifunctional agents such as porous titanium alloy surface recombination antibacterial, anticoagulant, skeletonization organizing
The newest direction in Engineering Bone field is research and development personalized customization multifunctional orthopaedics biomaterial, to the antibacterial ability of bone renovating material,
The functions such as blood compatibility give additional attention, and are not limited merely to Integrated implant ability.Rising etc. successfully to have developed has
Good antibacterial, 3D printing porous titanium alloy implants that are anticoagulant and facilitating bone composite multifunction, the research is in porous support table
Surface treatment is formed, and there is the differential arc oxidation of porous pattern to facilitate bone coating, and then be coupled fixing heparin sodium and vancomycin, pass through
Microorganism detection, bacterium dye anyway and violet staining, it is determined that its good anti-S. aureus L-forms and mycoderm performance.Pass through detection
Associated coagulation function determines that the bracket blood compatibility of test tube of hepari is improved.It is being propped up by human marrow mesenchymal stem cell
It is cultivated on frame, has detected its proliferation activity with cell count and cytoactive detection method.It should be studies have shown that modified by surface
3D printing porous titanium alloy implants possess stable antibacterial and promote osteogenesis function, while showing anticoagulant characteristic.It implies
Its customization reconstruction that complicated bone defect can be used in future.Law of the country fine jade uses CAD and electron beam melting
(CAD/EBM) technology prepares porous titanium alloy bracket, prepares gelatin nanosphere using improvement secondary aggregation method, compound azoles carrys out phosphine
Acid, gelatin nanosphere, porous titanium alloy bracket construct ZOL-NPs porous titanium alloy bracket, and carry out biomethanics, carry medicine
Amount carries medicine release test.This method efficiently solves the problems, such as that common metal merging object elasticity modulus and human body are unmatched, carries medicine
Rate is high, has good sustained-release effect in vitro.
With the raising of social standard of living, caused by the acceleration of aging of population process and vehicles number surge
Traffic accident increases, and China is often only bone defect patient and is as high as 3,000,000, and the sales volume of orthopaedics implant is every year with 20%
Speed increase.Therefore it is more and more to the diagnosis and treatment demand of bone defect, require it is also higher and higher.3D printing porous titanium alloy and its table
Face is modified to obtain satisfied osteogenic activity with especially important clinical meaning, and it is suitable for Bone Ingrowths circle of artificial joint prosthesis
Wheat flour makes, the reconstruction of bone defect caused by the printing of spinal interbody fusion device and wound, infection, bone tumour etc., is expected to solve
Certainly some intractable critical issues in bone defect healing treatment.The technology is orthopedic treatment, dentistry implant, cranial surgery, jaw face
The bone defect healing of surgery or even the development of 3D printing medical apparatus industry provide new opportunity.
In conclusion problem of the existing technology is:
(1) metal 3D printing porous titanium alloy promotes the most suitable micropore glass beads of Integrated implant not yet clear.
(2) rush Bone Ingrowth effect of the conventional coatings on 3D printing titanium alloy porous surface structure is dissatisfied.
(3) 3D printing porous titanium alloy surface can refer to using biologically active polypeptide (RGD) modification without successful experience.
(4) how sustained release agent and 3D printing porous titanium alloy structure composite is made in Bone Morphogenetic Protein BMP II and is played slow
Releasing effect, it is still necessary to study.
(5) insufficient, conventional coatings that there are still 3D printing porous titanium alloy " prosthese-bone tissue " Interface Bone integration abilities at present
The problems such as being difficult uniform deposition on porous titanium alloy surface and 3D printing part mechanical property is limited to.
It solves the meaning of above-mentioned technical problem: in Orthopedic Clinical, can usually encounter many reasons such as infection, wound, bone
Bone defect caused by tumour or bone and joint diseases, it is always the problem clinically faced that treatment, which is repaired, is consumed huge
Big medical insurance resource.Although autologous bone transplanting is the goldstandard of bone defect healing, due to taking, bone amount is limited, increases donor site damage
Etc. factors, autologous bone transplanting cannot usually fully meet clinical demand.Especially big section of homogeneous allogenic bone transplantation deep jelly bone bone grafting
There are potential antigen immune response and infection risk, therefore clinically commonly uses the decalcification ossiculum item of finishing, mechanical support
Performance and repairing bone defect range are all very limited.With the development of material science, miscellaneous artificial bone and tissue engineered bone
Equal bone impairment renovation materials are developed, but the reparation for the area's bone defect that especially bears a heavy burden for large segmental bone defect, use degradable people
Work bone or tissue engineered bone can not be competent at body biomechanics requirement because its mechanical strength is far from enough.Bone made for metal
Alternative materials, as tantalum, titanium and medical titanium alloy have satisfactory mechanical strength, but its elasticity modulus be much higher than human body
Cortex bone and cancellous bone are easy to produce stress shielding after implanting, and there are later period implantation materials to loosen, the risk of displacement；And
Common medical titanium alloy is due to itself metal-inert, the tissue compatible for the not specially treated titanium alloy surface that implants
Property and Bone Ingrowth ability are unsatisfactory.More it is essential that being deposited because Personal reason and the region of anatomy are different
In apparent bone defects individuation difference, therefore, the accurate reparation of large segmental bone defect and personalized implants Bone Ingrowth circle
The research and development in face (micro cavity layer structures) are all a huge challenges to clinician and Medical Research Work person.
Summary of the invention
In view of the problems of the existing technology, the present invention provides a kind of super porous titanium alloys of 3D printing, and bone surface to be facilitated to change
Property method.
The invention is realized in this way a kind of super porous titanium alloy of 3D printing facilitates bone surface method of modifying, the D printing
The adhesion characteristics and bone morphogenetic protein that super porous titanium alloy facilitates bone surface method of modifying that RGD biologically active polypeptide is excellent
BMP II reliably facilitates bone active to combine, and compound RGD-BMP II sustained-release micro-spheres surpass porous titanium alloy to 3D printing and facilitate bone
Surface is modified.
Further, the super porous titanium alloy of the 3D printing facilitates bone surface method of modifying further include:
(1) determination of the most suitable aperture of EBM metal 3D printing porous titanium alloy, porosity and microcellular structure；
(2) compound to be grafted to 3D printing titanium alloy more for the sustained-release micro-spheres of RGD activity adhesion polypeptide and Bone Morphogenetic Protein BMPII
Pore structure；
(3) BMSc cell inoculation to four groups of 3D printing porous titanium alloy (compound RGD/BMPII) structures and is detected into cell
Proliferation.
Further, the super porous titanium alloy of the 3D printing facilitates bone surface method of modifying to utilize EBM metal 3D printing technique,
The minimum-value aperture of EBM porous titanium alloy is printed to 200um, porosity and microcellular structure are adjusted to the most suitable parameter of experiment；
In the experiment for determining most suitable aperture by pore size grouping, 200um group is increased.
Further, the super porous titanium alloy of the 3D printing facilitates bone surface method of modifying to specifically include:
Step 1 prepares RGD activity adhesion polypeptide；
Step 2, titanium alloy facilitate bone preparation and titanium alloy surface processing；
Step 3, titanium alloy surface are grafted RGD activity adhesion polypeptide；
Step 4 prepares BMP II sustained-release micro-spheres, and in RGD activity adhesion polypeptide surface recombination BMP II sustained-release micro-spheres.
Further, it is Ti6Al4V titanium alloy that the titanium alloy in the step 2, which facilitates the material of bone,；The titanium alloy is facilitated
Bone preparation is prepared using the 3D printing of EBM metal, and it is 68.1% that bone porosity is facilitated in control.
Further, the preparation of the BMP II sustained-release micro-spheres, specifically includes:
The first step, blank microballoon are prepared using W/O/W emulsion-solvent evaporation method, take suitable quantity of water to be added to 2ml and contain
In the methylene chloride of 200mgPLGA, ultrasound 30s under condition of ice bath；
Second step pours into solution made from the first step in the 3%PVA solution of 15ml, and 600rpm is stirred under condition of ice bath
After 10min, its revolving speed is down to 300rpm and 35ml water is added, continues to stir 4h at room temperature；
Third step is filtered, washed, dry 48h under the conditions of vacuum phosphorus pentoxide；
4th step realizes the super porous titanium alloy of 3D printing in RGD activity adhesion polypeptide surface recombination BMP II sustained-release micro-spheres
Facilitate bone surface modified.
In conclusion advantages of the present invention and good effect are as follows:
(1) present invention is for simplifying the super porous titanium alloy of 3D printing " facilitating bone " surface-active-treatment method, improving orthopaedics
Personalized bone defect healing efficiency, expanded metal 3D printing porous titanium alloy technology have in the application in Bone Ingrowth, Bone Defect Repari field
Important theory significance and clinical value.
(2) present invention leads raising bone defect individualized therapy efficiency, expanded metal 3D printing technique in medicine Integrated implant
Application in domain has important theory significance and practical application value
(3) present invention by improve 3D printing manufacture porous titanium alloy quality, improve its osteoacusis, self-bone grafting ability and
Biomechanical property realizes the ability of better orthopaedics individualized therapy bone defect.
(4) link closely practical application request.The present invention passes through " RGD- around EBM 3D printing Ti6Al4V porous surface structure
Optimize after BMPII " is peptide modified as 3D printing microcellular structure urgently to be resolved in Bone Ingrowth interface or bone defect healing body,
The practical problems such as biocompatibility improves, osteogenic activity is promoted have carried out the cell biology and experimental zoology research of system.
(5) multi-crossed disciplines are strong.Present invention combination CAD, 3D printing, digital orthopaedics, materialogy, life
The development trend in the fields such as object chemistry, cell biology, experimental zoology, biomethanics, it is desirable to by these subjects into one
Step is intersected, and the effective way for solving the problems, such as basis and clinical application is sought.
(6) complete system framework.High-level application of the 3D printing in orthopedic treatment is personalized orthopaedics implant, together
When integration printing porous titanium alloy surface layer more its advanced and practical value, in the compound osteogenic activity factor of porous surface,
To improve titanium alloy material inert nature, increase osteogenic ability, in conjunction with inherent advantage of the 3D printing in personalized molding, can obtain
Obtain more excellent orthopedics clinic practice.The present invention to be related to CAD, metal 3D printing, cell biology and
The entire flows such as Experiment of Zoology verifying have carried out systematic research.
Detailed description of the invention
Fig. 1 is that the super porous titanium alloy of 3D printing provided in an embodiment of the present invention facilitates bone surface method of modifying flow chart.
Fig. 2 is EBM 3D printing cylindricality porous titanium alloy column (diameter 10mm, height 5mm) provided in an embodiment of the present invention.
Fig. 3 is EBM 3D printing cylindricality porous titanium alloy stick (diameter 3mm, height 10mm) provided in an embodiment of the present invention.
Fig. 4 is EBM 3D printing porous titanium alloy (blank group) the implantation pre- reality of rabbit condyle of femur provided in an embodiment of the present invention
Test schematic diagram.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
In view of the problems of the existing technology, the present invention provides a kind of super porous titanium alloys of 3D printing, and bone surface to be facilitated to change
Property method, is with reference to the accompanying drawing explained in detail the present invention.
As shown in Figure 1, the super porous titanium alloy of 3D printing provided in an embodiment of the present invention facilitates the bone surface method of modifying to include
Following steps:
S101: there is of suitable aperture and porosity by correlated digital orthopaedics and the preparation of EBM metal 3D printing technique
Property porous titanium alloy (Ti6Al4V) experimental part.
S102: the minimum-value aperture of EBM porous titanium alloy is printed to 200um, porosity and microcellular structure are adjusted to reality
The most suitable parameter tested.
S103: biologically active polypeptide RGD joint bone morphogenetic protein BMPII is given on EBM porous titanium alloy surface and is carried out
Surface modification.
S104: research cell behaviors are verified by Experiment of Zoology and biomechanics experiment.
The super porous titanium alloy of 3D printing provided in an embodiment of the present invention facilitates bone surface method of modifying further include:
(1) research in the most suitable aperture of EBM metal 3D printing porous titanium alloy；
(2) compound " RGD-BMPII " polypeptide of EBM 3D printing porous titanium alloy promotes the Osteoblast Differentiation ability of BMSc cell；
(3) skeletonization of EBM 3D printing porous titanium alloy compound " RGD-BMPII " peptide modified implantation in rabbit condyle of femur is studied
Ability；
(4) design biomechanics experiment detects the Integrated implant degree of four groups of prostheses.
The super porous titanium alloy of 3D printing provided in an embodiment of the present invention facilitates bone surface method of modifying further include:
(1) determination of the most suitable aperture of EBM metal 3D printing porous titanium alloy, porosity and microcellular structure；
(2) compound to be grafted to 3D printing titanium alloy more for the sustained-release micro-spheres of RGD activity adhesion polypeptide and Bone Morphogenetic Protein BMPII
Pore structure；
(3) BMSc cell inoculation to four groups of 3D printing porous titanium alloy (compound RGD/BMPII) structures and is detected into cell
Proliferation.
Further, the super porous titanium alloy of the 3D printing facilitates bone surface method of modifying to specifically include:
S101: preparation RGD activity adhesion polypeptide；
S102: titanium alloy facilitates bone preparation and titanium alloy surface processing；
S103: titanium alloy surface is grafted RGD activity adhesion polypeptide；
S104: preparation BMP II sustained-release micro-spheres, and in RGD activity adhesion polypeptide surface recombination BMP II sustained-release micro-spheres.
Further, it is Ti6Al4V titanium alloy that the titanium alloy in the step 2, which facilitates the material of bone,；The titanium alloy is facilitated
Bone preparation is prepared using the 3D printing of EBM metal, and it is 68.1% that bone porosity is facilitated in control.
Further, the preparation of the BMP II sustained-release micro-spheres, specifically includes:
S101: blank microballoon is prepared using W/O/W emulsion-solvent evaporation method, is taken suitable quantity of water to be added to 2ml and is contained
In the methylene chloride of 200mgPLGA, ultrasound 30s under condition of ice bath；
S102: solution made from the first step is poured into the 3%PVA solution of 15ml, and 600rpm is stirred under condition of ice bath
After 10min, its revolving speed is down to 300rpm and 35ml water is added, continues to stir 4h at room temperature；
S103: being filtered, washed, dry 48h under the conditions of vacuum phosphorus pentoxide；
S104: in RGD activity adhesion polypeptide surface recombination BMP II sustained-release micro-spheres, realize that the super porous titanium alloy of 3D printing promotees
It is modified at bone surface.
The super porous titanium alloy of 3D printing provided in an embodiment of the present invention facilitates bone surface method of modifying further include: specific packet
It includes:
(1) research in the most suitable aperture of EBM metal 3D printing porous titanium alloy
Actually or the present invention is carried out for the 200um of academia's arguement, the most suitable Bone Ingrowth in aperture of 600um 1000um
It is grouped zoopery comparative study, to find that the porous titanium alloy in which kind of aperture is more suitable for Bone Ingrowth.Contrast test both
The biomechanical property of porous titanium alloy printout, studies whether it can reach the biomechanics for meeting implantation human body requirement
Energy.
(2) compound " RGD-BMPII " polypeptide of EBM 3D printing porous titanium alloy promotes the Osteoblast Differentiation ability of BMSc cell
By 3D printing EBM porous titanium alloy cylindrical rod respectively with it is compound in RGD, RGD-BMPII, BMPII in vitro six well culture plates, not
Any ingredient 3D printing porous rod is added as blank control group；Four groups of testpieces are subjected to mixing training with BMSc cell respectively
It supports, observes and detect adherency situation of the BMSc on 3D printing porous rod by inverted phase contrast microscope, scanning electron microscope；
Stick experiment with centrifugation, concussion sticks experimental evaluation RGD peptide to the Adhesion property of MSCs；Changed with the surface CCK-8 experimental evaluation RGD
The proliferation activity of MSCs on property porous titanium alloy；On Western blot method detection RGD surface modified porous titanium alloy material
The expression of the Runx2 and OCN albumen of MSCs.
(3) skeletonization of EBM 3D printing porous titanium alloy compound " RGD-BMPII " peptide modified implantation in rabbit condyle of femur is studied
Ability
By the EBM porous titanium alloy cylindrical rod of 3D printing finished product respectively with RGD, RGD-BMP II, BMP II and do not add
Add the blank group of any ingredient, is implanted into rabbit bilateral condylus lateralis femoris respectively, postoperative 4 weeks, 8 time points Tuesday are to all rabbits
Hind leg double knee joint shoots positive side position X piece and Micro-CT scanning, observes and repairs at femoral lateral condyle bone defect through 3D printing stick
Poroma formational situation afterwards, and tissue mineral density.12 weeks after operation puts to death all rabbits, and production hard tissue slicing carries out Goldner'
The Bone Ingrowth ability of the 3D printing stick of s dyeing and fluorescence microscope different grouping.QPCR detects Runx2's and Osterix
Expression.To obtain the osteogenic ability of the compound different activities polypeptide of EBM 3D printing porous titanium alloy.
(4) design biomechanics experiment detects the Integrated implant degree of four groups of prostheses
To the 3D printing stick position opening of the femoral lateral condyles of the four groups of experimental rabbits put to death implantation, with taking fixed value
Limit trepan sclerotin around 3D printing stick tail portion is ground off into about 3mm depth, screw on broken nail extractor, then to connect omnipotent mechanics real
The drawstring for testing machine carries out prosthese resistance to plucking and goes out to test, by the comparison of the 3D printing stick maximum resisting pull out forces value to each group, indirectly
Prove that the experiment stick Integrated implant ability of which group is best.
Technical scheme of the present invention will be further described with reference to the accompanying drawing.
The super porous titanium alloy of 3D printing provided in an embodiment of the present invention facilitates bone surface method of modifying further include:
(1) determination of the most suitable aperture of EBM metal 3D printing porous titanium alloy, porosity and microcellular structure
Technological cooperation is carried out with Beijing Eyekon Inc., CAD (CAD) imports ARCAM (Sweden) high energy electricity
Beamlet melts (EBM) metal 3D printer, prints two kinds of form titanium alloy members.The first is cylindrical porous titanium alloy bar,
Diameter 10mm, high 5mm, micro-pore diameter is respectively 200um, 400um, 600um, 800um, 1000um；Porosity is 68.1%,
Every kind of quantity is 10 cylinder parts, is used for experimental verification optimal porosity range.Second is also cylindrical porous titanium
Alloy bar, diameter 4mm, high 10mm, micropore diameter are the mixing aperture structure less than 600um, porosity 68.1%, quantity 30.
It is (as shown in Figure 2) to be used to carry out when identical size and identical micro pores structure (including aperture, porosity, micropore configuration)
Blank group, compound RGD group, compound BMP II group, compound " RGD-BMP II " totally four groups of osteogenic ability comparative experiments.Using sweeping
Electronic Speculum, X-ray photoelectron spectroscopic analysis and fourier transform infrared spectroscopy are retouched to its surface microstructure, form and chemical group
At being characterized, aperture, porosity and microcellular structure are measured.Porous titanium alloy printout is tested using omnipotent mechanics machine
Resistance to compression, anti-shear performance, find out the implants micropore glass beads of relative ideal, be 3D printing in future artificial joint prosthesis surface it is micro-
The design of hole coating and personalized bone defect healing body provides reference.(as shown in Figure 3)
(2) compound to be grafted to 3D printing titanium alloy more for the sustained-release micro-spheres of RGD activity adhesion polypeptide and Bone Morphogenetic Protein BMPII
Pore structure, taking orthogonal test to draft RGD concentration is 0.5mg/ml, using numerator self-assembly technique by Electrochemical Modification and
The bioactivity coatings of titanium plate surface grafting rgd peptide after DOPA is amine-modified.It is observed by environmental scanning electron microscope more
The variation of hole titanium alloy surface pattern, x-ray photoelectron spectroscopy (X-rayphotoelectron spectroscopy, XPS) are right
The surface topography of each group and the changes of contents detection rgd peptide of surface-element are grafted situation.
(3) BMSc cell inoculation to four groups of 3D printing porous titanium alloy (compound RGD/BMPII) structures and is detected into cell
Proliferation observes BMSc cell culture and under inverted phase contrast microscope its growing multiplication state, by BMSc cell and four groups
Small cylinder prepared by (every group of 10 printouts) 3D printing porous titanium alloy (compound RGD/BMPII) carries out in 48 orifice plates
It co-cultures, is observed by inverted phase contrast microscope, scanning electron microscope and detection BMSc is on porous titanium alloy timbering material
Adherency situation；The hydrophily of RGD peptide modification of surfaces is measured with optical contact angle meter；Stick experiment with centrifugation, reality is sticked in concussion
It tests and comments
Adhesion property of the valence RGD peptide to MSCs；With MSCs on CCK-8 experimental evaluation RGD surface modified porous titanium alloy
Proliferation activity；With Runx2 the and OCN albumen of MSCs on Western blot method detection RGD surface modified porous titanium alloy material
Expression.
(4) Experiment of Zoology after the compound RGD/BMPII of EBM 3D printing porous titanium alloy is peptide modified
Take the EBM porous titanium alloy cylindrical rod 28 of 3D printing finished product, diameter 4mm, high 10mm, micropore diameter are less than
The mixing aperture structure of 600um, porosity 68.1%.It is divided into blank group (the pure not compound any active constituent of 3D printing part), answers
Close RGD group, compound BMP II group, totally four groups, every group 7 of compound " RGD-BMP II ".16 new zealand white rabbits are taken, random point
It is 4 groups, is drilled in rabbit bilateral condylus lateralis femoris with electro-medical and make bone defect, diameter 3.6mm, depth 10mm, by 4 groups of printouts
It is implanted at each group rabbit bilateral condylus lateralis femoris bone defect, is struck tightly respectively, guarantee and surrounding sclerotin near press-fit play implantation
Printed document type carries out mark, pays attention to the both legs that same group of printout is not implanted into same rabbit.Postoperative every rabbit is daily
800,000 unit of intramuscular injection penicillin, totally three days, the ordinary circumstance of observation experiment rabbit；Postoperative 4 weeks, 8 periods Tuesday are to all
Rabbit carries out double hind leg knee joints and shoots positive side position X piece, observes bone defect area poroma formational situation.Micro-CT is scanned and is measured
Diaphysis fraction and tissue mineral density.12 weeks after operation puts to death all rabbits, intercepts bilateral hind leg knee joint, porous to 3D printing
The position that titanium alloy repairs condyle of femur bone defect carries out gross examination of skeletal muscle, shoots double hind leg knee joint positive side positions X piece, and Micro-CT is swept
Retouch and measure diaphysis fraction and tissue mineral density；It makes hard tissue slicing and carries out Goldner's dyeing and fluorescence microscope
Observation.And carry out porous titanium alloy stick and extract its peak pullout load of experiment measurement, qPCR detects the expression of Runx2 and Osterix.
To obtain the osteogenic ability of the compound different activities polypeptide of EBM 3D printing porous titanium alloy.(as shown in Figure 4)
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within mind and principle.
Claims (6)
1. a kind of super porous titanium alloy of 3D printing facilitates bone surface method of modifying, which is characterized in that the super POROUS TITANIUM of 3D printing
Alloy facilitates bone surface method of modifying can by the excellent adhesion characteristics of RGD biologically active polypeptide and bone morphogenic protein BMP-2 II
That leans on facilitates bone active to combine, and in RGD activity adhesion polypeptide surface recombination BMP II sustained-release micro-spheres, realizes that 3D printing is super porous
Titanium alloy facilitates bone surface modified.
2. the super porous titanium alloy of 3D printing as described in claim 1 facilitates bone surface method of modifying, which is characterized in that the 3D
It prints super porous titanium alloy and facilitates bone surface method of modifying further include:
(1) determination of the most suitable aperture of EBM metal 3D printing porous titanium alloy, porosity and microcellular structure；
(2) sustained-release micro-spheres of RGD activity adhesion polypeptide and Bone Morphogenetic Protein BMPII are compound is grafted to the porous knot of 3D printing titanium alloy
Structure；
(3) BMSc cell inoculation to four groups of 3D printing porous titanium alloy (compound RGD/BMPII) structures and is detected into cell Proliferation.
3. the super porous titanium alloy of 3D printing as described in claim 1 facilitates bone surface method of modifying, which is characterized in that described
The super porous titanium alloy of 3D printing facilitates bone surface method of modifying using EBM metal 3D printing technique, most by EBM porous titanium alloy
Small-bore is printed to 200um, and porosity and microcellular structure are adjusted to the most suitable parameter of experiment；It is determined by pore size grouping
In the experiment in most suitable aperture, 200um group is increased.
4. the super porous titanium alloy of 3D printing as described in claim 1 facilitates bone surface method of modifying, which is characterized in that described
The super porous titanium alloy of 3D printing facilitates bone surface method of modifying to specifically include:
Step 1 prepares RGD activity adhesion polypeptide；
Step 2, titanium alloy facilitate bone preparation and titanium alloy surface processing；
Step 3, titanium alloy surface are grafted RGD activity adhesion polypeptide；
Step 4 prepares BMP II sustained-release micro-spheres, and in RGD activity adhesion polypeptide surface recombination BMP II sustained-release micro-spheres.
5. the super porous titanium alloy of 3D printing as described in claim 4 facilitates bone surface method of modifying, which is characterized in that described
It is Ti6Al4V titanium alloy that titanium alloy in step 2, which facilitates the material of bone,；The titanium alloy facilitates bone preparation using EBM metal 3D
Prepared by printing, and it is 68.1% that bone porosity is facilitated in control.
6. the super porous titanium alloy of 3D printing as described in claim 1 facilitates bone surface method of modifying, which is characterized in that described
The preparation of BMP II sustained-release micro-spheres, specifically includes:
The first step, blank microballoon are prepared using W/O/W emulsion-solvent evaporation method, take suitable quantity of water to be added to 2ml and contain 200mgPLGA
Methylene chloride in, ultrasound 30s under condition of ice bath；
Second step pours into solution made from the first step in the 3%PVA solution of 15ml, and 600rpm stirs 10min under condition of ice bath
Afterwards, its revolving speed is down to 300rpm and 35ml water is added, continue to stir 4h at room temperature；
Third step is filtered, washed, dry 48h under the conditions of vacuum phosphorus pentoxide；
4th step realizes that the super porous titanium alloy of 3D printing is facilitated in RGD activity adhesion polypeptide surface recombination BMP II sustained-release micro-spheres
Bone surface is modified.
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