CN205391219U - Load rhBMP -2 slow release system's neck interbody fusion cage - Google Patents
Load rhBMP -2 slow release system's neck interbody fusion cage Download PDFInfo
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- CN205391219U CN205391219U CN201620177280.8U CN201620177280U CN205391219U CN 205391219 U CN205391219 U CN 205391219U CN 201620177280 U CN201620177280 U CN 201620177280U CN 205391219 U CN205391219 U CN 205391219U
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Abstract
The utility model discloses a do you load rhBMP 2 slow release system's neck interbody fusion cage. The utility model discloses a three -dimensional that includes neck interbody fusion cage link up porous structure, and this three -dimensional link up porous structure and includes the porous metal support, located inside three -dimensional little support that constitutes by natural polymer material and bioceramic of porous metal support and the rhBMP who is located three -dimensional little support inside 2 slow release system. The utility model discloses a can neck interbody fusion cage directional slow release rhBMP 2 to it is induced to realize that bone tissue steady in a long -term is grown into, solve the bone material interface's combination problem improves the osseointegration ability.
Description
Technical field
The utility model belongs to fixed network in spinal fusion, relates to a kind of neck Invasive lumbar fusion device, is specifically related to one
Plant the neck Invasive lumbar fusion device being loaded with rhBMP-2 slow-released system.
Background technology
Disc herniation and cervical spinal instability that intervertebral disc degradation causes are the most common spinal surgery diseases,
Anterior cervical decompression intervertebral fusion internal fixation is the modus operandi being most frequently with at present.But this type of is performed the operation simultaneously
Also 3 hang-ups it are faced with: 1, the ACDF technology using anterior plate fixation fixing often can cause postoperative patient
Swallow discomfort, even have compressing oesophagus, cause the possibility that oesophagus leaks；2, bone grafting does not merges, and titanium cage sinks,
Pseudarthrosis is formed, and is likely to result in fragmentation of internal fixation objects, displacement etc.；3, spur is formed during intervertebral fusion backward,
May again oppress the spinal nerve at rear, need operative treatment again.
Invasive lumbar fusion device and inner fixing device are accommodated by anterior cervical vertebrae zero incisura intervertebral fusion internal fixation system completely
In intervertenral space, reducing the interference to cervical vertebra soft tissue, current many clinical researches show that it can substantially drop
Low postoperative patient swallow discomfort, and don't increase the incidence of other complication, thus enjoy spinal surgery to cure
Raw favor.
But due to the restriction of traditional handicraft, the zero incisura internal fixation system used clinically is titanium and hardens conjunction
The Invasive lumbar fusion device of PEEK material, the elastic modelling quantity of the two is different.And owing to PEEK material belongs to biological
Inert material, bone tissue cannot be grown into inside it to reach good fusion, be caused the combination of bone-material interface
Intensity is not enough, and for reaching enough support strength, PEEK material needs certain thickness more, thus
Further reduce the space that bone grafting merges, be easily caused Fusion failure and loosen.
Titanium alloy has good biocompatibility, is built by bone tissue CT scan, Computer Design, can
Titanium alloy to be printed as bionical personalized porous connection labyrinth, not only provide space to Bone Ingrowth,
The problem solving bone-material interface, also because loose structure reduces the elastic modelling quantity of titanium alloy, it is achieved that
With mating of normal bone tissues elastic modelling quantity, and there is no concern that not mating of degradation time and body demand.Simultaneously
The contact surface of holey reduces the pressure of local, can reduce the problem that tradition titanium cage sinks.
But, 3D prints porous titanium alloy support itself not self-bone grafting or osteoconductive, and market at present
Upper various 3D print porous titanium alloy material, and aperture is the biggest, and diameter about 300-1500 μm, for cell
For the diameter of average 10-20 μm, it is clear that excessively spacious, cell can only be sought connections with on its hole wall two-dimensional space
Growth, it is impossible to realize the growth of three-dimensional level in whole hole.Research previously also focuses on POROUS TITANIUM hole
Inner surface two-dimension layer activation transformation, such as give surface soda acid process, surface plasma spray-on coating,
Area load growth factor etc., in a word, two dimension transformation be difficulty with cell the seeking connections with of three-dimensional level, grow with
And the secretion of matrix and filling.And build in the hole of porous support and there is the micro rack of slow-released system can promote
Enter cell three dimensional growth in cavity.This intervertebral fusion and internal fixation system reduce tradition intervertebral fusion simultaneously
The risk that discomfort is swallowed in the front brought, the bone grafting of intervertebral does not merges and titanium cage sinks, rear spur is formed.
Summary of the invention
The purpose of this utility model is to provide one to have enough support strengths to maintain disc height and vertebra
Body stability, can stimulate new bone raw by the induced osteogenesis effect of its Internal biological active factors slow-released system again
Long, thus reach good Integrated implant, promote Bony union between centrum is loaded with rhBMP-2 slow-released system
Neck Invasive lumbar fusion device.
To achieve these goals, the technical solution adopted in the utility model is:
The utility model provides a kind of neck Invasive lumbar fusion device being loaded with rhBMP-2 slow-released system, described cervical vertebra
Between fusion device by three-dimensional through loose structure and not there is the entity portion of loose structure form, described entity portion with
The through loose structure of described three-dimensional is integrated, and described entity portion encloses three-dimensional through loose structure away from canalis spinalis
Simultaneously；The through loose structure of described three-dimensional is by porous metals support, is positioned at porous metals internal stent by natural
Three-dimensional micro rack that macromolecular material and bioceramic are constituted and being positioned within described three-dimensional micro rack
RhBMP-2 slow-released system forms；Three-dimensional through loose structure is the envelope without pore structure towards the one side of canalis spinalis
Close face；The middle part of three-dimensional through loose structure arranges the centre bore of a up/down perforation；Entity portion is provided with
The screw of multiple both sides up and down being adapted to extend to three-dimensional through loose structure.
In specific embodiments of the present utility model, entity portion arranges 4 for fixing described porous metals neck
The screw of Invasive lumbar fusion device, 4 described screws are located along the same line, through the screw court of middle two screws
Oliquely downward, it is 40 degree of angles with plane, through the screw of both sides screw towards oblique upper, is 40 degree with plane
Angle.
Further, described entity portion of the present utility model presents titanium plate spline structure.
Further, the diameter of the centre bore of described up/down perforation is 5mm.
Further, the porous metals support containing three-dimensional micro rack of the present utility model, the aperture of metallic support is
300-3000μm；Porosity is 60%-90%.
Further, the loose structure generally wedge shape that the three-dimensional of neck Invasive lumbar fusion device of the present utility model is through, rule
Lattice are: long (L): 13-16mm, wide (W): 12-14mm, and high (H): 5-8mm, wedge angle is 17
Degree.Its cross section is similar to the cross section of neck bone, and wedge-shaped design is easy in art be implanted in intervertenral space.Upper table
Face is the inclined-plane of 3-4 degree, is beneficial to maintain the physiological bending of cervical vertebra.
The utility model additionally provides the preparation method of foregoing neck Invasive lumbar fusion device, and concrete operation step is such as
Under:
(1) utilize conventional tissue engineered porous scaffold preparation technology preparation by foregoing entity portion with front
Porous metals described in face prop up the base body of the neck Invasive lumbar fusion device being configured to；
(2) rhBMP-2 slow-released system is prepared；
(3) rhBMP-2 slow-released system prepared by natural macromolecular material, bioceramic, step (2)
It is prepared as mixed liquor；
(4) mixed liquor prepared by step (3) is filled in base body prepared by step (1), chilled
It is dried and is prepared as the neck Invasive lumbar fusion device being loaded with rhBMP-2 slow-released system of the present utility model.
Further, porous metals support of the present utility model can be porous titanium alloy support, porous pure titanium support,
Porous stainless steel bracket, porous cobalt alloy support.In specific embodiments of the present utility model, described porous
Metallic support is porous titanium alloy support.
Further, the utility model use natural macromolecular material can be collagen, gelatin, fibroin albumen,
Zein, alginates, shitosan, Sodium Hyaluronate, sodium alginate, dextran sulfate, liquaemin, sulphur
One or more in aching and limp ossein or keratan sulfate.In specific embodiments of the present utility model, described
Natural macromolecular material is gelatin.
Further, the utility model use bioceramic can be nanometer hydroxyapatite, tricalcium phosphate or
One or more in calcium phosphate.In specific embodiment of the present utility model, described bioceramic is to receive
Rice hydroxyapatite.Preferably, a diameter of 20nm of described nanometer hydroxyapatite.
Further, described rhBMP-2 slow-released system is made up of with common slow-released carrier rhBMP-2.Institute
State slow-released carrier to include but not limited to: (1) tradition slow-released carrier: collagen, decalcified bone matrix, Fibrin Glue,
Bioactivity glass, tricalcium phosphate, biphasic calcium phosphate, calcium sulfate, calcium phosphate, hydroxyapatite, coral
Coral, gypsum, hyaluronic acid；(2) microsphere sustained-release carrier: PLA (polylactic acid, PLA), PVOH
Acid (polyglycolic acid, PGA), gelatin, polysaccharide-based hydrogel, shitosan, marine alga salt；(4) nanometer is delayed
Release carrier；(5) other: sodium hyaluronate, cellulose, chondroitin sulfate, silk and agarose, polyvinyl pyrrole
Alkane (polyvinyl pyrrolidone, PVP)；(6) composite slow release carrier.In specific embodiment party of the present utility model
In case, described slow-released carrier is shitosan.
The technology that can be used for preparing porous titanium alloy support in prior art includes Selective Laser Sintering
(SLS), selective laser fusion technology (SLM), electron beam melting technology (EBM), above-mentioned technology system
Standby porous titanium alloy support aperture is 100 μm-2000 μm, and elastic modelling quantity is less than 10GPa.The utility model
Neck Invasive lumbar fusion device use electron beam melting technology (EBM) and be prepared from.
In specific embodiments of the present utility model, the concrete operations of above-mentioned steps (1) are as follows:
A, CT image is imported the three-dimensional imaging software such as Mimics or CAD, obtain the three of targeted bony tissue
Dimension image, average Kong Zhuwei 100-1000 μm (intermediate value 300 μm), aperture are 300-3000 μm (intermediate value
1000 μm), with regular hexahedron, the filling of regular dodecahedron structural units, extend this image, obtain personalization
Porous connection three-dimensional digital model, the middle cavity diameter 5mm of support, rear wall closing atresia, front portion is titanium
Plate spline structure, inside has the screw duct towards two ends.
B, employing EOS M280 metal material 3D printer, with titanium alloy (Ti-6Al-4V) as raw material,
According to the base body printing the neck Invasive lumbar fusion device with entity portion and porous titanium alloy support that designs a model.
In specific embodiments of the present utility model, the concrete operation step of above-mentioned steps (2) is as follows: adopt
RhBMP-2/ chitosan microball is prepared with emulsion-crosslinking method.First 300mg shitosan is dissolved in 10ml first
In acid solution, add about 2.7mg rhBMP-2, be sufficiently stirred for.It is added dropwise over again containing surfactant
In the atoleine of span80,45 DEG C be sufficiently stirred for after add crosslinking agent vanillic aldehyde, continue stirring 6-7h, will
RhBMP-2/ chitosan microball is i.e. obtained after sediment washing, freeze-drying.
In specific embodiments of the present utility model, the concrete operation step of above-mentioned steps (3) is as follows: will
Gelatin particle joins in deionized water, and at 37 DEG C, in the magnetic stirring apparatus of 300r/min, 2h is to the most molten
Solve, the final concentration of 1.5-20% of gelatin；Then, by nanometer hydroxyapatite powder nHA (diameter 20nm)
Joining in gelatin solution, in the mixture of formation, nanometer hydroxyapatite is 1-4:4 with the mass ratio of gelatin,
Mixture is broken up to homogeneous state by nanometer ultrasonic cell disruptor, and adds prepared by step (2)
RhBMP-2/ chitosan microball uniformly mixes.
Preferably, the final concentration of 3-5% of described gelatin；It is furthermore preferred that described gelatin final concentration of 4%.
Preferably, in the mixture of formation, the mass ratio of nanometer hydroxyapatite and gelatin is 1:2.
In specific embodiments of the present utility model, the concrete operation step of above-mentioned steps (4) is as follows:
A, mixed liquor step (3) prepared inject, with syringe pressurization, the foregoing basis prepared
In body, and it is immersed in mixed liquor, is placed 4 DEG C of refrigerator freezings.
B, take out the gel piece after above-mentioned freezing, give scraper surface unnecessary gel, add 0.1mol/L sweet
Propylhomoserin solution, soaks, same to method, then soaks by deionized water, clean.
C, above-mentioned processed material is put into container, add deionized water and do not had the upper surface of processed material, then put
Enter-80 DEG C of refrigerator freezings.
D, take out frozen thing, put in vacuum freeze drier ,-46 DEG C of freeze-dryings, i.e. obtain having being loaded with
The neck Invasive lumbar fusion device of rhBMP-2 slow-released system.
Preferably, in step (a), 4 DEG C of refrigerator freezing times are 12h.
Preferably, in step (b), glycine soaking conditions is: 37 DEG C, the magnetic stirring apparatus of 300r/min
Middle immersion 2h.
Preferably ,-80 DEG C of refrigerator freezing 4h in step (c).
Preferably ,-46 DEG C of refrigerator freezing 48h in step (d).
The utility model additionally provides the foregoing neck Invasive lumbar fusion device being loaded with rhBMP-2 slow-released system and exists
Prepare the application in fixed system between cervical vertebra.
Advantage of the present utility model and beneficial effect:
(1) neck Invasive lumbar fusion device of the present utility model tool multistage network structure: first order network structure is metal
The porous metals support that 3D printing technique is prepared from, is interconnected between hole, Kong Zhuwei 100-1000 μm
(intermediate value 300 μm), aperture are 300-3000 μm (intermediate value 1000 μm), are beneficial to keep the same of mechanical strength
Time reduce elastic modelling quantity；The three-dimensional that second level network structure is natural macromolecular material and bioceramic is prepared from
Through loose structure, aperture 50-100 μm, beneficially cell migration and mass transfer.
(2) neck Invasive lumbar fusion device of the present utility model is loaded with rhBMP-2 slow-released system, this slow-released system
Can slowly discharge rhBMP-2, thus reach self-bone grafting effect steady in a long-term.
(3) neck Invasive lumbar fusion device of the present utility model contains the centre bore of a up/down perforation, this centre bore
Effect is to be to sting the autologous bone implantation thereins such as the hyperplasia spur removed by anterior decompression, coordinates BMP simultaneously, permissible
It is obviously promoted Bone Ingrowth, strengthens syncretizing effect, hemorrhage, the pain that it also avoid that ilium takes that bone brings, infection etc.
The extra charge that risk and use allograph bone are brought.
(4) the through loose structure of three-dimensional in neck Invasive lumbar fusion device of the present utility model is envelope towards the side of canalis spinalis
Closing, do not contain pore structure, the release that so may result in rhBMP-2 is not related to canalis spinalis periphery, prevents from keeping away
Exempt from spur rearward hyperplasia and invade canalis spinalis, cause the compressing of neural spinal cord.
Accompanying drawing explanation
Fig. 1 shows the integrally-built side of the neck Invasive lumbar fusion device being loaded with rhBMP-2 slow-released system with screw
View；
Fig. 2 shows that the integrally-built of neck Invasive lumbar fusion device being loaded with rhBMP-2 slow-released system with screw bows
View；
Fig. 3 shows and is loaded with the part plan of porous metals support in the neck Invasive lumbar fusion device of rhBMP-2 slow-released system
Figure；
Fig. 4 shows and is loaded with in the neck Invasive lumbar fusion device of rhBMP-2 slow-released system containing gelatin/nanometer hydroxyapatite
The partial plan layout of the porous metals support of three-dimensional micro rack；
Fig. 5 shows that rhBMP-2/ chitosan sustained-release system is loaded into containing gelatin/nanometer hydroxyapatite three-dimensional micro rack
Porous metals support in close-up schematic view；
Fig. 6 shows rhBMP-2 In-vitro release curves.
Detailed description of the invention
Below in conjunction with specific embodiment, the utility model is expanded on further, is only used for explaining the utility model, and
It is not intended that to restriction of the present utility model.
The experimental technique of unreceipted actual conditions in the following example, generally according to normal condition or according to institute of manufacturer
The condition examinations of suggestion.
The reagent in unreceipted source in the following example, all can obtain from commercial routes.
Embodiment 1 is loaded with the neck Invasive lumbar fusion device of rhBMP-2 slow-released system
A kind of neck Invasive lumbar fusion device being loaded with rhBMP-2 slow-released system, porous titanium alloy neck Invasive lumbar fusion device is
By three-dimensional through loose structure with do not have the entity portion of loose structure and form, entity portion ties with the through porous of three-dimensional
Structure is integrated, and entity portion encloses the three-dimensional through loose structure one side away from canalis spinalis；Three-dimensional through loose structure
It is by porous titanium alloy support, is positioned at what porous titanium alloy internal stent was made up of gelatin and nanometer hydroxyapatite
Three-dimensional micro rack and be positioned at three-dimensional rhBMP-2 slow-released system micro rack within and form；Three-dimensional through porous
Structure is not have the sealing surface of pore structure towards the one side of canalis spinalis；The middle part of three-dimensional through loose structure sets
Put the centre bore of a up/down perforation；Entity portion arranges 4 for fixing porous titanium alloy neck Invasive lumbar fusion device
Screw, 4 screws are located along the same line, and pass the screw of middle two screws obliquely downward, with plane
In 40 degree of angles, through the screw of both sides screw towards oblique upper, it is 40 degree of angles with plane.
The through loose structure of three-dimensional containing three-dimensional micro rack of the present utility model, the aperture of metallic support is
300-3000μm；Porosity is 60%-90%.
The diameter of the centre bore of up/down perforation is 5mm.
The loose structure generally wedge shape that the three-dimensional of neck Invasive lumbar fusion device of the present utility model is through, specification is: long
(L): 13-16mm, wide (W): 12-14mm, high (H): 5-8mm, wedge angle is 17 degree.It is horizontal
Cross section is similar to the cross section of neck bone, and wedge-shaped design is easy in art be implanted in intervertenral space.Upper surface is 3-4
The inclined-plane of degree, is beneficial to maintain the physiological bending of cervical vertebra.
Embodiment 2 is loaded with the preparation of the neck Invasive lumbar fusion device of rhBMP-2 slow-released system
1, the base body of neck Invasive lumbar fusion device is prepared
CT image is imported the three-dimensional imaging software such as Mimics or CAD by 1.1, obtains the three of targeted bony tissue
Dimension image, average Kong Zhuwei 100 μm, aperture are 300 μm, and with hexahedron structure unit filling, extension should
Image, obtains the porous connection three-dimensional digital model of personalization, the middle cavity diameter 5mm of support, rear wall
Closing atresia, front portion is titanium plate spline structure, inside has the screw duct towards two ends.
1.2 use EOS M280 metal material 3D printer, with titanium alloy (Ti-6Al-4V) as raw material,
According to the base body printing the neck Invasive lumbar fusion device with entity portion and porous titanium alloy support that designs a model.
2, use emulsion-crosslinking method prepare chitosan microball and load rhBMP-2, form rhBMP-2/ shitosan
Microballoon.First 300mg shitosan is dissolved in 10ml formic acid solution, adds about 2.7mg rhBMP-2, fill
Divide stirring.Being added dropwise in the atoleine containing surfactant span80,45 DEG C are sufficiently stirred for again
Rear addition crosslinking agent vanillic aldehyde, continues stirring 6-7h, i.e. obtains after sediment washing, freeze-drying
RhBMP-2/ chitosan microball.
3, gelatin particle is joined in deionized water, at 37 DEG C, 2h in the magnetic stirring apparatus of 300r/min
To thoroughly dissolving, gelatin final concentration of 1.5%.
4, nanometer hydroxyapatite powder nHA (diameter 20nm) is joined in gelatin solution, Qi Zhongna
Rice hydroxyapatite is 1:4 with the mass ratio of gelatin, and mixture is broken up by nanometer ultrasonic cell disruptor
To homogeneous state, and add rhBMP-2/ chitosan microball and uniformly mix.
5, above-mentioned mixed liquor is injected in the base body prepared with syringe pressurization, and be immersed in mixed
Close in liquid, place 4 DEG C of refrigerator 12h.
6, take out the gel piece after above-mentioned freezing, give scraper surface unnecessary gel, add 0.1mol/L sweet
Propylhomoserin solution, at 37 DEG C, soaks 2h, same to method, then uses deionized water in the magnetic stirring apparatus of 300r/min
Soak, clean 3 times.
7, above-mentioned processed material is put into container, add deionized water to not having the upper surface of processed material, put into
-80 DEG C of refrigerator freezing 4h.
8, taking out frozen thing, put in vacuum freeze drier ,-46 DEG C of freeze-drying 48h, i.e. obtaining can
It is loaded with the neck Invasive lumbar fusion device of rhBMP-2 slow-released system.
9, being put into by above-mentioned neck Invasive lumbar fusion device and carry out sterilizing in Epoxyethane sterilizing box, independent packing processes.
Embodiment 3 is loaded with the preparation of the neck Invasive lumbar fusion device of rhBMP-2 slow-released system
1, the base body of neck Invasive lumbar fusion device is prepared
CT image is imported the three-dimensional imaging software such as Mimics or CAD by 1.1, obtains the three of targeted bony tissue
Dimension image, average Kong Zhuwei 100 μm, aperture are 300 μm, and with hexahedron structure unit filling, extension should
Image, obtains the porous connection three-dimensional digital model of personalization, the middle cavity diameter 5mm of support, rear wall
Closing atresia, front portion is titanium plate spline structure, inside has the screw duct towards two ends.
1.2 use EOS M280 metal material 3D printer, with titanium alloy (Ti-6Al-4V) as raw material,
According to the base body printing the neck Invasive lumbar fusion device with entity portion and porous titanium alloy support that designs a model.
2, use emulsion-crosslinking method prepare chitosan microball and load rhBMP-2, form rhBMP-2/ shitosan
Microballoon.First 300mg shitosan is dissolved in 10ml formic acid solution, adds about 2.7mg rhBMP-2,
It is sufficiently stirred for.Being added dropwise in the atoleine containing surfactant span80,45 DEG C are fully stirred again
Add crosslinking agent vanillic aldehyde after mixing, continue stirring 6-7h, i.e. obtain after sediment washing, freeze-drying
RhBMP-2/ chitosan microball.
3, gelatin particle is joined in deionized water, at 37 DEG C, 2h in the magnetic stirring apparatus of 300r/min
To thoroughly dissolving, gelatin final concentration of 20%.
4, nanometer hydroxyapatite powder nHA (diameter 20nm) is joined in gelatin solution, Qi Zhongna
Rice hydroxyapatite is 1:1 with the mass ratio of gelatin, and mixture is broken up by nanometer ultrasonic cell disruptor
To homogeneous state, and add rhBMP-2/ chitosan microball and uniformly mix.
5, above-mentioned mixed liquor is injected in the base body prepared with syringe pressurization, and be immersed in mixed
Close in liquid, place 4 DEG C of refrigerator 12h.
6, take out the gel piece after above-mentioned freezing, give scraper surface unnecessary gel, add 0.1mol/L sweet
Propylhomoserin solution, at 37 DEG C, soaks 2h, same to method, then uses deionized water in the magnetic stirring apparatus of 300r/min
Soak, clean 3 times.
7, above-mentioned processed material is put into container, add deionized water to not having the upper surface of processed material, put into
-80 DEG C of refrigerator freezing 4h.
8, taking out frozen thing, put in vacuum freeze drier ,-46 DEG C of freeze-drying 48h, i.e. obtaining can
It is loaded with the neck Invasive lumbar fusion device of rhBMP-2 slow-released system.
9, being put into by above-mentioned neck Invasive lumbar fusion device and carry out sterilizing in Epoxyethane sterilizing box, independent packing processes.
Embodiment 4 is loaded with the preparation of the neck Invasive lumbar fusion device of rhBMP-2 slow-released system
1, the base body of neck Invasive lumbar fusion device is prepared
CT image is imported the three-dimensional imaging software such as Mimics or CAD by 1.1, obtains the three of targeted bony tissue
Dimension image, average Kong Zhuwei 100 μm, aperture are 300 μm, and with hexahedron structure unit filling, extension should
Image, obtains the porous connection three-dimensional digital model of personalization, the middle cavity diameter 5mm of support, rear wall
Closing atresia, front portion is titanium plate spline structure, inside has the screw duct towards two ends.
1.2 use EOS M280 metal material 3D printer, with titanium alloy (Ti-6Al-4V) as raw material,
According to the base body printing the neck Invasive lumbar fusion device with entity portion and porous titanium alloy support that designs a model.
2, use emulsion-crosslinking method prepare chitosan microball and load rhBMP-2, form rhBMP-2/ shitosan
Microballoon.First 300mg shitosan is dissolved in 10ml formic acid solution, adds about 2.7mg rhBMP-2, fill
Divide stirring.Being added dropwise in the atoleine containing surfactant span80,45 DEG C are sufficiently stirred for again
Rear addition crosslinking agent vanillic aldehyde, continues stirring 6-7h, i.e. obtains after sediment washing, freeze-drying
RhBMP-2/ chitosan microball.
3, gelatin particle is joined in deionized water, at 37 DEG C, 2h in the magnetic stirring apparatus of 300r/min
To thoroughly dissolving, gelatin final concentration of 3%.
4, nanometer hydroxyapatite powder nHA (diameter 20nm) is joined in gelatin solution, Qi Zhongna
Rice hydroxyapatite is 1:2 with the mass ratio of gelatin, and mixture is broken up by nanometer ultrasonic cell disruptor
To homogeneous state, and add rhBMP-2/ chitosan microball and uniformly mix.
5, above-mentioned mixed liquor is injected in the base body prepared with syringe pressurization, and be immersed in mixed
Close in liquid, place 4 DEG C of refrigerator 12h.
6, take out the gel piece after above-mentioned freezing, give scraper surface unnecessary gel, add 0.1mol/L sweet
Propylhomoserin solution, at 37 DEG C, soaks 2h, same to method, then uses deionized water in the magnetic stirring apparatus of 300r/min
Soak, clean 3 times.
7, above-mentioned processed material is put into container, add deionized water to not having the upper surface of processed material, put into
-80 DEG C of refrigerator freezing 4h.
8, taking out frozen thing, put in vacuum freeze drier ,-46 DEG C of freeze-drying 48h, i.e. obtaining can
It is loaded with the neck Invasive lumbar fusion device of rhBMP-2 slow-released system.
9, being put into by above-mentioned neck Invasive lumbar fusion device and carry out sterilizing in Epoxyethane sterilizing box, independent packing processes.
Embodiment 5 is loaded with the preparation of the neck Invasive lumbar fusion device of rhBMP-2 slow-released system
1, the base body of neck Invasive lumbar fusion device is prepared
CT image is imported the three-dimensional imaging software such as Mimics or CAD by 1.1, obtains the three of targeted bony tissue
Dimension image, average Kong Zhuwei 100 μm, aperture are 300 μm, and with hexahedron structure unit filling, extension should
Image, obtains the porous connection three-dimensional digital model of personalization, the middle cavity diameter 5mm of support, rear wall
Closing atresia, front portion is titanium plate spline structure, inside has the screw duct towards two ends.
1.2 use EOS M280 metal material 3D printer, with titanium alloy (Ti-6Al-4V) as raw material,
According to the base body printing the neck Invasive lumbar fusion device with entity portion and porous titanium alloy support that designs a model.
2, use emulsion-crosslinking method prepare chitosan microball and load rhBMP-2, form rhBMP-2/ shitosan
Microballoon.First 300mg shitosan is dissolved in 10ml formic acid solution, adds about 2.7mg rhBMP-2, fill
Divide stirring.Being added dropwise in the atoleine containing surfactant span80,45 DEG C are sufficiently stirred for again
Rear addition crosslinking agent vanillic aldehyde, continues stirring 6-7h, i.e. obtains after sediment washing, freeze-drying
RhBMP-2/ chitosan microball.
3, gelatin particle is joined in deionized water, at 37 DEG C, 2h in the magnetic stirring apparatus of 300r/min
To thoroughly dissolving, gelatin final concentration of 5%.
4, nanometer hydroxyapatite powder nHA (diameter 20nm) is joined in gelatin solution, Qi Zhongna
Rice hydroxyapatite is 3:4 with the mass ratio of gelatin, and mixture is broken up by nanometer ultrasonic cell disruptor
To homogeneous state, and add rhBMP-2/ chitosan microball and uniformly mix.
5, above-mentioned mixed liquor is injected in the base body prepared with syringe pressurization, and be immersed in mixed
Close in liquid, place 4 DEG C of refrigerator 12h.
6, take out the gel piece after above-mentioned freezing, give scraper surface unnecessary gel, add 0.1mol/L sweet
Propylhomoserin solution, at 37 DEG C, soaks 2h, same to method, then uses deionized water in the magnetic stirring apparatus of 300r/min
Soak, clean 3 times.
7, above-mentioned processed material is put into container, add deionized water to not having the upper surface of processed material, put into
-80 DEG C of refrigerator freezing 4h.
8, taking out frozen thing, put in vacuum freeze drier ,-46 DEG C of freeze-drying 48h, i.e. obtaining can
It is loaded with the neck Invasive lumbar fusion device of rhBMP-2 slow-released system.
9, being put into by above-mentioned neck Invasive lumbar fusion device and carry out sterilizing in Epoxyethane sterilizing box, independent packing processes.
Embodiment 6 is loaded with the preparation of the neck Invasive lumbar fusion device of rhBMP-2 slow-released system
1, the base body of neck Invasive lumbar fusion device is prepared
CT image is imported the three-dimensional imaging software such as Mimics or CAD by 1.1, obtains the three of targeted bony tissue
Dimension image, average Kong Zhuwei 100 μm, aperture are 300 μm, and with hexahedron structure unit filling, extension should
Image, obtains the porous connection three-dimensional digital model of personalization, the middle cavity diameter 5mm of support, rear wall
Closing atresia, front portion is titanium plate spline structure, inside has the screw duct towards two ends.
1.2 use EOS M280 metal material 3D printer, with titanium alloy (Ti-6Al-4V) as raw material,
According to the base body printing the neck Invasive lumbar fusion device with entity portion and porous titanium alloy support that designs a model.
2, use emulsion-crosslinking method prepare chitosan microball and load rhBMP-2, form rhBMP-2/ shitosan
Microballoon.First 300mg shitosan is dissolved in 10ml formic acid solution, adds about 2.7mg rhBMP-2, fill
Divide stirring.Being added dropwise in the atoleine containing surfactant span80,45 DEG C are sufficiently stirred for again
Rear addition crosslinking agent vanillic aldehyde, continues stirring 6-7h, i.e. obtains after sediment washing, freeze-drying
RhBMP-2/ chitosan microball.
3, gelatin particle is joined in deionized water, at 37 DEG C, 2h in the magnetic stirring apparatus of 300r/min
To thoroughly dissolving, gelatin final concentration of 4%.
4, nanometer hydroxyapatite powder nHA (diameter 20nm) is joined in gelatin solution, Qi Zhongna
Rice hydroxyapatite is 1:2 with the mass ratio of gelatin, and mixture is broken up by nanometer ultrasonic cell disruptor
To homogeneous state, and add rhBMP-2/ chitosan microball and uniformly mix.
5, above-mentioned mixed liquor is injected in the base body prepared with syringe pressurization, and be immersed in mixed
Close in liquid, place 4 DEG C of refrigerator 12h.
6, take out the gel piece after above-mentioned freezing, give scraper surface unnecessary gel, add 0.1mol/L sweet
Propylhomoserin solution, at 37 DEG C, soaks 2h, same to method, then uses deionized water in the magnetic stirring apparatus of 300r/min
Soak, clean 3 times.
7, above-mentioned processed material is put into container, add deionized water to not having the upper surface of processed material, put into
-80 DEG C of refrigerator freezing 4h.
8, taking out frozen thing, put in vacuum freeze drier ,-46 DEG C of freeze-drying 48h, i.e. obtaining can
It is loaded with the neck Invasive lumbar fusion device of rhBMP-2 slow-released system.
9, being put into by above-mentioned neck Invasive lumbar fusion device and carry out sterilizing in Epoxyethane sterilizing box, independent packing processes.
Embodiment 7 is loaded with the analysis of the mechanical property of the neck Invasive lumbar fusion device of rhBMP-2 slow-released system
Omnipotent dynamics measurement is used to be loaded with in the neck Invasive lumbar fusion device of rhBMP-2 slow-released system three-dimensional through many
The Compressive Mechanical Properties of pore structure.Using BAM artificial bone as comparison.Loading velocity is 5mm/min, support
Maximum pressure position F (N) that material flattens, according to formula P=F/A (A is compression area), tries to achieve compression strength.
Elastic modelling quantity is tried to achieve, (δ is that stress, ε are for straining) according to formula E=δ/ε.
Result: in neck Invasive lumbar fusion device prepared by the utility model, the elastic modelling quantity of three-dimensional through loose structure is
3.5 ± 0.5GPa, compression strength is 88.9 ± 9.4MPa.
The compression strength of three-dimensional through loose structure and springform in neck Invasive lumbar fusion device prepared by the utility model
Amount, close to normal person's bone, effectively avoids stress shielding, beneficially bone and merges, and can effectively prevent between cervical vertebra
The sinking of fusion device.
Embodiment 8 is loaded with the mensuration of the sustained release performance of the neck Invasive lumbar fusion device of rhBMP-2 slow-released system
The step of external rhBMP-2 release experiment:
1, the step preparation according to embodiment 6 is loaded with the neck Invasive lumbar fusion device of rhBMP-2 slow-released system.
2, the neck Invasive lumbar fusion device being loaded with rhBMP-2 slow-released system step 1 prepared is immersed in phosphate and delays
Rush (pH=7) in liquid, 37 DEG C of concussion stirrings；Every 5 days sucking-off soak 100 μ l/ time, according to rhBMP-2ELISA
The step of kit (R&D) specification, measures rhBMP-2 content in soak, and above-mentioned experiment repeats three
Secondary, calculate average.
As shown in Figure 6, rhBMP-2 is tired out result by the neck Invasive lumbar fusion device being loaded with rhBMP-2 slow-released system
Long-pending burst size presents mild increase trend, can extend to about 45d release time.
Embodiment described above only have expressed several embodiments of the present utility model, and it describes more concrete and detailed
Carefully, but therefore can not be interpreted as the restriction to the utility model the scope of the claims.It should be pointed out that, for
For those of ordinary skill in the art, without departing from the concept of the premise utility, it is also possible to if making
Dry deformation and improvement, these broadly fall into protection domain of the present utility model.Therefore, the guarantor of the utility model patent
The scope of protecting should be as the criterion with claims.
Claims (2)
1. the neck Invasive lumbar fusion device being loaded with rhBMP-2 slow-released system, it is characterised in that between described cervical vertebra
Fusion device is by three-dimensional through loose structure and does not have the entity portion of loose structure and forms, described entity portion and institute
Stating three-dimensional through loose structure to be integrated, described entity portion encloses the through loose structure of described three-dimensional away from canalis spinalis
One side；The through loose structure of described three-dimensional is by porous metals support, is positioned at described porous metals internal stent
The three-dimensional micro rack being made up of natural macromolecular material and bioceramic and be positioned at described three-dimensional micro rack
The rhBMP-2 slow-released system composition in portion；The through loose structure of described three-dimensional is not have towards the one side of canalis spinalis
The sealing surface of pore structure；The middle part of the through loose structure of described three-dimensional arranges the centre bore of a up/down perforation；
Described entity portion is provided with the screw of multiple both sides up and down being adapted to extend to the through loose structure of described three-dimensional.
Neck Invasive lumbar fusion device the most according to claim 1, it is characterised in that described entity portion arranges 4
The individual screw for fixing described porous metals neck Invasive lumbar fusion device, 4 described screws are located along the same line,
Pass the screw of middle two screws obliquely downward, be 40 degree of angles with plane, through the screw of both sides screw
Towards oblique upper, it is 40 degree of angles with plane.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105796214A (en) * | 2016-03-08 | 2016-07-27 | 吴志宏 | Porous metal cervical interbody fusion cage for directionally and slowly releasing rhBMP-2 |
| CN109550968A (en) * | 2018-12-27 | 2019-04-02 | 杭州电子科技大学 | A method of human body lumbar fusion cages are prepared using 3D printing technique |
-
2016
- 2016-03-08 CN CN201620177280.8U patent/CN205391219U/en active Active
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105796214A (en) * | 2016-03-08 | 2016-07-27 | 吴志宏 | Porous metal cervical interbody fusion cage for directionally and slowly releasing rhBMP-2 |
| CN109550968A (en) * | 2018-12-27 | 2019-04-02 | 杭州电子科技大学 | A method of human body lumbar fusion cages are prepared using 3D printing technique |
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Effective date of registration: 20180731 Address after: 100730 Wangfujing, Dongcheng District, Dongcheng District, Beijing Patentee after: Beijing Xiehe Hospital, Chinese Academy of Medical Sciences Address before: 100730 Peking Union Medical College Hospital, 1 Shuai Fu Garden, Dongcheng District, Beijing. Co-patentee before: Li Bo Patentee before: Wu Zhihong |