CN109730811A - Imitative bone Haversian system bioactive bracket and its preparation method and application - Google Patents
Imitative bone Haversian system bioactive bracket and its preparation method and application Download PDFInfo
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- CN109730811A CN109730811A CN201811542329.5A CN201811542329A CN109730811A CN 109730811 A CN109730811 A CN 109730811A CN 201811542329 A CN201811542329 A CN 201811542329A CN 109730811 A CN109730811 A CN 109730811A
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Abstract
The present invention relates to a kind of imitative bone Haversian system bioactive brackets and its preparation method and application, the imitative bone Haversian system bioactive bracket includes: hollow posts, the reticular structure in the hollow cavity of hollow posts and the more than one pipe being formed in the solid section of hollow posts, and the material of the bioactive bracket is bioactive materials.
Description
Technical field
The present invention relates to imitative bone Haversian system bioactive brackets and its preparation method and application, belong to biomaterial neck
Domain.
Background technique
At present by wound, inflammation, bone tumour operative treatment caused by large segmental bone defect reparation and regeneration be clinical
One of the difficult point for treating bone defect.And the bone tissue engineering scaffold that bone tissue engineer and biomaterial combine is research bone defect
The hot spot of reparation.Bone tissue engineering scaffold is broadly divided into three categories, including metallic support, polymeric stent and bioceramic at present
Bracket [1], wherein bioceramic scaffold becomes research large segmental bone defect due to its excellent compression strength and bioactivity and repairs
Multiple hot spot material.There are many kinds of the techniques for preparing ceramics bracket material, such as traditional pore creating material method, template method, bubble method.
However, all there is many shortcomings for these methods.The bracket holes size that pore creating material method is prepared is inhomogenous, between duct not
Enough connections；And the bracket of template method and the preparation of bubble method, mechanical strength are again relatively low, are unable to satisfy wanting for bone renovating material
It asks, and the bioceramic scaffold of 3D printing technique preparation is due to precision height, geomery is highly controllable and becomes the complicated knot of preparation
The first choice [2] of structure bioceramic scaffold.But the 3D printing technique of extruded type still cannot disposably prepare imitative bone Kazakhstan not at present
The bioceramic scaffold of this system structure.
By taking long bone as an example, the structure of bone includes cortex bone, cancellous bone and the ossis in center, and cortex bone is located at most table
Layer, is made of compact arranged bone plate, and adult cortex bone accounts for the 80% of bone gross weight, is that bone bears twisting stress, bending
The basis [3] of stress and compression.Inside, there are many longitudinal cylinder-like structures, referred to as Haversian system between outer circumferential lamella
(Harversian System), axis are the pipelines of a stringer, referred to as central canal (Harversian Canal), interior
Promising osteocyte provides the capillary [4] of nutrition and oxygen.Most histocytes of body by blood supply oxygen and
Nutriment, due to being limited by tissue oxygen gas diffusion, the survival range of cell is confined to neighbouring 100~200 μ of capillary
The region [5] of m, therefore the vascularization of bone tissue is very necessary.Cancellous bone is mutual by many sheets and acicular bone trabecula
It is woven into a mesh structure, this structure makes it have good shock resistance, while self metabolic rate of cancellous bone is fast, thorn
It is good to swash osteogenic action.
Existing technical literature:
[1]Deng C,Yao Q,Feng C,Li J,Wang L,Cheng G,et al.3D Printing of Bilineage
Constructive Biomaterials for Bone and Cartilage Regeneration.Advanced
Functional Materials 2017；27:1703117.
[2]Zhang W,Feng C,Yang G,Li G,Ding X,Wang S,et al.3D-printed scaffolds
with synergistic effect of hollow-pipe structure and bioactive ions for
vascularized bone regeneration.Biomaterials 2017；135:85-95.
[3]Buck DW,2nd,Dumanian GA.Bone biology and physiology:Part I.The
fundamentals.Plastic and reconstructive surgery 2012；129:1314-20.
[4]Wegst UG,Bai H,Saiz E,Tomsia AP,Ritchie RO.Bioinspired structural
materials.Nat Mater 2015；14:23-36.
[5]Carmeliet P,Jain RK.Angiogenesis in cancer and other diseases.Nature
2000；407:249..
Summary of the invention
In view of the problems of the existing technology, the purpose of the present invention is to provide a kind of imitative bone Haversian system bioactivity
Bracket and its preparation method and application.
On the one hand, the application provides a kind of imitative bone Haversian system bioactive bracket comprising: hollow posts are located at
Reticular structure in the hollow cavity of void column and the more than one pipe being formed in the solid section of hollow posts, the biology
The material of active scaffold is bioactive materials.
Bioactive bracket of the invention simulates the Haversian system structure of bone, wherein hollow posts are similar to have and hold
The cortex bone compact texture of recast, reticular structure are similar to the cancellous bone reticular structure with osteogenic action, and tubing is similar to have
There is into vasoactive central canal, which, which has, promotes skeletonization and the potential at blood vessel, can be used for bone defect healing.
Preferably, the hollow posts, reticular structure and pipe are integrated.
Preferably, the internal diameter of the hollow posts is 3~20mm, with a thickness of 3~10mm.
Preferably, the reticular structure is interweaved by multiple needle-shaped or sheet beam, it is preferable that the beam it is straight
Diameter is 200~500 μm.
Preferably, the pipe is along the axially extending of hollow posts, it is preferable that the pipe along hollow posts axial component run through
The solid section of the hollow posts, i.e., the unilateral solid section for running through the hollow posts, non-through side is still solid construction,
Axial length is 0.5~1mm.
Preferably, being interconnected between the pipe.
In the present invention, can be adjusted by adjusting diameter and/or the quantity of the pipe bracket compression strength and/
Or porosity, it is preferable that the quantity of the pipe is 2~8, and the diameter of the pipe is 0.3~1.6mm.
Preferably, the bioactive materials are bioceramic or metal.
Second aspect, the application provide the preparation method of above-mentioned imitative bone Haversian system bioactive bracket comprising with
Lower step:
Bracket green body is prepared using photocuring 3D printing technique；
By gained bracket blank sintering, the imitative bone Haversian system bioactive bracket is obtained.
According to the present invention, using photocuring 3D printing technique, it is raw can with controllable precise to prepare imitative bone Haversian system
Object active scaffold.
Preferably, carrying out modelling using three-dimensional graphics software, STL formatted file is exported as, stl file is imported into light
The software solidified in printer carries out slicing treatment, generates TDP formatted file and imports printer for printing.Preferably, institute
Stating three-dimensional graphics software is 3ds Max software or CAD.
The third aspect, the application provide above-mentioned imitative bone Haversian system bioactive bracket and are preparing bone impairment renovation material
In application.
Bioactive bracket of the invention simulates the Haversian system structure and physiological environment of bone well, has and promotes
Skeletonization and potential at blood vessel, can be used for bone defect healing.
Detailed description of the invention
Fig. 1 is the imitative bone Haversian system akermanite bracket optical photograph of different Nigel Havers calibers and pipe quantity.
Fig. 2 is bracket electromicroscopic photograph, and (a) (b) (c) is followed successively by design diameter 0.8mm, and the bracket of 1.2mm, 1.6mm are breathed out not
This tube portion is (d) cancellous bone portion of bracket, (e) is the sintering situation of bracket, it can be seen that bracket densified sintering product.
(a) in Fig. 3 is the bracket intensity test of different central canal diameters, it can be seen that bracket compression strength with
Nigel Havers caliber is reduced and is reduced；It (b) is the bracket intensity test of different central canal quantity, it can be seen that bracket resistance to compression
Intensity increases with central canal quantity and is improved.
(a) in Fig. 4 is that the brace aperture rate of different central canal diameters is tested, it can be seen that brace aperture rate is with breathing out not
This caliber increases and improves；(b) it is tested for the brace aperture rate of different central canal quantity, it can be seen that brace aperture rate is with Kazakhstan
Fu Si pipe quantity increases and improves.
(a) in Fig. 5, which is that the mono- culture of HBMSC that the bracket of different central canal quantity loads, HUVEC are mono-, to be cultivated and two kinds
Cell co-cultures 1,3,7 days proliferation results, it can be seen that the cultivation effect of co-cultivation group is substantially better than single culture group.(b) altogether
The cultivation effect of culture group different number of days is obvious.
(a) in Fig. 6, which is that the mono- culture of HBMSC that the bracket of different central canal diameters loads, HUVEC are mono-, to be cultivated and two kinds
Cell co-cultures 1,3,7 days proliferation results, it can be seen that the cultivation effect of co-cultivation group is substantially better than single culture group.(b) altogether
The cultivation effect of culture group different number of days is obvious.
The situation of sticking that Fig. 7 is the culture of co-cultivation group 1 day is copolymerized burnt microphoto, and (a) (b) (c) is followed successively by design diameter
The bracket central canal part of 0.8mm, 1.2mm, 1.6mm load HUVEC, (d) are the cancellous bone portion of bracket, load
HBMSC, it can be seen that two kinds of cell growth states of co-cultivation are good.
Fig. 8 is to stick situation stereoscan photograph in the culture of co-cultivation group 1 day, and (a) (b) is bracket cancellous bone portion, bear
HBMSC is carried, (c) (d) is bracket central canal part, loads HUVEC, it can be seen that two kinds of cell growth states of co-cultivation are good
Good, cell is sprawled, and pseudopodium is abundant.
Fig. 9 is the skeletonization of single culture and the culture three days of co-cultivation group and at blood vessel related gene expression.(a) co-cultivation group phase
Obviously rise than single culture group Bone formation-related gene COL-1, BMP2, ALP expression quantity；(b) co-cultivation group is compared to single culture composition
Blood vessel related gene VE-cad, eNOS, vegf expression amount obviously rise.
Specific embodiment
The present invention is further illustrated below in conjunction with attached drawing and following embodiments, it should be appreciated that attached drawing and following embodiments
It is merely to illustrate the present invention, is not intended to limit the present invention.
A kind of imitative bone Haversian system bioactive bracket (hereinafter referred to as bracket) is disclosed, imitates humans and animals
The three parts structure of bone: the cortex bone compact texture with load-bearing effect, the cancellous bone reticular structure with osteogenic action with
And have into vasoactive Haversian system tubular structure.
Fig. 1 shows the optical photograph of the bracket of an embodiment of the present invention.As shown in Figure 1, the bracket include: hollow posts,
Reticular structure in the hollow cavity of hollow posts and the more than one pipe being formed in the solid section of hollow posts.
Hollow posts imitation leather bone compact texture.The size and ratio of each section of bracket are adjustable.For example, hollow posts
Internal diameter can be 3~20mm, and it highly can be 2.5~40mm that thickness, which can be 3~10mm,.
Reticular structure imitates cancellous bone structure, can be interweaved by multiple needle-shaped or sheet beam.In one example,
Reticular structure is formed by the beam array of multilayer different orientation along hollow posts are axially stacked.The diameter of beam can be adjusted according to the needs,
It may be, for example, 0.2~1mm.
Reticular structure can be integrated with hollow posts.I.e. reticular structure can be connected with the inner wall of hollow posts, such as constitute netted
The both ends of each beam of structure are all located on the inner wall of hollow posts.
Pipe can be formed in the cavity in the solid section of hollow posts.Guan Kewei imitates central canal structure, can be in
Void column it is axially extending.In preferred embodiment, pipe along hollow posts axial component run through hollow posts.Manage incomplete axis
To the solid section for running through hollow posts.That is, one end of pipe is open out, other end closing.Closed end solid section
Axial length can be 0.5~1mm, guarantee sintering process closed end will not be made cracked or notch so as to cause cell suspension from
Bottom leaky influences cell-seeding-density, keeps cell inoculation quantitative change few more than the length that 1mm will affect pipe.And the length of pipe
As long as degree, which is greater than or equal to 2mm, can be used to inoculating cell.For example, the length of pipe can be the 2/3~39/40 of hollow column length.
Hollow cavity can be in the same manner as pipe, and one end is open out, other end closing, and the open end of hollow cavity and pipe is same
One end.Similarly, the axial length of hollow cavity closed end can be 0.5~1mm, and open end length can be greater than or equal to 2mm.
It can be interconnected between pipe, such as the horizontal pipeline by being similar to Fu Keman pipe (Volkmann canal) connects
It is logical.Furthermore it is preferred that pipe is not connected to the hollow cavity of hollow posts.
According to above structure, bracket has imitated the physiological environment of bone while accurately imitating the multilevel structure of bone, hollow
The pipe die of column solid section imitates central canal, and is connection between pipe, but with the reticular structure in hollow cavity be it is disconnected,
Guarantee that pipe inner cell is not directly contacted with reticular structure inner cell in inoculating cell, thus realize contactless co-cultivation, essence
True simulation is located at central canal inner cell and the fact that cancellous bone inner cell is not directly contacted under physiological environment, for research
The contactless co-cultivation of cell in vitro provides biologically active cell container.
The diameter of pipe is adjustable, such as can adjust within the scope of 0.3~1.6mm.The quantity of pipe is also adjustable, such as can be 2~8
In the range of adjust.Pass through the diameter and/or quantity of regulation pipe, the compression strength and/or porosity of adjustable bracket.Separately
Outside, by adjusting the mesh form and/or size etc. of reticular structure, the also compression strength and/or porosity of adjustable bracket.
In some embodiments, the compression strength of bracket is 14.8~21.9MPa, and porosity is 25%~34%.
In addition, the diameter of each pipe can be the same or different.In preferred embodiment, the identical multiple pipes of diameter are in
The central axis of void column is evenly distributed, to guarantee pipe to the evenly dispersed of axial stress.
In the present invention, the material of bracket is bioactive materials, for example, bioceramic, metal etc..Bioceramic is for example
Akermanite (Ca can be enumerated2MgSi2O7), tricalcium phosphate (β-TCP), bredigite (Ca7MgSi4O16), hydroxyapatite (Ca10
(PO4)6(OH)2), calcium silicates (Ca2SiO4) etc..Metal can for example enumerate iron etc..
In an embodiment of the present invention, bracket is prepared using photocuring 3D printing technique.Hereinafter, as an example, specifically
The preparation method of bright bracket.
Firstly, slurry of the preparation containing bioactive materials and photosensitive resin.In one example, by bioactive materials,
Sintering aid and photosensitive resin are according to mass ratio 1:(0.25~0.5): (0.6~1) mixing and ball milling obtains slurry.Sintering aid can
To be biological glass powder such as 45S5 biological glass powder, 52S4.6 biological glass powder, 55S4.3 biological glass powder, 60S3.8 biology
Glass powder etc..Photosensitive resin can use photosensitive resin well known in the art, such as urethane acrylate, epoxy acrylate
Or epoxy resin etc..
Also, it generates 3 D-printing file and is used for 3D printing.In one embodiment, model is carried out using three-dimensional graphics software
Then design carries out slicing treatment, generate 3 D-printing file.Such as threedimensional model file can be generated in the following way: benefit
Modelling is carried out with three-dimensional graphics software, exports as STL formatted file, stl file is imported soft in photocuring printer
Part carries out slicing treatment, generates TDP formatted file and imports printer for printing.3ds for example can be used in three-dimensional graphics software
Max software, CAD etc..
Then, slurry importing photocuring printer is printed, obtains bracket green body.
Then, bracket green body is sintered, obtains bracket.Sintering schedule can be selected according to material, such as can be 1100
~1350 DEG C are calcined 3~5 hours.
By such as human marrow mesenchymal stem cell of the cell with osteogenic action (HBMSC) and can have into blood vessel function
Cell such as Human umbilical vein endothelial cells (HUVEC) be inoculated in the cancellous bone portion (reticular structure) and Nigel Havers of bracket respectively
Tube portion (pipe) constitutes the co-culture system of two kinds of cells of bracket load.As a result, it has been found that being co-cultured compared to independent culture
Group cultivation effect becomes apparent from, and Bone formation-related gene COL-1, BMP2, ALP and at blood vessel related gene VE-cad, eNOS, VEGF
Expression quantity significantly improves.Therefore, the total training of imitative bone Haversian system bioactive bracket and HBMSC and HUVEC disclosed herein
Feeding system simulates the Haversian system structure and physiological environment of bone well, has and promotes skeletonization and the potential at blood vessel, energy
Enough implantation materials for making to repair large segmental bone defect.
The bioactive bracket for preparing imitative bone Haversian system is disclosed, it is disposable by photocuring 3D printing technique
Print size, the imitation leather bone of aperture controllable precise, cancellous bone and the structure-integrated bioactive bracket of central canal.
And by physiological environment in analogue body, a variety of skeletonization are constructed, at the co-culture system of blood vessel relevant cell, it was confirmed that this to have
The skeletonization of bone Haversian system structure-biological activity bracket, at vascular performance.
Enumerate embodiment further below with the present invention will be described in detail.It will similarly be understood that following embodiment is served only for this
Invention is further described, and should not be understood as limiting the scope of the invention, those skilled in the art is according to this hair
Some nonessential modifications and adaptations that bright above content is made all belong to the scope of protection of the present invention.Following examples are specific
Technological parameter etc. is also only an example in OK range, i.e. those skilled in the art can be done properly by the explanation of this paper
In the range of select, and do not really want to be defined in hereafter exemplary specific value.
Embodiment 1
Using 3ds Max software design stent model, design size is diameter 10mm, and the cylindric imitative bone of height 3mm is breathed out not
This system structure bracket, wherein central canal diameter is divided into 1.6mm, and tri- kinds of 1.2mm, 0.8mm, central canal quantity is 8.It will
The stent model output drawn is STL formatted file and imports photocuring printer and (tie up scientific and technological Limited Liability purchased from Beijing ten
Company, model autocera-m) included software carries out slicing treatment, and it generates TDP formatted file and simultaneously imports printer.
Pure akermanite powder (being purchased from Kunshan Huaqiao Science and Technology New Materials Co., Ltd) 60g, with 1.5g45S5 bio-vitric
Powder (is purchased from Kunshan Huaqiao Science and Technology New Materials Co., Ltd), 41g photosensitive resin (epoxy acrylic resin, purchased from ten thousand person of outstanding talent of Jinhua
Accessory Co., Ltd) mixing and ball milling obtains light sensitive ceramics slurry, and configured slurry is placed in and is printed to obtain in printer
Timbering material.
Printed bracket is calcined 3 hours at 1350 DEG C, obtains pure akermanite ceramics bracket.
Embodiment 2
Using 3ds Max software design stent model, design size is diameter 10mm, and the cylindric imitative bone of height 3mm is breathed out not
This system structure bracket, wherein central canal diameter is 1.6mm, and central canal quantity is divided into 2,4,8 three kinds.It will draw
Good stent model output is STL formatted file and imports the included software progress slicing treatment of photocuring printer, generates TDP
Formatted file simultaneously imports printer.
Pure akermanite powder 50g, with 1.25g45S5 bio-vitric powder, 51.25g photosensitive resin mixing and ball milling is obtained
Configured slurry is placed in and is printed to obtain timbering material in printer by light sensitive ceramics slurry.
Printed bracket is calcined 3 hours at 1350 DEG C, obtains pure akermanite ceramics bracket.
Embodiment 3
Using 3ds Max software design stent model, design size is diameter 10mm, and the cylindric imitative bone of height 3mm is breathed out not
This system structure bracket, wherein central canal diameter is 1.6mm, and central canal quantity is divided into 2,4,8 three kinds.It will draw
Good stent model output is STL formatted file and imports the included software progress slicing treatment of photocuring printer, generates TDP
Formatted file simultaneously imports printer.
Pure β-TCP powder (being purchased from Kunshan Huaqiao Science and Technology New Materials Co., Ltd) 50g, with 50g photosensitive resin mixing and ball milling
Light sensitive ceramics slurry is obtained, configured slurry is placed in and is printed to obtain timbering material in printer.
Printed bracket is calcined 3 hours at 1100 DEG C, obtains pure β-TCP ceramics bracket.
Resulting bracket is subjected to characterization and bioactivity, skeletonization and at the evaluation of vascular performance, it is specific as follows.
Fig. 1 is the imitative bone Haversian system akermanite bracket optical photograph of different Nigel Havers calibers and pipe quantity, can be with
Find out that the bracket has imitative bone Haversian system structure.
Fig. 2 is bracket electromicroscopic photograph, and (a) (b) (c) is followed successively by the diameter 0.8mm, 1.2mm, 1.6mm designed in embodiment 1
Bracket central canal part, (d) be bracket cancellous bone portion, (e) be bracket sintering situation, it can be seen that bracket burn
Knot is fine and close.
Test bracket compression strength by the following method: it is 10mm that bracket, which is prepared into diameter, is highly the cylinder of 11mm
(this, having a size of the size before sintering, i.e. design size, is diameter 8mm, the ceramics branch of height 9mm or so after sintered to shape sample
Frame, and all brackets for characterizing all are sintered) stent diameter D is measured, using universal testing machine with 0.5mm/
The loading velocity uniform load of min is broken to bracket, records maximum load P, compression strength σcCalculation formula be σc=4P/ π
D2, every group of sample size is 6.(a) in Fig. 3 is the bracket compression strength of the resulting different central canal diameters of embodiment 1
Test, it can be seen that bracket compression strength is respectively 20.2MPa, 20.8MPa, 18.6MPa, pipe diameter and solid section thickness
The ratio of (wall thickness of hollow posts) is respectively 0.53,0.4,0.26, and when pipe diameter and thickness ratio are 0.4, compression strength reaches
Peak value.(b) in Fig. 3 is the bracket intensity test of the resulting different central canal quantity of embodiment 2, it can be seen that bracket
Compression strength is respectively 14.6MPa, 17.6MPa, 20.2MPa, increases with central canal quantity and improves.
Test bracket porosity by the following method: using Archimedes's drainage, and ceramics bracket is dried in 100 DEG C
Night claims to obtain dry weight M1, then impregnates bracket in deionized water, is evacuated to bubble-free generation, takes out bracket and claims to obtain weight in wet base
M2, finally measures buoyant weight M3 for bracket immersion in deionized water, and the calculation formula of porosity P is P=(M2-M1)/(M2-M3)
× 100%, every group of sample size is 6.(a) in Fig. 4 is the brace aperture of the resulting different central canal diameters of embodiment 1
Rate test, it can be seen that brace aperture rate is respectively 27.5%, 30.1%, 33.9%, increases with Nigel Havers caliber and improves；
(b) tested for the brace aperture rate of different central canal quantity, it can be seen that brace aperture rate is respectively 22%, 24.6%,
33.9%, increase with central canal quantity and improves.
The skeletonization of bracket load and the foundation at blood vessel relevant cell three-dimensional co-culture system
The physiological environment for imitating bone, by the akermanite bracket and human bone marrow mesenchymal of different Nigel Havers calibers and pipe quantity
Stem cell (HBMSC) and Human umbilical vein endothelial cells (HUVEC) co-culture, and HBMSC is inoculated in bracket cancellous bone portion, will
HUVEC is inoculated in bracket central canal, constitutes the co-culture system of the HBMSC and HUVEC of bracket load.
Bracket load cell co-culture system skeletonization and at blood vessel differentiation potential study
The akermanite bracket for studying different central canal calibers and pipe quantity co-cultures two kinds of cells and individually cultivates
Adherency, proliferation and skeletonization and influence at blood vessel related gene expression.
(a) in Fig. 5 be the HBMSC of the bracket load of the resulting different central canal quantity of embodiment 2 it is mono- cultivate,
The mono- culture of HUVEC and two kinds of cells co-culture 1,3,7 days proliferation results, it can be seen that the cultivation effect of co-cultivation group is obviously excellent
In single culture group.(b) in Fig. 5 is the proliferation results of co-cultivation group different number of days, it can be seen that bright cultivation effect is obvious.
(a) in Fig. 6 be the HBMSC of the bracket load of the resulting different central canal diameters of embodiment 1 it is mono- cultivate,
The mono- culture of HUVEC and two kinds of cells co-culture 1,3,7 days proliferation results, it can be seen that the cultivation effect of co-cultivation group is obviously excellent
In single culture group.(b) in Fig. 6 is the proliferation results of co-cultivation group different number of days, it can be seen that bright cultivation effect is obvious.
The situation of sticking that Fig. 7 is the culture of co-cultivation group 1 day is copolymerized burnt microphoto, and (a) (b) (c) is followed successively by embodiment 1
Design diameter 0.8mm, 1.2mm, 1.6mm bracket central canal part, load HUVEC, (d) be bracket spongiosa osseous part
Point, load HBMSC, it can be seen that two kinds of cell growth states of co-cultivation are good.
Fig. 8 is to stick situation stereoscan photograph in the culture of co-cultivation group 1 day, and (a) (b) is bracket cancellous bone portion, bear
HBMSC is carried, (c) (d) is bracket central canal part, loads HUVEC, it can be seen that two kinds of cell growth states of co-cultivation are good
Good, cell is sprawled, and pseudopodium is abundant.
Fig. 9 is the skeletonization of single culture and the culture three days of co-cultivation group and at blood vessel related gene expression.(a) co-cultivation group phase
Obviously rise than single culture group Bone formation-related gene COL-1, BMP2, ALP expression quantity；(b) co-cultivation group is compared to single culture composition
Blood vessel related gene VE-cad, eNOS, vegf expression amount obviously rise.
The above result shows that the bracket of load co-cultured cell can promote the proliferation of two kinds of cells significantly, promote
The Osteoblast Differentiation of HBMSC and HUVEC at blood vessel differentiation.
Claims (10)
1. a kind of imitative bone Haversian system bioactive bracket characterized by comprising hollow posts, positioned at the hollow of hollow posts
Intracavitary reticular structure and the more than one pipe being formed in the solid section of hollow posts, the bioactive bracket
Material is bioactive materials.
2. imitative bone Haversian system bioactive bracket according to claim 1, which is characterized in that the hollow posts, net
Shape structure and pipe are integrated.
3. imitative bone Haversian system bioactive bracket according to claim 2, which is characterized in that the hollow posts it is interior
Diameter is 3~20mm, with a thickness of 3~10mm.
4. imitative bone Haversian system bioactive bracket according to any one of claim 1 to 3, which is characterized in that institute
It states reticular structure to be interweaved by multiple needle-shaped or sheet beam, it is preferable that the diameter of the beam is 200~500 μm.
5. imitative bone Haversian system bioactive bracket according to any one of claim 1 to 4, which is characterized in that institute
Pipe is stated along the axially extending of hollow posts, it is preferable that the pipe along hollow posts axial component it is solid through the hollow posts
Part, it is preferable that closed end solid section axial length be 0.5~1mm, it is preferable that between the pipe be interconnected, but not with
Reticular structure connection.
6. imitative bone Haversian system bioactive bracket according to any one of claim 1 to 5, which is characterized in that logical
Diameter and/or the quantity of the pipe are overregulated to adjust the compression strength and/or porosity of the bracket, it is preferable that the pipe
Quantity be 2~8, the diameter of the pipe is 0.3~1.6mm.
7. imitative bone Haversian system bioactive bracket according to any one of claim 1 to 6, which is characterized in that institute
Stating bioactive materials is bioceramic or metal.
8. the preparation method of imitative bone Haversian system bioactive bracket described in a kind of any one of claims 1 to 7, special
Sign is, comprising the following steps:
Bracket green body is prepared using photocuring 3D printing technique；
By gained bracket blank sintering, the imitative bone Haversian system bioactive bracket is obtained.
9. preparation method according to claim 8, which is characterized in that carry out modelling using three-dimensional graphics software, lead
Out it is STL formatted file, the software that stl file imports in photocuring printer is subjected to slicing treatment, generates TDP formatted file
And printer is imported for printing, it is preferable that the three-dimensional graphics software is 3ds Max software or CAD.
10. cell is non-in vitro connects for imitative bone Haversian system bioactive bracket described in a kind of any one of claims 1 to 7
Touch co-culture in application or preparing the application in bone impairment renovation material.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111110404A (en) * | 2020-01-10 | 2020-05-08 | 苏州诺普再生医学有限公司 | Multi-structure bone composite support for 3D printing |
| CN114195507A (en) * | 2021-12-29 | 2022-03-18 | 中国科学院上海硅酸盐研究所 | Preparation method and application of dendriform-like structure bioactive scaffold |
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| CN109730811B (en) | 2021-07-13 |
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