CN108888803A - A kind of biological support and preparation method thereof, purposes and aquogel system - Google Patents
A kind of biological support and preparation method thereof, purposes and aquogel system Download PDFInfo
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- CN108888803A CN108888803A CN201810757842.XA CN201810757842A CN108888803A CN 108888803 A CN108888803 A CN 108888803A CN 201810757842 A CN201810757842 A CN 201810757842A CN 108888803 A CN108888803 A CN 108888803A
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Abstract
This application provides a kind of biological support and its aquogel systems.The aquogel system includes：First gel, the second gel and nanometer bone alternate material or nanometer nerve alternative materials, first gel are formed by polyethylene alcohol and water, and second gel is formed by photoinitiator, photocrosslinking agent and water.The biological support is formed by the aquogel system.Present invention also provides the preparation method of the biological support and purposes.This application provides a kind of completely new biological supports, and the biological support can provide good growing environment for osteocyte and nerve cell, can be used for Bone Defect Repari or neural restoration.
Description
Technical field
This application involves but be not limited to field of medical materials, and in particular to but be not limited to a kind of biological support and its preparation side
Method, purposes and aquogel system.
Background technique
Tissue engineering technique be occur in recent years can rebuild defective tissue and promote its regenerated emerging technology, want substantially
Element includes seed cell, biological support and bioactie agent etc..Biological support provides a three dimensional growth for seed cell
Bracket, so that seed cell be made to be proliferated and break up, it plays a part of the extracellular matrix instead of tissue or organ, makes iuntercellular
Suitable spatial distribution and cell communication are formed, the extracellular matrix of manual simulation is become, constitutes the microenvironment of cell growth.With
Include in the biologic bracket material of organizational project：Bone, cartilage, blood vessel, nerve, skin and artificial organs, such as liver,spleen,kidney, bladder
Deng tissue stent material.
More better biological supports are found, life is repaired for the mankind and creates health again, it has also become the numerous scientists in the whole world
Common pursuit and the power studied diligently.
Summary of the invention
It is the general introduction to the theme being described in detail herein below.This general introduction is not the protection model in order to limit claim
It encloses.
This application provides a kind of aquogel systems for being used to prepare hydrogel biological support, and utilize the aquogel system
Biological support of preparation and preparation method thereof, the aquogel system can be prepared using 3D printing or injection molding method
Meet the biological support of different shape demand.
Specifically, this application provides a kind of aquogel system of biological support, the aquogel system includes：First is solidifying
Glue, the second gel and nanometer bone alternate material or nanometer nerve alternative materials, first gel is by polyethylene alcohol and water shape
At second gel is formed by photoinitiator, photocrosslinking agent and water.
In some embodiments, the nanometer bone alternate material can be selected from nanometer hydroxyapatite, nanometer tricresyl phosphate
In calcium, nano-bone meal, nano aluminium oxide and nano zircite any one or more.
Optionally, the ratio of the volume of the quality and water in the aquogel system of the nanometer bone alternate material can be with
For 1%-200%, wherein the unit of the quality of the nanometer bone alternate material is g, the volume of the water in the aquogel system
Unit be ml.
Optionally, the partial size of the nanometer bone alternate material can be 1-1000 nanometers, for example, can receive for 50-200
Rice.
In this application, term " bone meal " refers to (may be from the bone tissue of animal model animal or humanized antibody turns
Genetic animal) product that is obtained after oil refining, washing, drying and crushing.
In some embodiments, the nanometer nerve alternative materials can be received selected from nano-graphene, nano-graphite, carbon
In mitron, carbon nano-fiber, nanogold and nano silver any one or more.
Optionally, the ratio of the nanometer nerve alternative materials and the volume of the water in the aquogel system can be
1%-10%, wherein the unit of the quality of the nanometer nerve alternative materials is g, the volume of the water in the aquogel system
Unit be ml.
Optionally, the partial size of the nanometer nerve alternative materials can be 1-1000 nanometers, for example, can receive for 50-200
Rice.
The partial size of nano material is related with the dispersibility of material and specific surface area, the life of the better materials synthesis of dispersibility
Object bracket performance is better.
In some embodiments, the ratio of the quality of the polyvinyl alcohol and the volume of the water in the aquogel system
It can be 6%-10%, wherein the unit of the quality of the polyvinyl alcohol is g, the volume of the water in the aquogel system
Unit is ml.
Optionally, the alcoholysis degree of the polyvinyl alcohol can be 87%-88% or 97%-100%.
In some embodiments, the photocrosslinking agent can be selected from polyethyleneglycol derivative and methacrylic acid derivative
In any one or more.
In some embodiments, the ratio of the volume of the photocrosslinking agent and the water in the aquogel system can be
3%-60%, wherein the unit of the quality of the photocrosslinking agent is g, and the unit of the volume of the water in the aquogel system is
ml。
Optionally, the polyethyleneglycol derivative be polyethyleneglycol diacrylate, polyethylene glycol dimethacrylate,
5,000 acetic acid N- succinimide base ester of methoxy poly (ethylene glycol), methoxy poly (ethylene glycol) maleic amide and the poly- second two of vitamin E
In alcohol succinate any one or more；
Optionally, the methacrylic acid derivative is selected from methacrylic anhydride, N, N'- methylene-bisacrylamide, first
Base butyl acrylate, methyl methacrylate, Isobutyl methacrylate, allyl methacrylate, Glycidyl methacrylate
In glyceride, poly- (methyl methacrylate) and methacrylic acid N- succinimide ester any one or more.
In some embodiments, the photoinitiator can be selected from 2- hydroxyl -4'- (2- hydroxy ethoxy) -2- methylbenzene
In acetone, phenyl (2,4,6- trimethylbenzoyl) phosphoric acid lithium salts and camphorquinone any one or more.
Optionally, the ratio of the quality of the photoinitiator and the volume of the water in the aquogel system can be no more than
0.1%, also optionally 0.01%-0.1%, wherein the unit of the quality of the photoinitiator is g, the aquogel system
In water volume unit be ml.
In some embodiments, the aquogel system can also include third gel, and the third gel can be by
Soluble biomaterial and water are formed.
Optionally, the soluble biomaterial can be selected from alginic acid, alginate, hyaluronic acid (including modified
Hyaluronic acid, for example, methacrylated hyaluronic acid), gelatin (including modified gelatin, for example, methacrylated gelatin),
Polypeptide (for example, EFK, EFK-CA, RGD), acrylamide/bisacrylamide and chitosan (including modification of chitosan, for example, carboxylic
Methyl chitosan, hydroxyethyl chitosan) in any one or more.
Optionally, the content of the soluble biomaterial can be so that the viscosity of the aquogel system is no more than
600×106mPas。
Present invention also provides a kind of biological support, the biological support is formed by aquogel system as described above.
In some embodiments, it can also have been loaded on the biological support and promote bone or neural restoration and regenerated life
Object active factors and/or drug.
Optionally, promote Bone Defect Repari and regenerated bioactie agent that can be selected from transforming growth factor β, fibroblast
Growth factor, Platelet-derived growth factor beta receptor, insulin-like growth factor, vascular endothelial growth factor, growth and differentiation factor
With in Osteoblast Specific Factor any one or more.
Optionally, promote Bone Defect Repari and regenerated drug can be in bone morphogenetic protein and I-type collagen
Any one or more.
Optionally, promote neural restoration and regenerated bioactie agent can be selected from nerve growth factor, brain source property mind
Through appointing in growth factor, brain-derived neurotrophic factor, ciliary neurotrophic factor and basic fibroblast growth factor
Meaning is one or more of.
Optionally, promote neural restoration and regenerated drug that can be selected from methylprednisolone, gangliosides, endothelin receptor
Antagonist, calcium ion channel blocker, EAA antagonists, opiate receptor antagonist, nitric oxide synthetase inhibit
In agent, antioxidant, free radical scavenger, platelet activating factor antagonist, Neurotrophin3/4/5/6 and melatonin
Any one or more.
Present invention also provides the preparation methods of biological support as described above, and the method may include following step：
Photoinitiator and photocrosslinking agent are added into polyvinyl alcohol water solution, stirring keeps photoinitiator and photocrosslinking agent molten
Solution；
Nanometer bone alternate material or nanometer nerve alternative materials are added, stir evenly；
Optionally, soluble biomaterial powder is added, make the viscosity of the aquogel system obtained be no more than 600 ×
106mPas；
The aquogel system of acquisition is prepared into bracket；
Bracket is lyophilized, is sterilized；And
Optionally, load promotes bone or neural restoration and regenerated bioactie agent and/or drug on bracket.
In some embodiments, it is formed containing soluble biomaterial in the aquogel system of the biological support, it will
The mode that the aquogel system of acquisition is prepared into bracket can be 3 D-printing or injection moulding；Alternatively, forming the biology branch
Without containing soluble biomaterial in the aquogel system of frame, can be by the mode that the aquogel system of acquisition is prepared into bracket
Desivac, heating melting method, pore-foaming agent method, overmolded method.
Optionally, it after nanometer bone alternate material or nanometer nerve alternative materials being added, can stir 0-12 hours.
In some embodiments, load promotes bone or neural restoration to be used with regenerated bioactie agent or drug
Method that is, by the way that biological support is carried out basification can add EDC/NHS (1- (3- diformazan for NHS-EDC method
Aminopropyl) -3- ethyl carbodiimide/n-hydroxysuccinimide), by amidation process by drug loading to biological support
On.
Present invention also provides biological supports as described above for Bone Defect Repari or the purposes of neural restoration.
The molding mode multiplicity of the biological support of the application, it is convenient to prepare, and application field is wide.
Other features and advantage will illustrate in the following description, also, partly become from specification
It obtains it is clear that being understood and implementing the application.The purpose of the application and other advantages can be by specifications, right
Specifically noted structure is achieved and obtained in claim and attached drawing.
Detailed description of the invention
Attached drawing is used to provide to further understand technical scheme, and constitutes part of specification, with this
The embodiment of application is used to explain the technical solution of the application together, does not constitute the limitation to technical scheme.
Fig. 1 is the configuration of surface figure of the bracket of the embodiment of the present application 1.
Fig. 2 is configuration of surface figure of the bracket of the embodiment of the present application 1 under another enlargement ratio.
Fig. 3 is the configuration of surface figure of the bracket of the embodiment of the present application 2.
Fig. 4 is configuration of surface figure of the bracket of the embodiment of the present application 2 under another enlargement ratio.
Fig. 5 is cell viability result figure of the mouse Nerve cell on different brackets.
Fig. 6 is work-dead cell stain result figure of the mouse Nerve cell on the bracket of embodiment 1.
Fig. 7 is work-dead cell stain result figure of the Marrow Mesenchymal Stem Cells on the bracket of embodiment 2.
Fig. 8 is cellular morphology electron microscope of the mouse calvarium osteocyte on the bracket of embodiment 2.
Fig. 9 is fluorescent staining cell surface aspect graph of the mouse calvarium osteocyte on the bracket of embodiment 2.
Figure 10 is fluorescent staining cell surface aspect graph of the Marrow Mesenchymal Stem Cells on the bracket of embodiment 2.
Figure 11 is the crosslinking time comparison diagram of different aquogel systems.
Figure 12 is the intensity contrast figure of the bracket formed by different aquogel systems.
Specific embodiment
For the purposes, technical schemes and advantages of the application are more clearly understood, below in conjunction with attached drawing to the application
Embodiment be described in detail.It should be noted that in the absence of conflict, in the embodiment and embodiment in the application
Feature can mutual any combination.
Phosphate buffered saline employed in following embodiment (PBS), 1- (3- dimethylamino-propyl) -3- ethyl carbon
Diimine (EDC), n-hydroxysuccinimide (NHS), potassium hydroxide, 2- (N- morpholine) ethanesulfonic acid poly- (MES), Bones morphology occur
Albumen (BMP), brain-derived neurotrophic factor (BDNF), polyvinyl alcohol (PVA, alcoholysis degree are 87-88% or 97-100%), 2-
Hydroxyl -4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone (I2959), polyethyleneglycol diacrylate (PEGDA), methacrylic acid
Acid anhydride, N, N'- methylene-bisacrylamide, phenyl (2,4,6- trimethylbenzoyl) phosphoric acid lithium salts (LAP) and sodium alginate are equal
Purchased from Sigma Aldrich；
(partial size is in 50-200 nanometers of models for nano-graphene, nano-graphite, nanometer hydroxyapatite and nano tricalcium phosphate
In enclosing) it is purchased from Shanghai Aladdin biochemical technology limited liability company.
Other raw materials and reagents are ordinary commercial products.
The additive amount of each substance is indicated with mass volume ratio w/v (g/ml), indicates the quality (g) and aquogel system of substance
In water volume (ml) ratio.
Embodiment 1
To polyvinyl alcohol water solution, (mass volume ratio of the water in polyvinyl alcohol therein and aquogel system is 10%w/
V, g/ml) in be added 1%w/v N, N'- methylene-bisacrylamide, 0.1%w/v I2959,20%w/v PEGDA and 2.5%
W/v nano-graphene stirs 8 hours；
10%w/v sodium alginate is added to stir evenly, obtains the aquogel system that viscosity is 3000mPas；
By obtained aquogel system, using syringe or 3D printer, (Hangzhou victory promise flies biotechnology and produces, Bio-- Pro) it squeezes out, and it is irradiated curing molding using the ultraviolet source that wavelength is 360nm, obtain bracket；
Bracket is lyophilized, is subsequently placed in 75% alcohol and impregnates 24 hours, then cleans 3 removal alcohol with sterile PBS
Sterilized (the scanning electron microscope the result is shown in Figure 1-2 of the bracket obtained after sterilizing)；
Bracket after sterilizing is put into basification 45 minutes in the potassium hydroxide of 1mM, is then placed in MES-EDC-NHS
(MES:EDC:The molar ratio of NHS is 1:1:2.5) it is carried out bioactivation 1 hour in mixed solution；
PBS solution (the BDNF containing BDNF is placed in after bracket after bioactivation is cleaned with distilled water/distilled water/PBS
Concentration be 200ng/ml) in, impregnate 24 hours；
It is saved for use for 0 DEG C after thering is the bracket of BDNF to be cleaned with distilled water/distilled water/PBS load.
Embodiment 2
To polyvinyl alcohol water solution, (mass volume ratio of the water in polyvinyl alcohol therein and aquogel system is 10%w/
V, g/ml) in be added 1%w/v N, N'- methylene-bisacrylamide, 0.1%w/v I2959,20%w/v PEGDA, 15%w/
V nanometer hydroxyapatite stirs 8 hours；
10%w/v sodium alginate is added to stir evenly, obtains the aquogel system that viscosity is 3000mPas；
By obtained aquogel system, using syringe or 3D printer, (Hangzhou victory promise flies biotechnology and produces, Bio-- Pro) it squeezes out, and it is irradiated curing molding using the ultraviolet source that wavelength is 360nm, obtain bracket；
Bracket is lyophilized, is subsequently placed in 75% alcohol and impregnates 24 hours, then cleans 3 removal alcohol with sterile PBS
Sterilized (the scanning electron microscope result of the bracket obtained after sterilizing is shown in Fig. 3-4)；
Bracket after sterilizing is put into basification 45 minutes in the potassium hydroxide of 1mM, is then placed in MES-EDC-NHS
(MES:EDC:The molar ratio of NHS is 1:1:2.5) it is carried out bioactivation 1 hour in mixed solution；
By the bracket after bioactivation with distilled water/distilled water/PBS clean after merging the PBS solution containing BMP (BMP's
Concentration is 200ng/ml) in, it impregnates 24 hours；
It is saved for use for 0 DEG C after thering is the bracket of BDNF to be cleaned with distilled water/distilled water/PBS load.
Embodiment 3
To polyvinyl alcohol water solution, (mass volume ratio of the water in polyvinyl alcohol therein and aquogel system is 6%w/
V, g/ml) in be added 1%w/v N, N'- methylene-bisacrylamide, 0.1%w/v I2959,10%w/v PEGDA, 15%w/
V nano tricalcium phosphate stirs 8 hours；
10%w/v sodium alginate is added to stir evenly, obtains the aquogel system that viscosity is 3000mPas；
By obtained aquogel system, using syringe or 3D printer, (Hangzhou victory promise flies biotechnology and produces, Bio-- Pro) it squeezes out, and it is irradiated curing molding using the ultraviolet source that wavelength is 360nm, obtain bracket；
Bracket is lyophilized, is subsequently placed in 75% alcohol and impregnates 24 hours, then cleans 3 removal alcohol with sterile PBS
It sterilizes；
Bracket after sterilizing is put into basification 45 minutes in the potassium hydroxide of 1mM, is then placed in MES-EDC-NHS
(MES:EDC:The molar ratio of NHS is 1:1:2.5) it is carried out bioactivation 1 hour in mixed solution；
By the bracket after bioactivation with distilled water/distilled water/PBS clean after merging the PBS solution containing BMP (BMP's
Concentration is 200ng/ml) in, it impregnates 24 hours；
It is saved for use for 0 DEG C after thering is the bracket of BDNF to be cleaned with distilled water/distilled water/PBS load.
Embodiment 4
To polyvinyl alcohol water solution, (mass volume ratio of the water in polyvinyl alcohol therein and aquogel system is 6%w/
V, g/ml) in be added 0.1%w/v N, N'- methylene-bisacrylamide, 0.1%w/v phenyl (2,4,6- trimethylbenzoyls
Base) phosphoric acid lithium salts (LAP), 6%w/v PEGDA, 1%w/v nano tricalcium phosphate, are stirred 8 hours；
6%w/v sodium alginate is added to stir evenly, obtains the aquogel system that viscosity is 2000mPas；
By obtained aquogel system, using syringe or 3D printer, (Hangzhou victory promise flies biotechnology and produces, Bio-- Pro) it squeezes out, and it is irradiated curing molding using the ultraviolet source that wavelength is 360nm, obtain bracket；
Bracket is lyophilized, is subsequently placed in 75% alcohol and impregnates 24 hours, then cleans 3 removal alcohol with sterile PBS
Sterilized (the scanning electron microscope the result is shown in Figure 1-2 of the bracket obtained after sterilizing)；
Bracket after sterilizing is put into basification 45 minutes in the potassium hydroxide of 1mM, is then placed in MES-EDC-NHS
(MES:EDC:The molar ratio of NHS is 1:1:2.5) it is carried out bioactivation 1 hour in mixed solution；
By the bracket after bioactivation with distilled water/distilled water/PBS clean after merging the PBS solution containing BMP (BMP's
Concentration is 200ng/ml) in, it impregnates 24 hours；
It is saved for use for 0 DEG C after thering is the bracket of BDNF to be cleaned with distilled water/distilled water/PBS load.
Embodiment 5
To polyvinyl alcohol water solution (mass volume ratio of the water in polyvinyl alcohol therein and aquogel system is 10w/v,
G/ml 0.1%w/v N, N'- methylene-bisacrylamide, 0.1%w/v phenyl (2,4,6- trimethylbenzoyl) are added in)
Phosphoric acid lithium salts (LAP), 12%w/v PEGDA, 50%w/v nano tricalcium phosphate stir 8 hours；
3%w/v sodium alginate is added to stir evenly, obtains the aquogel system that viscosity is 3000mPas；
By obtained aquogel system, using syringe or 3D printer, (Hangzhou victory promise flies biotechnology and produces, Bio-- Pro) it squeezes out, and it is irradiated curing molding using the ultraviolet source that wavelength is 360nm, obtain bracket；
Bracket is lyophilized, is subsequently placed in 75% alcohol and impregnates 24 hours, then cleans 3 removal alcohol with sterile PBS
Sterilized (the scanning electron microscope the result is shown in Figure 1-2 of the bracket obtained after sterilizing)；
Bracket after sterilizing is put into basification 45 minutes in the potassium hydroxide of 1mM, is then placed in MES-EDC-NHS
(MES:EDC:The molar ratio of NHS is 1:1:2.5) it is carried out bioactivation 1 hour in mixed solution；
By the bracket after bioactivation with distilled water/distilled water/PBS clean after merging the PBS solution containing BMP (BMP's
Concentration is 200ng/ml) in, it impregnates 24 hours；
It is saved for use for 0 DEG C after thering is the bracket of BDNF to be cleaned with distilled water/distilled water/PBS load.
Embodiment 6
To polyvinyl alcohol water solution, (mass volume ratio of the water in polyvinyl alcohol therein and aquogel system is 6%w/
V, g/ml) in be added 1%w/v N, N'- methylene-bisacrylamide, 0.1%w/v I2959,10%w/v PEGDA and 8%w/
V nano-graphite stirs 8 hours；
The methacrylated hyaluronic acid of 6%w/v is added to stir evenly, obtains the water gel that viscosity is 3000mPas
System；
By obtained aquogel system, using syringe or 3D printer, (Hangzhou victory promise flies biotechnology and produces, Bio-- Pro) it squeezes out, and it is irradiated curing molding using the ultraviolet source that wavelength is 360nm, obtain bracket；
Bracket is lyophilized, is subsequently placed in 75% alcohol and impregnates 24 hours, then cleans 3 removal alcohol with sterile PBS
Sterilized (the scanning electron microscope the result is shown in Figure 1-2 of the bracket obtained after sterilizing)；
Bracket after sterilizing is put into basification 45 minutes in the potassium hydroxide of 1mM, is then placed in MES-EDC-NHS
(MES:EDC:The molar ratio of NHS is 1:1:2.5) it is carried out bioactivation 1 hour in mixed solution；
PBS solution (the BDNF containing BDNF is placed in after bracket after bioactivation is cleaned with distilled water/distilled water/PBS
Concentration be 200ng/ml) in, impregnate 24 hours；
It is saved for use for 0 DEG C after thering is the bracket of BDNF to be cleaned with distilled water/distilled water/PBS load.
The performance test of biological support
1, CCK-8 dyeing and CCK-8 Coloration experiment
(1) spare when mouse cell being passaged to 2,3 generation；
(2) branch to be detected is placed in 75% alcohol and is impregnated 24 hours, then clean 3 removals with sterile PBS
Alcohol sterilizes；
(3) bracket after step (2) sterilizing is put into 24 orifice plates, then instills the mouse cell that step (1) obtains,
Culture medium is added after 1 hour；
(4) CCK-8 dyeing test (operating according to the specification of CCK-8 kit), detection are done after cultivating 1,3,5 day respectively
Cell viability；Or
(4 ') labor after cultivating 1,3,5 day respectively-and dead cell stain is (according to work-dead cell stain kit specification
Operation).
Test result is shown in Fig. 5-7.
Fig. 5 is mouse Nerve cell respectively in the bracket of embodiment 1 (with sodium alginate+polyvinyl alcohol+brain source property mind in figure
Through nutrition factor representation), the cell viability result on pure sodium alginate bracket and sodium alginate+polyvinyl alcohol bracket.It can see
After mouse Nerve cell is cultivated 5 days on the bracket of embodiment 1 out, cell viability obviously increases.
Fig. 6 is work-dead cell stain of the mouse Nerve cell on the bracket of embodiment 1 as a result, Fig. 7 is between mouse bone marrow cells
Work-dead cell stain result of the mesenchymal stem cells on the bracket of embodiment 2.Green fluorescence point in figure is living cells, red
Phosphor dot is dead cell, it can be seen that rack surface cell is green substantially, indicates its survival.Moreover, mouse cell is propping up
In the fluorescent staining for sticking form on the hydrogel thin slice of frame, illustrate mouse Nerve cell on the bracket of embodiment 1, Mouse Bone
Bone marrow-drived mesenchymal stem shows on the bracket of embodiment 2 good sticks shape form.
2, the fluorescent staining experiment of bracket cell surface form
(1) spare when mouse cell being passaged to 2,3 generation；
(2) biological support prepared by embodiment 2 is placed in 75% alcohol and is impregnated 24 hours, it is then clear with sterile PBS
3 removal alcohol are washed to sterilize；
(3) bracket after step (2) sterilizing is put into 24 orifice plates, the mouse cell that step (1) obtains then is instilled, to 1
Culture medium is added after hour；
(4) gel film is first fixed 8 hours with glutaraldehyde, then fixes 1 hour with osmic acid, subsequent gradient alcohol dehydration, most
After be lyophilized, do scanning electron microscope (Fig. 8)；
(5) fluorescent staining (operating according to the specification of fluorescent dyeing reagent box) is carried out to mouse cell.
Fig. 8 is cellular morphology electron microscope of the mouse calvarium osteocyte on the bracket of embodiment 2, and Fig. 9 is mouse parietal bone
Fluorescent staining cell surface aspect graph of the cell on the bracket of embodiment 2, Figure 10 are Marrow Mesenchymal Stem Cells in reality
Apply the fluorescent staining cell surface aspect graph on the bracket of example 2.As can be seen that mouse cell is radially attached on bracket table
Face.
3, crosslinking time
The bracket for testing different aquogel systems respectively forms the time to form solid support from colloid, and test result is such as
Shown in Figure 11.In Figure 11, column diagram from left to right respectively indicates the single aquogel system of methacrylated gelatin, this Shen
Please embodiment the 1-5 sodium alginate used and the composite hydrogel system of polyvinyl alcohol, methacrylated hyaluronic acid list
The compound water congealing colloid of methacrylated hyaluronic acid and polyvinyl alcohol that one aquogel system and the embodiment of the present application 6 use
The crosslinking time of system.It can be seen from figure 11 that the crosslinking time for the composite hydrogel system that the embodiment of the present application uses is significantly small
In the crosslinking time of single aquogel system, illustrate the molding effect for the composite hydrogel system that the embodiment of the present application uses more
It is good.
4, support intensity
The intensity of different brackets is tested respectively, and test result is as shown in figure 12.In Figure 12, column diagram from left to right divides
It Biao Shi not be by the bracket of the composite hydrogel System forming of methacrylated hyaluronic acid, polyvinyl alcohol and hydroxyapatite
Intensity, as the bracket of sodium alginate and the composite hydrogel System forming of hydroxyapatite (i.e. made from the embodiment of the present application 2
Biological support) intensity, the intensity of the bracket formed by the single aquogel system of sodium alginate, by methacrylated gelatin
Single aquogel system formed bracket intensity and formed by the single aquogel system of methacrylated hyaluronic acid
Bracket intensity.Contain PEGDA in Figure 12 in all aquogel systems, but is not shown in the figure.It can be recognized from fig. 12 that
The intensity of the bracket formed by the Heshui gel rubber system comprising nano material is more preferable.
Although embodiment disclosed by the application is as above, the content only for ease of understanding the application and use
Embodiment is not limited to the application.Technical staff in any the application fields, is taken off not departing from the application
Under the premise of the spirit and scope of dew, any modification and variation, but the application can be carried out in the form and details of implementation
Scope of patent protection, still should be subject to the scope of the claims as defined in the appended claims.
Claims (12)
1. a kind of aquogel system of biological support, the aquogel system include：First gel, the second gel and nano bone
Alternative materials or nanometer nerve alternative materials, first gel are formed by polyethylene alcohol and water, and second gel is drawn by light
Hair agent, photocrosslinking agent and water are formed.
2. aquogel system according to claim 1, wherein the nanometer bone alternate material is selected from nano-hydroxy-apatite
In stone, nano tricalcium phosphate, nano-bone meal, nano aluminium oxide and nano zircite any one or more；Optionally, institute
The ratio for stating the quality of nanometer bone alternate material and the volume of the water in the aquogel system is 1%-200%, the nanometer
The unit of the quality of bone alternate material is g, and the unit of the volume of the water in the aquogel system is ml；Optionally, described to receive
The partial size of rice bone alternate material is 1-1000 nanometers.
3. aquogel system according to claim 1, wherein the nanometer nerve alternative materials be selected from nano-graphene,
In nano-graphite, carbon nanotube, carbon nano-fiber, nanogold and nano silver any one or more；Optionally, described to receive
The ratio of the neural alternative materials of rice and the volume of the water in the aquogel system is 1%-10%, and the nanometer nerve substitutes material
The unit of the quality of material is g, and the unit of the volume of the water in the aquogel system is ml；Optionally, the nanometer nerve replaces
Partial size for material is 1-1000 nanometers.
4. aquogel system according to any one of claim 1-3, wherein the quality of the polyvinyl alcohol and the water
The ratio of the volume of water in gel rubber system is 6%-10%, and the unit of the quality of the polyvinyl alcohol is g, the water gel
The unit of the volume of water in system is ml；Optionally, the alcoholysis degree of the polyvinyl alcohol is 87%-88% or 97%-100%.
5. aquogel system according to any one of claim 1-3, wherein the photocrosslinking agent spreads out selected from polyethylene glycol
Any one biological in methacrylic acid derivative or more；
Optionally, the polyethyleneglycol derivative is polyethyleneglycol diacrylate, polyethylene glycol dimethacrylate, methoxy
5,000 acetic acid N- succinimide base ester of base polyethylene glycol, methoxy poly (ethylene glycol) maleic amide and vitamin E polyethylene glycol amber
In amber acid esters any one or more；
Optionally, the methacrylic acid derivative is selected from methacrylic anhydride, N, N'- methylene-bisacrylamide, methyl-prop
Olefin(e) acid butyl ester, methyl methacrylate, Isobutyl methacrylate, allyl methacrylate, methyl propenoic acid glycidyl
In ester, poly- (methyl methacrylate) and methacrylic acid N- succinimide ester any one or more.
6. aquogel system according to any one of claim 1-3, wherein the photoinitiator is selected from 2- hydroxyl -4'-
It is any in (2- hydroxy ethoxy) -2- methyl phenyl ketone, phenyl (2,4,6- trimethylbenzoyl) phosphoric acid lithium salts and camphorquinone
It is one or more of；Optionally, the ratio of the quality of the photoinitiator and the volume of the water in the aquogel system does not surpass
Cross 0.1%, also optionally 0.01%-0.1%, the unit of the quality of the photoinitiator is g, in the aquogel system
The unit of the volume of water is ml.
7. aquogel system according to claim 1 to 6 further includes third gel, the third gel is by can
Dissolubility biomaterial and water are formed；Optionally, the soluble biomaterial is selected from alginic acid, alginate, hyaluronic acid, bright
Glue, polypeptide, in acrylamide/bisacrylamide and chitosan any one or more；Optionally, the soluble biology
The content of material makes the viscosity of the aquogel system be no more than 600 × 106mPas。
8. a kind of biological support, biological support aquogel system as described according to claim 1 any one of -7 is formed.
9. biological support according to claim 8, wherein be also loaded on the biological support and promoted bone or neural restoration
With regenerated bioactie agent and/or drug；
Optionally, Bone Defect Repari and regenerated bioactie agent is promoted to be selected from transforming growth factor β, Desmocyte growth factor
Son, Platelet-derived growth factor beta receptor, insulin-like growth factor, vascular endothelial growth factor, growth and differentiation factor and skeletonization
In cell-specific factors any one or more；Promote Bone Defect Repari and regenerated drug be selected from bone morphogenetic protein and
In I-type collagen any one or more；
Optionally, promote neural restoration and regenerated bioactie agent be selected from nerve growth factor, the growth of brain source nerve because
In son, brain-derived neurotrophic factor, ciliary neurotrophic factor and basic fibroblast growth factor any one or
It is more kinds of；Promote neural restoration and regenerated drug be selected from methylprednisolone, gangliosides, endothelin-receptor antagonists, calcium from
Subchannel retarding agent, EAA antagonists, opiate receptor antagonist, nitric oxide synthase inhibitor activity, antioxidant,
In free radical scavenger, platelet activating factor antagonist, Neurotrophin3/4/5/6 and melatonin any one or more
It is a variety of.
10. the preparation method of biological support according to claim 8 or claim 9, the method includes the following steps：
Photoinitiator and photocrosslinking agent are added into polyvinyl alcohol water solution, stirring dissolves photoinitiator and photocrosslinking agent；
Nanometer bone alternate material or nanometer nerve alternative materials are added, stir evenly；
Optionally, soluble biomaterial powder is added, the viscosity of the aquogel system obtained is made to be no more than 600 × 106mPas；
The aquogel system of acquisition is prepared into bracket；
Bracket is lyophilized, is sterilized；And
Optionally, load promotes bone or neural restoration and regenerated bioactie agent and/or drug on bracket.
11. according to the method described in claim 10, wherein, being formed in the aquogel system of the biological support containing solubility
The mode that the aquogel system of acquisition is prepared into bracket is 3 D-printing or injection moulding by biomaterial；Alternatively, described in being formed
Without containing soluble biomaterial in the aquogel system of biological support, the aquogel system of acquisition is prepared into the mode of bracket
For desivac, heating melting method, pore-foaming agent method, overmolded method；
Optionally, it after nanometer bone alternate material or nanometer nerve alternative materials being added, stirs 0-12 hours.
12. biological support according to claim 8 or claim 9 is for Bone Defect Repari or the purposes of neural restoration.
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