CN109771700A - A kind of nano combined biological support of magnetic thermal response-type shape memory multi-stage porous and its preparation and application based on the building of 3D printing lotion - Google Patents
A kind of nano combined biological support of magnetic thermal response-type shape memory multi-stage porous and its preparation and application based on the building of 3D printing lotion Download PDFInfo
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Abstract
The invention belongs to intelligent composites, biomedical material technology, disclose a kind of nano combined biological support of magnetic thermal response-type shape memory multi-stage porous and the preparation method and application thereof based on the building of 3D printing lotion.The method of the present invention the following steps are included: (1) using low molecular weight band carboxyl end group polylactic acid to magnetic inorganic nano corpuscle carry out hydrophobically modified, obtain hydrophobically modified magnetic inorganic nano corpuscle；(2) hydrophobically modified magnetic inorganic nano corpuscle, biodegradable shape memory polymeric, rheological agent are added in organic solvent and form oily phase；Distilled water is added in oily phase, mixing and emulsifying obtains the sticky pickering emulsion of water-in-oil type；(3) using the sticky pickering emulsion of water-in-oil type as ink, three-dimensional porous lotion bracket is obtained using extruded type 3D printing, it is dry, obtain compound bio bracket；For hierarchical porous structure, there are excellent biocompatibility, biodegradability, magnetic thermal response shape-memory properties etc., be suitable for field of biomedicine.
Description
Technical field
It is the invention belongs to intelligent composite, biomedical material technology, in particular to a kind of based on 3D printing cream
The nano combined biological support of magnetic thermal response-type shape memory multi-stage porous and the preparation method and application thereof of liquid building.
Background technique
Shape-memory polymer be one kind can certain external condition stimulation under be fixed as temporary shapes, when again by
The intelligent macromolecule material of original shape can be returned to when stimulation again, possesses that shape memory, deformation quantity are big, figuration is easy, matter
The gently characteristics such as inexpensive and corrosion-resistant.Wherein, biodegradable shape memory polymeric (BSMPs), it is non-toxic, good due to also having
Good biocompatibility, biodegradability, and catabolite such as can be absorbed by the body or be metabolized at the functional characters, lead in biomedicine
Domain is concerned and payes attention to, and just becomes one of the research hotspot of Intelligent medical Material Field.It is constructed using BSMPs as host material
Intelligent multiporous biological bracket, field of tissue engineering technology application when not only may be implemented it is minimally invasive implantation (can using tighten it is small
Volume implants, then under certain stimulation, due to shape memory effect, voluntarily replys large volume and unfolds shape), " from being adapted to "
Irregular defective tissue shape (in shape recovery process, can fill irregular tissue defect region automatically), can also keep away
Exempting from second operation, (biodegradable in vivo, catabolite are absorbed by organisms using or are arranged by normal metabolism
Except external, it is not required to second operation taking-up), not only reduced the operating pressure of cumbersome surgical procedure, doctor, but also alleviate patient's
Pain and expenses of surgical treatment.
So far, the BSMPs having been reported is the shape-memory polymer that can be used for tissue engineering bracket building mostly
It is all that (polymer can be replied from temporary shapes to original fixed shape thermotropic when being heated above its deformation recovery temperature
Shape), however environment is used directly to heat to BSMPs timbering material, it will lead to ambient temperature and increase and be easy local mistake
Heat, if easily causing thermostimulation to surrounding biologic body tissue when operating to the intracorporal BSMPs timbering material of implantation biology
Damage.Therefore it is highly desirable by the way of " remote control heating ", i.e., contactless induction induction heating method, comes real
The shape memory effect of existing BSMPs timbering material achievees the purpose that control shape memory.Magnetic inorganic nano corpuscle is in alternation
The magnetic hystersis loss or superparamagnetic relaxation behavior generated under magnetic fields is, it can be achieved that magnetic thermal transition causes material warms.Therefore by magnetic
Property inorganic nano-particle with BSMPs is compound constructs the nano-composite scaffolds material with induced by magnetic field shape memory function,
The performance of contactless induced shape-memory is made it have, it is special so as to meet the fields of biomedicine such as minimally invasive implantation in vivo
Application requirement.
It is worth noting that, be applied to the timbering material of field of tissue engineering technology, to realize excellent bionic function, in addition to by
The shadow with functional factors such as releases is loaded to biocompatibility, surface bioactive, biodegradability, mechanical strength, drug
Outside ringing, timbering material internal pore structure and shape also have important influence.Connectivity between bracket high porosity and good hole, both
Be conducive to the conveying of cytotrophy ingredient and metabolite excretion, be also beneficial to implantation adherency, growth and the migration of cell.Bracket is not
Different important function are played with aperture size, as microcellular structure (a few to tens of microns) is conducive to cell adhesion, intracellular letter
Number conduction, cell Proliferation etc., macroporous structure (several hundred microns) are conducive to cell migration, extracellular matrix aggregation and organize the formation of
Deng.In addition the shape needs of bracket are matched with the shape of tissue damage or deleted areas with size, in order to completely fill reparation
Damage or missing tissues space.Thus to realize excellent bionical tissue repair function, tissue engineering bracket should also have high hole
The connection hierarchical porous structure of gap rate, and with the matched personalized shape of defect.It thus is highly desirable to probe into compound more
Effective, convenient, the controllable building of grade hole biological support, constructed biological support is in biomedicines such as the minimally invasive implantation of organizational project
Field has important application value.
The 3D printing technique quickly grown in recent years be able to meet organizational project multi-stage porous biological support internal pore structure
Diversified demand.3D printing technique is the threedimensional model that Metal pylon is constructed according to data such as CAD software or analog images, in turn
Biomaterial is successively piled into 3D solid bracket by 3D printer, can according to actual demand to biological support shape,
Connectivity etc. is accurately controlled between aperture size, hole, meets the requirement of bracket individual character manufacturing.Chinese invention patent
201610232704.0 using first by polylactic acid base shape memory polyurethane (PCLAUs)/modification Fe3O4Composite material is in 140-
It is extruded into Filamentous wire rod at a high temperature of 160 DEG C, then PCLAUs/Fe is obtained by (FDM) 3D printing of Fused Deposition Modeling technology3O4It receives
Rice compound rest.Constructed personalized compound rest has good biocompatibility, biodegradability, and can pass through Fe3O4
Magnetothermal effect obtain the recovery of shape effect of contactless magnetic excitation.But either wire rod is extruded into the studies above
All refer to high temperature in the step of type or 3D printing building bracket, for thermally labile substance (drug of such as thermally labile,
Growth factor) it cannot directly be printed together with substrate, but later period electrostatic spinning is needed to be introduced into rack surface, this makes bracket
Step of preparation process becomes complicated, cumbersome, time-consuming, and prepared by the scale batch for being unfavorable for such tissue engineering bracket, to limit
The practical application of bracket processed.It is otherwise noted that individually constructing bracket using 3D printing technique, the precision of printing is higher,
Print speed will be slower, and the print time is longer, has the porous support materials of microcellular structure non-so as to cause 3D printing building
It is often time-consuming.
Emulsion template method is a kind of effective ways of the building with microcellular structure porous support using lotion as template, and
Easily bracket microcellular structure can be regulated and controled by type, the shapes and sizes of change emulsion template.Especially with solid
Lotion, that is, pickering emulsion of the body particle as emulsifier makes since solids are almost irreversible in the absorption of oil-water interfaces
Pickering emulsion is highly stable, can effectively construct the timbering material of setting microcellular structure, thus deep by functional support material
The concern of field researcher.Therefore, emulsion template method is introduced into 3D printing technique, in the macropore bracket of 3D printing
Introduce microcellular structure, so as to it is convenient, efficiently prepare the multi-stage porous timbering material with micropore and macroporous structure.Currently,
3D printing lotion building multi-stage porous bracket is often related to UV photocuring lotion continuous phase and carrys out fixed form, and prepared bracket is related to
The biology Incompatible Substance residue problem such as photoinitiator, monomer or crosslinking agent, the bracket for limiting building are raw in organizational project etc.
Application in object medical domain.In addition, based on 3D printing emulsion template and not being related to UV photocuring lotion continuous phase, effectively, just
Prompt, controllable building has magnetic thermal response-type shape memory magnetic nano-particle/BSMPs combined multi-stage hole biological support, and inquires into
It, in the application of the fields of biomedicine such as minimally invasive implantation, does not up to the present there is corresponding report also as tissue engineering bracket.
Summary of the invention
In order to overcome the shortcomings and deficiencies of the prior art described above, it is beaten the primary purpose of the present invention is that providing one kind based on 3D
Print the preparation method of the nano combined biological support of magnetic thermal response-type shape memory multi-stage porous of lotion building.Preparation method of the present invention
Process conditions are mild, operation is simple, lower to equipment requirement, easy to industrialized production.
Another object of the present invention is to provide a kind of magnetic heat based on the building of 3D printing lotion that the above method is prepared
The nano combined biological support of response type shape memory multi-stage porous.Timbering material of the present invention not only possess good biocompatibility,
Biodegradability, controllable magnetic thermal response-type shape memory, and there is hierarchical porous structure.
Still a further object of the present invention is to provide the above-mentioned magnetic thermal response-type shape memory multistage based on the building of 3D printing lotion
Application of the nano combined biological support in hole in field of biomedicine is applied to tissue repair especially as tissue engineering bracket
Etc. fields of biomedicine have good application potential.
The purpose of the present invention is realized by following proposal:
A kind of system of the nano combined biological support of magnetic thermal response-type shape memory multi-stage porous based on the building of 3D printing lotion
Preparation Method, specifically includes the following steps:
(1) hydrophobic change is carried out to magnetic inorganic nano corpuscle using low molecular weight band carboxyl end group polylactic acid (PLLA-COOH)
Property, obtain hydrophobically modified magnetic inorganic nano corpuscle；
(2) hydrophobically modified magnetic inorganic nano corpuscle, BSMPs, rheological agent are added in organic solvent and form oily phase；Steaming
Distilled water is added in oily phase, and mixing and emulsifying obtains the sticky pickering emulsion of water-in-oil type；
(3) using the sticky pickering emulsion of water-in-oil type as ink, three-dimensional porous lotion branch is obtained using extruded type 3D printing
Frame, it is dry, obtain the nano combined biological support of magnetic thermal response-type shape memory multi-stage porous constructed based on 3D printing lotion.
In the oil phase, quality volume fraction of the BSMPs in oily phase is preferably 4-16w/v%.
In the oil phase, quality volume fraction of the hydrophobically modified magnetic inorganic nano corpuscle in oily phase is preferably 2.5-
10w/v%.
In the oil phase, quality volume fraction of the rheological agent in oily phase is preferably 0.5-4w/v%.
The volume ratio of the water and oily phase is 1:2-3:1.
The mass ratio of preparation method of the present invention, PLLA-COOH and magnetic inorganic nano corpuscle used is preferably 1:1-1:4.
Preparation method of the present invention, the magnetic inorganic nano corpuscle can be Fe3O4Nanoparticle, Fe2O3In nanoparticle
At least one.The partial size of the magnetic inorganic nano corpuscle is preferably 10-60nm.
Preparation method of the present invention, the molecular weight of the PLLA-COOH are preferably 5 × 102-1×104G/mol, more preferably
1.5×103g/mol。
Preparation method of the present invention, the BSMPs are the biodegradable rouge of the synthesis with thermal shape memory effect
Fat adoption ester, including it is polylactic acid-carbonate copolymer, poly lactic-co-glycolic acid-carbonate copolymer, poly-
At least one of lactic acid-caprol acton-carbonate copolymer etc..The molecular weight of the BSMPs is preferably 5 × 103-
1.5×105g/mol。
Preparation method of the present invention, the rheological agent be hydrophobicity rheological agent, be mainly used for adjust lotion viscosity and
Rheological characteristic improves lotion printability, preferably at least one of hydrophobic nano-silica, ethyl cellulose etc..
In step (1), the progress hydrophobically modified is specially by low molecular weight band carboxyl end group polylactic acid, magnetic inorganic nanometer
Particle is scattered in solvent respectively, is uniformly mixed, is dried and removed solvent, be heat-treated and obtain under inert atmosphere.
Further, the heat treatment preferably calcines 5-48h at 180-210 DEG C, more preferably calcines at 200 DEG C
6-30h。
Further, described be uniformly mixed can pass through ultrasound or stirring is realized.
Further, the solvent can be the organic solvents such as methylene chloride.
Further, the inert atmosphere can be nitrogen etc..
Further, the dispersion carries out preferably in ice-water bath.
In step (2), the preparation process of the oil phase carries out preferably in ice-water bath and under ultrasonication.
In step (2), the organic solvent is low boiling point high volatile solvent, preferably methylene chloride.
In step (2), the mixing and emulsifying can be by vortex mixer in 800-3500r/min vortex oscillation 2-
30min is realized.
In step (3), the process conditions that three-dimensional porous lotion bracket is obtained using extruded type 3D printing are as follows: squeeze gas
Pressure is 0.01-0.2MPa；The internal diameter of syringe needle is 160-1120 μm；Print speed is 2-50mm/s.
In step (3), the drying can be by drying at room temperature 28-70h, or is freeze-dried 8-20h, at preferably -50 DEG C
It is freeze-dried 8-20h.
In preparation method of the present invention, hydrophobically modified is carried out to magnetic inorganic nano corpuscle using PLLA-COOH, then added
Enter in oily phase, both realized the stable dispersion of magnetic inorganic nano corpuscle, while playing particle emulsifier in emulsion preparation process
Effect, realize the excellent stability of lotion.Meanwhile hydrophobically modified magnetic inorganic nano corpuscle is doped to BSMPs backing substrate
In, the mechanical property of bracket can also be improved, recovery of shape stress is increased, shape memory controllability etc. is promoted, so that structure
The compound support frame material built has good application prospect in fields of biomedicine such as field of tissue engineering technology.
The method of the present invention preparation condition is mild, and operation is simple, reproducible, lower to equipment requirement, is able to satisfy branch
Frame personalization building.
The magnetic thermal response-type shape memory multi-stage porous nanometer based on the building of 3D printing lotion that the method for the present invention is prepared
Compound bio bracket is made of multiple dimensioned hole, including controllable connection macropore (having a size of 200-2500 μm) and micropore (1-100
μm) hierarchical porous structure that coexists, porosity 60-97%；It is rung with excellent biocompatibility, biodegradability, magnetic heat
The multi-functional property such as shape-memory properties is answered to be applied to suitable for field of biomedicine especially as tissue engineering bracket
The fields of biomedicine such as tissue repair have good application potential.
The present invention compared with the existing technology, have the following advantages and the utility model has the advantages that
(1) the present invention is based on 3D printing pickering emulsions to construct the nano combined biology of magnetic thermal response-type shape memory multi-stage porous
Bracket, it is highly effective, easily introduce microcellular structure in the macropore of 3D printing, can quickly, it is a large amount of, effectively obtain multistage
The bionical shape memory biological support in hole.Preparation process condition is mild, operation is simple, reproducible, high production efficiency, to setting
It is standby to require lower, raw material sources to enrich, be suitable for industrialized production.
(2) preparation condition of the present invention is controllable, can easily be regulated and controled by changing condition, 3D printing parameter prepared by lotion
Pore structure, performance and the shape of bracket realize that the bracket of design construction is matched with defective tissue properity, shape；Pass through tune
The amount of type, composition ratio and the molecular weight and magnetic inorganic nano corpuscle that save biodegradable aliphatic polyester controls
Shape-memory properties parameter (such as recovery of shape temperature, recovery of shape power), the mechanical strength, biodegradation rate of material.System
Standby controllability is convenient for meeting requirement of the practical application for bracket shape, structure and performance.
(3) present invention uses the surface PLLA-COOH modified magnetic inorganic nano-particle, modified on the one hand to make magnetic inorganic
Nanoparticle hydrophobicity increases, and can be used as particle emulsifier and stablizes water-in-oil type pickering emulsion, the lotion of preparation is very steady
It is fixed, be conducive to the formation of expected porous structure.It is modified on the other hand to make magnetic inorganic nano corpuscle and biodegradable fat
Adoption ester has good compatibility and dispersibility, enables magnetic inorganic nano corpuscle fine dispersion in nano-composite scaffolds material
In material.Magnetic inorganic nano corpuscle not only acts as the effect of magnetic thermal transition in nano-composite scaffolds material, also plays particle enhancing
Effect improves mechanical strength, the recovery of shape stress of shape memory biodegradable aliphatic polyester, favorably to a certain extent
Accelerate in bracket shape memory and resume speed.In addition used magnetic inorganic nano-particle has developability, is conducive to bracket plant
Enter and be marked in vivo, is convenient for implant surgery and postoperative inspection.
(4) the magnetic nano combined biological support of thermal response-type shape memory multi-stage porous constructed by the present invention in alternating magnetic field and
Heating under two kinds of inductive conditions has good shape memory function.In particular with magnetic inorganic nano corpuscle, can pass through
The generation magnetothermal effect of externally-applied magnetic field carrys out the contactless initiation shape memory biodegradable aliphatic polyester of remote excitation and occurs
Recovery of shape, convenient operation and control are heated more evenly, and thermal conversion efficiency is high, can effectively realize change in shape and recovery, be conducive to
Medically many tissue sites that is difficult to directly heat or not directly heat use.In addition currently preferred shape memory is raw
Biodegradable aliphatic polyester recovery of shape temperature is adjusted near body temperature, thus the transfer of shapes temperature of the biological support constructed
It spends controllable near body temperature, realizes that its shape-memory properties can be activated near body temperature, do not need excessively high outer
Boundary's heat, so that the driving of recovery of shape is easy to accomplish, it is convenient to realize shape memory function in vivo, make it in organizational project etc.
Field of biomedicine preferably plays a role.
(5) present invention constructs the nano combined biological support system of magnetic thermal response-type shape memory multi-stage porous using 3D printing lotion
During standby, it is not related to the bad condition that high temperature, ultraviolet etc. easily cause drug failure, thus can be when prepared by bracket, directly
Drug is loaded, makes bracket that can more preferably play its effect implanting.
(6) the nano combined biological support of shape memory multi-stage porous not only may be implemented in the bracket construction method that the present invention uses
Personalized customization, and the biological support constructed also has connection macropore and micropore and the hierarchical porous structure deposited, higher hole
Gap rate, good biocompatibility, the hot shape-memory properties of adjustable magnetic are loaded and are released with biodegradability, excellent drug
The functional characteristics such as putting property.Prepared biological support can not only play bionical when the fields of biomedicine such as organizational project are applied
Function, and minimally invasive implantation, non-contact remote drive-type recovery of shape may be implemented, second operation can also be avoided, thus side
Just the pain and medical expense of the implementation, mitigation patient performed the operation.
Detailed description of the invention
Fig. 1 is the digital photograph of pickering emulsion prepared by embodiment 1.
Fig. 2 is the 1 magnetic thermal response of digital photograph (left figure) and embodiment for the three-dimensional porous lotion bracket that embodiment 1 prints
The digital photograph (right figure) of the nano combined biological support of type shape memory multi-stage porous.
Fig. 3 is the scanning electricity in 1 magnetic thermal response-type shape memory multi-stage porous nano combined biological support lines section of embodiment
Mirror photo.
Fig. 4 is that the differential scanning calorimetry of the 1 nano combined biological support of magnetic thermal response-type shape memory multi-stage porous of embodiment is bent
Line.
Specific embodiment
Below with reference to embodiment, the present invention is described in further detail, and embodiments of the present invention are not limited thereto.
Material involved in the following example can be obtained from commercial channel.Dosage of each component in terms of mass parts, parts by volume,
g、mL。
Embodiment 1
(1) hydrophobically modified of ferriferrous oxide nano-particle: by 2 mass parts ferriferrous oxide nano-particles in ice-water bath
It is scattered in 30 parts by volume methylene chloride, adds 20 parts by volume PLLA-COOH dichloromethane solutions (containing 2 mass parts PLLA-
COOH, molecular weight 1.5 × 103G/mol it) mixes, ultrasound is fully dispersed to be uniformly mixed, and drying at room temperature removes solvent, then will do
Dry mixture is placed in 200 DEG C of heat treatments in the tube furnace of nitrogen atmosphere and for 24 hours, obtains hydrophobically modified ferriferrous oxide nano-particle.
(2) it the preparation of the sticky pickering emulsion of water-in-oil type: in ice-water bath, was prepared and is obtained by ultrasonication 30 minutes
3 parts by volume methylene chloride suspension, i.e., oily phase, wherein polylactic acid-carbonate copolymer (molecular weight is 5 ×
104G/mol, wherein lactic acid, trimethylene carbonate molar ratio be 70:30), it is improved ferroferric oxide nanoparticle, hydrophobic
The quality volume fraction of nano silica is 7w/v%, 5w/v%, 2w/v%；Oily phase is added portionwise in 9 parts by volume distilled water
In, emulsification 9min is vibrated in 3000r/min through vortex mixer after mixing, obtains the sticky pickering emulsion of water-in-oil type；
(3) 3D printing lotion constructs multi-stage porous bracket: the pickering emulsion that step (2) are obtained as ink, match by loading
Have in the extruded type 3D printer syringe of 20G micro needle head, and pressure is used to apply pressure, control to syringe for 0.03MPa air pump
Print speed 20mm/s processed is obtained according to the printing building of preset cuboid (25mm × 25mm × 5mm) stent model motion profile
Three-dimensional porous lotion bracket, then after lotion branch is placed on freeze 6 hours in -18 DEG C of refrigerators, then -50 DEG C of warp are freeze-dried
10h is obtained with the nano combined biological support of magnetic thermal response-type shape memory multi-stage porous.
The present embodiment pickering emulsion obtained, without mobility, illustrates that lotion has higher stickiness when bottle stands upside down
(see Fig. 1), lotion are able to maintain design branch using lotion bracket after extruded type 3D printer the energy smoothly printing and printing of smoothness
The shape (see Fig. 2 left figure) of frame model, the nano combined biological support that lotion bracket obtains after freeze-drying is also able to maintain good
Good printing shape (such as Fig. 2 right figure).The constructed nano combined biological support of magnetic thermal response-type shape memory multi-stage porous has
High porosity (up to 94%) and multiple dimensioned pore structure, i.e., macroporous structure (such as Fig. 2 for being about 1600-2000 μm with aperture
Right figure) be about 10-30 μm with aperture microcellular structure (such as Fig. 3), the glass transition temperature of bracket is 40.9 DEG C (such as Fig. 4), and
And bracket all shows good shape memory function in heating or alternating magnetic field.
Embodiment 2
(1) hydrophobically modified of ferriferrous oxide nano-particle: by 2 mass parts ferriferrous oxide nano-particles in ice-water bath
It is scattered in 30 parts by volume methylene chloride, adds 20 parts by volume PLLA-COOH dichloromethane solutions (containing 2 mass parts PLLA-
COOH, molecular weight 5 × 103G/mol it) mixes, ultrasound is fully dispersed to be uniformly mixed, and drying at room temperature removes solvent, then will dry
Mixture is placed in 200 DEG C of heat treatment 30h in the tube furnace of nitrogen atmosphere, obtains improved ferroferric oxide nanoparticle.
(2) it the preparation of the sticky pickering emulsion of water-in-oil type: in ice-water bath, was prepared and is obtained by ultrasonication 30 minutes
4 parts by volume methylene chloride suspension, i.e., oily phase, wherein polylactic acid-carbonate copolymer (molecular weight 5.3 ×
104G/mol, wherein lactic acid, trimethylene carbonate molar ratio be 80:20), it is improved ferroferric oxide nanoparticle, hydrophobic
The quality volume fraction of nano silica is 9w/v%, 4w/v%, 2w/v%；Oily phase is added portionwise in 8 parts by volume distilled water
In, emulsification 8min is vibrated in 2000r/min through vortex mixer after mixing, obtains the sticky pickering emulsion of water-in-oil type；
(3) 3D printing lotion constructs multi-stage porous bracket: the pickering emulsion that step (2) are obtained as ink, match by loading
Have in the extruded type 3D printer syringe of 20G micro needle head, and pressure is used to apply pressure, control to syringe for 0.02MPa air pump
Print speed 10mm/s processed is obtained according to the printing building of preset cuboid (50mm × 30mm × 7mm) stent model motion profile
Three-dimensional porous lotion bracket is obtained, then lotion branch is placed in liquid nitrogen and is freezed after five minutes, then -50 DEG C of freeze-drying 16h of warp, is obtained
To with the nano combined biological support of magnetic thermal response-type shape memory multi-stage porous.
Embodiment 3
(1) hydrophobically modified of ferric oxide nanoparticles: by 2 mass parts ferric oxide nanoparticles in ice-water bath
It is scattered in 30 parts by volume methylene chloride, adds 20 parts by volume PLLA-COOH dichloromethane solutions (containing 1.5 mass parts PLLA-
COOH, molecular weight 1.5 × 103G/mol it) mixes, ultrasound is fully dispersed to be uniformly mixed, and drying at room temperature removes solvent, then will do
Dry mixture is placed in 200 DEG C of heat treatment 30h in the tube furnace of nitrogen atmosphere, obtains modified ferric oxide nanoparticles.
(2) it the preparation of the sticky pickering emulsion of water-in-oil type: in ice-water bath, was prepared and is obtained by ultrasonication 30 minutes
The methylene chloride suspension of 6 parts by volume is obtained, i.e. oil phase, wherein poly lactic-co-glycolic acid-carbonate copolymer (molecule
Amount is 3 × 104G/mol, wherein lactic acid, hydroxyacetic acid, trimethylene carbonate molar ratio be 80:10:10), modified three oxygen
Change two Fe nanometer particles, the quality volume fraction of dewatering nano silica is 10w/v%, 3w/v%, 2w/v%；By 6 volumes
Part distilled water is added portionwise in oily phase, vibrates emulsification 6min in 2500r/min through vortex mixer after mixing, obtains water-in-oil type
Sticky pickering emulsion；
(3) 3D printing lotion constructs multi-stage porous bracket: the pickering emulsion that step (2) are obtained as ink, match by loading
Have in the extruded type 3D printer syringe of 18G micro needle head, and pressure is used to apply pressure, control to syringe for 0.04MPa air pump
Print speed 15mm/s processed is obtained three-dimensional according to preset round (Φ 30mm × 7mm) stent model motion profile printing building
Porous lotion bracket, then after lotion branch is placed on being freezed 6 hours in -18 DEG C of refrigerators, then -50 DEG C of freeze-drying 15h of warp, it obtains
With the nano combined biological support of magnetic thermal response-type shape memory multi-stage porous.
Embodiment 4
(1) hydrophobically modified of ferric oxide nanoparticles: by 2 mass parts ferric oxide nanoparticles in ice-water bath
It is scattered in 30 parts by volume methylene chloride, adds 20 parts by volume PLLA-COOH dichloromethane solutions (containing 2 mass parts PLLA-
COOH, molecular weight 3 × 103G/mol it) mixes, ultrasound is fully dispersed to be uniformly mixed, and drying at room temperature removes solvent, then will dry
Mixture is placed in 200 DEG C of heat treatments in the tube furnace of nitrogen atmosphere and for 24 hours, obtains modified ferric oxide nanoparticles.
(2) it the preparation of the sticky pickering emulsion of water-in-oil type: in ice-water bath, was prepared and is obtained by ultrasonication 30 minutes
The methylene chloride suspension of 5 parts by volume is obtained, i.e. oil phase, wherein polylactic acid-caprolactone-carbonate copolymer (molecular weight
It is 8 × 104G/mol, wherein lactic acid, caprolactone, trimethylene carbonate molar ratio be 80:10:10), modified three oxidation two
Fe nanometer particles, ethyl cellulose quality volume fraction be 10w/v%, 10w/v%, 2w/v%；8 parts by volume are distilled into moisture
It criticizes and is added in oily phase, vibrate emulsification 4min, the acquisition sticky pik woods of water-in-oil type in 3000r/min through vortex mixer after mixing
Lotion；
(3) 3D printing lotion constructs multi-stage porous bracket: the pickering emulsion that step (2) are obtained as ink, match by loading
Have in the extruded type 3D printer syringe of 21G micro needle head, and pressure is used to apply pressure, control to syringe for 0.03MPa air pump
Print speed 10mm/s processed is obtained three-dimensional according to preset round (Φ 30mm × 5mm) stent model motion profile printing building
Porous lotion bracket, then lotion branch is placed in liquid nitrogen and is freezed after five minutes, then -50 DEG C of freeze-drying 15h of warp, had
The nano combined biological support of magnetic thermal response-type shape memory multi-stage porous.
Embodiment 5
(1) hydrophobically modified of ferriferrous oxide nano-particle: by 2 mass parts ferriferrous oxide nano-particles in ice-water bath
It is scattered in 30 parts by volume methylene chloride, adds 20 parts by volume PLLA-COOH dichloromethane solutions (containing 2 mass parts PLLA-
COOH, molecular weight 1.5 × 103G/mol it) mixes, ultrasound is fully dispersed to be uniformly mixed, and drying at room temperature removes solvent, then will do
Dry mixture is placed in 200 DEG C of heat treatments in the tube furnace of nitrogen atmosphere and for 24 hours, obtains improved ferroferric oxide nanoparticle.
(2) it the preparation of the sticky pickering emulsion of water-in-oil type: in ice-water bath, was prepared and is obtained by ultrasonication 30 minutes
The methylene chloride suspension of 6 parts by volume is obtained, i.e. oil phase, wherein poly lactic-co-glycolic acid-carbonate copolymer (molecule
Amount is 3 × 104G/mol, wherein lactic acid, hydroxyacetic acid, trimethylene carbonate molar ratio be 80:10:10), polylactic acid-three
(molecular weight is 8 × 10 to methyl carbonic acid ester copolymer4G/mol, wherein lactic acid, trimethylene carbonate molar ratio be 85:
15), improved ferroferric oxide nanoparticle, dewatering nano silica quality volume fraction be 4w/v%, 6w/v%, 6w/
V%, 1.5w/v%；6 parts by volume distilled water are added portionwise in oily phase, are shaken through vortex mixer in 2000r/min after mixing
Emulsification 6min is swung, the sticky pickering emulsion of water-in-oil type is obtained；
(3) 3D printing lotion constructs multi-stage porous bracket: the pickering emulsion that step (2) are obtained as ink, match by loading
Have in the extruded type 3D printer syringe of 21G micro needle head, and pressure is used to apply pressure, control to syringe for 0.04MPa air pump
Print speed 20mm/s processed is obtained according to the printing building of preset cuboid (30mm × 30mm × 7mm) stent model motion profile
Three-dimensional porous lotion bracket is obtained, then lotion branch is placed on drying at room temperature 50h, is obtained multistage with magnetic thermal response-type shape memory
The nano combined biological support in hole.
Embodiment 6
(1) hydrophobically modified of ferriferrous oxide nano-particle: by 2 mass parts ferriferrous oxide nano-particles in ice-water bath
It is scattered in 30 parts by volume methylene chloride, adds 20 parts by volume PLLA-COOH dichloromethane solutions (containing 2 mass parts PLLA-
COOH, molecular weight 1.5 × 103G/mol it) mixes, ultrasound is fully dispersed to be uniformly mixed, and drying at room temperature removes solvent, then will do
Dry mixture is placed in 200 DEG C of heat treatments in the tube furnace of nitrogen atmosphere and for 24 hours, obtains improved ferroferric oxide nanoparticle.
(2) it the preparation of the sticky pickering emulsion of water-in-oil type: in ice-water bath, was prepared and is obtained by ultrasonication 30 minutes
6 parts by volume methylene chloride suspension, i.e., oily phase, wherein polylactic acid-carbonate copolymer (molecular weight is 8 ×
104G/mol, wherein lactic acid, trimethylene carbonate molar ratio be 75:25), it is improved ferroferric oxide nanoparticle, hydrophobic
Nano silica, the quality volume fraction of ethyl cellulose are 12w/v%, 7w/v%, 1.5w/v%, 2w/v%；By 6 volumes
Part distilled water is added portionwise in oily phase, vibrates emulsification 9min in 3500r/min through vortex mixer after mixing, obtains water-in-oil type
Sticky pickering emulsion；
(3) 3D printing lotion constructs multi-stage porous bracket: the pickering emulsion that step (2) are obtained as ink, match by loading
Have in the extruded type 3D printer syringe of 20G micro needle head, and pressure is used to apply pressure, control to syringe for 0.04MPa air pump
Print speed 20mm/s processed is obtained according to the printing building of preset cuboid (30mm × 30mm × 7mm) stent model motion profile
Three-dimensional porous lotion bracket, then after lotion branch is placed on freeze 6 hours in -18 DEG C of refrigerators, then -50 DEG C of warp are freeze-dried
15h is obtained with the nano combined biological support of magnetic thermal response-type shape memory multi-stage porous.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (10)
1. a kind of preparation of the nano combined biological support of magnetic thermal response-type shape memory multi-stage porous based on the building of 3D printing lotion
Method, it is characterised in that specifically includes the following steps:
(1) hydrophobically modified is carried out to magnetic inorganic nano corpuscle using low molecular weight band carboxyl end group polylactic acid, obtains hydrophobically modified
Magnetic inorganic nano corpuscle；
(2) hydrophobically modified magnetic inorganic nano corpuscle, BSMPs, rheological agent are added in organic solvent and form oily phase；Distilled water
It is added in oily phase, mixing and emulsifying obtains the sticky pickering emulsion of water-in-oil type；
(3) using the sticky pickering emulsion of water-in-oil type as ink, three-dimensional porous lotion bracket is obtained using extruded type 3D printing, is done
It is dry, obtain the nano combined biological support of magnetic thermal response-type shape memory multi-stage porous constructed based on 3D printing lotion.
2. the magnetic thermal response-type shape memory multi-stage porous nanometer according to claim 1 based on the building of 3D printing lotion is multiple
Close the preparation method of biological support, it is characterised in that: in the oil phase, quality volume fraction of the BSMPs in oily phase is 4-
16w/v%；Quality volume fraction of the hydrophobically modified magnetic inorganic nano corpuscle in oily phase is 2.5-10w/v%；Rheological agent exists
Quality volume fraction in oily phase is 0.5-4w/v%.
3. the magnetic thermal response-type shape memory multi-stage porous nanometer according to claim 1 based on the building of 3D printing lotion is multiple
Close the preparation method of biological support, it is characterised in that: the volume ratio of the water and oily phase is 1:2-3:1；Band carboxyl end group used is poly-
The mass ratio of lactic acid and magnetic inorganic nano corpuscle is 1:1-1:4.
4. the magnetic thermal response-type shape memory multi-stage porous nanometer according to claim 1 based on the building of 3D printing lotion is multiple
Close the preparation method of biological support, it is characterised in that: the magnetic inorganic nano corpuscle includes Fe3O4Nanoparticle, Fe2O3
At least one of nanoparticle；The BSMPs includes polylactic acid-carbonate copolymer, polylactic acid-glycolic base second
At least one of acid-carbonate copolymer, polylactic acid-caprolactone-carbonate copolymer；The rheology
Agent is at least one of hydrophobicity rheological agent, including hydrophobic nano-silica, ethyl cellulose.
5. the magnetic thermal response-type shape memory multi-stage porous nanometer according to claim 1 based on the building of 3D printing lotion is multiple
Close the preparation method of biological support, it is characterised in that: the molecular weight with carboxyl end group polylactic acid is 5 × 102-1×104g/
mol；The molecular weight of the BSMPs is 5 × 103-1.5×105g/mol。
6. the magnetic thermal response-type shape memory multi-stage porous nanometer according to claim 1 based on the building of 3D printing lotion is multiple
Close the preparation method of biological support, it is characterised in that: in step (1), the progress hydrophobically modified is specially by low molecular weight band
Carboxyl end group polylactic acid, magnetic inorganic nano corpuscle are scattered in solvent respectively, are uniformly mixed, are dried and removed solvent, inert atmosphere
Lower heat treatment obtains.
7. the magnetic thermal response-type shape memory multi-stage porous nanometer according to claim 6 based on the building of 3D printing lotion is multiple
Close the preparation method of biological support, it is characterised in that: the heat treatment is to calcine 5-48h at 180-210 DEG C.
8. the magnetic thermal response-type shape memory multi-stage porous nanometer according to claim 1 based on the building of 3D printing lotion is multiple
Close the preparation method of biological support, it is characterised in that: described that three-dimensional porous cream is obtained using extruded type 3D printing in step (3)
The process conditions of liquid bracket are as follows: extruding air pressure is 0.01-0.2MPa；The internal diameter of syringe needle is 160-1120 μm；Print speed is 2-
50mm/s。
9. a kind of nano combined biological support of magnetic thermal response-type shape memory multi-stage porous based on the building of 3D printing lotion, feature
It is that preparation method according to claim 1-8 obtains.
10. the magnetic thermal response-type shape memory multi-stage porous nano combined life as claimed in claim 9 based on the building of 3D printing lotion
Application of the object bracket in field of biomedicine.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101942191A (en) * | 2010-09-15 | 2011-01-12 | 华东师范大学 | Magnetic nano compound shape memory material and preparation method thereof |
| CN102675516A (en) * | 2012-05-16 | 2012-09-19 | 华南理工大学 | Intercommunicated porous magnetic polymer microsphere and preparation method thereof |
| CN105602213A (en) * | 2015-12-29 | 2016-05-25 | 哈尔滨工业大学 | Preparation of shape memory micro-nano composite material and application of shape memory micro-nano composite material in 4D (four-dimensional) printing |
| CN105944144A (en) * | 2016-04-29 | 2016-09-21 | 哈尔滨工业大学 | Bone tissue repair material based on shape memory composite material as well as preparation method and application method of bone tissue repair structure |
| CN106633721A (en) * | 2016-11-18 | 2017-05-10 | 中国科学院深圳先进技术研究院 | Self-repair material and article with shape memory effect and preparation method thereof |
| CN107115570A (en) * | 2017-03-30 | 2017-09-01 | 华南理工大学 | A kind of nano combined biological support of multistage controllable through-hole structure and preparation method and application |
| CN109010925A (en) * | 2018-09-07 | 2018-12-18 | 王翀 | A kind of preparation method of photo-thermal chemotherapy bone renovating material and tissue engineering bracket |
-
2019
- 2019-02-22 CN CN201910132509.4A patent/CN109771700B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101942191A (en) * | 2010-09-15 | 2011-01-12 | 华东师范大学 | Magnetic nano compound shape memory material and preparation method thereof |
| CN102675516A (en) * | 2012-05-16 | 2012-09-19 | 华南理工大学 | Intercommunicated porous magnetic polymer microsphere and preparation method thereof |
| CN105602213A (en) * | 2015-12-29 | 2016-05-25 | 哈尔滨工业大学 | Preparation of shape memory micro-nano composite material and application of shape memory micro-nano composite material in 4D (four-dimensional) printing |
| CN105944144A (en) * | 2016-04-29 | 2016-09-21 | 哈尔滨工业大学 | Bone tissue repair material based on shape memory composite material as well as preparation method and application method of bone tissue repair structure |
| CN106633721A (en) * | 2016-11-18 | 2017-05-10 | 中国科学院深圳先进技术研究院 | Self-repair material and article with shape memory effect and preparation method thereof |
| CN107115570A (en) * | 2017-03-30 | 2017-09-01 | 华南理工大学 | A kind of nano combined biological support of multistage controllable through-hole structure and preparation method and application |
| CN109010925A (en) * | 2018-09-07 | 2018-12-18 | 王翀 | A kind of preparation method of photo-thermal chemotherapy bone renovating material and tissue engineering bracket |
Non-Patent Citations (1)
| Title |
|---|
| 胡洋: "基于Pickering乳液模板法制备生物相容有机/无机纳米复合多孔支架", 《中国博士学位论文全文数据库 医药卫生科技辑》 * |
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