CN109701084A - A kind of compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters and preparation method thereof - Google Patents
A kind of compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to biomedical material technology, a kind of compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters and preparation method thereof is disclosed.The method of the present invention is prepared to obtain oily phase through ultrasonication the following steps are included: by Biodegradable shape-memory polyester, hydroxyapatite nano particle, rheology modifier addition organic solvent；It adds water in oily phase, forms water-in-oil type High Internal Phase Emulsion through emulsification；Using High Internal Phase Emulsion as ink, three-dimensional porous lotion bracket is obtained using extruded type 3D printing, solvent evaporation obtains biological support；The multiple dimensioned pore structure coexisted in the supporting structure containing controllable micropore and macropore, porosity is higher than 85%, and pore structure is interconnected, with excellent biocompatibility, biodegradability, bioactivity, shape memory effect, drug growth/factor loading and release property, can be applied in medicine controlled releasing field and tissue engineering bracket field.
Description
Technical field
The invention belongs to biomedical material technology, in particular to a kind of shape memory type biologically active nanometer grain
Compound multiple dimensioned hole biological support of son/biodegradable polyesters and preparation method thereof.
Background technique
The damaged bone as caused by a variety of causes such as wound, infection, tumour and birth defect or missing are that Orthopedic Clinical is daily
The treatment problem faced is all needed, thus effectively repairs the research hotspot that impaired or missing bone tissue has become field of biomedicine.
Bone defective locations, i.e. bone tissue engineer method are filled up using the systematism multiporous biological bracket constructed based on Bionic Idea, are one
Kind very ideal bone structure and function repair mode.In bone tissue engineer, multiporous biological bracket not only provide cell adhesion,
The class extracellular matrix environment of growth, proliferation and differentiation, and object is played to bone tissue reparation as interim three-dimensional function template
Manage supporting role.Therefore, the building of suitable configurations and the multiporous biological bracket of performance is that bone tissue engineer technology is carried out
One of key link.Ideal osseous tissue engineering stephanoporate biologic bracket material needs to have some specific functional characters, such as: 1.
Good biocompatibility, surface bioactive, in favor of the adherency of cell, growth, proliferation and differentiation；2. suitable biology can
Degradability, timbering material is gradually degraded in new bone tissue is formed, and does not influence the structure and function of new bone tissue；3. certain power
Intensity is learned, is able to maintain supporting structure stability and integrality, within a certain period of time after stenter to implant so that new bone tissue is long
At preset shape；4. excellent anti-inflammatory, antibacterial drug, active factors load and release performance, to avoid scorching in stenter to implant body
The problem of disease and bacterium infection, while being conducive to cell differentiation.It is worth noting that realize excellent bionic function, bone tissue is replaced
It is extremely important for the pore structure of multiporous biological bracket.Connectivity between high porosity and good hole, is on the one hand conducive to cytotrophy
On the other hand ingredient conveying and metabolite excretion are conducive to implantation adherency, growth and the migration of cell.Different pore size size hair
Different important function are waved, are increased as microcellular structure (a few to tens of microns) is conducive to cell adhesion, Cellular Signaling Transduction Mediated, cell
It grows, several hundred microns of hole (macroporous structure) is conducive to cell migration, extracellular matrix aggregation and organizes the formation of.In addition bone tissue work
The shape of journey multiporous biological bracket needs to match with the shape of bone injury or deleted areas with size, in order to complete correction damage
Wound or missing bone tissue space.Thus to realize that excellent bionic tone tissue repair function, multiporous biological bracket should also have height
The multiple dimensioned pore structure of the connection of porosity, and with the matched shape in bone defect position.
There are many typical preparation methods of bone tissue engineering scaffold, including solution casting/particle leaching method, gas at present
Foaming, mutually separation/freeze-drying, gas foaming method, method of electrostatic spinning, (internal phase volume is greater than High Internal Phase Emulsion template
74% lotion is as template) etc..However these methods want real biotic bone tissue engineering stent pore structure and acquire a certain degree of difficulty,
Such as poor connectivity between solution casting/particle leaching method building bracket holes, it is unfavorable for cell migration, while being easy residual pore
Agent reduces the biocompatibility of bracket；Phase separation/freeze-drying, method of electrostatic spinning are difficult to control microcellular structure hole in bracket
Size；The bracket of gas foaming method building has hole-closing structure mostly, is unfavorable for cell growth and migration；High Internal Phase Emulsion template
Method is usually used in the building of microcellular structure porous support, is difficult to obtain macroporous structure.In addition the above method is also difficult to realize with hole
The forming of the scale pore structure of gap gradient, it is difficult to realize the individual character manufacturing of multiporous biological bracket.Thus exploitation is effectively constructed
The method of biotic bone tissue engineering multiporous biological timbering material is necessary.
The diversification that 3D printing technique be able to meet multiporous biological internal stent pore structure requires.It is soft that it mainly passes through CAD
The threedimensional model of part or simulated image data building Metal pylon, and then be under the control of the computer successively piled into biomaterial
3D solid bracket.3D printing technique can be according to actual demand between connectivity multiporous biological bracket shape, aperture size, hole
Etc. being accurately controlled.Therefore it can get the multiporous biological branch of allied organization's micro-structure and organ shape using 3D printing technique
Frame, to manufactured according to actual demand to meet the personalized customization of bracket.However using 3D printing technique, there is printing
Precision (resolution ratio) is higher, and print speed will be slower, and the print time is longer, has microcellular structure so as to cause 3D printing building
Porous support materials it is very time-consuming.To solve this problem, High Internal Phase Emulsion template can be introduced into 3D printing technique, thus
Microcellular structure is introduced in the macropore bracket of 3D printing, the multiple dimensioned hole supporting structure that micropore macropore can be obtained in this way and deposited,
Bracket building speed can be greatly promoted again.Sears etc. (Macromol.Rapid Commun., 2016,37:1369-1374) knot
Light combination solidification 3D printing technique successfully provides efficient production tool by UV photocuring emulsion template with High Internal Phase Emulsion template
There is the multiple dimensioned polymer support of microcellular structure, but the above method is only used for photo curable material and constructs multiple dimensioned hole branch
Frame, and prepared bracket is related to the biological Incompatible Substance residue problem such as photoinitiator, monomer or crosslinking agent, limits building
Bracket bone tissue engineer etc. biomedicine in application.Chinese invention patent 201710203126.2 is steady by nanoparticle
Fixed High Internal Phase Emulsion template is introduced into 3D printing technique, is evaporated fixed emulsion template by solvent, is successfully prepared titanium dioxide
The nano combined biological support of silicon/biodegradable polyesters hierarchical porous structure.It will be appreciated that the main nothing of biological bone
Machine ingredient is hydroxyapatite, for good bionic tone tissue ingredient, obtains excellent biological osteogenic activity, building it is artificial
Inorganic constituents first choice is hydroxyapatite in bone multiporous biological bracket.Raising with clinical treatment requirement and treatment concept simultaneously
Development, it is expected that reduce the difficulty of operation over the course for the treatment of while mitigating the pain of patient, can by minimally invasive implantation come
Implement operation, this requires bone tissue multiporous biological bracket should also have specific function property, i.e., shape-memory properties (bracket with
Lesser volume is implanted by minimally invasive, then under certain stimulation shape memory restore its it is original unfold shape, thus with lacking
Position matching is damaged, to play effect).However multi-stage porous artificial bone scaffold constructed by Chinese invention patent 201710203126.2
It does not include hydroxyapatite, while the timbering material obtained is not directed to the functionalization i.e. shape-memory properties of material, it is difficult to meet
Bone tissue engineer practical application request.Therefore exploitation is highly desirable based on 3D printing High Internal Phase Emulsion, and convenient effective building contains
The multiple dimensioned hole bone tissue biological support of the shape memory type individual character manufacturing of hydroxyapatite, to realize excellent bionic function,
Defective bone tissue profile is matched, and meets minimally invasive implantation.
Summary of the invention
In order to overcome the above-mentioned timbering material in the prior art based on 3D printing High Internal Phase Emulsion not have hydroxyapatite
And the shortcomings that shape memory type and insufficient, the primary purpose of the present invention is that providing a kind of shape memory type biologically active nanometer grain
The preparation method of the compound multiple dimensioned hole biological support of son/biodegradable polyesters.
Another object of the present invention is to provide shape memory type active nanoparticles/life that the above method is prepared
The compound multiple dimensioned hole biological support of Biodegradable polyester.It include hydroxyapatite nano particle, biology in timbering material of the present invention
Degradable shape memory polyester.
Still a further object of the present invention is to provide a kind of above-mentioned shape memory type active nanoparticles/biodegradable poly
Application of the compound multiple dimensioned hole biological support of ester in medicine controlled releasing field and tissue engineering bracket field, holds especially as non-
The application of the bone tissue engineering scaffold of weight.
The purpose of the present invention is realized by following proposal:
A kind of system of the compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters
Preparation Method, comprising the following steps:
Biodegradable shape-memory polyester, hydroxyapatite nano particle, rheology modifier are added in organic solvent,
It prepares to obtain oily phase through ultrasonication；It adds water in oily phase, forms water-in-oil type High Internal Phase Emulsion through emulsification；It will be mutually newborn in height
Liquid obtains three-dimensional porous lotion bracket as ink, using extruded type 3D printing, and it is living to obtain shape memory type biology for solvent evaporation
The property compound multiple dimensioned hole biological support of nanoparticle/biodegradable polyesters.
The oil mutually preferably configures in ice-water bath.
In preparation method of the present invention, the Biodegradable shape-memory polyester has thermal shape memory effect, can
For the degradable shape memory polyester of artificial synthesising biological, polylactic acid-trimethylene carbonate copolymer, polylactic acid-is preferably included
At least one of hydroxyacetic acid-trimethylene carbonate copolymer, polylactic acid-caprolactone-trimethylene carbonate copolymer.
In preparation method of the present invention, the molecular weight of the Biodegradable shape-memory polyester is preferably 1 × 104-1.5
×105g/mol。
In preparation method of the present invention, the hydroxyapatite nano particle is hydrophobically modified hydroxyapatite nano particle,
By by the low molecular weight carboxyl end group polylactic acid of 1-3 mass parts hydroxyapatite and 0.5-2.5 mass parts in organic solvent system
In be uniformly mixed, after solvent flashing, in 180-210 DEG C of calcining 8-36h, obtain hydrophobically modified hydroxyapatite nano particle.
Hydroxyapatite used and the mass ratio of low molecular weight carboxyl end group polylactic acid are preferably 1:1.
The molecular weight of the low molecular weight carboxyl end group polylactic acid (PLLA) is preferably 1500g/mol.
The calcining is preferably calcined for 24 hours at 200 DEG C.
The organic solvent can be methylene chloride etc..
Described be uniformly mixed can be mixed by ultrasonication.
The solvent flashing can carry out at room temperature.
The hydrophobically modified hydroxyapatite nano particle that the present invention uses can be used as water-in-oil emulsion by hydrophobically modified
Emulsifier, and be conducive to it and disperse in shape memory polyester, realize excellent dispersion effect.
In preparation method of the present invention, the hydroxyapatite nano particle pattern is rodlike, a length of 15-80nm of short axle, long
Axial length is 60-250nm.The present invention has both particle cream using hydrophobically modified hydroxyapatite nano particle in emulsion preparation process
The effect of agent, stable emulsion.
In preparation method of the present invention, the rheology modifier preferably includes hydrophobic nano-silica and ethyl cellulose
At least one of element.Rheology modifier of the invention is the hydrophobicity rheology modifier with thickening properties, for adjusting cream
The viscosity and rheological characteristic of liquid improve lotion printability.
In preparation method of the present invention, quality volume fraction of the Biodegradable shape-memory polyester in oily phase
2w/v%-16w/v%, preferably 3w/v%-12w/v%.
In preparation method of the present invention, quality volume fraction of the hydroxyapatite nano particle in oily phase is 1.5w/
V%-15w/v%；Preferably 2w/v%-12.5w/v%.
In preparation method of the present invention, quality volume fraction of the rheology modifier in oily phase is preferably 0.5w/v%-
3.5w/v%.
In preparation method of the present invention, the organic solvent is preferably low boiling point high volatile solvent, preferably dichloromethane
Alkane.
In preparation method of the present invention, the emulsification can be by vortex mixer in 800-3000r/min vortex oscillation 3-
20min。
In preparation method of the present invention, in the water-in-oil type High Internal Phase Emulsion, internal phase volume score is preferably 75-85v/
V%.
In preparation method of the present invention, the process conditions of the extruded type 3D printing are as follows: extrusion air pressure is 0.01-0.2MPa,
The internal diameter of syringe needle is 100-1120 μm, print speed 2-60mm/s.
In preparation method of the present invention, drying at room temperature 30-70h, or freeze-drying is can be selected in the mode of the solvent evaporation, excellent
It is selected as in -50 DEG C of freeze-drying 10-20h.
Preparation method of the present invention specifically includes the following steps:
(1) in ice-water bath, Biodegradable shape-memory polyester, hydroxyapatite nano particle, rheology modifier
It is added in organic solvent, configures to obtain oily phase by ultrasonication；
(2) distilled water is added in the oily phase that step (1) obtains, is formed in water-in-oil type height after mixing through emulsification preparation
Phase emulsion；
(3) High Internal Phase Emulsion for obtaining step (2) is packed into the extruded type 3D printer for being furnished with micro needle head as ink
In syringe, and pressure is applied to syringe using air pump, control print speed, printing building obtains three-dimensional porous lotion bracket.
(4) the porous lotion bracket that step (3) obtain is placed to remove organic solvent and water, solvent evaporation obtains shape
The compound multiple dimensioned hole biological support of shape memory-type active nanoparticles/biodegradable polyesters.
Shape note is prepared in the complex technique of preparation method combination 3D printing technique and High Internal Phase Emulsion template of the present invention
Recall the compound multiple dimensioned hole biological support of type active nanoparticles/biodegradable polyesters.Contain in supporting structure of the present invention
The multiple dimensioned pore structure that controllable micropore and macropore coexists, porosity is higher than 85%, and pore structure is interconnected, wherein 3D printing
Technology introduces macropore (200-1000 μm), and pickering emulsion template obtains micropore (1-100 μm)；Hydroxyapatite nano particle edge
It is embedding or be attached to hole wall surface, realize that hole wall surface is coarse；It has adjustable multi-functional property, including excellent bio-compatible
The loading and release property of property, biodegradability, bioactivity, shape memory effect, drug growth/factor.
The compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters of the invention
It can be applied in medicine controlled releasing field and tissue engineering bracket field, answered especially as the bone tissue engineering scaffold of non-bearing
With.
The present invention compared with the existing technology, have the following advantages and the utility model has the advantages that
(1) preparation method of the present invention, can be highly effective, convenient by the way that High Internal Phase Emulsion template is introduced 3D printing technique
Ground introduces microcellular structure in the macropore of 3D printing, thus quickly, largely, effectively obtain multiple dimensioned bionical shape memory biology
Bracket.Whole preparation process mild condition, operation is simple, high production efficiency, lower to equipment requirement, production cost is low,
Suitable for industrialized production, there is biggish application and popularization value.
(2) preparation condition of the present invention is controllable, can by change High Internal Phase Emulsion preparation condition and 3D print parameters just
The pore structure and performance for regulating and controlling bracket promptly realize the bracket of design construction and the matching of actual demand supporting structure performance.It is special
It is not that 3D printing technique has designability, multiporous biological bracket shape can be designed according to actual demand a to realize
Propertyization preparation；Type, composition ratio and molecular weight of polyester etc. is remembered by adjustable shape to control the shape memory of material and turn
Temperature, mechanical strength, biodegradation rate etc..The controllability of preparation is convenient for meeting practical application for bracket shape, structure
With the requirement of performance.
(3) present invention stablizes phase in water-in-oil type height as particle emulsifier using hydrophobicity hydroxyapatite nano particle
The High Internal Phase Emulsion of lotion, preparation is highly stable, and the basic structure of lotion can be maintained in 3D printing and solvent evaporation process,
Be conducive to the formation of porous structure.It is the main inorganic composition of natural bone additionally, due to hydroxyapatite, there is fabulous biology
Activity, osteoconductive can directly form activity with bone tissue and be combined, so that constructed contains hydroxyapatite nano grain
The multiple dimensioned hole biological support of shape memory of son has good osteogenic activity；In addition, hydroxyapatite nano particle is doped to
Shape memory polyester matrix constructs multiple dimensioned hole biological support, additionally it is possible to improve bracket mechanical strength, shape memory controllability, hole
Wall roughness, drug growth/factor loading and release property, so that the biological support of building is in bone tissue engineer field,
There is good application prospect in terms of especially minimally invasive implantation.
(4) the thermal shape memory biology contained in the multiple dimensioned hole biological support of shape memory type constructed by the present invention can
Degradation polyester directly realizes that shape is restored by the entanglement of strand without being chemically and physically crosslinked, to reach shape memory effect
It answers.The transfer of shapes temperature adjustable for the biological support that the present invention constructs simultaneously realizes its shape memory near body temperature
Performance can be activated near body temperature, not need excessively high external heat, so that the driving of recovery of shape is easy to accomplish, thus
Make it that can preferably play a role in fields of biomedicine such as organizational projects.
(5) personalized customization of the multiple dimensioned hole bracket of shape memory type may be implemented in the bracket construction method that the present invention uses
(matched timbering material is constructed according to defective tissue shape and size)；And the multiple dimensioned hole biology branch of shape memory type of building
Frame not only has multiple dimensioned pore structure, high porosity, the pore structure of connection, coarse hole wall, also has biocompatibility, shape
The functional characteristics such as shape memory effect, biodegradability, drug growth/factor loading and release property, such stent applications in
When tissue repair, excellent bionic function can be not only played, but also minimally invasive implantation may be implemented (by reasonably presetting its deflation
Temporary shapes make it easier to be implanted into the patient, then under body temperature or the heat effect of external heat source, are restored to it voluntarily
Original-shape is needed, to play its repair), " from be adapted to " irregular defective tissue shape (can fill automatically and not advise
Tissue defect region then), moreover it is possible to second operation (can be degraded and absorb in vivo, be not required to second operation taking-up) is avoided, both
The implementation of operation is facilitated, and reduces wound, alleviates the pain of patient.
Detailed description of the invention
Fig. 1 is the rheological curve figure of the High Internal Phase Emulsion obtained of embodiment 1.
Fig. 2 is the three-dimensional porous lotion bracket number figure that 1 High Internal Phase Emulsion of embodiment is obtained through extruded type 3D printing.
Fig. 3 is 1 shape memory type active nanoparticles of embodiment/multiple dimensioned biological support of biodegradable polyesters
Number figure.
Fig. 4 is the compound multiple dimensioned hole biology of 1 shape memory type active nanoparticles of embodiment/biodegradable polyesters
Bracket lines cross-sectional scans electron microscope.
Fig. 5 is the compound multiple dimensioned hole biology of 1 shape memory type active nanoparticles of embodiment/biodegradable polyesters
The differential scanning calorimetric curve of bracket.
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.
Hydrophobicity hydroxyapatite used in embodiment is obtained by modified, and specific steps include g, mL: in ice water
Disperse 2 mass parts hydroxyapatites in 30 parts by volume methylene chloride in bath, then with 30 parts by volume low molecular weight carboxyl end groups
It is uniformly mixed under dichloromethane solution (containing 2 mass parts PLLA) ultrasonication of polylactic acid (PLLA, molecular weight 1500g/mol),
And volatilization removes methylene chloride at room temperature, then is placed in 200 DEG C of calcinings in Muffle furnace and the modified hydroxyl of surface hydrophobicity is prepared for 24 hours
Base apatite.
Embodiment 1
(1) in ice-water bath, the methylene chloride suspension for obtaining 4 parts by volume is prepared by ultrasonication 30min, i.e., it is oily
Phase, wherein (molecular weight is 5.2 × 10 to Biodegradable polylactic acids-trimethylene carbonate copolymer4G/mol, wherein lactic acid,
The molar ratio of trimethylene carbonate is 80:20), the quality volume of hydrophobicity hydroxyapatite, hydrophobic nano-silica
Score is 9w/v%, 7.5w/v%, 2w/v%；
(2) 12 parts by volume distilled water are added portionwise in the oily phase that step (1) obtains, are existed after mixing through vortex mixer
3000r/min oscillation emulsification 12min, obtains water-in-oil type High Internal Phase Emulsion；
(3) High Internal Phase Emulsion for obtaining step (2) is packed into the extruded type 3D equipped with 18G micro needle head and beats as ink
It prints in machine needle cylinder, and pressure is used to apply pressure to syringe for 0.05MPa air pump, control print speed 20mm/s, according to default
The printing building of cuboid (30mm × 30mm × 5mm) stent model motion profile obtain three-dimensional porous lotion bracket.
(4) the porous lotion branch that step (3) obtain is placed on after freezing 6h in -18 DEG C of refrigerators, then -50 DEG C of warp freezings are dry
Dry 16h obtains the compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters.
The present embodiment High Internal Phase Emulsion obtained has good 3D printing (shear shinning performance, see Fig. 1) and shape
Shape retention property (see Fig. 2).The shape memory type active nanoparticles of the acquisition/multiple dimensioned biology of biodegradable polyesters
The digital figure of bracket is shown in Fig. 3, and bracket lines cross-sectional scans electron microscope is shown in that Fig. 4, bracket differential scanning calorimetric curve are shown in Fig. 5.By Fig. 3
With Fig. 4 it can be seen that constructed biological support has multiple dimensioned pore structure, including macropore (about 600-750 μm) and micro-
Hole (about 8-50 μm), and biological support shows good shape memory in heating environment, as seen from Figure 5 institute's structure
The biological support transfer of shapes temperature built is 46.7 DEG C.
Embodiment 2
(1) in ice-water bath, the methylene chloride suspension for obtaining 4 parts by volume is prepared by ultrasonication 30min, i.e., it is oily
Phase, wherein (molecular weight is 5 × 10 to Biodegradable polylactic acids-trimethylene carbonate copolymer4G/mol, wherein lactic acid, three
The molar ratio of carbonate is 70:30), the mass body of hydrophobicity hydroxyapatite, hydrophobic nano-silica integrates
Number is 9w/v%, 9w/v%, 1w/v%；
(2) 13 parts by volume distilled water are added portionwise in the oily phase that step (1) obtains, are existed after mixing through vortex mixer
2500r/min oscillation emulsification 15min, obtains water-in-oil type High Internal Phase Emulsion；
(3) High Internal Phase Emulsion for obtaining step (2) is packed into the extruded type 3D equipped with 20G micro needle head and beats as ink
It prints in machine needle cylinder, and pressure is used to apply pressure to syringe for 0.02MPa air pump, control print speed 20mm/s, according to default
The printing building of cylinder (Φ 30mm × 7mm) stent model motion profile obtain three-dimensional porous lotion bracket.
(4) the porous lotion branch that step (3) obtain is placed on after freezing 4min in liquid nitrogen, then -50 DEG C of warp freeze-dryings
16h obtains the compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters.
Embodiment 3
(1) in ice-water bath, the methylene chloride suspension for obtaining 4 parts by volume is prepared by ultrasonication 30min, i.e., it is oily
Phase, wherein (molecular weight is 3 × 10 to Biodegradable polylactic acids-hydroxyacetic acid-trimethylene carbonate copolymer4G/mol,
Middle lactic acid, hydroxyacetic acid, trimethylene carbonate molar ratio be 80:10:10), hydrophobicity hydroxyapatite, ethyl cellulose
The quality volume fraction of element is 4w/v%, 9w/v%, 2w/v%；
(2) 12 parts by volume distilled water are added portionwise in the oily phase that step (1) obtains, are existed after mixing through vortex mixer
2500r/min oscillation emulsification 15min, obtains water-in-oil type High Internal Phase Emulsion；
(3) High Internal Phase Emulsion for obtaining step (2) is packed into the extruded type 3D equipped with 21G micro needle head and beats as ink
It prints in machine needle cylinder, and pressure is used to apply pressure to syringe for 0.04MPa air pump, control print speed 25mm/s, according to default
The printing building of the bracket cuboid model sport track (30mm × 30mm × 7mm) obtain three-dimensional porous lotion bracket.
(4) the porous lotion branch that step (3) obtain is placed in draught cupboard and spontaneously dries 48h at room temperature, obtain shape
The compound multiple dimensioned hole biological support of memory-type active nanoparticles/biodegradable polyesters.
Embodiment 4
(1) in ice-water bath, the methylene chloride suspension for obtaining 4 parts by volume is prepared by ultrasonication 30min, i.e., it is oily
Phase, wherein (molecular weight is 8 × 10 to Biodegradable polylactic acids-caprolactone-trimethylene carbonate copolymer4G/mol, wherein
Lactic acid, caprolactone, trimethylene carbonate molar ratio be 75:10:15), hydrophobicity hydroxyapatite, hydrophobic nano dioxy
The quality volume fraction of SiClx is 9w/v%, 7.5w/v%, 1.5w/v%；
(2) 16 parts by volume distilled water are added portionwise in the oily phase that step (1) obtains, are existed after mixing through vortex mixer
3000r/min oscillation emulsification 20min, obtains water-in-oil type High Internal Phase Emulsion；
(3) High Internal Phase Emulsion for obtaining step (2) is packed into the extruded type 3D equipped with 21G micro needle head and beats as ink
It prints in machine needle cylinder, and pressure is used to apply pressure to syringe for 0.05MPa air pump, control print speed 15mm/s, according to default
The cylindrical model sport track (Φ 30mm × 7mm) the printing building of bracket obtain three-dimensional porous lotion bracket.
(4) the porous lotion branch that step (3) obtain is placed in draught cupboard and is placed in -18 DEG C of refrigerators after freezing 6h, then
Through -50 DEG C of freeze-drying 16h, the compound multiple dimensioned hole of shape memory type active nanoparticles/biodegradable polyesters is obtained
Biological support.
Embodiment 5
(1) in ice-water bath, the methylene chloride suspension for obtaining 4 parts by volume is prepared by ultrasonication 30min, i.e., it is oily
Phase, wherein (molecular weight is 3 × 10 to Biodegradable polylactic acids-hydroxyacetic acid-polytrimethylene carbonate copolymer4G/mol,
Wherein lactic acid, hydroxyacetic acid, trimethylene carbonate molar ratio be 80:10:10), hydrophobicity hydroxyapatite, hydrophobicity
The quality volume fraction of nano silica is 9w/v%, 7.5w/v%, 1.5w/v%；
(2) 14 parts by volume distilled water are added portionwise in the oily phase that step (1) obtains, are existed after mixing through vortex mixer
2500r/min oscillation emulsification 20min, obtains water-in-oil type High Internal Phase Emulsion；
(3) High Internal Phase Emulsion for obtaining step (2) is packed into the extruded type 3D equipped with 20G micro needle head and beats as ink
It prints in machine needle cylinder, and pressure is used to apply pressure to syringe for 0.05MPa air pump, control print speed 30mm/s, according to default
The cylindrical model sport track (Φ 30mm × 9mm) the printing building of bracket obtain three-dimensional porous lotion bracket.
(4) the porous lotion branch that step (3) obtain is placed on after freezing 6h in -18 DEG C of refrigerators, then -50 DEG C of warp freezings are dry
Dry 16h obtains the compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters.
Embodiment 6
(1) in ice-water bath, the methylene chloride suspension for obtaining 4 parts by volume is prepared by ultrasonication 30min, i.e., it is oily
Phase, wherein (molecular weight is 5.2 × 10 to Biodegradable polylactic acids-trimethylene carbonate copolymer4G/mol, wherein lactic acid,
The molar ratio of trimethylene carbonate is 80:20), the quality volume of hydrophobicity hydroxyapatite, hydrophobic nano-silica
Score is 9w/v%, 5w/v%, 2w/v%；
(2) 12 parts by volume distilled water are added portionwise in the oily phase that step (1) obtains, are existed after mixing through vortex mixer
3500r/min oscillation emulsification 10min, obtains water-in-oil type High Internal Phase Emulsion；
(3) High Internal Phase Emulsion for obtaining step (2) is packed into the extruded type 3D equipped with 20G micro needle head and beats as ink
It prints in machine needle cylinder, and pressure is used to apply pressure to syringe for 0.05MPa air pump, control print speed 20mm/s, according to default
The printing building of the bracket cuboid model sport track (30mm × 30mm × 7mm) obtain three-dimensional porous lotion bracket.
(4) the porous lotion branch that step (3) obtain is placed on after freezing 4min in liquid nitrogen, then -50 DEG C of warp freeze-dryings
16h obtains the compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters.
Embodiment 7
(1) in ice-water bath, the methylene chloride suspension for obtaining 4 parts by volume is prepared by ultrasonication 30min, i.e., it is oily
Phase, wherein (molecular weight is 5 × 10 to Biodegradable polylactic acids-trimethylene carbonate copolymer4G/mol, wherein lactic acid, three
The molar ratio of carbonate is 75:25), hydrophobicity hydroxyapatite, ethyl cellulose quality volume fraction be 9w/
V%, 9w/v%, 1.5w/v%；
(2) 16 parts by volume distilled water are added portionwise in the oily phase that step (1) obtains, are existed after mixing through vortex mixer
800r/min oscillation emulsification 20min, obtains water-in-oil type High Internal Phase Emulsion；
(3) High Internal Phase Emulsion for obtaining step (2) is packed into the extruded type 3D equipped with 20G micro needle head and beats as ink
It prints in machine needle cylinder, and pressure is used to apply pressure to syringe for 0.05MPa air pump, control print speed 25mm/s, according to default
The printing building of the bracket cuboid model sport track (30mm × 30mm × 7mm) obtain three-dimensional porous lotion bracket.
(4) the porous lotion branch that step (3) obtain is placed on after freezing 4min in liquid nitrogen, then -50 DEG C of warp freeze-dryings
16h obtains the compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters.
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 compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters
Method, it is characterised in that the following steps are included:
Biodegradable shape-memory polyester, hydroxyapatite nano particle, rheology modifier are added in organic solvent, through super
Sound effect, which is prepared, obtains oily phase；It adds water in oily phase, forms water-in-oil type High Internal Phase Emulsion through emulsification；High Internal Phase Emulsion is made
For ink, three-dimensional porous lotion bracket is obtained using extruded type 3D printing, solvent evaporation obtains shape memory type bioactivity and receives
The compound multiple dimensioned hole biological support of rice corpuscles/biodegradable polyesters.
2. shape memory type active nanoparticles/biodegradable polyesters according to claim 1 are compound multiple dimensioned
The preparation method of hole biological support, it is characterised in that: the Biodegradable shape-memory polyester includes-three methylene of polylactic acid
Base carbonate copolymer, poly lactic-co-glycolic acid-trimethylene carbonate copolymer, polylactic acid-caprolactone-trimethylene carbon
At least one of acid ester copolymer；Molecular weight is 1 × 104-1.5×105g/mol。
3. shape memory type active nanoparticles/biodegradable polyesters according to claim 1 are compound multiple dimensioned
The preparation method of hole biological support, it is characterised in that: the hydroxyapatite nano particle is that hydrophobically modified hydroxyapatite is received
Rice corpuscles, by by the low molecular weight carboxyl end group polylactic acid of 1-3 mass parts hydroxyapatite and 0.5-2.5 mass parts organic molten
It is uniformly mixed in agent system, after solvent flashing, in 180-210 DEG C of calcining 8-36h, obtains hydrophobically modified hydroxyapatite nano grain
Son.
4. shape memory type active nanoparticles/biodegradable polyesters according to claim 1 are compound multiple dimensioned
The preparation method of hole biological support, it is characterised in that: the rheology modifier includes hydrophobic nano-silica and ethyl
At least one of cellulose.
5. shape memory type active nanoparticles/biodegradable polyesters according to claim 1 are compound multiple dimensioned
The preparation method of hole biological support, it is characterised in that: mass body of the Biodegradable shape-memory polyester in oily phase
Fraction 2w/v%-16w/v%；Quality volume fraction of the hydroxyapatite nano particle in oily phase is 1.5w/v%-
15w/v%；Quality volume fraction of the rheology modifier in oily phase is 0.5w/v%-3.5w/v%.
6. shape memory type active nanoparticles/biodegradable polyesters according to claim 1 are compound multiple dimensioned
The preparation method of hole biological support, it is characterised in that: in the water-in-oil type High Internal Phase Emulsion, internal phase volume score is 75-
85v/v%.
7. shape memory type active nanoparticles/biodegradable polyesters according to claim 1 are compound multiple dimensioned
The preparation method of hole biological support, it is characterised in that: the process conditions of the extruded type 3D printing are as follows: extrusion air pressure is 0.01-
0.2MPa, the internal diameter of syringe needle are 100-1120 μm, print speed 2-60mm/s.
8. shape memory type active nanoparticles/biodegradable polyesters according to claim 1 are compound multiple dimensioned
The preparation method of hole biological support, it is characterised in that specifically includes the following steps:
(1) in ice-water bath, Biodegradable shape-memory polyester, hydroxyapatite nano particle, rheology modifier are added
In organic solvent, configure to obtain oily phase by ultrasonication；
(2) distilled water is added in the oily phase that step (1) obtains, forms the high interior mutually cream of water-in-oil type through emulsification preparation after mixing
Liquid；
(3) High Internal Phase Emulsion for obtaining step (2) is packed into the extruded type 3D printer syringe for being furnished with micro needle head as ink
It is interior, and pressure is applied to syringe using air pump, print speed is controlled, printing building obtains three-dimensional porous lotion bracket；
(4) the porous lotion bracket that step (3) obtain is placed to remove organic solvent and water, solvent evaporation obtains shape note
Recall the compound multiple dimensioned hole biological support of type active nanoparticles/biodegradable polyesters.
9. a kind of compound multiple dimensioned hole biological support of shape memory type active nanoparticles/biodegradable polyesters, special
Sign is that preparation method according to claim 1-8 obtains.
10. the compound multiple dimensioned Kong Sheng of shape memory type active nanoparticles/biodegradable polyesters as claimed in claim 9
Application of the object bracket in medicine controlled releasing field and tissue engineering bracket field.
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