CN106867020A - A kind of temperature-induced self-healing porous material and its preparation method and application - Google Patents
A kind of temperature-induced self-healing porous material and its preparation method and application Download PDFInfo
- Publication number
- CN106867020A CN106867020A CN201710054864.5A CN201710054864A CN106867020A CN 106867020 A CN106867020 A CN 106867020A CN 201710054864 A CN201710054864 A CN 201710054864A CN 106867020 A CN106867020 A CN 106867020A
- Authority
- CN
- China
- Prior art keywords
- self
- healing
- porous material
- double bond
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
- C08J9/286—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum the liquid phase being a solvent for the monomers but not for the resulting macromolecular composition, i.e. macroporous or macroreticular polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/146—Porous materials, e.g. foams or sponges
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/66—Polyesters containing oxygen in the form of ether groups
- C08G63/664—Polyesters containing oxygen in the form of ether groups derived from hydroxy carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/78—Preparation processes
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/91—Polymers modified by chemical after-treatment
- C08G63/912—Polymers modified by chemical after-treatment derived from hydroxycarboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/28—Treatment by wave energy or particle radiation
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
- C08J2367/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Vascular Medicine (AREA)
- Veterinary Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Surgery (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention provides a kind of preparation method of temperature-induced self-healing porous material, including：In the presence of initiator or/and catalyst, there is polymerisation and obtain degradable block polymer in monomer, add double bond end-cap molecule, obtain degradable double bond end-blocking block polymer；The degradable double bond end-blocking block polymer that will be obtained is dissolved in solvent, crosslinking curing is carried out after addition crosslinking agent obtain primary material, primary material is soaked in being put into water-bath, snap frozen after immersion, freeze drier is placed in shape to obtain self-healing porous material, the self-healing porous material induces loose structure to heal by the change of temperature, is widely used in biomedical materials field.
Description
Technical field
The present invention relates to biomedical materials field, and in particular to a kind of temperature-induced self-healing porous material and its system
Preparation Method and application.
Background technology
In implantation intervention bio-medical material and instrument field, material or apparatus and the biocompatibility of human body are influences
The a great problem of successful surgery.Implant will first face the test of human immune system into human body, in brief：Biofacies
The bad material of capacitive will trigger the non-specific adsorption of protein with the intervention of apparatus in people's physical efficiency, attract immunocyte with inflammation
The enrichment of disease cell, and then cause the adverse reactions such as deposition of fibrous tissue hyperplasia.Therefore improved using coating technology material with
The biocompatibility of tissue, is of great significance for reconstructing normal organizational interface's tool.
Traditional bio-medical material is usually bio-inert material, such as the Endeavor branch of Medtronic with apparatus coating
, using polyphosphoric acid choline polymer as coating, the Xcience V supports of Abbott Laboratories are then using fluoropolymer as its surface for frame
Coating.This kind of biologically inert coating reduces the generation of immune response although the biocompatibility of material can be improved, but due to it
The characteristics of inertia, the vascular remodeling of implant site can not be promoted, improved adhesion of the cell on its surface and the function such as bred, therefore
Some bad risks are still suffered from implantation late period.Based on this, in recent years, bioactivity coatings technology is increasingly developed and studies,
This type coating injects polypeptide, functional protein, function DNA etc. with specific function by surface immobilizing biologically active molecule
Molecule, by promoting material and tissue, the interaction of cell, forms cellular layer, so as to reach in material surface quick in situ
Improve the effect of Biocompatibility and promotion organization regeneration.Such as by the covalent fixed packet on inert coatings containing special
The active peptides of property affinity sequence REDV, adhesion multiplication capacity of the vascular endothelial cell on its surface is significantly larger than smooth muscle
Cell, zoopery can reconstruct endodermis after proving implantation in rack surface, and the possibility of stent restenosis is reduced so as to reach；
And in energy such as material surface sessile antibody anti-34, blood vessel endothelial cell growth factor VEGFs by way of LBL self-assembly
The compatibility of material and endothelial cell is significantly improved, the growth of endothelial cell is adjusted, so as to equally reach fast in implant surface
Speed reconstruct endodermis, the adverse events probability of happening for reducing ISR and thrombus.
Although in field of scientific study, bioactivity coatings technology be extensively studied with exploitation, but one is at present
The application for being only really applied to actual clinical is rarely reported.Wherein OrbusNeich companies exploitation Genous supports by
Rack surface sessile antibody anti-CD34, therefore the support can realize attraction in situ and capture endothelial progenitor cells after implantation, so that
Improve the curative effect of support to a certain extent.Although Genous supports are different from traditional bracket for eluting medicament from principle,
Its appearance does not obtain corresponding effect, has many reason for possible.Its medium-height trestle will necessarily face sterilizing in preparation process
With the process of storage, especially will cause largely irreversible to the bioactive molecule that rack surface is fixed in sterilization process
Destruction so that some or all of failure of bioactive molecule, thus significantly weaken bioactive molecule effect.
In recent years, received come the technology of the bioactive molecules such as fixed drug molecule, vaccine, protein by self-healing material
To extensive concern and research.This kind of technology at the interface of material and is internally formed loose structure first, and these loose structures can
For adsorbing and storing active component, then under the stimulation of external environment, the molecular chain mobility of these porous materials is swashed
Living, by surface energy minimumization principle, these loose structures can fade away, so as to reach the effect of fixed active component.
It is this by way of dynamic structure self-healing come immobilizing biologically active molecule, represent the more advanced intelligent response side of a class
To.But, the self-healing design currently used for surface and interface coating is rarely reported, and can be used for the degradable self-healing coating of human body
Design is even more blank.
In sum, conventional medicament FirebirdTM coating will delay or line artery normal structure reconstruct, so as to
Implantation is fully present risk, and studies the positive reconstruct for finding that blood vessel can be accelerated by the load of bioactive molecule, but
Into, due to destruction of the process for bioactive molecule such as sterilizings, bioactive molecule is in current application during practical application
It is still more difficult.Therefore, a kind of coating is designed, the load of conventional medicament molecule and bioactive molecule can be realized, while avoiding life
Thing bioactive molecule is produced process and is destroyed, and is of great significance for novel intelligent coating reconstruct blood vessel structure tool.More
For importantly, this porous design that not only can be suitably used for smart coat of new intelligent self-healing, equally can also be applicable
With need bioactive molecule promotion organization reconstruct biomedical materials field, with gene therapy technology, Intelligent controlled release skill
Art is continued to develop, and this kind of intelligent self-healing porous material will be presented wide application prospect.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of temperature-induced self-healing porous material and its preparation side
Method and application, the porous material can induce loose structure to heal by the stimulation of external environment.
A kind of preparation method of temperature-induced self-healing porous material, including：
(1) degradable double bond blocks the synthesis of block polymer
In the presence of initiator or/and catalyst, there is polymerisation and obtain degradable block polymer in monomer, add
Double bond end-cap molecule, obtains degradable double bond end-blocking block polymer；
The monomer is glycolide, levorotatory lactide, DL lactide, glycolic, lactic acid, 6-caprolactone, dioxocyclohex
At least one in ketone, trimethylene carbonate and polyhydroxy-alkanoates；
The double bond end-cap molecule is methacrylic chloride, ethyl propylene acyl chlorides or methylacryoyloxyethyl isocyanic acid
Ester；
(2) the degradable double bond end-blocking block polymer that will be obtained in step (1) is dissolved in solvent, adds crosslinking agent to obtain
Mixed solution, mixed solution crosslinking curing in the form of heating or ultraviolet radiation obtains primary material, and primary material is put into water
Soaked in bath, snap frozen after immersion, be placed in freeze drier and shape to obtain self-healing porous material.
The synthetic method of the degradable double bond end-blocking block polymer is opened including ring-opening polymerisation method, direct polycondensation method etc.
Cyclopolymerization is that cyclic monomer is polymerized after open loop under initiator or catalyst action；Direct polycondensation method refers to difunctional or many officials
High molecular reaction, including melt polycondensation, solution polycondensation, interface contracting can be generated by the condensation reaction for repeating between single group body
Poly-, solid phase polycondensation etc..
The initiator is polyethylene glycol or n arm polyethylene glycol, and n >=3, number-average molecular weight is 100~50000；As certainly
Healing Dynamic coating, the selection of the temperature that heals counts for much for the success or not that the later stage loads, due to current most life
Thing bioactive molecule can not for a long time tolerate the temperature conditionss higher than 50 DEG C, and for small molecules such as some vaccines or medicines, its is resistance to
Also should not be higher than 80 DEG C by temperature, therefore the healing temperature of self-healing porous material have to be lower than 80 DEG C and be higher than 25 DEG C of room temperature,
The fusing point of polyethylene glycol or n arm polyethylene glycol has with its molecular size range and closely contacts, based on the requirement of self-healing temperature,
Preferably, the number-average molecular weight of the initiator is 1000~10000.
The dosage of the initiator is 0.2~2 times of monomer mass.
The selection of monomer affects the crystallization behavior of the post-consumer polymer of polymerization, and then influences the healing temperature of final material,
Application claims healing temperature is less than 80 DEG C, therefore the unsuitable crystal property of monomer of selection is excessively excellent, preferably, the list
Body is at least one in glycolide, levorotatory lactide, DL lactide and 6-caprolactone.
Further preferably, in step (1), the initiator is polyethylene glycol or three arm polyethylene glycol, and the monomer is second
At least one in lactide, levorotatory lactide, DL lactide and 6-caprolactone.
The catalyst is stannous octoate or dibutyl tin laurate, and the dosage of the catalyst is monomer mass
0.01~0.5%；Preferably, the dosage of the catalyst is the 0.01~0.1% of monomer mass.
The temperature of the polymerisation is 120~160 DEG C；The time of shown polymerisation is 2~6h.
The double bond end-cap molecule to add mole equal with the amount of the material of hydroxyl in the initiator.
In step (1), the number-average molecular weight of the degradable double bond end-blocking block polymer is 1000~100000；As
It is preferred that, the number-average molecular weight of the degradable double bond end-blocking block polymer is 2000~50000；Degradable double bond blocks block
The molecular weight effects of polymer the healing temperature of self-healing porous material after crosslinking, therefore, molecular weight is too short, and healing temperature is then
Can be too low, and molecular weight is long, due to the constantly improve of crystallization degree, healing temperature is higher, based on healing temperature requirement, enters one
Step is preferred, and the number-average molecular weight of the degradable double bond end-blocking block polymer is 3000~20000.
In step (2), the solvent be dichloromethane, chloroform, hexafluoroisopropanol, ethyl acetate and acetone in extremely
Few one kind.
In the mixed solution, the mass fraction of degradable double bond end-blocking block polymer is 0.1~20wt%；As excellent
Choosing, the mass fraction of degradable double bond end-blocking block polymer is 0.2~10wt%.
The crosslinking agent is thermal initiator or light trigger, including azodiisobutyronitrile (AIBN), benzoyl peroxide
Or I2959 (BPO)；The dosage of the crosslinking agent is the 0.1~5% of degradable double bond end-blocking block polymerization amount of substance, as
It is preferred that, the dosage of the crosslinking agent is the 0.1~2% of degradable double bond end-blocking block polymerization amount of substance, further preferably, institute
The dosage for stating crosslinking agent is the 0.2~1% of degradable double bond end-blocking block polymerization amount of substance.
Preferably, in step (2), mixed solution is coated on into matrix surface carries out crosslinking curing, for different materials
Material and demand, may be selected different painting methods, and the painting method includes but are not limited to Ultrasonic spraying, solution leaching
Painting, spin coating etc..Further preferably, mixed solution is sprayed at into matrix surface using Ultrasonic spraying technology be crosslinked admittedly
Change, Ultrasonic spraying technology can realize prepared by the coating of complicated interface, and meet the process control of stabilization.
Preferably, in step (2), the thickness that mixed solution is coated on matrix surface is 5~50 μm.Further preferably,
In step (2), the thickness that mixed solution is coated on matrix surface is 10~25 μm.
Loose structure is obtained by freeze-drying in the present invention, concrete principle is as follows：First in water-bath immersion process, due to
Degradable double bond blocks the amphipathic characteristic of block polymer, and hydrone can be penetrated into gradually in primary material, when bath temperature is high
It is primary with the infiltration of hydrone because sub-chain motion is activated when degradable double bond blocks the fusing point of block polymer
Material recurring structure is reconstructed；Then by primary material snap frozen, primary material sub-chain motion is frozen, and hydrone congeals into ice
Crystalline substance, subsequent freeze-drying process removes the moisture in coating, and pore space structure is retained.In step (2), bath temperature is 10~90
DEG C, soak time is 1~24h.
The extension over time of the rearrangement process of molecule segment will gradually tend towards stability in primary material, further excellent
Choosing, in step (2), bath temperature is 20~60 DEG C, and soak time is 2~12h.
Present invention also offers a kind of self-healing porous material obtained by above-mentioned preparation method, the porous material of self-healing
Material induces loose structure to heal by the change of temperature, by way of this self-healing, can meet different bioactive molecules
Load；More importantly, the self-healing porous material can meet before stenter to implant complete bioactive molecule it is controllable
Load.
In the self-healing porous material, the mechanism of temperature-induced self-healing is as follows：What is formed in freezing dry process is more
Pore structure be substantially due to removing moisture after strand re-form crystallization so as to prevent the closure of hole, therefore, when this
When loose structure runs into uniform temperature, polymer crystalline region is melted, and the restriction effect for locking molecular chain movement is released from,
Therefore, strand can be moved rapidly, so that cause the disappearance of microcellular structure according to the principle of surface energy minimumization, it is this
The formation of loose structure and agglutination, be substantially on micro-scale molecular chain movement opening with locking caused by.
The self-healing temperature of the self-healing porous material is 25~80 DEG C, when ambient temperature reaches self-healing temperature,
The loose structure of the self-healing porous material disappears.
Preferably, the self-healing temperature of the self-healing porous material is 30~60 DEG C, the self-healing temperature range has
Beneficial to the success rate for improving load bioactive molecule.
Present invention also offers a kind of above-mentioned self-healing porous material biomedical materials field application.
Brief description of the drawings
Fig. 1 is the SEM microstructure figures in self-healing porous material cross section prepared by embodiment 1；
Fig. 2 is the SEM microstructure figures of self-healing porous material upper surface prepared by embodiment 1；
Fig. 3 is the agglutination experimental result picture of self-healing porous material prepared by embodiment 1；
Fig. 4 is the optical photograph of the angiocarpy bracket of self-healing porous material prepared by surface coating embodiment 1, wherein,
(A) for surface coats optical photograph of the angiocarpy bracket of self-healing porous material before healing, (B) is that surface coats self-healing
Optical photograph after the angiocarpy bracket healing of porous material, (C) is the angiocarpy bracket that surface coats self-healing porous material
SEM microstructure figures before healing, (D) is that the SEM after the angiocarpy bracket healing of surface coating self-healing porous material shows
Micromorphology figure.
Specific embodiment
The present invention is described in detail with reference to the accompanying drawings and detailed description.
Embodiment 1
PDLLA-PEG-PDLLA-25 self-healing porous materials
(1) degradable double bond blocks the synthesis of block polymer：
The glass reaction kettle of 1L is vacuum dried 1h at 80 DEG C, is under nitrogen protection 2000 by 200g number-average molecular weights
Polyethylene glycol, vacuumized at being warming up to 120 DEG C and dry 2h.300g DLs lactide is subsequently adding in reactor, at 120 DEG C
It is lower to continue to be vacuum dried 1h.0.5g stannous octoates are subsequently adding, temperature 150 DEG C is brought up to, and be maintained at 150 DEG C, nitrogen guarantor
The lower reaction 3h of shield, is subsequently adding 0.5g polymerization inhibitor 4- metoxyphenols, after uniform stirring 30min, is added by the way of being added dropwise
31g methylacryoyloxyethyl isocyanates, obtains the degradable double bond end-blocking block polymer that number-average molecular weight is about 5000
(PDLLA-PEG-PDLLA-25)。
(2) preparation of self-healing porous material
The PDLLA-PEG-PDLLA-25 that step (1) is obtained is dissolved in ethyl acetate, light trigger I2959 is added,
It is made mixed solution.The mass fraction of PDLLA-PEG-PDLLA-25 is 2wt%, the matter of light trigger I2959 in mixed solution
Amount fraction is 0.02wt%.Primary coating is prepared using ultrasonic atomization technology spraying, coating layer thickness is 10~20 μm.Then use
Coating crosslinking curing is obtained primary material, irradiation luminous intensity 50mW/cm by the mode of ultraviolet light irradiation2, 2~10min of exposure time.
After the completion of crosslinking curing, primary material is put into aseptic water-bath and is soaked, bath temperature is 40~45 DEG C, and soak time is 8h,
Then with ultra low temperature freezer by swelling rear coating snap frozen, moisture removal is removed in drying in being subsequently placed into freeze drier, is shaped into
It is self-healing porous material.
The SEM microstructures figure in obtained self-healing porous material cross section is as shown in figure 1, the micro- shapes of the SEM of upper surface
Looks figure before material healing as shown in Fig. 2 from SEM microstructure figures, have loose structure.
The average pore size of gained self-healing porous material is 1 μm, and the degradable time is 1 month.
The agglutination of gained self-healing porous material is as shown in figure 3, the self-healing porous material keeps many at 37 DEG C
Pore structure, and when temperature rises to 40 DEG C, within 10 minutes, microcellular structure gradually self-healing, due to gradually disappearing for hole
Lose, originally because the white profile that micropore causes to light scattering is gradually evolved into transparent configuration.SEM microstructure figures in Fig. 3
It is the micropore microstructure of self-healing porous material different time at 40 DEG C, the material can be seen that by SEM microstructure figures
The microcellular structure of material faded away within 10 minutes.
What is more important, this porous material with temperature self-healing effect can be in complicated three-dimensional structure object table
Face realization, therefore, this self-healing porous material can be applied to angiocarpy bracket coating material, carry medicine ball capsule coating, Bone Defect Repari
Many bio-medical material coatings such as material coating.
Angiocarpy bracket surface is coated in using gained self-healing porous material as bio-medical material coating, its optics shines
Piece is as shown in figure 4, wherein, Fig. 4 (A) is that optics of the angiocarpy bracket of surface coating self-healing porous material before healing shines
Piece, Fig. 4 (B) is the optical photograph after the angiocarpy bracket healing of surface coating self-healing porous material, and Fig. 4 (C) is applied for surface
SEM microstructure figure of the angiocarpy bracket of self-healing porous material before healing is covered, Fig. 4 (D) is that surface coating self-healing is more
SEM microstructure figures after the angiocarpy bracket healing of Porous materials.
Embodiment 2
PDLLA-PEG-PDLLA-210 self-healing porous materials
(1) degradable double bond blocks the synthesis of block polymer：
The glass reaction kettle of 1L is vacuum dried 1h at 80 DEG C, is under nitrogen protection 2000 by 80g number-average molecular weights
Polyethylene glycol, vacuumized at being warming up to 120 DEG C and dry 2h.320g DLs lactide is subsequently adding in reactor, at 120 DEG C
It is lower to continue to be vacuum dried 1h.0.5g stannous octoates are subsequently adding, temperature 150 DEG C is brought up to, and be maintained at 150 DEG C, nitrogen guarantor
The lower reaction 3h of shield, is subsequently adding 0.5g polymerization inhibitor 4- metoxyphenols, after uniform stirring 30min, is added by the way of being added dropwise
12.5g methylacryoyloxyethyl isocyanates, obtains the degradable double bond end-blocking block polymerization that number-average molecular weight is about 10000
Thing (PDLLA-PEG-PDLLA-210).
(2) preparation of self-healing porous material
The PDLLA-PEG-PDLLA-210 that step (1) is obtained is dissolved in ethyl acetate, light trigger I2959 is added,
It is made mixed solution.The mass fraction of PDLLA-PEG-PDLLA-210 is 2wt%, the matter of light trigger I2959 in mixed solution
Amount fraction is 0.02wt%.Primary coating is prepared using ultrasonic atomization technology spraying, coating layer thickness is 10~20 μm.Then use
Coating crosslinking curing is obtained primary material, irradiation luminous intensity 50mW/cm by the mode of ultraviolet light irradiation2, 2~10min of exposure time.
After the completion of crosslinking curing, primary material is put into aseptic water-bath and is soaked, bath temperature is 45~50 DEG C, and soak time is 12h,
Then with ultra low temperature freezer by swelling rear coating snap frozen, moisture removal is removed in drying in being subsequently placed into freeze drier, is shaped into
It is self-healing porous material.
The average pore size of gained self-healing porous material is 1 μm, and self-healing temperature is 45 DEG C, and the degradable time is 2
Month.
Embodiment 3
PDLLA-PEG-PDLLA-110 self-healing porous materials
(1) degradable double bond blocks the synthesis of block polymer：
The glass reaction kettle of 1L is vacuum dried 1h at 80 DEG C, is under nitrogen protection 1000 by 50g number-average molecular weights
Polyethylene glycol, vacuumized at being warming up to 120 DEG C and dry 2h.450g DLs lactide is subsequently adding in reactor, at 120 DEG C
It is lower to continue to be vacuum dried 1h.0.5g stannous octoates are subsequently adding, temperature 150 DEG C is brought up to, and be maintained at 150 DEG C, nitrogen guarantor
The lower reaction 3h of shield, is subsequently adding 0.5g polymerization inhibitor 4- metoxyphenols, after uniform stirring 30min, is added by the way of being added dropwise
15.5g methylacryoyloxyethyl isocyanates, obtains the degradable double bond end-blocking block polymerization that number-average molecular weight is about 10000
Thing (PDLLA-PEG-PDLLA-110).
(2) preparation of self-healing porous material
The PDLLA-PEG-PDLLA-110 that step (1) is obtained is dissolved in ethyl acetate, light trigger I2959 is added,
It is made mixed solution.The mass fraction of PDLLA-PEG-PDLLA-110 is 2wt%, the matter of light trigger I2959 in mixed solution
Amount fraction is 0.02wt%.Primary coating is prepared using ultrasonic atomization technology spraying, coating layer thickness is 10~20 μm.Then use
Coating crosslinking curing is obtained primary material, irradiation luminous intensity 50mW/cm by the mode of ultraviolet light irradiation2, 2~10min of exposure time.
After the completion of crosslinking curing, primary material is put into aseptic water-bath and is soaked, bath temperature is 50~60 DEG C, and soak time is 12h,
Then with ultra low temperature freezer by swelling rear coating snap frozen, moisture removal is removed in drying in being subsequently placed into freeze drier, is shaped into
It is self-healing porous material.
The average pore size of gained self-healing porous material is 1 μm, and self-healing temperature is 55 DEG C, and the degradable time is 2
Month.
Embodiment 4
PLGA-PEG-PLGA-25 self-healing porous materials
(1) degradable double bond blocks the synthesis of block polymer：
The glass reaction kettle of 1L is vacuum dried 1h at 80 DEG C, is under nitrogen protection 2000 by 200g number-average molecular weights
Polyethylene glycol, vacuumized at being warming up to 120 DEG C and dry 2h.It is subsequently adding 150g levorotatory lactides and 150g glycolides to reaction
In kettle, continue to be vacuum dried 1h under the conditions of 120 DEG C.0.5g stannous octoates are subsequently adding, temperature 150 DEG C is brought up to, and protect
Hold and react 3h under 150 DEG C, nitrogen protection, be subsequently adding 0.5g polymerization inhibitor 4- metoxyphenols, after uniform stirring 30min, adopt
31g methylacryoyloxyethyl isocyanates is added with the mode being added dropwise, degradable pair that number-average molecular weight is about 5000 is obtained
Key blocks block polymer (PLGA-PEG-PLGA-25).
(2) preparation of self-healing porous material
The PLGA-PEG-PLGA-25 that step (1) is obtained is dissolved in acetone, light trigger I2959 is added, is made mixed
Close solution.The mass fraction of PLGA-PEG-PLGA-25 is 2wt% in mixed solution, and the mass fraction of light trigger I2959 is
0.02wt%.Primary coating is prepared using ultrasonic atomization technology spraying, coating layer thickness is 10~20 μm.Then use ultraviolet light spoke
According to mode coating crosslinking curing is obtained into primary material, irradiation luminous intensity 50mW/cm2, 2~10min of exposure time.Crosslinking curing
After the completion of, primary material being put into aseptic water-bath and is soaked, bath temperature is 40~45 DEG C, and soak time is 8h, then uses super
By swelling rear coating snap frozen, moisture removal is removed in drying to low temperature refrigerator in being subsequently placed into freeze drier, and sizing turns into self-healing
Porous material.
The average pore size of gained self-healing porous material is 1 μm, and self-healing temperature is 40 DEG C, and the degradable time is 3 weeks.
Embodiment 5
PLGA-PEG-PLGA-25-2 self-healing porous materials
(1) degradable double bond blocks the synthesis of block polymer：
The glass reaction kettle of 1L is vacuum dried 1h at 80 DEG C, is under nitrogen protection 2000 by 200g number-average molecular weights
Polyethylene glycol, vacuumized at being warming up to 120 DEG C and dry 2h.It is subsequently adding 210g levorotatory lactides and 90g glycolides to reaction
In kettle, continue to be vacuum dried 1h at 120 DEG C.0.5g stannous octoates are subsequently adding, temperature 150 DEG C is brought up to, and be maintained at
150 DEG C, the lower reaction 3h of nitrogen protection, are subsequently adding 0.5g polymerization inhibitor 4- metoxyphenols, after uniform stirring 30min, using drop
Plus mode add 31g methylacryoyloxyethyl isocyanates, obtain number-average molecular weight be about 5000 degradable double bond envelope
End block polymer (PLGA-PEG-PLGA-25-2).
(2) preparation of self-healing porous material
The PLGA-PEG-PLGA-25-2 that step (1) is obtained is dissolved in ethyl acetate, light trigger I2959 is added,
It is made mixed solution.The mass fraction of PLGA-PEG-PLGA-25-2 is 2wt%, the matter of light trigger I2959 in mixed solution
Amount fraction is 0.02wt%.Primary coating is prepared using ultrasonic atomization technology spraying, coating layer thickness is 10~20 μm.Then use
Coating crosslinking curing is obtained primary material, irradiation luminous intensity 50mW/cm by the mode of ultraviolet light irradiation2, 2~10min of exposure time.
After the completion of crosslinking curing, primary material is put into aseptic water-bath and is soaked, bath temperature is 40~45 DEG C, and soak time is 8h,
Then with ultra low temperature freezer by swelling rear coating snap frozen, moisture removal is removed in drying in being subsequently placed into freeze drier, is shaped into
It is self-healing porous material.
The average pore size of gained self-healing porous material is 1 μm, and self-healing temperature is 40 DEG C, and the degradable time is 1
Month.
Embodiment 6
PLGA-PEG-PLGA-210 self-healing porous materials
(1) degradable double bond blocks the synthesis of block polymer：
The glass reaction kettle of 1L is vacuum dried 1h at 80 DEG C, is under nitrogen protection 2000 by 80g number-average molecular weights
Polyethylene glycol, vacuumized at being warming up to 120 DEG C and dry 2h.It is subsequently adding 160g levorotatory lactides and 160g glycolides to reaction
In kettle, continue to be vacuum dried 1h at 120 DEG C.0.5g stannous octoates are subsequently adding, temperature 150 DEG C is brought up to, and be maintained at
150 DEG C, the lower reaction 3h of nitrogen protection, are subsequently adding 0.5g polymerization inhibitor 4- metoxyphenols, after uniform stirring 30min, using drop
Plus mode add 12.5g methylacryoyloxyethyl isocyanates, obtain the degradable double bond that number-average molecular weight is about 10000
End-blocking block polymer (PLGA-PEG-PLGA-210).
(2) preparation of self-healing porous material
The PLGA-PEG-PLGA-210 that step (1) is obtained is dissolved in chloroform, light trigger I2959, system is added
Into mixed solution.The mass fraction of PLGA-PEG-PLGA-210 is 2wt%, the quality point of light trigger I2959 in mixed solution
Number is 0.02wt%.Primary coating is prepared using ultrasonic atomization technology spraying, coating layer thickness is 10~20 μm.Then using ultraviolet
Coating crosslinking curing is obtained primary material, irradiation luminous intensity 50mW/cm by the mode of light irradiation2, 2~10min of exposure time.Crosslinking
After the completion of solidification, primary material is put into aseptic water-bath and is soaked, bath temperature is 45~50 DEG C, and soak time is 12h, then
With ultra low temperature freezer by swelling rear coating snap frozen, moisture removal is removed in drying in being subsequently placed into freeze drier, and sizing turns into certainly
Healing porous material.
The average pore size of gained self-healing porous material is 1 μm, and self-healing temperature is 42 DEG C, and the degradable time is 1
Month.
Embodiment 7
PCL-PEG-PCL-25 self-healing porous materials
(1) degradable double bond blocks the synthesis of block polymer：
The glass reaction kettle of 1L is vacuum dried 1h at 80 DEG C, is under nitrogen protection 2000 by 200g number-average molecular weights
Polyethylene glycol, vacuumized at being warming up to 120 DEG C and dry 2h.300g 6-caprolactones are subsequently adding in reactor, at 120 DEG C
Continue to be vacuum dried 1h.0.5g stannous octoates are subsequently adding, temperature 140 DEG C is brought up to, and be maintained at 140 DEG C, nitrogen protection
Lower reaction 3h, is subsequently adding 0.5g polymerization inhibitor 4- metoxyphenols, after uniform stirring 30min, 31g is added by the way of being added dropwise
Methylacryoyloxyethyl isocyanates, obtains the degradable double bond end-blocking block polymer that number-average molecular weight is about 5000
(PCL-PEG-PCL-25)。
(2) preparation of self-healing porous material
The PCL-PEG-PCL-25 that step (1) is obtained is dissolved in ethyl acetate, light trigger I2959 is added, is made
Mixed solution.The mass fraction of PCL-PEG-PCL-25 is 2wt% in mixed solution, and the mass fraction of light trigger I2959 is
0.02wt%.Primary coating is prepared using ultrasonic atomization technology spraying, coating layer thickness is 10~20 μm.Then use ultraviolet light spoke
According to mode coating crosslinking curing is obtained into primary material, irradiation luminous intensity 50mW/cm2, 2~10min of exposure time.Crosslinking curing
After the completion of, primary material being put into aseptic water-bath and is soaked, bath temperature is 40~45 DEG C, and soak time is 8h, then uses super
By swelling rear coating snap frozen, moisture removal is removed in drying to low temperature refrigerator in being subsequently placed into freeze drier, and sizing turns into self-healing
Porous material.
The average pore size of gained self-healing porous material is 1 μm, and self-healing temperature is 42 DEG C, and the degradable time is 3
Month.
Embodiment 8
PCL-PEG-PCL-210 self-healing porous materials
(1) degradable double bond blocks the synthesis of block polymer：
The glass reaction kettle of 1L is vacuum dried 1h at 80 DEG C, is under nitrogen protection 2000 by 80g number-average molecular weights
Polyethylene glycol, vacuumized at being warming up to 120 DEG C and dry 2h.320g 6-caprolactones are subsequently adding in reactor, at 120 DEG C
Continue to be vacuum dried 1h.0.5g stannous octoates are subsequently adding, temperature 140 DEG C is brought up to, and be maintained at 140 DEG C, nitrogen protection
Lower reaction 3h, is subsequently adding 0.5g polymerization inhibitor 4- metoxyphenols, after uniform stirring 30min, is added by the way of being added dropwise
12.5g methylacryoyloxyethyl isocyanates, obtains the degradable double bond end-blocking block polymerization that number-average molecular weight is about 10000
Thing (PCL-PEG-PCL-210).
(2) preparation of self-healing porous material
The PCL-PEG-PCL-210 that step (1) is obtained is dissolved in chloroform, light trigger I2959 is added, is made
Mixed solution.The mass fraction of PCL-PEG-PCL-210 is 2wt% in mixed solution, and the mass fraction of light trigger I2959 is
0.02wt%.Primary coating is prepared using ultrasonic spraying, coating layer thickness is 10~20 μm.Then by the way of ultraviolet light irradiation
Curing of coatings is obtained into primary material, irradiation luminous intensity 50mW/cm2, 2~10min of exposure time.After the completion of crosslinking curing, will be just
Level material soaks in being put into aseptic water-bath, and bath temperature is 45~50 DEG C, and soak time is 12h, then will with ultra low temperature freezer
Swelling rear coating snap frozen, moisture removal is removed in drying in being subsequently placed into freeze drier, and sizing turns into self-healing porous material.
The average pore size of gained self-healing porous material is 1 μm, and self-healing temperature is 45 DEG C, and the degradable time is 3
Month.
Claims (10)
1. a kind of preparation method of temperature-induced self-healing porous material, it is characterised in that including：
(1) degradable double bond blocks the synthesis of block polymer
In the presence of initiator or/and catalyst, there is polymerisation and obtain degradable block polymer in monomer, add double bond
End-cap molecule, obtains degradable double bond end-blocking block polymer；
The monomer is glycolide, levorotatory lactide, DL lactide, glycolic, lactic acid, 6-caprolactone, dioxanone, three
At least one in carbonate and polyhydroxy-alkanoates；
The double bond end-cap molecule is methacrylic chloride, ethyl propylene acyl chlorides or methylacryoyloxyethyl isocyanates；
(2) the degradable double bond end-blocking block polymer that will be obtained in step (1) is dissolved in solvent, adds crosslinking agent to mix
Solution, mixed solution crosslinking curing in the form of heating or ultraviolet radiation obtains primary material, and primary material is put into water-bath
Immersion, snap frozen after immersion is placed in freeze drier and shapes to obtain self-healing porous material.
2. preparation method according to claim 1, it is characterised in that the initiator is polyethylene glycol or the poly- second two of n arms
Alcohol, n >=3, number-average molecular weight is 100~50000.
3. preparation method according to claim 1, it is characterised in that the dosage of the initiator is monomer mass
0.2~2 times.
4. preparation method according to claim 1, it is characterised in that the catalyst is stannous octoate or tin dilaurate two
Butyl tin, the dosage of the catalyst is the 0.01~0.5% of monomer mass.
5. preparation method according to claim 1, it is characterised in that the degradable double bond blocks the number of block polymer
Average molecular weight is 1000~100000.
6. preparation method according to claim 1, it is characterised in that the degradable double bond blocks the number of block polymer
Average molecular weight is 3000~20000.
7. preparation method according to claim 1, it is characterised in that in step (2), bath temperature is 10~90 DEG C, leaching
The bubble time is 1~24h.
8. preparation method according to claim 1, it is characterised in that in step (2), bath temperature is 20~60 DEG C, leaching
The bubble time is 2~12h.
9. a kind of self-healing porous material that preparation method according to any one of claim 1~8 is obtained, its feature exists
In the self-healing temperature of the self-healing porous material is 25~80 DEG C.
10. application of a kind of self-healing porous material according to claim 9 in biomedical materials field.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710054864.5A CN106867020B (en) | 2017-01-24 | 2017-01-24 | A kind of temperature-induced self-healing porous material and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710054864.5A CN106867020B (en) | 2017-01-24 | 2017-01-24 | A kind of temperature-induced self-healing porous material and its preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106867020A true CN106867020A (en) | 2017-06-20 |
| CN106867020B CN106867020B (en) | 2019-05-28 |
Family
ID=59157810
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710054864.5A Active CN106867020B (en) | 2017-01-24 | 2017-01-24 | A kind of temperature-induced self-healing porous material and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106867020B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101045032A (en) * | 2006-03-28 | 2007-10-03 | 四川琢新生物材料研究有限公司 | Novel stop blooding and anti water seeping gel |
| CN101288782A (en) * | 2008-06-18 | 2008-10-22 | 武汉科技学院 | Preparation method of high intensity biodegradable supramolecule hydrogel |
| CN102010488A (en) * | 2010-10-28 | 2011-04-13 | 浙江大学 | Thermo-sensitive and degradable micro hydrogel as well as preparation method and application thereof |
| CN106046271A (en) * | 2016-06-28 | 2016-10-26 | 常州大学 | Preparation method and application of pH response type biodegradable hydrogel |
-
2017
- 2017-01-24 CN CN201710054864.5A patent/CN106867020B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101045032A (en) * | 2006-03-28 | 2007-10-03 | 四川琢新生物材料研究有限公司 | Novel stop blooding and anti water seeping gel |
| CN101288782A (en) * | 2008-06-18 | 2008-10-22 | 武汉科技学院 | Preparation method of high intensity biodegradable supramolecule hydrogel |
| CN102010488A (en) * | 2010-10-28 | 2011-04-13 | 浙江大学 | Thermo-sensitive and degradable micro hydrogel as well as preparation method and application thereof |
| CN106046271A (en) * | 2016-06-28 | 2016-10-26 | 常州大学 | Preparation method and application of pH response type biodegradable hydrogel |
Non-Patent Citations (3)
| Title |
|---|
| 卢国冬；燕青芝；宿新泰；刘中清；葛昌纯；: "多孔水凝胶研究进展", 《化学进展》 * |
| 薛巍，张渊明: "《生物医用水凝胶》", 31 December 2012, 暨南大学出版社 * |
| 魏宏亮；于怀清；钱立军；孙凌刚；冯增国: "一锅法合成甲基丙烯酰基封端的PLA-PEG-PLA大分子单体", 《功能高分子化学》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106867020B (en) | 2019-05-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | Development of innovative biomaterials and devices for the treatment of cardiovascular diseases | |
| CN108815552B (en) | A kind of drug controllably loads and the bio-medical coating material of long-acting slow-release and preparation method thereof | |
| Ulery et al. | Biomedical applications of biodegradable polymers | |
| Khor et al. | Implantable applications of chitin and chitosan | |
| Hoffman | Hydrogels for biomedical applications | |
| Kearney et al. | Macroscale delivery systems for molecular and cellular payloads | |
| US6713083B1 (en) | Coated bioabsorbable beads for wound treatment | |
| JP5941081B2 (en) | Silk-based drug delivery system | |
| WO2009049494A1 (en) | An artificial stent and its preparation method | |
| CN105536055B (en) | A kind of shape memory type high resiliency active nano fibrous framework and its application | |
| Wang et al. | Thermo-triggered ultrafast self-healing of microporous coating for on-demand encapsulation of biomacromolecules | |
| CN108721704B (en) | Long-acting sustained-release cardiovascular coating material with dual functions of calcification resistance and hyperplasia resistance and preparation method thereof | |
| Chen et al. | Mechanical properties, drug eluting characteristics and in vivo performance of a genipin-crosslinked chitosan polymeric stent | |
| CN107715175B (en) | A kind of compound porous bone tissue engineering scaffold of PLGA/ amphoteric ions and preparation method thereof | |
| US20040197374A1 (en) | Implantable pouch seeded with insulin-producing cells to treat diabetes | |
| CN108969800A (en) | The preparation method of Wholly-degradable magnesium alloy bracket drug-carried coat with protective layer | |
| CN101011600A (en) | Decalcification bone supporting stand with composite microsphere of stress release control function and its preparing process | |
| Lipsa et al. | Poly (α-hydroxyacids) in biomedical applications: synthesis and properties of lactic acid polymers | |
| CN201734994U (en) | Medicine-loading coronal artery bracket capable of loading medicine in the manner of gradient concentration | |
| CN101332311A (en) | Drug-loaded mesh grid with slow-release function, production method and use thereof | |
| CN106913915B (en) | A kind of self-healing bracket composite coating and its preparation method and application | |
| CN106867020B (en) | A kind of temperature-induced self-healing porous material and its preparation method and application | |
| Jin et al. | Poly (ferulic acid)-hybrid nanofibers for reducing thrombosis and restraining intimal hyperplasia in vascular tissue engineering | |
| RU2702239C1 (en) | Technology of producing functionally active biodegradable small-diameter vascular prostheses with drug coating | |
| CN102727946B (en) | Drug loaded coating and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |