CN107308502A - 3D printing support of composite load growth factor microballoon and preparation method thereof - Google Patents
3D printing support of composite load growth factor microballoon and preparation method thereof Download PDFInfo
- Publication number
- CN107308502A CN107308502A CN201610969574.9A CN201610969574A CN107308502A CN 107308502 A CN107308502 A CN 107308502A CN 201610969574 A CN201610969574 A CN 201610969574A CN 107308502 A CN107308502 A CN 107308502A
- Authority
- CN
- China
- Prior art keywords
- growth factor
- microballoon
- biological material
- composite load
- support
- 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.)
- Pending
Links
Classifications
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y70/00—Materials specially adapted for additive manufacturing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y80/00—Products made by additive manufacturing
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L89/00—Compositions of proteins; Compositions of derivatives thereof
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/622—Microcapsules
-
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Engineering & Computer Science (AREA)
- Manufacturing & Machinery (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides a kind of preparation method of the 3D printing support of composite load growth factor microballoon, comprise the following steps：Growth factor-loaded complex microsphere and synthesising biological material solution is provided, the growth factor-loaded complex microsphere is added into the synthesising biological material solution, stirs to form synthesising biological material/microspheres solution；Using the print parameters of the Cark Software for Design three-dimensional composite material supports of LDM systems, batch can, feed pipe, shower nozzle are sequentially connected, the synthesising biological material/microspheres solution is poured into batch can；When room temperature to be formed is down to 25~35 DEG C, start temperature control, numerical control, start to print moulding using the Cark software design patterns modeling parameters, being layering to form a three-dimensional and freeze support；The three-dimensional is freezed to carry out freeze-drying process after support takes out, the 3D printing support of composite load growth factor microballoon is obtained.
Description
Technical field
The invention belongs to biomedical sector, more particularly to a kind of composite load growth factor microballoon 3D printing support and
Its preparation method.
Background technology
Injury gained in sports, inflammation, tumour and retrogression of nature cause cartilage defect.Itself repair ability is limited after cartilage defect,
Particularly articular cartilage, self-heal is unable to after damage.It is estimated that only, to the year two thousand twenty, will just have 4,000 ten thousand correlations in the U.S.
Cartilage defect case.China is populous nation, in the crowd of arthroscopy of knee, and the incidence of disease of cartilage damage is in 61-68%
Between, and increased trend year by year is presented.The treatment method clinically commonly used at present mainly has microfrature, autologous cartilage thin
Born of the same parents' transplanting and prosthetic replacement etc., these restorative procedures respectively have shortcoming.The rise of organizational project is studied for cartilage defect repair
There is provided a new direction.During building artificial cartilage in vitro, problems, the length of such as active growth factor are faced
The accurate control of phase stable sustained-release, the regulation and control of cell behavior and brace aperture structure and size.Wherein, growth factor is long-term steady
Fixed sustained release is a key issue of external structure artificial cartilage.Particularly induction stem cell builds artificial to Chondrocyte Differentiation
, it is necessary to which growth factor plays effect steady in a long-term during cartilage.
Rapid shaping technique is also known as 3D printing technique (3DP).Low temperature rapid prototyping ＆ manufacturing technology (LDM) is based on fast rapid-result
Type technical principle, with reference to a kind of new rapid shaping technique of phase separation method.The 3DP system for developing into composite slow release microsphere support
It is standby to provide new selection.It prepares the process of support, is with other rapid shaping technique differences in its forming cavity warm
Degree is controlled in -30 DEG C or so, the solution rapid condensation at low temperature of shower nozzle extrusion, and shower nozzle presses journey under the control of the computer
Sequence is moved, and printable layer finally makes rack forming be three-dimensional structure by being layering, finally, and the support freezed is by freeze-drying
It is three-dimensional porous rack to remove solvent aftershaping.Compared with other conventional rapid shaping techniques, LDM is in processing materials process
Property and structure to material are not damaged, and belong to the scope of green manufacturing.
At present, there is researcher to attempt to utilize 3D printing technique, by programming, medicine is wrapped in medicine in print procedure
In piece, it is possible to achieve multi-medicament is administered simultaneously, but this method is suitable to heavy dose of be administered.There is researcher's active growth factor
As a result absorption show that active growth factor can be sustained quickly, support is lost long-term induced tissue on LDM printing three-dimensional racks
Power of regeneration.The characteristics of need not being heated using LDM shaped supports process, researcher attempts bioactive molecule directly to be mixed with solution
The problem of being printed after conjunction, and this can cause the prominent of bioactive molecule to release, and be still difficult to solve release steady in a long-term.
The content of the invention
It is an object of the invention to provide a kind of 3D printing support of composite load growth factor microballoon and preparation method thereof,
Aim to solve the problem that existing LDM shaped supports are difficult to solve the problem of growth factor discharges steadily in the long term.
The present invention is achieved in that a kind of preparation method of the 3D printing support of composite load growth factor microballoon, bag
Include following steps：
Growth factor-loaded complex microsphere and synthesising biological material solution is provided, described growth factor-loaded is combined
Microballoon adds the synthesising biological material solution, stirs to form synthesising biological material/microspheres solution；
Using the print parameters of the Cark Software for Design three-dimensional composite material supports of LDM systems, batch can, feeding are sequentially connected
Pipe, shower nozzle, the synthesising biological material/microspheres solution is poured into batch can；When room temperature to be formed is down to -25~-35 DEG C, open
Dynamic temperature control, numerical control, start to print moulding, being layering to form a three-dimensional and freeze using the Cark software design patterns modeling parameters
Support；The three-dimensional is freezed to carry out freeze-drying process after support takes out, the 3D for obtaining composite load growth factor microballoon is beaten
Print support.
And, a kind of 3D printing support of the composite load growth factor microballoon prepared by the above method is described multiple
The 3D printing support for closing growth factor-loaded microballoon is three that synthesising biological material and growth factor-loaded complex microsphere are made
Tie up porous support.
The preparation method of the 3D printing support for the composite load growth factor microballoon that the present invention is provided, load growth because
The complex microsphere of son provides one layer of basic guarantee for the sustained release of biotic factor；Further, growth factor-loaded is combined
After microballoon is mixed with synthesising biological material solution, three-dimensional stephanoporate compound stent is prepared using LDM technologies, there is support controllable
One-level aperture size and structure, not only assigning the support has an excellent mechanical property support, and the load growth because
The complex microsphere of son is overall dispersed in the synthesising biological material, while the synthesising biological material is given birth to the load
The complex microsphere of the long factor carries out local parcel, is that prominent release of growth factor is provided with current obstacle, so as to be growth factor
Stable long-term sustained release provides double-deck ensure.In addition, the present invention accurately controls the size of support one-level hole by LDM technologies,
Size is 10-50 μm or so of interconnected secondary porosity in support prepared by assigning, so as to delay for the stabilization of growth factor
Slow persistently release provides effective passage.
The 3D printing support for the composite load growth factor microballoon that the present invention is provided, not only with good mechanical property,
And the synthesising biological material carries out local parcel to the growth factor-loaded complex microsphere, is that the prominent of growth factor is released
There is provided double-deck current obstacle, so that the excellent stable sustained-release of the 3D printing support for assigning the composite load growth factor microballoon
Performance.
Brief description of the drawings
Fig. 1 is the schematic flow sheet of the ColI/CS complex microspheres provided in an embodiment of the present invention for preparing load TGF-β 1；
Fig. 2 is the stream of the preparation method of the 3D printing support of composite load growth factor microballoon provided in an embodiment of the present invention
Journey schematic diagram.
Embodiment
In order that technical problems, technical solutions and advantageous effects to be solved by the present invention are more clearly understood, below in conjunction with
Embodiment, the present invention will be described in further detail.It should be appreciated that specific embodiment described herein is only to explain
The present invention, is not intended to limit the present invention.
The embodiments of the invention provide a kind of preparation method of the 3D printing support of composite load growth factor microballoon, including
Following steps：
S01., growth factor-loaded complex microsphere and synthesising biological material solution is provided, will be described growth factor-loaded
Complex microsphere adds the synthesising biological material solution, stirs to form synthesising biological material/microspheres solution；
S02. using LDM systems Cark Software for Design three-dimensional composite material supports print parameters, be sequentially connected batch can,
Feed pipe, shower nozzle, the PLCL/ microspheres solutions are poured into batch can；When room temperature to be formed is down to -25~-35 DEG C, start temperature
Control, numerical control, using the Cark software design patterns modeling parameters start print moulding, be layering to be formed a three-dimensional freeze branch
Frame；The three-dimensional is freezed to carry out freeze-drying process after support takes out, the 3D printing of composite load growth factor microballoon is obtained
Support.
In above-mentioned steps S01, in the embodiment of the present invention, the microballoon in the growth factor-loaded complex microsphere is natural
The microballoon layer that material is made, so as to ensure the biocompatibility of the 3D supports.It is preferred that, the natural material includes day
Right macromolecule protein and polysaccharide.It is specific preferred, the natural material including collagen (ColI), chondroitin sulfate (CS),
One or both of chitosan (CH), fibroin (SF), hyaluronic acid (HA), sodium alginate (SA).Further, growth factor
Growth factor-loaded complex microsphere is combined to form with microballoon, good sustained release performance is assigned.Wherein, the growth factor includes
But it is not limited to TGF (TGF), bone morphogenetic protein (BMP), IGF (IGF).Further
Ground, when using two kinds of natural materials, a kind of natural material is mixed to form microballoon with the growth factor, another natural
Material is cross-linking in microsphere surface formation network structure, further increases slow release effect.
Microballoon in growth factor-loaded complex microsphere described in the embodiment of the present invention can be prepared using a variety of methods,
Including EFI method, oil-in-water method.As a specific embodiment, with reference to Fig. 1, the growth factor-loaded complex microsphere can be with
Prepared by following methods：Using 0.5mol/L spirit of vinegar as solvent, configuration concentration is 13mg/mL ColI solution, so
TGF-β 1 is added by 10 μ g/L amount afterwards and stirred and evenly mixed, obtain the solution of ColI/TGF- β 1；The solution of ColI/TGF- β 1 is added
After needle tubing, the positive pole of high pressure generator is connected on 27G syringe needle, sets and promotes speed to be 26mL/h, voltage is 18kV,
The solution of ColI/TGF- β 1 is pushed into after pump extrusion, is sprayed downwards under high-pressure electrostatic effect；Drop is with mass volume ratio
0.1% CS solution is received, and forms the ColI/CS microballoons of load TGF-β 1；The ColI/CS microballoons for loading TGF-β 1 are removed
Afterwards, with the glutaraldehyde cross-linking 30min that concentration is 0.25%, microballoon, which takes out, washes away freeze-drying after residual GA, obtains loading TGF-β
1 ColI/CS complex microspheres.Thus obtained growth factor-loaded complex microsphere, after TGF-β 1 is mixed with ColI solution
Spray into CS solution and form the ColI/CS microballoons of load TGF-β 1, the microballoon shell of active growth factor (TGF-β 1) is wrapped up
One layer of CS network structure, first layer guarantee is provided for the stable sustained-release of TGF-β 1, with good spherical-like morphology and structure, and slow
Better performances are released, degradation time is 8 weeks.Of course it is to be understood that this be prepare it is a kind of specific growth factor-loaded
The one of which method of complex microsphere, is not intended to limit the present invention.
Growth factor-loaded complex microsphere described in the embodiment of the present invention has good spherical-like morphology and structure, and sustained release
Better performances.But, if stating growth factor-loaded complex microsphere using described as timbering material main body and preparing biological support,
Resulting biological support is due to lacking enough mechanical properties, it is difficult to and surrounding defective tissue good integration, therefore it is available
Property is poor.In view of this, the embodiment of the present invention mixes the growth factor-loaded complex microsphere and synthesising biological material solution
Support is prepared, the mechanical property of biological support prepared by above-mentioned complex microsphere is improved.
It is preferred that, in the synthesising biological material/microspheres solution, the quality of the growth factor-loaded complex microsphere is dense
Spend for 0.001-1000mg/mL, property with specific reference to different growth factors and be adjusted using object.
It is preferred that, the mass concentration percentage of the synthesising biological material solution is preferably 8-20wt%, so as to protect
Demonstrate,prove suitable viscosity, so that LDM printings can be smoothly molded.It is further preferred that the synthesising biological material be D-lactic acid-
It is caprolactone copolymer (PLCL), poly lactic coglycolic acid (PLGA), PLA (PLA), PLLA (PLLA), poly-
Hydroxy fatty acid (PHA), polyglycolic acid or PGA (PGA), at least one of polyvinyl alcohol (PVA).It is used as a tool
Body embodiment, with the alkane of Isosorbide-5-Nitrae-dioxy six (DIO) for solvent, compound concentration is 13wt% PLCL solution.
As the presently preferred embodiments, the growth factor-loaded complex microsphere is being added into the synthesising biological material solution
Before, the growth factor-loaded complex microsphere is subjected to sieving processing, sieve mesh is 10-60 mesh, so that LDM printings can be smooth
Carry out.
In above-mentioned steps S02, using Computer Aided Modeling, layering and accumulation.Specifically, utilizing the Cark of LDM systems
Software, designs the print parameters of support.Then, batch can, feed pipe, shower nozzle are sequentially connected, the PLCL/ microspheres solutions are poured into
In batch can, refrigeration for refrigerator prepares shaping.Room temperature to be formed is down to -25~-35 DEG C or so, starts temperature control, numerical control, starts to make
Type.Under software, the movement locus and modeling parameters of nozzle software design patterns be scanned in X, Y-axis and extrude ejection it is molten
Liquid, in a low temperature of solution is in forming room, quick solidification.When first layer printing terminates, shaped platform declines certain height on Z axis
Degree, nozzle proceeds new one layer of printing, and being layering to form a three-dimensional and freeze support.Frozen state is in after shaping
Support is placed into freeze drier after taking out rapidly, and organic solvent such as Isosorbide-5-Nitrae-dioxane (DIO) of solidification distils, with support
Generation gas-solid is separated, so that organic solvent is removed, the 3D printing support final molding of composite load TGF-β.Wherein, freeze dry
The dry time is 70-80h, preferably 72h.Using the ColI/CS complex microspheres of PLCL DIO, Fig. 1 load TGF-β 1 prepared as
Example, the schematic flow sheet for preparing the 3D printing support of composite load growth factor microballoon is as shown in Figure 2.
As a preferred embodiment, the modeling parameters are set to：Support specification is 23.6 × 23.6 × 23.6cm3,
Forming temperature is at -30 DEG C or so, nozzle diameter 0.6mm, spinneret spacing 0.8mm, sweep speed 22mm/s, and spray head speed 1.0~
2.0mm/s。
The embodiment of the present invention is ensures that growth factor is sustained steadily in the long term, except growth factor is wrapped in inside and outside microballoon,
Also improve a coated stent material, so that multiple protective is formed, with sustained release behavior steady in a long-term.Specifically, in Compound Negative
The complex microsphere for carrying growth factor after the 3D printing rack forming of growth factor microballoon is evenly distributed in synthesising biological material, is
Prominent release of growth factor is provided with current obstacle, so as to provide the guarantee of the second layer for the stable long-term sustained release of growth factor.This
Outside, the material of the 3D printing support of the composite load growth factor microballoon is degradation material, with higher security
With good bio-compatible, and supporting structure has controllable aperture and pore structure.
The preparation method of the 3D printing support of composite load growth factor microballoon provided in an embodiment of the present invention, the load
The complex microsphere of growth factor provides one layer of basic guarantee for the sustained release of biotic factor；Further, will be growth factor-loaded
Complex microsphere mixed with synthesising biological material solution after, three-dimensional stephanoporate compound stent is prepared using LDM technologies, there is support
Controllable one-level aperture size and structure, not only assigning the support has excellent mechanical property support, and the load
The complex microsphere of growth factor is overall dispersed in the synthesising biological material, while the synthesising biological material is to described
Growth factor-loaded complex microsphere carries out local parcel, is that prominent release of growth factor is provided with current obstacle, so as to be growth
The stable long-term sustained release of the factor provides double-deck ensure.In addition, the present invention accurately controls support one-level hole by LDM technologies
Size is 10-50 μm or so of interconnected secondary porosity in size, the prepared support of imparting, so as to be the steady of growth factor
Fixed slow persistently release provides effective passage.
And, the embodiment of the present invention additionally provides a kind of composite load growth factor microballoon prepared by the above method
3D printing support, the 3D printing support of the composite load growth factor microballoon is synthesising biological material and growth factor-loaded
The three-dimensional porous rack that is made of complex microsphere.
As a specific embodiment, a kind of 3D of the composite load growth factor microballoon prepared by the above method is beaten
Support is printed, the 3D printing support of the composite load growth factor microballoon is combined micro- for PLCL and load TGF-β 1 ColI/CS
The unit porous support that ball is made, wherein, the ColI/CS complex microspheres of the load TGF-β 1 are formed including TGF-β 1 and ColI
Mixing microballoon, and the mixing microsphere surface parcel CS, and the CS and the ColI crosslinking combine to form surface mesh
Network structure.It is preferred that the composite load growth factor microballoon 3D printing support CS network structures and PLCL entirety
Dispersed and local parcel, is that prominent release of growth factor TGF-β 1 is provided with double-deck current obstacle, so as to assign described compound
The excellent stable sustained-release performance of the 3D printing support of growth factor-loaded microballoon.
The 3D printing support of composite load growth factor microballoon provided in an embodiment of the present invention, not only with good mechanics
Performance, and the synthesising biological material carries out local parcel to the growth factor-loaded complex microsphere, is growth factor
Prominent release be provided with double-deck current obstacle so that excellent steady of the 3D printing support for assigning the composite load growth factor microballoon
Determine sustained release performance.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
Any modifications, equivalent substitutions and improvements made within refreshing and principle etc., should be included in the scope of the protection.
Claims (10)
1. a kind of preparation method of the 3D printing support of composite load growth factor microballoon, comprises the following steps：
Growth factor-loaded complex microsphere and synthesising biological material solution is provided, by the growth factor-loaded complex microsphere
The synthesising biological material solution is added, stirs to form synthesising biological material/microspheres solution；
Using the print parameters of the Cark Software for Design three-dimensional composite material supports of LDM systems, be sequentially connected batch can, feed pipe,
Shower nozzle, the synthesising biological material/microspheres solution is poured into batch can；When room temperature to be formed is down to -25~-35 DEG C, start
Temperature control, numerical control, using the Cark software design patterns modeling parameters start print moulding, be layering to be formed a three-dimensional freeze branch
Frame；The three-dimensional is freezed to carry out freeze-drying process after support takes out, the 3D printing of composite load growth factor microballoon is obtained
Support.
2. the preparation method of the 3D printing support of composite load growth factor microballoon as claimed in claim 1, it is characterised in that
In the synthesising biological material/microspheres solution, the mass concentration of the growth factor-loaded complex microsphere is 0.001-
1000mg/mL。
3. the preparation method of the 3D printing support of composite load growth factor microballoon as claimed in claim 1, it is characterised in that
The mass concentration percentage of the synthesising biological material solution is 8-20wt%.
4. the preparation method of the 3D printing support of the composite load growth factor microballoon as described in claim 1-3 is any, it is special
Levy and be, before the growth factor-loaded complex microsphere is added into the synthesising biological material solution, the load is given birth to
The complex microsphere of the long factor carries out sieving processing, and sieve mesh is 10-60 mesh.
5. the preparation method of the 3D printing support of the composite load growth factor microballoon as described in claim 1-3 is any, it is special
Levy and be, the microballoon in the growth factor-loaded complex microsphere is the microballoon that natural material is made.
6. the preparation method of the 3D printing support of composite load growth factor microballoon as claimed in claim 5, it is characterised in that
The natural material includes natural polymer albumen and polysaccharide.
7. the preparation method of the 3D printing support of composite load growth factor microballoon as claimed in claim 6, it is characterised in that
The natural material including collagen, chondroitin sulfate, chitosan, fibroin, hyaluronic acid, one kind in sodium alginate or two
Kind.
8. the preparation method of the 3D printing support of the composite load growth factor microballoon as described in claim 1-3 is any, it is special
Levy and be, the growth factor includes TGF, BMP, IGF.
9. the preparation method of the 3D printing support of the composite load growth factor microballoon as described in claim 1-3 is any, it is special
Levy and be, the synthesising biological material includes PLCL, PLGA, PLLA, PLA, PHA, PGA, PVA.
10. a kind of 3D printing branch of the composite load growth factor microballoon prepared by any methods describeds of claim 1-9
Frame, the 3D printing support of the composite load growth factor microballoon is synthesising biological material and growth factor-loaded complex microsphere
The three-dimensional porous rack being made.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610969574.9A CN107308502A (en) | 2016-10-28 | 2016-10-28 | 3D printing support of composite load growth factor microballoon and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610969574.9A CN107308502A (en) | 2016-10-28 | 2016-10-28 | 3D printing support of composite load growth factor microballoon and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107308502A true CN107308502A (en) | 2017-11-03 |
Family
ID=60185453
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610969574.9A Pending CN107308502A (en) | 2016-10-28 | 2016-10-28 | 3D printing support of composite load growth factor microballoon and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107308502A (en) |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107982579A (en) * | 2017-11-21 | 2018-05-04 | 上海纳米技术及应用国家工程研究中心有限公司 | 3D printing carries preparation method of the nano combined artificial bone of Types of Medicine and products thereof and application |
| CN108030573A (en) * | 2017-12-15 | 2018-05-15 | 中国科学院深圳先进技术研究院 | Load complex stephanoporate bracket of drug bearing microsphere and its preparation method and application |
| CN108079371A (en) * | 2018-01-10 | 2018-05-29 | 深圳市第二人民医院 | It is sustained three-dimensional rack of Kartogenin and preparation method thereof |
| CN108379659A (en) * | 2018-05-06 | 2018-08-10 | 西北工业大学 | A kind of more gradient artificial cartilage preparation methods of cell density |
| CN108744065A (en) * | 2018-08-03 | 2018-11-06 | 广州博敏科技有限公司 | A kind of tissue recovery support and its preparation method and application |
| CN109330743A (en) * | 2018-09-21 | 2019-02-15 | 深圳市晶莱新材料科技有限公司 | A kind of 3D printing tissue engineering bracket and preparation method thereof |
| CN109646715A (en) * | 2019-01-25 | 2019-04-19 | 上海交通大学医学院附属第九人民医院 | Electrospinning 3D printing prepares the multilayer cartilage complex of factor-containing microballoon |
| CN109837215A (en) * | 2019-01-25 | 2019-06-04 | 上海交通大学医学院附属第九人民医院 | Melt the tendon synostosis three-phase bracket of electrospinning 3 D-printing preparation |
| CN110433331A (en) * | 2019-08-26 | 2019-11-12 | 四川大学 | A kind of bioactive bracket and preparation method thereof |
| CN112494728A (en) * | 2020-12-03 | 2021-03-16 | 广东省医疗器械研究所 | Microsphere-based stent and preparation method and application thereof |
| CN112755253A (en) * | 2020-12-03 | 2021-05-07 | 广东省医疗器械研究所 | Microsphere hydrogel stent and preparation method and application thereof |
| CN113858610A (en) * | 2021-09-06 | 2021-12-31 | 江苏卓见医疗用品有限公司 | Medical fibrous surface dressing and preparation method and application thereof |
| CN114796617A (en) * | 2022-05-25 | 2022-07-29 | 中山大学 | Composite 3D printing ink and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102886076A (en) * | 2012-09-27 | 2013-01-23 | 深圳清华大学研究院 | Bone repair porous bracket and rapid forming method |
| CN104623737A (en) * | 2014-12-31 | 2015-05-20 | 深圳清华大学研究院 | Personalized tissue repairing scaffold capable of realizing pulsed sustained release and preparation method thereof |
| CN105031718A (en) * | 2015-08-27 | 2015-11-11 | 华南理工大学 | Bone repair porous compound scaffold based on 3D (three-dimensional)-Bioplotter printing technology and preparation method thereof |
| CN105727368A (en) * | 2016-01-08 | 2016-07-06 | 深圳市第二人民医院 | Three-dimensional composite material support and preparation method thereof |
-
2016
- 2016-10-28 CN CN201610969574.9A patent/CN107308502A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102886076A (en) * | 2012-09-27 | 2013-01-23 | 深圳清华大学研究院 | Bone repair porous bracket and rapid forming method |
| CN104623737A (en) * | 2014-12-31 | 2015-05-20 | 深圳清华大学研究院 | Personalized tissue repairing scaffold capable of realizing pulsed sustained release and preparation method thereof |
| CN105031718A (en) * | 2015-08-27 | 2015-11-11 | 华南理工大学 | Bone repair porous compound scaffold based on 3D (three-dimensional)-Bioplotter printing technology and preparation method thereof |
| CN105727368A (en) * | 2016-01-08 | 2016-07-06 | 深圳市第二人民医院 | Three-dimensional composite material support and preparation method thereof |
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107982579A (en) * | 2017-11-21 | 2018-05-04 | 上海纳米技术及应用国家工程研究中心有限公司 | 3D printing carries preparation method of the nano combined artificial bone of Types of Medicine and products thereof and application |
| CN108030573A (en) * | 2017-12-15 | 2018-05-15 | 中国科学院深圳先进技术研究院 | Load complex stephanoporate bracket of drug bearing microsphere and its preparation method and application |
| CN108030573B (en) * | 2017-12-15 | 2020-06-05 | 中国科学院深圳先进技术研究院 | Composite porous scaffold loaded with drug-loaded microspheres as well as preparation method and application thereof |
| CN108079371A (en) * | 2018-01-10 | 2018-05-29 | 深圳市第二人民医院 | It is sustained three-dimensional rack of Kartogenin and preparation method thereof |
| CN108379659A (en) * | 2018-05-06 | 2018-08-10 | 西北工业大学 | A kind of more gradient artificial cartilage preparation methods of cell density |
| CN108744065B (en) * | 2018-08-03 | 2021-08-31 | 广州博敏科技有限公司 | Tissue repair stent and preparation method and application thereof |
| CN108744065A (en) * | 2018-08-03 | 2018-11-06 | 广州博敏科技有限公司 | A kind of tissue recovery support and its preparation method and application |
| CN109330743A (en) * | 2018-09-21 | 2019-02-15 | 深圳市晶莱新材料科技有限公司 | A kind of 3D printing tissue engineering bracket and preparation method thereof |
| CN109646715A (en) * | 2019-01-25 | 2019-04-19 | 上海交通大学医学院附属第九人民医院 | Electrospinning 3D printing prepares the multilayer cartilage complex of factor-containing microballoon |
| CN109837215A (en) * | 2019-01-25 | 2019-06-04 | 上海交通大学医学院附属第九人民医院 | Melt the tendon synostosis three-phase bracket of electrospinning 3 D-printing preparation |
| CN110433331A (en) * | 2019-08-26 | 2019-11-12 | 四川大学 | A kind of bioactive bracket and preparation method thereof |
| CN110433331B (en) * | 2019-08-26 | 2021-08-24 | 四川大学 | Bioactive scaffold and preparation method thereof |
| WO2021035842A1 (en) * | 2019-08-26 | 2021-03-04 | 四川大学 | Bioactive scaffold and preparation method therefor |
| CN112494728A (en) * | 2020-12-03 | 2021-03-16 | 广东省医疗器械研究所 | Microsphere-based stent and preparation method and application thereof |
| CN112755253A (en) * | 2020-12-03 | 2021-05-07 | 广东省医疗器械研究所 | Microsphere hydrogel stent and preparation method and application thereof |
| CN113858610A (en) * | 2021-09-06 | 2021-12-31 | 江苏卓见医疗用品有限公司 | Medical fibrous surface dressing and preparation method and application thereof |
| CN113858610B (en) * | 2021-09-06 | 2024-04-19 | 江苏卓见医疗用品有限公司 | Medical fibrous surface dressing and preparation method and application thereof |
| CN114796617A (en) * | 2022-05-25 | 2022-07-29 | 中山大学 | Composite 3D printing ink and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107308502A (en) | 3D printing support of composite load growth factor microballoon and preparation method thereof | |
| Hutmacher et al. | Scaffold design and fabrication | |
| Zhang et al. | A review of preparation methods of porous skin tissue engineering scaffolds | |
| Walker et al. | Processing and production of bioresorbable polymer scaffolds for tissue engineering | |
| Bhamidipati et al. | The future of carbon dioxide for polymer processing in tissue engineering | |
| Wu et al. | polymeric-based 3D printing for tissue engineering | |
| US6471993B1 (en) | Three-dimensional polymer matrices | |
| CN103057123B (en) | A kind of three dimensional biological print system and prepare the method for nerve regeneration implant based on three dimensional biological print system | |
| Zhang et al. | 3D printing method for bone tissue engineering scaffold | |
| Liu et al. | Multinozzle low‐temperature deposition system for construction of gradient tissue engineering scaffolds | |
| TWI264301B (en) | Multi-channel bioresorbable nerve regeneration conduit and preparation method for the same | |
| CN105457101B (en) | A kind of preparation method of three-decker small-caliber vascular stent | |
| Bártolo et al. | Advanced processes to fabricate scaffolds for tissue engineering | |
| Liu et al. | Development of biodegradable scaffolds for tissue engineering: a perspective on emerging technology | |
| CN114504407B (en) | 3D printing skull repairing titanium mesh containing growth factors and preparation method thereof | |
| Meng et al. | Melt-based, solvent-free additive manufacturing of biodegradable polymeric scaffolds with designer microstructures for tailored mechanical/biological properties and clinical applications | |
| CN108992212B (en) | Bone-cartilage integrated repair scaffold and preparation method thereof | |
| Kovylin et al. | Modern porous polymer implants: synthesis, properties, and application | |
| CN106390208A (en) | Three-dimensional support material containing hierarchical porous structures and preparation and application | |
| Karande et al. | Function and requirement of synthetic scaffolds in tissue engineering | |
| Safinsha et al. | Composite scaffolds in tissue engineering | |
| Ansari et al. | A review of bone regeneration mechanisms and bone scaffold fabrication techniques (conventional and non-conventional) | |
| Kozan et al. | Porous biomaterial scaffolds for skeletal muscle tissue engineering | |
| Yadav et al. | Applications of Scaffolds in Tissue Engineering: Current Utilization and Future Prospective | |
| CN108744065A (en) | A kind of tissue recovery support and its preparation method and application |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20171103 |
|
| RJ01 | Rejection of invention patent application after publication |