CN109078225A - The preparation method and application of the controllable multilayer functionality bracket of three-dimensional structure - Google Patents
The preparation method and application of the controllable multilayer functionality bracket of three-dimensional structure Download PDFInfo
- Publication number
- CN109078225A CN109078225A CN201810926315.7A CN201810926315A CN109078225A CN 109078225 A CN109078225 A CN 109078225A CN 201810926315 A CN201810926315 A CN 201810926315A CN 109078225 A CN109078225 A CN 109078225A
- Authority
- CN
- China
- Prior art keywords
- bracket
- dimensional structure
- preparation
- material strip
- polyethylene oxide
- 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
-
- 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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
-
- 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
-
- 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
- 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
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Botany (AREA)
- Cell Biology (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention belongs to medical material tech fields, disclose a kind of preparation method and application of the multilayer functionality bracket of three-dimensional controlled architecture, moisture is dried method includes the following steps: medical grade l-lactic acid pellet and polyethylene oxide pellet are placed in baking oven, it is subsequently placed in single screw extrusion machine and carries out melt blending, squeeze out material strip；Material strip is subjected to tensionless winkler foundation cooling using three-roller calendar, the material strip that length is 40 ~ 60cm is then cut into, obtains the polylactic acid with alternate multiple concentric cylinder configuration/polyethylene oxide extrudate；Polylactic acid/polyethylene oxide extrudate is cut into the material strip that length is 5 ~ 20mm again, obtains supporting frame prefabrication product through heat pressing process, drilling technology or winding process；Supporting frame prefabrication product are placed in removal polyethylene oxide layer, leaching in deionized water and obtain the controllable multilayer functionality bracket of three-dimensional structure.This method simple process, applicability is wide, low in cost, environmental-friendly, high production efficiency, and stent applications range is wide.
Description
Technical field
The invention belongs to medical material tech fields, and in particular to the preparation of the multilayer functionality bracket of three-dimensional controlled architecture
Method and application.
Background technique
The biology of nature has gradually evolved various exquisite structures, so that having in many cases outstanding
Function.As one of most representative and most attracting example, biological multi-tier systematic structure is shown respectively in organism
The form (such as bone, blood vessel and skin) of kind various kinds.Such structure plays support organism, avoids the function of oozing of blood and barrier
Energy.In general, biological multi-tier systematic structure consists of two parts, i.e., single micro- in the macroscopic view assembling and minute yardstick of microbedding
Layer.On a macroscopic scale (from several hundred microns to millimeter), the bracket with three-dimensional structure can not only simulate natural fabric structure,
Cell can also be made to grow into optimal tissue.On a microscopic scale, the local pattern of bracket can provide key for cell
Microenvironment is thus to control the various actions of cell (as being proliferated, differentiation etc.).Therefore, by the structural integrity of different scale to one
It is an a matter of great account feelings on a bracket.
By the inspiration of the Nature biological structure functional characteristic, a large amount of energy has had been put into researcher has to prepare
The functional bracket of multilayered structure.Perhaps multiple technologies, including the casting of electrospinning, solvent, mutually separate micro Process, is LBL self-assembly, cold
It is lyophilized and dry etc. has been used in the manufacture of this bracket.However, still there are many problems in the above method, such as using toxic solvent,
The organic solvent residue of internal stent is difficult to be mass produced etc..Therefore, it is highly desirable that with a kind of extensive and environmental protection
Mode manufacture the functional bracket of multilayered structure.On the other hand, due to being difficult to for ready preforming material being converted into
The new bracket with different structure and be obstructed, and greatly reduce the application range of multilayer bracket.Therefore, various in order to meet
The different demands of application, the flexible three-dimensional structure for converting bracket is another extremely important thing.
Summary of the invention
The purpose of the present invention is to provide a kind of preparation method of multilayer functionality bracket that three-dimensional structure is controllable, applicabilities
Extensively, low in cost, environmental-friendly, high production efficiency.
Another object of the present invention is to provide the multilayer functions of the scaffold three-dimensional structure-controllable of above-mentioned preparation method preparation
The application of property bracket.
To achieve the above object, the invention adopts the following technical scheme:
The preparation method of the controllable multilayer functionality bracket of three-dimensional structure, comprising the following steps:
Step 1: medical grade l-lactic acid pellet and polyethylene oxide pellet being placed in baking oven and dry moisture, is subsequently placed in list
Melt blending is carried out in screw extruder, squeezes out material strip；
Step 2: it is cooling that material strip obtained in step 1 using three-roller calendar is subjected to tensionless winkler foundation, then cut into length be 40 ~
The material strip of 60cm obtains the polylactic acid with alternate multiple concentric cylinder configuration/polyethylene oxide extrudate；
Step 3: polylactic acid obtained in step 2/polyethylene oxide extrudate is cut into the material strip that length is 5 ~ 20mm again,
Supporting frame prefabrication product are obtained through heat pressing process, drilling technology or winding process；
Step 4: supporting frame prefabrication product obtained in step 3 being placed in removal polyethylene oxide layer, leaching in deionized water and are obtained
The controllable multilayer functionality bracket of three-dimensional structure.
Further, the temperature of baking oven described in step 1 be 30 ~ 45 DEG C, drying time be 12 ~ for 24 hours.
Further, the mass ratio of the pellet of medical grade l-lactic acid described in step 1 and polyethylene oxide pellet is 1:
(0.6 ~ 1.5).
Further, the revolving speed of single screw extrusion machine described in step 1 is 10 ~ 60rpm/min, extrusion temperature is 170 DEG C.
Further, heat pressing process described in step 3 be 80 ~ 130 DEG C in hot pressing temperature at the material strip suppressed
Different macroshapes.
Further, drilling technology described in step 3 is that inside of different shapes is drilled out on the cross section of the material strip
Channel.
Further, winding process described in step 3 is the outer surface shape that enameled wire or gauze are wound to the material strip
At different surface topographies.
Further, supporting frame prefabrication product described in step 4 be placed in the time in deionized water be 15 days.
The present invention also provides the controllable multilayer functionality brackets of the three-dimensional structure of above-mentioned preparation method preparation to convey in drug
In application.
The present invention also provides the controllable multilayer functionality brackets of the three-dimensional structure of above-mentioned preparation method preparation to connect certainly in culture
Application in kind cell.
Compared with prior art, the beneficial effects of the present invention are:
1. the present invention prepares polylactic acid/polyethylene oxide with alternate multiple concentric cylinder configuration by melting extrusion processing
Extrudate, layer and interlayer clear-cut, it is connectionless, change its macroshape, internal structure through hot pressing, punching or winding processing
And surface topography obtains the controllable multilayer functionality bracket of three-dimensional structure and after removing PEO, the microbedding in bracket and
Gap be it is alternately arranged, brace aperture rate is up to 69%.
2. the controllable multilayer functionality bracket of three-dimensional structure prepared by the present invention have simultaneously macro-scale, micro-scale and
The structure of nanoscale, this structure result in bracket with powerful capillary force, facilitate hydrophily and lipophilic drugs
Absorption and cell from being inoculated with, and keep stent applications range wider, can satisfy the requirement of different field.
3. preparation method of the present invention uses the material and process equipment of simple general-purpose, appoint in process without addition
What poisonous and harmful solvent, environmental-friendly, simple process and low cost, easily controllable, high production efficiency solve existing preparation
The problem of scale, the inexpensive multilayer functionality bracket for producing structure-controllable are difficult in method.
Detailed description of the invention
Fig. 1 is polylactic acid of the present invention/polyethylene oxide extrudate preparation process schematic diagram.
Fig. 2 is that polylactic acid of the present invention/polyethylene oxide extrudate is placed in deionized water after removal polyethylene oxide phase
Electron scanning micrograph.
Fig. 3 is the clearance distance inside polylactic acid of the present invention/polyethylene oxide extrudate between microlayer thickness and microbedding
Statistic histogram.
Fig. 4 is the electron scanning micrograph of the multilayer functionality bracket in embodiment 1 with different macroshapes.
Fig. 5 is the electron scanning micrograph of the multilayer functionality bracket in embodiment 2 with different inner passages.
Fig. 6 is the photo of the multilayer functionality bracket in embodiment 3 with different surface morphology.
Fig. 7 is that the oil/water wetability of multilayer functionality bracket of the present invention detects figure.
Fig. 8 is the drug loading distribution map of multilayer functionality bracket of the present invention.
Fig. 9 is that multilayer functionality bracket of the present invention adsorbs the In-vitro release curves after two kinds of drugs.
Figure 10 is cell distribution maps of the multilayer functionality bracket of the present invention from inoculating cell.
Specific embodiment
The following examples are intended to illustrate the invention, but is not used to limit the scope of protection of the present invention.Unless otherwise specified, real
Apply the conventional means that technological means used in example is well known to those skilled in the art.Test method in following embodiments, such as
It is conventional method without special instruction.
Baking oven model ZKSFB-1 in following embodiments establishes instrument and meter Co., Ltd purchased from Shanghai；Single screw rod squeezes out
The model CJS-20 of machine is purchased from the triumphant Electromechanical Technology Co., Ltd of upper Hydron；The model Y002 of vacuum film pressing machine is purchased from Zhengzhou
Craftsman's mechanical equipment Co., Ltd；Medical grade l-lactic acid pellet (PLLA, 1.97 × 105G/mol) it is purchased from the U.S.
NatureWorks；Polyethylene oxide (PEO, 1 × 105G/mol) it is purchased from DOW Chemical.
Embodiment 1
The preparation method of the controllable multilayer functionality bracket of three-dimensional structure, comprising the following steps:
Step 1: 800g PLLA pellet and 1200g PEO pellet are placed in baking oven at 40 DEG C, 12h is dried, dries moisture,
It is put into OS OVER SIZE valve bag to be uniformly mixed, is subsequently placed in single screw extrusion machine and carries out melt blending, be 170 in extrusion temperature
DEG C, screw speed be 20rpm/min under squeeze out material strip.
Step 2: material strip obtained in step 1 being subjected to tensionless winkler foundation cooling using three-roller calendar, then cuts into length
For the material strip of 40cm, the polylactic acid with alternate multiple concentric cylinder configuration/polyethylene oxide extrudate is obtained.
Step 3: polylactic acid obtained in step 2/polyethylene oxide extrudate is cut into the material that length is 10mm again
Then item is fixed in triangle, rectangle and the oval mold of customization, vacuum film pressing machine is warming up to 100 DEG C, and will material
Item is placed in vacuum film pressing machine and keeps the temperature 10 minutes, then material strip is taken out manual pressure 1 minute, respectively obtains and cuts with triangle
The supporting frame prefabrication product in face, rectangular cross-sectional and elliptic cross-section, as shown in Fig. 4-a ~ 4-c.
The present invention does not limit the shape of mold specifically, and the shape of mold can also be other polygons, truncated cone-shaped
Deng.
Step 4: three kinds of supporting frame prefabrication product obtained in step 3 being placed in 15 days removal PEO phases in deionized water, are dripped
Filter obtains three kinds of multilayer functionality brackets with different macroshapes, as shown in Fig. 4-d ~ 4-f.
The signal of polylactic acid in step 2 of the present invention/polyethylene oxide extrudate preparation process is shown with reference to Fig. 1, Fig. 1
Figure, wherein 1-a is extrusion molding process schematic；1-b is the material strip cut after squeezing out；1-c is the polarisation picture of material strip.It will step
Polylactic acid/polyethylene oxide extrudate of the alternate multiple concentric cylinder configuration of rapid 2 preparation is along cross-sectional direction in ultra-thin section
On machine, the ultra-thin section with a thickness of 20 μm is cut, is subsequently placed in the petrographic microscope for being 50 times in amplification factor on glass slide
Microstructure is observed under (Olympus BX51 type), wherein perpendicular to extrusion direction, as a result as shown in fig 1-c cross section is.By
Fig. 1-c, which can be seen that, many regular concentric ring microbeddings in polarisation picture, this concentric ring microbedding by PLLA layer with
PEO layer alternately forms, and does not connect between layers.
With reference to Fig. 2, Fig. 2 shows polylactic acid of the present invention/polyethylene oxide extrudates (not carrying out heat pressing process processing) to put
It is placed in deionized water and removes the electron scanning micrograph after polyethylene oxide phase, wherein 2-a ~ 2-c is the transversal of bracket
Face picture；2-d ~ 2-f is the longitudinal section picture of bracket；2-g ~ 2-i is the inside microbedding surface of bracket.As seen from Figure 2, this
The bracket that kind method is prepared has multilayer concentric cylindrical structure, and does not connect between layers, microbedding and clearance height
It is orderly alternately arranged, forms perfect multilayered structure.This interesting morphology evolution should be mainly due to melt extrusion
Shearing Flow in the process, under the weak Shearing Flow that single screw extrusion machine is formed, discrete PLLA drop and PEO drop more have
It may merge rather than divide.Then, the PLLA drop and PEO drop individually coalesced can form complete microbedding, and due to
Shearing Flow and be further combined into an alternate multilayered structure.Microbedding forms under the action of flow field and is parallel to extrusion side
To groove, since PLLA crystallization yet forms the chip of nanoscale, this micro-nano structure facilitates the growth of cell.
It shows polylactic acid of the present invention/polyethylene oxide extrudate with reference to Fig. 3, Fig. 3 and is placed in remove in deionized water and gather
Inside microlayer thickness after ethylene oxide phase and the gap width statistic histogram between microbedding, wherein 3-a is microlayer thickness
Statistical chart, 3-b are gap width statistical chart.The cross section of extrudate is analyzed, and with Image J software to image into
Analysis is gone, to measure the microlayer thickness and gap width between adjacent microlayers.30 measurements have been carried out to each sample, have been surveyed altogether
10 samples are measured.From figure 3, it can be seen that microlayer thickness and gap width meet normal distribution, average value is respectively 10 μ
M and 20 μm, the structure of this concentric cylindrical can guarantee the high porosity of extrudate.
It is to show the scanning electricity of the multilayer functionality bracket in the present embodiment with different macroshapes with reference to Fig. 4, Fig. 4
Sub- microscope photograph, wherein 4-a ~ 4-c is the supporting frame prefabrication product with different macroshapes handled through heat pressing process；4-
D ~ 4-f is the controllable multilayer functionality bracket of the three-dimensional structure of the different macroshapes of removal PEO layer；4-g ~ 4-i is figure respectively
The amplification picture of microbedding in 4-d ~ 4-f.It can be seen that after heat pressing process is handled from Fig. 4-g ~ 4-i, multilayer functionality bracket
Microbedding is not destroyed.
Embodiment 2
The preparation method of the controllable multilayer functionality bracket of three-dimensional structure, comprising the following steps:
Step 1: 800g PLLA pellet and 1200g PEO pellet are placed in baking oven at 30 DEG C, drying for 24 hours, dries moisture,
It is put into OS OVER SIZE valve bag to be uniformly mixed, is subsequently placed in single screw extrusion machine and carries out melt blending, be 170 in extrusion temperature
DEG C, screw speed be 40rpm/min under squeeze out material strip.
Step 2: material strip obtained in step 1 being subjected to tensionless winkler foundation cooling using three-roller calendar, then cuts into length
For the material strip of 60cm, the polylactic acid with alternate multiple concentric cylinder configuration/polyethylene oxide extrudate is obtained.
Step 3: polylactic acid obtained in step 2/polyethylene oxide extrudate is cut into the material that length is 10mm again
Then item is fixed on scroll chuck and is put in Miniature electric drill in the following, the drill bit that diameter is 1mm, 0.6mm and 0.35mm is fixed on
Miniature electric drill, starting Miniature electric drill drill, respectively obtain triple channel that single channel, aperture that aperture is 1mm are 0.6mm and
Aperture is the supporting frame prefabrication product in six channels of 0.35mm, as shown in Fig. 5-a ~ 5-c.
Step 4: three kinds of supporting frame prefabrication product obtained in step 3 being placed in 15 days removal PEO phases in deionized water, are dripped
Filter obtains three kinds of multilayer functionality brackets with different inner passages, as shown in Fig. 5-d ~ 5-f.
Referring to figure 5., Fig. 5 shows the scanning electricity of the multilayer functionality bracket in the present embodiment with different inner passages
Sub- microscope photograph, wherein 5-a ~ 5-c is the supporting frame prefabrication product with different inner passages handled through drilling technology；5-
D ~ 5-f is the controllable multilayer functionality bracket of the three-dimensional structure of the different inner passages of removal PEO layer；5-g ~ 5-i is figure respectively
The amplification picture of microbedding in 5-d ~ 5-f.It can be seen that after drilling technology is handled from Fig. 5-g ~ 5-i, multilayer functionality bracket
Microbedding is not destroyed.
Embodiment 3
The preparation method of the controllable multilayer functionality bracket of three-dimensional structure, comprising the following steps:
Step 1: 800g PLLA pellet and 1200g PEO pellet are placed in baking oven at 40 DEG C, drying for 24 hours, dries moisture,
It is put into OS OVER SIZE valve bag to be uniformly mixed, is subsequently placed in single screw extrusion machine and carries out melt blending, be 170 in extrusion temperature
DEG C, screw speed be 30rpm/min under squeeze out material strip.
Step 2: material strip obtained in step 1 being subjected to tensionless winkler foundation cooling using three-roller calendar, then cuts into length
For the material strip of 40cm, the polylactic acid with alternate multiple concentric cylinder configuration/polyethylene oxide extrudate is obtained.
Step 3: polylactic acid obtained in step 2/polyethylene oxide extrudate is cut into the material that length is 20mm again
The enameled wire that diameter is 0.1mm is wound in a manner of helix material strip surface, leaves no gaps, obtain between line and line by item
Surface has the supporting frame prefabrication product of spiral grooves, as shown in Fig. 6-a；The enameled wire that diameter is 0.1mm is wound to one piece of side length
It is left no gaps between line to wind on the square iron sheet of 10mm, winding line length is 8mm, then will be stained on one side with adhesive tape
And separated both sides with scalpel to obtain the enameled wire of uniform parallel arrangement, enameled wire arranged in parallel is placed to material strip surface
And wrap to obtain the supporting frame prefabrication product that surface has parallel groove with enameled wire, as shown in Fig. 6-b；It is wound with the gauze of 500 mesh
Interface is clung to material strip surface blend compounds band, the supporting frame prefabrication product that surface has recess can be obtained, as shown in Fig. 6-c.
The present invention does not limit the diameter of enameled wire specifically, and diameter can be 0.1mm, 0.05mm and 0.2mm；This hair
It is bright to gauze specification without specifically limiting, gauze can be 500 mesh, 400 mesh and 300 mesh.
Step 4: three kinds of supporting frame prefabrication product obtained in step 3 being placed in 15 days removal PEO phases in deionized water, are dripped
Filter obtains three kinds of multilayer functionality brackets with different surface morphology, as shown in Fig. 6-d ~ 6-f.
Fig. 6 is please referred to, Fig. 6 shows the picture of the multilayer functionality bracket in the present embodiment with different surface morphology,
Wherein 6-a ~ 6-c is the super depth-of-field microscope picture of the supporting frame prefabrication product handled through winding process；6-d ~ 6-f is bracket
Scanning electron microscope diagram piece；6-g ~ 6-i is the three-dimensional Laser Scanning Confocal Microscope picture of bracket；6-j- ~ 6-l is 6-g ~ 6-i respectively
The corresponding Z axis depth picture of middle dotted line.From fig. 6, it can be seen that the microbedding of multilayer functionality bracket does not have after winding process is handled
It is destroyed.
Embodiment 4
The present embodiment is substantially the same manner as Example 1, the difference is that: by 800g PLLA pellet and 800g PEO in step 1
Material is placed in baking oven at 45 DEG C, and drying for 24 hours, dries moisture, is put into OS OVER SIZE valve bag and is uniformly mixed, is subsequently placed in single screw rod
Melt blending is carried out in extruder, squeezes out material strip in the case where extrusion temperature is 170 DEG C, screw speed is 60rpm/min.In step 3
Polylactic acid/polyethylene oxide extrudate is cut into the material strip that length is 5mm again, vacuum film pressing machine is warming up to 80 DEG C.
Embodiment 5
The present embodiment is substantially the same manner as Example 1, the difference is that: step 1: by 800g PLLA pellet and 480g PEO
Material is placed in baking oven at 30 DEG C, and drying for 24 hours, dries moisture, is put into OS OVER SIZE valve bag and is uniformly mixed, is subsequently placed in single screw rod
Melt blending is carried out in extruder, squeezes out material strip in the case where extrusion temperature is 170 DEG C, screw speed is 10rpm/min.In step 3
Polylactic acid/polyethylene oxide extrudate is cut into the material strip that length is 15mm again, vacuum film pressing machine is warming up to 130 DEG C.
Embodiment 6
Multilayer functionality bracket obtained in Example 1 is carried out using characterization:
(1) porosity of multilayer functionality bracket is measured using liquid displacement technique.The weight and volume for recording bracket first (divides
It Wei not W0And V0), then bracket is dipped in ethanol solution to saturation state, weight is denoted as W at this time1, then porosity calculates
Are as follows: (W1-W0)/(V0× ρ) × 100%, wherein ρ is the density of ethyl alcohol.Ten samples are measured and then average, and obtain it
Porosity is 69%.
(2) the oil/water wetability of multilayer functionality bracket is observed using high-speed camera.One oil dripping or water are vertically dripped
Bracket cross section is dropped down onto, as a result as shown in fig. 7, wherein 7-a is oil, 7-b is water.As seen from Figure 7, oil and water can be non-
It is inhaled into internal stent in often short time, showing bracket has excellent amphiphilic, can be very good to adsorb and load parent
Aqueous and lipophilic drugs.
(3) the distribution picture of multilayer functionality bracket absorption different pharmaceutical is observed using fluorescence microscope.By multilayer function
Energy property bracket is dipped to 10ml cumarin ethanol solution and rhodamine aqueous solution respectively, and time 12h is cut after then taking out drying
Piece watches drug distribution situation, and as a result as shown in figure 8, wherein 8-a is slice schematic diagram, 8-b, 8-c are lipophilic drugs tonka-bean
Plain load distribution figure, 8-d, 8-e are hydrophilic medicament rhodamine load distribution figure.As seen from Figure 8, drug can uniformly divide
Cloth in the bracket between and end；In Fig. 8-b and 8-d, the center of concentric circles and edge are also without color difference, it may be said that are illustrated
The homogeneity of drug loading.It can thus be seen that multilayer functionality bracket prepared by the present invention can effectively load hydrophily
Lipophilic drugs.
(4) the multilayer functionality bracket of above-mentioned carrying medicament is subjected to simulation extracorporeal releasing experiment, and uses spectrophotometer
Quantitative statistics calculating is carried out, as a result as shown in figure 9, wherein 9-a is cumarin, 9-b is rhodamine.It can be seen in figure 9 that two
The release of kind drug all has apparent sustained releasing character.
(5) multilayer functionality bracket prepared by the present invention test from inoculating cell, in order to prove capillary force
Effect, is arranged two kinds of brackets: soaking the bracket and dry bracket of cell culture medium in advance.By 100 microlitres of bracket end thereof contacts
Cell suspending liquid, wait several seconds for clock, liquid can be adsorbed into internal stent, then carry out sections observation, as a result as scheme
Shown in 10, wherein 10-a is inoculation experiments and sections observation schematic diagram, and 10-b is the multilayer function of soaking cell culture medium in advance
Property bracket from inoculating cell experimental fluorescence picture, it is glimmering that 10-c ~ 10-f is that dry multilayer functionality bracket is tested from inoculating cell
Light picture.Due to the capillary force that bracket itself has it can be seen from Figure 10-b, 10-c, cell can be adsorbed uniformly
To internal stent, the inoculation efficiency of cell is improved, facilitate regeneration and simplifies clinical application.
The embodiment of the above, only presently preferred embodiments of the present invention, is only used to explain the present invention, not limit
The scope of the present invention processed to those of ordinary skill in the art certainly can be according to skill disclosed in this specification
Art content makes other embodiments easily by way of replacing or changing, therefore all made in the principle of the present invention
Changes and improvements etc., should be included in scope of the present invention patent.
Claims (10)
1. a kind of preparation method for the multilayer functionality bracket that three-dimensional structure is controllable, which comprises the following steps:
Step 1: medical grade l-lactic acid pellet and polyethylene oxide pellet being placed in baking oven and dry moisture, is subsequently placed in list
Melt blending is carried out in screw extruder, squeezes out material strip；
Step 2: it is cooling that material strip obtained in step 1 using three-roller calendar is subjected to tensionless winkler foundation, then cut into length be 40 ~
The material strip of 60cm obtains the polylactic acid with alternate multiple concentric cylinder configuration/polyethylene oxide extrudate；
Step 3: polylactic acid obtained in step 2/polyethylene oxide extrudate is cut into the material strip that length is 5 ~ 20mm again,
Supporting frame prefabrication product are obtained through heat pressing process, drilling technology or winding process；
Step 4: supporting frame prefabrication product obtained in step 3 being placed in removal polyethylene oxide layer, leaching in deionized water and are obtained
The controllable multilayer functionality bracket of three-dimensional structure.
2. the preparation method of the controllable multilayer functionality bracket of three-dimensional structure according to claim 1, which is characterized in that step
The temperature of baking oven described in rapid 1 be 30 ~ 45 DEG C, drying time be 12 ~ for 24 hours.
3. the preparation method of the controllable multilayer functionality bracket of three-dimensional structure according to claim 1, which is characterized in that step
The mass ratio of medical grade l-lactic acid pellet described in rapid 1 and polyethylene oxide pellet is 1:(0.6 ~ 1.5).
4. the preparation method of the controllable multilayer functionality bracket of three-dimensional structure according to claim 1, which is characterized in that step
The revolving speed of single screw extrusion machine described in rapid 1 is 10 ~ 60rpm/min, extrusion temperature is 170 DEG C.
5. the preparation method of the controllable multilayer functionality bracket of three-dimensional structure according to claim 1, which is characterized in that step
Heat pressing process described in rapid 3 be hot pressing temperature be 80 ~ 130 DEG C at the material strip is suppressed to different macroshapes.
6. the preparation method of the controllable multilayer functionality bracket of three-dimensional structure according to claim 1, which is characterized in that step
Drilling technology described in rapid 3 is that inner passage of different shapes is drilled out on the cross section of the material strip.
7. the preparation method of the controllable multilayer functionality bracket of three-dimensional structure according to claim 1, which is characterized in that step
Winding process described in rapid 3 is that the outer surface that enameled wire or gauze are wound to the material strip forms different surface topographies.
8. the preparation method of the controllable multilayer functionality bracket of three-dimensional structure according to claim 1, which is characterized in that step
Supporting frame prefabrication product described in rapid 4 be placed in the time in deionized water be 15 days.
9. the controllable multilayer functionality bracket of the three-dimensional structure of the described in any item preparation method preparations of claim 1 ~ 8 is in drug
Application in conveying.
10. the controllable multilayer functionality bracket of the three-dimensional structure of the described in any item preparation method preparations of claim 1 ~ 8 is being trained
It supports from the application in inoculating cell.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810926315.7A CN109078225B (en) | 2018-08-15 | 2018-08-15 | Preparation method and application of multilayer functional scaffold with controllable three-dimensional structure |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810926315.7A CN109078225B (en) | 2018-08-15 | 2018-08-15 | Preparation method and application of multilayer functional scaffold with controllable three-dimensional structure |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109078225A true CN109078225A (en) | 2018-12-25 |
| CN109078225B CN109078225B (en) | 2021-04-13 |
Family
ID=64793466
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810926315.7A Active CN109078225B (en) | 2018-08-15 | 2018-08-15 | Preparation method and application of multilayer functional scaffold with controllable three-dimensional structure |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109078225B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115717123A (en) * | 2022-11-21 | 2023-02-28 | 东华大学 | Method for culturing three-dimensional cell spheres by using parting nanofibers |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110264235A1 (en) * | 2010-04-21 | 2011-10-27 | Taipei Medical University | Electrostatic-assisted fiber spinning method and production of highly aligned and packed hollow fiber assembly and membrane |
| CN103088442A (en) * | 2013-01-23 | 2013-05-08 | 上海交通大学 | Preparation method of hollow fiber in coaxial electrostatic spinning |
| CN103981635A (en) * | 2014-05-09 | 2014-08-13 | 浙江省纺织测试研究院 | Preparation method of porous fiber non-woven fabric |
| CN106947228A (en) * | 2017-05-05 | 2017-07-14 | 四川大学 | Multistage porous poly-lactic acid material and preparation method thereof |
-
2018
- 2018-08-15 CN CN201810926315.7A patent/CN109078225B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110264235A1 (en) * | 2010-04-21 | 2011-10-27 | Taipei Medical University | Electrostatic-assisted fiber spinning method and production of highly aligned and packed hollow fiber assembly and membrane |
| CN103088442A (en) * | 2013-01-23 | 2013-05-08 | 上海交通大学 | Preparation method of hollow fiber in coaxial electrostatic spinning |
| CN103981635A (en) * | 2014-05-09 | 2014-08-13 | 浙江省纺织测试研究院 | Preparation method of porous fiber non-woven fabric |
| CN106947228A (en) * | 2017-05-05 | 2017-07-14 | 四川大学 | Multistage porous poly-lactic acid material and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115717123A (en) * | 2022-11-21 | 2023-02-28 | 东华大学 | Method for culturing three-dimensional cell spheres by using parting nanofibers |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109078225B (en) | 2021-04-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhang et al. | Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip | |
| Mohanty et al. | Fabrication of scalable and structured tissue engineering scaffolds using water dissolvable sacrificial 3D printed moulds | |
| Chen et al. | Nano-fibrous poly (L-lactic acid) scaffolds with interconnected spherical macropores | |
| Sheikh et al. | 3D electrospun silk fibroin nanofibers for fabrication of artificial skin | |
| Kitagawa et al. | Patterned hydrogel microfibers prepared using multilayered microfluidic devices for guiding network formation of neural cells | |
| Jiang et al. | Construction of chitosan scaffolds with controllable microchannel for tissue engineering and regenerative medicine | |
| Wei et al. | Cell alignment guided by nano/micro oriented collagen fibers and the synergistic vascularization for nervous cell functional expression | |
| Ghavidel Mehr et al. | Poly (ε-caprolactone) scaffolds of highly controlled porosity and interconnectivity derived from co-continuous polymer blends: model bead and cell infiltration behavior | |
| KR101830236B1 (en) | Nanofiber scaffold having moisturising and skin regeneration effect and method for preparing thereof | |
| WO2011153340A2 (en) | Scaffolds and methods of forming the same | |
| JP2005502351A (en) | Methods and structures for growing living organic tissue | |
| CN110327134A (en) | Detachable particular manufacturing craft and the method for preparing multiple-limb channel complex organ precursor | |
| Ren et al. | Study of sacrificial ink-assisted embedded printing for 3D perfusable channel creation for biomedical applications | |
| CN104327297B (en) | A kind of porous nano silver polyurethane film and preparation method thereof for artificial skin | |
| CN109078225A (en) | The preparation method and application of the controllable multilayer functionality bracket of three-dimensional structure | |
| CN110506138A (en) | Porous fibre and adsorption column | |
| Chimerad et al. | Tissue engineered scaffold fabrication methods for medical applications | |
| CN102429745B (en) | Nanometer artificial bone framework with transverse gradient hole structure and preparation method thereof | |
| CN108635619B (en) | Preparation method of multifunctional nanofiber composite gel dressing | |
| CN103120808B (en) | Preparation method of three-dimensional soft bracket | |
| CN113332312A (en) | Self-forming platelet nano-vesicle based on physical whole particles and preparation method thereof | |
| SE537634C2 (en) | Titandioxidscaffold | |
| Hong et al. | Multi-scale fabrication techniques of collagen hydrogel for developing physiological 3D in vitro barrier model | |
| CN106620877B (en) | A kind of capillary network and preparation method thereof | |
| DE19919242A1 (en) | Modular cell support systems for three-dimensional cell growth |
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 |