CN105311683B - A kind of network containing internal channel and the bionical tissue engineering bracket of directional pore structure and the preparation method and application thereof - Google Patents
A kind of network containing internal channel and the bionical tissue engineering bracket of directional pore structure and the preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a kind of networks containing internal channel and the bionical tissue engineering bracket of directional pore structure and the preparation method and application thereof.The bionical tissue engineering bracket includes rack body and the channel network that is set in the rack body；The rack body has orientation micropore structure, and is mutually communicated between the orientation macropore of the orientation micropore structure by lateral aperture realization；The channel network has classification multiple-branching construction；It is mutually communicated between the branch of the channel network；The rack body is made of degradable natural macromolecular material.The present invention " preset-weight is molten " thinking combines " inner core " manufacturing process with the crystallographic orientation of " directed porosity ", thermal phase separation process, overcomes the technical bottleneck of direct forming complexity microchannel structure.Using rapid shaping technique or mold castings, especially the former, inner core shaped structure flexibility can be made, shaped the complex passages structure with any pattern, and channel design has perforation feature well.
Description
Technical field
The present invention relates to the bionical tissue engineering brackets and its preparation side of a kind of network containing internal channel and directional pore structure
Method and application, belong to organizational project and Biotechnology field.
Background technique
Organizational project (Tissue Engineering) is one in front of the door along interdisciplinary science, basic principle are as follows: by body
The three-dimensional composite of outer building cell and bracket, simulates biological vivo environment, and cultivate and trained, obtain having repair or
The tissue of alternative functions.Organizational project has obtained in fields such as skin, bone/cartilage, bladder, blood vessel, liver, nerves fast at present
Speed development brings new hope for most of difficult medical problems of facing mankind, such as cardiovascular disease, Alzheimer's disease, pa
The treatment of the diseases and various injuries of tissues and organs such as the gloomy disease of gold, congenital hereditary defect.
Tissue engineering bracket provides mechanical support by bionic extracellular matrix, for cell, promotion cell adhesion, growth,
Proliferation, migration and metabolism, are one of key factors of organizational project.For some natural tissues (as cardiac muscle, skeletal muscle,
Nerve), wherein parenchyma Orienting ordered arrangement, connection, as cardiac muscular tissue's cardiac myocyte is arranged and passed through along collagenous fibres
Intercalated disc connection, this tissue characteristics play an important role in terms of the conduction of myocardial electrical signals.Existing research shows that having micro-
The tissue engineering bracket of orientation micropore structure is seen, can be induced by the microstructure of material to a certain extent myocardium thin
Born of the same parents' aligns and connects (HTH Au, B Cui, et al.Cell culture chips for simultaneous
application of topographical and electrical cues enhance phenotype of
cardiomyocytes [J].Lab Chip,2009,9:564–575.)；Electrical field stimulation can promote cardiac muscle cell respectively along
Growth and arrangement (Radisic M, Park H, Shing H, the et al.Functional assembly of of direction of an electric field
engineered myocardium by electrical stimulation of cardiac myocytes cultured
on scaffolds.Proceedings of the National Academy of Sciences of the United
States of America,2004,101(52):18129-18134.)；External mechanical stretch stimulation can promote cell along
Stress direction growth and arrangement (Tandon et al.Alignment and Elongation of Human Adipose-
Derived Stem Cells in Response to Direct-Current Electrical Stimulation.Conf
Proc IEEE Eng Med Biol Soc.2009,1:6517-6521.), but corresponding action rule is there is not yet deep grinds
Study carefully report.Traditional tissue engineering bracket manufacturing method such as solution-cast/pore-foaming agent deposition method, thermally induced phase separation, Electrospun
Method, air pressure port-creating method etc., the bracket of preparation are mostly isotropism, uniformly random pore structure.It is microcosmic currently used for forming orientation
The method of pore structure bracket mainly has two kinds of Electrospun of crystallographic orientation-thermally induced phase separation and orientation.
On the other hand, vascularization problem is the common problem of Tissue Engineering Study, and restricts organizational project and further send out
The bottleneck of exhibition.For being metabolized vigorous tissue such as cardiac muscle, liver, since cell has very high substance and energetic supersession horizontal,
And the transmission range of oxygen and nutriment in bracket is limited, therefore how to establish effective blood vessel network, solves internal layer cell
Anoxic necrosis is always the important problem that organizational project is faced.Existing perfusion culture improves ambient enviroment oxygen content, addition
The modes such as the carrier of oxygen and internal transplanting can make the artificial organ living cells thickness degree of building reach 500 μm.Some researches show that add
Add the substances such as endothelial cell, angiogenic growth factor that capillary sample tissue after transplanting in vivo can be promoted to generate.But it is above-mentioned
Method there is no the blood vessel network for forming similar classification perforation, ask by the oxygen supply that can not fundamentally solve internal stent cell
Topic.Therefore, the orientation microscopic void bracket for constructing the network containing internal channel, for cardiac muscle tissue engineering and skeletal muscle, nerve fiber
Engineering is of great significance.
Summary of the invention
The object of the present invention is to provide the bionical tissue engineering bracket of a kind of network containing internal channel and directional pore structure and
The bionical tissue engineering bracket of preparation method and application, present invention network containing internal channel and directional pore structure sufficiently simulates
The knot of certain natural tissues such as feature-" cell directional ordered arrangement, the blood vessel network containing multistage " of cardiac muscle, skeletal muscle, nerve
Structure has orientation micropore structure and multiple-limb channel network, wherein it is small to there is the transverse direction being mutually communicated between orientation macropore
Hole, and multiple-limb channel network configuration directly penetrates through or connects perforation by orienting micropore structure.Bionical group of weaver of the invention
Engineering support can be provided oxygen and nutriment for internal stent cell, be promoted blood vessel with inducing cell oriented alignment, connection and growth
It generates, and improves bracket inner cell planting density and depth, form bulk tissue substitute, be expected to greatly improve disease damage organizer
The efficiency that official repairs.
The bionical tissue engineering bracket of network containing internal channel and directional pore structure provided by the present invention, including bracket master
Body and the channel network being set in the rack body；
The rack body has orientation micropore structure, and between the orientation macropore of the orientation micropore structure
It is mutually communicated by the realization of lateral aperture；
The rack body is made of degradable natural macromolecular material；
The channel network has classification multiple-branching construction；
It is mutually communicated between the branch of the channel network.
It is directly to penetrate through between the branch of the channel network in above-mentioned bionical tissue engineering bracket.
In above-mentioned bionical tissue engineering bracket, pass through the hole of the rack body between the branch of the channel network
It is mutually communicated.
In above-mentioned bionical tissue engineering bracket, the diameter of section of the orientation macropore can be 20 μm~250 μm, specifically may be used
It is 20~100 μm, 50~200 μm or 100~250 μm, the degree of orientation (Orientation Index, OI) can be 0.8~1, specifically
It can be 0.8~0.9,0.9~0.95 or 0.92~0.95；
The diameter of section of the branch of the channel network can be 50 μm~3000 μm, concretely 50~1500 μm, 200~
1000 μm or 1000~3000 μm；
The channel network has 1~4 grade of branched structure, such as 2 grades or 3 grades of hierarchical structures.
In above-mentioned bionical tissue engineering bracket, the degradable natural macromolecular material can be collagen, chitosan, sea
At least one of mosanom, gelatin, fibroin albumen, hyaluronic acid, fibrinogen and albumin.
Invention further provides the bionical tissue engineering brackets of the network containing internal channel and directional pore structure
Preparation method includes the following steps:
1) by speed forming method or injection molding, inner core material is formed, obtains that there is the interior of the channel network configuration
Cored structure；
2) core arrangement is fixed in orientation bracket mould, then by the degradable natural macromolecular material
Solution fill it is described orientation bracket mould type chamber；The orientation bracket mould is positioned below in 0 DEG C of orientation temperature field,
Realize the crystallographic orientation and Thermal inactive of the solution of the degradable natural macromolecular material, it is then freeze-dried to obtain
Containing core arrangement, with the tissue engineering bracket of oriented structure；
3) core arrangement in the tissue engineering bracket that step 2) obtains is removed to get network containing internal channel is arrived
With the bionical tissue engineering bracket of directional pore structure.
In above-mentioned preparation method, in step 1), the inner core material be with preferable soluble, biocompatibility and
The material of mechanical property, concretely at least one of saccharide compound, gelatin and alkali soluble light-sensitive polymer；
The saccharide compound can be at least one of glucose, maltose and sucrose；
The molecular weight of the gelatin can be 15000~250000Da, can be type A gelatin, be also possible to type B gelatin；
The alkali soluble light-sensitive polymer can be dimethyl-acrylamide, methacrylic acid and polyvinylpyrrolidone
Copolymer, the mass ratio of three is 11:11:3.
In above-mentioned preparation method, in step 1), continuous extrusion process, stereolithography work is can be used in the speed forming method
One of techniques such as skill and laser micro-cladding sintering；The injection molding specifically: the channel network configuration is contained by preparation
PDMS mold, liquid inner core material of casting wherein, by cooling or photopolymerization curing, forming multiple-limb form it is solvable
Property inner core.
In above-mentioned preparation method, when the inner core material is the saccharide compound and/or gelatin, before step 2),
The step that the method also includes being placed in the core arrangement in PLGA solution (such as concentration is 0.1~1mg/mL), in institute
The surface for stating core arrangement forms protective film；
In step 2), the temperature of the orientation temperature field changes along the length direction of the orientation bracket mould；
The temperature in the hot end of the orientation temperature field can be 0 DEG C, and the temperature of cold end can be -20 DEG C~-196 DEG C, temperature ladder
The value of degree can be 2~20K/mm；Concretely -20 DEG C, -80 DEG C, -196 DEG C, -20 DEG C~-80 DEG C of the temperature of the cold end
Or -80 DEG C~-196 DEG C；The value of the temperature gradient concretely 2K/mm, 8K/mm, 20K/mm, 2~8K/mm or 8~20K/
mm；
In step 3), before removing the core arrangement, the method also includes utilizing physical crosslinking and/or chemical crosslinking
Mode the step of stablizing the tissue engineering bracket；
When the inner core material is the saccharide compound and/or the alkali soluble light-sensitive polymer, using such as lower section
Method removes the core arrangement: being soaked in deionized water, distilled water, NaOH aqueous solution or PBS buffer solution；
When the core arrangement is the gelatin, the core arrangement is removed with the following method: utilizing its " gel-
The temperature-sensing property of colloidal sol " transformation is placed in the dissolution of gelling temp point.
The bionical tissue engineering bracket of network containing internal channel and directional pore structure provided by the invention can be used for preparing group
Knit substitute, medicaments sifting model and pathological study model etc.；
The tissue substituent can be myocardium substitute, skeletal muscle substitute or neural substitute etc..
Compared with prior art, the present invention has the following advantages and outstanding effects:
(1) tissue engineering bracket of the present invention has significant biomimetic features feature.Main part: the thin of natural tissues is simulated
Extracellular matrix architecture constructs the bracket with orientation micropore structure, can promote oriented alignment and the connection of parenchyma；
The perforation of longitudinal direction or non-fully through channel network, simulate the multi-branch complex vascular access structure in natural tissues, favorably
In the transmission of oxygen and nutriment, and further promote the vascularization of endothelial cell, is conducive to improve cell seeding density and depth
Degree, to provide possibility for building bulk engineering tissue.
(2) crystallographic orientation of the present invention " preset-weight molten " thinking by " inner core " manufacturing process with " directed porosity ", thermotropic phase
Separating technology combines, and overcomes the technical bottleneck of direct forming complexity microchannel structure.Using rapid shaping technique or mold
Casting, especially the former, inner core shaped structure flexibility can be made, shaped the complex passages structure with any pattern,
And channel design has perforation feature well.
Detailed description of the invention
Fig. 1 is that the structure of the bionical tissue engineering bracket of network containing internal channel provided by the invention and directional pore structure is shown
It is intended to, wherein Fig. 1 (a) is that the structure of the bionical tissue engineering bracket comprising the multiple-branching construction class blood vessel access directly penetrated through is shown
It is intended to, Fig. 1 (b) is the bionical tissue engineering bracket of the multiple-branching construction class blood vessel access comprising being penetrated through indirectly by directed porosity
Structural schematic diagram.
Fig. 2 is the mold for being formed with the soluble core arrangement in multiple-limb channel.
Fig. 3 is the wherein class blood vessel network shape in Fig. 3 (a) and Fig. 1 (a) with multiple-limb shape model core arrangement schematic diagram
State is corresponding, and Fig. 3 (b) is corresponding with the class blood vessel network form in Fig. 1 (b).
Fig. 4 is the cross of channel network in the bionical tissue engineering bracket of network containing internal channel and directional pore structure of the invention
Section electromicroscopic photograph.
Fig. 5 is that orientation is big in the bionical tissue engineering bracket of network containing internal channel provided by the invention and directional pore structure
The electromicroscopic photograph in hole (Fig. 5 (a)) and lateral aperture (Fig. 5 (b)).
Wherein, it is respectively marked in attached drawing as follows:
1 brace aperture main structure body, 2 bionical class blood vessel access network structures, 3 core arrangements, 4 surface protective films, 5 cross
To aperture.
Specific embodiment
Experimental method used in following embodiments is conventional method unless otherwise specified.
The materials, reagents and the like used in the following examples is commercially available unless otherwise specified.
Fig. 1 is the signal of the bionical tissue engineering bracket of network containing internal channel provided by the invention and directional pore structure
Figure.The tissue engineering bracket includes brace aperture main structure body 1 and the bionical class blood vessel access network that is arranged in rack body
Structure 2；Wherein rack body 1 has orientation micropore structure, there is the transverse direction being mutually communicated between orientation macropore therein
Aperture 5；Bionical class blood vessel access network 2 has classification multiple-branching construction, indirect by directed porosity in the form of Fig. 1 (a)
Perforation is directly penetrated through in the form of Fig. 1 (b)；Rack body 1 is made of degradable natural macromolecular material.
The diameter of section of orientation macropore in rack body 1 is 20 μm~250 μm, and the OI value of the degree of orientation is 0.8~1；It is imitative
The diameter of section of raw class blood vessel access network 2 is 50 μm~3000 μm, has 1~4 grade of branched structure.
Degradable natural macromolecular material uses collagen, chitosan, sodium alginate, gelatin, fibroin albumen, hyalomitome
The compound of one or more of acid, fibrinogen and albumin material.
The bionical tissue engineering bracket of network containing internal channel and directional pore structure of the invention is prepared using following step:
1) soluble inner core material is dissolved, the solution that mass percentage concentration is 0.1%~5% is made；
2) inner core material is passed through into quick molding method or die methods, the core arrangement 3 of forming classification multiple-branching construction；It will
Core arrangement 3 is immersed in closed preservation a period of time in PLGA solution (0.1~10mg/mL), takes out and air-dries 12 hours or more,
Form surface protective film 4.
3) core arrangement 3 is fixed on to the longitudinal direction of orientation bracket mould, then by the molten of degradable natural polymer
Liquid fills the type chamber of orientation bracket mould, mold is placed below in 0 DEG C of orientation temperature field, realizes the crystallographic orientation of solution
And Thermal inactive, it is then freeze-dried, forms Embedded Web structure, the tissue engineering bracket with directional pore structure；
4) bracket is full cross-linked, it can be one or more of physical crosslinking, chemical crosslinking, then dissolve in bracket
Network structure (i.e. core arrangement 3), obtain the directed porosity bracket containing bionical class blood vessel access network structure 2.It, should after sterilizing
Network containing internal channel, oriented structure tissue engineering bracket can be used.
Soluble inner core material used should have preferable soluble, biocompatibility and mechanical property, can be sugar
The compound of one or more of materials of class compound, gelatin and alkali soluble light-sensitive polymer.
Speed forming method forming can be in the techniques such as continuous extrusion process, stereolithography processes, laser micro-cladding sintering
One kind.
Injection molding forming, by preparing the PDMS mold containing channel network configuration, liquid inner core material of casting wherein leads to
Supercooling is photopolymerization curing, shapes the soluble inner core of multiple-limb form.
Embodiment 1, biomimetic features tissue engineering bracket are used for rat heart muscle defect repair
Gelatin (Gelatin, 15000~250000Da) is dissolved in PBS solution, being prepared into mass fraction is 0.5%
Gelatin solution；Sodium alginate is dissolved in PBS solution, the sodium alginate soln that mass fraction is 3.0% is prepared into；It will be upper
State two kinds of solution be prepared into uniformly, bubble-free, the mixed solution without precipitating, the mass ratio of gelatin and sodium alginate is 1:1；It will
PLGA (PLA:PGA=75:25, molar ratio, viscosity 0.93dl/g, CHCl3/ 25 °C) it is dissolved in chloroform, compound concentration
For the PLGA solution of 2mg/mL.Sucrose, maltose, glucose uniformly mixed by the mass ratio of 1:12:2, is placed in and builds
In the spray head material chamber of melting extrusion equipment based on vapour-pressure type, and fusing is heated at 130 DEG C, it is solidifying that half is continuously squeezed out by spray head
Gu sugar material, according to the soluble inner core for the structure and path construction multiple-limb form being pre-designed (shown in such as Fig. 3 (a)).Inner core
After forming, it is immersed in closed preservation 20min in PLGA solution (2mg/mL).Inner core is taken out from PLGA solution, is air-dried
12 hours, make surface protective film drying kinetics, obtains stable multiple-limb shape inner core.Inner core is fixed on orientation bracket mould
Longitudinal direction, then " gelatin-sodium alginate " mixed solution is filled to the type chamber of mold, mold is placed on 0~-80 DEG C and is determined
To temperature field, (length direction along mold changes, and the temperature in mold upper end (hot end) is 0 DEG C, and the temperature of lower end (cold end) is -80
DEG C, bracket longitudinal length is 10mm, temperature gradient 8K/mm) in, realize the crystallographic orientation and Thermal inactive of solution, then
It is freeze-dried to form the tissue engineering bracket that there is oriented structure containing inner core.Bracket is full cross-linked in calcium chloride solution,
Then a few hours are impregnated in PBS solution, dissolve the soluble inner core of multiple-limb shape, obtain bionical class blood vessel access network.
In the biomimetic features tissue engineering bracket of above-mentioned preparation, the diameter of section for orienting macropore is 50~200 μm, the degree of orientation
(OI) value is 0.9~0.95；The diameter of section of bionical class blood vessel access network structure 2 is 200~1000 μm, has 3 grades of branches
Structure.
The cross section electromicroscopic photograph of bionical class blood vessel access network 2 is such as in the biomimetic features tissue engineering bracket of above-mentioned preparation
Shown in Fig. 4, it can be seen from this figure that channel design shape keeps preferable.
The electricity of the orientation macropore of the micropore structure of the biomimetic features tissue engineering bracket of above-mentioned preparation and lateral aperture
Such as (Fig. 5 (a)) and (Fig. 5 (b)) is shown respectively for mirror photo, it can be seen from this figure that directional pore structure orientation with higher
Degree, while passing through lateral fine pore perforation.
Neonatal rat myocyte and endothelial cell are extracted as seed cell, is put into 37 DEG C of cell incubators and incubates respectively
Educate, make its completely it is adherent, and be subject to external static culture (37 DEG C, 5%CO2).Then by external " perfusion-perfusion " combined type
Culture bioreactors, initial stage plants cardiac muscle cell and endothelial cell mixture at orientation rack body position, in channel interior
Simultaneously endothelial cell is perfused in modification endothelial growth factors, and the later period realizes the dynamic cultivation of simulated body fluid circulation, and applies certain power
Learn training (strain 5~10%) and electro photoluminescence (5~8V/cm of electric field strength).After 7 days, obtain has class cardiac muscle in vitro
The bulk cardiac muscle substitute of tissue characteristic.
The organizational project cardiac muscle of above-mentioned acquisition is implanted into rat heart infarcted region, detects visible defect after two months
There is newborn cardiac muscular tissue, and has the feature of local vascular.
Embodiment 2 is used for three-dimensional skeletal muscle tissue external structure containing internal channel, oriented structure biomimetic scaffolds
Prepare 1wt% acetum.It is molten that rat-tail type i collagen (SIGMA company, product number C7661) is dissolved in acetic acid
In liquid, it is prepared into the collagen solution that mass fraction is 1.0%；It dissolves chitosan in acetum, is prepared into mass fraction
For 1.0% chitosan solution；Above two solution is prepared into uniform, bubble-free, without the mixed solution of precipitating, collagen and shell
The mass ratio of glycan is 1:5.PDLGA is dissolved in chloroform, the PDLGA solution of compound concentration 0.4mg/mL.Preparation is containing logical
The PDMS mold of road structure, as shown in Fig. 2, gelatin of casting wherein, constructs the gelatin network structure of multiple-limb form.To inner core
After forming, gelatin network structure is immersed in closed preservation 10min in PDLGA solution.Inner core is taken out from PDLGA solution,
It air-dries 12 hours, makes surface protective film drying kinetics, obtain stable multiple-limb shape inner core.Inner core is fixed on orientation bracket
The longitudinal direction of mold, then " collagen-chitin " mixed solution is filled to the type chamber for orienting bracket mould, mold is placed on 0
(length direction along mold changes, and the temperature in mold upper end (hot end) is 0 DEG C, lower end (cold end) for~-20 DEG C of orientation temperature field
Temperature be -20 DEG C, bracket longitudinal length is 10mm, temperature gradient 2K/mm) in, realize the crystallographic orientation of solution and thermotropic
Mutually separate, it is then freeze-dried to form the tissue engineering bracket that there is oriented structure containing inner core.By bracket in 0.5wt% poly
It is full cross-linked in the PBS solution of sodium phosphate, a few hours in 37 DEG C of baking ovens are subsequently placed in, make gelatin inner core that " gel-sol " occur
Transformation dissolution, obtains bionical class blood vessel access network.
In the biomimetic features tissue engineering bracket of above-mentioned preparation, the diameter of section for orienting macropore is 100~250 μm, orientation
Spending (OI) value is 0.8~0.9；The diameter of section of bionical class blood vessel access network 2 is 1000~3000 μm, has 2 grades of branch's knots
Structure.
After sterilizing, rack surface is coated with Matrigel, plants SD newborn rat sarcoblast at bracket oriented structure position,
And applying cyclic tension stimulation (strain 10%), it is in spindle shape, arrangement rule that sarcoblast is observed after culture 7 days, under scanning electron microscope
Rule, cell long axis are parallel to each other；After culture 21 days, the expression of Myogenin, Desmin gene is detected, it was demonstrated that it is closer to
The biological characteristics of body muscular tissue, it was demonstrated that the present invention is building skeletal muscle tissue substitution containing internal channel, oriented structure biomimetic scaffolds
Object, and further building vascularization, the muscular tissue offer possibility of neuralization from now on.
Embodiment 3, biomimetic features tissue engineering bracket are used for the reparation of peripheral nerve defect in rats
Prepare 2wt% acetum.Fibroin albumen (silk fiber) is dissolved in acetum, quality point is prepared into
The silk fibroin protein solution that number is 0.4%；It dissolves chitosan in acetum, it is poly- to be prepared into the shell that mass fraction is 2.0%
Sugar juice；Above two solution is prepared into uniform, bubble-free, without the mixed solution of precipitating, the matter of fibroin albumen and chitosan
Amount is than being 1:1.By alkali soluble light-sensitive polymer, (dimethyl-acrylamide, methacrylic acid and polyvinylpyrrolidone are total to
Polymers, the mass ratio of three are 11:11:3), (shown in such as Fig. 3 (b), pass through cubic light according to the structure and path that are pre-designed
Carving technology shapes (Stereolithography), constructs the alkali solubility network structure of multiple-limb form.Network structure is fixed on
The longitudinal direction of bracket mould is oriented, then " fibroin-chitosan " mixed solution is filled to the type chamber of orientation bracket mould,
Mold is placed on 0~-196 DEG C of orientation temperature field, and (length direction along mold changes, and the temperature in mold upper end (hot end) is 0
DEG C, the temperature of lower end (cold end) is -196 DEG C, and bracket longitudinal length is 10mm, temperature gradient 20K/mm) in, realize solution
Crystallographic orientation and Thermal inactive, it is then freeze-dried to form the tissue engineering bracket that there is oriented structure containing inner core.It will branch
Frame is full cross-linked in sodium polyphosphate, and multiple-limb shape core arrangement is then dissolved in NaOH aqueous, obtains bionical class blood
Tube passage network.
In the biomimetic features tissue engineering bracket of above-mentioned preparation, the diameter of section for orienting macropore is 20~100 μm, the degree of orientation
(OI) value is 0.92~0.95；The diameter of section of bionical class blood vessel access network 2 is 50~1500 μm, has 4 grades of branched structures.
After sterilizing, rack surface is coated with Matrigel, bridges SD rat sciatic nerve 10mm defect with it.12 weeks after operation
Lower limb exercise is observed, by the visible a large amount of regenerated nervous fibers of transmission electron microscope and immunofluorescence dyeing, electro physiology detection nerve is passed
Speed and wave amplitude are led close to nerve autograft.
Claims (6)
1. a kind of preparation method of the bionical tissue engineering bracket of network containing internal channel and directional pore structure, including walk as follows
It is rapid:
1) by speed forming method or injection molding, inner core material is formed, the core arrangement with channel network configuration is obtained；
The inner core material is at least one of saccharide compound, gelatin and alkali soluble light-sensitive polymer；
2) core arrangement is fixed in orientation bracket mould, then infuses the solution of degradable natural macromolecular material
The type chamber of the full orientation bracket mould；The orientation bracket mould is positioned below in 0 DEG C of orientation temperature field, then through cold
Jelly is dried to obtain containing the core arrangement, with the tissue engineering bracket of oriented structure；
3) core arrangement in the tissue engineering bracket that step 2) obtains is removed to get arriving network containing internal channel and determining
To the bionical tissue engineering bracket of pore structure；
The bionical tissue engineering bracket includes rack body and the channel network that is set in the rack body；
The rack body has orientation micropore structure, and passes through between the orientation macropore of the orientation micropore structure
Lateral aperture realization is mutually communicated；
The diameter of section of the orientation macropore is 20 μm~250 μm, and the degree of orientation is 0.8~1；
The channel network has 1~4 grade of branched structure；
The diameter of section of the branch of the channel network is 50 μm~3000 μm；
It is directly to penetrate through or be mutually communicated by the hole of the rack body between the branch of the channel network.
2. preparation method according to claim 1, it is characterised in that: the degradable natural macromolecular material is glue
At least one of original, chitosan, sodium alginate, gelatin, fibroin albumen, hyaluronic acid, fibrinogen and albumin.
3. preparation method according to claim 1 or 2, it is characterised in that: the inner core material is the saccharide compound
And/or when gelatin, before step 2), the step that the method also includes being placed in the core arrangement in PLGA solution；
In step 2), the temperature of the orientation temperature field changes along the length direction of the orientation bracket mould；
The temperature in the hot end of the orientation temperature field is 0 DEG C, and the temperature of cold end is -20 DEG C~-196 DEG C, and the value of temperature gradient is 2
~20K/mm；
In step 3), before removing the core arrangement, the method also includes the sides using physical crosslinking and/or chemical crosslinking
Formula stablizes the step of tissue engineering bracket.
4. the bionical tissue engineering bracket of any one of -3 the methods preparation according to claim 1.
5. bionical tissue engineering bracket described in claim 4 is in preparation tissue substituent, drug screening and case mode research
Application.
6. application according to claim 5, it is characterised in that: the tissue substituent replaces for myocardium substitute, skeletal muscle
For object or neural substitute.
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| DE102016110328B3 (en) * | 2016-06-03 | 2017-09-07 | Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts, Universitätsmedizin | perforated plate |
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| CN113144289A (en) * | 2021-04-27 | 2021-07-23 | 武汉理工大学 | Silk fibroin/polylactic acid composite scaffold with function of directionally inducing peripheral nerve regeneration and preparation method thereof |
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| CN113813444B (en) * | 2021-09-10 | 2022-09-20 | 深圳大学 | 3D multi-branch bionic stent and preparation method and application thereof |
| CN113856479B (en) * | 2021-09-18 | 2022-11-25 | 浙江大学 | Fish gill-like polymer straight-through hole membrane and preparation method and application thereof |
| CN114732949B (en) * | 2022-03-25 | 2023-01-24 | 上海工程技术大学 | Rotator cuff patch with oriented structure and preparation method thereof |
| CN115814152A (en) * | 2022-11-23 | 2023-03-21 | 中国人民解放军陆军军医大学 | Preparation method of high-strength interpenetrating network hydrogel blood vessel with directionally arranged fiber microstructure |
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