CN106166308B - A kind of three-dimensional stephanoporate compound stent and preparation method thereof - Google Patents
A kind of three-dimensional stephanoporate compound stent and preparation method thereof Download PDFInfo
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- CN106166308B CN106166308B CN201610715160.3A CN201610715160A CN106166308B CN 106166308 B CN106166308 B CN 106166308B CN 201610715160 A CN201610715160 A CN 201610715160A CN 106166308 B CN106166308 B CN 106166308B
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- hyaluronic acid
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 108010022355 Fibroins Proteins 0.000 claims abstract description 75
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 33
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 32
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 32
- 239000012460 protein solution Substances 0.000 claims abstract description 32
- 239000000243 solution Substances 0.000 claims abstract description 28
- 239000000661 sodium alginate Substances 0.000 claims abstract description 25
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 25
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 25
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000011259 mixed solution Substances 0.000 claims abstract description 5
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 45
- 239000008367 deionised water Substances 0.000 claims description 29
- 229910021641 deionized water Inorganic materials 0.000 claims description 29
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 14
- 238000000502 dialysis Methods 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 10
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- 239000007924 injection Substances 0.000 claims description 5
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
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- 150000004781 alginic acids Chemical class 0.000 description 3
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- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- AEMOLEFTQBMNLQ-AZLKCVHYSA-N (2r,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-AZLKCVHYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-SYJWYVCOSA-N (2s,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-SYJWYVCOSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 208000032984 Intraoperative Complications Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
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- 238000001415 gene therapy Methods 0.000 description 1
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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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/48—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/60—Materials for use in artificial skin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Composite Materials (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a kind of three-dimensional stephanoporate compound stents and preparation method thereof, the compound rest is prepared using 2~10wt% silk fibroin protein solution, hyaluronic acid and sodium alginate as raw material, wherein, the ratio of hyaluronic acid and silk fibroin protein solution is 0.1g:5~30ml, the ratio of the mixed solution and sodium alginate of silk fibroin protein solution and hyaluronic acid composition is 15~25ml:0.1g, the solution and fibroin albumen of hyaluronic acid and sodium alginate are subjected to physical mixed, three-dimensional stephanoporate compound stent can be obtained after freeze-dried.The advantages of obtained bracket not only contributes to fibroblastic adherency and increment, also has preferable hydrophily etc., overcomes some problems of existing timbering material shortcoming, and many kinds of substance is compound, maintains original matter, solves the deficiency of original material property.Preparation process of the present invention is simple, and required in required raw material ratio cost is relatively low, is suitble to mass production.
Description
Technical field
The invention belongs to technical field of polymer materials, in particular to a kind of fibroin albumen/hyaluronic acid/sodium alginate three
Tie up porous compound support frame and preparation method thereof.
Background technique
Skin is the maximum organ of human body, is broadly divided into epidermis, skin corium and subcutaneous tissue, is had to human body important
Barrier, machinery, perception and the function of regulation.But skin is human body most fragile and is most susceptible to one of organ of injury, skin
The major reason that skin festers, wound, surgical injury and burn are skin damages, wherein the main reason for burn is skin damage.
For China, the patient to burn every year is 10,000,000 or more, wherein because serious burn needs dermatoplastic patient to reach
3000000 or more.But skin deficiency can be available for due to the limited source of self skin, when encountering large area skin serious defect,
Significantly limit its extensive use in skin repair.Substitute of the artificial skin as autologous skin, in skin wound
It is played an increasingly important role in reparation.In the case where autologous skin insufficient supply, widespread skin damages the wounded and is benefited.
Recently as the development of organizational project and regenerative medicine, researcher has passed through tissue engineering bracket, growth because
Son, the methods of seed cell and gene therapy develop the artificial skin substitute of Various Tissues engineering rack.
Fibroin albumen (Silk fibroin, SF) is a kind of hydrophobic protein, excellent in mechanical performance, stable structure,
With good biocompatibility, and abundance, it is low in cost, it is a kind of excellent natural high molecular material.It is based on
These advantages of fibroin albumen, are widely used in field of tissue engineering technology always, as repair of cartilage, reticular connective tissue reparation,
Bone Defect Repari and neural restoration etc..Some researches show that, fibroblastic proliferation can be promoted with fibroin albumen, broken up, it is right
Skin wound healing has facilitation, so fibroin albumen can be used as dressing for skin.
Hyaluronic acid (Hyaluronic Acid, HA) is a kind of unique linear macromolecule mucopolysaccharide, is extracellular matrix
Main component, In vitro cell experiment shows hyaluronic acid not only and can promote sticking and being proliferated for cell, but also biological
In prosthetic, hyaluronic acid can separating tissues surface as a kind of mechanical protection agent can prevent adhesion and fibroid after surgery
It organizes the formation of.High concentration, high molecular weight hyaluronic acid can not only inhibit bleeding, reduce the clot that can form permanent adhesion skeleton
Quantity, and fibroblastic movement and activity can be inhibited.The microporous barrier of hyaluronic acid benzyl ester, which has been studied, is proved to be culture
It is burnt with the active keratinocyte of conveying, the material that one kind of chronic ulcer treatment is excellent.
Sodium alginate (sodium alginate, Alg) is a kind of polyanionic polysaccharide extracted from natural brown alga, by
Beta-D-mannuronic acid and α-L- guluronic acid link, have good biocompatibility and can divalent ion such as
Ca2+Gel is formed Deng under the action of, is widely used in field of tissue engineering technology.
It is used as dressing for skin as three-dimensional rack currently with fibroin albumen and has become hot spot, hyaluronic acid and alginic acid
Respectively application of the advantage on bracket also emerges one after another sodium, and nowadays the more persons of fibroin albumen hyaluronic acid sodium alginate mix very much
Performance requires study, such as water imbibition, the degradation characteristic under biotic environment, blood compatibility etc..More person's blending ratios are not
The appropriate or improper one-tenth porosity that will affect bracket of mixing condition and pore size are unfavorable for the adherency increment of cell, into
And it also will affect the application performance of bracket.
Summary of the invention
Based on this, in order to overcome the defects of the prior art described above, the present invention utilizes fibroin albumen, hyaluronic acid, alginic acid
Sodium three respective advantage in skin repair provides a kind of three-dimensional stephanoporate compound stent and preparation method thereof.
In order to achieve the above-mentioned object of the invention, this invention takes following technical schemes:
A kind of three-dimensional stephanoporate compound stent, the compound rest be with 2~10wt% silk fibroin protein solution, hyaluronic acid and
Sodium alginate is what raw material was prepared, wherein the ratio of hyaluronic acid and silk fibroin protein solution are as follows: 0.1g:5~30ml, 2~
The ratio of 10wt% silk fibroin protein solution and hyaluronic acid mixed solution and sodium alginate are as follows: 15~25ml:0.1g.
In wherein some embodiments, the concentration of the silk fibroin protein solution is 3.5wt%, the hyaluronic acid and fibroin
The ratio of protein solution are as follows: 0.1g:20ml.
In wherein some embodiments, the ratio of silk fibroin protein solution and hyaluronic acid mixed solution and sodium alginate are as follows:
21ml:0.1g.
The present invention also provides the preparation methods of above-mentioned three-dimensional stephanoporate compound stent, comprising the following steps:
(1), the silk fibroin protein solution of 2~10wt% is added in hyaluronic acid solution, 25~35min is stirred at room temperature,
It adds 0.05~0.5gEDC/NHS and stirs 30~45min；Wherein, 5~30ml fibroin albumen is added in every 0.1g hyaluronic acid
Solution；
(2), 0.05~0.2g sodium alginate is dissolved in 10~24ml deionized water, then the solution obtained with step (1)
Be uniformly mixed, injection orifice plate forms gel, and refrigeration forms ice crystalline solid, freeze-drying to get；Wherein, every 0.1g sodium alginate adds
Enter the solution of 15~25ml step (1).
In wherein some embodiments, fibroin albumen described in step (1) the preparation method comprises the following steps: 8g silk cocoon is taken to be placed in big burning
In cup, 400ml deionized water is added, while 2g natrium carbonicum calcinatum is added, boils half an hour taking-up, cleaned several times with deionized water
It to neutrality, repeats and boils a taking-up, wash clean is placed in baking oven and dries.
In wherein some embodiments, the silk cocoon is the silk cocoon of pupa.
In wherein some embodiments, silk fibroin protein solution described in step (1) the preparation method comprises the following steps: weigh 2~4g
Fibroin sets the lithium-bromide solution that 9.8mol/L is added in a round bottom flask, and 40~60 DEG C of heating water baths are dissolved 3~5 hours, taken
Fibroin albumen mixed liquor is placed in bag filter and dialyses 3~5 days out, replaces 1~3 deionized water daily, will complete the molten of dialysis
Liquid is centrifuged 8~15 minutes, finally takes out centrifuge tube, supernatant liquor is silk fibroin protein solution.
In wherein some embodiments, the molecular cut off of the bag filter is 8-14kD.
In wherein some embodiments, the centrifugal condition is 25 DEG C, 5000r/min, 10~15min.
In wherein some embodiments, refrigeration crystallization temperature described in step (2) is -80 DEG C.
In wherein some embodiments, lyophilisation condition described in step (2) is -60 DEG C, 48h.
The present invention also provides application of the above-mentioned three-dimensional stephanoporate compound stent in terms of skin repair.
Compared with prior art, the invention has the following advantages:
1, three-dimensional stephanoporate compound stent uniform pore diameter of the invention, one-tenth porosity is high, and blood compatibility is good, not only contributes into
The adherency and increment of fibrocyte also have preferable hydrophily etc., overcome existing timbering material because of the compound system of more persons
Preparation Method is improper so that bracket aperture rate substantially reduces, not degradable, and seriously affects tissue local environment and then to skin
Damage etc. problems.The advantages of many kinds of substance of the present invention is compound, maintains original matter, solves original material property
Deficiency, can reduce compromised skin infection and promote skin reparation, accelerate wound healing；
2, the preparation method of three-dimensional stephanoporate compound stent of the invention is simple, at low cost, high production efficiency, is suitble to industrialization
Mass production.
Detailed description of the invention
Fig. 1 is the outside drawing of the three-dimensional stephanoporate compound stent of the embodiment of the present invention 1；
Fig. 2 is the structure chart of the three-dimensional stephanoporate compound stent of embodiment 1 under a scanning electron microscope, as seen from the figure aperture
Uniformly, average pore size is 30-120 μm, and the porosity measured is about 76%；
Fig. 3 is embodiment 1, and the FT-IR of the porous support of comparative example 1,2,3 schemes, 1 composite support of embodiment known in figure
Frame is physical mixed, the performance comprising monomeric substance；
Fig. 4 is the degradation figure of the three-dimensional stephanoporate compound stent of embodiment 1, and pH keeps steady change, do not change environment pH；
Fig. 5 is the degradation figure of the three-dimensional stephanoporate compound stent of embodiment 1, substantially non-degradable, b under a broken line display buffer liquid
Broken line shows and slowly degrades under enzyme；
Fig. 6 is embodiment 1, the quality analysis figure of the porous support of comparative example 1,2,3；
Fig. 7 is embodiment 1, the hemolysis rate figure of the porous support of comparative example 1,2,3.
Specific embodiment
It is further discussed below the present invention in the following with reference to the drawings and specific embodiments, the present invention does not address place and is suitable for existing skill
Art.It is given below specific embodiments of the present invention, but embodiment is not intended to limit this merely to this explanation is described in further detail
The claim of invention.Raw material used in following embodiment all derives from commercially available.
1 three-dimensional stephanoporate compound stent of embodiment and preparation method thereof
The preparation method of the three-dimensional stephanoporate compound stent of the present embodiment includes the following steps:
(1), it takes 8g silk cocoon to be placed in large beaker, 400ml deionized water is added, while 2g natrium carbonicum calcinatum is added, boils
Half an hour takes out, and cleans several times to neutrality with deionized water, repeats above-mentioned steps, be placed in baking oven and dry, obtain fibroin egg
It is white stand-by；
(2), it takes 2.5g fibroin albumen that the lithium-bromide solution of 25ml 9.8mol/L is added, at 60 DEG C after heating water bath 5h, uses
Bag filter dialysis (molecular cut off of bag filter is that 8kD dialyses 3 days, changes 3 water daily), then in 25 DEG C, under 5000r/min
Centrifugation 10 minutes, obtains the silk fibroin protein solution of 3.5wt%；
(3), it weighs 0.1g hyaluronic acid to be dissolved in 1ml deionized water, concussion shakes up or so half an hour, to be formed uniformly molten
The silk fibroin protein solution of 20ml step (2) is added after liquid, is stirred under room temperature 1 hour or so, 0.1g EDC/NHS then is added again
Stirring 2~3 hours, mixing speed are 300~400r/min；
(4), it weighs 0.1g sodium alginate to be added at room temperature into 12ml deionized water, stirring and dissolving, then solution is added
Be uniformly mixed in the solution of step (3), then by solution injection hole plate, preservative film sealing, and prick appropriate aperture, by orifice plate in
Even low speed concussion is until form coagulant liquid under 37 DEG C of environment.Coagulant liquid is placed in refrigeration at -80 DEG C again and forms ice crystalline solid, most
It takes out afterwards and is placed in 2 days three-dimensional stephanoporate compound stents taken out to get the present embodiment of -60 DEG C of freeze-dryings in freeze dryer.
Fig. 1 is the outside drawing of the three-dimensional stephanoporate compound stent of the present embodiment 1；Fig. 2 is that three-dimensional stephanoporate compound stent is scanning
Structure chart under electron microscope, the three-dimensional stephanoporate compound stent uniform pore diameter that the present embodiment obtains as seen from the figure, average pore size
It is 30-120 μm, the porosity measured is about 76%；Fig. 4,5 for the present embodiment three-dimensional stephanoporate compound stent degradation figure, from
It is found that pH keeps steady change in figure, not changing environment pH, three-dimensional stephanoporate compound stent is substantially non-degradable under buffer,
Three-dimensional stephanoporate compound stent is slowly degraded under enzyme.Table 1 is the water absorption rate of the three-dimensional stephanoporate compound stent of embodiment 1.As the result is shown
The water absorption rate of bracket reaches the ratio that mass ratio is about 42 times, and effect is obvious.
The water absorption rate of the three-dimensional stephanoporate compound stent of 1 embodiment 1 of table
| V0 | Dry weight±SD(mg) | V±SD(ml) | R±SD |
| 10 | 35.74±6.34 | 8.5±0.23 | 41.97±0.86 |
2 three-dimensional stephanoporate compound stent of embodiment and preparation method thereof
The preparation method of the three-dimensional stephanoporate compound stent of the present embodiment includes the following steps:
(1), it takes 8g silk cocoon to be placed in large beaker, 400ml deionized water is added, while 2g natrium carbonicum calcinatum is added, boils
Half an hour takes out, and cleans several times to neutrality with deionized water, repeats above-mentioned steps, be placed in baking oven and dry, obtain fibroin egg
It is white stand-by；
(2), take 1g fibroin albumen that the lithium-bromide solution of 25ml 9.8mol/L is added, at 60 DEG C after heating water bath 3h, with saturating
Bag dialysis (molecular cut off of bag filter is 10kD) dialysis 3 days is analysed, 3 water are changed daily, then in 25 DEG C, under 5000r/min
Centrifugation 10 minutes, obtains the silk fibroin protein solution of 2wt%；
(3), it weighs 0.1g hyaluronic acid to be dissolved in 1ml deionized water, concussion shakes up or so half an hour, to be formed uniformly molten
The silk fibroin protein solution of 20ml step (2) is added after liquid, is stirred under room temperature 1 hour or so, 0.1g EDC/NHS then is added again
Stirring 2~3 hours, mixing speed are 300~400r/min；
(4), it weighs 0.1g sodium alginate to be added at room temperature into 12ml deionized water, stirring and dissolving, then solution is added
Be uniformly mixed in the solution of step (3), then by solution injection hole plate, preservative film sealing, and prick appropriate aperture, by orifice plate in
Even low speed concussion is until form coagulant liquid under 37 DEG C of environment.Coagulant liquid is placed in refrigeration at -80 DEG C again and forms ice crystalline solid, most
It takes out afterwards and is placed in 2 days three-dimensional stephanoporate compound stents taken out to get the present embodiment of -60 DEG C of freeze-dryings in freeze dryer.
The performance phase of the performance of the three-dimensional stephanoporate compound stent of the embodiment and the three-dimensional stephanoporate compound stent of embodiment 1
Seemingly.
3 three-dimensional stephanoporate compound stent of embodiment and preparation method thereof
The preparation method of the three-dimensional stephanoporate compound stent of the present embodiment includes the following steps:
(1), it takes 8g silk cocoon to be placed in large beaker, 400ml deionized water is added, while 2g natrium carbonicum calcinatum is added, boils
Half an hour takes out, and cleans several times to neutrality with deionized water, repeats above-mentioned steps, be placed in baking oven and dry, obtain fibroin egg
It is white stand-by；
(2), it takes 7.5g fibroin albumen that the lithium-bromide solution of 25ml 9.8mol/L is added, at 60 DEG C after heating water bath 3h, uses
Bag filter dialysis (molecular cut off of bag filter be 12kD) dialysis 3 days, changes 3 water daily, then in 25 DEG C, 5000r/min
Lower centrifugation 10 minutes, obtains the silk fibroin protein solution of 10wt%；
(3), it weighs 0.1g hyaluronic acid to be dissolved in 1ml deionized water, concussion shakes up or so half an hour, to be formed uniformly molten
The silk fibroin protein solution of 20ml step (2) is added after liquid, is stirred under room temperature 1 hour or so, 0.1g EDC/NHS then is added again
Stirring 2~3 hours, mixing speed are 300~400r/min；
(4), it weighs 0.1g sodium alginate to be added at room temperature into 12ml deionized water, stirring and dissolving, then solution is added
Be uniformly mixed in the solution of step (3), then by solution injection hole plate, preservative film sealing, and prick appropriate aperture, by orifice plate in
Even low speed concussion is until form coagulant liquid under 37 DEG C of environment.Coagulant liquid is placed in refrigeration at -80 DEG C again and forms ice crystalline solid, most
It takes out afterwards and is placed in 2 days three-dimensional stephanoporate compound stents taken out to get the present embodiment of -60 DEG C of freeze-dryings in freeze dryer.
The performance phase of the performance of the three-dimensional stephanoporate compound stent of the embodiment and the three-dimensional stephanoporate compound stent of embodiment 1
Seemingly.
1 porous fibroin albumen bracket of comparative example and preparation method thereof
The preparation method of the porous fibroin albumen bracket of this comparative example includes the following steps:
(1), it takes 8g silk cocoon to be placed in large beaker, 400ml deionized water is added, while 2g natrium carbonicum calcinatum is added, boils
Half an hour takes out, and cleans several times to neutrality with deionized water, repeats above-mentioned steps, be placed in baking oven and dry, obtain fibroin egg
It is white stand-by；
(2), it takes 2.5g fibroin albumen that the lithium-bromide solution of 25ml 9.8mol/L is added, at 60 DEG C after heating water bath 5h, uses
Bag filter dialysis (molecular cut off of bag filter is 8kD) dialysis 3 days, changes 3 water, then in 25 DEG C, under 5000r/min daily
Centrifugation 10 minutes, obtains the silk fibroin protein solution of 3.5wt%；
(3), it takes to be lyophilized 2 days at -60 DEG C of silk fibroin protein solution of 3.5wt% and obtains silk fibroin bracket.
2 porous fibroin albumen of comparative example/hyaluronic acid scaffold and preparation method thereof
Porous fibroin albumen/hyaluronic acid scaffold preparation method of this comparative example includes the following steps:
(1), it takes 8g silk cocoon to be placed in large beaker, 400ml deionized water is added, while 2g natrium carbonicum calcinatum is added, boils
Half an hour takes out, and cleans several times to neutrality with deionized water, repeats above-mentioned steps, be placed in baking oven and dry, obtain fibroin egg
It is white stand-by；
(2), it takes 2.5g fibroin albumen that the lithium-bromide solution of 25ml 9.8mol/L is added, at 60 DEG C after heating water bath 5h, uses
Bag filter dialysis (molecular cut off of bag filter is 8kD) dialysis 3 days, changes 3 water, then in 25 DEG C, under 5000r/min daily
Centrifugation 10 minutes, obtains the silk fibroin protein solution of 3.5wt%；
(3), it weighs 0.1g hyaluronic acid to be dissolved in 1ml deionized water, concussion shakes up or so half an hour, to be formed uniformly molten
The silk fibroin protein solution of 20ml step (2) is added after liquid, is stirred under room temperature 1 hour or so, 0.1g EDC/NHS then is added again
Stirring 2~3 hours, mixing speed are 300~400r/min；
(4), it takes above-mentioned fibroin albumen/hyaluronic acid mixed liquor to be lyophilized 2 days at -60 DEG C and obtains fibroin albumen/hyalomitome
Sour combined support.
3 porous fibroin albumen of comparative example/sodium alginate bracket and preparation method thereof
Porous fibroin albumen/sodium alginate bracket preparation method of this comparative example includes the following steps:
(1), it takes 8g silk cocoon to be placed in large beaker, 400ml deionized water is added, while 2g natrium carbonicum calcinatum is added, boils
Half an hour takes out, and cleans several times to neutrality with deionized water, repeats above-mentioned steps, be placed in baking oven and dry, obtain fibroin egg
It is white stand-by；
(2), it takes 2.5g fibroin albumen that the lithium-bromide solution of 25ml 9.8mol/L is added, at 60 DEG C after heating water bath 5h, uses
Bag filter dialysis (molecular cut off of bag filter is 8kD) dialysis 3 days, changes 3 water, then in 25 DEG C, under 5000r/min daily
Centrifugation 10 minutes, obtains the silk fibroin protein solution of 3.5wt%；
(3), it weighs 0.1g sodium alginate to be added at room temperature into 12ml deionized water, stirring and dissolving, then solution is added
It is uniformly mixed in the solution of step (3)；
(4), it takes above-mentioned fibroin albumen/sodium alginate mixed liquor to be lyophilized 2 days at -60 DEG C and obtains fibroin albumen/alginic acid
Sodium combined support.
Feature in the case where obtaining embodiment 1 and 1~3 material of comparative example between comparison does following analysis experiment:
(1), it takes the dry levigate rear tabletting of appropriate KBr to be put into Fourier infrared spectrograph to measure.Spectral scanning range is
500-4000cm-1, resolution ratio 4cm-1, KBr spectrum schemes as background contrast, by embodiment 1 and comparative example 1~3 and respectively with
KBr is about measured with being put into Fourier infrared spectrograph after the dry tabletting of the amount mixed grinding of 1:100, obtains infrared spectroscopy,
As shown in figure 3, the absorption peak of 1~3 sample of embodiment 1 and comparative example is substantially similar as shown in Figure 3, major absorbance peak exists
1667cm-1(amide I), 1532cm-1(amide II), 1244cm-1(amide III) 678cm-1(amide V), these characteristic peaks are main
It is related with the random coil of fibroin albumen or α-helixstructure, illustrate that the addition of hyaluronic acid sodium alginate does not change
The structural behaviour of fibroin albumen.
(2), 1~3 sample holder of above-described embodiment 1 and comparative example of dry about 10mg is weighed respectively, is packed into one and is done
In net small aluminium foil pot, N is full of in instrument2In the environment of, 700 DEG C are always heated to from room temperature, heating rate is 10 DEG C/
min.Thermogravimetric analyzer starts to collect data, and then obtains thermogravimetric analysis map, as shown in fig. 6, as seen from Figure 60 DEG C arrive
At 250 DEG C, the weight of every kind of bracket is all reduced, and the reduction speed of SF/HA/Alg bracket is moderate, this stage is mainly
The loss of rack surface absorption water.And become very steep suddenly in about 250 DEG C to 325 DEG C this interval curves, it can be seen that sample
Quality start significantly to decompose, and temperature be greater than 400 DEG C after sample Mass lost become more and more slowly, gradually decrease
To 0, and the reducing speed of SF/HA/Alg compound is constantly in moderate state, schemes in conjunction with above-mentioned FT-IR it is found that compound belong to
Physical bond, does not change the structure of important group, and compound substance has the characteristic of independent substance.And mass loss is unhappy not
Slowly, illustrate that the mixing of 1 sample of embodiment is more uniform, and the more stable variation of bracket hot property.
(3), clean red blood cell suspension will be collected in appropriate PBS, the volume with erythroblast accounts for total volume 16%
Red blood cell suspension.1~3 bracket sample of appropriate embodiment 1 and comparative example is taken respectively, impregnates 24 with PBS (PH=7.4) buffer
Hour, taking-up is impregnated with liquid and numbers respectively, and PBS and deionized water take above-mentioned each respectively as negative control group and positive controls
50 μ L red cell suspensions are added in centrifuge tube in sample 1ml, and experiment is divided into 5 time points, hatch 0h, 0.5h at 37 DEG C,
1h, 1,5h, 2h then take out 1000 × g and are centrifuged 2~3min, pipette supernatant in 96 orifice plates, measured by microplate reader
Absorbance at 540nm, experiment are done 3 times in parallel.The hemolysis rate of red blood cell calculates as follows:
Hemolysis rate (%)=[(A-A0)/(A1-A0)] * 100
A------ experimental group light absorption value；
A0------ negative control group light absorption value；
A1------ positive controls light absorption value.
It calculates to draw and obtains hemolysis rate, as shown in Figure 7.It is remained from the hemolysis rate of embodiment 1 known to Fig. 7 hemolysis rate figure
5% hereinafter, and all remain stable in different time sections, it is more excellent compared with other comparative examples.
Each technical characteristic of embodiment described above can be combined arbitrarily, for simplicity of description, not to above-mentioned reality
It applies all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited
In contradiction, all should be considered as described in this specification.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
It cannot therefore be construed as limiting the scope of the patent.It should be pointed out that coming for those of ordinary skill in the art
It says, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to protection of the invention
Range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (10)
1. a kind of three-dimensional stephanoporate compound stent, which is characterized in that the compound rest be with 2~10wt% silk fibroin protein solution,
Hyaluronic acid and sodium alginate are what raw material was prepared, wherein the ratio of hyaluronic acid and silk fibroin protein solution be 0.1g:5~
The ratio of 30ml, the mixed solution and sodium alginate of silk fibroin protein solution and hyaluronic acid composition are 15~25ml:0.1g.
2. three-dimensional stephanoporate compound stent according to claim 1, which is characterized in that the concentration of the silk fibroin protein solution is
The ratio of 3.5wt%, the hyaluronic acid and silk fibroin protein solution is 0.1g:20ml.
3. three-dimensional stephanoporate compound stent according to claim 1, which is characterized in that silk fibroin protein solution and hyaluronic acid
The ratio of mixed solution and sodium alginate is 21ml:0.1g.
4. the preparation method of three-dimensional stephanoporate compound stent described in claim 1, which comprises the following steps:
(1), the silk fibroin protein solution of 2~10wt% is added in hyaluronic acid solution, is stirred at room temperature 25~35min, then plus
Enter 0.05~0.5gEDC/NHS and stirs 30~45min；Wherein, it is molten that 5~30ml fibroin albumen is added in every 0.1g hyaluronic acid
Liquid；
(2), 0.05~0.2g sodium alginate is dissolved in 10~24ml deionized water, then the solution obtained with step (1) mixes
Uniformly, injection orifice plate forms gel, and refrigeration forms ice crystalline solid, freeze-drying to get；Wherein, every 0.1g sodium alginate is added 15
The solution of~25ml step (1).
5. the preparation method of three-dimensional stephanoporate compound stent according to claim 4, which is characterized in that described in step (1)
Fibroin albumen the preparation method comprises the following steps: 8g silk cocoon is taken to be placed in large beaker, 400ml deionized water is added, while the anhydrous carbon of 2g is added
Sour sodium boils half an hour taking-up, cleans several times to neutrality with deionized water, repeats and boil a taking-up, wash clean is placed in baking oven
Middle drying.
6. the preparation method of three-dimensional stephanoporate compound stent according to claim 5, which is characterized in that the silk cocoon is to remove pupa
Silk cocoon.
7. the preparation method of three-dimensional stephanoporate compound stent according to claim 4, which is characterized in that described in step (1)
Silk fibroin protein solution the preparation method comprises the following steps: weigh 2~4g fibroin albumen set the lithium bromide that 9.8mol/L is added in a round bottom flask
Solution, 40~60 DEG C of heating water baths dissolve 3~5 hours, and taking-up fibroin albumen mixed liquor, which is placed in bag filter, dialyses 3~5 days, often
Its 1~3 deionized water of replacement, the solution for completing dialysis is centrifuged 8~15 minutes, finally takes out centrifuge tube, supernatant liquor is
For silk fibroin protein solution.
8. the preparation method of three-dimensional stephanoporate compound stent according to claim 7, which is characterized in that the bag filter is cut
Staying molecular weight is 8-14kD, and the centrifugal condition is 25 DEG C, 5000r/min, 10~15min.
9. the preparation method of three-dimensional stephanoporate compound stent according to claim 7, which is characterized in that described in step (2)
Refrigerating crystallization temperature is -80 DEG C.
10. the preparation method of three-dimensional stephanoporate compound stent according to claim 7, which is characterized in that described in step (2)
Lyophilisation condition is -60 DEG C, 48h.
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