CN106581748A - Production method of three-dimensional structured poly(glycerol-sebacate)-based macro-porous scaffold - Google Patents

Production method of three-dimensional structured poly(glycerol-sebacate)-based macro-porous scaffold Download PDF

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Publication number
CN106581748A
CN106581748A CN201611129281.6A CN201611129281A CN106581748A CN 106581748 A CN106581748 A CN 106581748A CN 201611129281 A CN201611129281 A CN 201611129281A CN 106581748 A CN106581748 A CN 106581748A
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China
Prior art keywords
sill
pgs
dimensional structure
sebacic acid
alcohol ester
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CN201611129281.6A
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Chinese (zh)
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CN106581748B (en
Inventor
何创龙
杜海波
王伟忠
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Donghua University
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Donghua University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222Gelatin
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08LCOMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L89/00Compositions of proteins; Compositions of derivatives thereof

Abstract

The invention relates to a production method of a three-dimensional structured poly(glycerol-sebacate)-based macro-porous scaffold. The production method comprises the following steps: pouring an aqueous gelatin solution to a three-dimensional die, and refrigerating the die in a -20 - -80 DEG C for 4-24 h to obtain a three-dimensional structured gelatin macro-porous scaffold; dissolving a poly(glycerol-sebacate) (PGS) base material in a solvent to obtain a PGS base material solution; and immersing the gelatin macro-porous scaffold in the PGS base material solution under a vacuum condition to make the solution completely enter gaps of the gelatin macro-porous scaffold in order to obtain a PGS base material solution adsorbed gelatin scaffold, taking out the scaffold, solidifying the scaffold, cleaning the solidified scaffold, and freeze-drying the cleaned scaffold in order to obtain the three-dimensional structured poly(glycerol-sebacate)-based macro-porous scaffold. Compared with traditional macro-porous scaffold production methods, the method disclosed in the invention has the advantages of simplicity in operation and low production cost.

Description

A kind of preparation method of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support
Technical field
The invention belongs to field of tissue engineering technology, more particularly to a kind of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore The preparation method of support.
Background technology
Sebacic acid and propyl tri-alcohol ester (PGS) sill is a kind of thermosets, and its prepolymer is at ambient temperature viscous Thick shape, it is impossible to directly apply to support preparation, needs carry out heat cure under the hot conditions of anaerobic low pressure could be used to organize Engineering rack application, and the PGS sills for solidifying have good biocompatibility, biodegradable properties and elasticity Energy.And PGS sills are prepared into into the macropore support with complex three-dimensional structure and are even more current Research Challenges, because routine Hole forming technology, such as gas foaming method, freeze-drying, it is impossible to directly combined with the curing process of PGS sills.
The method for being usually used at present preparing PGS sill macropore supports is salt pore method, and two kinds of enforcement skills are generally included again Art.One kind is salt crystallisation, be will supersaturation saline solution be applied to die surface and by mould as hot environment in, with water The loss for dividing, salt can gradually be separated out and form crystal growth in die surface.Its shortcoming is:
(1) in the mould of complex three-dimensional structure, the crystal density heterogeneity if cavity is excessive, it is difficult to make salt pass through crystallization Mode make to be contacted with each other between salt and salt, thus be difficult to prepare complex three-dimensional structure stand;
(2) salt crystallization is susceptible to cave in during perfusion PGS sill solution, prepares inconvenient.
Another kind of implementation is to fill up after salt to compress in mould, makes to be contacted between salt particle, to reach aperture The purpose of UNICOM, its shortcoming is:
(1) though used by salt grain through grinding, cannot ensure that its granular size is homogeneous;
(2) in complex three-dimensional mould is tamped, because unbalance stress causes the Density inhomogeneity of each several part salt.
Because in actual application, tissue engineering bracket often needs to make a variety of complex three-dimensional structures, therefore Explore a kind of simple to operation, it is with low cost, cell will not be had a negative impact, complex three-dimensional structure PGS can be prepared The method of sill macropore support is particularly important.
The content of the invention
The technical problem to be solved is to provide a kind of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore The preparation method of support, the method has no adverse effect using gelatin macropore support as pore-foaming agent to cell;As pore-foaming agent Gelatin macropore support can obtain different porositys by the different of aqueous gelatin solution concentration, and by mould of different shapes Be prepared into it is various want shape the features such as;At the same time, the method is simple to operation, low cost, without the need for main equipment.
A kind of preparation method of the three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support of the present invention, including:
(1) aqueous gelatin solution is poured in specific three-dimensional mould, in -20 DEG C~-80 DEG C 4~24h is freezed, it is dry in freezing Freeze-drying is carried out in dry machine, the gelatin macropore support with complex three-dimensional structure is obtained;
(2) sebacic acid and propyl tri-alcohol ester PGS sills are dissolved in solvent, obtain PGS sill solution;
(3) in the PGS sill solution that the gelatin macropore support in step (1) is soaked in step (2), vacuum condition Under make solution be completely immersed in the space of gelatin macropore support (to be placed in vacuum drying chamber and be evacuated to solution and be completely immersed in gelatin (bubble generation is there is no longer when vacuumizing, can confirm that solution is completely immersed in gelatin macropore support in the hole of macropore support In hole), obtain adsorbing the gelatin support of PGS sill solution, solidify afterwards (while solvent is vapored away) are taken out, cleaning (is washed Remove gelatin), freeze-drying obtains (complicated or simple shape) three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore Frame.
The concentration of aqueous gelatin solution is 1%~10% (w/v) in the step (1).
Three-dimensional mould in the step (1) is specific three-dimensional mould, so as to the complex three-dimensional structure needed for obtaining The perforating agent of frame;The specific three-dimensional mould is referred to and use according to actual needs three-dimensional mould of different shapes, had The three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support of simple or complicated shape structure.
The complex three-dimensional structure of the support depends on the shape of mould.
PGS sills are sebacic acid and propyl tri-alcohol ester PGS, PGSLP etc. in the step (2).
Solvent is absolute ethyl alcohol, tetrahydrofuran or 1,4- dioxane in the step (2).
The concentration of PGS sill solution is 10%~70% (w/v) in the step (2).
The vacuum of vacuum condition is in the step (3):Less than 10Pa.
The condition of solidification is in the step (3):150 DEG C are placed in, 24~96h in the vacuum drying chamber of 100Pa.
Clean in the step (3) and be:It is immersed in 45~60 DEG C of water and cleans.
Cryodesiccated condition is in the step (3):- 80 DEG C of freeze-dryings 2~3 days.
The size of the macropore of complex three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support is in the step (3) 50~800 μm.
It is g/ml that the w/v is corresponding.
Complex three-dimensional structure sebacic acid and propyl tri-alcohol (PGS) sill macropore support is prepared in the present invention, is by solution What the mode freezed after mold was obtained, not only can easily prepare the three-dimensional appearance of various complexity, and its internal each portion Point aperture is homogeneous, connection.Additionally, pore-foaming agent raw material used is gelatin, its feature is adhesion and the propagation that can help to cell, Thus the residual after removing, can only positive impact be brought to the cell compatibility of tissue engineering bracket.
Beneficial effect
(1) the method operating procedure for preparing PGS sill macropore supports of the invention is simple, low cost, without the need for main equipment;
(2) pore-foaming agent for being used for preparing PGS sill macropore supports of the invention can be by simple that physical method is removed, use In PGS sill macropore supports are built, can farthest reduce pore-foaming agent and remove not exclusively to the negative effect of cell;
(3) PGS sill macropores support prepared by the present invention can be according to required three-dimensional structure, using specific three-dimensional mould Tool is obtained specific three-dimensional appearance, so as to be adapted to various needs;
(4) pore-foaming agent that the present invention is prepared used by PGS sill macropore supports can be reclaimed again by the method for evaporative crystallization Utilize, be conducive to environmental protection.
Description of the drawings
Fig. 1 is the SEM pictures of the PGSLP macropore supports prepared in embodiment 1.
Specific embodiment
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate the present invention Rather than restriction the scope of the present invention.In addition, it is to be understood that after the content for having read instruction of the present invention, people in the art Member can make various changes or modifications to the present invention, and these equivalent form of values equally fall within the application appended claims and limited Scope.
Embodiment 1
(1) gelatin is dissolved in into water it is configured to the aqueous solution of 3% (w/v) and pours the three-dimensional mould with certain three-dimensional structure into In, freeze 1 day in -20 DEG C, freeze-drying in freeze drier is placed in, gelatin macropore support is obtained as pore-foaming agent;
(2) PGSLP is dissolved in tetrahydrofuran the PGS sill solution for being configured to 10% (w/v);
(3) in the PGS sill solution that the gelatin macropore support in step (1) is immersed in step (2), it is placed in true In empty drying box, the circulation under the vacuum less than 10Pa is evacuated to and is produced without bubble, illustrates that solution is completely immersed in gelatin In the macropore hole of support, then the gelatin support of absorption PGS sill solution is taken out, be placed in temperature is for 150 DEG C, air pressure 48h in the vacuum drying chamber of 100Pa, makes solvent volatilize and solidifies PGS sills;
(4) with the immersion of 60 DEG C of water to remove pore-foaming agent (gelatin), -80 DEG C of freeze-dryings 2 days obtain 100~600 μm The complex three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support in aperture.
Embodiment 2
(1) gelatin is dissolved in into water it is configured to the aqueous solution of 1% (w/v) and pours the three-dimensional mould with certain three-dimensional structure into In, freeze 1 day in -20 DEG C, freeze-drying in freeze drier is placed in, gelatin macropore support is obtained as pore-foaming agent;
(2) PGSLP is dissolved in absolute ethyl alcohol the PGS sill solution for being configured to 10% (w/v);
(3) in the PGS sill solution that the gelatin macropore support in step (1) is immersed in step (2), it is placed in true In empty drying box, the circulation under the vacuum less than 10Pa is evacuated to and is produced without bubble, illustrates that solution is completely immersed in gelatin In the macropore hole of support, then the gelatin support of absorption PGS sill solution is taken out, be placed in temperature is for 150 DEG C, air pressure 48h in the vacuum drying chamber of 100Pa, makes solvent volatilize and solidifies PGS sills;
(4) with the immersion of 50 DEG C of water to remove pore-foaming agent, -80 DEG C of freeze-dryings 3 days obtain 200~800 μm of apertures Complex three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support.
Embodiment 3
(1) gelatin is dissolved in into water it is configured to the aqueous solution of 5% (w/v) and pours the three-dimensional mould with certain three-dimensional structure into In, freeze 1 day in -20 DEG C, freeze-drying in freeze drier is placed in, gelatin macropore support is obtained as pore-foaming agent;
(2) sebacic acid and propyl tri-alcohol ester (PGS) is dissolved in 1,4- dioxane the PGS base materials for being configured to 10% (w/v) Material solution;
(3) in the PGS sill solution that the gelatin macropore support in step (1) is immersed in step (2), it is placed in true In empty drying box, the circulation under the vacuum less than 10Pa is evacuated to and is produced without bubble, illustrates that solution is completely immersed in gelatin In the macropore hole of support, then the gelatin support of absorption PGS sill solution is taken out, be placed in temperature is for 150 DEG C, air pressure 96h in the vacuum drying chamber of 100Pa, makes solvent volatilize and solidifies PGS sills;
(4) with the immersion of 45 DEG C of water to remove pore-foaming agent, -80 DEG C of freeze-dryings 2.5 days obtain aperture for 50~400 μ The complex three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support in m apertures.

Claims (10)

1. a kind of preparation method of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support, including:
(1) aqueous gelatin solution is poured in three-dimensional mould, in -20 DEG C~-80 DEG C 4~24h is freezed, freeze-drying is had The gelatin macropore support of complex three-dimensional structure;
(2) sebacic acid and propyl tri-alcohol ester PGS sills are dissolved in solvent, obtain PGS sill solution;
(3) in the PGS sill solution that the gelatin macropore support in step (1) is soaked in step (2), make under vacuum condition Solution is completely immersed in the space of gelatin macropore support, obtains adsorbing the gelatin support of PGS sill solution, takes out solidify afterwards, Cleaning, freeze-drying obtains three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support.
2. the preparation side of a kind of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support according to claim 1 Method, it is characterised in that the concentration of aqueous gelatin solution is 1%~10% (w/v) in the step (1).
3. the preparation side of a kind of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support according to claim 1 Method, it is characterised in that PGS sills are sebacic acid and propyl tri-alcohol ester PGS or PGSLP in the step (2).
4. the preparation side of a kind of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support according to claim 1 Method, it is characterised in that solvent is absolute ethyl alcohol, tetrahydrofuran or Isosorbide-5-Nitrae-dioxane in the step (2).
5. the preparation side of a kind of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support according to claim 1 Method, it is characterised in that the concentration of PGS sill solution is 10%~70% (w/v) in the step (2).
6. the preparation side of a kind of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support according to claim 1 Method, it is characterised in that the vacuum of vacuum condition is in the step (3):Less than 10Pa.
7. the preparation side of a kind of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support according to claim 1 Method, it is characterised in that the condition of solidification is in the step (3):150 DEG C are placed in, 24~96h in the vacuum drying chamber of 100Pa.
8. the preparation side of a kind of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support according to claim 1 Method, it is characterised in that cleaning in the step (3) is:It is immersed in 45~60 DEG C of water and cleans.
9. the preparation side of a kind of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support according to claim 1 Method, it is characterised in that cryodesiccated condition is in the step (3):- 80 DEG C of freeze-dryings 2~3 days.
10. the preparation side of a kind of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support according to claim 1 Method, it is characterised in that the size of the macropore of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore support in the step (3) For 50~800 μm.
CN201611129281.6A 2016-12-09 2016-12-09 A kind of preparation method of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore bracket Expired - Fee Related CN106581748B (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112807491A (en) * 2020-12-31 2021-05-18 东华大学 Elastic tissue engineering scaffold with communicated macroporous structure and preparation method thereof

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CN101176799A (en) * 2007-12-06 2008-05-14 同济大学 Method for preparing polyalcohol stephanoporate bracket for tissue project by poragen agglutinating filtering off method
CN102423272A (en) * 2011-09-20 2012-04-25 复旦大学 Porous stent with network passage and preparation method of porous stent
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112807491A (en) * 2020-12-31 2021-05-18 东华大学 Elastic tissue engineering scaffold with communicated macroporous structure and preparation method thereof

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