CN110124105A - The biological 3D printing ink-manufacturing method of controllable gel-sol phase transition temperature - Google Patents
The biological 3D printing ink-manufacturing method of controllable gel-sol phase transition temperature Download PDFInfo
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- CN110124105A CN110124105A CN201910299325.7A CN201910299325A CN110124105A CN 110124105 A CN110124105 A CN 110124105A CN 201910299325 A CN201910299325 A CN 201910299325A CN 110124105 A CN110124105 A CN 110124105A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/26—Mixtures of macromolecular compounds
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- 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
- A61L27/52—Hydrogels or hydrocolloids
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2389/00—Characterised by the use of proteins; Derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2405/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
- C08J2405/04—Alginic acid; Derivatives thereof
Abstract
The invention discloses a kind of biological 3D printing ink-manufacturing methods of controllable gel-sol phase transition temperature, the present invention by regulation gelatin/sodium alginate 3D printing aquogel system Sol-gel phase transition temperature, by control within the temperature range of most suitable cell is grown.Then the cartilage frame that high resolution is printed using cell 3D printing technique improves the printability and biocompatibility of hydrogel material.Inorganic nanoparticles are added in this basic aquogel system, the mechanical property of cartilage frame can be improved, to solve the technical problem that printing shaping temperature is mismatched with cell growth temperature and hydrogel material mechanical property is bad.
Description
Technical field
It the present invention relates to the use of the technical field of material more particularly to one that biological 3D printing prepares artificial cartilage bracket
Kind prepares the preparation with the cartilage frame that sodium alginate/glutin is basic marking ink of controllable colloidal sol-gel transition temperature
Method.
Background technique
The patient of cartilage defect caused by the reasons such as fat, movement, age or lesion is more and more, becomes human health
One big killer.Currently, repair of cartilage is still clinical medical a great problem.In recent years, the development of cell 3D printing technique promoted
Application of the increases material manufacturing technology in field of tissue engineering technology.Cell 3D printing technique not only passes through the micro- of high-precision control organization bracket
Structure, shape and composition so that the mechanical property to bracket regulates and controls, and also have a fixing for cell quantity and distribution
It rings.
It is main group of extracellular matrix since the polysaccharide matrixes such as gelatin, sodium alginate, chitosan derive from natural tissues
At ingredient and there is good biocompatibility, therefore through the biometric print ink frequently as biological 3D printing.With gelatin/sea
The sol-gel condition conversion of marking ink system based on mosanom is reversible, in some specific temperature, marking ink
The condition conversion that sol-gel can occur, enables bracket printing shaping.Therefore, gelatin/sodium alginate bio-ink is fought each other
Print temperature requirement with higher.Meanwhile cell is very sensitive for the temperature of living environment, therefore to printing temperature requirement pole
It is high.But the temperature range for being suitble to the sol-gel transition temperature of bracket printing shaping that may not be able to grow with suitable cell
Match.If the two cannot match, it will be affected using the printability of the marking ink of cell mixing, and be encapsulated in printing
Cell activity in ink also will receive adverse effect.The application that 3D printing cartilage frame repairs damaged cartilage is restricted.It opens
Sending out the preparation for being suitble to the biometric print ink of cell 3D printing to be used for cartilage frame is a challenge.Therefore, inventing one kind has
Marking ink based on the gelatin/sodium alginate of adjustable Sol-gel phase transition temperature is that this field technology urgently to be resolved is difficult
Topic.
Summary of the invention
The deficiencies in the prior art of the present invention, it is an object of the invention to prepare with adjustable Sol-gel phase transition temperature
Gelatin/sodium alginate system improves the printing precision of cell mixing printing slurry.The present invention can regulate and control gelatin/sodium alginate
The Sol-gel phase transition temperature of 3D printing aquogel system, by control within the temperature range of most suitable cell is grown.Then
The cartilage frame that high resolution is printed using cell 3D printing technique improves the printability and bio-compatible of hydrogel material
Property.Inorganic nanoparticles are added in this basic aquogel system, the mechanical property of cartilage frame can be improved, to solve
Printing shaping temperature and the technical problem that cell growth temperature mismatches and hydrogel material mechanical property is bad.
The technical scheme is that being to realize in this way:
It is molten with the temperature-sensitive hydrogel system that gelatin/sodium alginate is basic marking ink that the present invention provides a kind of regulation
Glue-gel transition temperature method, preparation process are as follows:
Gelatin powder is dissolved or dispersed in deionized water by step (1), and the temperature of heating water bath is 65 DEG C~90 DEG C, is turned
Speed is that 10~30r/min is stirred, and 20~45min of heating stirring is made into gelatin solution.
Sodium alginate is dissolved or dispersed in gelatin solution by step (2), and the temperature of heating water bath is 65 DEG C~90 DEG C, is turned
Speed is that 10~30r/min is stirred, and 80~150min of heating stirring is made into sodium alginate/glutin solution mixing hydrogel solution.
Step (3) is by sodium alginate/glutin solution mixing hydrogel solution, and Temperature fall is to 20 DEG C~28 in water-bath
℃；Obtain sodium alginate/glutin mixing hydrogel；
Step (4) again executes the heating of sodium alginate/glutin solution mixing hydrogel solution and cooling cycle multiple；By
Different heating and cooling number；Obtain having the sodium alginate/glutin mixing hydrogel of different phase transition temperatures to get to not
With the biological 3D printing ink of phase transition temperature.
Wherein heating means are as follows: by 65 DEG C of the temperature of sodium alginate/glutin solution mixing hydrogel solution heating water bath~
90 DEG C, revolving speed is 10~30r/min stirring, 50~120min of heating stirring；
Cooling means are as follows: by sodium alginate/glutin solution mixing hydrogel solution in water-bath Temperature fall to 20 DEG C
~28 DEG C.
Preferably, the bath temperature in step (1) is 78 DEG C；
Preferably, the revolving speed in step (1) is 20r/min；
Preferably, step (1) and step (2) heating stirring summation are 110-130min；
Preferably, being intended to stop stirring and Temperature fall in cooling procedure；
Preferably, the mass ratio of above-mentioned gelatin and sodium alginate is 4:1, gelatin and sodium alginate are remixed in solution
Concentration is respectively 8%~8.8% and 2.0%~2.2%.
Preferably, first at room temperature will in sodium alginate/glutin solution mixing hydrogel solution cooling procedure
The uniform ultrasonic disperse of nano particle is into deionization, when sodium alginate/glutin solution mixing hydrogel solution stops heating stirring
Afterwards, when temperature is reduced to 50 DEG C, then nano particle unit for uniform suspension is added to sodium alginate/glutin solution mixing hydrogel
In 50 DEG C of heating stirring 60min in solution.
The gelatin/sodium alginate mixing marking ink containing inorganic nanoparticles that will be prepared, is existed using cell assembler
Be printed as 3D cartilage frame under room temperature, carry out ionomer using calcium chloride solution, it is available have compared with high bioactivity and
Biocompatibility and the porous cartilage frame of composite hydrogel 3D with certain precision.
Gelatin described above, sodium alginate, commercially available from inorganic nanoparticles, deionized water is made by equipment.
Compared with prior art, the invention has the following advantages that
1) present invention is controllable using gelatin/sodium alginate as the colloidal sol-of the temperature-sensitive hydrogel material of biometric print slurry
Gel transition temperature and viscosity.
2) a variety of inorganic nanoparticles can be added to the water gel that slurry is printed based on gelatin/sodium alginate
System, the mechanical property and cell adhesion that can enhance hydrogel have an impact.
3) present invention process method is simple, low in cost, convenient for being suitble to industrialized production, can be widely applied to biologic medical
Field.
4) with commonsense method preparation gelatin/sodium alginate aquogel system compared with, the present invention can balance 3D printing precision,
Bracket activity and cell compatibility can prepare fine cartilage frame with excellent mechanical performances and carry out repair of cartilage.
Detailed description of the invention
Fig. 1 is conversion temperature when being 31.6 DEG C storage modulu and loss modulus with temperature trend chart；
Fig. 2 is conversion temperature when being 30.5 DEG C storage modulu and loss modulus with temperature trend chart；
Fig. 3 is conversion temperature when being 29.2 DEG C storage modulu and loss modulus with temperature trend chart；
Fig. 4 is the variation of the viscosity with temperature of the basis printing slurry of different disposal method；
Fig. 5 is the phase transition temperature figure of the basis printing slurry of different disposal method；
Fig. 6 (a), (b) are the structure chart for heating with being printed after cooling cycle execution three times under the conditions of 21 DEG C；
Fig. 7 is the structure chart for heating with being printed after cooling cycle execution three times under the conditions of 25 DEG C；
Fig. 8 is the structure chart for heating with being printed after cooling cycle execution twice under the conditions of 25 DEG C；
Fig. 9 is the structure chart for heating with being printed after cooling cycle execution once under the conditions of 25 DEG C.
Specific embodiment
It elaborates, but should not be understood as pair to technical solution of the present invention and technical effect below with reference to embodiment
The restriction of enforceable range of the present invention.
In the examples below, gelatin, sodium alginate, nano-grade hydroxy apatite, nano-cellulose are that this field is normal
Material can be obtained by commercially available range.
Several specific embodiments presented below are to help to understand the present invention.
Embodiment 1: 4g gelatin powder is swollen 30min in the beaker for filling 20ml deionized water, secondary beaker is put into
It is 20.0% (W/V) that concentration, which is made, with the speed heating stirring 30min of 20r/min in the water-bath magnetic stirrer that water temperature is 78 DEG C
Aqueous gelatin solution, 1g sodium alginate powder, 25ml deionized water, magnetic agitation are added in the beaker of Xiang Shengyou aqueous gelatin solution
Device heating temperature remains unchanged, and revolving speed is adjusted to 10r/min, heating stirring 80min, and finally obtaining concentration is about 2.2% (W/V)
Sodium alginate and concentration be about 8.8% (W/V) gelatin-compounded solution；The heating temperature of magnetic stirring apparatus is adjusted to 28
DEG C, the temperature of composite solution is gradually decrease to 20 DEG C with water temperature, and it is spare to take out deepfreeze.Existed using the controlled kludge of cell
3D cartilage hydrogel scaffold is printed at room temperature.Printed branch is placed on to 4% CaCl2Be crosslinked in solution, by bracket from
CaCl2It is taken out in solution, is rinsed bracket 3 times with deionized water, obtain the preferable hydrogel scaffold of mechanical property.
Embodiment 2: 4g gelatin powder is swollen 30min in the beaker for filling 20ml deionized water, beaker is put into water
Temperature is 20.0% (W/V) for concentration is made with the speed heating stirring 30min of 20r/min in 78 DEG C of water-bath magnetic stirrer
1g sodium alginate powder, 25ml deionized water, magnetic stirring apparatus are added in the beaker of Xiang Shengyou aqueous gelatin solution for aqueous gelatin solution
Heating temperature remains unchanged, and revolving speed is adjusted to 14r/min, heating stirring 90min, and finally obtaining concentration is about 2.2% (W/V)
The gelatin-compounded solution that sodium alginate and concentration are about 8.8% (W/V)；The heating temperature of magnetic stirring apparatus is adjusted to 28 DEG C,
Revolving speed is set as 0r/min, and the temperature of composite solution is gradually decrease to 28 DEG C with water temperature；78 DEG C are set by heating temperature again,
Revolving speed is set as 14r/min, and it is spare to take out deepfreeze for cooling processing again after heating stirring 60min.Taking-up is heated to room temperature,
It takes out a part of material and does rheology testing, loss modulus and storage modulu as the variation of temperature is as shown in Figure 2.It utilizes
The controlled kludge of cell prints 3D cartilage hydrogel scaffold at room temperature.Printed branch is placed on to 4% CaCl2In solution
It is crosslinked 10min, by bracket from CaCl2It is taken out in solution, is rinsed bracket 3 times with deionized water, obtain the preferable water of mechanical property
Gel stent.
Embodiment 3: 4g gelatin powder is swollen 30min in the beaker for filling 20ml deionized water, secondary beaker is put into
It is 20.0% (W/V) that concentration, which is made, with the speed heating stirring 30min of 20r/min in the water-bath magnetic stirrer that water temperature is 78 DEG C
Aqueous gelatin solution, 1g sodium alginate powder, 25ml deionized water, magnetic agitation are added in the beaker of Xiang Shengyou aqueous gelatin solution
Device heating temperature remains unchanged, and revolving speed is adjusted to 14r/min, heating stirring 90min, and finally obtaining concentration is about 2.2% (W/V)
Sodium alginate and concentration be about 8.8% (W/V) gelatin-compounded solution；The heating temperature of magnetic stirring apparatus is adjusted to 28
DEG C, revolving speed is set as 0r/min, and the temperature of composite solution is gradually decrease to 28 DEG C with water temperature；78 are set by heating temperature again
DEG C, revolving speed is set as 14r/min, cooling processing again after heating stirring 60min；Heating and cooling processing are repeated, low temperature cold is taken out
It hides spare.Taking-up is heated to room temperature, takes out a part of material and does rheology testing, loss modulus and storage modulu are with temperature
The variation of degree is as shown in Figure 3.3D cartilage hydrogel scaffold is printed at room temperature using the controlled kludge of cell.By printed branch
It is placed on 4% CaCl210min is crosslinked in solution, by bracket from CaCl2It takes out in solution, is rinsed bracket 3 times with deionized water,
Obtain the preferable hydrogel scaffold of mechanical property.
Embodiment 4: 4g gelatin powder is swollen 30min in the beaker for filling 20ml deionized water, secondary beaker is put into
It is 20.0% (W/V) that concentration, which is made, with the speed heating stirring 20min of 20r/min in the water-bath magnetic stirrer that water temperature is 78 DEG C
Aqueous gelatin solution, 1g sodium alginate powder, 25ml deionized water, magnetic agitation are added in the beaker of Xiang Shengyou aqueous gelatin solution
Device heating temperature remains unchanged, and revolving speed is adjusted to 14r/min, heating stirring 90min, and finally obtaining concentration is about 2.2% (W/V)
Sodium alginate and concentration be about 8.8% (W/V) gelatin-compounded solution；The heating temperature of magnetic stirring apparatus is adjusted to 28
DEG C, revolving speed is set as 20r/min, and the temperature of composite solution is gradually decrease to 28 DEG C with water temperature；Again set heating temperature to
78 DEG C, revolving speed is set as 14r/min, and it is spare to take out deepfreeze for cooling processing again after heating stirring 60min.Take out gelatin/sea
Mosanom basis composite hydrogel prints slurry, and 0.55g nano-grade hydroxy apatite is added to base water to 50 DEG C in heating water bath
Gel rubber system heating stirring 1h.Room temperature cooling is to room temperature, the then gelatin/sodium alginate hydrogel containing nanometer hydroxyapatite
It is stored refrigerated spare.3D cartilage frame is printed at room temperature using the controlled kludge of cell.Printed branch is placed on 4%
CaCl210min is crosslinked in solution, by bracket from CaCl2It is taken out in solution, is rinsed bracket 3 times with deionized water, obtain mechanical property
It can preferable hydrogel scaffold.
Embodiment 5: 4g gelatin powder is swollen 30min in the beaker for filling 23ml deionized water, secondary beaker is put into
It is 20.0% (W/V) that concentration, which is made, with the speed heating stirring 30min of 10r/min in the water-bath magnetic stirrer that water temperature is 65 DEG C
Aqueous gelatin solution, 1g sodium alginate powder, 25ml deionized water, magnetic agitation are added in the beaker of Xiang Shengyou aqueous gelatin solution
Device heating temperature remains unchanged, and revolving speed is adjusted to 10r/min, heating stirring 80min, and finally obtaining concentration is about 2.2% (W/V)
Sodium alginate and concentration be about 8.8% (W/V) gelatin-compounded solution；The heating temperature of magnetic stirring apparatus is adjusted to 20
DEG C, revolving speed is set as 10r/min, and the temperature of composite solution is gradually decrease to 20 DEG C with water temperature；Again set heating temperature to
65 DEG C, revolving speed is set as 10r/min, and it is spare to take out deepfreeze for cooling processing again after heating stirring 50min.Using cell by
Control kludge prints 3D cartilage frame at room temperature.Printed branch is placed on to 4% CaCl2It is crosslinked in solution, by bracket
From CaCl2It is taken out in solution, is rinsed bracket 3 times with deionized water, obtain gelatin/sodium alginate hydrogel scaffold.
Embodiment 6: 4g gelatin powder is swollen 30min in the beaker for filling 25ml deionized water, secondary beaker is put into
It is 20.0% (W/V) that concentration, which is made, with the speed heating stirring 45min of 30r/min in the water-bath magnetic stirrer that water temperature is 90 DEG C
Aqueous gelatin solution, 1g sodium alginate powder, 25ml deionized water, magnetic agitation are added in the beaker of Xiang Shengyou aqueous gelatin solution
Device heating temperature remains unchanged, and revolving speed is adjusted to 30r/min, heating stirring 150min, and finally obtaining concentration is about 2.2% (W/
V the gelatin-compounded solution that sodium alginate and concentration) is about 8.8% (W/V)；The heating temperature of magnetic stirring apparatus is adjusted to 28
DEG C, revolving speed is set as 30r/min, and the temperature of composite solution is gradually decrease to 28 DEG C with water temperature；Again set heating temperature to
90 DEG C, revolving speed is set as 30r/min, and it is spare to take out deepfreeze for cooling processing again after heating stirring 120min.Using cell by
Control kludge prints 3D cartilage frame at room temperature.Printed branch is placed on to 4% CaCl2It is crosslinked in solution, by bracket
From CaCl2It is taken out in solution, is rinsed bracket 3 times with deionized water, obtain gelatin/sodium alginate hydrogel scaffold.
As can be seen from Figure 4, increase the heating of gelatin sodium alginate mixing hydrogel solution, cooling number leads to gelatin sodium alginate
The viscosity presentation of mixing hydrogel is substantially reduced trend.
As can be seen from Figure 5, increase the heating of gelatin sodium alginate mixing hydrogel solution, cooling number leads to its colloidal sol-gel
Transition temperature presentation be substantially reduced trend.
Fig. 5, in 6, A: B of processing: processing C twice: processing is three times.
The 3D printing environment temperature of Fig. 6 is 21 DEG C since the phase transition temperature of the less bio-ink of number of processes is relatively high,
Cause to print at a lower temperature and the case where fracture of wire accumulation occur, as shown in the left side two stands of Fig. 6；By heat treatment 3 times
Bracket have relatively low conversion temperature, printing shaping precision is relatively high under the conditions of 21 DEG C, and fracture of wire situation does not occur.
Gelatin/sodium alginate hydrogel solution is handled using different processing methods, the 3D for obtaining different phase transition temperatures is beaten
Print bio-ink.It is printed under the conditions of room temperature is 25 DEG C, from figure 7 it can be seen that the biological 3D printing ink of processing three times squeezes out
Silk thread be not easy solidification bracket caused easily to collapse, this is because there is the bio-ink that obtains three times of processing lower colloidal sol-to coagulate
Glue conversion temperature；And it can be seen in figure 9 that the primary biological 3D printing ink of processing to be easy fracture of wire molding effect bad, this
It is the biological 3D printing ink with higher conversion temperature less due to number of processes；As can be seen from Figure 8, molding effect
Best 3D printing bio-ink is handled twice.Therefore, under certain specific temperature, the phase of hydrogel material can be regulated and controled
Temperature make at this temperature molding effect it is best.
Claims (7)
1. the biological 3D printing ink-manufacturing method of controllable gel-sol phase transition temperature, which is characterized in that this method is specifically wrapped
Include following steps:
Gelatin powder is dissolved or dispersed in deionized water by step (1), and the temperature of heating water bath is 65 DEG C~90 DEG C, and revolving speed is
10~30r/min stirring, 20~45min of heating stirring are made into gelatin solution；
Sodium alginate is dissolved or dispersed in gelatin solution by step (2), and the temperature of heating water bath is 65 DEG C~90 DEG C, and revolving speed is
10~30r/min stirring, 80~150min of heating stirring are made into sodium alginate/glutin solution mixing hydrogel solution；
Sodium alginate/glutin solution mixing hydrogel solution in water-bath is stopped stirring and Temperature fall is to 20 by step (3)
DEG C~28 DEG C；Obtain sodium alginate/glutin mixing hydrogel；
Step (4) again executes the heating of sodium alginate/glutin solution mixing hydrogel solution and cooling cycle multiple；By difference
Heating and cooling number；Obtain having the sodium alginate/glutin mixing hydrogel of different phase transition temperatures to get to different phases
The biological 3D printing ink of temperature；
Wherein heating means are as follows: by 65 DEG C~90 DEG C of temperature of sodium alginate/glutin solution mixing hydrogel solution heating water bath,
Revolving speed is 10~30r/min stirring, 50~120min of heating stirring；
Cooling means are as follows: sodium alginate/glutin solution mixing hydrogel solution is stopped into stirring and Temperature fall in water-bath
To 20 DEG C~28 DEG C.
2. the biological 3D printing ink-manufacturing method of controllable gel-sol phase transition temperature according to claim 1, special
Sign is: the water bath heating temperature in step (1) is 78 DEG C.
3. the biological 3D printing ink-manufacturing method of controllable gel-sol phase transition temperature according to claim 1, special
Sign is: the revolving speed in step (1) is 20r/min.
4. the biological 3D printing ink-manufacturing method of controllable gel-sol phase transition temperature according to claim 1, special
Sign is: step (1) and step (2) heating stirring summation are 110-130min.
5. the biological 3D printing ink-manufacturing method of controllable gel-sol phase transition temperature according to claim 1, special
Sign is: being intended to stop stirring and Temperature fall in cooling procedure.
6. the extendible ink-manufacturing method of 3D printing of controllable gel-sol phase transition temperature according to claim 1,
It is characterized in that: in sodium alginate/glutin solution mixing hydrogel solution cooling procedure, first at room temperature by nano particle
Uniform ultrasonic disperse after sodium alginate/glutin solution mixing hydrogel solution stops heating stirring, works as temperature into deionization
When being reduced to 50 DEG C, then nano particle unit for uniform suspension is added in sodium alginate/glutin solution mixing hydrogel solution
50 DEG C of heating stirring 60min.
7. the biological 3D printing ink-manufacturing method of controllable gel-sol phase transition temperature according to claim 1, special
Sign is: the mass ratio of the gelatin and sodium alginate is 4:1, and gelatin and sodium alginate remix the mass concentration in solution
Respectively 8%~8.8% and 2.0%~2.2%.
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| CN111320767A (en) * | 2020-03-04 | 2020-06-23 | 西南交通大学 | Preparation method of thixotropic hydrogel for 3D bioprinting |
| CN114681675A (en) * | 2022-04-08 | 2022-07-01 | 张楷乐 | Preparation method of 3D printing hydrogel urethral stent |
| CN114796617A (en) * | 2022-05-25 | 2022-07-29 | 中山大学 | Composite 3D printing ink and application thereof |
| CN115845146A (en) * | 2022-11-29 | 2023-03-28 | 杭州电子科技大学 | Preparation method of biological ink and preparation method of cell scaffold |
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