CN114147952B - Macroporous hydrogel 3D printing device and printing method - Google Patents
Macroporous hydrogel 3D printing device and printing method Download PDFInfo
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- CN114147952B CN114147952B CN202111445153.3A CN202111445153A CN114147952B CN 114147952 B CN114147952 B CN 114147952B CN 202111445153 A CN202111445153 A CN 202111445153A CN 114147952 B CN114147952 B CN 114147952B
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- 238000007639 printing Methods 0.000 title claims abstract description 222
- 239000000017 hydrogel Substances 0.000 title claims abstract description 153
- 238000010146 3D printing Methods 0.000 title claims abstract description 60
- 238000000034 method Methods 0.000 title claims description 25
- 239000011521 glass Substances 0.000 claims abstract description 133
- 238000002347 injection Methods 0.000 claims abstract description 130
- 239000007924 injection Substances 0.000 claims abstract description 130
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 66
- 239000007788 liquid Substances 0.000 claims abstract description 62
- 238000010438 heat treatment Methods 0.000 claims abstract description 43
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- 230000002209 hydrophobic effect Effects 0.000 claims description 14
- 230000005514 two-phase flow Effects 0.000 claims description 10
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- 238000004132 cross linking Methods 0.000 claims description 7
- 230000004886 head movement Effects 0.000 claims 1
- 239000006260 foam Substances 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 15
- 239000011148 porous material Substances 0.000 description 8
- 239000000758 substrate Substances 0.000 description 5
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- 238000010586 diagram Methods 0.000 description 4
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- 238000000635 electron micrograph Methods 0.000 description 2
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/10—Processes of additive manufacturing
- B29C64/106—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/30—Auxiliary operations or equipment
- B29C64/379—Handling of additively manufactured objects, e.g. using robots
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y10/00—Processes of additive manufacturing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y40/00—Auxiliary operations or equipment, e.g. for material handling
- B33Y40/20—Post-treatment, e.g. curing, coating or polishing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y50/00—Data acquisition or data processing for additive manufacturing
- B33Y50/02—Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
- B29K2105/00—Condition, form or state of moulded material or of the material to be shaped
- B29K2105/04—Condition, form or state of moulded material or of the material to be shaped cellular or porous
- B29K2105/041—Microporous
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Abstract
The invention discloses a macroporous hydrogel 3D printing device which comprises a gas injection pump, a barometer, a T-shaped channel, a gas inlet capillary glass tube, an outlet capillary glass tube, a horizontal moving support, a water bath sleeve, a liquid injection pump, a flowmeter, a D printing nozzle, a printing bottom plate, a submersible pump and a constant-temperature water bath heating device. The macroporous hydrogel prepared by the device can ensure good shape and size precision on the appearance structure, can accurately control the spatial position and size of the foam hole, and has strong editability; the device can realize various types of macroporous hydrogel structures including uniform cell structures, cell structures presenting density gradients and cell structures presenting size gradients by adjusting gas phase flow and the like, and can be used for various purposes.
Description
Technical Field
The invention relates to the field of micro-fluidic and the fields of medicine, biology, tissue engineering and the like, in particular to a 3D printing device and a printing method for macroporous hydrogel.
Background
The macroporous hydrogel material is a composite porous material formed by further introducing micron-to-submillimeter-sized macropores outside the porous structure of the hydrogel polymer. Since the pore size of the hydrogel material itself is typically on the order of nanometers to several microns, these additional introduced micron to sub-millimeter scale pores are generally referred to in the art as macropores. The macroporous hydrogel has controllable porosity on nano and micron scales, provides swelling and interface properties of the hydrogel, also provides transmission characteristics of a macroporous material, and is widely researched and applied in tissue engineering, organ construction and drug delivery. For example, macroporous hydrogels can enhance cell survival and function in hydrogels, and can be used to mimic porous organs and tissues such as bone/cartilage tissue, lung tissue, and kidney. In these tissues, the porous structure is generally composed of pores of different sizes and densities, which form a specific anisotropic spatial arrangement and gradient relationship with each other.
At present, the cellular structure in the macroporous hydrogel is still uncontrollable, and the structure is single, so that the macroporous hydrogel becomes a main restriction factor for the wider application of the macroporous hydrogel. Therefore, the search for an effective method for preparing spatially controlled macroporous hydrogels remains an important problem to be solved urgently.
Disclosure of Invention
In view of the technical problems, the invention provides a 3D printing device and a printing method for macroporous hydrogel, which can ensure stable preparation of the macroporous hydrogel, control the relative fixation of the size and the position of the foam hole, and realize the preparation of the macroporous hydrogel with a specific shape and an internal structure.
The purpose of the invention is realized by the following technical scheme:
a macroporous hydrogel D printing device comprises a gas injection pump, a barometer, a T-shaped channel, a gas inlet capillary glass tube, an outlet capillary glass tube, a horizontal moving bracket, a water bath sleeve, a liquid injection pump, a flowmeter, a D printing nozzle, a printing bottom plate, a submersible pump and a constant-temperature water bath heating device;
the air inlet capillary glass tube and the outlet capillary glass tube are both nested in the T-shaped channel, the upper end of the air inlet capillary glass tube is fixedly connected to the T-shaped channel, the upper end of the outlet capillary glass tube is nested and fixedly connected to the lower end of the T-shaped channel, and the outlet of the air inlet capillary glass tube and the inlet of the outlet capillary glass tube are kept to be (0.3-1) times of the number of the capillary glass tubes; the air inlet capillary glass tube, the outlet capillary glass tube and the T-shaped channel are fixed in the water bath sleeve together after being nested; the water bath sleeve is sequentially connected with the submersible pump and the constant-temperature water bath heating device to form a stable bubble generation temperature environment, and the bubble generation temperature is accurately controlled; the gas injection pump is communicated with one end of the air inlet capillary glass tube, and a gas pressure meter is arranged on a pipeline between the gas injection pump and the air inlet capillary glass tube; the liquid injection pump is communicated with the single transverse structure of the T-shaped channel, the flowmeter is arranged on a pipeline between the liquid injection pump and the T-shaped channel, and temperature-sensitive hydrogel is contained in the liquid injection pump;
the cross sections of the inner channels of the air inlet capillary glass tube and the outlet capillary glass tube are both circular;
the printing bottom plate is a heating bottom plate, and the temperature of the bottom plate can be adjusted;
the water bath sleeve and the D printing nozzle are fixed on the horizontal moving support and move in coordination with the printing bottom plate along with the control of the printer.
A macroporous hydrogel D printing device comprises a gas injection pump, a barometer, a T-shaped channel, a gas inlet capillary glass tube, a horizontal moving support, a water bath sleeve, a liquid injection pump, a flow meter, a D printing spray head, a printing bottom plate, a submersible pump and a constant-temperature water bath heating device;
the air inlet capillary glass tube is nested in the T-shaped channel, the upper end of the air inlet capillary glass tube is fixedly connected to the T-shaped channel, and the lower end of the T-shaped channel is communicated with the D-printing sprayer; the air inlet capillary glass tube and the T-shaped channel are nested and then fixed in the water bath sleeve together; the water bath sleeve is sequentially connected with the submersible pump and the constant-temperature water bath heating device to form a stable bubble generation temperature environment, and the bubble generation temperature is accurately controlled; the gas injection pump is communicated with one end of the air inlet capillary glass tube, and a gas pressure meter is arranged on a pipeline between the gas injection pump and the air inlet capillary glass tube; the liquid injection pump is communicated with the single transverse structure of the T-shaped channel, the flowmeter is arranged on a pipeline between the liquid injection pump and the T-shaped channel, and temperature-sensitive hydrogel is contained in the liquid injection pump;
the cross section of an internal channel of the air inlet capillary glass tube is rectangular, and the length-width ratio of the internal channel is greater than 10;
the printing bottom plate is a heating bottom plate, and the temperature of the bottom plate can be adjusted;
the water bath sleeve and the D printing nozzle are fixed on the horizontal moving support and move in coordination with the printing bottom plate along with the control of the printer.
A macroporous hydrogel D printing device comprises a gas injection pump, a barometer, a T-shaped channel, a gas inlet capillary glass tube, an outlet capillary glass tube, a horizontal moving bracket, a water bath sleeve, a liquid injection pump, a flowmeter, a D printing nozzle, a high-energy ultraviolet light source, a printing bottom plate, a submersible pump and a constant-temperature water bath heating device;
the air inlet capillary glass tube and the outlet capillary glass tube are both nested in the T-shaped channel, the upper end of the air inlet capillary glass tube is fixedly connected to the T-shaped channel, the upper end of the outlet capillary glass tube is nested and fixedly connected to the lower end of the T-shaped channel, and the outlet of the air inlet capillary glass tube and the inlet of the outlet capillary glass tube are kept in a (0.3-1) times of thickness of the capillary glass tube; the air inlet capillary glass tube, the outlet capillary glass tube and the T-shaped channel are fixed in the water bath sleeve together after being nested; the water bath sleeve is sequentially connected with the submersible pump and the constant-temperature water bath heating device to form a stable bubble generation temperature environment, and the bubble generation temperature is accurately controlled; the gas injection pump is communicated with one end of the air inlet capillary glass tube, and a gas pressure meter is arranged on a pipeline between the gas injection pump and the air inlet capillary glass tube; the liquid injection pump is communicated with the single transverse structure of the T-shaped channel, the flowmeter is arranged on a pipeline between the liquid injection pump and the T-shaped channel, and photosensitive hydrogel is contained in the liquid injection pump;
the cross sections of the inner channels of the air inlet capillary glass tube and the outlet capillary glass tube are both circular;
the water bath sleeve, the D printing nozzle and the high-energy ultraviolet light source are all fixed on the horizontal moving support and move with the printing bottom plate in a coordinated manner along with the control of the printer; the high-energy ultraviolet light source is focused at the high position of the printing layer below the D printing spray head and is used for enabling hydrogel to generate a crosslinking effect.
A macroporous hydrogel D printing device comprises a gas injection pump, a barometer, a T-shaped channel, a gas inlet capillary glass tube, a horizontal moving support, a water bath sleeve, a liquid injection pump, a flow meter, a D printing spray head, a high-energy ultraviolet light source, a printing bottom plate, a submersible pump and a constant-temperature water bath heating device;
the air inlet capillary glass tube is nested in the T-shaped channel, the upper end of the air inlet capillary glass tube is fixedly connected to the T-shaped channel, and the lower end of the T-shaped channel is communicated with the D-printing spray head; the air inlet capillary glass tube and the T-shaped channel are nested and then fixed in the water bath sleeve together; the water bath sleeve is sequentially connected with the submersible pump and the constant-temperature water bath heating device to form a stable bubble generation temperature environment, and the bubble generation temperature is accurately controlled; the gas injection pump is communicated with one end of the air inlet capillary glass tube, and a gas pressure meter is arranged on a pipeline between the gas injection pump and the air inlet capillary glass tube; the liquid injection pump is communicated with the single transverse structure of the T-shaped channel, the flowmeter is arranged on a pipeline between the liquid injection pump and the T-shaped channel, and photosensitive hydrogel is contained in the liquid injection pump;
the cross section of an internal channel of the air inlet capillary glass tube is rectangular, and the length-width ratio of the internal channel is greater than 10;
the water bath sleeve, the high-energy ultraviolet light source and the D printing nozzle are all fixed on the horizontal moving support and move with the printing bottom plate in a coordinated manner along with the control of the printer; the high-energy ultraviolet light source is focused at the high position of the printing layer below the D printing spray head and is used for enabling hydrogel to generate a crosslinking effect.
Further, the inner wall of the D printing spray head is subjected to hydrophobic treatment.
A macroporous hydrogel D printing method with adjustable cellular structure is realized based on the macroporous hydrogel D printing device, and the method comprises the following steps:
preparing a temperature-sensitive and ion-crosslinkable multi-component hydrogel solution as biological printing ink, and adding the biological printing ink into the liquid injection pump; starting the submersible pump and the constant-temperature water bath heating device to enable the whole bubble generation micro-channel structure in the water bath sleeve to be in a constant-temperature state;
determining the height and width of a printing layer and the moving speed of a D printing nozzle through printing performance according to the gas-liquid two-phase flow and the size of the D printing nozzle when a stable and continuous strip-shaped hydrogel with bubbles can be formed, and slicing and editing the printing die and guiding the printing die into a D printer;
covering a layer of hydrophobic film on the printing bottom plate, and adjusting the temperature of the heating bottom plate to make itAbove the printable temperature, starting printing; recording the pressure P generated by the gas injection pump at the moment of just generating bubbles initially 1 And the moving speed of the nozzle with the best printing effect at the flow rate is recorded as v 1 And the pressure generated by the gas injection pump (1) is increased to the bubble generation micro-channel structure, so that stable bubbles cannot be formed, and the corresponding pressure P is formed when continuous gas flow is formed 2 And the optimum moving speed v of the nozzle at the flow rate 2 ；
(4) Varying the speed v of movement of the spray head layer by layer 1～ v 2 Adjusting the flow rate and the generated pressure of the corresponding gas injection pump according to the volume change, realizing the density gradient change of the bubbles layer by layer, and printing the macroporous hydrogel with longitudinal density gradient change;
splitting the preprinting model into a plurality of sub-models according to the required change of the transverse bubble density gradient, realizing the change of the transverse bubble density gradient by changing the combination mode of the sub-models and adjusting the pressure generated by a gas injection pump, and printing the macroporous hydrogel with the specific change of the transverse bubble density gradient;
the macroporous hydrogel with bubble size gradient is printed by adjusting the gap between the corresponding ports of the air inlet capillary glass tube and the outlet capillary glass tube, adjusting the corresponding pressure of the air injection pump, and changing the printing moving speed of the spray head through volume balance.
(5) And (3) immersing the sample into a solution of the ion-crosslinkable hydrogel, adjusting the temperature of the solution to be consistent with the printing temperature of the printing base plate, and keeping the temperature for more than 15min to obtain the final macroporous hydrogel sample.
A3D printing method of macroporous hydrogel with adjustable cellular structure is realized based on the 3D printing device of macroporous hydrogel, and comprises the following steps:
(1) preparing a temperature-sensitive and ion-crosslinkable multi-component hydrogel solution as biological printing ink, and adding the biological printing ink into the liquid injection pump; starting the submersible pump and the constant-temperature water bath heating device to enable the whole bubble generation micro-channel structure in the water bath sleeve to be in a constant-temperature state;
(2) determining the height and width of a printing layer and the moving speed of a 3D printing nozzle through printing performance according to the gas-liquid two-phase flow and the size of the 3D printing nozzle when a stable and continuous strip-shaped hydrogel with bubbles can be formed, and editing the section of the printing mould and guiding the section into a 3D printer;
(3) covering a layer of hydrophobic film on the printing bottom plate, adjusting the temperature of the heating bottom plate to be higher than the printable temperature, and starting printing; recording the pressure P generated by the gas injection pump at the moment of just generating bubbles initially 1 And the moving speed of the nozzle with the best printing effect at the flow rate is recorded as v 1 And the pressure P corresponding to the pressure P generated when the pressure generated by the gas injection pump is increased to the bubble generation micro-channel structure and cannot form stable bubbles to form continuous gas flow 2 And the optimum moving speed v of the nozzle at the flow rate 2 ；
(4) By varying the speed v of movement of the spray head layer by layer 1～ v 2 Adjusting the flow rate and the generated pressure of the corresponding gas injection pump according to the volume change, realizing the density gradient change of the bubbles layer by layer, and printing the macroporous hydrogel with longitudinal density gradient change;
splitting the preprinting model into a plurality of sub-models according to the required change of the density gradient of the transverse bubbles, changing the combination mode of the sub-models, adjusting the flow of the gas injection pump to realize the change of the density gradient of the transverse bubbles, and printing the macroporous hydrogel with the specific change of the density gradient of the transverse bubbles;
(5) and (3) immersing the sample into a solution of the ion-crosslinkable hydrogel, adjusting the temperature of the solution to be consistent with the printing temperature of the printing base plate, and keeping the temperature for more than 15min to obtain the final macroporous hydrogel sample.
A3D printing method of macroporous hydrogel with adjustable cellular structure is realized based on the 3D printing device of macroporous hydrogel, and comprises the following steps:
(1) preparing a photosensitive hydrogel solution capable of being instantly cured by light as biological printing ink, and adding the biological printing ink into the liquid injection pump; starting the submersible pump and the constant-temperature water bath heating device to enable the whole bubble generation micro-channel structure in the water bath sleeve to be in a constant-temperature state; starting a high-energy ultraviolet light source for printing;
(2) determining the height and width of a printing layer and the moving speed of a 3D printing nozzle through printing performance according to the gas-liquid two-phase flow and the size of the 3D printing nozzle when a stable and continuous strip-shaped hydrogel with bubbles can be formed, and editing the section of the printing mould and guiding the section into a 3D printer;
(3) covering a layer of hydrophobic film on the printing bottom plate, and starting printing; recording the pressure P generated by the gas injection pump at the moment of just generating bubbles initially 1 And the moving speed of the nozzle with the best printing effect at the flow rate is recorded as v 1 And the pressure P corresponding to the pressure P generated when the pressure generated by the gas injection pump is increased to the bubble generation micro-channel structure and cannot form stable bubbles to form continuous gas flow 2 And the optimum moving speed v of the nozzle at the flow rate 2 ；
(4) Varying the speed v of movement of the spray head layer by layer 1～ v 2 Adjusting the flow rate and the generated pressure of the corresponding gas injection pump according to the volume change, realizing the density gradient change of the bubbles layer by layer, and printing the macroporous hydrogel with longitudinal density gradient change;
splitting the preprinting model into a plurality of sub-models according to the required change of the transverse bubble density gradient, realizing the change of the transverse bubble density gradient by changing the combination mode of the sub-models and adjusting the pressure generated by a gas injection pump, and printing the macroporous hydrogel with the specific change of the transverse bubble density gradient;
the macroporous hydrogel with bubble size gradient is printed by adjusting the gap between the corresponding ports of the air inlet capillary glass tube and the outlet capillary glass tube, adjusting the corresponding pressure of the air injection pump, and changing the printing moving speed of the spray head through volume balance.
The macroporous hydrogel with bubble size gradient is printed by adjusting the gap between the corresponding ports of the air inlet capillary glass tube and the outlet capillary glass tube, adjusting the flow of the air injection pump, and changing the printing moving speed of the spray head through volume balance.
A3D printing method of macroporous hydrogel with adjustable cellular structure is realized based on the 3D printing device of macroporous hydrogel, and comprises the following steps:
(1) preparing a photosensitive hydrogel solution capable of being instantly cured by light as biological printing ink, and adding the biological printing ink into the liquid injection pump; starting the submersible pump and the constant-temperature water bath heating device to enable the whole bubble generation micro-channel structure in the water bath sleeve to be in a constant-temperature state; starting a high-energy ultraviolet light source for printing;
(2) determining the height and width of a printing layer and the moving speed of a 3D printing nozzle through printing performance according to the gas-liquid two-phase flow and the size of the 3D printing nozzle when a stable and continuous strip-shaped hydrogel with bubbles can be formed, and editing the section of the printing mould and guiding the section into a 3D printer;
(3) covering a layer of hydrophobic film on the printing bottom plate, and starting printing; recording the pressure P generated by the gas injection pump at the moment of just generating bubbles initially 1 And the moving speed of the nozzle with the best printing effect at the flow rate is recorded as v 1 And the pressure P corresponding to the pressure P generated when the pressure generated by the gas injection pump is increased to the bubble generation micro-channel structure and cannot form stable bubbles to form continuous gas flow 2 And the optimum moving speed v of the nozzle at the flow rate 2 ；
(4) Varying the speed v of movement of the spray head layer by layer 1～ v 2 Adjusting the flow rate and the generated pressure of the corresponding gas injection pump according to the volume change, realizing the density gradient change of the bubbles layer by layer, and printing the macroporous hydrogel with longitudinal density gradient change;
and splitting the preprinting model into a plurality of sub-models according to the required change of the transverse bubble density gradient, changing the combination mode of the sub-models, adjusting the pressure generated by the gas injection pump to realize the change of the transverse bubble density gradient, and printing the macroporous hydrogel with the specific change of the transverse bubble density gradient.
The invention has the following beneficial effects:
(1) compared with the traditional preparation of the irregular pores of the macroporous hydrogel, the macroporous hydrogel prepared by the device disclosed by the invention not only can ensure good shape and size precision on the appearance structure, but also can realize the precise control on the spatial position and size of the pores, and has strong editability.
(2) The device can realize various types of macroporous hydrogel structures including uniform cell structures, cell structures presenting density gradients and cell structures presenting size gradients by adjusting gas phase flow and the like, and can produce various purposes.
Drawings
FIG. 1 is a schematic configuration diagram of a printing apparatus according to embodiment 1;
FIG. 2 is a schematic configuration diagram of a printing apparatus according to embodiment 2;
FIG. 3 is a schematic configuration diagram of a printing apparatus according to embodiment 3;
FIG. 4 is a schematic configuration diagram of a printing apparatus according to embodiment 4;
FIG. 5 is a photograph of a hexahedral macroporous hydrogel sample with two distinct density changes obtained using the apparatus of example 1;
FIG. 6 is a photograph of a hexahedral macroporous hydrogel sample with three distinct density changes obtained using the apparatus of example 1;
FIG. 7 is a photograph of a hexahedral macroporous hydrogel sample with a distinct density change from dense to sparse to dense obtained using the apparatus of example 1;
FIG. 8 is a photograph of a sample of hexahedral macroporous hydrogel with a distinct density change from sparse to dense to sparse obtained using the apparatus of example 1;
FIG. 9 is a photograph of a hexahedral macroporous hydrogel sample with a uniform cell structure obtained using the apparatus of example 2;
FIG. 10 is a cross-sectional electron micrograph of the sample of FIG. 9;
FIG. 11 is a photograph of a cylindrical macroporous hydrogel sample with a uniform cell structure obtained using the apparatus of example 2;
FIG. 12 is a photograph of a triangular prism macroporous hydrogel sample having a uniform cell structure obtained using the apparatus of example 2.
Detailed Description
The present invention will be described in detail below with reference to the accompanying drawings and preferred embodiments, and the objects and effects of the present invention will become more apparent, it being understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.
As shown in fig. 1, the device comprises a gas injection pump 1, a barometer 2, a T-shaped channel 3, an air inlet capillary glass tube 4, an outlet capillary glass tube 5, a horizontal moving bracket 6, a water bath sleeve 7, a liquid injection pump 8, a flow meter 9, a 3D printing spray head 10, a printing bottom plate 12, a submersible pump 13 and a thermostatic water bath heating device 14.
The air inlet capillary glass tube 4 and the outlet capillary glass tube 5 are both nested in the T-shaped channel 3, the upper end of the air inlet capillary glass tube 4 is fixedly connected to the T-shaped channel 3 through light curing glue, the upper end of the outlet capillary glass tube 5 is nested and fixedly connected to the lower end of the T-shaped channel 3, and the distance of 0.3-1d (d is the diameter of the capillary glass tube) is kept between the outlet of the air inlet capillary glass tube 4 and the inlet of the outlet capillary glass tube 5. The bubble generation micro-channel structure is composed of an external T-shaped channel 3, an internal longitudinal air inlet capillary glass tube 4 and an internal longitudinal outlet capillary glass tube 5, and forms a coaxial flow micro-channel structure of outward liquid and inward gas. The air inlet capillary glass tube 4, the outlet capillary glass tube 5 and the T-shaped channel 3 are fixed in a water bath sleeve 7 after being nested; the water bath sleeve 7 is sequentially connected with the submersible pump 13 and the constant-temperature water bath heating device 14 to form a stable temperature environment for generating bubbles, accurately control the bubble generation temperature in the T-shaped channel 3, eliminate the influence of temperature change on the size of the bubbles and ensure that the state of a solution when the bubbles are generated can be accurately controlled when the temperature-sensitive hydrogel is used as the bioprinting ink;
the gas injection pump 1 is communicated with one end of the air inlet capillary glass tube 4, and a gas pressure meter 2 is arranged on a pipeline between the air inlet capillary glass tube and the air inlet capillary glass tube; the liquid injection pump 8 is communicated with the single transverse structure of the T-shaped channel 3, a flow meter 9 is arranged on a pipeline between the liquid injection pump 8 and the T-shaped channel 3, and the temperature-sensitive hydrogel is contained in the liquid injection pump 8. The cross sections of the inner passages of the air inlet capillary glass tube 4 and the outlet capillary glass tube 5 are both circular. The printing substrate 12 is a heating substrate, and the temperature of the substrate can be adjusted. The water bath sleeve 7 and the 3D printing nozzle 10 are both fixed on the horizontal moving support 6 and move with the printing bottom plate 12 under the control of the printer.
The printing method adopting the set of device comprises the following specific steps:
(1) preparing a temperature-sensitive and ion-crosslinkable multi-component hydrogel solution as 25 wt.% Plournic F127 and 1.5 wt.% sodium alginate solution of biological printing ink, and adding the solution into an injection pump 8; and starting the submersible pump 13 and the thermostatic waterbath heating device 14 to enable the whole bubble generation micro-channel structure in the waterbath sleeve 7 to be in a thermostatic state of 25 ℃.
(2) Selecting a liquid injection pump 8 with the flow rate of 0.1mL/min, a gas injection pump with the initial flow rate of 0.1mL/min, a printing nozzle 10 with the aperture of 0.3mm, an air inlet capillary glass tube with the inner diameter of 0.3mm, and an outlet capillary glass tube with the gap of 0.1mm, determining the printing layer with the height of 0.31mm, the layer width of 0.35mm and the initial moving speed of the 3D printing nozzle 10 of 20mm/s through printing performance, editing the printing mould into slices, and guiding the slices into a 3D printer;
(3) a layer of hydrophobic film is covered on the printing bottom plate 12, so that a hydrogel sample with a complete shape can be obtained conveniently after printing is finished, and the bottom can be kept immersed in liquid under the condition that the hydrogel sample needs to be immersed in a solution for further crosslinking; the temperature of the heating bottom plate 12 is adjusted to be 37 ℃, the hydrogel is changed from sol to gel state by changing the ambient temperature and the temperature of the heating bottom plate 12, and printing is started; recording the corresponding pressure of the gas injection pump 1 as 48kPa when bubbles are just generated initially and the nozzle moving speed with the best printing effect under the pressure as 14mm/s, and recording the pressure generated by the gas injection pump 1 until the bubble generation micro-channel structure can not form stable bubbles, the corresponding pressure of 54kPa when continuous gas flow is formed and the optimal nozzle moving speed under the flow as 26 mm/s;
(4) changing the moving speed of the spray head by 14-26 mm/s layer by layer, adjusting the pressure generated by the corresponding gas injection pump 1 according to the volume change, realizing the gradient change of the bubble density layer by layer, and printing the macroporous hydrogel with the longitudinal density gradient change.
Splitting the preprinting model into a plurality of sub-models according to the required change of the transverse bubble density gradient, changing the combination mode of the sub-models, adjusting the corresponding pressure of the gas injection pump 1 to realize the change of the transverse bubble density gradient, and printing the macroporous hydrogel with the specific change of the transverse bubble density gradient;
the method comprises the steps of adjusting the gap between corresponding ports of an air inlet capillary glass tube 4 and an outlet capillary glass tube 5, adjusting the corresponding pressure of an air injection pump 1, and changing the printing moving speed of a spray head through volume balance calculation, so as to print macroporous hydrogel with bubble size gradient;
(5) removing the film, and soaking the printed product in 5 wt.% CaCl 2 The temperature of the solution is adjusted to 40 ℃ and kept for more than 15min, so that the shape of the hydrogel sample is more fixed in the ion-containing solution which is further crosslinked by the hydrogel sample, and the final macroporous hydrogel sample is obtained.
A total of four types of macroporous hydrogels with specific transverse bubble density gradients were printed as follows:
splitting a model with 20 x 10 x 3mm and sparse-dense cell density gradient into two 10 x 3mm sub-models, respectively editing the moving speed parameters of a printing nozzle to be 14mm/s and 26mm/s, and printing to obtain a hexahedron macroporous hydrogel sample with two obvious density changes as shown in figure 5;
splitting the model with the density gradient of sparse-medium-high density cells of 30 x 10 x 3mm into three sub models with the density gradient of 10 x 3mm, editing the moving speed parameters of the printing spray head to be 14mm/s, 20mm/s and 26mm/s respectively, and printing to obtain a hexahedral macroporous hydrogel sample with three obvious density changes as shown in figure 6;
thirdly, splitting the model with the density gradient of sparse, dense and sparse cells of 20 x 10 x 3mm into three sub models with the density gradient of 10 x 3mm, respectively editing the moving speed parameters of the printing spray head to be 14mm/s, 26mm/s and 14mm/s, and printing to obtain the hexahedral macroporous hydrogel sample with the density change obviously from dense to dense as shown in figure 7;
and fourthly, splitting the model with the density gradient of dense-sparse-dense cells of 20 x 10 x 3mm into three sub models with the density gradient of dense-sparse-dense cells of 10 x 3mm, editing the moving speed parameters of the printing spray head to be 26mm/s, 14mm/s and 26mm/s respectively, and printing to obtain the hexahedral macroporous hydrogel sample with the density change from sparse to dense obviously as shown in the figure 8.
As shown in fig. 2, in this apparatus, compared to the apparatus of example 1, the lower end of the T-shaped channel 3 directly communicates with the 3D print head 10, the outlet capillary glass tube is reduced, and the internal channel of the inlet capillary glass tube 4 is rectangular in cross section and has an aspect ratio greater than 10. The device adopts the step emulsification principle to generate macroporous hydrogel, the size of the bubbles is stable, and finally the bubbles with uniform and stable sizes can be generated.
The method for printing by adopting the device of the embodiment comprises the following steps:
(1) preparing a temperature-sensitive and ion-crosslinkable multi-component hydrogel solution as a 25 wt.% Plournic F127 and 1.5 wt.% sodium alginate solution of biological printing ink, and adding the solution into an injection pump 8; starting the submersible pump 13 and the constant-temperature water bath heating device 14 to enable the whole bubble generation micro-channel structure in the water bath sleeve 7 to be in a constant-temperature state of 25 ℃;
(2) selecting a liquid injection pump 8 with the flow rate of 0.1mL/min, a gas injection pump with the flow rate of 0.1mL/min, a printing nozzle 10 with the aperture of 0.3mm, a rectangular capillary glass tube 4 with the specification of 0.5 x 0.05mm, determining the printing layer height of 0.31mm and the layer width of 0.35mm through the printing performance and the initial moving speed of the 3D printing nozzle 10 of 20mm/s, and editing the printing mould into slices and guiding the slices into a 3D printer;
(3) covering a layer of hydrophobic film on the printing bottom plate 12, adjusting the temperature of the heating bottom plate 12 to be 37 ℃, and starting printing;
(4) keeping the flow rates of the gas injection pump 1 and the liquid injection pump 8 unchanged, and printing samples with different external dimensions;
(5) the samples were immersed in 5 wt.% CaCl 2 The temperature of the solution is adjusted to 40 ℃ and kept for more than 15min, and the final macroporous hydrogel sample is obtained. As shown in FIG. 9, a hexahedron 12X 5mm large pore hydrogel sample with a uniform cell structure was obtained, which was cross-sectionedThe electron micrograph is shown in FIG. 10. Slicing a sample of cylinder phi 10 x 3mm, and printing to obtain a cylindrical macroporous hydrogel sample with a uniform cell structure shown in FIG. 11; the triangular prism 14 x 12mm samples were cut and printed to give triangular prism large pore hydrogel samples with uniform cell structure as shown in figure 12.
As shown in fig. 3, compared with the printing apparatus of example 1, a high-energy uv light source 11 fixed on the horizontally moving support 6 is added, and the high-energy uv light source 11 is focused on the high position of the printing layer below the 3D printing nozzle 10 for cross-linking the hydrogel. In addition, the printing substrate 12 may not have a heating function.
(1) Preparing 5 wt.% GelMA solution capable of being instantly cured by light as photosensitive biological printing ink, and adding the photosensitive biological printing ink into a liquid injection pump 8; the printing ink can maintain a stable strip-shaped hydrogel shape while being irradiated by the high-energy ultraviolet light source 11 through the 3D printing nozzle 10, and the strips of hydrogel have enough adhesion effect. Starting the submersible pump 13 and the thermostatic waterbath heating device 14 to enable the whole bubble generation micro-channel structure in the waterbath sleeve 7 to be in a thermostatic state; starting the high-energy ultraviolet light source 11 to print;
(2) determining the height and width of a printing layer and balancing the moving speed of the 3D printing nozzle 10 through the volume relation according to the gas-liquid two-phase flow and the size of the 3D printing nozzle 10 when a stable and continuous strip-shaped hydrogel with bubbles can be formed, and editing the printing mould by slicing and guiding the printing mould into a 3D printer;
(3) covering a layer of hydrophobic film on the printing bottom plate 12, and starting printing; recording the corresponding pressure P of the gas injection pump 1 when bubbles are just generated initially 1 And the moving speed of the nozzle with the best printing effect at the flow rate is recorded as v 1 And the pressure P corresponding to the formation of the continuous gas flow when the pressure corresponding to the gas injection pump 1 is increased to the bubble generation micro-channel structure and no stable bubble is formed 2 And an optimum moving speed v of the head at the pressure 2 ；
(4) Varying the speed v of movement of the spray head layer by layer 1～ v 2 Adjusting the flow rate and the corresponding pressure of the gas injection pump 1 according to the volume change, realizing the density gradient change of bubbles layer by layer, and printing out the macroporous hydrogel with longitudinal density gradient change;
splitting the preprinting model into a plurality of sub-models according to the required change of the transverse bubble density gradient, changing the combination mode of the sub-models, adjusting the pressure generated by the gas injection pump 1 to realize the change of the transverse bubble density gradient, and printing the macroporous hydrogel with the specific change of the transverse bubble density gradient;
the macroporous hydrogel with bubble size gradient is printed by adjusting the gap between the corresponding ports of the air inlet capillary glass tube 4 and the outlet capillary glass tube 5, adjusting the pressure generated by the gas injection pump 1, and changing the printing moving speed of the spray head through volume balance.
As shown in fig. 4, the apparatus of this embodiment is added with a high-energy uv light source 11 fixed on the horizontally moving support 6, compared with the apparatus of embodiment 2, and the high-energy uv light source 11 is focused at the height of the printing layer below the 3D printing nozzle 10 for cross-linking the hydrogel. In addition, the printing substrate 12 may not have a heating function.
The printing method based on the device comprises the following steps:
(1) preparing 5 wt.% GelMA solution capable of being instantly cured by light as photosensitive biological printing ink, and adding the photosensitive biological printing ink into a liquid injection pump 8; starting the submersible pump 13 and the thermostatic waterbath heating device 14 to enable the whole bubble generation micro-channel structure in the waterbath sleeve 7 to be in a thermostatic state; starting the high-energy ultraviolet light source 11 to print;
(2) determining the printing layer height, the printing layer width and the moving speed of the 3D printing nozzle 10 according to the gas-liquid two-phase flow and the size of the 3D printing nozzle 10 when a stable and continuous strip-shaped hydrogel with bubbles can be formed, slicing and editing the printing mould, and guiding the printing mould into a 3D printer;
(3) covering a layer of hydrophobic film on the printing bottom plate 12, and starting printing; recording the corresponding pressure P of the gas injection pump 1 when bubbles are just generated initially 1 And the moving speed of the nozzle with the best printing effect under the pressure is recorded as v 1 And the pressure P corresponding to the formation of the continuous gas flow when the pressure corresponding to the gas injection pump 1 is increased to the bubble generation micro-channel structure and no stable bubble is formed 2 And an optimum moving speed v of the head at the pressure 2 ；
(4) Varying the speed v of movement of the spray head layer by layer 1～ v 2 Adjusting the flow rate and the corresponding pressure of the gas injection pump 1 according to the volume change, realizing the density gradient change of bubbles layer by layer, and printing out the macroporous hydrogel with longitudinal density gradient change;
and splitting the preprinting model into a plurality of sub-models according to the required change of the transverse bubble density gradient, changing the combination mode of the sub-models, adjusting the pressure generated by the gas injection pump 1 to realize the change of the transverse bubble density gradient, and printing the macroporous hydrogel with the specific change of the transverse bubble density gradient.
It will be understood by those skilled in the art that the foregoing is only a preferred embodiment of the present invention, and is not intended to limit the invention, and although the invention has been described in detail with reference to the foregoing examples, it will be apparent to those skilled in the art that various changes in the form and details of the embodiments may be made and equivalents may be substituted for elements thereof. All modifications, equivalents and the like which come within the spirit and principle of the invention are intended to be included within the scope of the invention.
Claims (9)
1. A macroporous hydrogel 3D printing device is characterized by comprising a gas injection pump (1), a barometer (2), a T-shaped channel (3), a gas inlet capillary glass tube (4), an outlet capillary glass tube (5), a horizontal moving support (6), a water bath sleeve (7), a liquid injection pump (8), a flowmeter (9), a 3D printing nozzle (10), a printing bottom plate (12), a submersible pump (13) and a constant-temperature water bath heating device (14);
the air inlet capillary glass tube (4) and the outlet capillary glass tube (5) are nested in the T-shaped channel (3), the upper end of the air inlet capillary glass tube (4) is fixedly connected to the T-shaped channel (3), the upper end of the outlet capillary glass tube (5) is nested and fixedly connected to the lower end of the T-shaped channel (3), the distance between the outlet of the air inlet capillary glass tube (4) and the inlet of the outlet capillary glass tube (5) is kept between 0.3d and d, and d is the inner diameter of the air inlet capillary glass tube (4); the air inlet capillary glass tube (4), the outlet capillary glass tube (5) and the T-shaped channel (3) are nested and then fixed in the water bath sleeve (7) together; the water bath sleeve (7) is sequentially connected with the submersible pump (13) and the constant-temperature water bath heating device (14) to form a stable temperature environment for generating bubbles and accurately control the bubble generation temperature; the gas injection pump (1) is communicated with one end of the air inlet capillary glass tube (4), and a gas pressure meter (2) is arranged on a pipeline between the air inlet capillary glass tube and the air inlet capillary glass tube; the liquid injection pump (8) is communicated with the single transverse structure of the T-shaped channel (3), the flowmeter (9) is arranged on a pipeline between the liquid injection pump and the T-shaped channel, and temperature-sensitive hydrogel is contained in the liquid injection pump (8);
the cross sections of the inner channels of the air inlet capillary glass tube (4) and the outlet capillary glass tube (5) are both circular;
the printing bottom plate (12) is a heating bottom plate, and the temperature of the bottom plate can be adjusted;
the water bath sleeve (7) and the 3D printing nozzle (10) are fixed on the horizontal moving support (6) and move in cooperation with the printing bottom plate (12) along with control of the printer.
2. A macroporous hydrogel 3D printing device is characterized by comprising a gas injection pump (1), a barometer (2), a T-shaped channel (3), a gas inlet capillary glass tube (4), a horizontal moving support (6), a water bath sleeve (7), a liquid injection pump (8), a flowmeter (9), a 3D printing nozzle (10), a printing bottom plate (12), a submersible pump (13) and a constant-temperature water bath heating device (14);
the air inlet capillary glass tube (4) is nested in the T-shaped channel (3), the upper end of the air inlet capillary glass tube (4) is fixedly connected to the T-shaped channel (3), and the lower end of the T-shaped channel (3) is communicated with the 3D printing nozzle (10); the air inlet capillary glass tube (4) and the T-shaped channel (3) are fixed in the water bath sleeve (7) after being nested; the water bath sleeve (7) is sequentially connected with the submersible pump (13) and the constant-temperature water bath heating device (14) to form a stable temperature environment for generating bubbles and accurately control the bubble generation temperature; the gas injection pump (1) is communicated with one end of the air inlet capillary glass tube (4), and a gas pressure meter (2) is arranged on a pipeline between the air inlet capillary glass tube and the air inlet capillary glass tube; the liquid injection pump (8) is communicated with a single transverse structure of the T-shaped channel (3), the flowmeter (9) is arranged on a pipeline between the liquid injection pump and the T-shaped channel, and temperature-sensitive hydrogel is contained in the liquid injection pump (8);
the section of an inner channel of the air inlet capillary glass tube (4) is rectangular, and the length-width ratio of the inner channel is greater than 10;
the printing bottom plate (12) is a heating bottom plate, and the temperature of the bottom plate can be adjusted;
the water bath sleeve (7) and the 3D printing nozzle (10) are fixed on the horizontal moving support (6) and move in cooperation with the printing bottom plate (12) along with control of the printer.
3. A macroporous hydrogel 3D printing device is characterized by comprising a gas injection pump (1), a barometer (2), a T-shaped channel (3), a gas inlet capillary glass tube (4), an outlet capillary glass tube (5), a horizontal moving support (6), a water bath sleeve (7), a liquid injection pump (8), a flow meter (9), a 3D printing spray head (10), a high-energy ultraviolet light source (11), a printing bottom plate (12), a submersible pump (13) and a constant-temperature water bath heating device (14);
the air inlet capillary glass tube (4) and the outlet capillary glass tube (5) are nested in the T-shaped channel (3), the upper end of the air inlet capillary glass tube (4) is fixedly connected to the T-shaped channel (3), the upper end of the outlet capillary glass tube (5) is nested and fixedly connected to the lower end of the T-shaped channel (3), the outlet of the air inlet capillary glass tube (4) and the inlet of the outlet capillary glass tube (5) keep a distance of 0.3d-d times, and d is the inner diameter of the air inlet capillary glass tube (4); the air inlet capillary glass tube (4), the outlet capillary glass tube (5) and the T-shaped channel (3) are nested and then fixed in the water bath sleeve (7) together; the water bath sleeve (7) is sequentially connected with the submersible pump (13) and the constant-temperature water bath heating device (14) to form a stable temperature environment for generating bubbles and accurately control the bubble generation temperature; the gas injection pump (1) is communicated with one end of the air inlet capillary glass tube (4), and a gas pressure meter (2) is arranged on a pipeline between the air inlet capillary glass tube and the air inlet capillary glass tube; the liquid injection pump (8) is communicated with the single transverse structure of the T-shaped channel (3), the flowmeter (9) is arranged on a pipeline between the liquid injection pump and the T-shaped channel, and photosensitive hydrogel is contained in the liquid injection pump (8);
the cross sections of the inner channels of the air inlet capillary glass tube (4) and the outlet capillary glass tube (5) are both circular;
the water bath sleeve (7), the 3D printing nozzle (10) and the high-energy ultraviolet light source (11) are all fixed on the horizontal moving support (6) and move with the printing bottom plate (12) in a coordinated manner along with the control of the printer; the high-energy ultraviolet light source (11) is focused at the high position of the printing layer below the 3D printing spray head (10) and is used for enabling hydrogel to generate a crosslinking effect.
4. A macroporous hydrogel 3D printing device is characterized by comprising a gas injection pump (1), a barometer (2), a T-shaped channel (3), a gas inlet capillary glass tube (4), a horizontal moving support (6), a water bath sleeve (7), a liquid injection pump (8), a flowmeter (9), a 3D printing nozzle (10), a high-energy ultraviolet light source (11), a printing bottom plate (12), a submersible pump (13) and a constant-temperature water bath heating device (14);
the air inlet capillary glass tube (4) is nested in the T-shaped channel (3), the upper end of the air inlet capillary glass tube (4) is fixedly connected to the T-shaped channel (3), and the lower end of the T-shaped channel (3) is communicated with the 3D printing nozzle (10); the air inlet capillary glass tube (4) and the T-shaped channel (3) are fixed in the water bath sleeve (7) after being nested; the water bath sleeve (7) is sequentially connected with the submersible pump (13) and the constant-temperature water bath heating device (14) to form a stable temperature environment for generating bubbles and accurately control the bubble generation temperature; the gas injection pump (1) is communicated with one end of the air inlet capillary glass tube (4), and a gas pressure meter (2) is arranged on a pipeline between the air inlet capillary glass tube and the air inlet capillary glass tube; the liquid injection pump (8) is communicated with the single transverse structure of the T-shaped channel (3), the flowmeter (9) is arranged on a pipeline between the liquid injection pump and the T-shaped channel, and photosensitive hydrogel is contained in the liquid injection pump (8);
the cross section of an internal channel of the air inlet capillary glass tube (4) is rectangular, and the length-width ratio of the internal channel is more than 10;
the water bath sleeve (7), the high-energy ultraviolet light source (11) and the 3D printing nozzle (10) are all fixed on the horizontal moving support (6) and move with the printing bottom plate (12) in a coordinated manner along with the control of a printer; the high-energy ultraviolet light source (11) is focused at the high position of the printing layer below the 3D printing spray head (10) and is used for enabling hydrogel to generate a crosslinking effect.
5. The macroporous hydrogel 3D printing device according to claim 1, 2, 3 or 4, wherein the inner wall of the 3D printing nozzle (10) is subjected to hydrophobic treatment.
6. A3D printing method of macroporous hydrogel with adjustable cellular structure is realized based on the 3D printing device of macroporous hydrogel of claim 1, and the method comprises the following steps:
(1) preparing a temperature-sensitive and ion-crosslinkable multi-component hydrogel solution as biological printing ink, and adding the biological printing ink into the liquid injection pump (8); starting the submersible pump (13) and the thermostatic waterbath heating device (14) to enable the whole bubble generation micro-channel structure in the waterbath sleeve (7) to be in a thermostatic state;
(2) determining the height and width of a printing layer and the moving speed of the 3D printing nozzle (10) according to the gas-liquid two-phase flow and the size of the 3D printing nozzle (10) when a stable and continuous strip-shaped hydrogel with bubbles can be formed, and slicing and editing the printing mould and guiding the printing mould into a 3D printer;
(3) covering a layer of hydrophobic film on the printing bottom plate (12), adjusting the temperature of the printing bottom plate (12) to be higher than the printable temperature, and starting printing; recording the pressure P generated by the gas injection pump (1) just at the time of bubble generation initially 1 And the moving speed of the nozzle with the best printing effect at the flow rate is recorded as v 1 And the pressure generated by the gas injection pump (1) is increased to the bubble generation micro-channel structure, so that stable bubbles cannot be formed, and the corresponding pressure P is formed when continuous gas flow is formed 2 And the optimum moving speed v of the nozzle at the flow rate 2 ；
(4) Varying the speed v of movement of the spray head layer by layer 1~ v 2 Adjusting the flow and the generated pressure of the corresponding gas injection pump (1) according to the volume change, realizing the density gradient change of the bubbles layer by layer, and printing out the macroporous hydrogel with longitudinal density gradient change;
splitting the preprinting model into a plurality of sub-models according to the required change of the transverse bubble density gradient, changing the combination mode of the sub-models, adjusting the pressure generated by the gas injection pump (1), realizing the change of the transverse bubble density gradient, and printing the macroporous hydrogel with the specific change of the transverse bubble density gradient;
the method comprises the steps of adjusting the gap between corresponding ports of an air inlet capillary glass tube (4) and an outlet capillary glass tube (5), adjusting the corresponding pressure of an air injection pump (1), and changing the printing moving speed of a spray head through volume balance, so as to print the macroporous hydrogel with bubble size gradient;
(5) and (3) immersing the sample into a solution of the ion-crosslinkable hydrogel, adjusting the temperature of the solution to be consistent with the printing temperature of the printing bottom plate (12) and keeping the temperature for more than 15min to obtain the final macroporous hydrogel sample.
7. A3D printing method of macroporous hydrogel with adjustable cellular structure is realized based on the 3D printing device of macroporous hydrogel of claim 2, and the method comprises the following steps:
(1) preparing a temperature-sensitive and ion-crosslinkable multi-component hydrogel solution as biological printing ink, and adding the biological printing ink into the liquid injection pump (8); starting the submersible pump (13) and the thermostatic waterbath heating device (14) to enable the whole bubble generation micro-channel structure in the waterbath sleeve (7) to be in a thermostatic state;
(2) determining the height and width of a printing layer and the moving speed of the 3D printing nozzle (10) according to the gas-liquid two-phase flow and the size of the 3D printing nozzle (10) when a stable and continuous strip-shaped hydrogel with bubbles can be formed, and slicing and editing the printing mould and guiding the printing mould into a 3D printer;
(3) covering a layer of hydrophobic film on the printing bottom plate (12), adjusting the temperature of the printing bottom plate (12) to be higher than the printable temperature, and starting printing; recording the pressure P generated by the gas injection pump (1) just at the time of bubble generation initially 1 And the moving speed of the nozzle with the best printing effect at the flow rate is recorded as v 1 And the pressure generated by the gas injection pump (1) is increased to the bubble generation micro-channel structure, so that stable bubbles cannot be formed, and the corresponding pressure P is formed when continuous gas flow is formed 2 And the optimum moving speed v of the nozzle at the flow rate 2 ；
(4) Varying the speed v of movement of the spray head layer by layer 1~ v 2 Adjusting the flow and the generated pressure of the corresponding gas injection pump (1) according to the volume change, realizing the density gradient change of the bubbles layer by layer, and printing out the macroporous hydrogel with longitudinal density gradient change;
splitting the preprinting model into a plurality of sub-models according to the required change of the transverse bubble density gradient, realizing the change of the transverse bubble density gradient by changing the combination mode of the sub-models and adjusting the flow of the gas injection pump (1), and printing the macroporous hydrogel with the specific change of the transverse bubble density gradient;
(5) and (3) immersing the sample into a solution of the ion-crosslinkable hydrogel, adjusting the temperature of the solution to be consistent with the printing temperature of the printing bottom plate (12) and keeping the temperature for more than 15min to obtain the final macroporous hydrogel sample.
8. A3D printing method of macroporous hydrogel with adjustable cellular structure is realized based on the 3D printing device of macroporous hydrogel of claim 3, and the method comprises the following steps:
(1) preparing a photosensitive hydrogel solution capable of being instantly cured by light as a biological printing ink, and adding the biological printing ink into the liquid injection pump (8); starting the submersible pump (13) and the thermostatic waterbath heating device (14) to enable the whole bubble generation micro-channel structure in the waterbath sleeve (7) to be in a thermostatic state; starting a high-energy ultraviolet light source (11) to print;
(2) determining the height and width of a printing layer and the moving speed of the 3D printing nozzle (10) according to the gas-liquid two-phase flow and the size of the 3D printing nozzle (10) when a stable and continuous strip-shaped hydrogel with bubbles can be formed, and slicing and editing the printing mould and guiding the printing mould into a 3D printer;
(3) covering a layer of hydrophobic film on the printing bottom plate (12) and starting printing; recording the pressure P generated by the gas injection pump (1) just before the initial generation of bubbles 1 And the moving speed of the nozzle with the best printing effect at the flow rate is recorded as v 1 And the pressure generated by the gas injection pump (1) is increased to the bubble generation micro-channel structure, so that stable bubbles cannot be formed, and the corresponding pressure P is formed when continuous gas flow is formed 2 And the optimum moving speed v of the nozzle at the flow rate 2 ；
(4) Varying the speed v of movement of the spray head layer by layer 1~ v 2 Adjusting the flow and the generated pressure of the corresponding gas injection pump (1) according to the volume change, realizing the density gradient change of the bubbles layer by layer, and printing out the macroporous hydrogel with longitudinal density gradient change;
splitting the preprinting model into a plurality of sub-models according to the required change of the transverse bubble density gradient, changing the combination mode of the sub-models, adjusting the pressure generated by the gas injection pump (1), realizing the change of the transverse bubble density gradient, and printing the macroporous hydrogel with the specific change of the transverse bubble density gradient;
the method comprises the steps of adjusting the gap between corresponding ports of an air inlet capillary glass tube (4) and an outlet capillary glass tube (5), adjusting the corresponding pressure of an air injection pump (1), and changing the printing moving speed of a spray head through volume balance, so as to print the macroporous hydrogel with bubble size gradient;
the macroporous hydrogel with bubble size gradient is printed by adjusting the gap between the corresponding ports of the air inlet capillary glass tube (4) and the outlet capillary glass tube (5), adjusting the flow of the air injection pump (1) and changing the printing moving speed of the spray head through volume balance.
9. A macroporous hydrogel 3D printing method with adjustable cellular structure is characterized in that the method is realized based on the macroporous hydrogel 3D printing device of claim 4, and the method comprises the following steps:
(1) preparing a photosensitive hydrogel solution capable of being instantly cured by light as a biological printing ink, and adding the biological printing ink into the liquid injection pump (8); starting the submersible pump (13) and the thermostatic waterbath heating device (14) to enable the whole bubble generation micro-channel structure in the waterbath sleeve (7) to be in a thermostatic state; starting a high-energy ultraviolet light source (11) to print;
(2) determining the height and width of a printing layer and the moving speed of the 3D printing nozzle (10) according to the gas-liquid two-phase flow and the size of the 3D printing nozzle (10) when a stable and continuous strip-shaped hydrogel with bubbles can be formed, and slicing and editing the printing mould and guiding the printing mould into a 3D printer;
(3) covering a layer of hydrophobic film on the printing bottom plate (12) and starting printing; recording the pressure P generated by the gas injection pump (1) just at the time of bubble generation initially 1 And printing the best jet at the flow rateThe head movement velocity is recorded as v 1 And the pressure generated by the gas injection pump (1) is increased to the bubble generation micro-channel structure, so that stable bubbles cannot be formed, and the corresponding pressure P is formed when continuous gas flow is formed 2 And the optimum moving speed v of the nozzle at the flow rate 2 ；
(4) Varying the speed v of movement of the spray head layer by layer 1~ v 2 Adjusting the flow and the generated pressure of the corresponding gas injection pump (1) according to the volume change, realizing the density gradient change of the bubbles layer by layer, and printing out the macroporous hydrogel with longitudinal density gradient change;
and splitting the preprinting model into a plurality of sub-models according to the required change of the transverse bubble density gradient, changing the combination mode of the sub-models, and adjusting the pressure generated by the gas injection pump (1) to realize the change of the transverse bubble density gradient, so as to print the macroporous hydrogel with the specific change of the transverse bubble density gradient.
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| US6843272B2 (en) * | 2002-11-25 | 2005-01-18 | Sandia National Laboratories | Conductance valve and pressure-to-conductance transducer method and apparatus |
| EP2179751A1 (en) * | 2008-10-21 | 2010-04-28 | Stichting Dutch Polymer Institute | Macroporous polymeric crosslinked materials, method for manufacture thereof and use |
| WO2014149279A1 (en) * | 2013-03-15 | 2014-09-25 | The George Washington University, A Congressionally Chartered Not-For-Profit Corporation | Biomimetic biphasic 3d nanocomposite scaffold for osteochondral regeneration |
| CN104708821B (en) * | 2015-02-12 | 2017-03-01 | 清华大学 | A kind of 3 D-printing method for the manufacture of tissue/organ integrated chip and device |
| CN205255520U (en) * | 2015-06-10 | 2016-05-25 | 中国科学技术大学 | Three -dimensional printing device of imitative body of biological tissue optics |
| WO2017066727A1 (en) * | 2015-10-15 | 2017-04-20 | The Regents Of The University Of California | Systems, apparatus and methods for cryogenic 3d printing |
| CN205313572U (en) * | 2015-12-30 | 2016-06-15 | 四川蓝光英诺生物科技股份有限公司 | Bio -printer |
| EP3585620B1 (en) * | 2017-02-27 | 2024-05-15 | Kornit Digital Technologies Ltd. | 3d printing devices including mixing nozzles |
| CN109124821B (en) * | 2018-08-31 | 2021-07-06 | 上海大学 | Construction system and method of three-dimensional multi-scale vascularization stent |
| CN110229352B (en) * | 2019-07-03 | 2022-07-08 | 上海大学 | Preparation method of composite hydrogel material and composite bracket printing method thereof |
| CN110549618A (en) * | 2019-08-22 | 2019-12-10 | 浙江大学 | Biological 3D printing system |
| CN113172880B (en) * | 2021-05-05 | 2023-03-31 | 西北工业大学 | Continuous gradient bionic manufacturing method based on pneumatic precise control of active cartilage support |
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