CN114103099A - Preparation method of polyethylene lactone-hydrogel coaxial stent based on low-temperature biological 3D printing - Google Patents

Preparation method of polyethylene lactone-hydrogel coaxial stent based on low-temperature biological 3D printing Download PDF

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CN114103099A
CN114103099A CN202111410277.8A CN202111410277A CN114103099A CN 114103099 A CN114103099 A CN 114103099A CN 202111410277 A CN202111410277 A CN 202111410277A CN 114103099 A CN114103099 A CN 114103099A
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coaxial
hydrogel
temperature
biological
low
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CN114103099B (en
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刘天琪
吴斌
张祥林
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Huazhong University of Science and Technology
Ezhou Institute of Industrial Technology Huazhong University of Science and Technology
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Huazhong University of Science and Technology
Ezhou Institute of Industrial Technology Huazhong University of Science and Technology
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive 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
    • B29C64/10Processes of additive manufacturing
    • B29C64/106Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive 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
    • B29C64/30Auxiliary operations or equipment
    • B29C64/307Handling of material to be used in additive manufacturing
    • B29C64/314Preparation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive 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
    • B29C64/30Auxiliary operations or equipment
    • B29C64/379Handling of additively manufactured objects, e.g. using robots
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE 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
    • B33Y10/00Processes of additive manufacturing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE 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
    • B33Y40/00Auxiliary operations or equipment, e.g. for material handling
    • B33Y40/10Pre-treatment
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE 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
    • B33Y40/00Auxiliary operations or equipment, e.g. for material handling
    • B33Y40/20Post-treatment, e.g. curing, coating or polishing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE 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
    • B33Y70/00Materials specially adapted for additive manufacturing
    • B33Y70/10Composites of different types of material, e.g. mixtures of ceramics and polymers or mixtures of metals and biomaterials

Abstract

A method for preparing a coaxial polyethylene lactone-hydrogel stent based on low-temperature biological 3D printing, which comprises the following steps: preparing a polyethylene lactone/glacial acetic acid solution with a preset concentration; taking a preset amount of the polyethylene lactone/glacial acetic acid solution for cooling; filling the polyethylene lactone/glacial acetic acid solution into a first spray head material cavity of a low-temperature coaxial biological 3D printer; placing the first spray head material cavity in a centrifuge for centrifuging and removing bubbles; preparing a hydrogel solution with a preset concentration; filling the hydrogel solution into a second spray head material cavity of the low-temperature coaxial biological 3D printer; placing the second spray head material cavity in a centrifuge for centrifuging and removing bubbles; setting working parameters of the low-temperature coaxial biological 3D printer; printing the polycaprolactone-hydrogel coaxial composite stent by the low-temperature coaxial biological 3D printer; and carrying out post-treatment on the polycaprolactone-hydrogel coaxial composite stent. The method can form the bracket with the rough surface and the multilayer composite structure.

Description

Preparation method of polyethylene lactone-hydrogel coaxial stent based on low-temperature biological 3D printing
Technical Field
The invention belongs to the technical field of medical products, and particularly relates to a method for preparing a polyethylene lactone-hydrogel coaxial bracket based on low-temperature biological 3D printing.
Background
In recent years, the preparation of biological scaffolds having a specific structure using various types of biomaterials through various 3D printing techniques has received much attention. Among many materials, polyethylene lactone (PCL) is widely used due to good plasticity, biocompatibility and biodegradability, and hydrogel materials have excellent biocompatibility and ion transport capacity, so that the PCL has the potential of being widely applied to medical fields such as bionic materials, artificial tissues and the like.
The currently common PCL-based biological 3D printing method has a plurality of problems: first, for a single PCL material, efficient repair of damaged tissues cannot be achieved due to the biological inertia of the PCL material, and common improvement measures include modification of an active substance of the PCL or separate molding of the PCL and the active substance by using a multi-nozzle fusion printing device. However, the former method is only suitable for preparing homogeneous biological scaffolds and cannot meet the actual clinical requirements, and the latter method cannot be doped with bioactive drugs due to high temperature, so that the application range of the former method is limited.
Whereas hydrogel-based bio 3D printing has to solve the problem of crosslinking of the hydrogel. There are currently crosslinking by ultraviolet light through modification of hydrogels, and chemical crosslinking through post-printing treatments. However, these treatments are difficult to process and limited in hydrogel strength, and their applicability is limited.
The coaxial biological 3D printing technology is separated from the traditional extrusion type biological 3D printing technology, and in the research of recent years, the coaxial printing technology has unique advantages in damaged organization vascularization because the coaxial printing technology enables the traditional hydrogel printing which needs a crosslinking agent to have certain strength to be possible due to the unique double-layer structure.
Disclosure of Invention
In view of the above, the present invention provides a method for preparing a coaxial polyethylene lactone-hydrogel scaffold based on low temperature biological 3D printing, which overcomes or at least partially solves the above problems.
In order to solve the technical problem, the invention provides a method for preparing a polyethylene lactone-hydrogel coaxial stent based on low-temperature biological 3D printing, which comprises the following steps:
preparing a polyethylene lactone/glacial acetic acid solution with a preset concentration;
taking a preset amount of the polyethylene lactone/glacial acetic acid solution for cooling;
filling the polyethylene lactone/glacial acetic acid solution into a first spray head material cavity of a low-temperature coaxial biological 3D printer;
placing the first spray head material cavity in a centrifuge for centrifuging and removing bubbles;
preparing a hydrogel solution with a preset concentration;
filling the hydrogel solution into a second spray head material cavity of the low-temperature coaxial biological 3D printer;
placing the second spray head material cavity in a centrifuge for centrifuging and removing bubbles;
setting working parameters of the low-temperature coaxial biological 3D printer;
printing the polycaprolactone-hydrogel coaxial composite stent by the low-temperature coaxial biological 3D printer;
and carrying out post-treatment on the polycaprolactone-hydrogel coaxial composite stent.
Preferably, the preparation of the predetermined concentration of the polyethylene lactone/glacial acetic acid solution comprises the steps of:
preparing polyethylene lactone and pure glacial acetic acid in a preset ratio;
putting the polyethylene lactone and the pure glacial acetic acid into a conical flask;
adding a magnetic rotor to the erlenmeyer flask;
sealing a sealing layer outside the conical flask;
placing the conical flask in a heating magnetic stirrer;
setting working parameters of the heating magnetic stirrer;
the plate was heated to stir the solution in the flask.
Preferably, the mass ratio of the polyethylene lactone to the pure glacial acetic acid in the polyethylene lactone/glacial acetic acid solution is 2: 3.
Preferably, the ambient temperature around the low-temperature coaxial biological 3D printer is 15 ℃ to 30 ℃.
Preferably, the temperature of the low-temperature forming platform of the low-temperature coaxial biological 3D printer is-10 ℃ to-30 ℃.
Preferably, the relative humidity of the low-temperature coaxial biological 3D printer is 35% -50%.
Preferably, the air pressure of compressed air on the inner layer and the outer layer of the low-temperature coaxial biological 3D printer is 10KPa-150 KPa.
Preferably, the three-dimensional platform movement speed of the low-temperature coaxial biological 3D printer is 3-20 mm/s.
Preferably, the printing layer height of the low-temperature coaxial biological 3D printer is 100-500 μm.
Preferably, the post-treatment of the polycaprolactone-hydrogel coaxial composite stent comprises the steps of:
pre-cooling the polycaprolactone-hydrogel coaxial composite stent;
freezing the polycaprolactone-hydrogel coaxial composite scaffold;
and carrying out vacuum freeze drying treatment on the polycaprolactone-hydrogel coaxial composite scaffold.
One or more technical solutions in the embodiments of the present invention have at least the following technical effects or advantages: the application provides a preparation method of a polyethylene lactone-hydrogel coaxial bracket based on low-temperature biological 3D printing, which adopts a low-temperature coaxial biological 3D printing technology, can overcome the defects that a thermal sensitive growth factor cannot be loaded when PCL is melted and printed, and can enable hydrogel needing to be crosslinked to be directly molded under the action of low temperature. The method can form the bracket with the rough surface and the multilayer composite structure, is more favorable for the climbing growth of the hemangioblast and the histiocyte, and is more expected to further accelerate the repair of the damaged tissue by doping cells, growth factors and the like.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on the drawings without creative efforts.
Fig. 1 is a schematic diagram of a PLC-SA composite scaffold prepared by a method for preparing a coaxial scaffold based on a polylactone-hydrogel based on low-temperature biological 3D printing provided in embodiment 1 of the present invention;
fig. 2 is a schematic diagram of an experiment in printing of a PLC-SA composite stent prepared by a method for preparing a coaxial stent of a polylactone-hydrogel based on low-temperature biological 3D printing according to embodiment 1 of the present invention;
fig. 3 is a schematic diagram of a PLC-SA composite stent prepared by a method for preparing a coaxial polyethylene-lactone-hydrogel stent based on low-temperature biological 3D printing according to embodiment 1 of the present invention.
Detailed Description
The present invention will be described in detail below with reference to specific embodiments and examples, and the advantages and various effects of the present invention will be more clearly apparent therefrom. It will be understood by those skilled in the art that these specific embodiments and examples are for the purpose of illustrating the invention and are not to be construed as limiting the invention.
Throughout the specification, unless otherwise specifically noted, terms used herein should be understood as having meanings as commonly used in the art. Accordingly, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. If there is a conflict, the present specification will control.
Unless otherwise specifically stated, various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or can be prepared by existing methods.
In an embodiment of the application, the invention provides a method for preparing a coaxial polyethylene lactone-hydrogel stent based on low-temperature biological 3D printing, which comprises the following steps:
s1: preparing a polyethylene lactone/glacial acetic acid solution with a preset concentration;
in the embodiment of the present application, the preparation of the predetermined concentration of the polyethylene lactone/glacial acetic acid solution comprises the steps of:
preparing polyethylene lactone and pure glacial acetic acid in a preset ratio;
putting the polyethylene lactone and the pure glacial acetic acid into a conical flask;
adding a magnetic rotor to the erlenmeyer flask;
sealing a sealing layer outside the conical flask;
placing the conical flask in a heating magnetic stirrer;
setting working parameters of the heating magnetic stirrer;
the plate was heated to stir the solution in the flask.
In the embodiment of the application, the concentration of the polyethylene lactone/glacial acetic acid solution is 40 wt%, the mass ratio of the polyethylene lactone to the pure glacial acetic acid in the polyethylene lactone/glacial acetic acid solution is 2: 3, the sealing layer is used for preventing acetic acid from evaporating, the sealing layer can be specifically a multilayer preservative film, an elastic band and an insulating adhesive, and the working parameters of the heating magnetic stirrer are as follows: the heat preservation temperature is 60 ℃, the rotation speed is 16r/s, and the heating and stirring time is 3 hours.
S2: taking a preset amount of the polyethylene lactone/glacial acetic acid solution for cooling;
in the examples of the present application, the erlenmeyer flask containing the solution was removed and cooled to room temperature before being unsealed in order to avoid that much of the acetic acid would evaporate and spill out due to unsealing at higher temperatures.
S3: filling the polyethylene lactone/glacial acetic acid solution into a first spray head material cavity of a low-temperature coaxial biological 3D printer;
s4: placing the first spray head material cavity in a centrifuge for centrifuging and removing bubbles;
in this application embodiment, place the first shower nozzle material chamber of the coaxial biological 3D printer of low temperature in centrifuge and carry out centrifugation and get rid of the bubble, if the shower nozzle material chamber is inconvenient to be dismantled, then must carry out centrifugation and get rid of bubble work before packing into. Setting the parameters of the centrifuge to 2000r/s of rotation speed, keeping the time for 3min, and putting the temporarily unused spray nozzle container into a 37 ℃ incubator for heat preservation to prevent the solution from deteriorating.
S5: preparing a hydrogel solution with a preset concentration;
in the embodiment of the present application, the concentration of the hydrogel solution may be selectively prepared according to the need, specifically, the hydrogel is prepared according to the physicochemical properties of the hydrogel to be added, the process and the ratio parameters need to be adjusted according to the need, and a pre-configuration experiment needs to be performed to explore. However, the preparation process of the biomaterial solution has the following requirements: (1) the hydrogel chosen must be soluble in some useful agent to produce a solution; (2) the viscosity of the resulting solution is required: it must be possible to extrude smoothly in the head of a 3D printer.
S6: filling the hydrogel solution into a second spray head material cavity of the low-temperature coaxial biological 3D printer;
s7: placing the second spray head material cavity in a centrifuge for centrifuging and removing bubbles;
in this application embodiment, place the second shower nozzle material chamber of the coaxial biological 3D printer of low temperature in centrifuge and carry out centrifugation and get rid of the bubble, if the shower nozzle material chamber is inconvenient to be dismantled, then must carry out centrifugation and get rid of bubble work before packing into.
S8: setting working parameters of the low-temperature coaxial biological 3D printer;
in the embodiment of the application, the working parameters of the low-temperature coaxial biological 3D printer are as follows: the environment temperature is 15-30 ℃, the temperature of the low-temperature forming platform is-10-30 ℃, the relative humidity is 35-50%, the air pressure of compressed air of the inner layer and the outer layer is 10KPa-150KPa, the movement speed of the three-dimensional platform is 3mm/s-20mm/s, the height of a printing layer is 100-500 mu m, and the preferred printing needle is 20G 27G. The temperature of the PLC material cavity is 25-37 ℃, and the temperature of the spray head of the raw hydrogel material is adjusted according to the physicochemical property of the raw hydrogel material.
S9: printing the polycaprolactone-hydrogel coaxial composite stent by the low-temperature coaxial biological 3D printer;
s10: and carrying out post-treatment on the polycaprolactone-hydrogel coaxial composite stent.
In the embodiment of the application, the post-treatment of the polycaprolactone-hydrogel coaxial composite stent comprises the following steps:
pre-cooling the polycaprolactone-hydrogel coaxial composite stent;
freezing the polycaprolactone-hydrogel coaxial composite scaffold;
and carrying out vacuum freeze drying treatment on the polycaprolactone-hydrogel coaxial composite scaffold.
In the embodiment of the application, the polycaprolactone-hydrogel coaxial composite bracket to be processed is printed and placed in a refrigerator freezing chamber at the temperature of-20 ℃, a pre-cooling cold trap and a storage rack of a freeze dryer are opened for 30 minutes, and the pre-cooling temperature is about-40 ℃; after the pre-cooling is finished, the sample is placed in a storage rack to be frozen for more than 2 hours, and the freezing temperature is minus 40 ℃ to minus 60 ℃; and (3) changing the sample to another shelf, covering a vacuum cover, vacuumizing, and carrying out vacuum freeze drying for about 24 hours at the temperature of minus 40 ℃ to minus 60 ℃ to obtain the final dry composite stent.
The following is a detailed description of specific embodiments.
Example 1:
the application provides a method for preparing a polyethylene lactone-hydrogel coaxial bracket based on low-temperature biological 3D printing, which can be used for preparing an outer layer framework supported by PCL (polycaprolactone-styrene) and a hydrogel material with SA (sodium alginate) as an inner layer, and comprises the following steps:
(1) 10ml of a 40% strength by weight PCL/glacial acetic acid solution were prepared: weighing 16g of PCL and 24g of glacial acetic acid, heating and stirring for 6 hours, wherein the water bath heating temperature is 55-65 ℃, and the rotating speed is 16 r/s;
(2) prepare 10ml of SA solution: magnetically stirring 0.03g of SA and 10ml of purified water at 40 ℃ for 3 hours at the rotating speed of 16r/s to obtain a uniform solution;
(3) and (3) carrying out centrifugal bubble removal operation on the PCL/glacial acetic acid solution and the SA solution, wherein the rotation speed of a centrifugal machine is 2000n/s, and the time duration is 3 min. Then, filling PCL/glacial acetic acid solution into an outer layer feeding barrel of the coaxial needle, filling SA solution into an inner layer feeding barrel of the coaxial needle, wherein the extrusion air pressure of the SA solution is 35kPa, the extrusion air pressure of the PCL solution is 100kPa, the temperature of a material cavity is 37 ℃, the ambient temperature is 25 ℃, the temperature of a low-temperature forming platform is-20 ℃, the relative humidity is 40-45%, and the movement speed of the three-dimensional platform is 8 mm/s;
(4) and pre-freezing the printed composite scaffold in an environment of-60 ℃ for 2 hours, and then freeze-drying for 36-48 hours.
The application provides a preparation method of a polyethylene lactone-hydrogel coaxial bracket based on low-temperature biological 3D printing, which adopts a low-temperature coaxial biological 3D printing technology, can overcome the defects that a thermal sensitive growth factor cannot be loaded when PCL is melted and printed, and can enable hydrogel needing to be crosslinked to be directly molded under the action of low temperature. The method can form the bracket with the rough surface and the multilayer composite structure, is more favorable for the climbing growth of the hemangioblast and the histiocyte, and is more expected to further accelerate the repair of the damaged tissue by doping cells, growth factors and the like.
The preparation method of the polyethylene lactone-hydrogel coaxial bracket based on low-temperature biological 3D printing, which is provided by the application, adopts a composite structure of polyethylene lactone and hydrogel, and can make up for the defect of insufficient strength of the hydrogel through the strength of PCL; the biological inertia of the PCL is compensated through the stronger biocompatibility of the hydrogel, so that the range of tissue repair is further improved; the low-temperature coaxial biological 3D printing technology can prepare a scaffold structure with a rough surface at low temperature, so that the cell tissue can be attached more conveniently; the coaxial structure of the inner layer and the outer layer is more favorable for vascularization, thereby accelerating the repair of tissues. This improves the efficiency of tissue repair.
The preparation method of the polyethylene lactone-hydrogel coaxial bracket based on low-temperature biological 3D printing has the following beneficial effects:
(1) compared with a single PCL and a single hydrogel system, the PCL with higher strength can be used as an outer layer to provide support through a coaxial printing process, the inner layer is added with a hydrogel material, a composite structure can be established, the biocompatibility of the stent is enhanced, the composite structure is favorable for realizing other functions such as drug slow release and the like, and the use range of the stent is favorably widened.
(2) Compared with PCL molding under a melting condition, the PCL molding at low temperature can enable the PCL surface layer to form a rough and porous structure, is more favorable for the adhesion growth of cell tissues, and further accelerates the repair of damaged tissues
(3) The low temperature can lead the hydrogel material which needs to be subjected to complex crosslinking in the reprinting process to be directly formed under the influence of the temperature, thereby simplifying the forming process.
(4) The coaxial process can integrate the advantages of the hydrogel material and the PCL, thereby not only ensuring the strength, but also ensuring the biological activity.
(5) The composite structure of the inner layer and the outer layer realized by the coaxial process is beneficial to increasing the vascularization capacity of the stent, and the composite structure can realize the slow release of the medicament and the realization of the multi-gradient composite function.
It is noted that, in this document, relational terms such as "first" and "second," and the like, may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other identical elements in a process, method, article, or apparatus that comprises the element. The above description is merely exemplary of the present application and is presented to enable those skilled in the art to understand and practice the present application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the application. Thus, the present application is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
In short, the above description is only a preferred embodiment of the present invention, and is not intended to limit the scope of the present invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A method for preparing a polyethylene lactone-hydrogel coaxial stent based on low-temperature biological 3D printing is characterized by comprising the following steps:
preparing a polyethylene lactone/glacial acetic acid solution with a preset concentration;
taking a preset amount of the polyethylene lactone/glacial acetic acid solution for cooling;
filling the polyethylene lactone/glacial acetic acid solution into a first spray head material cavity of a low-temperature coaxial biological 3D printer;
placing the first spray head material cavity in a centrifuge for centrifuging and removing bubbles;
preparing a hydrogel solution with a preset concentration;
filling the hydrogel solution into a second spray head material cavity of the low-temperature coaxial biological 3D printer;
placing the second spray head material cavity in a centrifuge for centrifuging and removing bubbles;
setting working parameters of the low-temperature coaxial biological 3D printer;
printing the polycaprolactone-hydrogel coaxial composite stent by the low-temperature coaxial biological 3D printer;
and carrying out post-treatment on the polycaprolactone-hydrogel coaxial composite stent.
2. The method for preparing the coaxial polyethylene lactone-hydrogel scaffold based on low-temperature biological 3D printing according to claim 1, wherein the step of preparing the polyethylene lactone/glacial acetic acid solution with preset concentration comprises the following steps:
preparing polyethylene lactone and pure glacial acetic acid in a preset ratio;
putting the polyethylene lactone and the pure glacial acetic acid into a conical flask;
adding a magnetic rotor to the erlenmeyer flask;
sealing a sealing layer outside the conical flask;
placing the conical flask in a heating magnetic stirrer;
setting working parameters of the heating magnetic stirrer;
the plate was heated to stir the solution in the flask.
3. The method for preparing the coaxial polyethylene lactone-hydrogel scaffold based on low-temperature biological 3D printing according to claim 2, wherein the mass ratio of polyethylene lactone to pure glacial acetic acid in the polyethylene lactone/glacial acetic acid solution is 2: 3.
4. The method for preparing the coaxial polyethylene lactone-hydrogel scaffold based on low-temperature biological 3D printing according to claim 1, wherein the ambient temperature around the low-temperature coaxial biological 3D printer is 15-30 ℃.
5. The method for preparing the polyethylene lactone-hydrogel coaxial stent based on the low-temperature biological 3D printing of claim 1, wherein the low-temperature forming platform of the low-temperature biological 3D printer is at a temperature of-10 ℃ to-30 ℃.
6. The method for preparing the coaxial polyethylene lactone-hydrogel scaffold based on low-temperature biological 3D printing according to claim 1, wherein the relative humidity of the low-temperature coaxial biological 3D printer is 35% -50%.
7. The method for preparing the coaxial polyethylene lactone-hydrogel scaffold based on low-temperature biological 3D printing according to claim 1, wherein the air pressure of compressed air in the inner layer and the outer layer of the low-temperature coaxial biological 3D printer is 10KPa-150 KPa.
8. The method for preparing the coaxial polyethylene lactone-hydrogel scaffold based on the cryogenic biological 3D printing of claim 1, wherein the three-dimensional platform moving speed of the cryogenic biological 3D printer is 3mm/s-20 mm/s.
9. The method for preparing the coaxial polyethylene lactone-hydrogel scaffold based on low-temperature biological 3D printing according to claim 1, wherein the printing layer height of the low-temperature coaxial biological 3D printer is 100-500 μm.
10. The method for preparing the coaxial polycaprolactone-hydrogel stent based on the cryobiological 3D printing according to claim 1, wherein the post-treatment of the coaxial polycaprolactone-hydrogel composite stent comprises the steps of:
pre-cooling the polycaprolactone-hydrogel coaxial composite stent;
freezing the polycaprolactone-hydrogel coaxial composite scaffold;
and carrying out vacuum freeze drying treatment on the polycaprolactone-hydrogel coaxial composite scaffold.
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