Injectable hollow stent based on flexible sugar sacrificial carrier and preparation method thereof

Through the combination of flexible sugar sacrificial carrier and PCL coating, the hard trait problem of existing 3D printed scaffolds is solved, and flexible, deformable injectable hollow scaffolds are realized, simplifying the printing process, improving the accuracy of complex organ reconstruction and cell maturation integration efficiency.

CN120393118APending Publication Date: 2025-08-01FOURTH MILITARY MEDICAL UNIVERSITY
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Patent Information

Application Number
CN202510373910.2
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-03-27
Publication Date
2025-08-01

AI Technical Summary

Technical Problem

Due to the rigid properties of existing 3D printed stents, the printing process is complicated and cannot be further adaptively modified, making it difficult to meet the requirements of patients' customized stent structure.

Method used

Using flexible sugar sacrificial carrier, by mixing sucrose, fructose, dextran, glucose and distilled water, stirring and crosslinking at high temperature, the flexible sugar mesh plane substrate is printed using 3D printing technology, and by hand shaping, coating the PCL coating, the flexible sugar carrier is dissolved to prepare an injectable hollow scaffold.

Benefits of technology

The flexible deformation and toughness of the scaffold are achieved, the printing process is simplified, the simulation accuracy and feasibility of complex organ morphology is improved, cell maturation and integration are promoted, and operation efficiency and biocompatibility are improved.

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Abstract

The preparation method comprises the following steps: mixing and dissolving sucrose, fructose, glucan and glucose in distilled water, continuously stirring at high temperature to obtain a viscous solution, and performing high-temperature crosslinking to obtain a sugar printing material; printing a flexible sugar net plane base material in a plane by using a sugar printing material, wherein the flexible sugar net plane base material is in a soft, flexible and deformable state; shaping the flexible sugar net plane base material to obtain a flexible sugar sacrifice carrier, and coating the flexible sugar sacrifice carrier with a plurality of layers of PCL coating liquid to obtain a double-layer stent; and dissolving the flexible sugar sacrificial carrier in distilled water to obtain the injectable hollow stent. By accurately controlling the proportion of the components in the flexible sugar sacrificial carrier, the character of the flexible sugar sacrificial carrier can be kept in a soft, flexible and deformable state within a period of time, only a base material needs to be printed in a two-dimensional plane, then shaping treatment is carried out, simulation of a specific organ shape is achieved, and the accuracy and feasibility of complex organ reconstruction are improved.
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Description

Technical Field

[0001] The present invention relates to the technical field of biomedical engineering, and particularly relates to an injectable hollow scaffold based on a flexible sugar sacrificial carrier and a preparation method thereof. Background Art

[0002] In tissue engineering, the selection and preparation of scaffolds are crucial for cell growth, differentiation, and tissue regeneration. With the progress of 3D printing technology, nanotechnology, and biomaterial science, the design and preparation of tissue engineering scaffolds have increasingly focused on personalization and precision, and can customize the scaffold structure and materials according to the specific needs of patients. At present, significant progress has been made in the application of tissue engineering scaffolds in the field of regenerative medicine, especially in bone, cartilage, skin, and soft tissue repair. How to maintain the printing performance of materials, ensure the compatibility of printing parameters between multi-component materials, and how to maintain cell viability during and after the production process are still challenges in this field.

[0003] Classical tissue engineering scaffolds usually use natural degradable inorganic materials such as coral hydroxyapatite (CHA) or synthetic degradable polymer materials such as polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), etc. In particular, polycaprolactone (PCL)-based biopolymer scaffolds are widely used in the field of tissue engineering, including skin, bone, heart, and nerve tissue engineering. However, such biopolymer scaffolds have limitations in the ability to reshape the structure of specific morphological implants. In simulating defects with complex morphological structures, such as trachea, ear, nose, etc., it is necessary to construct a 3D solid structure model of the trachea, ear, nose, etc. through CAD software, etc., and plan the printing path containing three dimensions of the X-axis, Y-axis, and Z-axis. When using a 3D printer to print the scaffold, it is also necessary to print a three-dimensional solid structure with height, width, and depth. The process is complex, the efficiency is low, and for concave structures, the printing effect is often not good. In addition, the scaffolds constructed by this process are mostly hard in shape, cannot be extruded, stretched, bent, or plastically deformed, are not easy to be adaptively modified, and have extremely poor flexibility, and cannot meet the requirements of patients for customizing the scaffold structure.

[0004] Therefore, it is necessary to propose new measures to overcome the above defects. Summary of the Invention

[0005] The purpose of the present invention is to provide an injectable hollow scaffold based on a flexible sugar sacrificial carrier and a preparation method thereof, so as to solve the problems such as complex printing process and inability to be further adaptively modified existing in the existing 3D printed scaffolds due to their hard shape.

[0006] In order to achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0007] Provide a method for preparing an injectable hollow scaffold based on a flexible sugar sacrificial carrier, the preparation method comprising:

[0008] Mix sucrose, fructose, dextran, and glucose in proportion and dissolve them in distilled water, and continuously stir at high temperature to obtain a viscous solution;

[0009] Place the viscous solution in a high-temperature environment for high-temperature cross-linking to obtain a sugar printing material;

[0010] With the aid of a 3D printer, use the sugar printing material to print a flexible sugar mesh planar substrate in a plane, and the flexible sugar mesh planar substrate is in a soft, flexible, and deformable state;

[0011] According to the shape of the printing object, cut, extrude, stretch, bend, knead, assemble, and bond the flexible sugar mesh planar substrate to obtain a flexible sugar sacrificial carrier;

[0012] Prepare a PCL coating solution containing a porogen, and coat the PCL coating solution on the flexible sugar sacrificial carrier in multiple layers to obtain a double-layer scaffold;

[0013] Place the double-layer scaffold in distilled water to dissolve the flexible sugar sacrificial carrier and obtain an injectable hollow scaffold.

[0014] Furthermore, the mass mixing ratio of sucrose, fructose, dextran, glucose:distilled water is 10:1:1:2:10.

[0015] Furthermore, the temperature of continuous stirring at high temperature is 300 °C.

[0016] Furthermore, the temperature of high-temperature cross-linking is 100 °C and the time is 8 hours.

[0017] Furthermore, preparing a PCL coating solution containing a porogen includes:

[0018] Dissolve PCL at a concentration of 5% in hexafluoroisopropanol;

[0019] Add sodium chloride with a mass three times that of PCL as a porogen;

[0020] After stirring, seal the lid and stir thoroughly to dissolve.

[0021] Furthermore, after shaping the flexible sugar sacrificial carrier, immerse it in anhydrous ethanol for dehydration and hardening.

[0022] Furthermore, coating the PCL coating solution on the flexible sugar sacrificial carrier in multiple layers includes:

[0023] Immerse the dehydrated and hardened flexible sugar sacrificial carrier in the PCL coating solution, take it out and let it dry to form a coating;

[0024] Then repeat the operation to form multiple coatings on the surface of the dehydrated and hardened flexible sugar sacrificial carrier.

[0025] Further, the double-layer scaffold is placed in distilled water to dissolve the flexible sugar sacrificial carrier and the porogen simultaneously, obtaining an injectable hollow scaffold with holes in the solid part.

[0026] On the other hand, an injectable hollow scaffold obtained by the preparation method as described above is provided.

[0027] Further, the injectable hollow scaffold has a hollow channel, which is obtained by dissolving the internal flexible sugar sacrificial carrier and is used for injecting and filling seed cells, cell aggregates, and micro-nano scale adult tissues.

[0028] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0029] The present invention provides an injectable hollow scaffold based on a flexible sugar sacrificial carrier and a preparation method thereof. By precisely controlling the proportion of each component in the flexible sugar sacrificial carrier, its properties can be maintained in a soft, flexible, and deformable state for a period of time, with good toughness and plasticity. When using 3D printing technology for printing, no modeling, path planning, or three-dimensional solid printing with height, width, and depth is required. Only a flexible sugar mesh planar substrate needs to be printed in a two-dimensional plane, and then it is cut into different shapes required according to the complex shape of the constructed object. Finally, reprocessing and shaping are carried out through manual extrusion, stretching, bending, kneading, assembling, bonding, etc. to obtain the flexible sugar sacrificial carrier of the constructed object. After coating with a coating material and dissolving the sacrifice, an injectable hollow scaffold is obtained. This process can precisely control the macroscopic configuration of the scaffold, realize the simulation of the morphology of specific organs, and improve the accuracy and feasibility of complex organ reconstruction. Description of the Drawings

[0030] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the following drawings are only some embodiments of the present invention, and those of ordinary skill in the art can obtain the drawings of other embodiments without creative efforts.

[0031] Figure 1 It is a schematic diagram of the preparation and printing process of the printing raw materials of the flexible sugar mesh planar substrate in the embodiment of the present invention. In the figure, (i), (ii), (iii), and (iv) show the preparation process of the flexible sugar printing raw materials, and (v) shows the printing process.

[0032] Figure 2 It is a schematic diagram of the preparation process of the PCL coating solution in the embodiment of the present invention. In the figure, (a) is the process of dissolving the solute (PCL) (in hexafluoroisopropanol), and (b) is the process of adding and stirring the porogen (NaCl).

[0033] Figure 3 It is a schematic diagram of the deformation of the flexible sugar mesh planar substrate in the embodiment of the present invention. In the figure, (a) is the plane, (b) is the opposite-side curved surface, (c) is the diagonal curved surface, and (d) is the hyperbolic surface.

[0034] Figure 4 It is a schematic diagram of the plastic process of the flexible sugar sacrificial carrier in the embodiment of the present invention.

[0035] Figure 5 It is a schematic diagram of the plastic process of the flexible sugar sacrificial carrier of the tracheal stent in the embodiment of the present invention.

[0036] Figure 6 It is a schematic diagram of the plastic process of the flexible sugar sacrificial carrier of the ear stent in the embodiment of the present invention.

[0037] Figure 7 It is a schematic diagram of the coating and sugar removal process of the flexible sugar sacrificial carrier of the tracheal stent in the embodiment of the present invention.

[0038] Figure 8 It is a microstructural diagram of the injectable hollow stent in the embodiment of the present invention.

[0039] Figure 9 It is a quantitative result diagram of the performance characterization of the hollow stent with different coatings in the embodiment of the present invention (including coating thickness, compressive strength, tensile strength, porosity).

[0040] Figure 10 It is a display of the biocompatibility verification of the hollow stent with different coatings in the embodiment of the present invention. In the figure, (a) is the display of the live and dead cell staining on the surface of each group of materials, and (b) is the quantitative analysis display of the live cells in each group of materials.

[0041] Figure 11 It is a display diagram of the osmotic effect of the injectable hollow stent in the embodiment of the present invention. In the figure, (1), (2), (3), and (4) in (a) are the four stages of the osmotic process, (b) is the change of the absorbance (540 nm) of the ink diffusing through the hollow stent with different coatings over time, and (c) is the quantitative analysis of the ink diffusion time in different coatings.

[0042] Figure 12 It is a display diagram of the injectability of the injectable hollow stent in the embodiment of the present invention.

[0043] Figure 13 It is a display diagram of the in vivo embedding effect of the injectable hollow stent in the embodiment of the present invention. In the figure, (a) is the macroscopic image of each group of grafts 2 weeks after implantation and the tissue sections of tracheal grafts in different groups (H&E, Alcian blue, and type II collagen staining), and (b) is the immunofluorescence staining of CD 31 in each group of grafts. Detailed implementation manners

[0044] To facilitate the understanding of the present invention, the present invention will be described more comprehensively below with reference to the relevant drawings. Preferred embodiments of the present invention are shown in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, these embodiments are provided to make the disclosure of the present invention more thorough and comprehensive.

[0045] In the description of the present invention, it should be understood that all technologies and scientific terms used have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention pertains. When there are contradictions, the definitions in this specification shall prevail. Unless otherwise specified, the technical means used in the examples are conventional means well-known to those skilled in the art, the reagents used in the examples are commercially available products, and the devices used in the examples are existing devices. The limitation of the means, reagents, or devices should not be construed as a limitation to the present invention, and means, reagents, or devices of the same type for solving the same technical problems are within the protection scope of the present invention.

[0046] In the description of the present invention, it should be understood that when an equivalent, concentration, or other value or parameter is expressed as a range, a preferred range, or a range defined by a series of upper limit preferred values and lower limit preferred values, this should be understood as specifically disclosing all ranges formed by any pairing of any range upper limit or preferred value with any range lower limit or preferred value, regardless of whether the range is separately disclosed. When a numerical range is described herein, unless otherwise stated, this range is intended to include its end values and all integers and fractions within the range.

[0047] It should also be noted that although the order of steps is involved in the method description, in some cases, it can be executed in a different order from that herein and should not be construed as a limitation to the order of steps.

[0048] The present invention provides a method for preparing an injectable hollow scaffold based on a flexible sugar sacrificial carrier. Through a specially formulated sugar printing material, a soft deformable planar substrate is obtained by using 3D bioprinting technology, and then a flexible sugar sacrificial carrier is obtained by manual kneading. After coating a layer and dissolving the sacrifice, an injectable hollow scaffold with a hollow channel is obtained, which can complete the precise shaping of a specific-shaped graft and significantly improve the efficiency.

[0049] Specifically, as Figure 1 , the preparation method specifically includes the following steps:

[0050] S1: Mix sucrose, fructose, dextran, and glucose in proportion and dissolve them in distilled water, and continuously stir at high temperature to boil and obtain a viscous solution.

[0051] Among them, glucan specifically uses glucan 70 with a molecular weight of 70,000, and fructose uses D-fructose. The mass mixing ratio of sucrose, fructose, glucan, glucose to distilled water is 10:1:1:2:10.

[0052] In this step, the temperature of continuous high-temperature stirring is 300 °C. Specifically, the mixture is continuously stirred with a glass rod under the condition of 300 °C on an induction cooker until the solution becomes viscous and light yellow.

[0053] S2: Place the viscous solution in a high-temperature environment for high-temperature cross-linking to obtain a sugar printing material.

[0054] Specifically, the temperature of high-temperature cross-linking is 100 °C and the time is 8 hours. It can be completed using an oven to finally obtain a melt-extrusion type printing raw material.

[0055] S3: With the aid of a 3D printer, use the sugar printing material to print a flexible sugar mesh planar substrate in a plane. The flexible sugar mesh planar substrate is in a soft, flexible and deformable state. Specifically:

[0056] Load the sugar printing material into a Particle Cloud 3D printer, adjust the parameters: the heating temperature of the barrel is 95 °C, the temperature of the extrusion head is 95 °C, the air pressure is 0.05 MPa, the printing rate is 5 mm / s, and the diameter of the printing extrusion head is 0.5 mm. Print according to the preset trajectory (generated by an STL file) to obtain a flexible sugar mesh planar substrate.

[0057] S4: According to the shape of the printing object, cut, extrude, stretch, bend, knead, assemble, and bond the flexible sugar mesh planar substrate to obtain a flexible sugar sacrificial carrier.

[0058] Based on the above special sugar mixing formula and the special temperature process of boiling and cross-linking, the flexible sugar mesh planar substrate finally obtained by the present invention has good toughness and plasticity, is soft and deformable, can be arbitrarily cut into different shapes as needed, and can be manually extruded, stretched, bent, kneaded, assembled, and bonded to obtain the required three-dimensional structure, and can maintain the required three-dimensional configuration for a long time, such as Figure 3 .

[0059] If only sucrose is used to prepare the sugar printing material, printing syrup can be formed under high temperature, but the printing syrup will quickly cool and crystallize, turning into a hard state and unable to deform. Therefore, when only sucrose is used to prepare the sugar printing material, it is necessary to directly print a three-dimensional solid structure. Such a printing mode necessarily requires 3D modeling and printing path planning. While the present invention can quickly print a flexible sugar mesh planar substrate, which is a two-dimensional planar structure, and then directly manually shape it to obtain the required three-dimensional structure. When necessary, some molds can also be used, with higher efficiency, more accurate shaping, and the ability to fine-tune the soft three-dimensional structure at any time.

[0060] As Figure 4 , by folding, curling, and bonding a flexible sugar mesh planar substrate, various target morphological structure scaffolds can be obtained, and if the operation is not accurate enough, they can be restored. As Figure 5 , when printing a flexible sugar mesh planar substrate, a planar material is designed by simulating the shape of a natural gas pipe, and then a tracheal stent with multiple C-shaped rings is obtained by bending the flexible sugar mesh planar substrate. As Figure 6 , a complex-shaped ear can also be obtained by kneading as an ear stent. If sucrose is used to prepare the sugar printing material, the ear needs to be modeled and the printing path planned, and a three-dimensional ear stent is directly printed, which is in the state of hard candy as a whole. This is not only complex in operation but also cannot be further shaped and modified.

[0061] After shaping the flexible sugar sacrificial carrier, the flexible sugar sacrificial carrier can be immersed in absolute ethanol for dehydration and hardening, and then dried. The flexible sugar sacrificial carrier is no longer soft and has support force.

[0062] S5: Prepare a PCL coating solution containing a pore-forming agent, and multi-layer coat the PCL coating solution onto the flexible sugar sacrificial carrier to obtain a double-layer scaffold.

[0063] As Figure 2 , preparing a PCL coating solution containing a pore-forming agent specifically includes the following steps:

[0064] S501: Dissolve PCL (polycaprolactone) in hexafluoroisopropanol at a concentration of 5%;

[0065] S502: Add sodium chloride (screened through a 500-mesh sieve, with a particle size of about 38 μm) three times the mass of PCL as a pore-forming agent;

[0066] S503: Place it in a fume hood, stir with a magnetic stirrer at 60 °C, cover it, stir and dissolve it thoroughly, and let it stand overnight.

[0067] In other embodiments, according to different requirements for the mechanics and degradation rate of the defect site, polycaprolactone can be replaced with other medical polymer materials such as polyurethane, polyglycolic acid, and polylactic acid.

[0068] Multi-layer coating the PCL coating solution onto the flexible sugar sacrificial carrier specifically includes the following steps:

[0069] S504: Immerse the dehydrated and hardened flexible sugar sacrificial carrier in the PCL coating solution, take it out and dry it to form a coating;

[0070] S505: Then repeat the operation (such as 2 - 6 times) to form multiple coatings on the surface of the dehydrated and hardened flexible sugar sacrificial carrier to increase the coating thickness.

[0071] S6: Place the double-layer scaffold in distilled water to dissolve the flexible sugar sacrificial carrier, obtaining an injectable hollow scaffold.

[0072] As Figure 7 , when the double-layer scaffold is placed in distilled water, the porogen is dissolved while the flexible sugar sacrificial carrier is dissolved, obtaining an injectable hollow scaffold with holes in the solid part. As Figure 8 , the more the coating, the thicker the solid part of the injectable hollow scaffold, which can be only used for defect reconstruction in different parts. In addition, the particle size and dosage of the porogen will also affect the pore distribution in the solid part of the injectable hollow scaffold.

[0073] The injectable hollow scaffold can be dried and then placed in 75% ethanol for disinfection and standby.

[0074] Through the flexible sugar sacrificial carrier that can be precisely shaped, the present invention prepares a hollow tissue engineering scaffold with good morphological pre-construction, which can be processed into various shapes according to needs, such as ears, noses, joint surfaces, complex craniofacial bone defects, etc. This method can precisely control the shape and structure of the scaffold, and at the same time optimize the mechanical properties and biocompatibility of the scaffold by adjusting the proportion of sugar, the composition of the coating solution and the coating thickness. In addition, seed cells, cell aggregates, micro-nano scale adult tissues, etc. can also be injected and filled into the injectable hollow scaffold of the present invention to achieve the mature integration of cells in the scaffold, thereby constructing a defect graft with a specific morphology. Through in vitro culture or in vivo pre-embedding, cells can mature and integrate in the scaffold, and finally form an organizational structure with specific functions, overcoming the limitations of the prior art in terms of morphology control, cell compatibility and tissue function restoration, and providing a new solution for the preparation of tissue engineering scaffolds with complex morphological structures.

[0075] The injectable hollow scaffold obtained by the preparation method of the present invention has a hollow channel, which is obtained by dissolving the internal flexible sugar sacrificial carrier, and is used for injecting and filling seed cells, cell aggregates, micro-nano scale adult tissues, etc. According to the defect site, the seed cells can also be replaced by bone marrow mesenchymal stem cells, chondrocytes, fibroblasts, etc.

[0076] According to the shape of the defective trachea, an injectable hollow scaffold for the trachea is constructed by the method of the present invention. Using cartilage microparticle cell aggregates as the injection component, representing the seed cells, they are filled into the injectable hollow scaffold of the present invention. The mixed seed cells and tissue aggregates are injected into the injectable hollow scaffold through a round-tip syringe (aperture 1 mm), and the hollow scaffold is filled with biological components, realizing the reshaping of the in vitro complex structure scaffold and cell seeding. Based on the morphological reshaping of the hollow scaffold, the cell culture process of traditional tissue engineering is avoided, greatly shortening the in vitro forming and construction time of specific morphological organ defects. With the support of the coated scaffold, the graft after injection filling has excellent mechanical properties and can be directly implanted into the body for defect repair.

[0077] In addition, the tracheal stent after injection filling was embedded under the body mucosa, and samples were taken two weeks later, and its regeneration effect was verified histologically. For example, Figure 13 (a) In the gross observation of the implanted stent in the body, the integrity of the tissue morphology was shown. This indicates that the hollow stent obtained by using the sacrificial flexible sugar can maintain a stable structure after implantation, providing a stable support environment for the growth of cells in the hollow pipeline, reducing the tissue structure damage caused by stent degradation or deformation, and can be effectively applied to morphologically complex organs such as trachea, ear, and nose. Histological sections showed that the cartilage microparticles had normal morphology and no necrosis or apoptosis. For example, Figure 13 (b) It can be seen that obvious angiogenesis phenomena exist in each group of coated stents, which can provide sufficient nutrition and oxygen for the tissue. This indicates that the hollow stent obtained by using the sacrificial flexible sugar can provide a good living environment for cells and accelerate tissue regeneration.

[0078] After experimental verification, the injectable hollow stent constructed by the present invention has the following technical advantages:

[0079] 1. Improving the mechanical properties and biocompatibility of the stent:

[0080] Although traditional stent materials such as sodium alginate and chitosan have good biocompatibility, there are technical challenges in forming a hollow tubular structure. These problems are mainly reflected in aspects such as the shape maintenance, mechanical properties, and cell compatibility of the stent. For example, some stents may not match the target tissue in terms of biomechanical properties, or the degradation rate is not synchronized with the speed of new tissue formation, resulting in limited treatment effects.

[0081] By precisely controlling the thickness of the PCL coating, the injectable hollow stent prepared by the present invention is closer to natural tissue in terms of mechanical properties, can achieve sufficient nutrient interaction between the transplanted tissue in the pipeline and the outside world, promote the formation of good trans-wall vascularization, facilitate the survival and proliferation of cells in the pipeline, the micro-nano structure promotes the formation of trans-wall vascularization, and at the same time maintains good biocompatibility, reducing the risk of long-term foreign body reaction and inflammation.

[0082] 2. Precision of morphological pre-construction:

[0083] Many traditional methods are difficult to precisely control the microscopic and macroscopic structures of the stent, especially when it is necessary to simulate the morphology of specific organs such as the trachea, ear, and nose. This limits the application potential of the stent in complex organ reconstruction.

[0084] The present invention precisely controls the proportion of sugar to obtain a soft and tough substrate. By using 3D printing technology and reprocessing and shaping treatment, it can precisely control the macroscopic structure of the injectable hollow scaffold, realize the simulation of the morphology of specific organs, such as trachea, ear, nose, etc., and improve the accuracy and feasibility of complex organ reconstruction.

[0085] 3. Promotion of cell maturation and integration:

[0086] Although traditional scaffolds can support the initial attachment and proliferation of cells, they are ineffective in promoting cell differentiation and tissue-specific function expression, which is crucial for achieving long-term stability and functional recovery of tissues.

[0087] The present invention promotes the maturation and integration of cells in the injectable hollow scaffold by injecting and filling seed cells and mature micro-nano tissues, helps to form tissue structures with specific functions, and thus improves the long-term stability and functional recovery of tissues.

[0088] 4. Simplicity and efficiency of operation:

[0089] The present invention simplifies the preparation process of the scaffold, simplifies three-dimensional printing to two-dimensional printing, and each step from raw material preparation to scaffold forming and then to cell seeding has clear operation parameters and methods, making the whole preparation process more simple and efficient.

[0090] 5. Saving materials and costs:

[0091] By optimizing the material ratio and coating technology, the present invention reduces material waste and reduces production costs without sacrificing the performance of the scaffold.

[0092] The above uses specific examples to elaborate on the present invention, which is only used to help understand the present invention and is not intended to limit the present invention. For those skilled in the technical field to which the present invention pertains, based on the idea of the present invention, several simple deductions, deformations or substitutions can also be made.

Claims

1. Preparation method of injectable hollow scaffold based on flexible sugar sacrificial carrier, characterized in that: The preparation method includes: Mix sucrose, fructose, dextran, and glucose in proportion and dissolve them in distilled water, and continuously stir at high temperature to obtain a viscous solution; Place the viscous solution in a high-temperature environment for high-temperature cross-linking to obtain a sugar printing material; With the aid of a 3D printer, use the sugar printing material to print a flexible sugar mesh planar substrate in a plane, and the flexible sugar mesh planar substrate is in a soft, flexible, and deformable state; According to the shape of the printing object, cut, extrude, stretch, bend, knead, assemble, and bond the flexible sugar mesh planar substrate to obtain a flexible sugar sacrificial carrier; Prepare a PCL coating solution containing a porogen, and coat the PCL coating solution on the flexible sugar sacrificial carrier in multiple layers to obtain a double-layer scaffold; Place the double-layer scaffold in distilled water to dissolve the flexible sugar sacrificial carrier and obtain an injectable hollow scaffold.

2. The preparation method of injectable hollow scaffold based on flexible sugar sacrificial carrier according to claim 1, characterized in that: The mass mixing ratio of sucrose, fructose, dextran, glucose: distilled water is 10:1:1:2:

10.

3. The preparation method of injectable hollow scaffold based on flexible sugar sacrificial carrier according to claim 2, characterized in that: The temperature of continuous stirring at high temperature is 300 °C.

4. The preparation method of injectable hollow scaffold based on flexible sugar sacrificial carrier according to claim 3, characterized in that: The temperature of high-temperature cross-linking is 100 °C and the time is 8 hours.

5. The preparation method of injectable hollow scaffold based on flexible sugar sacrificial carrier according to claim 4, characterized in that: Preparing a PCL coating solution containing a porogen includes: Dissolve PCL in hexafluoroisopropanol at a concentration of 5%; Add sodium chloride with a mass 3 times that of PCL as a porogen; Seal the lid after stirring and stir thoroughly to dissolve.

6. The preparation method of injectable hollow scaffold based on flexible sugar sacrificial carrier according to claim 5, characterized in that: After shaping the flexible sugar sacrificial carrier, immerse it in anhydrous ethanol for dehydration and hardening.

7. The preparation method of injectable hollow scaffold based on flexible sugar sacrificial carrier according to claim 6, characterized in that: Coating the PCL coating solution on the flexible sugar sacrificial carrier in multiple layers includes: Immerse the dehydrated and hardened flexible sugar sacrificial carrier in the PCL coating solution, take it out and dry it to form a coating; Then repeat the operation to form multiple coatings on the surface of the dehydrated and hardened flexible sugar sacrificial carrier.

8. The preparation method of injectable hollow scaffold based on flexible sugar sacrificial carrier according to claim 7, characterized in that: Place the double-layer scaffold in distilled water to dissolve the flexible sugar sacrificial carrier and dissolve the porogen at the same time, and obtain an injectable hollow scaffold with holes in the solid part.

9. An injectable hollow scaffold obtained by the preparation method as claimed in claim 8.

10. The injectable hollow scaffold according to claim 9, characterized in that: The injectable hollow scaffold has a hollow channel, which is obtained by dissolving the internal flexible sugar sacrificial carrier and is used for injecting and filling seed cells, cell aggregates, and micro-nano scale adult tissues.