A porous structure conducive to cell growth and preparation method thereof

The porous structure is prepared by sparse three-dimensional scatter plots from the inside to the outside and alternate printing ink materials, which solves the problem of mismatch in pore distribution in the prior art, and effectively grows and grows cells on the 3D printing scaffold, improving biocompatibility and controllable degradability.

CN116277933BActive Publication Date: 2025-09-02GUANGDONG REGEN-MED SCI & TECH LTD
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Patent Information

Application Number
CN202310216501.2
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-03-08
Publication Date
2025-09-02
Estimated Expiration
2043-03-08

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Abstract

The present invention relates to the field of biomedical technology, and specifically discloses a porous structure that is conducive to cell ingrowth and a preparation method thereof, wherein the preparation method includes the following steps: obtaining a three-dimensional model; generating a 3D printing model based on the three-dimensional model; and performing 3D printing according to the 3D printing model to obtain a porous structure; wherein the step of generating the 3D printing model based on the three-dimensional model includes: randomly generating a three-dimensional scatter plot with a density gradually decreasing from the inside to the outside based on the centroid of the three-dimensional model; obtaining multiple segmentation layers by layered slicing; projecting the scatter points respectively into the segmentation layers with the smallest distance therefrom; generating a corresponding Thiessen polygon graph based on the projected scatter points in each segmentation layer, and forming a 3D printing model with the edges of all Thiessen polygon graphs as printing paths; the porous structure prepared by the preparation method has pores of different shapes and pores with pores that gradually increase in diameter from the inside to the outside, which conforms to the structural characteristics of human tissue / bone and is conducive to cell ingrowth.
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Description

Technical Field

[0001] The present application relates to the field of biomedical technology, and in particular to a porous structure that is conducive to cell ingrowth and a preparation method thereof. Background Art

[0002] As an emerging material manufacturing technology, 3D printing has found numerous applications in medical regeneration, such as printing human bone tissue and hearts. Compared to existing scaffold manufacturing technologies, 3D printing allows for both controlled scaffold shape and fine-tuned pore size and structure.

[0003] Existing 3D printing technology mainly uses computers to set preset topological structures inside biological models to create suitable porous structures for implants or tissue culture. The preset pore structure style is difficult to match the internal and external morphology of the tissue to produce a suitable pore distribution, making it difficult to induce cell incorporation and growth.

[0004] There is currently no effective technical solution to the above problems. Summary of the Invention

[0005] The purpose of the present application is to provide a porous structure that is conducive to cell ingrowth and a preparation method thereof, and to adaptively generate a porous structure that matches the target prosthesis to promote cell ingrowth.

[0006] In a first aspect, the present application provides a method for preparing a porous structure that is conducive to cell ingrowth, the method comprising the following steps:

[0007] obtaining a three-dimensional model of a target prosthesis;

[0008] generating a 3D printing model based on the three-dimensional model;

[0009] Performing 3D printing according to the 3D printing model using a pre-adjusted ink material to obtain the porous structure;

[0010] The step of generating a 3D printing model based on the three-dimensional model includes:

[0011] Randomly generating a three-dimensional scatter plot with decreasing density from inside to outside based on the centroid of the three-dimensional model;

[0012] Slicing the three-dimensional model in layers according to the printing thickness to obtain multiple segmentation layers;

[0013] Projecting the scattered points in the three-dimensional scatter plot onto the segmentation layer with the smallest distance therefrom;

[0014] A corresponding Thiessen polygon graph is generated according to the projected scattered points in each segmented layer, and the edges of all Thiessen polygon graphs are used as printing paths to form a 3D printing model.

[0015] The preparation method of the porous structure that is conducive to cell growth in the present application generates a sparse three-dimensional scatter plot from the inside to the outside according to the centroid of the three-dimensional model, and establishes a 3D printing model based on this, so that each level structure of the 3D printing model has pores of different shapes, so that the porous structure prepared by 3D printing has pores of different shapes and the pores are gradually larger from the inside to the outside, which conforms to the structural characteristics of the human tissue / bone and is conducive to cell growth.

[0016] The method for preparing a porous structure that is conducive to cell ingrowth, wherein the pre-adjusted ink material includes a frame ink material, and the frame ink material is used to form the frame of the porous structure during the 3D printing process;

[0017] The frame ink material includes a first ink material and a second ink material;

[0018] The first ink material is obtained by mixing 50-60% by mass of PCL, 0.1-2% by mass of cell growth factor, 0.1-0.4% by mass of anti-inflammatory and hemostatic drugs, and the balance of deionized water;

[0019] The second ink material is obtained by mixing 50-60% by mass of PGA, 1-5% by mass of collagen, and the remainder of deionized water.

[0020] The method of the present application utilizes a first ink material and a second ink material to alternately print layers to prepare a framework, so that the porous structure has excellent biocompatibility, biodegradability, and bioactivity, which can effectively meet the controllable degradation characteristics in the body and the need to supply nutrients and metabolic channels for cell growth. It can not only promote cell growth and proliferation, but also accelerate coagulation.

[0021] The method for preparing a porous structure that is conducive to cell ingrowth, wherein the pre-adjusted ink material further includes a filling ink material, and the filling ink material is used to fill the frame during the 3D printing process;

[0022] The filling ink material includes agarose hydrogel and active powder uniformly mixed in the agarose hydrogel.

[0023] In the method for preparing the porous structure that is conducive to cell growth, the frame is generated based on high-temperature printing, and the filling ink material is injected into the frame based on low-temperature printing.

[0024] The method for preparing the porous structure that is conducive to cell ingrowth, wherein the method further comprises the following steps:

[0025] Cooling the porous structure to below -15°C to condense water in the porous structure into ice;

[0026] The porous structure is rapidly heated to above 100° C. to remove moisture.

[0027] In the method for preparing a porous structure that is conducive to cell ingrowth, the step of obtaining a three-dimensional model of the target prosthesis includes:

[0028] Acquire a preliminary model based on the shape of the target prosthesis, wherein the preliminary model is composed of triangular facets;

[0029] reconstructing the preliminary model based on a preset surface library to obtain a reconstructed model;

[0030] The intersection of the curved surfaces in the reconstructed model is smoothed to generate the three-dimensional model.

[0031] In the method for preparing a porous structure that is conducive to cell ingrowth, the step of reconstructing the preliminary model based on a preset surface library to obtain a reconstructed model includes:

[0032] Segmenting the preliminary model based on a cube of a preset size to obtain a plurality of segmented blocks including local surfaces of the preliminary model;

[0033] Based on feature matching, a surface in the surface library is called to replace the local surface on each segmentation block, and the reconstructed model is generated based on the segmentation blocks after replacement.

[0034] In the method for preparing a porous structure that is conducive to cell ingrowth, the step of obtaining a three-dimensional model of the target prosthesis further comprises:

[0035] The three-dimensional model is verified based on an intersection-over-union ratio between the three-dimensional model and a preliminary model.

[0036] The method for preparing a porous structure that is conducive to cell ingrowth, wherein the step of generating a 3D printing model based on the three-dimensional model further comprises:

[0037] Obtaining a pore size range of the 3D printed model according to the printing path and the printing pin diameter;

[0038] When the pore size interval exceeds a preset range, the dispersion change gradient and the initial dispersion density of the three-dimensional scatter plot are adjusted to adjust the pore size interval to within the preset range.

[0039] In a second aspect, the present application further provides a porous structure that facilitates cell ingrowth, and the porous structure is prepared based on the preparation method of the porous structure that facilitates cell ingrowth as provided in the first aspect.

[0040] The porous structure that is conducive to cell growth in the present application is made by generating a sparse three-dimensional scatter plot from the inside to the outside based on the centroid of the three-dimensional model, and establishing a 3D printing model based on the three-dimensional scatter plot for 3D printing. The porous structure has pores of different shapes and gradually increasing diameters from the inside to the outside, which conforms to the structural characteristics of human tissue / bone and is conducive to cell growth.

[0041] From the above, it can be seen that the present application provides a porous structure that is conducive to cell growth and a preparation method thereof, wherein the preparation method generates a sparse three-dimensional scatter plot from the inside to the outside according to the centroid of the three-dimensional model, and establishes a 3D printing model based on this, so that each level structure of the 3D printing model has pores of different shapes, so that the porous structure prepared by 3D printing has pores of different shapes and the pores are gradually larger from the inside to the outside, which conforms to the structural characteristics of the human tissue / bone and is conducive to cell growth. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 Flowchart of a method for preparing a porous structure that is conducive to cell ingrowth provided in an embodiment of the present application. DETAILED DESCRIPTION

[0043] The technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all of the embodiments. The components of the embodiments of the present application generally described and shown in the drawings here can be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of the present application provided in the drawings is not intended to limit the scope of the application for protection, but merely represents the selected embodiments of the present application. Based on the embodiments of the present application, all other embodiments obtained by those skilled in the art without making creative work fall within the scope of protection of the present application.

[0044] It should be noted that similar reference numerals and letters represent similar items in the following drawings. Therefore, once an item is defined in one drawing, it does not need to be further defined or explained in subsequent drawings. At the same time, in the description of this application, the terms "first", "second", etc. are only used to distinguish the description and should not be understood as indicating or implying relative importance.

[0045] First, please refer to Figure 1 Some embodiments of the present application provide a method for preparing a porous structure that is conducive to cell ingrowth, the method comprising the following steps:

[0046] S1. Obtain a three-dimensional model of the target prosthesis;

[0047] S2, generating a 3D printing model based on the three-dimensional model;

[0048] S3, performing 3D printing according to the 3D printing model using pre-adjusted ink materials to obtain a porous structure;

[0049] The steps of generating a 3D printing model based on the three-dimensional model include:

[0050] S21. Randomly generate a three-dimensional scatter plot with decreasing density from the inside to the outside based on the centroid of the three-dimensional model;

[0051] S22, slicing the three-dimensional model according to the printing thickness to obtain multiple segmentation layers;

[0052] S23, projecting the scattered points in the three-dimensional scatter plot onto the segmentation layer with the smallest distance therefrom;

[0053] S24. Generate a corresponding Thiessen polygon graph according to the projected scattered points in each segmentation layer, and use the edges of all Thiessen polygon graphs as printing paths to form a 3D printing model.

[0054] Specifically, the target prosthesis is a local biological structure of an object to be repaired or a missing object in the human body or a preset biological scaffold, such as cartilage tissue, biological scaffold, etc.; the target prosthesis can be a scanning result obtained based on the real image or multi-angle image data of the corresponding local biological structure.

[0055] More specifically, the three-dimensional model is a digital entity model constructed for the target prosthesis.

[0056] More specifically, a 3D printing model is a digital model constructed for three-dimensional model conversion that complies with the usage rules of corresponding 3D printing equipment and software.

[0057] More specifically, in general, for a target prosthesis with a large difference in density distribution, the three-dimensional model can determine the center of mass position based on the density distribution of the target prosthesis. For a target prosthesis with a small difference in density distribution, the three-dimensional model can be regarded as a solid model with uniform density, so the center of mass of the three-dimensional model is located at the geometric center of the model shape; the center of mass reflects the mass concentration area of ​​the target prosthesis. In general, the tissue density or bone density in the mass concentration area of ​​the target prosthesis is greater than that in the remaining areas. Therefore, the 3D printed model generally needs to design a material with a larger density distribution in the corresponding mass concentration area (generally manifested as a smaller number of pores or a smaller pore diameter); in the application embodiment, steps S21-step S24 adaptively generate a printing path with a gradually decreasing density from the inside to the outside according to the center of mass position of the three-dimensional model, so that the 3D printed model has pores with increasing diameter from the inside to the outside, which meets the structural requirements of the target prosthesis.

[0058] More specifically, step S21 preferably generates three-dimensional scattered points by all-around dispersion with the centroid of the three-dimensional model as the center according to a preset dispersion change gradient and initial dispersion density to form a spherical initial three-dimensional scatter plot, and then removes the scattered points outside the three-dimensional model in the initial three-dimensional scatter plot to generate a three-dimensional scatter plot, which has scattered points that are gradually sparsely dispersed from the centroid of the three-dimensional model to the surface.

[0059] More specifically, the 3D printing technology of the prior art is generally performed by printing layer by layer, and for this purpose, it is necessary to construct a printing path for each layer; the preparation method of the embodiment of the present application uses steps S22-step S24 to automatically establish interconnected and morphologically different layer structures, so that different layer structures have different printing paths so that the finally obtained porous structure has pores with different distribution shapes at different layers to simulate the structural characteristics of human tissue / bone; wherein, step S22 segments the three-dimensional model according to the printing thickness of each layer of the 3D printing device (generally determined by the printing diameter of the printing needle), so as to use the segmented layer obtained by segmentation as the printing path The segmentation layer is a segmentation interface without thickness. The scattered points in the three-dimensional scatter plot are scattered between each segmentation layer and each segmentation layer. Therefore, it is necessary to use step S23 to assign all scattered points in the three-dimensional model to the appropriate segmentation layer according to the distance relationship between the scattered points and the segmentation layer. The method of the embodiment of the present application preferably projects each scattered point on the segmentation layer with the smallest distance thereto by projection, so that the segmentation layer completely divides all scattered points. Since the three-dimensional scatter plot has the characteristic of sparseness from the inside to the outside, the projected scattered points in each segmentation layer also have the characteristic of sparseness from the inside to the outside; the Thiessen polygon in step S24 The graph is also called the Voronoi diagram. The Voronoi diagram (Voronoi diagram) is a means of partitioning a space plane based on Thiessen polygons. Thiessen polygons are a set of continuous polygons composed of perpendicular bisectors of line segments connecting two adjacent points. The distance from any point in a Thiessen polygon to the Voronoi points constituting the polygon is less than the distance to the Voronoi points of other polygons. Step S24 uses the scattered points projected in the segmentation layer as Voronoi points to generate a Delaunay triangulation, and then generates Thiessen polygons based on the Delaunay triangulation to obtain a Thiessen polygon graph. Since the scattered points projected in each segmentation layer also have a sparse distribution from the inside to the outside, Characteristics, so the Thiessen polygons in each Thiessen polygon diagram also have the characteristics of getting larger from the inside to the outside, and each Thiessen polygon has a different shape, which is consistent with the structural characteristics of the human tissue / bone. Subsequently, step S24 uses these Thiessen polygons to establish a printing path to gradually determine the interlayer structure of the 3D printed model, so that different layers of the 3D printed model have pores with different shapes and pores with diameters that gradually increase from the inside to the outside, so that the porous structure generated by printing based on the 3D printed model in step S3 has pores with different shapes and pores with diameters that gradually increase from the inside to the outside, which is consistent with the structural characteristics of the human tissue / bone and is conducive to cell growth.

[0060] The method for preparing a porous structure that is conducive to cell growth in an embodiment of the present application generates a sparse three-dimensional scatter plot from the inside to the outside based on the centroid of the three-dimensional model, and establishes a 3D printing model based on this, so that each level structure of the 3D printing model has pores of different shapes, so that the porous structure prepared by 3D printing has pores of different shapes and the diameter gradually increases from the inside to the outside, which conforms to the structural characteristics of the human tissue / bone and is conducive to cell growth.

[0061] In some preferred embodiments, the pre-adjusted ink material includes a frame ink material, which is used to form a frame of a porous structure during the 3D printing process;

[0062] The frame ink material includes a first ink material and a second ink material;

[0063] The first ink material is obtained by mixing 50-60% by mass of PCL (polycaprolactone), 0.1-2% by mass of cell growth factor, 0.1-0.4% by mass of anti-inflammatory and hemostatic drugs, and the balance of deionized water;

[0064] The second ink material is obtained by mixing 50-60% by mass of PGA (polyglycolide), 1-5% by mass of collagen, and the remainder of deionized water.

[0065] Specifically, the frame can be regarded as the above-mentioned porous structure itself, or as the matrix of the above-mentioned porous structure, which is formed by printing layer by layer along the printing path of the 3D printing model using the frame ink, and has pores consistent with the 3D printing model; wherein, the first ink material and the second ink material are preferably in a gel state before printing.

[0066] More specifically, the above-mentioned porous structure is generally used for cell culture or implantation into the human body. It needs to have certain controllable degradation characteristics in the body and the characteristics of supplying nutrients and metabolic channels for cell growth. The pores in the porous structure meet the latter requirement, while the former requirement requires the preparation of suitable 3D printing ink for frame printing.

[0067] More specifically, the method of the embodiment of the present application uses a first ink material and a second ink material to prepare a frame. The frame can be printed by mixing the two ink materials, or the frame can be printed by partitioning the two ink materials, or the two ink materials can be used alternately to print different level structures. In the embodiment of the present application, it is preferred to alternately use the first ink material and the second ink material to print different level structures to obtain a frame, which is equivalent to printing two levels with two ink materials as composite material levels, so that the porous structure can establish an organizational structure with different physical and chemical properties according to usage requirements.

[0068] More specifically, the cell growth factor mixed in the first ink material is a protein molecule that can promote the proliferation of various types of cells and is used for cell chemotaxis, proliferation and reconstruction; cell growth factors include basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor, neurotrophic factor, transforming growth factor, keratinocyte growth factor, platelet-derived growth factor, etc., which can be selected according to the actual object of the target prosthesis; the anti-inflammatory and hemostatic drugs mixed in the first ink material have the effect of accelerating coagulation.

[0069] More specifically, PGA (polyglycolic acid) is a simple polyester with excellent biodegradability and biocompatibility. Its final degradation products are carbon dioxide and water, which are excreted from the body through normal metabolism. Collagen is a protein with a three-dimensional helical structure that is widely present in the connective tissue of animals and has good biocompatibility, biodegradability and bioactivity. The method of the embodiment of the present application mixes collagen with PGA to prepare a second ink material, so that the second ink material is in a gel-like state with PGA as the matrix and evenly covered with collagen particles, effectively improving the biocompatibility of the framework, so that the framework can increase the biological activity of cells in contact with it or cells inoculated thereon, thereby promoting the corresponding cell growth and proliferation.

[0070] More specifically, the method of the embodiment of the present application utilizes a first ink material and a second ink material to alternately print layers to prepare a framework, so that the porous structure has excellent biocompatibility, biodegradability and bioactivity, which can effectively meet the controllable degradation characteristics in the body and the need to supply nutrients and metabolic channels for cell growth. It can not only promote cell growth and proliferation, but also accelerate coagulation.

[0071] In some preferred embodiments, the pre-adjusted ink material further includes a filling ink material, and the filling ink material is used to fill the frame during the 3D printing process;

[0072] The filling ink material includes agarose hydrogel and active powder uniformly mixed in the agarose hydrogel.

[0073] Specifically, in the embodiment of the present application, the filling ink material is preferably printed and filled in each pore at each level of the frame, so that there is enough active material in the pore to activate cells to promote cell growth and proliferation.

[0074] More specifically, the active powder includes one or more of recombinant protein freeze-dried powder, hydroxyapatite, tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, calcium oxide, calcium silicate, calcium sulfate, calcium carbonate, strontium carbonate, strontium phosphate, sodium phosphate, magnesium phosphate, magnesium oxide, silicon oxide, zinc phosphate, zinc oxide, active glass, and metallic magnesium powder.

[0075] More specifically, in the embodiment of the present application, the filling ink material preferably includes recombinant protein lyophilized powder and active glass mixed in agarose hydrogel, which can promote the growth of soft tissue cells.

[0076] In some preferred embodiments, the frame is generated based on high-temperature printing, and the filling ink material is injected into the frame based on low-temperature printing.

[0077] Specifically, high-temperature printing places the corresponding frame ink material under high-temperature conditions for mixing, and then uses the corresponding printing needle for extrusion printing. In the embodiment of the present application, it is preferred to heat the corresponding frame ink material for 5-20 minutes in an environment of 125-175°C, and then adjust the temperature according to the working requirements of the corresponding 3D printing equipment for printing to generate a frame.

[0078] More specifically, low-temperature printing mixes the corresponding filling ink materials at room temperature or low temperature, and then uses the corresponding printing needle to extrude and print. In the embodiment of the present application, it is preferred to mix the filling ink materials in an environment of 10-30°C, and then adjust the temperature according to the working requirements of the corresponding 3D printing equipment to print and generate a frame.

[0079] More specifically, the method of the embodiment of the present application preferably uses high-temperature printing and low-temperature printing alternately, that is, after completing a layer structure by high-temperature printing, low-temperature printing is used to print and inject filling ink material into the pores within the corresponding layer structure to ensure that the material is fully filled while quickly cooling the high-temperature printed layer structure to achieve initial solidification.

[0080] In some preferred embodiments, the method further comprises the following steps:

[0081] S4, cooling the porous structure to below -15°C, so that the water in the porous structure condenses into ice;

[0082] S5. Rapidly heating the porous structure to above 100° C. to remove moisture.

[0083] Specifically, in order to fix the porous structure and generate more pores to promote cell growth, in the embodiment of the present application, it is also necessary to remove the moisture evenly dispersed in the material under the premise that the above-mentioned porous structure is finalized to form more evenly distributed small pores. The method of the embodiment of the present application can conveniently achieve the above purpose by executing steps S4-step S5.

[0084] More specifically, steps S4 to S5 are preferably performed by controlling the temperature change in a temperature control box; wherein, the cooling process of step S4 is performed by slow cooling (generally cooling to the target lowest temperature for 12-24 hours for slow cooling), and the slowly cooled water condenses into ice and expands to form larger pores inside the porous structure. The frame prepared with the first ink material and the second ink material has a certain elasticity and can maintain structural integrity without collapse or cracks during the condensation of water; the heating process of step S5 is performed by rapid heating (generally heating to the target highest temperature for rapid heating for 0.1-0.5 hours), and the condensed ink material will solidify again during the heating process, and the ice generated by the condensation in step S4 will melt into water and fall out of the solidified gel, so that the solidified gel structure will produce small pores due to the melting of ice into water, thereby making the porous structure of the embodiment of the present application produce more pores suitable for cell growth; it should be noted that the purpose of using rapid heating is to promote rapid solidification of the gel and prevent the gel from filling the small pores again.

[0085] More specifically, since the water is evenly dispersed in the corresponding material before executing step S4, and the condensed ice has the characteristic of uniform grains, the porous structure finally obtained not only has pores with gradually increasing diameters from the inside to the outside formed based on the printing path, but also has small pores evenly distributed throughout the porous structure, which is more human-friendly and effectively avoids stress shielding, and also forms a certain degree of rough surface to facilitate cell attachment and regeneration.

[0086] In some preferred embodiments, the step of obtaining a three-dimensional model of the target prosthesis includes:

[0087] S11. Acquire a preliminary model based on the shape of the target prosthesis, where the preliminary model is composed of triangular facets;

[0088] S12, reconstructing the preliminary model based on a preset surface library to obtain a reconstructed model;

[0089] S13. Smoothing the intersections of the curved surfaces in the reconstructed model to generate a three-dimensional model.

[0090] Specifically, step S11 can obtain an initial model based on physical scanning or automatic reconstruction based on multi-angle CT photos. The initial models generated by these methods generally have many burrs or cross-sections and cannot be used directly as models. Triangulation processing can obtain a preliminary model with a multi-planar structure. The preliminary model can be used as a 3D printing model, but the planar characteristics are not suitable for use as a biomaterial structure, so it needs to be combined with steps S12-step S13 for fine processing.

[0091] More specifically, the preset surface library has various types of surface structures, such as G-type surfaces (G0, G1, G2, G3, G4), P-type surfaces and R-type surfaces. Step S12 can be to split the surface of the preliminary model into regions to perform surface pairing to reconstruct the surfaces of the preliminary model to obtain a reconstructed model, or it can be to replace the triangular facets with the corresponding surface based on the concave and convex features of each vertex of the triangular facets to obtain the reconstructed model.

[0092] More specifically, after step S12 obtains the reconstructed model based on the surface, there may be inappropriate sharp corners at the intersections between different surfaces. The connections that do not conform to the shape of biological tissue need to be smoothed to obtain a three-dimensional model that conforms to the target prosthesis shape and meets 3D printing requirements.

[0093] In some preferred embodiments, the step of reconstructing the preliminary model based on the preset surface library to obtain the reconstructed model includes:

[0094] S121, segmenting the preliminary model based on a cube of a preset size to obtain a plurality of segmentation blocks including local surfaces of the preliminary model;

[0095] S122 , calling a surface in a surface library based on feature matching to replace a local surface on each segmented block, and generating a reconstructed model based on the segmented blocks after the replacement process.

[0096] Specifically, in this embodiment, step S121 is equivalent to splitting the preliminary model using a multi-order Rubik's Cube structure to generate a plurality of segmentation blocks, and the segmentation blocks occupying the local surface data of the preliminary model are objects that need to reconstruct the surface.

[0097] It should be noted that the surfaces in the preset surface library are surfaces that can be matched with the internal space of the above-mentioned cube. Therefore, when the surfaces in the surface library are called in step S122, there is no need to scale, rotate, etc. the surfaces, thereby improving data matching efficiency.

[0098] More specifically, step S121-step S122 is equivalent to splitting the surface of the entire preliminary model into multiple feature blocks of similar spatial size, and then realizing modular reorganization through reconstruction of the feature blocks to obtain the reconstructed model, which effectively simplifies the reconstruction process of the reconstructed model. In the reconstruction process, the feature data of the triangular facets on each feature block can be replaced by the surface, effectively retaining the shape characteristics of each triangular facet.

[0099] More specifically, in the embodiment of the present application, step S122 preferably performs surface matching based on the spatial features of all vertices of all triangular facets on each segmentation block to obtain a surface that completely overlaps with these vertices or overlaps as much as possible to replace the local surface.

[0100] In some preferred embodiments, the step of obtaining a three-dimensional model of the target prosthesis further comprises:

[0101] S14. Verify the 3D model based on the intersection-and-union ratio between the 3D model and the preliminary model.

[0102] Specifically, the three-dimensional model automatically generated based on steps S12 and S13 may have a large error with the target prosthesis. Therefore, the method implemented in the present application needs to verify the structural accuracy of the three-dimensional model; in order to simplify the verification logic, the method of the embodiment of the present application uses the intersection-over-union ratio to verify the accuracy of the three-dimensional model, that is, by analyzing the overlap of the preliminary model and the three-dimensional model with a specific coordinate center, the correlation between the two is determined as a verification indicator of structural accuracy, which has the characteristics of rapid analysis and accurate judgment.

[0103] More specifically, in the embodiment of the present application, when the intersection-union ratio is 0.95-1.05, it indicates that the three-dimensional model verification has passed. When the three-dimensional model verification fails, the method of the embodiment of the present application needs to return to step S11 or step S12 or step S13 to generate a new three-dimensional model.

[0104] In some preferred embodiments, the step of generating a 3D printing model based on the three-dimensional model further includes:

[0105] S25, obtaining a pore size range of the 3D printed model according to the printing path and the printing needle diameter;

[0106] S26. When the pore size interval exceeds the preset range, adjusting the dispersion change gradient and the initial dispersion density of the three-dimensional scatter plot to adjust the pore size interval to within the preset range.

[0107] Specifically, it can be seen from the above content that the porosity and pore size of the porous structure are determined based on the printing needle diameter and the Thiessen polygon diagram. Therefore, in the model design stage, when the design elements such as porosity and pore size do not meet the expected design requirements, they can be reconstructed by changing the design parameters of the Thiessen polygon diagram. The method of the embodiment of the present application can change the distribution morphology of the Thiessen polygon diagram by changing the dispersion change gradient and the initial dispersion density of the three-dimensional scatter diagram, thereby realizing rapid adjustment of the 3D printing model to conveniently construct and print a porous structure with appropriate porosity and pore size; wherein the initial dispersion density is related to the minimum pore diameter, the dispersion change gradient is related to the change of the pore diameter from the inside to the outside, and the initial dispersion density and the dispersion change gradient determine the maximum pore diameter and porosity.

[0108] In a second aspect, some embodiments of the present application further provide a porous structure that facilitates cell ingrowth, and the porous structure is prepared based on the preparation method of the porous structure that facilitates cell ingrowth as provided in the first aspect.

[0109] The porous structure that is conducive to cell growth in the embodiment of the present application is made by generating a sparse three-dimensional scatter plot from the inside to the outside based on the centroid of the three-dimensional model, and establishing a 3D printing model based on the three-dimensional scatter plot for 3D printing. The porous structure has pores of different shapes and gradually increasing diameters from the inside to the outside, which conforms to the structural characteristics of human tissue / bone and is conducive to cell growth.

[0110] In summary, the embodiments of the present application provide a porous structure that is conducive to cell growth and a preparation method thereof, wherein the preparation method generates a sparse three-dimensional scatter plot from the inside to the outside according to the centroid of the three-dimensional model, and establishes a 3D printing model based on this, so that each level structure of the 3D printing model has pores of different shapes, so that the porous structure prepared by 3D printing has pores of different shapes and the pores are gradually larger from the inside to the outside, which conforms to the structural characteristics of the human tissue / bone and is conducive to cell growth.

[0111] In this document, relational terms such as first and second, etc. are used merely to distinguish one entity or operation from another entity or operation, but do not necessarily require or imply any actual relationship or order between these entities or operations.

[0112] The above description is merely an embodiment of the present application and is not intended to limit the scope of protection of the present application. For those skilled in the art, various modifications and variations of the present application are possible. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present application shall be included in the scope of protection of the present application.

Claims

1. A method for preparing a porous structure that is conducive to cell ingrowth, characterized in that: The method comprises the following steps: obtaining a three-dimensional model of a target prosthesis; generating a 3D printing model based on the three-dimensional model; Performing 3D printing according to the 3D printing model using a pre-adjusted ink material to obtain the porous structure; The step of generating a 3D printing model based on the three-dimensional model includes: Randomly generating a three-dimensional scatter plot with decreasing density from inside to outside based on the centroid of the three-dimensional model; Slicing the three-dimensional model in layers according to the printing thickness to obtain multiple segmentation layers; Projecting the scattered points in the three-dimensional scatter plot onto the segmentation layer with the smallest distance therefrom; Generate a corresponding Thiessen polygon graph according to the projected scattered points in each segmented layer, and use the edges of all Thiessen polygon graphs as printing paths to form a 3D printing model; Obtaining a pore size range of the 3D printed model according to the printing path and the printing pin diameter; When the pore size interval exceeds a preset range, adjusting the dispersion change gradient and the initial dispersion density of the three-dimensional scatter plot to adjust the pore size interval to within the preset range; The step of obtaining a three-dimensional model of the target prosthesis comprises: Acquire a preliminary model based on the shape of the target prosthesis, wherein the preliminary model is composed of triangular facets; reconstructing the preliminary model based on a preset surface library to obtain a reconstructed model; Smoothing the intersections of the curved surfaces in the reconstructed model to generate the three-dimensional model; The step of reconstructing the preliminary model based on the preset surface library to obtain a reconstructed model includes: Segmenting the preliminary model based on a cube of a preset size to obtain a plurality of segmented blocks including local surfaces of the preliminary model; Based on feature matching, a surface in the surface library is called to replace the local surface on each segmentation block, and the reconstructed model is generated based on the segmentation blocks after replacement.

2. The method for preparing a porous structure conducive to cell ingrowth according to claim 1, characterized in that: The pre-adjusted ink material includes a frame ink material, and the frame ink material is used to form the frame of the porous structure during the 3D printing process; The frame ink material includes a first ink material and a second ink material; The first ink material is obtained by mixing 50-60% by mass of PCL, 0.1-2% by mass of cell growth factor, 0.1-0.4% by mass of anti-inflammatory and hemostatic drugs, and the balance of deionized water; The second ink material is obtained by mixing 50-60% by mass of PGA, 1-5% by mass of collagen, and the remainder of deionized water.

3. The method for preparing a porous structure conducive to cell ingrowth according to claim 2, characterized in that: The pre-adjusted ink material further includes a filling ink material, and the filling ink material is used to be filled in the frame during the 3D printing process; The filling ink material includes agarose hydrogel and active powder uniformly mixed in the agarose hydrogel.

4. The method for preparing a porous structure conducive to cell ingrowth according to claim 3, characterized in that: The frame is generated based on high-temperature printing, and the filling ink material is injected into the frame based on low-temperature printing.

5. The method for preparing a porous structure conducive to cell ingrowth according to claim 3, characterized in that: The method further comprises the following steps: Cooling the porous structure to below -15°C to condense water in the porous structure into ice; The porous structure is rapidly heated to above 100° C. to remove moisture.

6. The method for preparing a porous structure conducive to cell ingrowth according to claim 1, characterized in that: The step of obtaining a three-dimensional model of the target prosthesis further comprises: The three-dimensional model is verified based on an intersection-over-union ratio between the three-dimensional model and a preliminary model.

7. A porous structure that facilitates cell ingrowth, characterized in that: It is prepared based on the preparation method of the porous structure that is conducive to cell growth as described in any one of claims 1 to 6.

Citation Information

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