Bone cartilage bionic gradient scaffold and integrated manufacturing method

Abstract

The present invention provides an integrated design and manufacturing technology for a bone cartilage biomimetic gradient scaffold. The invention includes a functionally graded integrated bone cartilage biomimetic gradient scaffold, a transition structure for achieving graded transition between hard bone and cartilage tissue, and a biomimetic cartilage formation and post-processing method. The integrated bone cartilage biomimetic gradient scaffold is a porous interconnected ceramic structure that can be manufactured through integrated additive manufacturing. The transition structure is a special structure for firmly connecting hard bone and cartilage. The biomimetic cartilage formation and post-processing method involves performing special treatment on the 3D-printed bone scaffold to form biomimetic cartilage, thereby improving the strength of the cartilage layer and preventing cartilage damage caused by joint friction. The bone cartilage biomimetic scaffold structure proposed by the present invention has effective functional grading to mimic natural bone cartilage tissue, which is beneficial for preventing stress shielding and can be manufactured in one piece using 3D additive manufacturing technology.

Description

Technical Field

[0001] The present invention relates to the field of bone defect repair, and in particular to an osteochondral bionic gradient scaffold and an integrated manufacturing method thereof. Background Art

[0002] A bone defect is a large gap formed by bone loss due to factors such as trauma, infection, and tumors. Although bone tissue has a strong regenerative capacity within a certain range, it becomes difficult to repair itself when the bone defect exceeds 30mm. Bone defects are clinically prevalent, with tens of millions of patients worldwide suffering from bone defects each year due to severe trauma, fractures with infection, improper post-fracture treatment, bone tumors, or other complications.

[0003] Bone defects are generally treated with surgery, and commonly used methods include autologous bone transplantation and artificial bone transplantation. As a common method for treating bone defects, autologous bone transplantation has the advantages of no rejection reaction, no pollution, low material cost, complete absorption, and the ability to induce bone reconstruction. However, it has some significant disadvantages. If the amount of bone taken is small, the bone harvesting site needs to be increased, the anesthesia and operation time are increased, the probability of complications is relatively high, and the bone harvesting site may be painful or uncomfortable for up to half a year or longer. In view of the limitations of autologous bone transplantation, considering the feasibility and optimization of artificial bone transplantation has become an important research direction.

[0004] Bone tissue engineering for artificial bone transplantation is currently a highly promising research area. Bone tissue engineering involves the in vitro culturing and expansion of isolated, autologous, high-density osteoblasts, bone marrow stromal stem cells, or chondrocytes, followed by their implantation on a natural or synthetic, biocompatible, and gradually degradable and absorbable cell scaffold, or extracellular matrix. This biomaterial scaffold provides a three-dimensional space for the cells to survive, facilitating their access to nutrients, gas exchange, and waste removal, allowing them to grow within the prefabricated three-dimensional scaffold. This cell hybrid is then implanted into the bone defect, where the implanted bone cells continue to proliferate as the biomaterial gradually degrades, ultimately repairing the bone tissue defect.

[0005] In bone tissue engineering, the design and manufacture of bone scaffolds has always been a challenge. Bone scaffolds must not only exhibit excellent biocompatibility to promote natural bone tissue growth, but also possess strength comparable to native bone tissue to prevent stress shielding. Good biocompatibility requires a substantial surface area, which can be achieved through a porous structure. Achieving strength comparable to native bone tissue requires a functional grading of the designed scaffold's strength.

[0006] Functional grading of bone scaffolds can be achieved by using structural transitions of the same material or by combining different materials. Currently, when creating functionally graded bone scaffolds using different materials, most methods involve manufacturing the different graded components separately and then assembling them. This method is not only complex but can also lead to insecure structural connections, potentially causing scaffold detachment. Summary of the Invention

[0007] The purpose of the present invention is to solve the deficiencies in the prior art and to provide a bone cartilage biomimetic gradient scaffold and an integrated manufacturing method thereof, which is simple to operate, has a firm structure, and is not easy to fall off.

[0008] In order to solve the above technical problems, the technical method adopted by the present invention is: comprising the following steps:

[0009] S1. Using 3D printing technology, print a hard bone scaffold similar to natural hard bone tissue, and print a cartilage mold scaffold on one side of the hard bone scaffold along the length of the hard bone scaffold;

[0010] S2. Immersing the cartilage mold scaffold into a polymer solution, allowing the polymer material to fully adhere to the cartilage mold scaffold and solidify to form a cartilage layer;

[0011] S3. Repeat step S2 multiple times to continuously increase the thickness of the cartilage layer until the desired thickness is achieved.

[0012] Furthermore, in step S1, a transition layer is 3D printed at the connection between the hard bone scaffold and the cartilage mold scaffold; the transition layer is a thin plate structure with a plurality of tapered holes; the tapered holes penetrate the transition layer;

[0013] In step S2, when the cartilage mold scaffold is immersed in the polymer solution, the transition layer is also immersed in the polymer solution; the polymer solution is filled into the conical hole and, after solidification, serves to connect the cartilage layer and the bone layer.

[0014] Furthermore, the transition layer includes an upper docking surface connected to the cartilage mold support and a lower docking surface connected to the hard bone support; the bottom surface of the tapered hole faces the lower bottom surface.

[0015] Furthermore, the tapered hole has an adjustable aperture, and a serrated protrusion is provided on the side surface of the inner wall of the tapered hole.

[0016] Furthermore, after step S3, the cartilage layer is compressed, and the difference in compressibility between polymer and ceramic is utilized to crush the cartilage mold scaffold without damaging the cartilage layer.

[0017] Furthermore, the hard bone scaffold is an internally interconnected porous ceramic structure.

[0018] Furthermore, the cartilage mold scaffold is an internally interconnected porous ceramic structure;

[0019] The thickness of the cartilage mold scaffold is smaller than that of the hard bone scaffold; the porosity of the cartilage mold scaffold is higher than that of the hard bone scaffold.

[0020] Furthermore, the permeability of the transition layer is changed by adjusting the opening size of the tapered hole, thereby controlling the material exchange between the cartilage layer and the hard bone layer.

[0021] The present invention also discloses an osteocartilage biomimetic gradient scaffold, which is prepared according to the above-mentioned integrated manufacturing method of the osteocartilage biomimetic gradient scaffold.

[0022] Beneficial effects:

[0023] Compared to existing technologies, the present invention utilizes 3D printing technology to print a single bone-cartilage biomimetic gradient scaffold on a single machine, resolving a number of issues encountered in previously proposed methods. The present invention's manufacturing and processing of the bone scaffold allows for cross-mechanical biomimetic effects on both cartilage and bone. This improves the hardness of the cartilage surface while maintaining the structural strength of the cartilage, effectively preventing cartilage damage caused by friction between the biomimetic cartilage structure and natural cartilage tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Schematic diagram of the overall structure of the osteochondral bionic gradient scaffold of the present invention;

[0025] Figure 2 Schematic diagram of the specific structure of the transition layer of the osteochondral biomimetic gradient scaffold of the present invention;

[0026] Figure 3 is a three-dimensional schematic diagram of the transition layer in the present invention;

[0027] Figure 4 This is a schematic diagram of the osteochondral bionic gradient scaffold in the present invention in use;

[0028] Figure 5 Schematic diagram of the manufacturing process of the osteochondral biomimetic gradient scaffold of the present invention;

[0029] Figure 6 This is a schematic diagram of the structure of the cartilage mold scaffold of the present invention when it is not broken;

[0030] Figure 7 This is a schematic diagram of the structure of the cartilage mold scaffold after it is broken in the present invention.

[0031] Among them, 1-cartilage layer, 2-bone layer, 3-transition layer, 4-conical hole, 5-cartilage mold scaffold, 6-bone scaffold, 7-polymer substance, 8-polymer solution, 9-fragmented cartilage mold scaffold, 10-bone tissue defect site. DETAILED DESCRIPTION

[0032] The present invention will be described in further detail below with reference to the accompanying drawings and specific implementation methods.

[0033] like Figure 1-4 As shown in FIG. 1 , the bone cartilage biomimetic gradient scaffold of the present invention is used to fill the bone tissue defect 10. The structure is mainly composed of a cartilage layer 1 and a bone layer 2. The cartilage layer 1 and the bone layer 2 can be made of the same or different materials to perform functional grading. The biomimetic cartilage and bone layers are connected and interlocked through a transition structure. The structure is as follows: Figure 2 The transition structure 3 shown in FIG. 3 has a three-dimensional schematic diagram as shown in FIG. Figure 3 shown.

[0034] like Figure 2 As shown, the transition layer 3 is directly connected to the cartilage mold scaffold 5 and the hard bone scaffold 6 through integrated 3D printing, including an upper bottom surface 41 connected to the cartilage mold scaffold 5 and a lower bottom surface 42 connected to the hard bone scaffold 6. The bottom surface of the tapered hole 4 is located on the lower bottom surface 42. The transition layer 3 has a connected tapered hole 4; the side surface 43 of the inner wall of the tapered hole 4 is provided with a serrated protrusion. A solidified polymer material 7 is placed inside the tapered hole 4.

[0035] The polymer solution may be hydrogel or polycaprolactone.

[0036] If the cartilage layer 1 and the hard bone layer 2 are made of different materials, the scaffold must be printed using a multi-material 3D printer. When printing reaches the transition layer 3, the two materials are alternately printed to complete the transition. This transition does not require consideration of the viscosity between the two materials, as the cartilage layer 1 structure only serves as the cartilage mold scaffold during biomimetic cartilage fabrication. The transition layer 3 only truly serves as the transition between soft and hard bone after the biomimetic cartilage is formed.

[0037] The biomimetic cartilage layer is formed by adhering two different materials. The dark, porous structure in the image is a cartilage mold scaffold created using 3D printing. It serves as a base for the polymer material to adhere to during the biomimetic cartilage manufacturing process. The light, translucent layer on the scaffold serves as the polymer material for the main biomimetic cartilage structure, fulfilling its primary function.

[0038] like Figure 5The integrated manufacturing method of the bone-cartilage biomimetic gradient scaffold of the present invention requires the preparation of an integrated printed bone scaffold and a specific polymer attachment solution before processing. Then, the end of the bionic bone scaffold where the cartilage layer is located is immersed in the polymer solution for attachment and curing treatment. After repeated multiple times, the thickness of the cartilage layer is greatly improved. The main component material of the bionic cartilage becomes polymer, and the ceramic cartilage mold scaffold only accounts for a small part.

[0039] The specific steps include:

[0040] S1. Use 3D printing technology to print a hard bone scaffold 6 similar to natural hard bone tissue, and print a cartilage mold scaffold 5 on one side of the hard bone scaffold 6 along the length direction of the hard bone scaffold 6; wherein, a transition layer 3 is 3D printed at the connection between the hard bone scaffold 6 and the cartilage mold scaffold 5; the transition layer 3 is a thin plate structure with connected conical holes 4; wherein, the permeability between the cartilage layer 1 and the hard bone layer 2 can be adjusted by setting the aperture size of the conical hole 4; by adjusting the opening size of the conical hole 4, the permeability of the transition layer is changed, thereby controlling the material exchange between the cartilage layer and the hard bone layer, promoting the transmission of nutrients between the soft and hard bone layers and preventing cell migration.

[0041] S2. The cartilage mold scaffold 5 and the transition layer are immersed in the polymer solution 8; the polymer solution 8 is fully attached to the cartilage mold scaffold 5 and the tapered hole 4, solidifying to form a cartilage layer 1 and the transition layer 3;

[0042] S3. Repeat step S2 multiple times to continuously increase the thickness of the cartilage layer 1 until the desired thickness is achieved.

[0043] S4. The cartilage layer 1 is compressed, and the difference in compressibility between polymer and ceramic is utilized to crush the cartilage mold scaffold 5 without destroying the cartilage layer 1. The impact of the fragments remaining in the bionic cartilage on the bionic cartilage is significantly reduced.

[0044] like Figure 5-7 The schematic diagram of the bone cartilage mold scaffold 5 before and after crushing is shown. During the processing, the bone cartilage scaffold needs to be fixed and pressure is applied to one side of the cartilage layer. Since the polymer material has better compressibility than ceramics, the bone cartilage mold scaffold 5 will reach the fracture strength first and be completely crushed and destroyed to form a broken cartilage mold scaffold 9. The broken cartilage mold scaffold 9 remains in the bionic cartilage, but no longer provides support. The mechanical properties of the bionic cartilage will be determined by the polymer material. This treatment can effectively reduce the adverse effects of the cartilage mold scaffold on the mechanical properties of the bionic cartilage.

[0045] The basic principles, main features, and advantages of the present invention are shown and described above. Those skilled in the art should understand that the present invention is not limited to the foregoing embodiments. The foregoing embodiments and descriptions are merely illustrative of the principles of the present invention. Various changes and modifications may be made to the present invention without departing from the spirit and scope of the present invention. Such changes and modifications are intended to fall within the scope of the present invention. The scope of protection claimed in the present invention is defined by the appended claims and their equivalents.

Claims

1. An integrated manufacturing method for a bone cartilage biomimetic gradient scaffold, characterized in that: The steps include: Step S1. Using 3D printing technology, a hard bone scaffold (6) similar to natural hard bone tissue is printed, and a cartilage mold scaffold (5) is printed on one side of the hard bone scaffold (6) along the length direction of the hard bone scaffold (6); the hard bone scaffold (6) is an internally interconnected porous ceramic structure; the cartilage mold scaffold (5) is an internally interconnected porous ceramic structure; The thickness of the cartilage mold scaffold (5) is smaller than that of the hard bone scaffold (6); the porosity of the cartilage mold scaffold (5) is higher than that of the hard bone scaffold (6); Step S2: immersing the cartilage mold scaffold (5) in a polymer solution, allowing the polymer material to fully adhere to the cartilage mold scaffold (5) and solidify to form a cartilage layer (1); Step S3. Repeating step S2 multiple times to continuously increase the thickness of the cartilage layer (1) until the desired thickness is obtained; Step S4: compressing the cartilage layer (1) and crushing the cartilage mold scaffold (5) without destroying the cartilage layer (1) by utilizing the difference in compressibility between polymer and ceramic. The crushed cartilage mold scaffold remains in the cartilage layer and no longer provides support.

2. The integrated manufacturing method of the osteochondral biomimetic gradient scaffold according to claim 1, characterized in that: In step S1, a transition layer (3) is 3D printed at the connection between the hard bone scaffold (6) and the cartilage mold scaffold (5); the transition layer (3) is a thin plate structure having a plurality of tapered holes (4); the tapered holes (4) penetrate the transition layer (3); In step S2, when the cartilage mold scaffold (5) is immersed in a polymer solution, the transition layer is also immersed in the polymer solution; the polymer solution is filled into the conical hole (4), and after solidification, it plays a role in connecting the cartilage layer and the hard bone layer.

3. The integrated manufacturing method of the osteochondral biomimetic gradient scaffold according to claim 2, characterized in that: The transition layer (3) comprises an upper docking surface (41) connected to the cartilage mold support (5) and a lower docking surface (42) connected to the hard bone support (6); the bottom surface of the tapered hole (4) faces the lower docking surface (42).

4. The integrated manufacturing method of the osteochondral biomimetic gradient scaffold according to claim 3, characterized in that: A serrated protrusion is provided on the side surface (43) of the inner wall of the tapered hole (4).

5. The integrated manufacturing method of the osteochondral biomimetic gradient scaffold according to any one of claims 1 to 4, characterized in that: The permeability of the transition layer is changed by adjusting the opening size of the conical hole (4), thereby controlling the material exchange between the cartilage layer and the hard bone layer.

6. A bone cartilage biomimetic gradient scaffold, characterized by: The osteochondral biomimetic gradient scaffold is prepared according to the integrated manufacturing method of any one of claims 1-4.

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