Three-dimensional embedded cartilage and bone integrated repair material and preparation method thereof

Abstract

The invention provides a three-dimensional embedded cartilage and bone integrated repair material and a preparation method thereof, and belongs to the technical field of biomedical materials. The three-dimensional embedded cartilage and bone integrated repair material is formed by embedding two repair layers up and down, the upper layer is a cartilage layer, and the lower layer is a bone layer; the repairing material of the cartilage layer is polyurethane synthesized by taking soluble starch and polyethylene glycol 400 as soft segments and isophorone diisocyanate as a hard segment through reaction; the repairing material of the bone layer comprises an organic component and an inorganic component, the inorganic component adopts nano-hydroxyapatite, and the organic component adopts polyurethane with the same or different proportions for the cartilage layer. The polyurethane soft segment adopts natural renewable high polymer soluble starch, is wide in source and low in price, has a three-dimensional structure of a three-dimensional embedded cartilage and bone integrated repair material system, and can meet different requirements of bone and cartilage regeneration on a mechanical environment and a biological environment; the method has important research significance and potential application value for cartilage and bone tissue regeneration and repair.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a three-dimensional embedded cartilage and bone integrated repair material and a preparation method thereof. Background Art

[0002] Cartilage and bone injuries are common clinical conditions in orthopedics. They can be caused by a wide range of factors, including but not limited to trauma, osteoarthritis, osteochondritis, and osteomalacia, all of which can lead to damage or defects in cartilage and subchondral bone. Full-thickness articular cartilage damage can expose the underlying bone, leading to bone cystic degeneration and subsequent subchondral bone damage. Late-stage bone necrosis can lead to collapse of the articular surface, disrupting the articular cartilage structure. Therefore, regardless of whether the primary lesion is in the articular cartilage or bone, both bone and cartilage are damaged and destroyed in the later stages. Current treatments for combined cartilage and subchondral bone injuries are ineffective. Although natural bone tissue possesses the ability to regenerate and repair itself, excessive bone defects are unable to heal through self-repair, necessitating bone transplantation. Cartilage tissue has a very limited capacity for self-repair. Injuries near the synovium at the joint margin can be repaired through the proliferation of synovial cells, resulting in fibrocartilage. However, injuries elsewhere are nearly incapable of self-repair once damaged or missing, as mature chondrocytes lack the ability to proliferate and divide. Combining bone and cartilage tissue engineering to biomimetically construct a bone-cartilage double-layer scaffold to achieve simultaneous repair of cartilage and subchondral bone is a treatment method worth trying.

[0003] In recent years, researchers have used innovative biomaterials and advanced manufacturing technologies to construct high-performance bone-cartilage bilayer scaffolds to promote tissue regeneration and repair. However, despite significant progress, this field still faces a series of challenges, especially in the selection and preparation of materials: (1) High cost. Some high-performance biomaterials, such as ceramic materials, have high raw material costs, which limits their widespread clinical application; (2) Preparation complexity. The material processing process is complex and requires specific equipment and technology, which not only increases the manufacturing cost but also may affect the large-scale production of bone-cartilage bilayer scaffolds; (3) Pore structure regulation is difficult. The ideal bone-cartilage bilayer scaffold needs to have a precisely controlled pore structure to support cell migration, proliferation and differentiation. However, not all materials can easily achieve this requirement; (4) Insufficient mechanical properties. Bone tissue and cartilage tissue have different mechanical properties, requiring the scaffold to provide appropriate mechanical support between the two layers. However, some materials may not meet this requirement, resulting in the scaffold being unable to effectively support the surrounding tissue after implantation.

[0004] Therefore, it is of great significance to continue exploring new biomedical materials, especially those that are cost-effective, easy to process and can meet the mechanical performance requirements of bone-cartilage double-layer scaffolds. Summary of the Invention

[0005] In response to the deficiencies in the prior art, the present invention discloses a three-dimensional embedded cartilage and bone integrated repair material and a preparation method thereof, so as to solve the problems of high material cost, complex preparation, difficult to control pore structure and insufficient mechanical properties of the prior art bone-cartilage double-layer scaffold.

[0006] In order to achieve the above technical objectives, on the one hand, the present invention proposes a three-dimensional embedded cartilage and bone integrated repair material, which is composed of two repair layers embedded in an upper and lower manner, the upper layer is a cartilage layer, and the lower layer is a bone layer; the repair material of the cartilage layer adopts polyurethane synthesized by reacting soluble starch and polyethylene glycol 400 as soft segments and isophorone diisocyanate as a hard segment; the repair material of the bone layer includes organic components and inorganic components, the inorganic component adopts nano-hydroxyapatite, and the organic component adopts polyurethane in the same or different proportions as used for the cartilage layer.

[0007] The present invention simulates cartilage tissue and subchondral bone tissue based on components, structure and function, and integrates biomass-based polyurethane for cartilage repair (upper layer) and hydroxyapatite / biomass-based polyurethane composite material for bone repair (lower layer) into a three-dimensional inlaid bone and cartilage integrated repair material, which can simultaneously meet the repair and reconstruction of cartilage tissue and bone tissue.

[0008] Polyurethanes (PUs) are widely used in the biomedical field due to their excellent biocompatibility, superior mechanical properties, non-toxicity, and ease of processing. PUs are block polymers composed of soft and hard segments. During the manufacturing process, hydroxyl-containing soft segments chemically react with cyano-containing hard segments to form PUs. By selecting different soft and hard segment materials, or adjusting their ratio, PUs with varying physical and chemical properties can be produced. Therefore, the selection of raw materials is crucial in the preparation of PUs.

[0009] In order to solve the problem of repairing cartilage and bone damage in different layers, the present invention uses soluble starch and polyethylene glycol 400 as soft segments and isophorone diisocyanate as hard segments to design and develop a new biomass-based polyurethane, which is used to synthesize cartilage repair materials by biomimetic simulation of the network structure of cartilage tissue. Soluble starch, as one of the soft segment components, is a natural renewable polymer and contains a large number of hydroxyl groups. It has the advantages of wide sources, low price, and good biocompatibility. In the polyurethane of the present invention, the addition of soluble starch can increase the hydrophilicity and biodegradability of the material, while giving the polyurethane strength and toughness. Polyethylene glycol 400, as another soft segment component of the present invention, has good hydrophilicity and flexibility, which helps to form a polyurethane material that biomimetic simulation of the network structure of cartilage tissue. Its low molecular weight enables good segment mobility to be provided in the polyurethane, thereby giving the material good elasticity and recovery. Isophorone diisocyanate, as a hard segment component, is an aliphatic isocyanate that provides the strength and stability required for polyurethane while being biosafe compared to aromatic isocyanates. Isophorone diisocyanate is a commonly used diisocyanate. The isocyanate groups in its molecular structure can react with the hydroxyl groups in polyethylene glycol 400 and soluble starch to form a cross-linked structure of polyurethane.

[0010] The present invention utilizes the organic-inorganic composite characteristics of natural bone tissue and proposes the in-situ compounding of nanohydroxyapatite and a novel biomass-based polyurethane to prepare a bone repair material. Nanohydroxyapatite is a commonly used inorganic biomaterial with a chemical composition and microstructure similar to that of natural bone tissue. In-situ compounding of nanohydroxyapatite in a polyurethane matrix can simulate the organic-inorganic composite structure of natural bone tissue, thereby improving the material's bone bonding ability and mechanical properties. By compounding the novel biomass-based polyurethane designed and developed with isophorone diisocyanate as the hard segment and polyethylene glycol 400 and soluble starch as the soft segments with nanohydroxyapatite, a bone repair material with excellent mechanical properties and biocompatibility can be prepared. This material not only has good bone bonding ability, but also can promote cell adhesion and proliferation, thereby accelerating the repair and regeneration of bone tissue.

[0011] It should be noted that the mechanical properties of bone and cartilage are directly related to age, gender, and health status. Therefore, by using the same or different ratios of polyurethane in the bone and cartilage layers, the mechanical properties of the repair material can be adjusted. This allows for the production of personalized and differentiated repair materials based on clinical needs.

[0012] Furthermore, in the polyurethane, soluble starch accounts for 5-30% of the mass content of the soft segment, and polyethylene glycol 400 accounts for 70-95% of the mass content of the soft segment. In the embodiments of the present invention, by precisely controlling the ratio of soluble starch and polyethylene glycol 400 in the soft segment, the mechanical properties (compressive strength) and structural properties (porosity) of the material can be further optimized.

[0013] Furthermore, the molar ratio of the reactive groups -NCO and -OH in the polyurethane is 1:(1-1.3). Within this molar ratio range, the NCO groups and OH groups can undergo an effective cross-linking reaction to form a polyurethane network structure, preferably 1:1.1. In the polyurethane of the present invention, the soft segments of soluble starch and polyethylene glycol 400 contain -OH, and the hard segments of isophorone diisocyanate contain -NCO.

[0014] Furthermore, the bone repair material contains 5-15% nanohydroxyapatite by weight and 85-95% polyurethane by weight. In embodiments of the present invention, by adjusting the content of nanohydroxyapatite and polyurethane in the bone repair material, the mechanical properties (compressive strength) and structural properties (porosity) of the material can be further optimized, with a porosity of 80-86% and a compressive strength of 2-6 MPa.

[0015] On the other hand, the present invention also provides a method for preparing a three-dimensional inlaid cartilage and bone integrated repair material, comprising the following steps:

[0016] (1) Bone layer reaction section: Nano-hydroxyapatite, soluble starch, and polyethylene glycol 400 are mixed evenly, and then isophorone diisocyanate, a catalyst, and a chain extender are added and stirred at a certain temperature to mix evenly;

[0017] (2) Bone layer foaming stage: adding a foaming agent to the mixture of step (1) to obtain a bone layer repair material through foaming;

[0018] (3) Cartilage layer reaction section: soluble starch and polyethylene glycol 400 are mixed evenly, and then isophorone diisocyanate, catalyst, and chain extender are added and stirred at a certain temperature until evenly mixed;

[0019] (4) Cartilage layer foaming section and double-layer mosaic: Add a foaming agent to the mixture of step (3), mix evenly, and pour into the mold with the bone layer repair material in step (2) as the base, and obtain a three-dimensional embedded cartilage and bone integrated repair material through foaming.

[0020] The method for preparing a three-dimensional intercalated cartilage and bone integrated repair material includes a reaction stage and a foaming stage, both of which are continuous reactions. A simple and easy secondary foaming molding method is used to intercalate a biomass-based polyurethane (upper layer) for cartilage repair and a hydroxyapatite / biomass-based polyurethane composite material (lower layer) for bone repair to form the three-dimensional intercalated bone and cartilage integrated repair material. The method for preparing the three-dimensional intercalated cartilage and bone integrated repair material is simple, efficient, and reliable, providing a new solution for bone and cartilage tissue repair.

[0021] Furthermore, the catalyst in step (1) is stannous octoate, and the catalyst accounts for 2-3% of the mass of the reaction raw materials in step (1), preferably 2.5-3%;

[0022] And / or, the catalyst in step (3) is stannous octoate, and the catalyst accounts for 3-4% of the mass of the reaction raw materials in step (3), preferably 3-3.5%.

[0023] Furthermore, the chain extender in step (1) is 1,4-butanediol, and the chain extender is 2-3% by mass of the reaction raw materials in step (1), preferably 2-2.5%;

[0024] And / or, the chain extender in step (3) is 1,4-butanediol, and the chain extender accounts for 2-3% of the mass of the reaction raw materials in step (3), preferably 2.25-2.75%.

[0025] Furthermore, the foaming agent in step (2) is water, and the foaming agent is 1-2% by mass of the reaction raw materials in step (1), preferably 1.5-2%;

[0026] And / or, the foaming agent in step (4) is water, and the foaming agent accounts for 1.5-2.5% of the reaction raw materials in step (3), preferably 2-2.5%.

[0027] It should be noted that the mass of the reaction raw materials in step (1) is the total mass of nano-hydroxyapatite, soluble starch, polyethylene glycol 400 and isophorone diisocyanate;

[0028] The mass of the reaction raw materials in step (3) is the total mass of soluble starch, polyethylene glycol 400 and isophorone diisocyanate.

[0029] Furthermore, the reaction time of the reaction section of step (1) and / or step (3) is 3 to 6 hours.

[0030] Furthermore, the foaming time of the foaming section in step (2) and / or step (4) is 3 to 12 hours.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] (1) The soft segment of the polyurethane in the three-dimensional embedded cartilage and bone integrated repair material of the present invention adopts natural renewable polymer soluble starch, which is widely available and inexpensive.

[0033] (2) The three-dimensional embedded cartilage and bone integrated repair material system of the present invention is a three-dimensional porous structure, which meets the different requirements of bone and cartilage regeneration for mechanical environment and biological environment, and has important research significance and potential application value for the regeneration and repair of cartilage and bone tissue.

[0034] (3) The preparation method of the three-dimensional embedded cartilage and bone integrated repair material of the present invention is simple, easy, efficient and reliable, and provides a new solution for the large-scale production of bone and cartilage tissue repair. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] The accompanying drawings, which constitute part of this application, are intended to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are intended to explain the present invention and do not constitute an undue limitation of the present invention. In the accompanying drawings:

[0036] Figure 1 A physical diagram showing a three-dimensional inlaid cartilage and bone integrated repair material according to Example 1 of the present invention;

[0037] Figure 2 A photo of a cartilage layer repair material according to embodiment 1 of the present invention is shown;

[0038] Figure 3 A physical diagram of a bone repair material according to embodiment 1 of the present invention is shown;

[0039] Figure 4 A scanning electron microscope image of a cartilage layer repair material according to Example 1 of the present invention is shown;

[0040] Figure 5 A scanning electron microscope image of a bone layer repair material according to Example 1 of the present invention is shown. DETAILED DESCRIPTION

[0041] To facilitate understanding of the present invention, the present invention will be described in more detail below, with preferred embodiments of the present invention provided. However, it should be understood that these embodiments are merely for the purpose of further explanation and are not to be construed as limiting the present invention in any form, i.e., they are not intended to limit the scope of protection of the present invention.

[0042] Unless otherwise defined, the technical terms used in the following examples have the same meanings as commonly understood by those skilled in the art to which this invention belongs. The experimental reagents used in the following examples, unless otherwise specified, are conventional biochemical reagents; the experimental methods described, unless otherwise specified, are conventional methods.

[0043] Porosity testing method in the embodiment of the present invention:

[0044] The porosity of the upper and lower three-dimensional embedded cartilage and bone integrated repair materials was determined using the liquid substitution method, with three parallel samples in each group. The three-dimensional embedded cartilage and bone integrated repair materials were cut into cubes, and the length, width, and height were accurately measured with a vernier caliper. The volume V of each sample was calculated and weighed to obtain W0. The three-dimensional embedded cartilage and bone integrated repair material was completely immersed in deionized water. The vacuum was repeatedly applied to allow the deionized water to completely penetrate the internal pores of the sample. The sample was removed and weighed again to obtain W1. The density of water was recorded as d. The porosity was calculated using the following formula:

[0045] Porosity = (W1-W0) / (V×d)×100%

[0046] The compressive strength test method in the embodiment of the present invention is:

[0047] The three-dimensional embedded cartilage and bone integrated repair material was made into a cube of approximately 1cm×1cm×1cm and subjected to a compression test on an electronic universal material testing machine. The test was carried out at room temperature with a compression rate of 1mm / min. The experiment was stopped when the sample was compressed to 40% of its height.

[0048] Example 1

[0049] A three-dimensional inlaid cartilage and bone integrated repair material, the actual picture is as follows Figure 1 As shown, it consists of two repair layers interlocked in an upper and lower manner, the upper layer being the cartilage layer and the lower layer being the bone layer; the repair material for the cartilage layer uses polyurethane synthesized by reacting soluble starch and polyethylene glycol 400 as the soft segment and isophorone diisocyanate as the hard segment, wherein the soluble starch content in the soft segment is 10%, the polyethylene glycol 400 content is 90%, and the molar ratio of -NCO to -OH is 1:1.1; the repair material for the bone layer includes organic components and inorganic components, wherein the inorganic component uses nanohydroxyapatite, and the organic component uses the polyurethane used for the cartilage layer, wherein the nanohydroxyapatite content is 10%, and the polyurethane content (the soft segment is 30% soluble starch and 70% polyethylene glycol 400, the hard segment is isophorone diisocyanate, and the molar ratio of -NCO to -OH is 1:1.1) is 90%.

[0050] The preparation method of the three-dimensional inlaid cartilage and bone integrated repair material of this embodiment is as follows:

[0051] (1) Bone layer reaction section: The reaction section is carried out in a 60°C oil bath. Turn on the electric stirrer and maintain a certain speed. Add 6g of soluble starch and 14g of polyethylene glycol 400 in sequence. After stirring evenly, add 20g of isophorone diisocyanate dropwise. After the addition is complete, stir thoroughly for 10 minutes and add 0.1mL of catalyst stannous octoate dropwise. After 0.5h, add 4.4g of nanohydroxyapatite and continue stirring for 5h. Then add 1ml of chain extender 1,4-butanediol and stir for 1h.

[0052] (2) Bone layer foaming stage: Add 0.8 ml of water as a foaming agent to the mixture of step (1), stir thoroughly for 1-2 minutes, and then discharge. After discharge, place the sample in a 60°C oven for foaming for 4 hours to obtain a bone layer repair material;

[0053] (3) Cartilage layer reaction section: The reaction section is carried out in a 60°C oil bath. Turn on the electric stirrer and maintain a certain speed. Add 2g of soluble starch and 18g of polyethylene glycol 400 in sequence. After stirring evenly, add 20g of isophorone diisocyanate dropwise. After the addition is complete, stir thoroughly for 10 minutes and add 0.1mL of the catalyst stannous octoate dropwise. After continuing to stir the reaction for 5 hours, add 1mL of the chain extender 1,4-butanediol and stir for 1 hour.

[0054] (4) Cartilage layer foaming section and double-layer mosaic: Add 0.8 ml of water as a foaming agent to the mixture of step (3), mix evenly and pour into the mold with the bone layer repair material in step (2) as the base, place it in a 60°C oven for foaming for 4 hours to obtain a three-dimensional embedded cartilage and bone integrated repair material.

[0055] It should be noted that since the three-dimensional embedded cartilage and bone integrated repair material is composed of a bone layer and a cartilage layer, the upper and lower layers of the three-dimensional embedded cartilage and bone integrated repair material are not uniform, and the porosity and compressive strength test experiments require testing of uniform materials. Therefore, when conducting porosity and compressive strength tests, bone layer repair materials and cartilage layer repair materials are prepared separately, and their porosity and compressive strength are tested.

[0056] The preparation method of the bone layer repair material is as follows:

[0057] (1) Bone layer reaction section: The reaction section is carried out in a 60°C oil bath. Turn on the electric stirrer and maintain a certain speed. Add 6g of soluble starch and 14g of polyethylene glycol 400 in sequence. After stirring evenly, add 20g of isophorone diisocyanate dropwise. After the addition is complete, stir thoroughly for 10 minutes and add 0.1mL of catalyst stannous octoate dropwise. After 0.5h, add 4.4g of nanohydroxyapatite and continue stirring for 5h. Then add 1ml of chain extender 1,4-butanediol and stir for 1h.

[0058] (2) Bone layer foaming stage: Add 0.8 ml of water as a foaming agent to the mixture of step (1), stir thoroughly for 1-2 minutes, and then discharge. After discharge, place the sample in a 60°C oven for foaming for 4 hours to obtain a bone layer repair material.

[0059] The porosity and compressive strength tests of the bone repair material showed that the porosity was 83±5% and the compressive strength was 3.7MPa. Figure 3 As shown, the scanning electron microscope image of the bone repair material is as follows Figure 5 shown.

[0060] The preparation method of the cartilage layer repair material is as follows:

[0061] (1) Cartilage layer reaction section: The reaction section is carried out in a 60°C oil bath. Turn on the electric stirrer and maintain a certain speed. Add 2g of soluble starch and 18g of polyethylene glycol 400 in sequence. After stirring evenly, add 20g of isophorone diisocyanate dropwise. After the addition is complete, stir thoroughly for 10 minutes and add 0.1mL of stannous octoate as a catalyst. After stirring for 5 hours, add 1ml of chain extender 1,4-butanediol and stir for 1 hour.

[0062] (2) Cartilage layer foaming stage: Add 0.8 ml of water as a foaming agent to the mixture of step (1), stir thoroughly for 1-2 minutes, and then discharge. After discharge, place the sample in a 60°C oven for foaming for 4 hours to obtain a cartilage layer repair material.

[0063] The porosity and compressive strength tests of the cartilage repair material showed that the porosity was 76±2% and the compressive strength was 0.63 MPa. Figure 2 As shown, the scanning electron micrograph of the cartilage repair material is shown in Figure 4 shown.

[0064] Example 2

[0065] Based on the three-dimensional embedded cartilage and bone integrated repair material of Example 1, this example changes the content of soluble starch and polyethylene glycol 400 in the polyurethane soft segment of the cartilage layer repair material. The specific process is as follows:

[0066] (1) Cartilage layer reaction section: The reaction section is carried out in a 60°C oil bath. Turn on the electric stirrer and maintain a certain speed. Add different proportions of soluble starch and polyethylene glycol 400 in sequence. After stirring evenly, add 20g of isophorone diisocyanate dropwise. After the addition is complete, stir thoroughly for 10 minutes and add 0.1mL of the catalyst stannous octoate dropwise. After continuing to stir the reaction for 5 hours, add 1mL of the chain extender 1,4-butanediol and stir for 1 hour.

[0067] (2) Cartilage layer foaming stage: Add 0.8 ml of water as a foaming agent to the mixture of step (1), stir thoroughly for 1-2 minutes, and then discharge. After discharge, place the sample in a 60°C oven for foaming for 4 hours to obtain a cartilage layer repair material.

[0068] The porosity and compressive strength of the cartilage layer repair material in the prepared three-dimensional embedded cartilage and bone integrated repair material were tested, and the test results are shown in Table 1.

[0069] Table 1

[0070]

[0071] As can be seen from the test results in Table 1, the contents of soluble starch and polyethylene glycol 400 in the soft segment of the cartilage repair material need to be within a certain ratio range to exhibit excellent porosity and compressive strength. When soluble starch accounts for 5-30% of the soft segment content and polyethylene glycol 400 accounts for 70-95% of the soft segment content, the prepared cartilage repair material has a compressive strength range of 0.08-1 MPa and a porosity of 73-80%. When the porosity exceeds 75%, cells are more likely to migrate and proliferate inward. Therefore, the test performance of Examples 2.2 and 2.3 is better than that of Example 2.4. For Examples 2.2 and 2.3, the appropriate cartilage repair material can be selected according to the compressive strength requirements of the specific application scenario. If soluble starch is not used (Example 2.1), the ideal pore structure cannot be formed, and the porosity and compressive strength cannot be measured.

[0072] Example 3

[0073] Based on the three-dimensional embedded cartilage and bone integrated repair material of Example 1, this example changes the molar ratio of -NCO and -OH in the cartilage layer repair material. The specific process is as follows:

[0074] (1) Cartilage layer reaction section: The reaction section was carried out in a 60°C oil bath. An electric stirrer was turned on and maintained at a constant speed. 2 g of soluble starch and 18 g of polyethylene glycol 400 were added in sequence. After stirring evenly, different proportions of isophorone diisocyanate were added dropwise. After the addition was complete, the mixture was stirred thoroughly for 10 minutes and 0.1 mL of stannous octoate catalyst was added dropwise. After continuous stirring for 5 hours, 1 mL of chain extender 1,4-butanediol was added and stirred for 1 hour.

[0075] (2) Cartilage layer foaming stage: Add 0.8 ml of water as a foaming agent to the mixture of step (1), stir thoroughly for 1-2 minutes, and then discharge. After discharge, place the sample in a 60°C oven for foaming for 4 hours to obtain a cartilage layer repair material.

[0076] The porosity and compressive strength of the cartilage layer repair material in the prepared three-dimensional embedded cartilage and bone integrated repair material were tested, and the test results are shown in Table 2.

[0077] Table 2

[0078]

[0079] As can be seen from the test results in Table 2, when the molar ratio of -NCO to -OH in the cartilage repair material is 1:1 to 3, the porosity is 73 to 80%, and the compressive strength is in the range of 0.3 to 3.4 MPa. When the porosity exceeds 75%, cells are more likely to migrate inward and proliferate. Therefore, the test performance of Examples 3.1 and 3.2 is better than that of Example 3.3. For Examples 3.1 and 3.2, the appropriate cartilage repair material can be selected according to the compressive strength requirements of the specific application scenario.

[0080] Example 4

[0081] Based on the three-dimensional embedded cartilage and bone integrated repair material of Example 1, this example changes the content of nano-hydroxyapatite and polyurethane (the soft segment of the polyurethane is 30% soluble starch and 70% polyethylene glycol 400, the hard segment is isophorone diisocyanate, and the molar ratio of -NCO to -OH is 1:1) in the bone layer repair material. The specific process is as follows:

[0082] (1) Bone layer reaction section: The reaction section is carried out in a 60°C oil bath. Turn on the electric stirrer and maintain a certain speed. Add 6g of soluble starch and 14g of polyethylene glycol 400 in sequence. After stirring evenly, add 20g of isophorone diisocyanate dropwise. After the addition is complete, stir thoroughly for 10 minutes and add 0.1mL of catalyst stannous octoate dropwise. After 0.5h, add different proportions of nanohydroxyapatite and continue stirring for 5h. After that, add 1ml of chain extender 1,4-butanediol and stir for 1h.

[0083] (2) Bone layer foaming stage: Add 0.8 ml of water as a foaming agent to the mixture of step (1), stir thoroughly for 1-2 minutes, and then discharge. After discharge, place the sample in a 60°C oven for foaming for 4 hours to obtain a bone layer repair material.

[0084] The porosity and compressive strength of the bone layer in the prepared three-dimensional embedded cartilage and bone integrated repair material were tested. The test results are shown in Table 3.

[0085] Table 3

[0086]

[0087] It can be seen from the test results in Table 3 that when the nanohydroxyapatite content in the bone layer repair material is 5-15% and the polyurethane content is 85-95%, the porosity is in the range of 80-86% and the compressive strength is in the range of 2-6 MPa. It should be noted that when the nanohydroxyapatite content in the bone layer repair material is 15% and the polyurethane content is 85%, the porosity of the bone layer repair material can reach 86% and the compressive strength can reach 5.8 MPa.

[0088] It should be noted that the above content is a further detailed description of the present invention in conjunction with specific implementation methods, and the specific implementation of the present invention cannot be considered to be limited to these descriptions; the dimensional data of this embodiment does not necessarily limit the technical solution, but only illustrates one specific working condition. For those skilled in the art of the present invention, simple improvements and modifications can be made without departing from the concept of the present invention, and all of these should be considered to fall within the scope of protection of the present invention.

Claims

1. A three-dimensional inlaid cartilage and bone integrated repair material, characterized in that: The invention is composed of two repair layers interlocked in an upper and lower manner, the upper layer being a cartilage layer and the lower layer being a bone layer; the repair material of the cartilage layer adopts polyurethane synthesized by reacting soluble starch and polyethylene glycol 400 as soft segments and isophorone diisocyanate as hard segments; the repair material of the bone layer includes organic components and inorganic components, the inorganic component adopts nano-hydroxyapatite, and the organic component adopts polyurethane in the same or different proportions as that used in the cartilage layer.

2. The three-dimensional inlaid cartilage and bone integrated repair material according to claim 1, characterized in that: In the polyurethane, the soluble starch accounts for 5-30% of the mass content of the soft segment, and the polyethylene glycol 400 accounts for 70-95% of the mass content of the soft segment.

3. The three-dimensional inlaid cartilage and bone integrated repair material according to claim 1, characterized in that: The molar ratio of the reactive groups -NCO to -OH of the polyurethane is 1:(1-1.3).

4. The three-dimensional inlaid cartilage and bone integrated repair material according to claim 1, characterized in that: The bone layer repair material contains 5-15% by mass of nano-hydroxyapatite and 85-95% by mass of polyurethane.

5. A method for preparing the three-dimensional embedded cartilage and bone integrated repair material according to any one of claims 1 to 4, characterized in that: The steps include: (1) Bone layer reaction section: Mix nano-hydroxyapatite, soluble starch, and polyethylene glycol 400 evenly, then add isophorone diisocyanate, catalyst, and chain extender and stir at 60-80°C to mix evenly; (2) Bone layer foaming stage: adding a foaming agent to the mixture of step (1) to obtain a bone layer repair material through foaming; (3) Cartilage layer reaction section: Mix soluble starch and polyethylene glycol 400 evenly, then add isophorone diisocyanate, catalyst, and chain extender and stir at 60-80°C to mix evenly; (4) Cartilage layer foaming section and double-layer mosaic: Add a foaming agent to the mixture of step (3), mix evenly, and pour into the mold with the bone layer repair material in step (2) as the base, and obtain a three-dimensional embedded cartilage and bone integrated repair material through foaming.

6. The method for preparing the three-dimensional embedded cartilage and bone integrated repair material according to claim 5, characterized in that: The catalyst in step (1) is stannous octoate, and the catalyst accounts for 2-3% of the mass of the reaction raw materials in step (1); And / or, the catalyst in step (3) is stannous octoate, and the catalyst accounts for 3-4% of the mass of the reaction raw materials in step (3).

7. The method for preparing the three-dimensional embedded cartilage and bone integrated repair material according to claim 5, characterized in that: The chain extender in step (1) is 1,4-butanediol, and the chain extender is 2-3% of the mass of the reaction raw materials in step (1); And / or, the chain extender in step (3) is 1,4-butanediol, and the chain extender accounts for 2-3% of the mass of the reaction raw materials in step (3).

8. The method for preparing the three-dimensional embedded cartilage and bone integrated repair material according to claim 5, characterized in that: The foaming agent in step (2) is water, and the foaming agent is 1-2% of the mass of the reaction raw materials in step (1); And / or, the foaming agent in step (4) is water, and the foaming agent accounts for 1.5-2.5% of the reaction raw materials in step (3).

9. The method for preparing the three-dimensional embedded cartilage and bone integrated repair material according to claim 5, characterized in that: The reaction time of the reaction section of step (1) and / or step (3) is 3 to 6 hours.

10. The method for preparing the three-dimensional embedded cartilage and bone integrated repair material according to claim 5, characterized in that: The foaming time of the foaming section in step (2) and / or step (4) is 3 to 12 hours.

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