A high-strength, low-friction, swell-resistant, self-adhesive hydrogel material and a method for preparing the same

Abstract

The application belongs to the technical field of hydrogel preparation, and relates to a high-strength low-friction swelling-resistant self-adhesive hydrogel material and a preparation method. The preparation method of the hydrogel comprises four steps of preparation of a precursor hydrogel containing a drag-reducing layer and a tough layer, preparation of a mineralization layer, pre-swelling, and preparation of an adhesive layer. The obtained hydrogel has a four-layer structure of the drag-reducing layer, the tough layer, the mineralization layer, and the adhesive layer. The preparation method is simple, and ideal effects are obtained through simple soaking and smearing. The obtained four-layer hydrogel has high strength, low friction, swelling resistance, self-adhesion, and excellent bone induction potential. The water content of the hydrogel is about 70%, the swelling rate is close to 0, the compressive strength can reach 78 MPa, the friction coefficient is as low as 0.024, the adhesion strength to the bone and the skin is as high as 123 kPa and 79 kPa, respectively. The performance of the hydrogel obtained by the application is better than the comprehensive level of the existing cartilage replacement hydrogel material, and has important significance for widening the application of the hydrogel in the field of artificial cartilage.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of hydrogel preparation, and particularly relates to a preparation method of a high-strength low-friction swelling-resistant self-adhesion hydrogel material. BACKGROUND

[0002] Articular cartilage is an indispensable tissue of the human body, and cartilage damage caused by movement or aging is the main pathogenic factor of osteoarthritis. The water content of cartilage is above 60%, the compressive strength is above 50 MPa, the friction coefficient is lower than 0.1, and the cartilage has good bonding force with the subchondral bone. The structure of hydrogel is similar to that of cartilage, and the hydrogel has adjustable mechanical properties and friction coefficient, and is praised as the most ideal cartilage replacement material. However, most hydrogels significantly swell in water, resulting in a serious increase in volume and deterioration of mechanical properties, and causing damage to the surrounding tissues. Therefore, it is crucial for the cartilage replacement to maintain stable volume and strength in a physiological environment. The ideal hydrogel replacement should meet the following standards: (1) the compressive strength is close to that of natural cartilage; (2) the volume and strength are stable in a simulated body fluid environment; (3) the friction coefficient is close to that of natural cartilage; (4) the hydrogel has osteogenic potential and promotes bonding with the subchondral bone; (5) the hydrogel has excellent anti-swelling ability; and (6) the hydrogel has self-adhesion performance. Although great progress has been made in the technology of implanting biomaterials, there are still many problems, especially the good and stable integration between the implanted biomaterials and the original cartilage, which is still a great challenge for researchers in the field of hydrogel material technology. The good and stable integration between the implanted biomaterials and the original cartilage requires that the cartilage replacement hydrogel has a certain self-adhesion ability.

[0003] Most current cartilage replacement hydrogels cannot simultaneously meet the above requirements. For example, Chinese patent application CN202211686242 discloses an ultra-hard, high-strength, and tough hydrogel, its preparation method, and applications. It involves reacting ethyl methacrylate (2-isocyanate) with isopropanol to form the monomer IMA; then, the IMA monomer is mixed with a hydrophilic monomer, a crosslinking agent, an initiator, and an organic solvent for polymerization. Subsequently, it is immersed in water for solvent displacement until equilibrium is reached, yielding a high-strength, ultra-tough hydrogel (compressive strength ≈ 232.45 MPa). While this hydrogel is immersed in water until swelling equilibrium is reached during preparation, giving it anti-swelling properties, its water content is only 27%, lower than natural cartilage, and it lacks self-adhesion and osteoinductive potential. Furthermore, due to the excessively low water content, the hydration layer on the hydrogel surface cannot provide effective support for low friction (friction coefficient ≈ 0.18, higher than natural cartilage). CN202210850842 discloses a method for preparing a high-performance, low-friction nanocomposite hydrogel, yielding a Ti3C2-PSBMA composite hydrogel. This hydrogel possesses excellent tribological properties (friction coefficient ≈ 0.0126), but its water content is approximately 50%, lower than that of natural cartilage, its compressive strength is only 0.217 MPa, and it lacks self-adhesion, osteoinduction potential, and anti-swelling ability. CN201711282008 discloses a method for preparing an adhesive, super-strong antibacterial hydrogel for bone / cartilage repair. The hydrogel prepared by this method has a water content of approximately 66%, exhibits self-adhesion, and can be loaded with growth factors, providing osteoinduction potential. However, this hydrogel has poor mechanical properties (tensile strength ≈ 0.11 MPa) and lacks anti-swelling properties. Furthermore, as a monolithic self-adhesive hydrogel, its surface tribological properties are inevitably affected by its adhesive ability, resulting in a high friction coefficient.

[0004] Therefore, there is an urgent need to develop a hydrogel material that simultaneously possesses high strength, low friction, swelling resistance, and self-adhesion properties to solve the technical problems faced in the preparation of cartilage substitute materials in the field of hydrogel technology and meet the needs of tissue engineering and medical health fields. Summary of the Invention

[0005] To address the problems and shortcomings of existing technologies, the primary objective of this invention is to provide a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel material. This invention utilizes biomimetic principles, employing high-molecular-weight materials capable of forming ionic bonds with chitosan, such as hyaluronic acid, alginate, grape seed protein, carboxymethyl cellulose, and polyacrylic acid, as raw materials. Grape seed protein and tannic acid are mixed with deionized water to obtain a thickening agent, thus preparing a hydrogel with a four-layer structure: a drag-reducing layer, a toughening layer, a mineralization layer, and an adhesion layer. The hydrogel of this invention exhibits excellent compressive strength, tribological properties, swelling resistance, and self-adhesion.

[0006] Another objective of this invention is to provide a method for preparing a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel material, comprising four steps: preparation of a precursor hydrogel, preparation of a mineralization layer, pre-swelling, and preparation of an adhesion layer.

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] A high-strength, low-friction, swelling-resistant, self-adhesive hydrogel material is characterized by having a four-layer structure: a drag-reducing layer, a toughening layer, a mineralization layer, and an adhesion layer. The drag-reducing layer contains carboxylate anions on its surface, resulting in a friction coefficient as low as 0.024. The toughening layer contains multiple non-covalent bonds that synergistically crosslink, leading to a compressive strength of over 50 MPa. The mineralization layer contains hydroxyapatite, exhibiting osteoinductive potential. The hydrogel's swelling rate is close to 0, and its compressive strength retention rate is close to 100%. The introduction of the adhesion layer allows the hydrogel's bottom surface to acquire a large number of catechol groups, enabling the formation of numerous hydrogen bonds, ionic complexes, and π-π interactions with skin and bone. This results in excellent adhesion properties, with skin and bone adhesion strengths reaching 79 kPa and 123 kPa, respectively.

[0009] A method for preparing a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel material, characterized in that the preparation method includes four steps: preparation of a precursor hydrogel containing a drag-reducing layer and a toughening layer, preparation of a mineralization layer, pre-swelling, and preparation of an adhesive layer, specifically:

[0010] S01. Preparation of precursor hydrogels containing drag-reducing and toughening layers

[0011] 1) Heat 10-20 parts of polyvinyl alcohol, 1-5 parts of chitosan and 80-90 parts of deionized water at 90°C for 6 hours to obtain a homogeneous solution. Then, pour the resulting solution into a mold and let it stand at room temperature to remove air bubbles. Place it in a freezer at -40°C to -20°C for 8-12 hours, transfer it to room temperature for 2-6 hours, and repeat the freeze-thaw cycle 2-7 times to obtain polyvinyl alcohol-chitosan (PVA-CS) pregel.

[0012] 2) The above pregel was freeze-dried to remove the moisture to obtain polyvinyl alcohol-chitosan aerogel;

[0013] 3) The above aerogel is completely immersed in an aqueous solution of a polymer material that can form ionic bonds with chitosan for 1-12 hours to obtain a high-strength, low-friction precursor hydrogel A, which constitutes the drag-reducing layer and toughening layer of the target hydrogel; the drag-reducing layer on the surface of the precursor hydrogel A is rich in water molecules and carboxylate anions, and the toughening layer inside contains a variety of non-covalent bonds for coordinated cross-linking.

[0014] In the preparation of precursor hydrogels, this invention employs a one-step method to simultaneously prepare precursor hydrogel A, which has both a tough layer and a drag-reducing layer. Simply put, in step S01, step 3), polyvinyl alcohol-chitosan (PVA-CS) aerogel is completely immersed in an aqueous solution of a polymer material capable of forming ionic bonds with chitosan for 1-12 hours to obtain precursor hydrogel A. This hydrogel contains various non-covalent bonds that coordinate cross-linking, and the ionic bonds act as additional bonds to consume external loads, ensuring the high strength of the target hydrogel, thus forming the tough layer. Simultaneously, the hydrogel surface is rich in carboxyl groups, which not only improves surface hydration but also creates electrostatic repulsion between the ionized carboxyl groups and the substrate surface, ensuring low friction, thus forming the drag-reducing layer.

[0015] In step S01, step 3) of this invention involves preparing the aerogel by completely immersing it in the solution. Compared to partial immersion, this method has the following advantages: Firstly, complete immersion provides more channels for ions and water molecules to enter the aerogel, ensuring sufficient ions to form ionic bonds with chitosan and adequate water content. Secondly, complete immersion makes the entry of ions more uniform, preventing problems such as decreased mechanical strength caused by different degrees of cross-linking in different regions. At the same time, complete immersion also ensures the ion and water molecule content on its outer surface, providing important support for reducing surface friction.

[0016] S02. Preparation of mineralized layer

[0017] After covering the bottom of the precursor hydrogel A obtained in step S01 with an iron plate, vertically immerse it in an aqueous solution of K2HPO4 with a depth less than two-thirds of the total height of the hydrogel for 50-150 seconds. Then, vertically immerse it in an aqueous solution of CaCl2 with a depth less than two-thirds of the total height of the hydrogel for 50-150 seconds. Repeat this cycle 2-8 times to obtain a hydrogel in which hydroxyapatite is introduced from the side to form a mineralized layer. Wash with deionized water to remove residual substances on the surface.

[0018] S03. Pre-swelling preparation of swelling-resistant hydrogels

[0019] The hydrogel with mineralized layer obtained in step S02 is completely immersed in deionized water at room temperature for 24-48 hours to reach swelling equilibrium, thus obtaining a mineralized swelling-resistant hydrogel.

[0020] Pre-swelling allows the hydrogel to reach swelling equilibrium in advance, which in turn increases the water content and removes impurities while giving the hydrogel excellent anti-swelling properties.

[0021] S04. Preparation of the Adhesive Layer

[0022] Grape seed protein and tannic acid are dissolved in deionized water and stirred to obtain a thickener. The thickener is then applied to the bottom layer of the mineralized swelling-resistant hydrogel prepared in step S03, that is, applied to the bottom surface of the hydrogel near the mineralized layer, to obtain the target hydrogel with a four-layer structure, namely a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel.

[0023] Furthermore, the time for standing at room temperature to remove bubbles as described in step S01 is 20-24 hours.

[0024] Furthermore, the aqueous solution of the polymer material in step S01 has a mass fraction of 0.1% to saturation; the polymer material is any one of hyaluronic acid, sodium hyaluronate, alginate, grape seed protein, carboxymethyl cellulose, and polyacrylic acid.

[0025] Furthermore, in step S02, the molar concentration of the K2HPO4 aqueous solution is 0.1~0.6mM, and the molar concentration of the CaCl2 aqueous solution is 0.2~0.8mM.

[0026] Furthermore, in step S02, the depths of the K2HPO4 aqueous solution and the CaCl2 aqueous solution are one-third of the total height of the hydrogel.

[0027] Furthermore, the specific preparation method of the thickener mentioned in step S04 is to dissolve 5-10 parts of grape seed protein and 5-10 parts of tannic acid in 10-20 parts of deionized water and stir to obtain the thickener.

[0028] Furthermore, the grape seed protein described in step S04 is obtained using the extraction method disclosed in Chinese patent application CN201810129805.4.

[0029] The method for extracting grape seed protein disclosed in Chinese patent application CN201810129805.4 is as follows:

[0030] Extraction and purification of grape seed protein:

[0031] 1) Pretreatment: Weigh grape seeds, soak them in 0.05mol / L NaOH solution for 10-20 minutes, rinse, dry, and crush;

[0032] 2) Degreasing: Degrease the grape seeds with petroleum ether and dry them;

[0033] 3) Decolorization and phenol removal: Decolorize with polyvinylpyrrolidone, remove phenol with acidified ethanol, centrifuge to remove supernatant, dry, and refrigerate;

[0034] 4) Alkaline extraction: Dissolve the decolorized and phenol-free powder in 0.1 mol / L NaOH solution, place in a water bath at 40-50℃ for 40-60 min, centrifuge to remove residue, and obtain supernatant;

[0035] 5) Acid precipitation: Add 1.0 mol / L HCl to the supernatant to adjust the pH to 3-4 to precipitate, centrifuge to remove the supernatant, and obtain flocculent precipitate;

[0036] 6) Purification: Wash the flocculent precipitate with deionized water until neutral, then freeze-dry to obtain grape seed protein.

[0037] The four-layer gradient hydrogel obtained by this invention has a simple and easy-to-operate preparation method. In the preparation of the SO2 mineralization layer, an iron plate is used to cover the bottom of the hydrogel, and a vertical immersion method is employed. The hydrogel is sequentially and alternately immersed in an aqueous solution of K2HPO4 and an aqueous solution of CaCl2, with the depth of both solutions being less than two-thirds of the total height of the hydrogel. This step not only ensures that the low-friction properties of the hydrogel surface are not affected by mineralization, but also uses the iron plate to cover the bottom to prevent the infiltration of hydroxyapatite, protecting the original structure of the bottom. This makes it easier for the catechol structure of tannic acid (TA) in the adhesion layer to form hydrogen bonds with the bulk hydrogel chains; at the same time, it also prevents a decrease in the water content of the hydrogel due to large-area mineralization.

[0038] The hydrogel obtained in this invention has a four-layer structure consisting of a drag-reducing layer, a toughening layer, a mineralization layer, and an adhesion layer. This four-layer hydrogel exhibits excellent compressive strength, tribological properties, swelling resistance, and self-adhesion, while also possessing excellent osteoinductive potential. Achieving high strength, low friction, swelling resistance, self-adhesion, and excellent osteoinductive potential simultaneously, and realizing good and stable integration between implanted biomaterials and native cartilage, has always been a significant challenge in the field of cartilage replacement materials. Based on the relationship between material structure and performance, and inspired by the structure of natural cartilage, the inventors of this invention designed the target hydrogel as a four-layer structure. Utilizing the synergistic effect of chemical structure and tissue engineering, a drag-reducing layer mimicking the upper surface of cartilage was applied to the hydrogel to achieve low friction; a tough layer mimicking cartilage was applied to the middle of the hydrogel to provide strength support; hydroxyapatite was introduced into the sides of the hydrogel to achieve osteoinductive properties; pre-swelling allowed the hydrogel to reach swelling equilibrium in advance, increasing water content and removing impurities while simultaneously achieving excellent anti-swelling properties. The swelling rate of the hydrogel obtained in this invention is close to 0, and the compressive strength retention rate is close to 100%. The bottom of the hydrogel mimics the high integration of cartilage and the lower bone to achieve self-adhesion.

[0039] In the field of cartilage replacement materials, common implanted biomaterials, over time, may experience detachment due to weak integration under suboptimal mechanical load transfer, ultimately leading to the failure of cartilage replacement or regeneration. Similarly, the integration between the implanted hydrogel and the tissue is crucial for effective tissue regeneration, especially for cartilage, as effective integration promotes healing and the recovery of mechanical function. Poor integration between implanted biomaterials and native cartilage often leads to tissue fibrosis, resulting in low efficiency in mechanical load transfer, failure of new cartilage to integrate with native cartilage, and ultimately, failure of cartilage replacement. However, if a monolithic adhesive system is used, it will inevitably have an adverse effect on surface friction properties (as shown in Comparison 1 in Table 1). This invention uses a bottom-coated adhesive layer, giving the hydrogel excellent adhesion and avoiding the adverse effects of poor integration, while ensuring that the low-friction properties of the upper surface of the material are not affected.

[0040] The beneficial effects of this invention are:

[0041] Compared with the prior art, the present invention has the following outstanding substantive features and significant progress.

[0042] (1) Based on the relationship between material structure and performance, the inventors of this invention prepared a four-layer hydrogel using biomimetic principles. The resulting hydrogel has a four-layer structure: a drag-reducing layer, a toughening layer, a mineralization layer, and an adhesion layer. The drag-reducing layer on the upper surface of the hydrogel mimics the upper surface of cartilage to achieve low friction; hydroxyapatite is introduced into the side of the hydrogel to achieve osteoinductive properties; due to the synergistic cross-linking effect of multiple non-covalent bonds in the toughening layer in the middle of the hydrogel, the resulting hydrogel has high compressive strength; and the bottom of the hydrogel mimics the high integration of cartilage and lower bone to achieve self-adhesion.

[0043] (2) The four-layer hydrogel obtained in this invention simultaneously possesses high strength, low friction, swelling resistance, self-adhesion, and excellent osteoinductive potential. The four-layer hydrogel obtained in this invention has a water content of approximately 70%, a compressive strength of up to 78 MPa, a friction coefficient as low as 0.024, adhesion strength to bone and skin as high as 123 kPa and 79 kPa, respectively, and a swelling rate of 0.03-0.05 g / g. This provides a guarantee of strength and durability for the hydrogel material implanted into the organism. The inventors have summarized the performance parameters of the hydrogels obtained in Examples 16-20 of this invention and compared them with relevant literature data on existing cartilage replacement hydrogel materials, as detailed in Table 1:

[0044] .

[0045] (3) The present invention uses a bottom-coated adhesive layer to enable the hydrogel to have adhesive properties. The excellent adhesion strength of the four-layer hydrogel of the present invention avoids the adverse effects that may be caused by poor bonding, while the bottom-coated adhesive layer also protects the low friction performance of the upper surface layer from being affected.

[0046] (4) The four-layer hydrogel of this invention has excellent osteoinductive potential, supports efficient osteogenic formation, and provides a new approach to promoting biological cell growth and bone integration. This invention mineralizes hydroxyapatite in the hydrogel, giving it extremely high osteoinductive potential. However, overall mineralization may reduce the water content and mechanical properties of the hydrogel, and also increase the surface roughness, leading to an increase in the coefficient of friction. This is detrimental to sliding speed and contact dynamics, and cannot meet the requirements of cartilage replacement materials (as shown in Table 1, comparing data from 6). This invention introduces hydroxyapatite from the side of the hydrogel, cleverly avoiding the problems of increased surface friction and reduced mechanical strength caused by overall mineralization. This invention designs a layered structure. During the preparation of the mineralized layer, an iron plate is used to cover the bottom of the hydrogel, and a vertical immersion method is employed. The hydrogel is sequentially and alternately immersed in an aqueous solution of K2HPO4 and an aqueous solution of CaCl2, with the depth of both solutions being one-third of the total height of the hydrogel. This step not only ensures that the low frictional properties of the hydrogel surface are not affected by mineralization, but also uses the iron plate to cover the bottom to prevent the infiltration of hydroxyapatite, protecting the original structure of the bottom. This makes it easier for the catechol structure of tannic acid (TA) in the adhesion layer to form hydrogen bonds with the bulk hydrogel chains. At the same time, it also prevents the decrease in water content of the hydrogel caused by large-area mineralization.

[0047] (4) The hydrogel preparation method of the present invention is simple and ingenious. By soaking and coating, a four-layer hydrogel is obtained, which integrates the contradictory properties of hydrogels into a multi-layer hydrogel. While improving the strength of the hydrogel, its water content is maintained. It endows the material with osteoinductive potential and self-adhesion ability, while giving it excellent tribological properties. This is something that existing cartilage replacement hydrogels cannot achieve.

[0048] (5) This invention not only provides a method for preparing a four-layer hydrogel, which provides a new method for expanding the preparation of hydrogel materials, but also provides a new idea for integrating the contradictory properties of hydrogel materials during the preparation process. It is of great significance to the research, development and application of hydrogel materials in the field of artificial cartilage. Attached Figure Description

[0049] Figure 1 This is a schematic diagram of the synthesis of the high-strength, low-friction, swelling-resistant, self-adhesive hydrogel with a four-layer structure according to the present invention. Implementation

[0050] The technical solution of the present invention will be described in detail below with reference to the accompanying drawings, but the implementation of the present invention is not limited thereto. Example 1

[0051] Preparation of precursor hydrogels

[0052] Weigh 10 parts polyvinyl alcohol and 1 part chitosan by weight, add them to 90 parts deionized water, and dissolve them at 90℃ for 6 hours to form a homogeneous solution. Then, pour the solution into a mold and let it stand for 24 hours to remove air bubbles. Freeze it in a -20℃ freezer for 12 hours, then transfer it to room temperature to thaw for 2 hours. Repeat this cycle twice to synthesize a physically cross-linked polyvinyl alcohol-chitosan pregel. After dehydrating the polyvinyl alcohol-chitosan pregel in a freeze dryer, soak it in a saturated sodium hyaluronate aqueous solution for 1 hour to obtain the precursor hydrogel A1.

[0053] The properties of the precursor hydrogel A1 obtained in Example 1 were tested. The test results showed that the precursor hydrogel obtained in Example 1 had a water content of 72%, a compressive strength of 52 MPa, a coefficient of friction of 0.068, a swelling rate of 1.5 g / g, and did not possess self-adhesion ability or osteoinductive potential. Example 2

[0054] Preparation of precursor hydrogels

[0055] Weigh out 20 parts by weight of polyvinyl alcohol and 5 parts by weight of chitosan, add them to 80 parts by weight of deionized water, and dissolve them at 90℃ for 6 hours to form a homogeneous solution. Then, pour the solution into a mold and let it stand for 24 hours to remove air bubbles. Place it in a -40℃ freezer for 8 hours, then transfer it to room temperature to thaw for 6 hours. Repeat this cycle three times to synthesize a physically cross-linked polyvinyl alcohol-chitosan pregel. After dehydrating the polyvinyl alcohol-chitosan pregel in a freeze dryer, soak it in a 0.1% sodium alginate aqueous solution for 2 hours to obtain the precursor hydrogel A2. Example 3

[0056] Preparation of precursor hydrogels

[0057] Weigh out 14 parts polyvinyl alcohol and 3 parts chitosan by weight, add them to 86 parts deionized water, and dissolve them at 90℃ for 6 hours to form a homogeneous solution. Then, pour the solution into a mold and let it stand for 24 hours to remove air bubbles. Place it in a freezer at -30℃ for 10 hours, then transfer it to room temperature to thaw for 3 hours. Repeat this cycle seven times to synthesize a physically cross-linked polyvinyl alcohol-chitosan pregel. After dehydrating the polyvinyl alcohol-chitosan pregel in a freeze dryer, soak it in a 12% (w / w) carboxymethyl cellulose aqueous solution for 12 hours to obtain the precursor hydrogel A3. Example 4

[0058] Preparation of precursor hydrogels

[0059] Weigh out 16 parts polyvinyl alcohol and 2 parts chitosan by weight, add them to 84 parts deionized water, and dissolve them at 90℃ for 6 hours to form a homogeneous solution. Then, pour the solution into a mold and let it stand for 24 hours to remove air bubbles. Freeze at -35℃ for 9 hours, then transfer to room temperature to thaw for 4 hours. Repeat this cycle three times to synthesize a physically cross-linked polyvinyl alcohol-chitosan pregel. After dehydrating the polyvinyl alcohol-chitosan pregel in a freeze dryer, soak it in a 50% (w / w) aqueous solution of polyacrylic acid for 12 hours to obtain the precursor hydrogel A4. Example 5

[0060] Preparation of precursor hydrogels

[0061] Weigh 18 parts polyvinyl alcohol and 4 parts chitosan by weight, add them to 82 parts deionized water, dissolve at 90°C for 6 hours to form a homogeneous solution, pour into a mold, and let stand for 24 hours to remove air bubbles. Freeze at -25°C for 11 hours, then transfer to room temperature to thaw for 5 hours, repeating this cycle four times to synthesize a physically cross-linked polyvinyl alcohol-chitosan pregel. Grape seed protein was extracted using the extraction method disclosed in Chinese patent application CN201810129805.4. Weigh 50 parts grape seed protein and dissolve it in 50 parts deionized water to obtain a grape seed protein aqueous solution. After dehydrating the polyvinyl alcohol-chitosan pregel in a freeze dryer, soak it in the grape seed protein aqueous solution for 4 hours to obtain precursor hydrogel A5. Example 6

[0062] Preparation of hydrogel A1-h containing a mineralized layer

[0063] First, the bottom of the precursor hydrogel A1 obtained in Example 1 was attached tightly to an iron plate and vertically immersed in an aqueous solution of 0.1 mM K2HPO4 with a depth of one-third of the total height of the hydrogel for 110 seconds. Then, it was vertically immersed in an aqueous solution of 0.2 mM CaCl2 with a depth of one-third of the total height of the hydrogel for 110 seconds. This cycle was repeated 8 times. The hydrogel was then mineralized in situ at 37°C for 8 hours to form a mineralized layer containing hydroxyapatite. The surface residue was removed by washing with deionized water to obtain hydrogel A1-h containing the mineralized layer. Example 7

[0064] Preparation of hydrogel A2-h containing a mineralized layer

[0065] First, the bottom of the precursor hydrogel A2 obtained in Example 2 was attached tightly to an iron plate and vertically immersed in an aqueous solution of 0.6 mM K2HPO4 with a depth of one-third of the total height of the hydrogel for 50 seconds. Then, it was vertically immersed in an aqueous solution of 0.5 mM CaCl2 with a depth of one-third of the total height of the hydrogel for 50 seconds. This cycle was repeated twice. The hydrogel was then mineralized in situ at 37°C for 8 hours to form a mineralized layer containing hydroxyapatite. The surface residue was removed by washing with deionized water to obtain hydrogel A2-h containing the mineralized layer. Example 8

[0066] Preparation of hydrogel A3-h containing a mineralized layer

[0067] First, the bottom of the precursor hydrogel A3 obtained in Example 3 was attached tightly to an iron plate and vertically immersed in an aqueous solution of 0.3 mM K2HPO4 with a depth of one-third of the total height of the hydrogel for 150 seconds. Then, it was vertically immersed in an aqueous solution of 0.8 mM CaCl2 with a depth of one-third of the total height of the hydrogel for 150 seconds. This cycle was repeated 4 times. The hydrogel was then mineralized in situ at 37°C for 8 hours to form a mineralized layer containing hydroxyapatite. The surface residue was removed by washing with deionized water to obtain hydrogel A3-h containing the mineralized layer. Example 9

[0068] Preparation of hydrogel A4-h containing a mineralized layer

[0069] First, the bottom of the precursor hydrogel A4 obtained in Example 4 was attached tightly to an iron plate and vertically immersed in an aqueous solution of 0.4 mM K2HPO4 with a depth of one-third of the total height of the hydrogel for 80 seconds. Then, it was vertically immersed in an aqueous solution of 0.5 mM CaCl2 with a depth of one-third of the total height of the hydrogel for 80 seconds. This cycle was repeated 4 times. The hydrogel was then mineralized in situ at 37°C for 8 hours to form a mineralized layer containing hydroxyapatite. The surface residue was removed by washing with deionized water to obtain hydrogel A4-h containing the mineralized layer. Example 10

[0070] Preparation of hydrogel A5-h containing a mineralized layer

[0071] First, the bottom of the precursor hydrogel A5 obtained in Example 5 was attached tightly to an iron plate and vertically immersed in an aqueous solution of 0.5 mM K2HPO4 with a depth of one-third of the total height of the hydrogel for 60 seconds. Then, it was vertically immersed in an aqueous solution of 0.2 mM CaCl2 with a depth of one-third of the total height of the hydrogel for 60 seconds. This cycle was repeated 5 times. The hydrogel was then mineralized in situ at 37°C for 8 hours to form a mineralized layer containing hydroxyapatite. The surface residue was removed by washing with deionized water to obtain hydrogel A5-h containing the mineralized layer. Example 11

[0072] Preparation of swelling-resistant hydrogels with mineralized layers

[0073] The hydrogel A1-h with a mineralized layer obtained in Example 6 was soaked in deionized water for 24 hours to allow swelling equilibrium, resulting in a swelling-resistant hydrogel s-A1-h with a mineralized layer. Example 12

[0074] Preparation of swelling-resistant hydrogels with mineralized layers

[0075] The hydrogel A2-h with a mineralized layer obtained in Example 7 was soaked in deionized water for 30 hours to allow swelling equilibrium, resulting in a swelling-resistant hydrogel s-A2-h with a mineralized layer. Example 13

[0076] Preparation of swelling-resistant hydrogels with mineralized layers

[0077] The hydrogel A3-h with a mineralized layer obtained in Example 8 was soaked in deionized water for 36 hours to allow swelling equilibrium, resulting in a swelling-resistant hydrogel s-A3-h with a mineralized layer. Example 14

[0078] Preparation of swelling-resistant hydrogels with mineralized layers

[0079] The hydrogel A4-h with a mineralized layer obtained in Example 9 was soaked in deionized water for 42 hours to allow swelling equilibrium, resulting in a swelling-resistant hydrogel s-A4-h with a mineralized layer. Example 15

[0080] Preparation of swelling-resistant hydrogels with mineralized layers

[0081] The hydrogel A5-h with a mineralized layer obtained in Example 10 was soaked in deionized water for 48 hours to allow swelling equilibrium, resulting in a swelling-resistant hydrogel s-A5-h with a mineralized layer. Example 16

[0082] Preparation of hydrogels with a four-layer structure

[0083] Take 5 parts of grape seed protein and 5 parts of tannic acid and dissolve them in 10 parts of deionized water to obtain a thickener. Apply the thickener to the bottom layer of the swelling-resistant hydrogel s-A1-h with a mineralized layer obtained in Example 11 to obtain the target hydrogel with a four-layer structure, namely a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel.

[0084] A schematic diagram of the synthesis of the high-strength, low-friction, swelling-resistant, self-adhesive hydrogel with a four-layer structure obtained in Example 16 is shown below. Figure 1 .

[0085] The properties of the four-layer hydrogel obtained in Example 16 were tested. The test results showed that the four-layer hydrogel obtained in Example 16 had a water content of 70%, a compressive strength of 78 MPa, a coefficient of friction of 0.024, a swelling ratio of 0.03 g / g, and adhesion strengths to bone and skin of 123 kPa and 79 kPa, respectively, indicating that it possesses bone induction potential. Example 17

[0086] Preparation of hydrogels with a four-layer structure

[0087] Take 7 parts of grape seed protein and 10 parts of tannic acid and dissolve them in 20 parts of deionized water to obtain a thickener. Apply the thickener to the bottom layer of the swelling-resistant hydrogel s-A2-h with a mineralized layer obtained in Example 12 to obtain the target hydrogel with a four-layer structure, namely a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel.

[0088] The properties of the four-layer hydrogel obtained in Example 17 were tested. The test results showed that the four-layer hydrogel obtained in Example 17 had a water content of 66%, a compressive strength of 72 MPa, a coefficient of friction of 0.034, a swelling ratio of 0.05 g / g, and adhesion strengths to bone and skin of 110 kPa and 68 kPa, respectively, indicating that it possesses bone induction potential. Example 18

[0089] Preparation of hydrogels with a four-layer structure

[0090] Take 10 parts of grape seed protein and 7 parts of tannic acid and dissolve them in 20 parts of deionized water to obtain a thickener. Apply the thickener to the bottom layer of the swelling-resistant hydrogel s-A3-h with a mineralized layer obtained in Example 13 to obtain the target hydrogel with a four-layer structure, namely a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel.

[0091] The properties of the four-layer hydrogel obtained in Example 18 were tested. The test results showed that the four-layer hydrogel obtained in Example 18 had a water content of 68%, a compressive strength of 68 MPa, a coefficient of friction of 0.028, a swelling ratio of 0.04 g / g, and adhesion strengths to bone and skin of 93 kPa and 55 kPa, respectively, indicating that it possesses bone induction potential. Example 19

[0092] Preparation of hydrogels with a four-layer structure

[0093] Take 8 parts of grape seed protein and 7 parts of tannic acid and dissolve them in 10 parts of deionized water to obtain a thickener. Apply the thickener to the bottom layer of the swelling-resistant hydrogel s-A4-h with a mineralized layer obtained in Example 13 to obtain the target hydrogel with a four-layer structure, namely a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel.

[0094] The properties of the four-layer hydrogel obtained in Example 19 were tested. The test results showed that the four-layer hydrogel obtained in Example 19 had a water content of 68%, a compressive strength of 65 MPa, a coefficient of friction of 0.036, a swelling ratio of 0.03 g / g, and adhesion strengths to bone and skin of 100 kPa and 62 kPa, respectively, indicating that it possesses bone induction potential. Example 20

[0095] Preparation of hydrogels with a four-layer structure

[0096] Take 6 parts of grape seed protein and 7 parts of tannic acid and dissolve them in 17 parts of deionized water to obtain a thickener. Apply the thickener to the bottom layer of the swelling-resistant hydrogel s-A5-h with a mineralized layer obtained in Example 13 to obtain the target hydrogel with a four-layer structure, namely a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel.

[0097] The properties of the four-layer hydrogel obtained in Example 20 were tested. The test results showed that the four-layer hydrogel obtained in Example 20 had a water content of 62%, a compressive strength of 70 MPa, a coefficient of friction of 0.032, a swelling ratio of 0.04 g / g, and adhesion strengths to bone and skin of 77 kPa and 45 kPa, respectively, indicating that it possesses bone induction potential.

[0098] To facilitate comparison between the performance of the four-layer hydrogel material obtained in this invention and the performance of the precursor hydrogel, the performance data of the precursor hydrogel obtained in Example 1 and the performance data of the four-layer hydrogel material obtained in Examples 16-20 are summarized in Table 2:

[0099] .

[0100] As can be seen from Table 2, after the precursor hydrogel is prepared into a four-layer structure hydrogel in this invention, the resulting four-layer structure hydrogel still has a high water content, significantly improved compressive strength, significantly reduced friction coefficient, excellent osteoinductive potential, and a swelling rate close to 0. At the same time, it also has very high adhesion strength, with an adhesion strength to bone as high as 123 kPa and an adhesion strength to skin as high as 79 kPa.

[0101] The inventors of this invention have employed the aforementioned ingenious method to integrate the contradictory properties of hydrogel materials into a multilayer hydrogel structure. This method improves the strength of the hydrogel while maintaining its water content, endowing the material with osteoinductive potential and self-adhesion capabilities, and giving it excellent tribological properties. Moreover, the preparation method is simple, achieving ideal results through simple soaking and coating. The resulting hydrogel outperforms the overall performance of existing cartilage replacement hydrogel materials (see Tables 1 and 2 for details), which is of great significance for broadening the application of hydrogels in the field of artificial cartilage.

[0102] The above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of the invention. Any technical solution implemented within the scope of the claims of this application, or any possible variations and modifications made by those skilled in the art using the methods disclosed above, shall fall within the protection scope of the present invention.

Claims

1. A method for preparing a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel material, characterized in that, The hydrogel has a four-layer structure consisting of a drag-reducing layer, a toughening layer, a mineralization layer, and an adhesion layer; the surface of the drag-reducing layer contains carboxylate anions; and the toughening layer contains multiple non-covalent bonds that are synergistically cross-linked. The mineralization layer contains hydroxyapatite; the adhesion layer contains catechol groups; the preparation method includes four steps: preparation of a precursor hydrogel containing a drag-reducing layer and a toughening layer, preparation of the mineralization layer, pre-swelling, and preparation of the adhesion layer. Specifically: S01. Preparation of precursor hydrogels containing drag-reducing and toughening layers 1) Heat 10-20 parts of polyvinyl alcohol, 1-5 parts of chitosan and 80-90 parts of deionized water at 90°C for 6 hours to obtain a homogeneous solution. Then, pour the resulting solution into a mold and let it stand at room temperature to remove air bubbles. Place it in a freezer at -40°C to -20°C for 8-12 hours, transfer it to room temperature for 2-6 hours, and repeat the freeze-thaw cycle 2-7 times to obtain polyvinyl alcohol-chitosan pregel. 2) The above pregel was freeze-dried to remove the moisture to obtain polyvinyl alcohol-chitosan aerogel; 3) The above aerogel is completely immersed in an aqueous solution of a polymer material that can form ionic bonds with chitosan for 1-12 hours to obtain a high-strength, low-friction precursor hydrogel A, which constitutes the drag-reducing layer and toughening layer of the target hydrogel; the drag-reducing layer on the surface of the precursor hydrogel A is rich in water molecules and carboxylate anions, and the toughening layer inside contains a variety of non-covalent bonds for coordinated cross-linking. S02. Preparation of mineralized layer After covering the bottom of the precursor hydrogel A obtained in step S01 with an iron plate, vertically immerse it in an aqueous solution of K2HPO4 with a depth of one-third of the total height of the hydrogel for 50-150 seconds, and then vertically immerse it in an aqueous solution of CaCl2 with a depth of one-third of the total height of the hydrogel for 50-150 seconds. Repeat this process 2-8 times to obtain a hydrogel in which hydroxyapatite is introduced from the side to form a mineralized layer. Wash with deionized water to remove residual substances on the surface. S03. Pre-swelling preparation of swelling-resistant hydrogels The hydrogel with mineralized layer obtained in step S02 is completely immersed in deionized water at room temperature for 24-48 hours to reach swelling equilibrium, thus obtaining a mineralized swelling resistant hydrogel. S04. Preparation of the Adhesive Layer Grape seed protein and tannic acid are dissolved in deionized water and stirred to obtain a thickener. The thickener is then applied to the bottom layer of the mineralized swelling-resistant hydrogel prepared in step S03, that is, applied to the bottom surface of the hydrogel near the mineralized layer, to obtain the target hydrogel with a four-layer structure, namely a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel. The time for removing air bubbles at room temperature as described in step S01 is 20-24 hours; The aqueous solution of the polymer material in step S01 has a mass fraction of 0.1% to saturation; the polymer material is any one of hyaluronic acid, sodium hyaluronate, alginate, grape seed protein, carboxymethyl cellulose, and polyacrylic acid. In step S02, the molar concentration of the K2HPO4 aqueous solution is 0.1~0.6 mM, and the molar concentration of the CaCl2 aqueous solution is 0.2~0.8 mM. The specific preparation method of the thickener mentioned in step S04 is to dissolve 5-10 parts of grape seed protein and 5-10 parts of tannic acid in 10-20 parts of deionized water and stir to obtain the thickener.

2. The preparation method of the high-strength, low-friction, swelling-resistant, self-adhesive hydrogel material as described in claim 1, characterized in that, The extraction method of grape seed protein described in steps S02 and S04 is as follows: extraction and purification of grape seed protein: 1) Pretreatment: Weigh grape seeds, soak them in 0.05mol / L NaOH solution for 10-20 minutes, rinse, dry, and crush; 2) Degreasing: Degrease the grape seeds with petroleum ether and dry them; 3) Decolorization and phenol removal: Decolorize with polyvinylpyrrolidone, remove phenol with acidified ethanol, centrifuge to remove supernatant, dry, and refrigerate; 4) Alkaline extraction: Dissolve the decolorized and phenol-free powder in 0.1 mol / L NaOH solution, place in a water bath at 40-50℃ for 40-60 min, centrifuge to remove residue, and obtain supernatant; 5) Acid precipitation: Add 1.0 mol / L HCl to the supernatant to adjust the pH to 3-4 to precipitate, centrifuge to remove the supernatant, and obtain flocculent precipitate; 6) Purification: Wash the flocculent precipitate with deionized water until neutral, then freeze-dry to obtain grape seed protein.

3. The method for preparing the high-strength, low-friction, swelling-resistant, self-adhesive hydrogel material as described in claim 1, characterized in that, The preparation method is specifically as follows: Weigh 10 parts polyvinyl alcohol and 1 part chitosan by weight, add them to 90 parts deionized water, dissolve at 90℃ for 6 hours to form a homogeneous solution, then pour the solution into a mold and let it stand for 24 hours to remove air bubbles; place it in a -20℃ freezer for 12 hours, then transfer it to room temperature to thaw for 2 hours, repeat the cycle twice to synthesize physically cross-linked polyvinyl alcohol-chitosan pregel; after dehydrating the polyvinyl alcohol-chitosan pregel in a freeze dryer, soak it in a saturated sodium hyaluronate aqueous solution for 1 hour to obtain precursor hydrogel A1; After the bottom of the obtained precursor hydrogel A1 was pressed tightly against the iron plate, it was vertically immersed in an aqueous solution of 0.1 mM K2HPO4 with a depth of one-third of the total height of the hydrogel for 110 seconds. Then it was vertically immersed in an aqueous solution of 0.2 mM CaCl2 with a depth of one-third of the total height of the hydrogel for 110 seconds. This cycle was repeated 8 times. The hydrogel was then mineralized in situ at 37°C for 8 hours to form a mineralized layer containing hydroxyapatite. The surface residue was removed by washing with deionized water to obtain hydrogel A1-h containing the mineralized layer. The obtained hydrogel A1-h with a mineralized layer was soaked in deionized water for 24 hours to allow swelling equilibrium, resulting in a swelling-resistant hydrogel s-A1-h with a mineralized layer. Take 5 parts of grape seed protein and 5 parts of tannic acid and dissolve them in 10 parts of deionized water to obtain a thickener. Apply the thickener to the bottom layer of the swelling-resistant hydrogel s-A1-h with a mineralized layer to obtain the target hydrogel with a four-layer structure, namely a high-strength, low-friction, swelling-resistant, self-adhesive hydrogel.

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