A gradient heterogeneous structure PVA hydrogel and its preparation method and application based on freeze-drying-annealing synergistic process

Abstract

The present invention belongs to the field of hydrogel preparation technology, and relates to a kind of gradient heterogeneous structure PVA hydrogel and its preparation method and application based on freeze-drying annealing collaborative process, the product is an integrated continuous gradient heterogeneous structure; from outside to inside, the pore size and water content of the gradient heterogeneous structure PVA hydrogel gradually increase, and the crystallinity and compression modulus gradually decrease; during preparation, the PVA aqueous solution is first injection molded in a mold, and then the mold is frozen and placed in a vacuum freeze dryer, and freeze-dried under conditions of a vacuum degree of 0.1~1mbar and a temperature of 50~30°C, the freeze-drying time is 8~48h, and finally the freeze-dried hydrogel is taken out from the mold for annealing treatment, and after the hydrogel is cooled to room temperature, it is placed in deionized water to absorb water and swell to obtain the product; it is applied to load-bearing soft tissue. The gradient heterogeneous structure PVA hydrogel of the present invention has excellent dynamic mechanical response and energy dissipation capacity; the preparation method is simple; and the application prospect is good.

Description

Technical Field

[0001] The present invention belongs to the technical field of hydrogel preparation, and relates to a gradient heterogeneous structure PVA hydrogel and a preparation method and application thereof based on a freeze-drying-annealing collaborative process. Background Art

[0002] In the field of modern materials science, developing hydrogels that combine high water content with high strength, while also being both rigid and flexible, is a core goal of many cutting-edge research efforts. However, the mechanical properties of hydrogels often face an inherent contradiction between rigidity and flexibility—increasing compressive strength is usually accompanied by a decrease in water content and elasticity, while maintaining a high water content makes it difficult to achieve high load-bearing capacity. For example, in a flexible, high-load scenario, an ideal hydrogel needs to provide flexible cushioning (low modulus) at low strains, rigid support (higher modulus) at high strains, and protect surrounding structures through energy dissipation. Due to their unique combination of properties, this type of material shows great potential in fields such as biomedicine, industrial cushioning, and flexible electronics.

[0003] In particular, in the biomedical field, load-bearing cartilage tissues between bones (such as the intervertebral disc and meniscus) exhibit high water content (65%–90%), high flexibility and strength (low modulus at low strain, high modulus >100 MPa at high strain), high energy dissipation, and excellent stress transfer and dispersion (converting compressive forces into tensile forces). These tissues are not homogeneous but rather exhibit distinct gradient heterogeneous structures, characterized by a soft interior and a hard exterior, offering promising avenues for biomimetic design. However, existing research has yet to fully address this challenge.

[0004] To achieve these goals, researchers have explored various methods to prepare high-water-content, high-strength hydrogel materials. For example, Reference 1 (Network of cyano-p-aramid nanofibres creates ultrastiff and water-rich hydrospongels. Nat. Mater. 1–10 (2024) doi:10.1038 / s41563-023-01760-5.) uses nano-aramid fibers to create a hydrogel sponge. The hydrogel exhibits an elastic modulus of 50–80 MPa at a water content exceeding 90%. However, the hydrogel has difficulty recovering rapidly under high loads, limiting its application. Reference 2 (Water-Rich Biomimetic Composites with Abiotic Self-Organizing Nanofiber Network. Adv. Mater. 30, 1703343 (2018)) uses nano-aramid fibers reinforced with polyvinyl alcohol (PVA) to produce high-water-content hydrogels with a water content of 70% to 92% and a compressive strength of 26 MPa. However, these hydrogels exhibit excessively high initial modulus, lacking the flexibility to withstand loads. Therefore, such a single structure is unable to achieve both rigidity and flexibility, necessitating inspiration from natural load-bearing tissues.

[0005] To mimic the gradient heterogeneous structures of natural tissue and achieve both rigidity and flexibility, researchers have focused on core-shell structures, core-shell structures, or 3D-printed composite structures. For example, Reference 3 (Cellulose nanofiber-carbon nanotube / polyvinyl alcohol-borax hybrid conductive hydrogel. Fuhe CailiaoXuebaoActa Mater. Compos. Sin. 34, 2312–2320 (2017)) uses PVA and sodium alginate to prepare core-shell structures of varying hardness. While these structures exhibit certain rigid-flexible mechanical properties, the process is complex, involves harmful crosslinking agents such as glutaraldehyde, and exhibits low compressive strength. Reference 4 (High-resolution 3D printing of angle-plyannulus fibrosus scaffolds for intervertebral disc regeneration. Biofabrication 15, 015015 (2022)) uses 3D printing technology to construct a PCL annulus fibrosus and uses GelMA as the nucleus pulposus to create a biomimetic gradient heterogeneous structure intervertebral disc. However, due to the significant mechanical differences between the two materials, interface bonding issues and overall shear mechanics issues have limited its clinical application. Patent CN111938883A discloses a biomimetic intervertebral disc that uses a braided structure to construct an annulus fibrosus to improve strength. Flexible materials are embedded in upper and lower rigid cartilage plates, achieving a certain degree of mechanical transmission. However, the multiple components lack consistent gradients, resulting in interface issues, complex manufacturing processes, and nonlinear mechanical transmission. In summary, these methods face problems such as low interface bonding strength, lack of gradients, discontinuous force transmission dispersion, high manufacturing costs, complex processes, and biocompatibility issues, and fail to meet relevant requirements.

[0006] PVA hydrogel has attracted much attention due to its excellent biocompatibility and adjustable physicochemical properties. PVA hydrogel mainly forms a three-dimensional network structure through hydrogen bonds, which makes it have a high water content. However, although traditional preparation methods such as the freeze-thaw method can achieve a water content of about 90%, its compressive strength is usually less than 1MPa, which cannot meet the strength requirements under load-bearing environments. In order to solve the above problems, reference 5 (A Synthetic Hydrogel Composite with a Strength and Wear Resistance Greater than Cartilage. Adv. Funct. Mater. 32, (2022).) prepared a PVA and bacterial cellulose composite hydrogel by annealing, and its compressive strength can reach 50~100MPa, but this is usually accompanied by a drop in water content below 50% and a decrease in elastic properties. In addition, reference 6 (Solvent-Exchange-Assisted Wet Annealing: A New Strategy for Superstrong, Tough, Stretchable, and Anti-Fatigue Hydrogels. Adv. Mater. 35, (2023).) improved the water content and strength of PVA hydrogel by wet annealing, but the process is complicated and the use of DMSO as a solvent has certain toxicity.

[0007] Therefore, it is of great significance to study a gradient heterogeneous structure PVA hydrogel and its preparation method and application based on the freeze-drying-annealing synergistic process to solve the problems existing in the existing technology. Summary of the Invention

[0008] The purpose of the present invention is to solve the problems existing in the prior art and provide a gradient heterogeneous structure PVA hydrogel and a preparation method and application thereof based on a freeze-drying-annealing collaborative process.

[0009] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0010] A gradient heterostructure PVA hydrogel is an integrally formed continuous gradient heterostructure; from the outside to the inside, the pore size and water content of the gradient heterostructure PVA hydrogel gradually increase, while the crystallinity and compression modulus gradually decrease.

[0011] As the preferred technical solution:

[0012] As described above, the gradient heterostructured PVA hydrogel has a pore size that gradually increases from 20 to 200 nm to 2 to 20 μm from the outside to the inside, a water content that gradually increases from 40 to 70% to 70 to 90%, a crystallinity that gradually decreases from 13 to 30% to 2 to 15%, and a compression modulus that gradually decreases from 100 to 300 MPa to 100 KPa to 10 MPa.

[0013] As described above, a gradient heterogeneous structure PVA hydrogel mimics the mechanical response characteristics of natural load-bearing soft tissue, achieving mechanical properties that are both rigid and flexible. In the low strain stage, the compression modulus is ≤0.1 MPa, providing flexible buffering, and in the high strain stage, the compression modulus is ≥200 MPa, achieving rigid support. The low strain stage refers to a strain of 0-20%, and the high strain stage refers to a strain of 60-80%. The gradient heterogeneous structure PVA hydrogel has a compressive strength of 20-60 MPa, an energy dissipation rate of ≥70%, and a compressive strength attenuation rate of ≤10% after 1000 times of 50% strain compression. It can achieve the same load-bearing mode as natural load-bearing soft tissue, converting the compressive force into a tensile force in the peripheral high modulus zone.

[0014] The present invention also provides a method for preparing a gradient heterostructured PVA hydrogel as described in any of the above items, comprising: first, injection molding a PVA aqueous solution in a mold; then, freezing the mold and placing it in a vacuum freeze dryer; and freeze-drying the solution under conditions of a vacuum degree of 0.1 to 1 mbar and a temperature of -50 to -30°C for 8 to 48 hours. Under these conditions, incomplete freeze-drying can be achieved; finally, the freeze-dried hydrogel is removed from the mold and annealed. After the hydrogel is cooled to room temperature, it is placed in deionized water to absorb water and swell, thereby obtaining a gradient heterostructured PVA hydrogel.

[0015] To address the core challenges of existing high-water-content hydrogels, such as their difficulty balancing high strength and flexible load-bearing, insufficient interfacial bonding within heterogeneous structures, poor stress transfer and dispersion capabilities, and complex processing, this paper proposes a novel lyophilization-annealing synergistic process to construct a continuous gradient heterogeneous structure (referred to as a gradient heterogeneous PVA hydrogel) within a single PVA matrix, overcoming the limitations of traditional technology. Specifically, through the control of vacuum and temperature fields, the crystallinity and hydrogen bonding of the PVA segments gradually decrease from the outside to the inside, the water content gradually increases, and the mechanical properties gradually weaken, thus forming a gradient heterogeneous hydrogel.

[0016] The present invention creatively proposes to prepare gradient heterogeneous structure PVA hydrogel by combining freeze-drying and annealing methods. The key point lies in the vacuum freeze-drying step. Incomplete freeze-drying causes part of the water in the outer layer to be extracted, resulting in a low water content and forming a dense structure. The water content increases as the structure moves inward, and the crystallinity decreases from the outside to the inside. This difference is amplified by subsequent annealing, enhancing the mechanical and internal and external heterogeneity differences.

[0017] As the preferred technical solution:

[0018] As described above, in the preparation method of a gradient heterogeneous structure PVA hydrogel, the PVA aqueous solution is obtained by dissolving PVA particles in deionized water under a high temperature and high pressure environment of 120-130° C. and 1.5-2.5 atm, and the dissolution time is 30-120 minutes.

[0019] In the above-mentioned method for preparing a gradient heterogeneous structure PVA hydrogel, the mass concentration of the PVA aqueous solution is 10-50 wt%.

[0020] As described above, a method for preparing a gradient heterogeneous structure PVA hydrogel, injection molding refers to injecting a PVA aqueous solution into a customized mold to form a preform with a target shape (including but not limited to a cylindrical, intervertebral disc, meniscus or spherical shape), the injection pressure is 5~10 MPa, the injection temperature is 60~100℃, and the injection time is 1~5 min.

[0021] As described above, the preparation method of a gradient heterogeneous structure PVA hydrogel, the annealing process is as follows: the freeze-dried hydrogel is placed in an oven, raised from room temperature to the target temperature (60~120℃) at a rate of 2~5℃ / min, maintained for 30~120min, and then slowly cooled to room temperature at a rate of 1~3℃ / min.

[0022] The present invention also provides an application of a gradient heterostructured PVA hydrogel as described in any of the above items, which is applied to load-bearing soft tissues, such as bionic intervertebral disc scaffolds, bionic meniscus scaffolds or bionic cartilage scaffolds; the gradient heterostructured PVA hydrogel has high strength, flexibility and high load-bearing performance, similar to natural tissue.

[0023] Beneficial effects:

[0024] (1) The gradient heterogeneous structure PVA hydrogel of the present invention has excellent dynamic mechanical response and energy dissipation capabilities; it can provide flexible buffering (modulus ≤ 0.1 MPa) in the low strain stage and achieve rigid support (modulus ≥ 200 MPa) in the high strain stage, with a maximum compressive strength of 60 MPa. A hydrogel weighing 10 g can withstand the crushing of a car; at the same time, the material can convert compressive stress into tensile stress, which is consistent with natural load-bearing tissue; in addition, the compressive energy dissipation rate of the material is not less than 70%, and it has excellent fatigue resistance, which is significantly better than traditional materials.

[0025] (2) The present invention provides a method for preparing a gradient heterogeneous structure PVA hydrogel, which adopts a one-stop process combining freeze-drying and annealing, uses a single material, and does not require the use of toxic chemical cross-linking agents or complex multi-step composite processes. This not only simplifies the manufacturing process and improves the preparation efficiency, but also makes the raw material utilization rate as high as over 99%, while supporting flexible customization of different mechanical properties and water content, and has good prospects for industrial transformation.

[0026] (3) The present invention provides a method for preparing a gradient heterogeneous structure PVA hydrogel, which designs a continuous gradient heterogeneous structure with a gradually increasing water content from the outside to the inside and from rigid to flexible. This design not only avoids the common delamination risk of traditional heterogeneous materials, but also mimics the gradient heterogeneous structure of natural intervertebral discs.

[0027] (4) The application of the gradient heterogeneous structure PVA hydrogel of the present invention can be applied to multiple fields such as bioengineering, cushioning materials, flexible sensors, and aerospace shock absorption; when used as a bionic intervertebral disc, it can ensure the linearization of mechanical transmission without the risk of interface delamination; when used as an industrial cushioning material, the single impact energy absorption rate can exceed 70% and maintain stability within a wide temperature range. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 Schematic diagram of cylindrical gradient heterogeneous PVA hydrogel;

[0029] Figure 2 This is a cross-sectional view of a cylindrical gradient heterogeneous PVA hydrogel;

[0030] Figure 3 Schematic diagram of PVA hydrogel with biomimetic intervertebral disc structure;

[0031] Figure 4 Schematic diagram of PVA hydrogel with biomimetic meniscus structure;

[0032] Figure 5 Schematic diagram of core-shell structure PVA hydrogel;

[0033] Figure 6This is a SEM image of the gradient heterostructure PVA in Example 1 at a magnification of 600 times;

[0034] Figure 7 for Figure 6 The enlarged view of the framed part is the SEM image with a magnification of 3000 times;

[0035] Figure 8 The crystallinity of the outer layer, transition layer and inner layer of different samples calculated by DSC curve in Example 1;

[0036] Figure 9 The crystallinity at different freeze-drying times calculated by DSC curve in Example 1;

[0037] Figure 10 Waxs spectra of different samples in Example 1;

[0038] Figure 11 Waxs two-dimensional curves of different samples in Example 1;

[0039] Figure 12 Compression mechanics curves of different samples in Example 1;

[0040] Figure 13 The figure shows the comparison of the compression modulus and compression strength of different samples in Example 1, where 20% represents the modulus when compressed to 20%, and 80% represents the modulus when compressed to 80%;

[0041] Figure 14 Compression finite element of the gradient heterostructured PVA hydrogel (i.e., AN24 sample) of Example 1;

[0042] Figure 15 is the compression hysteresis curve of Example 1;

[0043] Figure 16 Comparison of the compression modulus of Example 1 of the present invention and the high-strength and high-water-content hydrogel;

[0044] Figure 17 Comparison of the compressive strength of Example 1 of the present invention and the high-strength and high-water-content hydrogel;

[0045] Among them, 1-1 is the cylindrical outer layer, and 1-2 is the cylindrical inner layer;

[0046] The terms that appear in the figure are as follows:

[0047] The number 24 represents lyophilization for 24 hours; O represents the outer layer, M represents the middle layer, and I represents the inner layer; FT represents the frozen sample, FD represents the lyophilized sample, and AN represents the gradient heterogeneous structure PVA hydrogel sample; AN24-O represents the outer layer of the gradient heterogeneous structure PVA hydrogel sample obtained by lyophilization for 24 hours and annealing, AN16-O represents the outer layer of the gradient heterogeneous structure PVA hydrogel sample obtained by lyophilization for 16 hours and annealing, AN8-O represents the outer layer of the gradient heterogeneous structure PVA hydrogel sample obtained by lyophilization for 8 hours and annealing, AN24-M represents the outer layer of the gradient heterogeneous structure PVA hydrogel sample obtained by lyophilization for 24 hours and annealing. The transition layer of the gradient heterostructure PVA hydrogel sample was obtained by freeze-drying for 16 hours and annealing, AN16-M was the transition layer of the gradient heterostructure PVA hydrogel sample obtained by freeze-drying for 16 hours and annealing, AN24-I was the inner layer of the gradient heterostructure PVA hydrogel sample obtained by freeze-drying for 24 hours and annealing; AN8-I was the inner layer of the gradient heterostructure PVA hydrogel sample obtained by freeze-drying for 8 hours and annealing; FD24-O was the outer layer of the PVA hydrogel that was freeze-dried for 24 hours, FD24-M was the middle layer of the PVA hydrogel that was freeze-dried for 24 hours, and FD24-I was the inner layer of the PVA hydrogel that was freeze-dried for 24 hours;

[0048] CY-ANF is cyano-aramid nanofiber; BANF is double-network aramid nanofiber; Articular cartilage is articular cartilage; BC is bacterial cellulose; BC-gelatin is bacterial cellulose-gelatin composite; PVA-graphene is polyvinyl alcohol-graphene composite hydrogel; PVA-CNC is polyvinyl alcohol-cellulose nanocrystal composite; PVA-ANF is polyvinyl alcohol-aramid nanofiber composite; PVA-ANF is polyvinyl alcohol-aramid nanofiber composite; Alginate is alginate; PEG is polyethylene glycol; PAAm-silkfibroin is polyacrylamide-silk fibroin composite; PAMPS-PDMAAM is poly(2-acrylamido-2-methylpropanesulfonic acid)-poly(N,N-dimethylacrylamide) double network; g-CN-AHPA is graphitic carbon nitride-aminohydroxyapatite composite. DETAILED DESCRIPTION

[0049] Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiments are only used to illustrate the present invention and are not used in limiting the scope of the present invention.In addition, should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall equally within the scope limited by the appended claims of the application.

[0050] The test methods involved in the performance indicators in the embodiments and comparative examples of the present invention are as follows:

[0051] Moisture content: GB / T 6284-2006.

[0052] Crystallinity: ISO 11357-3:2018, the melting enthalpy of the material is measured by differential scanning calorimetry (DSC), and the crystallinity is calculated indirectly.

[0053] Compression modulus: ISO 604-2002, compression test using a universal testing machine, measuring the compression modulus at 10%, 20%, 60% and 80%.

[0054] Energy dissipation rate: ASTM D 4065-20 standard, which is used to determine the energy loss of a material during loading and unloading through dynamic mechanical analysis (DMA) or cyclic compression testing. Test method: The energy dissipation rate is calculated from the hysteresis area of the compression-recovery curve.

[0055] Compression Strength Decay Rate: ASTM D695-15. This standard is used to evaluate the rate of strength degradation of a material under cyclic compressive loading. Test method: The compression strength decay rate is obtained by observing the peak stress through continuous compression cycles.

[0056] Example 1

[0057] A method for preparing a gradient heterogeneous structure PVA hydrogel, the specific steps are as follows:

[0058] (1) PVA particles were dissolved in deionized water at 120°C and 1.5 atm for 30 min to obtain a PVA aqueous solution with a mass concentration of 20 wt%;

[0059] (2) The PVA aqueous solution was injection molded in a cylindrical mold at an injection pressure of 7 MPa, an injection temperature of 80 °C, and an injection time of 1 min;

[0060] (3) Freeze-drying;

[0061] After freezing the mold in step (2) (referred to as FT sample), place it in a vacuum freeze dryer and freeze-dry it at a vacuum degree of 1 mbar and a temperature of -30°C for 24 hours. The freeze-dried sample is referred to as FD sample.

[0062] (4) Annealing treatment;

[0063] The freeze-dried hydrogel was placed in an oven, heated from room temperature to 90°C at a rate of 5°C / min, maintained for 60 minutes, then cooled to room temperature at a rate of 1°C / min, and finally placed in deionized water to absorb water and swell for 24 hours to obtain a cylindrical gradient heterogeneous structure PVA hydrogel (denoted as AN sample).

[0064] The cylindrical gradient heterostructure PVA hydrogel finally obtained is an integrally formed continuous gradient heterostructure; Figure 6As shown in the figure, from the outside to the inside, the pore size of the gradient heterostructured PVA hydrogel gradually increases from 100 nm to 10 μm, the water content gradually increases from 65% to 90%, the crystallinity gradually decreases from 13% to 2%, and the compression modulus gradually decreases from 256 MPa to 100 KPa; the compression modulus of the cylindrical gradient heterostructured PVA hydrogel is 0.1 MPa at the low strain stage of 20%, and the compression modulus is 256 MPa at the high strain stage of 80%; the compressive strength of the cylindrical gradient heterostructured PVA hydrogel is 37 MPa, the energy dissipation rate is 72%, and the compressive strength attenuation rate is 10% after 1000 times of 50% strain compression; the cylindrical gradient heterostructured PVA hydrogel is used in load-bearing soft tissues, such as intervertebral discs or cartilage.

[0065] The cylindrical gradient heterostructured PVA hydrogels prepared Figure 1 、 Figure 2 and Figure 6 As shown, the outer cylindrical layer 1-1 with a low moisture content and the inner cylindrical layer 1-2 with a high moisture content are formed. Due to the integrated molding process, the outer and inner layers are not separated. The pore size gradually increases from the outer layer to the inner layer, weakening the mechanical gradient and increasing the moisture content gradient, eliminating the problem of insufficient interfacial bonding strength. The overall mechanical properties, the mechanical properties of the inner and outer layers, and the moisture content can all be customized through the process. Specifically, increasing the concentration improves mechanical properties and reduces moisture content; increasing the freeze-drying time increases the thickness of the outer layer, reducing the overall moisture content and improving mechanical properties; increasing the annealing temperature improves overall mechanical properties and reduces moisture content; and increasing the annealing time reduces the overall moisture content and improves mechanical properties.

[0066] The crystallinity of the outer layer, transition layer and inner layer was quantitatively measured by DSC experiment (O is the outer layer, M is the transition layer, and I is the inner layer), as shown in Figure 8 As shown in the figure, the outer layer of the AN sample has a high crystallinity and gradually transitions to the inner layer with a low crystallinity. The inner layer of the AN sample has a crystallinity comparable to that of the traditional freeze-thaw cycle high moisture content sample FT. Therefore, a gradient heterogeneous structure with decreasing crystallinity from the outside to the inside is formed. The crystallinity of PVA is also closely related to mechanics. The higher the crystallinity, the stronger the mechanics. Freeze-drying time will also affect the degree of crystallinity, such as Figure 9 As shown in Figure 2, as the freeze-drying time increases, the crystallinity of the outer layer of the PVA hydrogel gradually increases, proving that the crystallization of gradient heterogeneous PVA can be customized. Figure 10 The waxs curve shown and Figure 11The waxs two-dimensional curve shown in the figure shows that the (101) crystal plane of the waxs curve of the AN group decreases from the outer layer to the inner layer, proving that the crystallinity decreases toward the inner layer and also proving the formation of a gradient heterogeneous structure. The waxs results of the freeze-dried group also prove that a heterogeneous structure has been formed, and annealing amplifies this heterogeneity. The gradient heterogeneous PVA hydrogel has high resilience, high strength, can withstand the impact of a 30kg dumbbell, and is highly soft, proving that it is a material that is both rigid and soft. Figure 12 and Figure 13 It can be seen that the gradient heterostructured PVA has a lower modulus of 0.15 MPa at low strain, and a high modulus (greater than 200 MPa) at high strain, a difference of 1000 times, achieving flexible high load-bearing, with a compressive strength of up to 37 MPa and a water content of 70%, which is also the water content range of natural load-bearing soft tissue.

[0067] Figure 14 The compression finite element can also prove that the stress of the outer layer is greater than that of the inner layer. This is achieved by converting the compressive force into the tensile force of the outer layer to achieve the flexible high load-bearing capacity, which is consistent with the natural load-bearing soft tissue. Figure 15 It can be seen from the compression hysteresis curve that the AN sample has a large hysteresis curve, which shows that it has a strong energy dissipation ability, and the energy dissipation rate is greater than 70%, which is very suitable for areas that require energy absorption and buffering. Figure 16 and Figure 17 As shown, by comparing the present invention with other high-strength hydrogels with high water content (from Document 1), it can be found that the present invention has higher strength and modulus, as well as higher water content. The performance can be adjusted by the water content. In addition, it has only one component and a simple molding method, and has good application prospects.

[0068] Example 2

[0069] A method for preparing a gradient heterogeneous structure PVA hydrogel, the specific steps are as follows:

[0070] (1) PVA particles were dissolved in deionized water at 120°C and 1.5 atm for 30 min to obtain a PVA aqueous solution with a mass concentration of 10 wt%;

[0071] (2) The PVA aqueous solution was injection molded in a bionic intervertebral disc-shaped mold at an injection pressure of 5 MPa, an injection temperature of 60 °C, and an injection time of 1 min;

[0072] (3) Freeze-drying;

[0073] The mold of step (2) was frozen at -20°C and placed in a vacuum freeze dryer, and freeze-dried for 8 hours at a vacuum degree of 0.1 mbar and a temperature of -30°C;

[0074] (4) Annealing treatment;

[0075] The freeze-dried hydrogel was placed in an oven, heated from room temperature to 60°C at a rate of 2°C / min, maintained for 30 minutes, then cooled to room temperature at a rate of 3°C / min, and finally placed in deionized water to absorb water and swell for 24 hours to obtain a biomimetic intervertebral disc-shaped gradient heterogeneous structure PVA hydrogel.

[0076] like Figure 3 As shown in the figure, the final biomimetic intervertebral disc-shaped gradient heterostructure PVA hydrogel is an integrally formed continuous gradient heterostructure; from the outside to the inside, the pore size of the gradient heterostructure PVA hydrogel gradually increases from 200 nm to 20 μm, the water content gradually increases from 70% to 90%, the crystallinity gradually decreases from 15% to 5%, and the compression modulus gradually decreases from 100 MPa to 0.1 MPa; the compression modulus of the biomimetic intervertebral disc-shaped gradient heterostructure PVA hydrogel is 0.1 MPa at the low strain stage of 10%, and the compression modulus is 200 MPa at the high strain stage of 60%, achieving rigid support; the compressive strength of the biomimetic intervertebral disc-shaped gradient heterostructure PVA hydrogel is 20 MPa, the energy dissipation rate is 80%, and the compression strength attenuation rate is 5% after 1000 times of 50% strain compression.

[0077] Biomimetic intervertebral disc-shaped gradient heterostructured PVA hydrogel is applied to biomimetic intervertebral disc scaffold.

[0078] Example 3

[0079] A method for preparing a gradient heterogeneous structure PVA hydrogel, the specific steps are as follows:

[0080] (1) PVA particles were dissolved in deionized water at 120°C and 2 atm for 60 min to obtain a PVA aqueous solution with a mass concentration of 30 wt%;

[0081] (2) The PVA aqueous solution was injection molded in a bionic meniscus-shaped mold at an injection pressure of 5 MPa, an injection temperature of 80 °C, and an injection time of 3 min;

[0082] (3) Freeze-drying;

[0083] Freeze the mold from step (2) at -20°C and place it in a vacuum freeze dryer for 24 hours at a vacuum degree of 1 mbar and a temperature of -30°C.

[0084] (4) Annealing treatment;

[0085] The freeze-dried hydrogel was placed in an oven, heated from room temperature to 90°C at a rate of 3°C / min, maintained for 90 minutes, then cooled to room temperature at a rate of 1°C / min, and finally placed in deionized water to absorb water and swell for 24 hours to obtain a biomimetic meniscus-shaped gradient heterogeneous structure PVA hydrogel.

[0086] like Figure 4 As shown in the figure, the final biomimetic meniscus-shaped gradient heterostructure PVA hydrogel is an integrally formed continuous gradient heterostructure; from the outside to the inside, the pore size of the biomimetic meniscus-shaped gradient heterostructure PVA hydrogel gradually increases from 100 nm to 10 μm, the water content gradually increases from 60% to 90%, the crystallinity gradually decreases from 20% to 8%, and the compression modulus gradually decreases from 240 MPa to 0.5 MPa; the compression modulus of the biomimetic meniscus-shaped gradient heterostructure PVA hydrogel is 0.1 MPa at the low strain stage of 20%, and the compression modulus is 240 MPa at the high strain stage of 80%, achieving rigid support; the compressive strength of the biomimetic meniscus-shaped gradient heterostructure PVA hydrogel is 30 MPa, the energy dissipation rate is 70%, and the compression strength attenuation rate is 10% after 1000 times of 50% strain compression.

[0087] Biomimetic meniscus-shaped gradient heterostructured PVA hydrogel is applied to biomimetic meniscus scaffold.

[0088] Example 4

[0089] A method for preparing a gradient heterogeneous structure PVA hydrogel, the specific steps are as follows:

[0090] (1) PVA particles were dissolved in deionized water at a high temperature and high pressure environment of 130°C and 2.5 atm for 120 min to obtain a PVA aqueous solution with a mass concentration of 40 wt%;

[0091] (2) The PVA aqueous solution was injection molded in a core-shell mold at an injection pressure of 10 MPa, an injection temperature of 100 °C, and an injection time of 4 min;

[0092] (3) Freeze-drying;

[0093] The mold of step (2) was frozen at -80°C and placed in a vacuum freeze dryer, and freeze-dried for 48 hours at a vacuum degree of 1 mbar and a temperature of -50°C;

[0094] (4) Annealing treatment;

[0095] The freeze-dried hydrogel was placed in an oven, heated from room temperature to 90°C at a rate of 4°C / min, maintained for 90 minutes, then cooled to room temperature at a rate of 1°C / min, and finally placed in deionized water to absorb water and swell for 24 hours to obtain a core-shell gradient heterostructured PVA hydrogel.

[0096] like Figure 5 As shown in the figure, the core-shell gradient heterostructure PVA hydrogel finally obtained is an integrally formed continuous gradient heterostructure; from the outside to the inside, the pore size of the core-shell gradient heterostructure PVA hydrogel gradually increases from 50nm to 10μm, the water content gradually increases from 65% to 90%, the crystallinity gradually decreases from 25% to 10%, and the compression modulus gradually decreases from 250MPa to 5MPa; the compression modulus of the core-shell gradient heterostructure PVA hydrogel is 0.099MPa at the low strain stage of 20%, and the compression modulus is 250MPa at the high strain stage of 80%, achieving rigid support; the compressive strength of the core-shell gradient heterostructure PVA hydrogel is 30MPa, the energy dissipation rate is 70%, and the compressive strength attenuation rate is 10% after 1000 times of 50% strain compression.

[0097] Core-shell gradient heterostructured PVA hydrogels are used in shock-absorbing microspheres for precision instruments.

[0098] Example 5

[0099] A method for preparing a gradient heterogeneous structure PVA hydrogel, the specific steps are as follows:

[0100] (1) PVA particles were dissolved in deionized water at a high temperature and high pressure environment of 130°C and 2.5 atm for 120 min to obtain a PVA aqueous solution with a mass concentration of 50 wt%;

[0101] (2) The PVA aqueous solution was injection molded in a cylindrical mold at an injection pressure of 10 MPa, an injection temperature of 100 °C, and an injection time of 5 min;

[0102] (3) Freeze-drying;

[0103] The mold of step (2) was frozen at -80°C and placed in a vacuum freeze dryer, and freeze-dried for 48 hours at a vacuum degree of 1 mbar and a temperature of -50°C;

[0104] (4) Annealing treatment;

[0105] The freeze-dried hydrogel was placed in an oven, heated from room temperature to 120°C at a rate of 5°C / min, maintained for 120 minutes, then cooled to room temperature at a rate of 1°C / min, and finally placed in deionized water to absorb water and swell for 24 hours to obtain a gradient heterogeneous structure PVA hydrogel.

[0106] The final cylindrical gradient heterostructure PVA hydrogel is an integrally molded continuous gradient heterostructure; from the outside to the inside, the pore size of the cylindrical gradient heterostructure PVA hydrogel gradually increases from 20nm to 2μm, the water content gradually increases from 40% to 70%, the crystallinity gradually decreases from 30% to 15%, and the compression modulus gradually decreases from 300MPa to 10MPa; the compression modulus of the cylindrical gradient heterostructure PVA hydrogel is 0.1MPa in the low strain stage of 20%, and the compression modulus is 300MPa in the high strain stage of 80%, achieving rigid support; the compressive strength of the cylindrical gradient heterostructure PVA hydrogel is 60MPa, the energy dissipation rate is 70%, and the compressive strength attenuation rate is 10% after 1000 times of 50% strain compression.

[0107] Cylindrical gradient heterostructured PVA hydrogels were applied to cartilage scaffolds.

Claims

1. A gradient heterogeneous structure PVA hydrogel, characterized by: It is an integrally formed continuous gradient heterogeneous structure; from the outside to the inside, the pore size and water content of the gradient heterogeneous structure PVA hydrogel gradually increase, and the crystallinity and compression modulus gradually decrease; The preparation method of gradient heterogeneous structure PVA hydrogel is as follows: First, a PVA aqueous solution is injection-molded in a mold. The mold is then frozen and placed in a vacuum freeze dryer for freeze-drying at a vacuum of 0.1 to 1 mbar and a temperature of -50 to -30°C for 8 to 48 hours. Finally, the freeze-dried hydrogel is removed from the mold and annealed. After the hydrogel cools to room temperature, it is placed in deionized water to absorb water and swell, thereby obtaining a gradient heterogeneous structure PVA hydrogel. The annealing process is as follows: placing the freeze-dried hydrogel in an oven, heating the temperature from room temperature to 60-120°C at a rate of 2-5°C / min, maintaining the temperature for 30-120 minutes, and then cooling the hydrogel to room temperature at a rate of 1-3°C / min.

2. The gradient heterostructure PVA hydrogel according to claim 1, characterized in that: From outside to inside, the pore size of the gradient heterogeneous structure PVA hydrogel gradually increases from 20 to 200 nm to 2 to 20 μm, the water content gradually increases from 40 to 70% to 70 to 90%, the crystallinity gradually decreases from 13 to 30% to 2 to 15%, and the compression modulus gradually decreases from 100 to 300 MPa to 100 KPa to 10 MPa.

3. The gradient heterostructure PVA hydrogel according to claim 2, characterized in that: The compression modulus of the gradient heterostructured PVA hydrogel is ≤0.1MPa in the low strain stage and ≥200MPa in the high strain stage, where the low strain stage refers to a strain of 0 to 20% and the high strain stage refers to a strain of 60 to 80%. The compression strength of the gradient heterostructured PVA hydrogel is 20 to 60MPa, the energy dissipation rate is ≥70%, and the compression strength attenuation rate is ≤10% after 1000 times of 50% strain compression.

4. The gradient heterostructure PVA hydrogel according to claim 1, characterized in that: The PVA aqueous solution is obtained by dissolving PVA particles in deionized water under a high temperature and high pressure environment of 120 to 130° C. and 1.5 to 2.5 atm, with the dissolution time being 30 to 120 minutes.

5. The gradient heterostructure PVA hydrogel according to claim 1, characterized in that: The mass concentration of the PVA aqueous solution is 10 to 50 wt%.

6. The gradient heterostructure PVA hydrogel according to claim 1, characterized in that: The injection molding pressure is 5-10 MPa, the injection molding temperature is 60-100°C, and the injection molding time is 1-5 min.

7. Use of a gradient heterogeneous structure PVA hydrogel according to any one of claims 1 to 6, characterized in that: For use on weight-bearing soft tissues.

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