Gradient heterostructure PVA hydrogel as well as preparation method and application thereof based on freeze-drying-annealing synergistic process

Abstract

The invention belongs to the technical field of hydrogel preparation, and relates to gradient heterostructure PVA hydrogel and a preparation method and application thereof based on a freeze-drying-annealing synergistic process, and the product is of an integrally formed continuous gradient heterostructure; from outside to inside, the pore diameter and the water content of the gradient heterostructure PVA hydrogel are gradually increased, and the crystallinity and the compression modulus of the gradient heterostructure PVA hydrogel are gradually reduced; the preparation method comprises the following steps: carrying out injection molding on a PVA aqueous solution in a mold, freezing the mold, putting the mold into a vacuum freeze dryer, carrying out freeze-drying for 8-48 h under the conditions of a vacuum degree of 0.1-1 mbar and a temperature of-50 to-30 DEG C, taking the freeze-dried hydrogel out of the mold, carrying out annealing treatment, cooling the hydrogel to a room temperature, putting the hydrogel into deionized water, and carrying out water absorption swelling so as to obtain the hydrogel. The product is obtained; the method is applied to bearing soft tissues. The gradient heterostructure PVA hydrogel disclosed by the invention has excellent dynamic mechanical response and energy dissipation capability; the preparation method is simple; the application prospect is good.

Description

Technical Field

[0001] The 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, the development of hydrogels that have both high water content and high strength, as well as both rigidity and flexibility, is the core goal of many cutting-edge research. 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 and high-load scenario, an ideal hydrogel needs to provide flexible cushioning (lower modulus) at low strains, rigid support (higher modulus) at high strains, and protect surrounding structures through energy dissipation. Due to its unique combination of properties, this type of material has shown great potential in the fields of biomedicine, industrial cushioning, flexible electronics, etc.

[0003] In particular, in the biomedical field, the load-bearing cartilage tissue between bones (such as intervertebral discs and menisci) has high water content (65%~90%), high flexibility and high strength (low strain and low modulus, high strain and high modulus>100MPa), high energy dissipation, excellent stress transmission and dispersion performance (converting compression force into tension force). These tissues are not a single homogeneous structure, but have obvious gradient heterogeneous structural characteristics of soft inside and hard outside, which provides ideas for bionic design. However, existing research has not yet completely solved this problem.

[0004] To achieve the above goals, researchers have explored a variety of methods to prepare high-water-content and 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.) prepared a hydrogel sponge using nano-aramid. When the water content exceeds 90%, the elastic modulus is 50~80MPa, but it is difficult to recover quickly under high load conditions, which limits its application. Reference 2 (Water-RichBiomimetic Composites with Abiotic Self-Organizing Nanofiber Network. Adv.Mater. 30, 1703343 (2018).) uses nano-aramid fiber to reinforce polyvinyl alcohol (PVA) to prepare a high-water content hydrogel with a water content of 70% to 92% and a compressive strength of 26MPa, but its initial modulus is too high and does not have flexible load-bearing capacity. Therefore, this type of single structure can no longer achieve mechanical properties that combine rigidity and flexibility, and it is necessary to seek inspiration from natural load-bearing tissues.

[0005] In order to imitate the gradient heterogeneous structure of natural tissues to achieve the characteristics of 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-carbonnanotube / polyvinyl alcohol-borax hybrid conductive hydrogel. Fuhe CailiaoXuebaoActa Mater. Compos. Sin. 34, 2312–2320 (2017).) used PVA and sodium alginate to prepare core-shell structures of different hardness, which have certain rigid-flexible mechanical properties, but the process is relatively complicated, and harmful cross-linking agents such as glutaraldehyde are introduced, and the compressive strength is low. 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 PCL fiber rings, and uses GelMA as the nucleus pulposus to make a bionic gradient heterogeneous structure intervertebral disc, but due to the large mechanical difference between the two materials, the interface bonding problem and the overall shear mechanics problem limit its clinical application. Patent CN111938883A discloses a bionic intervertebral disc, which constructs the fiber ring through a braided structure to improve the strength, and the flexible material is embedded in the upper and lower rigid cartilage plates to achieve a certain degree of mechanical transmission, but multiple components lack consistent gradients and have interface problems. At the same time, the process is complex and the mechanical transmission is nonlinear. In summary, these methods face problems such as low interface bonding strength, lack of gradient, discontinuous force transmission dispersion, high manufacturing cost, complex process, and biocompatibility problems, and cannot 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 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 PVA and bacterial cellulose composite hydrogel by annealing method, 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 freeze-drying-annealing synergistic process to solve the problems existing in the prior art. Summary of the invention

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

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

[0010] A gradient heterogeneous structure PVA hydrogel is an integrally formed 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.

[0011] As the preferred technical solution:

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

[0013] A gradient heterogeneous structure PVA hydrogel as described above, the gradient heterogeneous structure PVA hydrogel biomimetic mechanical response characteristics of natural load-bearing soft tissue, achieves mechanical properties of both rigidity and flexibility, the compression modulus is ≤0.1MPa in the low strain stage, providing flexible buffering, and the compression modulus is ≥200MPa in the high strain stage, 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 compression strength of the gradient heterogeneous structure PVA hydrogel is 20~60MPa, the energy dissipation rate is ≥70%, and the compression strength attenuation rate after 1000 times of 50% strain compression is ≤10%, which can achieve the same load-bearing mode as natural load-bearing soft tissue and convert the compressive force into the tensile force of the peripheral high modulus zone.

[0014] The present invention also provides a method for preparing a gradient heterogeneous structure PVA hydrogel as described in any of the above items, firstly, a PVA aqueous solution is 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. Under this condition, incomplete freeze-drying can be achieved. Finally, the freeze-dried hydrogel is taken out of the mold for annealing treatment. After the hydrogel is cooled to room temperature, it is placed in deionized water to absorb water and swell, so as to obtain a gradient heterogeneous structure PVA hydrogel.

[0015] In view of the core challenges of existing high-water-content hydrogels, such as the difficulty in balancing high strength and flexible load-bearing, insufficient interface bonding strength of heterogeneous structures, poor stress transfer and dispersion capabilities, and complex processes, the present invention proposes a new freeze-drying-annealing collaborative process to construct a continuous gradient heterogeneous structure with soft inside and hard outside (referred to as gradient heterogeneous PVA hydrogel) in a single PVA matrix, breaking through the limitations of traditional technology. Specifically, through the control of vacuum field and temperature field, the crystallinity and hydrogen bonds of the PVA segments gradually decrease from the outside to the inside, the water content gradually increases, and the mechanical properties gradually weaken, thereby forming a gradient heterogeneous structure 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, forming a dense structure. The further inward, the higher the water content, the looser the structure, and the lower the crystallinity from the outside to the inside. This difference is amplified by subsequent annealing, thereby enhancing the difference in mechanics and internal and external heterogeneity.

[0017] As the preferred technical solution:

[0018] In the preparation method of a gradient heterogeneous structure PVA hydrogel as described above, 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 1.5-2.5atm, and the dissolution time is 30-120min.

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

[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 1~5min.

[0021] In the preparation method of a gradient heterogeneous structure PVA hydrogel as described above, the annealing process is as follows: the freeze-dried hydrogel is placed in an oven, the temperature is raised from room temperature to the target temperature (60-120°C) at a rate of 2-5°C / min, maintained for 30-120 minutes, and then slowly cooled to room temperature at a rate of 1-3°C / 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 a bionic intervertebral disc scaffold, a bionic meniscus scaffold or a bionic cartilage scaffold; the gradient heterostructured PVA hydrogel has high strength, flexibility and high load-bearing performance, which is 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 capacity; 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, and the compressive strength can reach up to 60 MPa. A hydrogel weighing 10g 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 tissues; 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%. At the same time, it supports flexible customization of different mechanical properties and water content, and has good prospects for industrial transformation.

[0026] (3) The present invention discloses a method for preparing a gradient heterogeneous structure PVA hydrogel, which designs a continuous gradient heterogeneous structure with a water content gradually increasing 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 transfer without the risk of interface stratification; 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 It 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 of 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] Fig. 9 The crystallinity at different freeze-drying times calculated by DSC curve in Example 1;

[0037] Fig.10 The waxes spectra of different samples in Example 1;

[0038] Fig.11 The waxs two-dimensional curves of different samples in Example 1;

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

[0040] Fig.13 The figure is a comparison chart of compression modulus and compression strength of different samples in Example 1, wherein 20% represents the modulus when compressed to 20%, and 80% represents the modulus when compressed to 80%;

[0041] Fig.14 The gradient heterogeneous structure PVA hydrogel (i.e., AN24 sample) of Example 1 is compressed by finite element;

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

[0043] Fig.16 The compression modulus of Example 1 of the present invention is compared with that of the high-strength and high-water-content hydrogel;

[0044] Fig.17 The compressive strength comparison between Example 1 of the present invention and the high-strength and high-water-content hydrogel;

[0045] Among them, 1-1 is a cylindrical outer layer, and 1-2 is a 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 is the outer layer of the gradient heterogeneous structure PVA hydrogel sample obtained by lyophilization for 24 hours and annealing, AN16-O is the outer layer of the gradient heterogeneous structure PVA hydrogel sample obtained by lyophilization for 16 hours and annealing, AN8-O is the outer layer of the gradient heterogeneous structure PVA hydrogel sample obtained by lyophilization for 8 hours and annealing, AN24-M is the outer layer of the gradient heterogeneous structure PVA hydrogel sample obtained by lyophilization for 24 hours and annealing. AN16-M is the transition layer of the gradient heterostructure PVA hydrogel sample obtained by freeze-drying for 16 hours and annealing, AN24-I is the inner layer of the gradient heterostructure PVA hydrogel sample obtained by freeze-drying for 24 hours and annealing; AN8-I is the inner layer of the gradient heterostructure PVA hydrogel sample obtained by freeze-drying for 8 hours and annealing; FD24-O is the outer layer of the PVA hydrogel that has been freeze-dried for 24 hours, FD24-M is the middle layer of the PVA hydrogel that has been freeze-dried for 24 hours, and FD24-I is the inner layer of the PVA hydrogel that has been freeze-dried for 24 hours;

[0048] CY-ANF is cyano-aramid nanofiber; BANF is double network aramid nanofiber; Articularcartilage 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 protein composite; PAMPS-PDMAAM is poly(2-acrylamide-2-methylpropanesulfonic acid)-poly(N,N-dimethylacrylamide) double network; g-CN-AHPA is graphite phase carbon nitride-aminohydroxyapatite composite. DETAILED DESCRIPTION

[0049] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it 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 within the scope limited by the appended claims of the application equally.

[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 by universal testing machine, measuring 10%, 20%, 60% and 80% compression modulus.

[0054] Energy dissipation rate: ASTMD 4065-20 standard, the purpose of this standard: to determine the energy loss of materials during loading-unloading by dynamic mechanical analysis (DMA) or cyclic compression test. Test method: Calculate the energy dissipation rate by the hysteresis area of ​​the compression recovery curve.

[0055] Compression strength decay rate: ASTM D695-15, the purpose of this standard: to evaluate the strength degradation rate of materials under cyclic compression loads. Test method: observe the peak stress through continuous compression cycles to obtain the compression strength decay rate.

[0056] Example 1

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

[0058] (1) dissolving PVA particles 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] The mold of step (2) was frozen (referred to as FT sample) and placed in a vacuum freeze dryer for freeze drying at a vacuum degree of 1 mbar and a temperature of -30°C for 24 h. The freeze dried sample was referred to as FD sample.

[0062] (4) Annealing treatment;

[0063] The freeze-dried hydrogel was placed in an oven and heated from room temperature to 90°C at a rate of 5°C / min and maintained for 60 min. It was 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 h 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 outside to inside, the pore size of the gradient heterostructure PVA hydrogel gradually increases from 100nm to 10μm, the water content gradually increases from 65% to 90%, the crystallinity gradually decreases from 13% to 2%, and the compression modulus gradually decreases from 256MPa to 100KPa; the compression modulus of the cylindrical gradient heterostructure PVA hydrogel is 0.1MPa at the low strain stage of 20%, and the compression modulus is 256MPa at the high strain stage of 80%; the compression strength of the cylindrical gradient heterostructure PVA hydrogel is 37MPa, the energy dissipation rate is 72%, and the compression strength attenuation rate is 10% after 1000 times of 50% strain compression; the cylindrical gradient heterostructure PVA hydrogel is applied to 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, a cylindrical outer layer 1-1 with a low moisture content and a cylindrical inner layer 1-2 with a high moisture content are formed. Due to the integrated molding process, the outer layer and the inner layer are not layered, the pore size gradually increases from the outer layer to the inner layer, the mechanical gradient is weakened, and the moisture content gradient is increased, and there is no problem of insufficient interface bonding force. 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, the mechanical properties are improved and the moisture content is reduced when the concentration is increased; the outer layer thickness is increased when the freeze-drying time is increased, the overall moisture content is reduced, and the mechanical properties are improved; the annealing temperature is increased, the overall mechanical properties are improved, and the moisture content is reduced; the annealing time is increased, the overall moisture content is reduced, and the mechanical properties are improved.

[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 a 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 size of the crystallinity, such as Fig. 9 As shown in the figure, 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. Fig.10 The waxs curve and Fig.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 is 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 flexible. Fig.12 and Fig.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] Fig.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 high load-bearing capacity of flexibility, which is consistent with the natural load-bearing soft tissue. Fig.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 fields that require energy absorption and buffering. Fig.16 and Fig.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, and the performance can be adjusted by the water content. 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) dissolving PVA particles 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 bionic intervertebral disc-shaped gradient heterogeneous structure PVA hydrogel.

[0076] like Figure 3 As shown, the final bionic intervertebral disc-shaped gradient heterostructure PVA hydrogel is an integrated continuous gradient heterostructure; from outside to inside, the pore size of the gradient heterostructure PVA hydrogel gradually increases from 200nm to 20μm, the water content gradually increases from 70% to 90%, the crystallinity gradually decreases from 15% to 5%, and the compression modulus gradually decreases from 100MPa to 0.1MPa; the compression modulus of the bionic intervertebral disc-shaped gradient heterostructure PVA hydrogel is 0.1MPa at the low strain stage of 10%, and the compression modulus is 200MPa at the high strain stage of 60%, achieving rigid support; the compressive strength of the bionic intervertebral disc-shaped gradient heterostructure PVA hydrogel is 20MPa, 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 used in bionic intervertebral disc scaffolds.

[0078] Example 3

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

[0080] (1) dissolving PVA particles 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] The mold of step (2) was frozen at -20°C and placed in a vacuum freeze dryer, and freeze-dried 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 min, 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 h to obtain a bionic meniscus-shaped gradient heterogeneous structure PVA hydrogel.

[0086] like Figure 4 As shown, the bionic meniscus-shaped gradient heterostructure PVA hydrogel finally prepared is an integrated continuous gradient heterostructure; from the outside to the inside, the pore size of the bionic meniscus-shaped gradient heterostructure PVA hydrogel gradually increases from 100nm to 10μm, the water content gradually increases from 60% to 90%, the crystallinity gradually decreases from 20% to 8%, and the compression modulus gradually decreases from 240MPa to 0.5MPa; the compression modulus of the bionic meniscus-shaped gradient heterostructure PVA hydrogel is 0.1MPa at the low strain stage of 20%, and the compression modulus is 240MPa at the high strain stage of 80%, achieving rigid support; the compressive strength of the bionic meniscus-shaped gradient heterostructure PVA hydrogel is 30MPa, 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) dissolving the PVA particles in deionized water at a high temperature and high pressure 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 for freeze drying at a vacuum degree of 1 mbar and a temperature of -50°C for 48 hours;

[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 min, 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 h to obtain a core-shell gradient heterostructured PVA hydrogel.

[0096] like Figure 5 As shown, the core-shell gradient heterostructure PVA hydrogel finally obtained is an integrated 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 compression strength of the core-shell gradient heterostructure PVA hydrogel is 30MPa, the energy dissipation rate is 70%, and the compression 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) dissolving PVA particles 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 for freeze drying at a vacuum degree of 1 mbar and a temperature of -50°C for 48 hours;

[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 min, 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 h to obtain a gradient heterogeneous structure PVA hydrogel.

[0106] The final cylindrical gradient heterostructure PVA hydrogel is an integrated 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 compression 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 in that: It is an integrally formed 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.

2. A 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 20-200 nm to 2-20 μm, the water content gradually increases from 40-70% to 70-90%, the crystallinity gradually decreases from 13-30% to 2-15%, and the compression modulus gradually decreases from 100-300 MPa to 100 KPa-10 MPa.

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

4. The method for preparing a gradient heterogeneous structure PVA hydrogel according to any one of claims 1 to 3, characterized in that: First, the PVA aqueous solution is injection molded in a mold, and then the mold is frozen and placed in a vacuum freeze dryer for freeze drying under the conditions of a vacuum degree of 0.1~1mbar and a temperature of -50~-30℃ for 8~48h. Finally, the freeze-dried hydrogel is taken out of the mold for annealing. After the hydrogel is cooled to room temperature, it is placed in deionized water to absorb water and swell to obtain a gradient heterogeneous structure PVA hydrogel.

5. The method for preparing a gradient heterogeneous structure PVA hydrogel according to claim 4, 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 120-130°C and 1.5-2.5atm, and the dissolution time is 30-120min.

6. The method for preparing a gradient heterogeneous structure PVA hydrogel according to claim 5, characterized in that: The mass concentration of PVA aqueous solution is 10~50wt%.

7. The method for preparing a gradient heterogeneous structure PVA hydrogel according to claim 4, characterized in that: The injection pressure is 5~10 MPa, the injection temperature is 60~100℃, and the injection time is 1~5min.

8. The method for preparing a gradient heterogeneous structure PVA hydrogel according to claim 4, characterized in that: The annealing process is as follows: the freeze-dried hydrogel is placed in an oven, the temperature is raised from room temperature to 60-120°C at a rate of 2-5°C / min, maintained for 30-120 minutes, and then cooled to room temperature at a rate of 1-3°C / min.

9. The use of a gradient heterogeneous structure PVA hydrogel according to any one of claims 1 to 3, characterized in that: For use on weight-bearing soft tissues.

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