Pure pva hydrogel and preparation method, composite oil hydrogel, biological tissue repair material, dressing

Abstract

The application provides a pure PVA hydrogel and a preparation method, a composite oil hydrogel, a biological tissue repair material and a dressing, and relates to the technical field of medical materials; the pure PVA hydrogel solves the technical problem that the existing PVA hydrogel is difficult to simultaneously consider the single composition, excellent mechanical property and good biocompatibility. The pure PVA hydrogel provided in the application has simple composition, excellent mechanical property, the elongation at break reaches 420%, the tensile modulus is 6500kPa, the elastic modulus is 300kPa, and the biocompatibility is excellent.

Description

Technical Field

[0001] This invention relates to the technical field of medical materials, and in particular to a pure PVA hydrogel and its preparation method, a composite oil-hydrogel, a biological tissue repair material, and a dressing. Background Technology

[0002] PVA hydrogel materials have become a popular candidate material for medical materials due to their good biocompatibility, certain mechanical properties and elongation at break. They are popular research materials in fields such as dressings and biomimetic materials.

[0003] However, the mechanical strength of existing PVA hydrogel materials is still insufficient to meet the requirements of many medical applications. To improve the strength of PVA hydrogel materials, the main methods currently employed include: (1) By adding cross-linking components, such as inorganic salt ions and polar organic reagents (such as glycerol, DMSO, etc.), random crystalline domains are formed in the PVA molecular chain, thereby increasing the overall crystallinity of PVA and thus increasing the overall modulus of PVA gel. However, this method will lead to the residue of other additives or organic reagents, which is not conducive to wound or medical recovery.

[0004] (2) Stimulation by applying an external force field to promote the rearrangement of PVA molecular chains, such as stress tensile annealing. This method usually requires complex molds, precise deformation control, temperature control and other operations; and the PVA prepared by this method usually has a low elongation at break, only about 100%; it may cause discomfort due to mechanical mismatch when applied to the body surface. Summary of the Invention

[0005] The purpose of this application is to provide a pure PVA hydrogel with good mechanical properties and elongation at break.

[0006] Another objective of this application is to provide a method for preparing pure PVA hydrogels.

[0007] Another objective of this application is to provide a biological tissue repair material.

[0008] Another object of this application is to provide a dressing.

[0009] In a first aspect, this application provides a pure PVA hydrogel with an anisotropic porous structure, wherein the anisotropic porous structure is composed of crystalline PVA crosslinking domains and non-crystalline PVA crosslinking domains.

[0010] Furthermore, in some embodiments of this application, the crystalline PVA crosslinking domains and the amorphous PVA crosslinking domains are arranged alternately.

[0011] Furthermore, in some embodiments of this application, the non-crystalline PVA crosslinking domains are located between adjacent crystalline PVA crosslinking domains.

[0012] Furthermore, in some embodiments of this application, scanning electron microscope (SEM) images of the pure PVA hydrogel are obtained in a direction perpendicular to the extension direction of the crystalline PVA crosslinking domains, and the SEM area of ​​the non-crystalline PVA crosslinking domains is 10-50% of the SEM area of ​​the crystalline PVA crosslinking domains.

[0013] Furthermore, in some embodiments of this application, the pore size of the anisotropic porous structure is 5-50 μm.

[0014] Furthermore, in some embodiments of this application, the thickness of the crystalline PVA crosslinked domains is 0.05-5 μm, and the ratio of their length to thickness is not less than 50.

[0015] Furthermore, in some embodiments of this application, the pure PVA hydrogel does not contain any additional inorganic salts, chemical crosslinking agents, initiators, or organic solvents; the concentration of inorganic salt ions in the pure PVA hydrogel is not higher than 500 ppm, and the concentration of organic solvents is not higher than 1000 ppm.

[0016] Furthermore, in some embodiments of this application, the pure PVA hydrogel has a tensile strength of not less than 6500 kPa, an elongation at break of not less than 420%, and an elastic modulus of not less than 300 kPa.

[0017] Secondly, this application also provides a method for preparing the pure PVA hydrogel described in the first aspect, comprising the following steps: Provide PVA aqueous solution; The PVA aqueous solution was subjected to multiple freeze-thaw cycles to obtain a PVA gel prepolymer. The PVA gel prepolymer was dehydrated under pressure and then rehydrated to obtain the pure PVA hydrogel.

[0018] Furthermore, in some embodiments of this application, the number of freeze-thaw cycles is at least 5 times; the interval is 12 to 24 hours.

[0019] Furthermore, in some embodiments of this application, the freezing-thawing cycle is -20 to -90°C; the thawing temperature is 4 to 90°C; and the interval between two freezing-thawing cycles is the same.

[0020] Furthermore, in some embodiments of this application, the PVA gel prepolymer is dehydrated and rehydrated under pressure at least once.

[0021] Furthermore, in some embodiments of this application, the pressure applied during pressurization is >0.05 MPa; the direction of pressure application is perpendicular to the gel surface.

[0022] The water content in the dehydrated PVA gel prepolymer is no higher than 5%.

[0023] Furthermore, in some embodiments of this application, the concentration of PVA in the PVA aqueous solution is 5-20% by mass fraction.

[0024] Thirdly, this application also provides a composite oil-hydrogel, which also has the structure of a pure PVA hydrogel as described in the first aspect, namely: an anisotropic porous structure, wherein the anisotropic porous structure is composed of crystalline PVA crosslinking domains and non-crystalline PVA crosslinking domains; the non-crystalline PVA crosslinking domains are further distributed with hydrophobic components, wherein the mass percentage of the hydrophobic components is 5% to 25%, and the hydrophobic components are selected from one or more of medical-grade anhydrous lanolin, food-grade beeswax, medical silicone gel, petrolatum, long-chain alkanes, and solid oils.

[0025] Fourthly, this application also provides a dressing, comprising the pure PVA hydrogel prepared by the method described in the first aspect or the method described in the second aspect, or the PVA hydrogel described in the third aspect.

[0026] Fifthly, this application also provides a biological tissue repair material, including the pure PVA hydrogel prepared by the method described in the first aspect or the pure PVA hydrogel prepared by the method described in the second aspect, or the PVA hydrogel described in the third aspect.

[0027] This application provides a pure PVA hydrogel, which is prepared from an aqueous PVA solution to form an anisotropic porous structure with specific ordered arrangements of crystalline and non-crystalline domains. It does not contain any other additives or organic solvents, thus minimizing its adverse effects on human tissues when used in the human body. Furthermore, the anisotropic porous structure formed by the ordered arrangement of specific crystalline and non-crystalline domains gives it not only good tensile strength but also good elongation at break, broadening its application range and improving its mechanical compatibility with the human body. It is particularly suitable for implantable materials to replace or repair certain human tissues. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the specific embodiments of this application or the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0029] Figure 1 This is a longitudinal cross-sectional SEM image of the PVA gel prepolymer obtained in Comparative Example 3 of this application without pressure dehydration and rehydration, where the small image on the right is an enlarged view of area A in the small image on the left. Figure 2 The image shows a longitudinal cross-sectional SEM image of the pure PVA hydrogel before rehydration, obtained from the PVA gel prepolymer of Comparative Example 3 in this application after pressure dehydration. Figure 3 This is a cross-sectional SEM image of the pure PVA hydrogel obtained by pressure dehydration and rehydration in Example 1 of this application after S1, S2 and S3, where the small image on the right is an enlarged view of area A of the small image on the left. Figure 4 This is a cross-sectional SEM image of the pure PVA hydrogel obtained by pressure dehydration and rehydration in Example 1 of this application after S1, S2 and S3. The small images on the right and left are SEM images of crystalline PVA crosslinking domains of different sizes (in the figures, crystalline PVA crosslinking domains are labeled as crystalline domains; non-crystalline PVA crosslinking domains are labeled as non-crystalline domains).

[0030] Figure 5 The XRD patterns are of the PVA gel prepolymer obtained in Comparative Example 3 without pressure dehydration and rehydration and the pure PVA hydrogel obtained in Example 1 after pressure dehydration and rehydration in S1, S2, and S3. Detailed Implementation

[0031] The technical solutions of this application will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0032] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0033] The following disclosure provides many different embodiments or examples for implementing different structures of this application. To simplify the disclosure, specific examples of components and arrangements are described below. Of course, these are merely examples and are not intended to limit the scope of this application. Furthermore, reference numerals and / or letters may be repeated in different examples; such repetition is for simplification and clarity and does not in itself indicate a relationship between the various embodiments and / or arrangements discussed. In addition, examples of various specific materials are provided in this application, but those skilled in the art will recognize the application of other processes and / or the use of other materials.

[0034] Based on this, this application provides a pure PVA hydrogel with an anisotropic porous structure, wherein the anisotropic porous structure is composed of crystalline PVA crosslinking domains and non-crystalline PVA crosslinking domains.

[0035] In this application, the anisotropic porous structure in the pure PVA hydrogel is formed by the arrangement and connection of crystalline PVA crosslinking domains and non-crystalline PVA crosslinking domains in a specific order to form an anisotropic porous membrane structure. The "anisotropy" here includes not only the different pore structures in different directions, but also the different distribution structures of the crystalline PVA crosslinking domains and non-crystalline PVA crosslinking domains.

[0036] The crystalline PVA crosslinked domains are roughly long-fiber structures, distributed in layers within the pure PVA hydrogel, with a certain spacing between adjacent crystalline PVA crosslinked domains. Non-crystalline PVA crosslinked domains connect adjacent crystalline PVA crosslinked domains, forming a porous structure that roughly resembles the pore structure of lignin. Because the crystalline PVA crosslinked domains in this pure PVA hydrogel have a long-fiber structure, they provide high tensile strength, resulting in high tensile strength. Simultaneously, the porous structure formed by the non-crystalline PVA crosslinked domains located between the layered crystalline PVA crosslinked domains, along with the non-crystalline PVA crosslinked domains themselves, provides structural and material support for improving its elongation at break, thus exhibiting excellent elongation at break properties. Therefore, it possesses both excellent tensile strength and elongation at break.

[0037] The pure PVA hydrogel is imaged using a scanning electron microscope (SEM) in a direction perpendicular to the extension direction of the crystalline PVA crosslinking domains. The SEM area of ​​the crystalline PVA crosslinking domains accounts for 10-50% of the total SEM area of ​​crystalline and amorphous PVA crosslinking domains. Preferably, the SEM area of ​​amorphous PVA crosslinking domains is 20-30% of the SEM area of ​​crystalline PVA crosslinking domains. The proportion of crystalline PVA crosslinking domains in the pure PVA hydrogel should not be too high or too low. An excessively high proportion of crystalline PVA crosslinking domains will lead to overall PVA crystallization and a lower elongation at break, while an excessively low proportion of crystalline PVA crosslinking domains will easily lead to a lower overall strength. Furthermore, the proportion of the SEM area of ​​crystalline PVA crosslinking domains to the total area is characterized by the following method: First, the SEM grayscale images of the PVA samples were preprocessed to achieve background homogenization and Gaussian noise reduction. An adaptive thresholding method was then used to binarize and segment the preprocessed images, initially separating the high-grayscale protruding regions from the low-grayscale flat amorphous substrate regions. Only horizontally continuous linear protrusions were retained, completely eliminating isolated bright spots, scattered short-range protrusions, and other discontinuous interference regions, ensuring that only horizontally striation-shaped crystalline PVA cross-linked domains were included in the effective statistical range. Finally, a pixel-based statistical method was used to count the total number of pixels in the effective crystalline cross-linked domain region and the total number of pixels in the entire SEM image. The ratio of these two values ​​represents the proportion of the crystalline PVA cross-linked domains (horizontal striations) to the total area of ​​the sample observation region.

[0038] In some embodiments, the pore size of the anisotropic porous structure is 5-50 μm, preferably 10 μm to 30 μm. The pore size of the anisotropic porous structure should not be too high or too low. Too high a pore size will lead to unstable pore structure and stress concentration when subjected to force, while too low a pore size will lead to pore closure during dehydration compression and no pore structure after rehydration.

[0039] In some embodiments, the thickness of the crystalline PVA crosslinked domains is 0.05-5 μm, and the length-to-thickness ratio is not less than 50. Since the crystalline PVA crosslinked domains have a layered structure similar to a long fiber, they have a large length-to-thickness ratio, and their long fiber-like structure also provides them with good tensile strength. Preferably, the thickness of the crystalline PVA crosslinked domains is 0.2-2 μm, and the length-to-thickness ratio is not less than 100.

[0040] In some embodiments, the concentration of inorganic salt ions in the pure PVA hydrogel is no higher than 500 ppm, and the concentration of organic solvents is no higher than 1000 ppm. Since the pure PVA hydrogel provided in this application does not contain any additional exogenous additives such as inorganic salts, chemical crosslinking agents, initiators, or organic solvents during its preparation, the concentration of inorganic salt ions in the resulting hydrogel is extremely low or almost non-existent. Simultaneously, the content of organic solvents, such as glutaraldehyde, DMSO, and glycerol, is also extremely low or almost non-existent. Furthermore, the pure PVA hydrogel provided in this application does not contain any other reinforcing particles, making it exhibit pure PVA hydrogel characteristics. This is particularly advantageous for its use in implantable materials, avoiding the potential adverse effects on the human body from inorganic salt ions, organic solvents, and other reinforcing particles.

[0041] In some embodiments, the pure PVA hydrogel has a tensile strength of not less than 6500 kPa, with a typical value of 8297 ± 65 kPa; an elongation at break of not less than 420%, with a typical value of 480 ± 25%; and an elastic modulus of not less than 300 kPa, with a typical value of 378 ± 15 kPa.

[0042] This application also provides a composite oil-hydrogel, which also has the structure of a pure PVA hydrogel as described in the first aspect, namely: an anisotropic porous structure, wherein the anisotropic porous structure is composed of crystalline PVA crosslinking domains and non-crystalline PVA crosslinking domains, wherein the non-crystalline PVA crosslinking domains are further distributed with hydrophobic components, the mass percentage of the hydrophobic components is 5% to 25%, and the hydrophobic components are selected from one or more of medical grade anhydrous lanolin, food grade beeswax, medical silicone gel, petrolatum, long-chain alkanes, and solid oils.

[0043] To facilitate those skilled in the art in better implementing or obtaining the pure PVA hydrogel provided in this application, this application also provides a method for preparing the pure PVA hydrogel described in the first aspect in a second aspect, comprising the following steps: Provide PVA aqueous solution; The PVA aqueous solution was subjected to multiple freeze-thaw cycles to obtain a PVA gel prepolymer. The PVA gel prepolymer was dehydrated under pressure and then rehydrated to obtain the pure PVA hydrogel.

[0044] The PVA hydrogel is an aqueous solution of PVA monomers, with a PVA concentration of 5-20% by mass fraction, preferably 8-13%. The concentration of the PVA aqueous solution should not be too high or too low. Excessively high PVA concentration leads to increased crystallinity and lower elongation at break after freeze-thaw cycles, making it difficult for the material to lose water during pressure dehydration and increasing the pressure required for PVA crystallization. Conversely, excessively low PVA concentration results in low crosslinking network density and poor mechanical strength of the hydrogel after freeze-thaw cycles, making it prone to water loss and brittle under pressure during pressure dehydration.

[0045] It should also be noted that "rehydration" in this application refers to: re-contaminating the dehydrated PVA gel prepolymer with water, allowing water to re-enter the PVA gel prepolymer, thereby restoring the porous structure that was compressed and collapsed due to pressure dehydration.

[0046] In this application, the PVA aqueous solution undergoes multiple freeze-thaw cycles to polymerize the PVA into a porous prepolymer structure that combines crystalline PVA gel and amorphous PVA gel. Through pressure dehydration, the crystalline PVA gel exhibits a layered structure and gradually fuses to form an alternating morphology of crystalline PVA and amorphous PVA with long fiber structures. The rehydration process restores the porous structure of the gel and endows the amorphous PVA with excellent tensile properties, as well as providing space and connection for the sliding of amorphous PVA domains between the long fiber structures formed by crystalline PVA.

[0047] The "pressure dehydration" refers to removing water from the PVA gel prepolymer under pressure. Taking a 10% PVA aqueous solution as an example, the pressure for pressure dehydration is >0.05 MPa, the time is 24-168 hours, and the water content after dehydration is controlled to be below 5%. The pressure for pressure dehydration should not be too high or too low. Too high a dehydration pressure will induce large-area crystallization of PVA, while too low a dehydration pressure will make it difficult to remove water from the PVA gel prepolymer to below 5%, affecting the recombination and fusion of dendritic PVA. The pressure is applied perpendicular to the surface of the pure PVA gel to promote the preferential orientation of crystalline PVA perpendicular to the direction of the applied force, which is beneficial to the formation of anisotropic hydrogel layer structures. Preferably, the pressure for pressure dehydration is greater than 0.05 MPa and less than 1 MPa.

[0048] In addition, the PVA gel prepolymer in its rehydration process should be in contact with water for more than 24 hours. The rehydration time should not be too short, otherwise it will not be able to give the amorphous PVA region sufficient tensile properties and provide sufficient space and connection for the amorphous PVA domain to slide between the long fiber structures formed by the crystalline PVA.

[0049] In some embodiments, the number of freeze-thaw cycles is at least 5 times, with an interval of 12 to 24 hours, to form crystalline PVA gel, providing a crystalline material basis for subsequent pressure dehydration and rehydration to form long-fiber crystalline PVA crosslinked domains; preferably, the number of freeze-thaw cycles is 5 to 8 times, with an interval of 12 to 24 hours.

[0050] Preferably, the freezing temperature in the freeze-thaw cycle is -20 to -45°C; the thawing temperature is 4 to 20°C; and the interval between two freeze-thaw cycles is the same.

[0051] Furthermore, the PVA gel prepolymer is dehydrated and rehydrated under pressure at least once.

[0052] The concentration of PVA in the PVA aqueous solution is 5-20% by mass fraction, preferably 8-13%.

[0053] Thirdly, this application also provides a dressing, comprising the pure PVA hydrogel prepared by the method described in the first aspect or the method described in the second aspect.

[0054] Fourthly, this application also provides a biological tissue repair material, including the pure PVA hydrogel prepared by the method described in the first aspect or the pure PVA hydrogel prepared by the method described in the second aspect.

[0055] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0056] Example 1 This embodiment provides a pure PVA hydrogel, and the specific preparation steps are as follows: S1 Preparation of PVA aqueous solution Take 10g of PVA with a molecular weight of 89,000~98,000 and a degree of alcoholysis of 98%~99%, add it to 90g of deionized water, stir in a 95℃ water bath until completely dissolved, filter to remove bubbles, and obtain a 10% PVA aqueous solution by mass. S2 Preparation of PVA gel prepolymer The above PVA aqueous solution was injected into a horizontally placed flat mold with a thickness of 2 mm. After sealing, it was placed in a -40°C environment for 12 hours and then placed in a 25°C environment for 4 hours to thaw, completing one freeze-thaw cycle. The above cycle was repeated a total of 6 times with consistent cycle intervals to obtain a PVA gel prepolymer film. S3 Preparation of pure PVA hydrogel A PVA gel prepolymer membrane was placed between two parallel stainless steel metal plates, and a pressure of 0.1 MPa was applied perpendicular to the surface of the gel membrane. The pressure was maintained for 72 hours, and the membrane was dehydrated until the water content of the gel prepolymer was ≤3%, thus obtaining a dehydrated PVA gel prepolymer. The dehydrated PVA gel prepolymer was completely immersed in deionized water at 25°C, allowed to stand for 24 hours to rehydrate, and then removed to remove surface water, yielding pure PVA hydrogel. Figures 1-4 As shown.

[0057] Example 2 Compared to Example 1, this embodiment only adjusts the mass fraction of the PVA aqueous solution in step S1 to 8%, while the remaining steps and parameters are the same as in Example 1, resulting in pure PVA hydrogel.

[0058] Example 3 Compared to Example 1, this embodiment only adjusts the mass fraction of the PVA aqueous solution in step S1 to 13%, while the remaining steps and parameters are the same as in Example 1, resulting in pure PVA hydrogel.

[0059] Example 4 Compared to Example 1, this embodiment only adjusts the number of freeze-thaw cycles in step S2 to 5 times, while the remaining steps and parameters are the same as in Example 1, resulting in pure PVA hydrogel.

[0060] Example 5 Compared to Example 1, this embodiment only adjusts the number of freeze-thaw cycles in step S2 to 8 times, while the other steps and parameters are the same as in Example 1, resulting in pure PVA hydrogel.

[0061] Example 6 Compared to Example 1, this embodiment only adjusts the pressure of dehydration in step S3 to 0.06 MPa, while the other steps and parameters are the same as in Example 1, resulting in pure PVA hydrogel.

[0062] Example 7 Compared to Example 1, this embodiment only adjusts the pressure of dehydration in step S3 to 0.5 MPa, while the remaining steps and parameters are the same as in Example 1, resulting in pure PVA hydrogel.

[0063] Example 8 Compared to Example 1, this embodiment only adjusts the number of cycles of pressurized dehydration-rehydration in step S3 to 2 times (that is, after completing the first pressurized dehydration-rehydration, repeat the pressurized dehydration-rehydration operation once). The remaining steps and parameters are the same as in Example 1, and pure PVA hydrogel is obtained.

[0064] Example 9 Compared to Example 1, step S1 in this embodiment is adjusted as follows: 10g of PVA is added to 90g of deionized water, stirred in a 95°C water bath until completely dissolved, cooled to 80°C, and 5g of medical-grade petrolatum is added. The mixture is then kept warm and ultrasonically emulsified for 3 minutes to obtain a uniform emulsion, which is then filtered to remove bubbles. The remaining steps and parameters are the same as in Example 1, resulting in a modified PVA hydrogel.

[0065] Example 10 Compared to Example 9, this embodiment only replaces the added hydrophobic component with food-grade beeswax, while the amount added remains the same. All other steps and parameters are consistent with Example 9, resulting in a modified PVA hydrogel.

[0066] Example 11 Compared to Example 9, this embodiment only replaces the added hydrophobic component with medical silicone gel, while the amount added remains the same. All other steps and parameters are the same as in Example 9, resulting in a modified PVA hydrogel.

[0067] Comparative Example 1 Compared to Example 1, this comparative example only changed the number of freeze-thaw cycles in step S2 to 1 time, while the other steps and parameters were the same as in Example 1, resulting in a comparative sample.

[0068] Comparative Example 2 Compared to Example 1, this comparative example only changed the number of freeze-thaw cycles in step S2 to 3 times, while the other steps and parameters were the same as in Example 1, resulting in a comparative sample.

[0069] Comparative Example 3 Compared to Example 1, this comparative example omits the pressurized dehydration-rehydration operation in step S3. Instead, the PVA gel prepolymer prepared in step S2 is directly immersed in deionized water for 24 hours and then removed. All other parameters are consistent with those in Example 1, resulting in a comparative sample.

[0070] Comparative Example 4 Compared to Example 1, this comparative example replaces the pressure dehydration in step S3 with heating and drying at 60°C under normal pressure until the gel moisture content is ≤3%. All other steps and parameters are the same as in Example 1, resulting in a comparative sample.

[0071] Comparative Example 5 Compared to Example 1, this comparative example replaces the pressure dehydration in step S3 with vacuum freeze drying at -50°C until the gel moisture content is ≤1%. All other steps and parameters are the same as in Example 1, resulting in a comparative sample.

[0072] Comparative Example 6 Compared to Example 1, this comparative example only changed the pressure of pressurization and dehydration in step S3 to 0.04 MPa. All other steps and parameters were the same as in Example 1, resulting in a comparative sample.

[0073] Comparative Example 7 Compared to Example 1, this comparative example only changed the pressure of pressurization and dehydration in step S3 to 1.5 MPa. All other steps and parameters were the same as in Example 1, resulting in a comparative sample.

[0074] Comparative Example 8 Compared to Example 1, this comparative example only changed the mass fraction of the PVA aqueous solution in step S1 to 3%, while the remaining steps and parameters were the same as in Example 1, resulting in a comparative sample.

[0075] Comparative Example 9 Compared to Example 1, this comparative example only changed the mass fraction of the PVA aqueous solution in step S1 to 25%, while the remaining steps and parameters were the same as in Example 1, resulting in a comparative sample.

[0076] Comparative Example 10 This comparative example is an existing chemically cross-linked PVA hydrogel. The preparation steps are as follows: Take 100g of 10% PVA aqueous solution, add 0.5% by mass of glutaraldehyde cross-linking agent and 0.1mol / L hydrochloric acid catalyst, stir evenly and then inject into a mold, cross-link at 40℃ for 4h to obtain a chemically cross-linked PVA hydrogel comparative sample.

[0077] Comparative Example 11 The specific steps for this comparison are as follows: S1 Take 5g of PVA with a molecular weight of 50,000 and a degree of alcoholysis of 98% and dissolve it in 45g of deionized water to obtain an aqueous PVA solution; add 5g of petrolatum to obtain a prepolymer solution; S2 was ultrasonically emulsified at 80℃ for 3 min to obtain an emulsion; S3 The emulsion was injected into a flat mold, frozen at -20°C for 12 hours, and thawed at 25°C for 2 hours. This cycle was repeated twice to obtain the primary gel material. S4 was dried at 25℃ and normal pressure until completely dehydrated, and then immersed in deionized water for 12 hours to obtain the control sample.

[0078] Test methods The samples obtained in Examples 1-11 and Comparative Examples 1-11 were subjected to microstructure characterization, mechanical property testing, residual substance detection, and biocompatibility testing, respectively.

[0079] 1. Microstructure characterization The morphology of the longitudinal section (perpendicular to the pressurization direction) of the sample was observed using scanning electron microscopy (SEM): the sample was frozen and fractured by liquid nitrogen, freeze-dried, sputter-coated with gold, and then SEM images were taken.

[0080] Crystalline / non-crystalline PVA cross-linked domain area ratio: Following the method described in the instruction manual, the SEM image is preprocessed, binarized, segmented, and pixel counted to calculate the SEM area ratio of non-crystalline PVA cross-linked domains to crystalline PVA cross-linked domains; Length-to-thickness ratio of cross-linked domains in crystalline PVA: The thickness and length of crystalline domains in SEM images were measured, the length / thickness ratio of a single crystalline domain was calculated, and the average value of 20 sets of data was taken. Pore ​​diameter of porous structures: The equivalent diameter of the pores in the SEM images was statistically analyzed using ImageJ software, and the average value of 100 sets of data was taken.

[0081] 2. Mechanical property testing Referring to the GB / T 528-2009 standard, the sample was cut into dumbbell-shaped specimens and tested using a universal testing machine at a test temperature of 25℃ and a tensile rate of 5mm / min.

[0082] Tensile strength (fracture strength): The maximum stress at which the specimen breaks, measured in kPa; Elongation at break: The elongation of the specimen at break, expressed as % . Elastic modulus: The slope of the stress-strain curve in the range of 5% to 10% of the sample elongation, in kPa.

[0083] 3. Residual substance detection Inorganic salt ion concentration: The total inorganic ion content in the sample was measured using inductively coupled plasma optical emission spectrometry (ICP-OES), in ppm. Organic solvent residue: The total amount of organic solvent residue in the sample was determined by gas chromatography-mass spectrometry (GC-MS), in ppm.

[0084] 4. Biocompatibility testing Cytotoxicity test: The cell viability of L929 mouse fibroblasts cultured in the sample extract for 24 h was tested using the CCK-8 method according to ISO 10993-5:2009 standard to evaluate the cytotoxicity level. Hemolysis rate test: The hemolysis rate of the sample was tested according to ISO 10993-4:2017 standard.

[0085] 5. Crystallinity test The crystal structure of the sample sheet was tested using a Bruker D8 Advance X-ray diffractometer. The original spectrum was processed by background subtraction, Kα2 stripping and smoothing using EVA software. The peak separation method was used to separate the diffraction peaks of the crystalline phase and the diffuse peaks of the amorphous phase. The crystallinity was (101) crystal plane: 2θ≈19.6°. The ratio of the integrated area to the total integrated area.

[0086] The core performance test results of each embodiment and comparative example are shown in Table 1.

[0087] Table 1 Performance test results of the examples and comparative examples

[0088] As can be seen from Table 1, the pure PVA hydrogel provided in this application has a specific anisotropic pore structure formed by crystalline and amorphous domains, and the content of crystalline domains is controlled so that the ratio of the integral area of ​​the peak formed at 2θ≈19.6° to the total area in the XRD pattern of this material is between 30% and 50%. This makes the pure PVA hydrogel exhibit excellent properties of fracture strength, elongation at break and elastic modulus, thus improving the defect of PVA hydrogels in the prior art that it is difficult to achieve fracture strength, elongation at break and elastic modulus.

[0089] In summary, the pure PVA hydrogel provided in this application not only possesses excellent elongation at break but also good tensile strength and elastic modulus. Furthermore, it contains virtually no inorganic salt ions or organic solvents, and the PVA hydrogel itself exhibits excellent biocompatibility. Therefore, it is advantageous for application as a bio-replacement / repair material that comes into contact with body tissues and is implanted within the body. In particular, its high elongation at break, high tensile strength, and high elastic modulus meet the mechanical requirements of human tissue replacement / repair materials, making it even more suitable for implantation as a bio-replacement / repair material.

[0090] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.

Claims

1. A pure PVA hydrogel, characterized in that: It is an anisotropic porous structure, and the anisotropic porous structure is composed of crystalline PVA crosslinked domains and non-crystalline PVA crosslinked domains.

2. The pure PVA hydrogel according to claim 1, characterized in that, The cross-linking domains of crystalline PVA and the cross-linking domains of amorphous PVA are arranged alternately.

3. The pure PVA hydrogel according to claim 2, characterized in that, The non-crystalline PVA crosslinking domains are located between adjacent crystalline PVA crosslinking domains.

4. The pure PVA hydrogel according to claim 1, characterized in that, A scanning electron microscope (SEM) image of the pure PVA hydrogel was obtained in a direction perpendicular to the extension direction of the crystalline PVA crosslinking domains. The SEM area of ​​the non-crystalline PVA crosslinking domains was 10-50% of the SEM area of ​​the crystalline PVA crosslinking domains.

5. The pure PVA hydrogel according to claim 1, characterized in that, The anisotropic porous structure has a pore size of 5-50 μm.

6. The pure PVA hydrogel according to claim 1, characterized in that, The thickness of the crystalline PVA crosslinked domains is 0.05-5 μm, and the ratio of their length to thickness is not less than 50.

7. The pure PVA hydrogel according to claim 1, characterized in that, The pure PVA hydrogel does not contain any additional inorganic salts, chemical crosslinking agents, initiators, or organic solvents. The concentration of inorganic salt ions is not higher than 500 ppm, and the concentration of organic solvents is not higher than 1000 ppm.

8. The pure PVA hydrogel according to claim 1, characterized in that, The pure PVA hydrogel has a tensile strength of not less than 6500 kPa, an elongation at break of not less than 420%, and an elastic modulus of not less than 300 kPa.

9. The method for preparing the pure PVA hydrogel according to any one of claims 1 to 8, characterized in that, Includes the following steps: Provide PVA aqueous solution; The PVA aqueous solution was subjected to multiple freeze-thaw cycles to obtain a PVA gel prepolymer. The PVA gel prepolymer was dehydrated under pressure and then rehydrated to obtain the pure PVA hydrogel.

10. The method for preparing pure PVA hydrogel according to claim 9, characterized in that, The freeze-thaw cycle is repeated at least 5 times, with an interval of 12 to 24 hours.

11. The method for preparing pure PVA hydrogel according to claim 9, characterized in that, The freezing temperature in the freeze-thaw cycle is -20 to -90°C; the thawing temperature is 4 to 90°C; and the interval between two freeze-thaw cycles is the same.

12. The method for preparing pure PVA hydrogel according to claim 9, characterized in that, The PVA gel prepolymer is dehydrated and rehydrated under pressure at least once.

13. The method for preparing pure PVA hydrogel according to claim 9, characterized in that, The pressure applied during pressurization is >0.05 MPa; the direction of pressure application is perpendicular to the surface of the pure PVA hydrogel; the water content in the dehydrated PVA gel prepolymer is not higher than 5%.

14. The method for preparing pure PVA hydrogel according to claim 9, characterized in that, The concentration of PVA in the PVA aqueous solution is 5-20% by mass fraction.

15. A composite oil-hydrogel, characterized in that, It is an anisotropic porous structure, and the anisotropic porous structure is composed of crystalline PVA crosslinking domains and non-crystalline PVA crosslinking domains; the non-crystalline PVA crosslinking domains also contain hydrophobic components, the mass percentage of the hydrophobic components is 5% to 25%, and the hydrophobic components are selected from one or more of medical grade anhydrous lanolin, food grade beeswax, medical silicone gel, petrolatum, long-chain alkanes, and solid oils.

16. A dressing, characterized in that, The pure PVA hydrogel prepared by the method of preparing the pure PVA hydrogel according to any one of claims 1 to 8 or any one of claims 9 to 14, or the composite oil-hydrogel according to claim 15.

17. A biological tissue repair material, characterized in that, The pure PVA hydrogel prepared by the method of preparing the pure PVA hydrogel according to any one of claims 1 to 8 or any one of claims 9 to 14, or the composite oil-hydrogel according to claim 15.

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