Polyvinyl alcohol powder and hydrogel, and preparation method therefor and use thereof

Abstract

Provided in the present invention are a polyvinyl alcohol powder and hydrogel, and a preparation method therefor and the use thereof. The method mainly comprises: preparing a polyvinyl alcohol powder from polyvinyl alcohol, then mixing same with water and swirling same to make the powder swell into discrete microgel particles, and applying pressure to make polyvinyl alcohol molecular chains at the interface of the microgel diffuse, entangle and link with each other and crystallize and fuse, so as to prepare a polyvinyl alcohol hydrogel. With regard to the polyvinyl alcohol powder, the preparation method therefor comprises direct pulverization, or physical crosslinking prior to pulverization, or casting into a film prior to pulverization, etc.; and preferably, the powder is prepared by first performing casting into a film and then pulverizing same, which can make the powder more uniform in terms of crystallinity and more stable in terms of performance. With regard to the swelling process of the polyvinyl alcohol powder, it is necessary to strictly control the ratio of the powder to water, the temperature and the time to ensure that before swelling is complete, transferral into a mold is conducted and pressure is applied to form a hydrogel. Products meeting different performance requirements, including prostheses for the soft tissues of various locomotor systems, medical and esthetic filling materials, etc., are prepared by adjusting process parameters; and the polyvinyl alcohol powder can also be used for preparing PVA plastics having a three-dimensional structure, and thus has broad application prospects.

Description

Polyvinyl alcohol powder, hydrogel and preparation method and application thereof TECHNICAL FIELD

[0001] The present application relates to the technical field of polyvinyl alcohol material preparation, in particular to a polyvinyl alcohol powder, a hydrogel and a preparation method and application thereof. BACKGROUND

[0002] Human movement system soft tissues include tendons, ligaments, cartilages, menisci and the like, which play the functions of shock absorption, buffering, weight bearing and mechanical transmission. In order to play the normal physiological functions, these tissues all have the characteristics of high strength, high toughness and fatigue resistance, and these mechanical properties are derived from a large amount of extracellular matrix composed of water and fiber network in the tissues. However, since these tissues lack cells, they are difficult to regenerate after injury, and in clinical treatment, it is necessary to use a prosthesis material to reconstruct the function of the movement system soft tissues. With the progress of social aging, the demand for high-performance prosthesis materials by the population is increasing. In addition to ensuring biological safety, the movement system soft tissue prosthesis material also needs to match the mechanical characteristics of the corresponding tissue, that is, to have high strength, high toughness and fatigue resistance, and these properties are difficult to achieve in artificial synthetic materials. Hydrogel is a kind of polymer material with three-dimensional network structure containing a large amount of water, which has great similarity with extracellular matrix, and is an ideal biomedical material, but the strength of traditional hydrogel material is low, which cannot meet the requirements of the field of movement system soft tissue prosthesis materials, tissue engineering and other biomedical materials.

[0003] Breast prosthesis is used to complete breast reconstruction, breast augmentation, rhinoplasty, forehead augmentation and other plastic surgery procedures. The prosthesis material must be made of a material that is harmless to the human body, has no rejection reaction, does not deteriorate for a long time, has certain softness, is easy to shape and easy to remove. Silicone and expanded polytetrafluoroethylene are currently commercially available medical and aesthetic filling materials. However, silicone prosthesis has the following problems. 1. The silicone rubber filling material is a solid structure and cannot form a firm biological fixation with the surrounding tissue, which is prone to dislocation in the body for a long time; 2. Since the tissue cannot grow into the silicone prosthesis, immune reactions can cause a layer of capsule to form on the surface of the prosthesis, causing capsule contracture, which will cause the prosthesis to deform over a long period of time and cause unnatural appearance after surgery; 3. When subjected to a large pressure, it can deform or even break. If the filler is a silicone gel, it can cause silicone to leak into the lymphatic system or adjacent tissues, causing lymph node inflammation and mild swelling, siliconomas, muscle spasm pain, skin rash, hair loss, joint swelling and pain, and other complications (Chinese patent CN210673507U, patent WO2006079905A2, Chinese patent CN107412873A). Compared with silicone, expanded polytetrafluoroethylene material has pores on the surface that allow tissue to grow into, so it can avoid capsule contracture. However, expanded polytetrafluoroethylene material has poor toughness and high hardness, and does not match the mechanical properties of natural tissue, which affects comfort and appearance after implantation. Traditional hydrogel materials do not have enough elasticity and toughness, and do not have the properties of soft and rapid rebound of human soft tissue, which cannot meet the requirements of medical and aesthetic filling materials.

[0004] Polyvinyl alcohol (PVA) hydrogel has good biocompatibility, does not degrade in vivo, and has stable chemical properties, which has been approved by the US Food and Drug Administration (FDA) for implantation of medical devices. Due to its unique crystalline structure, the strength, toughness and fatigue resistance of polyvinyl alcohol hydrogel are expected to meet the requirements of various soft tissue prosthesis materials.

[0005] The preparation methods of traditional PVA hydrogel mainly include chemical crosslinking and physical crosslinking. However, these methods have potential defects, including uncontrollable crosslinking structure, low strength, introduction of other chemical reagents to reduce biological safety, complex operation process, etc. It is still a great challenge to prepare strong and tough polyvinyl alcohol hydrogel with fatigue resistance.

[0006] Chemical crosslinking is to make polyvinyl alcohol macromolecular chains form a network structure by adding a chemical crosslinking agent, thereby constructing a gel. Commonly used crosslinking agents for polyvinyl alcohol include glutaraldehyde, chloropropyl alcohol, boric acid and genipin, etc. Chemical crosslinking can improve the strength of polyvinyl alcohol hydrogel, but at the same time increases the brittleness of the material, i.e. reduces the toughness of the material. At the same time, chemical crosslinking has the problems of complex preparation process, residual crosslinking agent difficult to remove, etc., which reduces the biological safety.

[0007] Physical crosslinking, also known as freeze-thaw method or repeated freeze-thaw method, is the most common method for preparing PVA hydrogel. First, the PVA aqueous solution is frozen at low temperature (about minus 20°C), and the water in the PVA aqueous solution forms crystals (ice) at low temperature. The ice formed as a template, the polyvinyl alcohol molecules are close to each other, and many hydrogen bonds are formed, thereby generating crystalline fragments in the polyvinyl alcohol molecular chain. Subsequently, the frozen PVA aqueous solution is restored to room temperature, and these crystalline fragments are retained. At this time, the PVA aqueous solution is converted into PVA hydrogel, and the PVA molecular chain is physically crosslinked through the above-mentioned crystalline fragments to form a three-dimensional network structure. The above process is called a freeze-thaw cycle. Generally, one cycle can obtain a hydrogel, and with the increase of the number of cycles, the crystalline fragments in the PVA hydrogel increase, and thus the strength of the PVA hydrogel increases.

[0008] The physical crosslinking method has low cost and good biological safety. In theory, increasing the number of freeze-thaw cycles can control the mechanical properties of the final product, so that the mechanical properties of the product can be close to various human soft tissues (including strong and tough sports systems and medical and aesthetic filling tissues). In addition, the preparation process includes pouring the PVA aqueous solution into the mold for freeze-thaw, and then demolding to obtain the product, so theoretically various shaped products can be prepared by designing the mold. However, the only PVA hydrogel commercial product prepared based on this method is a cartilage prosthesis (trade name Cartiva, patent EP3277228B1, patent WO2012162552A1), and neither products with different mechanical properties nor products with complex shapes have been developed. Therefore, based on the current development status of the preparation method (repeated freeze-thaw) and the analysis and reasoning of the preparation method (repeated freeze-thaw), we believe that this method has the following shortcomings. 1. During the repeated freezing and thawing process, the heating conditions of different parts of the material are not uniform, so it may be difficult to maintain the shape during processing, and long-term freeze-thaw cycles can cause the material to shrink due to water loss (doi.org / 10.1016 / j.ces.2022.118120); 2. During the repeated freeze-thaw process, the material may interact with the container, making it difficult to demold and obtain complex shapes; 3. The repeated freeze-thaw process causes a large number of crystalline fragments to form inside the material, but the crystalline fragments are randomly distributed inside the material, making it difficult to stably control the mechanical properties of the material; 4. Although increasing the number of freeze-thaw cycles can improve the mechanical strength of the PVA hydrogel, the process is very time-consuming and consumes a large amount of energy (doi.org / 10.3390 / polym15183782).

[0009] To improve the strength and toughness of PVA hydrogel, researchers have carried out a lot of work. Most of these works are based on physically cross-linked PVA hydrogel, and the purpose is to improve the crystallinity of the hydrogel by various methods. For example, Lin et al. (DOI: 10.1126 / sciadv.aau8528) annealed the physically cross-linked PVA hydrogel to improve the crystallinity and obtained fatigue-resistant PVA hydrogel; Lin et al. (DOI: 10.1073 / pnas.1903019116) improved the orientation of the hydrogel network by mechanically training the physically cross-linked PVA hydrogel, and obtained PVA hydrogel with similar muscle mechanical properties; Chinese patent CN106432759A discloses a method for improving the strength of PVA hydrogel, which immerses the PVA hydrogel obtained by freeze-thaw cycle in saturated sodium chloride aqueous solution to improve the strength of PVA hydrogel; Hua et al. (DOI: 10.1038 / s41586-021-03212-z) obtained PVA hydrogel with high strength and toughness by directional freezing combined with salting-out method; Chinese patent CN110229374B discloses a method for preparing high-strength oriented PVA hydrogel, which further improves the strength and toughness of PVA hydrogel by pre-stretching, freeze-drying and salting-out of physically cross-linked PVA hydrogel. Although these methods have improved the mechanical properties of PVA hydrogel to some extent, the materials obtained by these methods still cannot meet the needs of sports system soft tissue prosthesis materials. Specifically, first, although some methods improve the strength and toughness, the obtained hydrogel does not have enough stiffness, i.e. the elongation at break of the material is too large (more than 200%), while the deformation range of tissues in the human body (such as ligaments and cartilage) is usually not more than 20%. Second, the preparation process of high-strength and high-toughness materials usually designs a salting-out step, and high-concentration ions will reduce the biological safety of PVA hydrogel. In addition, the anti-fatigue performance of the materials obtained by these methods is unknown, i.e. it cannot be confirmed whether the materials can withstand long-term mechanical stimulation in the in vivo stress environment, and the effectiveness of these materials has not been confirmed by in vivo experiments. Finally, the preparation process of some methods is too complex, it is difficult to control the morphology of the material, and it is difficult to obtain PVA hydrogel materials with natural tissue morphology.

[0010] In addition, PVA is a thermoplastic polymer, but its thermoplastic processing is a recognized world problem. This is determined by the molecular structure of PVA. PVA is a crystalline polymer containing a large number of intramolecular and intermolecular hydrogen bonds, with a melting point of more than 220℃. However, the decomposition temperature of PVA is relatively low, and it starts to dehydrate and etherize at 160℃, and starts to decompose at 200℃. Therefore, the melting point and decomposition temperature of PVA overlap, and it is difficult to obtain sufficient thermoplastic processing window. For this reason, the commonly used forming methods of PVA are all solution methods, such as solution spinning, solution casting film, etc. However, PVA based on solution processing forming can only prepare low-dimensional products such as films and fibers, and cannot obtain three-dimensional PVA products.

[0011] Therefore, it is urgent to find a polyvinyl alcohol hydrogel that can improve mechanical properties and consider biological safety, and has a tensile / compressive mechanical property closer to that of natural movement system soft tissue, and a preparation method thereof, so that it can be used to prepare various polyvinyl alcohol hydrogel products, such as soft tissue prosthesis, medical filling material, three-dimensional PVA plastic, etc.

[0012] SUMMARY

[0013] To solve the above problems, the present application provides a polyvinyl alcohol powder, a hydrogel and a preparation method and application thereof. The polyvinyl alcohol powder is prepared, and then mixed with water to form microgels. The polyvinyl alcohol molecular chains at the interface of the microgels are diffused, entangled, connected and crystallized to form a polyvinyl alcohol hydrogel. The preparation method of the polyvinyl alcohol powder includes direct pulverization, physical crosslinking and then pulverization, or film casting and then pulverization, etc. The film casting and then pulverization is preferred, which can make the powder more uniform in crystallinity and more stable in performance. The ratio of the powder to water, the temperature and the time need to be strictly controlled during the swelling process of the polyvinyl alcohol powder, so as to ensure that the hydrogel is formed by transferring to a mold and applying pressure during the incomplete swelling period. Different performance requirements of products can be prepared by adjusting the process parameters, including various movement system soft tissue prostheses, medical filling materials, etc. The polyvinyl alcohol hydrogel can also be used to prepare three-dimensional PVA plastic, which has a wide application prospect.

[0014] All existing technologies for preparing polyvinyl alcohol hydrogel are achieved by crosslinking polyvinyl alcohol solution, and the difference is only in the crosslinking method and the enhancement treatment after crosslinking. The chemical crosslinking hydrogel has low toughness, complex process, additive residue and low safety; the hydrogel obtained by repeated freeze-thaw method has low strength; the hydrogel obtained by freeze-thaw + annealing or freeze-thaw + mechanical training has complex operation and is difficult to match the modulus of natural tissue, and cannot simulate the morphology of natural tissue; the hydrogel obtained by freeze-thaw + salting or directional freezing + salting is easy to leave ions to reduce safety, has low modulus and complex operation.

[0015] The present application proposes a brand new preparation method of polyvinyl alcohol hydrogel without cross-linking polyvinyl alcohol solution, which can be called Hydrafusion.

[0016] For the convenience of understanding, the origin of the definition will be introduced first: the name comes from the process of bonding of thermoplastic polymer parts through Thermal fusion. Specifically, when thermoplastic polymers are heated, the mobility of the molecular chains on the surface increases. When the surfaces of two parts come into contact, the molecular chains can diffuse into each other. When the temperature decreases, the molecular chains that diffuse into each other are stabilized by entanglement and crystallization, so that the two parts are firmly connected.

[0017] The principle of Hydrafusion of the present application is similar to that of Thermal fusion, but the specific steps are different. First, polyvinyl alcohol raw materials are dissolved and cast into a film, which is air-dried to obtain a polyvinyl alcohol film. Next, the polyvinyl alcohol film is crushed to obtain polyvinyl alcohol powder particles. Then, the polyvinyl alcohol powder and water are mixed and stirred to obtain a microgel that has undergone partial swelling. Finally, the microgel is injected into a mold of a specific shape, and is kept for a period of time to allow the polyvinyl alcohol molecular chains to diffuse into each other at the interface of the microgel and form entanglement and crystallization, thereby obtaining a polyvinyl alcohol hydrogel with stable shape and structure.

[0018] The polyvinyl alcohol hydrogel prepared by the present application does not use any additives in the preparation process, ensuring the biological safety of the product. The obtained hydrogel material has a typical granular structure and has similar tensile / compressive mechanical properties to natural soft tissues of the musculoskeletal system. After being compressed or stretched for a long time, it can recover to the initial performance, and it can improve the mechanical properties of polyvinyl alcohol while considering biological safety. It can be used to develop corresponding prosthesis materials, medical and beauty filling materials, plastics and the like.

[0019] On the one hand, the present application provides a preparation method of polyvinyl alcohol powder for preparing hydrogel, which uses polyvinyl alcohol as raw material and is prepared by any one of the following four methods:

[0020] First, direct crushing;

[0021] Second, first prepare a polyvinyl alcohol solution, then physically cross-link, dry and crush;

[0022] Third, first prepare a polyvinyl alcohol solution, cast into a film, dry and crush;

[0023] Fourth, polyvinyl alcohol hot melt extrusion casting film and crushing.

[0024] The polyvinyl alcohol hydrogel preparation method provided by the application mainly involves two steps and produces two new products (polyvinyl alcohol powder and polyvinyl alcohol hydrogel). The first step is to prepare polyvinyl alcohol powder from commercially available polyvinyl alcohol; the second step is to prepare polyvinyl alcohol hydrogel from polyvinyl alcohol powder.

[0025] The polyvinyl alcohol powder can be prepared by direct crushing, physical crosslinking, or film casting. In theory, polyvinyl alcohol powder prepared by any method can be used to prepare polyvinyl alcohol hydrogel according to the method provided by the application. However, because chemical crosslinking requires the addition of a chemical crosslinking agent to change the molecular structure of PVA, the polyvinyl alcohol powder obtained by crushing cannot be used to prepare hydrogel through water fusion. This is because the process of preparing hydrogel relies on the diffusion, entanglement, and crystallization of PVA molecular chains, but chemical crosslinking restricts the movement of molecular chains, so that the powder particles cannot be fused enough to be shaped. Therefore, polyvinyl alcohol powder cannot be prepared by chemical crosslinking.

[0026] The polyvinyl alcohol powder provided by the application for preparing polyvinyl alcohol hydrogel is a new product that can be purchased and used to prepare polyvinyl alcohol hydrogel according to the operation steps in the product instructions. Only polyvinyl alcohol powder that meets the requirements can be used to prepare polyvinyl alcohol hydrogel with excellent performance, so the performance of polyvinyl alcohol powder is very important. At the same time, the performance of polyvinyl alcohol powder is closely related to its preparation process, so the preparation method of polyvinyl alcohol powder is a very important link.

[0027] Studies have shown that polyvinyl alcohol powder used to prepare hydrogel must have a suitable crystallinity, and the crystallinity of each powder must be uniform and stable to prepare polyvinyl alcohol hydrogel with excellent performance.

[0028] Crystallinity refers to the proportion of crystalline regions in polymer particles. Crystallization is an ordered arrangement of molecular chains, and the higher the crystallinity, the more regular the arrangement of molecular chains.

[0029] The crystallinity of the polyvinyl alcohol powder is the most important parameter affecting the process of preparing the hydrogel, and directly affects the mechanical properties of the polyvinyl alcohol hydrogel. Because the preparation process of the polyvinyl alcohol hydrogel provided by the present application is actually a process of diffusing the PVA molecular chains in the shell layer of a certain thickness on the surface of the powder due to swelling, and then causing the PVA molecular chains to diffuse each other between the interfaces of the microgels and entangle and crystallize. The higher the crystallinity, the more difficult the PVA molecular chains to diffuse, and the slower the diffusion. At the same time, the crystallinity cannot be too low, because if the crystallinity is too low, the diffusion speed will be too fast to control, and the PVA molecular chains will be fully swollen (diffused) before they contact each other, which makes it difficult for them to diffuse each other between the interfaces of the microgels, and thus they cannot entangle and fuse.

[0030] It can be understood that during the swelling process of the polyvinyl alcohol powder, the PVA molecular chains begin to diffuse, but have not yet diffused completely, and then after extrusion, the PVA molecular chains continue to diffuse and diffuse each other between the interfaces of the microgels, thereby entangling and crystallizing into a hydrogel. Therefore, the polyvinyl alcohol powder needs to have a suitable and uniform crystallinity to control the preparation of the polyvinyl alcohol hydrogel, so as to obtain a hydrogel with more excellent mechanical properties. The mechanical properties of the hydrogel are related to the diffusion of the PVA molecular chains, and the better the diffusion between the particles, the better the fusion of the particles, and the better the mechanical properties of the prepared hydrogel.

[0031] The crystallinity of the polyvinyl alcohol powder can be directly measured by DSC (Differential Scanning Calorimetry), and is related to the alcoholysis degree of the polyvinyl alcohol raw material. When other conditions are unchanged, the higher the alcoholysis degree of the raw material, the higher the crystallinity of the powder. At the same time, it is also related to the preparation process of the polyvinyl alcohol powder. The powder obtained by directly crushing the raw material has the highest crystallinity, the crystallinity obtained by casting a film and then crushing is significantly lower than that obtained by direct crushing, and the crystallinity obtained by physical cross-linking and drying and then crushing is related to the physical cross-linking method, which is generally low. Therefore, different processing technologies of the polyvinyl alcohol powder will result in different crystallinities of the polyvinyl alcohol powder, and the uniformity of the crystallinity between different powder particles will also be different, thereby affecting the preparation of the polyvinyl alcohol hydrogel.

[0032] Further, any one of the four methods is used to prepare the powder, and the powder with a particle size of 1-1000 μm also needs to be screened.

[0033] The polyvinyl alcohol powder used to prepare hydrogels must have a suitable particle size, as the particle size of the polyvinyl alcohol powder has a significant impact on the preparation of polyvinyl alcohol hydrogels. When other conditions remain unchanged, the smaller the particle size, the easier it is for the PVA molecular chains to diffuse. However, the particle size cannot be too small. If the particle size is too small, the powder will immediately diffuse fully upon contact with water and will no longer be able to fuse. At the same time, the particle size cannot be too large. If the thickness of the interface where diffusion occurs is similar, the larger the powder particle size, the smaller the area of ​​fusion, which will inevitably affect the performance of the hydrogel.

[0034] Therefore, the crystallinity and particle size of polyvinyl alcohol powder must be optimized within specific ranges, and the combination of the two can produce high-performance polyvinyl alcohol hydrogels. Particle size can be screened after pulverization, while crystallinity is not only related to the polyvinyl alcohol raw material but also needs to be controlled through specific processing techniques.

[0035] However, it is understandable that the crystallinity and particle size of polyvinyl alcohol powder can be selected within a wide range, thereby producing various types of polyvinyl alcohol hydrogels with different mechanical properties to meet the needs of different products.

[0036] In some embodiments, the polyvinyl alcohol powder is preferably a powder with a particle size of 50 to 150 μm.

[0037] The particle size of polyvinyl alcohol powder can be obtained by sieving after crushing. For example, for powder with a particle size of 1-1000um, sieving can yield powders with different particle size ranges such as 1-50um, 50-100um, 100-150um, 150-200um, 200-250um, and above 250um.

[0038] In some embodiments, the particle size of the polyvinyl alcohol powder is preferably 100-150 μm.

[0039] Compared to the case with a particle size of 100-150μm, when the particle size of polyvinyl alcohol powder is 50-100μm, the diffusion is faster at higher temperatures, so lower temperatures and shorter reaction times are needed to control the diffusion rate, which increases the difficulty of control and is not conducive to the preparation of hydrogels.

[0040] Furthermore, the degree of polymerization of the polyvinyl alcohol is 200-5000, and the degree of alcoholysis is 80-100%.

[0041] Furthermore, the degree of polymerization of the polyvinyl alcohol is 1500-2500, and the degree of hydrolysis is 97%-99%.

[0042] The degree of polymerization and degree of alcoholysis are determined by the polyvinyl alcohol raw material and do not change during processing. They directly affect the properties of polyvinyl alcohol powder, and thus also affect the properties of the prepared polyvinyl alcohol hydrogel.

[0043] The mechanical properties of the hydrogel are related to the diffusion of the PVA molecular chains. The better the PVA molecular chains diffuse, the better the particles fuse, and the greater the mechanical strength of the hydrogel obtained.

[0044] The greater the degree of polymerization of the polyvinyl alcohol, the longer the PVA molecular chains, and the more difficult it is for the polyvinyl alcohol powder to diffuse during the swelling process. The smaller the degree of polymerization of the polyvinyl alcohol, the shorter the PVA molecular chains, and the faster the polyvinyl alcohol powder diffuses during the swelling process. Therefore, polyvinyl alcohol with a degree of polymerization that is too large causes the PVA molecular chains to be difficult to diffuse or to diffuse too slowly, resulting in insufficient diffusion and entanglement of the microgels during the extrusion process, which directly affects the mechanical properties of the polyvinyl alcohol hydrogel. Polyvinyl alcohol with a degree of polymerization that is too small may cause the PVA molecular chains to diffuse too quickly, swell too quickly, and not be able to continue to diffuse and entangle during the extrusion process, which also affects the mechanical properties of the polyvinyl alcohol hydrogel.

[0045] The alcoholysis degree of the polyvinyl alcohol raw material affects the crystallinity of the polyvinyl alcohol powder. The greater the alcoholysis degree, the greater the crystallinity of the polyvinyl alcohol powder, and the more difficult it is for the PVA molecular chains to diffuse. The smaller the alcoholysis degree, the smaller the crystallinity, and the more likely it is that the diffusion speed will be too fast to control.

[0046] Therefore, the degree of polymerization and the alcoholysis degree of the polyvinyl alcohol raw material are preferably within a suitable range, so that polyvinyl alcohol powder that is more suitable for preparing a hydrogel in all aspects can be prepared, and thus can be used to prepare a better hydrogel.

[0047] Of course, the degree of polymerization and the alcoholysis degree of the polyvinyl alcohol raw material can also be selected within a larger range, so that polyvinyl alcohol powders of various properties can be prepared, and the diffusion effect when reacting with water is different, so that polyvinyl alcohol hydrogels of various mechanical properties can be prepared to meet the needs of different products.

[0048] In some embodiments, the polyvinyl alcohol has a degree of polymerization of 1700 and an alcoholysis degree of 99%.

[0049] In some embodiments, the polyvinyl alcohol has a degree of polymerization of 2400 and an alcoholysis degree of 99%.

[0050] In some embodiments, the polyvinyl alcohol has a degree of polymerization of 1700 and an alcoholysis degree of 88%.

[0051] Further, the polyvinyl alcohol solution in the second method (physical crosslinking) or the third method (flow casting) includes an aqueous solution of polyvinyl alcohol.

[0052] In some ways, the aqueous solution of polyvinyl alcohol contains polycarboxyl or polyhydroxy compounds, including but not limited to any one or more of citric acid, ethylenediaminetetraacetic acid, tannic acid, gallic acid, catecholamine, polyacrylic acid.

[0053] The present application has been studied and proved that the addition of polycarboxyl or polyhydroxy compounds capable of forming hydrogen bonds with polyvinyl alcohol in the polyvinyl alcohol solution for preparing powder does not affect the preparation process of polyvinyl alcohol powder and polyvinyl alcohol hydrogel, and the additional hydrogen bonds can improve the strength of the material by strengthening the high molecular network in the polyvinyl alcohol hydrogel.

[0054] Further, the mass percentage of polyvinyl alcohol in the polyvinyl alcohol solution is 5-20%.

[0055] The mass percentage of polyvinyl alcohol in the polyvinyl alcohol solution is also an important parameter. If the content of polyvinyl alcohol in the polyvinyl alcohol solution is too high or too low, although it can be cast into a film, the crystallinity uniformity of the powder prepared after crushing will be affected. Therefore, when preparing the polyvinyl alcohol solution, the appropriate content of polyvinyl alcohol should be selected to obtain more uniform and stable polyvinyl alcohol powder with appropriate crystallinity, thereby helping to prepare polyvinyl alcohol hydrogel with excellent performance in the later stage.

[0056] Further, the physical crosslinking of the second method is a polyvinyl alcohol hydrogel prepared without covalent crosslinking. For example, freeze-thaw, freeze-drying, solvent exchange, directional freezing salting-out, etc.

[0057] In theory, PVA obtained by any physical crosslinking method can be used to prepare polyvinyl alcohol hydrogel after drying and crushing. There are many physical crosslinking methods, such as freeze-thaw, freeze-drying, solvent exchange, directional freezing salting-out, etc., which are difficult to enumerate.

[0058] It is found that the crystallinity of polyvinyl alcohol powder prepared by physical crosslinking method is low, and the crystallinity of polyvinyl alcohol powder prepared by casting film is between direct crushing and physical crosslinking method.

[0059] Further, the freeze-thaw refers to freezing the polyvinyl alcohol solution and then thawing it, which is one cycle, and the total cycle is 1-10 times; the solvent exchange refers to dissolving the polyvinyl alcohol in dimethyl sulfoxide first, and then performing solvent exchange with water to prepare polyvinyl alcohol solvent exchange hydrogel.

[0060] Further, the polyvinyl alcohol as raw material can contain water or not. When the polyvinyl alcohol contains water, the first method is: drying first, then directly crushing, and screening out the powder with particle size of 1-500 μm.

[0061] Further, the third method is preferred for preparing the polyvinyl alcohol powder.

[0062] The crystallinity of the polyvinyl alcohol powder obtained by direct crushing varies with different batches of polyvinyl alcohol raw materials, even if the same polymerization degree and alcoholysis degree are selected. The stability problem may affect the mechanical properties of the hydrogel. The crystallinity of the polyvinyl alcohol powder prepared by the film casting method is more uniform, and is more suitable for preparing polyvinyl alcohol hydrogel. The uniformity of the polyvinyl alcohol powder prepared by the physical crosslinking method is improved, but the operation process is complicated, so it is difficult to control the crystallinity of the polyvinyl alcohol powder and even the stability of the mechanical properties of the polyvinyl alcohol hydrogel. During the hot melt extrusion film casting process, the crystallinity uniformity of the powder obtained after crushing is affected due to the difference in heating of different areas. Therefore, the third method (water solution film casting) is preferred for preparing the polyvinyl alcohol powder, the crystallinity of the prepared powder is the most suitable, and the consistency is very good, the operation is simple, the performance is more stable, and it can be used to prepare polyvinyl alcohol hydrogel products with more excellent performance.

[0063] Further, the film casting refers to placing the polyvinyl alcohol solution in a container, and condensing into a film after the water content is reduced.

[0064] Further, the film casting refers to placing the polyvinyl alcohol solution in a container and air drying to obtain a film with a thickness of 30-150 μm.

[0065] The thickness of the film is related to the volume of the liquid poured into the container. The more poured in, the thicker the film. The thickness of the film only affects the particle size of the powder after crushing. The thinner the film, the smaller the particle size of the powder. However, regardless of the film, the particle size of the powder after crushing still needs to be controlled by a screen, and the influence of the film thickness is not obvious. Of course, too thick film may cause poor uniformity, and too thin film is inconvenient to operate, so the thickness of the film is preferably 30-150 μm.

[0066] Further, the container is any one or more of silica gel, polytetrafluoroethylene, and polystyrene.

[0067] Further, the temperature of the hot melt extrusion in the fourth method is not more than 180℃.

[0068] Since the decomposition temperature of polyvinyl alcohol is low, the temperature of the hot melt extrusion is too high, which may damage the structure of the PVA molecular chain, thereby affecting the preparation of the hydrogel, so the temperature of the hot melt extrusion needs to be controlled to be not more than 180℃.

[0069] On the other hand, the present application provides a polyvinyl alcohol powder, the crystallinity of the polyvinyl alcohol powder is 30-60%, and the polyvinyl alcohol powder is prepared from polyvinyl alcohol with a polymerization degree of 200-5000 and an alcoholysis degree of 80-100%.

[0070] Further, the polyvinyl alcohol powder has a crystallinity of 40-48%, and is prepared from polyvinyl alcohol with a polymerization degree of 1500-2500 and an alcoholysis degree of 97-99%.

[0071] Further, the polyvinyl alcohol powder is prepared by the method as described above.

[0072] In another aspect, the present application provides a use of a polyvinyl alcohol powder for preparing a polyvinyl alcohol hydrogel, wherein the polyvinyl alcohol powder is prepared by the method as described above.

[0073] Further, the polyvinyl alcohol hydrogel is formed by swelling and connecting the polyvinyl alcohol powder, and has a granular material structure.

[0074] Further, the polyvinyl alcohol hydrogel is prepared by mixing and reacting the polyvinyl alcohol powder with water.

[0075] In another aspect, the present application provides a use of a polyvinyl alcohol powder as a raw material for preparing a polyvinyl alcohol hydrogel with adjustable mechanical properties, wherein the polyvinyl alcohol powder is prepared by the method as described above, and the mechanical properties of the polyvinyl alcohol hydrogel include any one or more of adjustable strength, rigidity, toughness and fatigue resistance.

[0076] In some embodiments, the fatigue resistance includes the ability to recover to the initial state after multiple long-time compression or stretching.

[0077] In another aspect, the present application provides a polyvinyl alcohol hydrogel, which is formed by swelling and connecting the polyvinyl alcohol powder, has a granular material structure, and has pores.

[0078] The polyvinyl alcohol hydrogel prepared by the polyvinyl alcohol powder has a typical granular structure, and under electron microscope, it can be clearly seen that it is prepared by fusion of particles, and there are micrometer-scale pores between adjacent particles that are not fused with each other. The hydrogel prepared by other methods has a relatively dense surface, and does not have a granular structure and micrometer-scale pores, so the polyvinyl alcohol hydrogel prepared by the present application is a brand new product.

[0079] Further, the polyvinyl alcohol powder has a crystallinity of 30-60%, and is prepared from polyvinyl alcohol with a polymerization degree of 200-5000 and an alcoholysis degree of 80-100%.

[0080] The preparation process of the polyvinyl alcohol hydrogel is essentially to destroy the crystallization of the polyvinyl alcohol powder in the process of swelling the polyvinyl alcohol powder with water, increase the activity of the polyvinyl alcohol molecular chain, and then make the polyvinyl alcohol molecular chain diffuse between the powder particles under the action of pressure in the mold, and make the polyvinyl alcohol powder fuse by the entanglement and crystallization of the molecular chain. Therefore, all factors affecting crystallization and diffusion, including the crystallinity, polymerization degree, alcoholysis degree, particle size, etc. of the polyvinyl alcohol powder, are very crucial to the preparation of the hydrogel and affect each other. For example, the higher the crystallinity of the polyvinyl alcohol powder, the higher the temperature and the longer the time required for reaction with water, and the lower the crystallinity of the polyvinyl alcohol powder, the lower the temperature and the shorter the time required for reaction with water.

[0081] The characteristic of the polyvinyl alcohol powder that can fuse to form a hydrogel under pressure in the swelling process may be related to the molecular chain structure of the polyvinyl alcohol, which is a straight chain structure and can diffuse in the swelling. The present application also attempts to process other natural or synthetic polymers in a similar way, but it is impossible to prepare a hydrogel.

[0082] Further, the particle size of the polyvinyl alcohol powder is 1-1000 μm, and the gap between the adjacent particles that are not fused with each other in the polyvinyl alcohol hydrogel is 1-400 μm.

[0083] Further, the particle size of the polyvinyl alcohol powder is 50-150 μm, and the gap between the adjacent particles that are not fused with each other in the polyvinyl alcohol hydrogel is 5-50 μm, and the solid content is 10%-70%.

[0084] The gap size between the adjacent particles that are not fused with each other in the polyvinyl alcohol hydrogel is determined by the particle size of the polyvinyl alcohol powder particles, and the existence of the gap between the particles also improves the fatigue resistance of the polyvinyl alcohol hydrogel, because the pore structure in the porous material can play the functions of dispersing stress and transmitting load, avoiding stress concentration, and the existence of the gap between the particles is also beneficial to the growth of cells, improving the repair effect. The polyvinyl alcohol hydrogel can recover to the initial state after being compressed or stretched for many times and for a long time, and is more suitable for preparing soft tissues of human motion system (including tendons, ligaments, cartilages, menisci, etc.), playing better functions of shock absorption, buffering, load bearing and mechanical transmission.

[0085] The solid content of the polyvinyl alcohol hydrogel also affects its mechanical properties. In general, the higher the solid content, the higher the strength.

[0086] In some ways, the solid content of the polyvinyl alcohol hydrogel prepared by the present application is between 30% and 70% by weight.

[0087] In some ways, the solid content of the polyvinyl alcohol hydrogel prepared by the present application is between about 40% and about 60% by weight.

[0088] The polyvinyl alcohol hydrogel prepared by the present application can also have a wide range of mechanical properties by adjusting the parameters of the above process. For example, in the unconfined compression test, the material can withstand more than 95% strain without breaking and can rebound after the pressure is removed, so the compression stress of the material at 95% compression strain is defined as the compression strength. In the tensile test, the peak stress of the material when it is pulled apart is defined as the tensile strength. The compression strength of the material is 1 MPa to 40 MPa, and the tensile strength of the material is 1 MPa to 20 MPa.

[0089] The polyvinyl alcohol hydrogel obtained by the method of the present application has a typical granular material structure, i.e. the bulk hydrogel is assembled by forming firm connections between the particles, so the mechanical properties of the hydrogel are determined by two factors: 1. the connection force between the particles; 2. the performance of the particles themselves. Regarding the connection force between the particles. During the molding process, diffusion and entanglement of polyvinyl alcohol molecular chains and crystallization occur between the particles. Due to the unique structure of polyvinyl alcohol with a large number of hydroxyl groups, the molecular chains entangle and recrystallize at the interface, thereby firmly connecting the particles together, so that the material does not fail when subjected to stress. For the polyvinyl alcohol hydrogel particles themselves, the load-bearing capacity is largely affected by the solid content. For any hydrogel, when the water content is high, the mechanical properties are weak, and when the water content is low, the mechanical properties are strong. Since the mutual connection of the polyvinyl alcohol microgels in the present application is completed during the swelling process of the microgels, i.e. the water content of the microgels is not high during molding, and the entanglement and crystallization at the interface further limit the water absorption of the particles, therefore, according to the process of the present application, the solid content of the polyvinyl alcohol hydrogel prepared is still high even in the fully swollen state, and can reach 70%, and by controlling the process parameters, the solid content can be generally controlled in the range of 40%-60%. Therefore, considering the above two aspects, the material has excellent mechanical properties.

[0090] In another aspect, the present application provides a method for preparing a polyvinyl alcohol hydrogel, which is prepared by swelling and connecting polyvinyl alcohol powder.

[0091] Further, the method comprises the following steps:

[0092] (1) preparing polyvinyl alcohol powder, the crystallinity of the polyvinyl alcohol powder is 30-60%, which is prepared from polyvinyl alcohol with a polymerization degree of 200-5000 and an alcoholysis degree of 80-100%;

[0093] (2) mixing the polyvinyl alcohol powder with water and stirring to make the polyvinyl alcohol powder start to swell and form microgels, and providing pressure during the swelling process to make the polyvinyl alcohol molecular chains at the interface of the microgels diffuse, entangle and connect, and crystallize and fuse to form a hydrogel.

[0094] It can be understood that as long as pressure is applied to the microgels during the swelling process, the originally separate microgels can be fused, and the direction of the pressure can be from top to bottom, from bottom to top, from left to right, from right to left, or from the middle to the outside in a hollow ring shape, and the microgels can be fused into hydrogels.

[0095] As described above, the polyvinyl alcohol hydrogel prepared by the present application is closely related to the molecular chain diffusion effect between the polyvinyl alcohol powder particles during the preparation and processing process. The more the molecular chains diffuse at the interface of the powder particles, the better the fusion, the more the crystallization formed in the fused area or the interior of the powder, and the better the strength, toughness, stiffness, and fatigue resistance of the hydrogel material, which is more suitable for use in strong and tough sports soft tissue. On the contrary, the material will be softer, which is suitable for some medical and aesthetic filling materials.

[0096] Further, the ratio of the polyvinyl alcohol powder to water in step (2) is 1:(0.5-9).

[0097] The preparation method of the polyvinyl alcohol hydrogel provided by the present application is to mix polyvinyl alcohol powder and water to prepare microgels. By controlling the ratio of the powder to water, the temperature of the water, and the mixing time, the diffusion effect of the molecular chains in the powder can be effectively controlled, so that the prepared hydrogel can better meet the needs of the product.

[0098] Further, the ratio of the polyvinyl alcohol powder to water in step (2) is 1:(2-5).

[0099] In some ways, the ratio of the polyvinyl alcohol powder to water in step (2) is 1:2.5.

[0100] The polyvinyl alcohol powder needs to be fully swollen, and the water content needs to reach more than 90%. Therefore, when the ratio of the polyvinyl alcohol powder to water is in the range of 1:(0.5-9), the microgels cannot be fully swollen, and the reaction process can be more easily controlled.

[0101] Preferably, the amount of water can be reduced, so that the water content of the microgels is low and the solid content is higher, which helps to improve the mechanical properties of the hydrogel.

[0102] Further, step (2) provides pressure during the swelling process, including providing pressure during the swelling of the polyvinyl alcohol powder to form microgels and the period when the swelling is not complete. The pressure causes the microgel particles to connect with each other to form a hydrogel. The swelling that has not been completed includes that the water content of the microgels is not more than 90%.

[0103] During the initial swelling process of polyvinyl alcohol powder, the polyvinyl alcohol molecular chains begin to diffuse and form microgels. When the diffusion reaches a certain extent, extrusion is performed. During the extrusion process, the PVA molecular chains at the microgel interface continue to diffuse and entangle with each other, and then form stable connections through crystallization to form a hydrogel.

[0104] Once the microgel has fully swollen, it is impossible to prepare a hydrogel by extrusion because the PVA molecular chains cannot continue to diffuse during the extrusion process after full swelling, and therefore cannot entangle and bond together.

[0105] Furthermore, step (2) describes providing pressure during the swelling of the polyvinyl alcohol powder, including providing pressure when the water content of the microgel is between 10% and 85%.

[0106] Different water contents in microgels indicate different degrees of swelling and diffusion, which will lead to differences in the properties of hydrogels prepared by extrusion.

[0107] Furthermore, step (2) describes providing pressure during the swelling of the polyvinyl alcohol powder, including providing pressure when the water content of the microgel is between 20% and 30%.

[0108] Further, the pressure in step (2) is (10 3 ~10 8 )Pa.

[0109] Furthermore, the pressure in step (2) is 5 to 500 kPa.

[0110] Studies have shown that as long as the microgel interfaces can fuse, the pressure range has little impact on the hydrogel's performance over a relatively large area. Understandably, if the pressure is too low, the microgels will struggle to bond together to form a hydrogel; if the pressure is too high, not only will the cost be higher, but the hydrogel may also be destroyed. Therefore, considering both convenience and cost, a pressure range of 5–500 kPa is preferred.

[0111] Further, the polyvinyl alcohol powder in step (2) is mixed with water, wherein the temperature of the water is 0 to 40°C.

[0112] Furthermore, the stirring in step (2) includes magnetic stirring, and the stirring time is 0.1 to 10 minutes.

[0113] Furthermore, step (2) describes providing pressure during the swelling process, which includes placing the microgel, which has not yet fully swollen, in a container and then compressing it.

[0114] Furthermore, step (2) involves providing pressure during the swelling process, which includes placing the microgel that has not yet fully swollen in a container, pressing it, and then placing the container together in an oven for heat preservation, wherein the oven temperature is 5 to 80°C.

[0115] In some embodiments, the container is a mold designed according to the product needs, which can be of any shape as long as the microgel can be extruded therein, including a mold base for placing the hydrogel and a pressing member for pressing the hydrogel, the pressing member can press the microgel from outside to inside, and the shape of the pressing member can also be designed as needed.

[0116] The microgel is injected into the mold for molding: the temperature and time of molding are controlled to allow fusion between the microgels, obtaining a polyvinyl alcohol hydrogel, and the shape of the mold is controlled to obtain polyvinyl alcohol hydrogels of various shapes.

[0117] Further, the holding time is 10-60 min, and then the hydrogel is removed from the container.

[0118] After holding in the oven at a certain temperature, the polyvinyl alcohol molecular chain can form more stable crystals on the interface of the microgel, thereby allowing the polyvinyl alcohol hydrogel to be shaped and fused more tightly.

[0119] After demolding, the polyvinyl alcohol hydrogel can be considered to have been prepared.

[0120] In order to better protect the polyvinyl alcohol hydrogel or improve its performance, the hydrogel can be placed in water for long-term storage after demolding, or it can be first dried and then placed in water for long-term storage. The purpose of drying is to stabilize the crystals generated at the interface of the microgel by dehydration, thereby enhancing the strength of the hydrogel.

[0121] Further, the water in step (2) can contain kosmotropic ions and / or chaotropic ions.

[0122] Further, the kosmotropic ions include any one or more of sulfate, carbonate, citrate, acetate, nitrate, chloride, iodide, and the chaotropic ions include any one or more of lithium ion, sodium ion, potassium ion, magnesium ion, calcium ion, and strontium ion.

[0123] During the process of reacting with water to form microgels, some salt solutions can be used instead of mixing water and polyvinyl alcohol powder, including kosmotropic ions such as sulfate, carbonate, citrate, acetate, nitrate, chloride, iodide, etc.; and chaotropic ions such as lithium ion, sodium ion, potassium ion, magnesium ion, calcium ion, strontium ion, etc. The obtained microgels can also be subjected to subsequent processes to obtain polyvinyl alcohol hydrogels, and the performance of the obtained hydrogels is not significantly changed.

[0124] The higher the crystallinity of the polyvinyl alcohol powder, the higher the temperature and the longer the time required, or the addition of chaotropic ions to ensure that sufficient diffusion and firm fusion between the powders can occur to ensure material forming; conversely, the lower the crystallinity of the polyvinyl alcohol powder, the lower the temperature and the shorter the time required, or the addition of kosmotropic ions to ensure that too much diffusion does not occur before the powders contact each other, so that the powders can fuse and fix when they contact each other, so that the material can be formed.

[0125] Further, the polyvinyl alcohol powder of step (1) is prepared by any one of the following four methods:

[0126] First: using polyvinyl alcohol as raw material, directly crushing and screening out powders with a particle size of 1-1000 μm;

[0127] Second: first preparing a polyvinyl alcohol solution, then physically crosslinking, drying, and crushing and screening out powders with a particle size of 1-1000 μm;

[0128] Third: first preparing a polyvinyl alcohol solution, then casting a film, crushing, and screening out powders with a particle size of 1-1000 μm;

[0129] Fourth: using polyvinyl alcohol hot melt extrusion to cast a film, crushing, and screening out powders with a particle size of 1-1000 μm.

[0130] In another aspect, the application provides a preservation method for a polyvinyl alcohol hydrogel material, wherein the polyvinyl alcohol hydrogel is a polyvinyl alcohol hydrogel prepared by the method described above or prepared by the method described above, and the polyvinyl alcohol hydrogel is first dried after demolding, then soaked in water to swell and stored; or directly soaked in water for storage.

[0131] The process of drying and dehydrating the polyvinyl alcohol hydrogel is beneficial to the recrystallization of PVA molecules, so that the connection between the microgel particles can be more firm, and thus the mechanical properties are better.

[0132] If not dried, directly soaked in water for storage, the prepared hydrogel material will be weak in strength and other mechanical properties, but can be used in some application scenarios with low requirements for mechanical properties.

[0133] The polyvinyl alcohol hydrogel has good stability and does not naturally degrade, so it can be stored in water for a long time. In addition, the newly prepared hydrogel material will usually swell by absorbing water, and long-term storage in water can obtain the material in a swollen and balanced state, in which the mechanical properties and size of the hydrogel are relatively stable, and it is more conducive to the characterization of the physical and chemical properties of the material.

[0134] In some embodiments, the air-drying can be replaced by oven-drying at about 40 degrees Celsius for 24 hours, and the sample is considered to be dried if the weight does not change after further standing.

[0135] In some embodiments, the dried polyvinyl alcohol hydrogel can be annealed.

[0136] In some embodiments, the annealing is performed at 80-160 degrees Celsius for 2 hours.

[0137] In some embodiments, the annealing is performed at 140 degrees Celsius for 2 hours.

[0138] Annealing refers to heating a material above a certain temperature to increase the crystallinity of the material. The higher the annealing temperature, the greater the strength of the hydrogel after re-swelling. The minimum temperature that can effectively increase the crystallinity of polyvinyl alcohol material is 90 degrees Celsius, but since it starts to decompose and melt at 180 degrees Celsius, the annealing temperature range should be set to 100-160 degrees Celsius. Preferably, it is 120-140 degrees Celsius, within this temperature range, the crystallinity can be increased without causing the material to decompose and denature.

[0139] In some embodiments, the dried polyvinyl alcohol hydrogel can be machined to achieve a more complex shape.

[0140] The polyvinyl alcohol hydrogel preparation method provided by the present application can be used to prepare a variety of different products, including sports system soft tissue prostheses, medical and aesthetic filling materials, and polyvinyl alcohol plastics with three-dimensional structures, by adjusting the parameters of the preparation process. For different products, there are different performance indicators: for cartilage or meniscus prosthesis products, the compression mechanical properties and friction properties need to be highlighted; for tendon or ligament prostheses, the tensile mechanical properties and suture strength properties need to be highlighted; for medical and aesthetic filling materials, machining performance is required. For each prosthesis product, good biocompatibility is required; for polyvinyl alcohol plastics, different indicators are required in different products.

[0141] In another aspect, the present application provides a method for preparing a cartilage prosthesis, comprising the following steps:

[0142] (1) preparing polyvinyl alcohol powder, the crystallinity of the polyvinyl alcohol powder is 30-50%, which is prepared from polyvinyl alcohol with a polymerization degree of 1000-3000, an alcoholysis degree of 80-100%, and a particle size of 100-400 um;

[0143] (2) mixing the polyvinyl alcohol powder with water and stirring to make the polyvinyl alcohol powder start to swell and form microgels, during the swelling process, the microgels are transferred to a mold, the mold is compressed, and placed in an oven for heat preservation;

[0144] (3) demolding to obtain a polyvinyl alcohol hydrogel, air-drying, rehydrating in water to swell, and preparing a cartilage prosthesis.

[0145] In another aspect, the present application provides a cartilage prosthesis prepared by the method described above.

[0146] In some embodiments, the prepared cartilage prosthesis has a solid content of 40%-50%, a compressive strength of 10-15 MPa, a cylindrical shape, a diameter of 5-10 mm, and a height of 5-10 mm.

[0147] In another aspect, the present application provides a method for preparing a tendon prosthesis, comprising the following steps:

[0148] (1) preparing a polyvinyl alcohol powder having a crystallinity of 30-50%, which is prepared from polyvinyl alcohol having a polymerization degree of 1000-3000, an alcoholysis degree of 80-100%, and a particle size of 200-600 um;

[0149] (2) mixing the polyvinyl alcohol powder with water and stirring to make the polyvinyl alcohol powder start to swell and form microgels, transferring the microgels to a mold during the swelling process, compacting the mold, and placing it in an oven for heat preservation;

[0150] (3) demolding to obtain a polyvinyl alcohol hydrogel, air-drying, cutting the material into a specific strip shape, annealing at 140°C for 2 hours, rehydrating in water to swell, and preparing a tendon prosthesis.

[0151] In another aspect, the present application provides a tendon prosthesis prepared by the method described above.

[0152] In some embodiments, the prepared tendon prosthesis has a solid content of 50%-60%, a tensile strength of 20 MPa, a cubic shape, a length of 15-25 mm, a width of 3-7 mm, and a height of 1-3 mm.

[0153] In another aspect, the present application provides a method for preparing a medical and aesthetic filling material, comprising the following steps:

[0154] (1) preparing a polyvinyl alcohol powder having a crystallinity of 30-50%, which is prepared from polyvinyl alcohol having a polymerization degree of 1000-3000, an alcoholysis degree of 80-100%, and a particle size of 300-800 um;

[0155] (2) mixing the polyvinyl alcohol powder with water and stirring to make the polyvinyl alcohol powder start to swell and form microgels, transferring the microgels to a mold during the swelling process, compacting the mold, and placing it in an oven for heat preservation;

[0156] (3) demolding to obtain polyvinyl alcohol hydrogel, air-drying, rehydrating in water to swell, and preparing medical and aesthetic filling material.

[0157] In another aspect, the application provides a medical and aesthetic filling material prepared by the method as described above.

[0158] In some modes, the medical and aesthetic filling material prepared has a solid content of 30%-40% and a compressive strength of 5-10 MPa, and can be classified into maxillofacial filling implant and chest filling implant according to the shape of the site to be filled.

[0159] In another aspect, the application provides a preparation method of three-dimensional PVA plastic, comprising the following steps:

[0160] (1) preparing polyvinyl alcohol powder, wherein the crystallinity of the polyvinyl alcohol powder is 30-50%, and the polyvinyl alcohol powder is prepared from polyvinyl alcohol with a polymerization degree of 1000-3000 and an alcoholysis degree of 80-100% and a particle size of 100-400 um;

[0161] (2) mixing the polyvinyl alcohol powder with water and stirring to make the polyvinyl alcohol powder begin to swell to form microgel, and transferring the microgel to a mold during the swelling process, compacting the mold, and placing it in an oven for heat preservation;

[0162] (3) demolding to obtain polyvinyl alcohol hydrogel, air-drying, annealing at 160℃ for 6 hours, and preparing three-dimensional PVA plastic.

[0163] In another aspect, the application provides a three-dimensional PVA plastic prepared by the method as described above.

[0164] In some modes, the three-dimensional PVA plastic prepared has a bending strength of 120 MPa.

[0165] The polyvinyl alcohol powder and the polyvinyl alcohol hydrogel prepared therefrom provided by the application have the following beneficial effects:

[0166] 1. A brand-new preparation method of polyvinyl alcohol hydrogel is created, wherein the polyvinyl alcohol is first processed into polyvinyl alcohol powder, and then mixed with water to make the powder swell to form microgel, and then the polyvinyl alcohol molecular chains at the interface of the microgel are diffused, intertwined, connected and crystallized to prepare polyvinyl alcohol hydrogel;

[0167] 2. The polyvinyl alcohol powder can be prepared by various methods, including direct crushing, crushing after physical crosslinking, etc., and a preferred method of crushing after film casting is also provided, and the polyvinyl alcohol powder with highly consistent crystallinity can be prepared, and the performance of the hydrogel is significantly improved;

[0168] 3. A new preparation process is provided, in which polyvinyl alcohol powder is first swelled, and pressure is applied to make it into a hydrogel before it is completely swelled, and the mutual relationship between various parameters in the entire process is studied in depth, and the technical scheme is optimized and improved;

[0169] 4. The method is simple to operate, has strong repeatability, and controllable performance;

[0170] 5. Good biocompatibility, no need for additives, high safety, green and environmentally friendly;

[0171] 6. Excellent mechanical properties, can be used for in vivo motion system soft tissue reconstruction, can successfully prepare cartilage prosthesis products, tendon prosthesis products, and can also adjust process parameters to obtain medical and beauty filling materials with mechanical properties matching human tissues, etc.;

[0172] 7. Solving the problem of PVA thermoplasticity, successfully constructing PVA plastic with three-dimensional structure. BRIEF DESCRIPTION OF DRAWINGS

[0173] Figure 1 is a flow chart of PVA powder preparation;

[0174] Figure 2 is a photograph of the prepared PVA powder;

[0175] Figure 3 is a photograph of the prepared PVA hydrogel;

[0176] Figure 4 is a schematic diagram of the compression mechanical test results of the PVA hydrogel;

[0177] Figure 5 is a schematic diagram of the cyclic compression performance test results of the PVA powder prepared hydrogel;

[0178] Figure 6 is a flow chart of PVA hydrogel preparation by PVA powder swelling;

[0179] Figure 7 is an electron microscope photograph of the morphology structure of the PVA hydrogel material, wherein the upper left graph is a PVA powder prepared hydrogel with a particle size of less than 100 μm, the upper middle graph is a PVA powder prepared hydrogel with a particle size of 100-200 μm, the upper right graph is a PVA powder prepared hydrogel with a particle size of more than 200 μm, and the lower graph is a hydrogel prepared according to the reference patent EP3277228B1;

[0180] Figure 8 is a photograph of the microgel interface connection microstructure recorded by micro-SEM and super-resolution fluorescence during the preparation of the PVA hydrogel, wherein the left graph is a micro-SEM photograph, and the right graph is a super-resolution fluorescence photograph;

[0181] Figure 9 is a photograph of the microgel preparation hydrogel process after complete swelling, wherein A is a syringe extrusion photograph, B is a flowability display photograph, and C is a photograph of the fusion of the completely swelled microgel;

[0182] Figure 10 is a cross-sectional photograph of the process of preparing PVA hydrogel by fusing two PVA films, and the cross-section of two PVA films is observed by a freeze scanning electron microscope, wherein the left and right photographs are freeze scanning electron microscope photographs at different magnifications;

[0183] Figure 11 is a photograph of a meniscus, cartilage, trachea / vascular, and nucleus pulposus prosthesis prepared by PVA hydrogel;

[0184] Figure 12 is a photograph of a tendon prosthesis prepared by PVA hydrogel;

[0185] Figure 13 is a result of safety verification of PVA hydrogel material leaching liquid in vitro culture C3H cells. DETAILED DESCRIPTION

[0186] The preferred embodiments of the present application are further described in detail below with reference to the accompanying drawings, it should be noted that the following embodiments are intended to facilitate the understanding of the present application, and do not have any limiting effect on the present application. If not specifically pointed out, the raw materials and equipment used in the following specific embodiments are known products, which are obtained by purchasing commercially available products.

[0187] Firstly, the present application provides a preparation method of polyvinyl alcohol powder

[0188] In the specific implementation process, the research team of the present application has conducted in-depth research on the polyvinyl alcohol powder (hereinafter referred to as PVA powder) prepared by different methods, and the influence on the performance of the subsequent preparation of hydrogel. The preparation flow chart of PVA powder is shown in Figure 1, and the specific preparation examples of PVA powder are given below. Among them, examples 1-3 are prepared by crushing after water solution casting film, example 4 is prepared by crushing after hot melt casting film, examples 5-7 are directly prepared by crushing, example 8 is prepared by crushing after repeated freezing and thawing (physical crosslinking), example 9 is prepared by crushing after freeze-drying (physical crosslinking), and example 10 is prepared by crushing after solvent exchange (physical crosslinking). The polyvinyl alcohol raw material used is purchased from Macklin manufacturers of 1799, 1788 and other models, and other reagent raw materials are purchased from Macklin manufacturers if not specified separately.

[0189] Example 1, preparation of PVA powder by crushing after water solution casting film

[0190] PVA (polymerization degree 1700, alcoholysis degree 99%) with the brand of 1799 is dissolved in water to prepare a 10% aqueous solution, the aqueous solution is cast into a film, and a PVA film with a thickness of about 50 um is obtained. The film is crushed to obtain PVA powder, and the powder with a particle size of 100-150 um is sieved out for the subsequent preparation of hydrogel material.

[0191] Example 2, Preparation of PVA powder by pulverization after water solution casting film formation (tannic acid is added to PVA aqueous solution)

[0192] PVA (polymerization degree 1700, alcoholysis degree 99%) of grade 1799 was dissolved in water to prepare a 10% aqueous solution. Tannic acid was added to the aqueous solution to make the solid content of tannic acid 10% of PVA. After the tannic acid was sufficiently dissolved to obtain a clear solution, a film was formed by casting. A PVA and tannic acid composite film having a thickness of about 50 um was obtained. The film was pulverized to obtain a composite powder. The powder having a particle size of 100-150 um was sieved and used for the subsequent production of hydrogel material.

[0193] Example 3, Preparation of PVA powder by pulverization after water solution casting film formation (PVA raw material with low alcoholysis degree was changed)

[0194] PVA (polymerization degree 1700, alcoholysis degree 88%) of grade 1788 was dissolved in water to prepare a 15% aqueous solution. The aqueous solution was cast to form a film. A PVA film having a thickness of about 80 um was obtained. The film was pulverized to obtain a PVA powder. The powder having a particle size of 100-150 um was sieved and used for the subsequent production of hydrogel material.

[0195] Example 4, Preparation of PVA powder by pulverization after hot melt casting film formation

[0196] PVA particles of grade 1799 were supplied to a casting machine. The PVA raw material was heated to 170°C by a heating system to make it flowable. Subsequently, the heated PVA raw material was calendered into a film and cooled on a cooling roll to solidify and stabilize its shape. A PVA film having a thickness of about 50 um was obtained. The film was pulverized to obtain a PVA powder. The powder having a particle size of 100-150 um was sieved and used for the subsequent production of hydrogel material.

[0197] Example 5, Preparation of PVA powder by direct pulverization

[0198] PVA (polymerization degree 1700, alcoholysis degree 99%) of grade 1799 was pulverized to obtain a PVA powder. The powder having a particle size of 100-150 um was sieved and used for the subsequent production of hydrogel material.

[0199] Example 6, Preparation of PVA powder by direct pulverization (PVA raw material with low alcoholysis degree was changed)

[0200] PVA (polymerization degree 1700, alcoholysis degree 88%) of grade 1788 was pulverized to obtain a PVA powder. The powder having a particle size of 100-150 um was sieved and used for the subsequent production of hydrogel material.

[0201] Example 7, Preparation of PVA powder by direct pulverization (PVA raw material with high polymerization degree was changed)

[0202] PVA with grade 2499 (polymerization degree 2400, alcoholysis degree 99%) was crushed to obtain PVA powder, and the powder with particle size of 100-150 um was sieved out for subsequent preparation of hydrogel materials.

[0203] Example 8, Preparation of PVA powder by crushing after repeated freeze-thawing

[0204] PVA with grade 1799 (polymerization degree 1700, alcoholysis degree 99%) was dissolved in water to prepare a 10% aqueous solution. The aqueous solution was frozen at -20°C for 8 hours, and then thawed at 25°C for 8 hours, which was one freeze-thaw cycle. The freeze-thaw cycle was repeated for 5 times to obtain a PVA freeze-thaw hydrogel. The freeze-thaw hydrogel was air-dried, and then crushed to obtain PVA powder, and the powder with particle size of 100-150 um was sieved out for subsequent preparation of hydrogel materials.

[0205] Example 9, Preparation of PVA powder by crushing after freeze-drying

[0206] PVA with grade 1799 (polymerization degree 1700, alcoholysis degree 99%) was dissolved in water to prepare a 10% aqueous solution. The aqueous solution was freeze-dried to obtain a PVA freeze-dried hydrogel. The freeze-dried hydrogel was crushed to obtain PVA powder, and the powder with particle size of 100-150 um was sieved out for subsequent preparation of hydrogel materials.

[0207] Example 10, Preparation of PVA powder by crushing after solvent exchange

[0208] PVA with grade 1799 (polymerization degree 1700, alcoholysis degree 99%) was dissolved in dimethyl sulfoxide to prepare a 10% aqueous solution. The dimethyl sulfoxide solution was immersed in a large amount of water for 48 hours to obtain a PVA solvent-exchanged hydrogel. The solvent-exchanged hydrogel was washed in water for 3 days to ensure that the residual dimethyl sulfoxide was removed, and then air-dried and crushed to obtain PVA powder, and the powder with particle size of 100-150 um was sieved out for subsequent preparation of hydrogel materials.

[0209] Example 11, Detection analysis

[0210] The PVA powder prepared in each of Examples 1 to 10 was taken respectively to detect the crystallinity thereof, and mixed with water, the mass ratio of water to PVA powder being 2.5:1, the temperature of water being 10℃, and the microgel mixture being obtained by magnetic stirring for 2 min, the microgel mixture was poured into a cylindrical mold with a diameter of 8 mm, the mold was compacted, and the mold was transferred to an oven at 40℃ for 30 min. Subsequently, the mold was demolded, and the material was dehydrated and dried by standing for 24 hours, and then was fully rehydrated and swelled in water to obtain 10 kinds of cylindrical PVA hydrogel materials. The solid content, compression strength, tensile strength, rigidity and elongation at break of the 10 kinds of PVA hydrogel materials were detected respectively, wherein the detection method of crystallinity was that the PVA hydrogel was freeze-dried to remove water, and then was detected by DSC (differential scanning calorimetry); the detection method of solid content was that the mass of the PVA hydrogel before and after freeze-drying was weighed; the tensile strength, compression strength, rigidity and elongation at break were obtained by compression test and tensile test; wherein the crystallinity of each PVA hydrogel material was repeated 5 times to investigate the stability of the crystallinity, and the detection results are shown in Table 1; the other detection indexes were repeated 3 times for each PVA hydrogel material, and the average value was taken, and the existing PVA hydrogel was taken as a control, and the detection results are shown in Table 2.

[0211] Table 1, crystallinity of PVA powder prepared by different methods

[0212] Table 2, influence of PVA powder prepared by different methods on preparation of hydrogel

[0213] According to Table 1, it can be seen that, comparing Examples 1 to 11, the crystallinity of the PVA powder prepared by direct pulverization (Examples 5 to 7) is the highest, the crystallinity of the PVA powder prepared by pulverization after physical crosslinking (Examples 8 to 10) is the lowest, and the crystallinity of the PVA powder prepared by the method of flow casting and then pulverization (Examples 1 to 4) is in the middle, and the consistency of five detections is the highest, and the CV value is lower than 0.001, indicating that the PVA powder prepared by the method of flow casting and then pulverization has the most stable performance and the best uniformity of crystallinity.

[0214] According to Table 2, it can be seen that the performance of the PVA hydrogel prepared in Examples 1 to 4 is obviously better than that of the PVA hydrogel prepared in Examples 5 to 10. It can be seen that the PVA powder prepared by the method of flow casting and then pulverization can also improve the performance of the PVA hydrogel. At the same time, the PVA powder prepared in Examples 1 to 10 is prepared into hydrogel by the process of the present application, and is similar to the existing PVA hydrogel, and can also surpass the existing PVA hydrogel in most cases.

[0215] Among them, the hydrogel material prepared by the PVA powder prepared by the casting film preparation has the strongest mechanical property, the maximum strength and the maximum compression modulus, and is most suitable for the soft tissue prosthesis resisting compression. Meanwhile, although the tensile strength and the rigidity of the examples 1-3 are also the largest, the elongation at break in each example is relatively high, and thus the annealing treatment is needed to further improve the rigidity so as to be used for the soft tissue prosthesis resisting tension. The reason why the PVA powder prepared by the casting film preparation can obtain the hydrogel material with better mechanical property is that the crystallinity of the powder is the highest, and the subsequent PVA hydrogel preparation process is the most suitable, so that the diffusion effect of the PVA molecular chain is the best, and more microgel interfaces are generated during fusion, and the mechanical property is more outstanding. Meanwhile, the uniformity of the crystallinity of the PVA powder prepared by the casting film preparation is the best, and thus the PVA hydrogel with more excellent performance can be prepared.

[0216] As can be seen from the comparative examples 1-4, the mechanical property of the PVA hydrogel prepared by the hot melt extrusion film preparation method decreases, which is probably because the hot melt process can damage the PVA molecular chain to some extent, thereby affecting the diffusion and fusion of the PVA molecular chain.

[0217] As can be seen from the comparative example 1 and the example 3, when the polyvinyl alcohol raw material with lower alcoholysis degree is used, the crystallinity of the PVA powder prepared decreases, and the compression strength and the tensile strength of the PVA hydrogel prepared decrease. The reason is that the alcoholysis degree of the polyvinyl alcohol raw material can directly affect the crystallinity of the powder, and the lower the crystallinity of the PVA powder, the less the recrystallization of the PVA molecular chain during the fusion of the microgel after diffusion, thereby affecting the compression strength and the tensile strength of the PVA hydrogel.

[0218] Therefore, the polymerization degree and the alcoholysis degree of the polyvinyl alcohol raw material, and the crystallinity of the PVA powder prepared will affect each other during the preparation of the PVA hydrogel, and will affect the diffusion and fusion effect of the PVA molecular chain, thereby affecting the performance of the PVA hydrogel. Therefore, the polymerization degree and the alcoholysis degree of the polyvinyl alcohol raw material, and the crystallinity of the PVA powder should be determined according to the performance requirements of the product, so as to find more suitable process conditions, and prepare the PVA hydrogel product more suitable for the product requirements.

[0219] As can be seen from the comparative example 1 and the example 2, the PVA powder prepared by adding 10% tannic acid in the polyvinyl alcohol aqueous solution has little effect on the performance of the hydrogel, which shows that the polycarboxylic or polyhydroxy compound capable of forming hydrogen bond with the polyvinyl alcohol in the polyvinyl alcohol aqueous solution does not have obvious bad effect on the preparation of the polyvinyl alcohol powder and the polyvinyl alcohol hydrogel.

[0220] The photo of the PVA powder prepared by Example 1 is shown in Figure 2, and the photo of the prepared PVA hydrogel is shown in Figure 3. Figure 4 is the compression mechanics test result of the PVA hydrogel, wherein the HF is the hydrogel prepared by the PVA powder provided by Example 1, the detection method is the quasi-static compression test, the compression speed is 2mm / min, and the compression deformation is 95%. The FT is the hydrogel prepared by the repeated freezing and thawing method, and the FT+S is the hydrogel prepared by the repeated freezing and thawing + salting-out method. As can be seen from Figure 4, the compression resistance of the PVA hydrogel prepared by the process of the present application is significantly higher than that of the existing PVA hydrogel. Figure 5 is the cyclic compression performance test result of the hydrogel prepared by the PVA powder provided by Example 1. As can be seen from Figure 5, the PVA hydrogel prepared by the process of the present application can recover to the initial performance after 120S after compression to 95%.

[0221] Example 12, Effect of Particle Size of Polyvinyl Alcohol Powder on Preparation of Hydrogel

[0222] In this example, the PVA powder is prepared by the method provided in Example 1, wherein after obtaining the powder, PVA powders with particle sizes of 0-50um, 50-100um, 100-150um, 150-200um, 200-250um, and 250-300um are respectively screened out, and their crystallinity is detected. The microgel mixture is obtained by mixing water and the PVA powder with a mass ratio of 2.5:1, and the temperature of the water is 10℃, and the magnetic stirring is 2min. The microgel mixture is poured into a cylindrical mold with a diameter of 8mm, the mold is compacted, and the mold is transferred to a 40℃ oven for 30min. Subsequently, the mold is demolded, the obtained PVA hydrogel is dried, and then fully rehydrated and swelled in water to obtain six kinds of cylindrical PVA hydrogel materials. The solid content, strength, compression modulus, stiffness, and elongation at break of the six kinds of PVA hydrogel materials are respectively detected, and the detection method is shown in Example 11. The detection results are shown in Table 3, and each PVA hydrogel material is repeated for 3 times, and the average value is taken.

[0223] Table 3, Effect of PVA powder with different particle sizes on preparation of hydrogel

[0224] As can be seen from Table 3, the particle size of the PVA powder directly affects the mechanical properties of the PVA hydrogel, and the reason should be that the particle size of the powder affects the swelling speed and the diffusion effect of the PVA molecular chain. Under the process parameter conditions provided in the present embodiment, the PVA powder with a particle size of 100-150 um is preferably used to prepare the PVA hydrogel, which can significantly improve the mechanical properties of the PVA hydrogel and is more suitable for preparing soft tissue prosthesis of the movement system. Of course, it can be understood that many parameters in the preparation process provided by the present application will affect the diffusion effect of the PVA molecular chain, such as the crystallinity of the PVA powder, the particle size, the amount of water added in the reaction, the water temperature in the swelling process, etc. These factors are interrelated, for example, if the crystallinity is too low and the diffusion is too fast, the diffusion speed can be slowed down by increasing the particle size or reducing the water temperature in the swelling process; if the particle size is too small and the diffusion is too fast, the diffusion speed can also be adjusted by reducing the water temperature and shortening the swelling time. Therefore, the process parameters most suitable for the product need to be explored according to the performance requirements of the product, so as to find the most suitable process conditions, so as to prepare the PVA hydrogel product that meets the product requirements.

[0225] Secondly, the present application provides a preparation method of the polyvinyl alcohol hydrogel

[0226] Example 13, preparation of PVA hydrogel material

[0227] In this embodiment, the PVA powder prepared in Example 1 is used to prepare the PVA hydrogel, and the preparation process is shown in Figure 6. The PVA powder prepared in Example 1 (crystallinity 45%, particle size 100-150 um) is mixed with water, and the mass ratio of water to PVA powder is 2.5:1. The temperature of the water is 10℃, and the microgel mixture is obtained by magnetic stirring for 2 min. The microgel mixture is poured into a cylindrical mold with a diameter of 8 mm, the mold is pressed tightly, and then the mold is transferred to a 40℃ oven for 30 min. Then, the mold is demolded, and the obtained PVA hydrogel is placed in a 140℃ constant temperature box for heating for 2 hours, and then fully rehydrated and swelled in water to obtain a cylindrical PVA hydrogel material.

[0228] In this embodiment, the PVA powder with different particle sizes is also used to prepare the hydrogel, and the electron microscope photos of the appearance structure of the prepared PVA hydrogel material are shown in the upper part of Figure 7. The upper left photo is the hydrogel prepared by the PVA powder with a particle size less than 100 um, the upper middle photo is the hydrogel prepared by the PVA powder with a particle size of 100-200 um, and the upper right photo is the hydrogel prepared by the PVA powder with a particle size of more than 200 um. It can be seen that the PVA hydrogel material has a typical granular structure. The lower part of Figure 7 is the appearance structure photo of the hydrogel prepared according to the reference patent EP3277228B1, and it can be seen that the surface of the hydrogel is flat and has no granular structure. As can be seen from Figure 7, the PVA hydrogel prepared by the present application and other existing PVA hydrogel materials have completely different surface microstructures.

[0229] The microstructure of the interface connection of the microgels was recorded by micro-SEM and super-resolution fluorescence photos for the prepared PVA hydrogel, as shown in Figure 8, in which the left photo is the micro-SEM photo and the right photo is the super-resolution fluorescence photo. It can be obviously seen that the diffusion of the PVA molecular chains indeed occurs between the microgel particles.

[0230] Example 14, Effect of different swelling stages on the preparation of hydrogel

[0231] In this example, the PVA powder prepared in Example 1 (crystallinity 45%, particle size 100-150 um) was used to prepare PVA hydrogel according to the method of Example 13, in which the following two groups were carried out during the swelling process: 1. The mass ratio of water to PVA powder was 10:1, the temperature of water was 10℃, and magnetic stirring was carried out for 20 min to obtain the completely swollen microgel mixture; 2. The mass ratio of water to PVA powder was 2.5:1, the temperature of water was 10℃, and magnetic stirring was carried out for 2 min to obtain the microgel mixture in the process of swelling; the microgel mixtures of the two groups were poured into the mold respectively, the mold was pressed tightly, and the mold was transferred to a 40℃ oven for 30 min. Subsequently, the mold was removed, and it was found that the second group could successfully prepare PVA hydrogel material with excellent performance, while the microgels of the first group could not fuse, as shown in Figure 9, in which A is the photo of syringe extrusion, B is the photo of flowability display, which shows that the completely swollen microgels have good flowability and can be extruded from the syringe, but cannot be molded, C is the photo of the fusion of completely swollen microgels, in which the green color is the fluorescently labeled microgels, and it can be seen that the completely swollen microgels cannot fuse with each other and are separated from each other, and PVA hydrogel cannot be prepared, and the reason may be that after complete swelling, the PVA molecular chains have already diffused completely, and during the extrusion process, the PVA molecular chains cannot continue to diffuse, so they cannot entangle and fuse. Therefore, it is necessary to transfer the mold into the hydrogel during the swelling process.

[0232] In this example, the PVA powder prepared in Example 1 (crystallinity 45%, particle size 100-150 um) was used to prepare PVA hydrogel according to the method of Example 13, in which the following two groups were carried out during the swelling process: 1. The mass ratio of water to PVA powder was 10:1, the temperature of water was 10℃, and magnetic stirring was carried out for 20 min to obtain the completely swollen microgel mixture; 2. The mass ratio of water to PVA powder was 2.5:1, the temperature of water was 10℃, and magnetic stirring was carried out for 2 min to obtain the microgel mixture in the process of swelling; the microgel mixtures of the two groups were poured into the mold respectively, the mold was pressed tightly, and the mold was transferred to a 40℃ oven for 30 min. Subsequently, the mold was removed, and it was found that the second group could successfully prepare PVA hydrogel material with excellent performance, while the microgels of the first group could not fuse, as shown in Figure 9, in which A is the photo of syringe extrusion, B is the photo of flowability display, which shows that the completely swollen microgels have good flowability and can be extruded from the syringe, but cannot be molded, C is the photo of the fusion of completely swollen microgels, in which the green color is the fluorescently labeled microgels, and it can be seen that the completely swollen microgels cannot fuse with each other and are separated from each other, and PVA hydrogel cannot be prepared, and the reason may be that after complete swelling, the PVA molecular chains have already diffused completely, and during the extrusion process, the PVA molecular chains cannot continue to diffuse, so they cannot entangle and fuse. Therefore, it is necessary to transfer the mold into the hydrogel during the swelling process.

[0233] Example 15, Effect of different water and powder ratio on the preparation of hydrogel

[0234] The PVA powder (crystallinity 45%, particle size 100-150 um) prepared in Example 1 was used to prepare PVA hydrogel according to the method of Example 13, wherein the mass ratio of water to PVA powder was 0.5:1, 1:1, 2.5:1, 5:1, and 8:1, respectively, to carry out the swelling reaction, thereby preparing five kinds of PVA hydrogel materials. The solid content, strength, compression modulus, stiffness, and elongation at break of the five kinds of PVA hydrogel materials were detected, and the detection method is shown in Example 11. The detection results are shown in Table 4. Each PVA hydrogel material was repeated three times, and the average value was taken.

[0235] Table 4, Effect of different water and powder ratios on the preparation of hydrogel

[0236] As can be seen from Table 4, the mass ratio of water to PVA powder directly affects the mechanical properties of the PVA hydrogel. The reason should be that the mass ratio of water to PVA powder affects the swelling speed and swelling degree, and affects the diffusion effect of the PVA molecular chain. Under the preparation process parameters provided in this example, it is preferred to use water and PVA powder with a mass ratio of (1-5):1 to prepare PVA hydrogel, and most preferably water and PVA powder with a mass ratio of 2.5:1, which can significantly improve the mechanical properties of PVA hydrogel and is more suitable for preparing soft tissue prosthesis. Of course, it can be understood that since there are many parameters in the preparation process provided by the present application that will affect the diffusion effect of the PVA molecular chain, and will affect each other, such as the crystallinity and particle size of the PVA powder, the water temperature, the stirring method, the reaction time, etc. of the swelling process. These factors are related to each other, such as increasing the water temperature to speed up the swelling reaction, which can be controlled by shortening the swelling stirring time or increasing the amount of water to control the swelling degree, while low water temperature will reduce the swelling reaction speed, which can be controlled by prolonging the swelling stirring time or reducing the amount of water to control the swelling speed. For example, high water content will also accelerate diffusion, and by controlling the mass ratio of water to powder not to exceed 8:1, it can also ensure that complete swelling does not occur, but it also cannot be reacted for a long time, and the stirring and mixing time still needs to be controlled to control the diffusion effect. Therefore, no matter how the specific reaction parameters are adjusted, the ultimate goal is to control the diffusion effect, thereby controlling the entanglement and fusion effect of the molecular chain. The process parameters suitable for the product need to be explored according to the performance requirements of different products, so as to find the most suitable process conditions, so as to prepare PVA hydrogel products that better meet the product requirements.

[0237] Example 16, Effect of annealing treatment after demolding and drying on the preparation of hydrogel

[0238] The PVA powder prepared in Example 1 (crystallinity 45%, particle size 100-150 um) was used to prepare PVA hydrogel according to the method of Example 13, wherein after demolding, the following two treatment methods were used respectively: 1, after air drying, the PVA hydrogel was fully rehydrated and swelled in water; 2, the PVA hydrogel was directly rehydrated and swelled in water; 3, after air drying, the PVA hydrogel was placed in a constant temperature oven at 140°C for 2 hours, and then fully rehydrated and swelled in water. Two kinds of PVA hydrogel materials were prepared. The solid content, strength, compression modulus, stiffness and elongation at break of the two kinds of PVA hydrogel materials were detected respectively, and the detection method was shown in Example 11, and the detection results were shown in Table 5. Each kind of PVA hydrogel material was repeated for 3 times, and the average value was taken. The influence of different treatment methods on the preparation of hydrogel materials was investigated.

[0239] Table 5, influence of treatment method after demolding on preparation of hydrogel

[0240] As can be seen from Table 5, compared with direct rehydration and swelling and rehydration and swelling after drying, the drying treatment of heating in a constant temperature oven at 140°C for 2 hours after drying can obviously improve the mechanical properties of the hydrogel. The reason may be that the process of drying and dehydrating the PVA hydrogel is beneficial to the recrystallization of PVA molecules, so that the connection between the microgel particles can be more firm, and thus the mechanical properties are better.

[0241] Example 17, preparation of hydrogel using other polymer materials

[0242] In this example, other polymer materials were tried to be used to prepare hydrogel according to the process provided by the application:

[0243] 1, after dissolving the silk fibroin, a series of silk fibroin films with different crystallinities were prepared, and the films were crushed to obtain powder, but it was impossible to connect the powder to each other in the process of swelling the powder in water, which may be because the molecular chain of silk fibroin is more complex than PVA, and the diffusion between the powder particles cannot be completed, so the fusion cannot be completed.

[0244] 2, polyglutamic acid was processed in the same way, because of its strong hygroscopicity, after crushing to obtain powder, it will spontaneously absorb water from the atmosphere and form microgel, and it is impossible to controllably swell the powder in water and shape.

[0245] 3, the crystallinity of gelatin molecules is very low, although the powder can be prepared, but after the powder contacts water, it will be quickly dissolved, and will not form microgel like polyvinyl alcohol.

[0246] It can be seen that the preparation of hydrogel by swelling of polyvinyl alcohol powder is the most suitable processing technology for polyvinyl alcohol raw materials, which is related to the molecular weight structure and properties of polyvinyl alcohol, and is difficult to achieve for other polymer materials. Polyvinyl alcohol has a simple molecular structure, a controllable swelling rate, and an appropriate crystallinity to maintain the stability of the powder material in water, which is an important factor for polyvinyl alcohol to be processed into hydrogel by the aforementioned method.

[0247] Example 18, preparation of hydrogel by chemical crosslinking of PVA

[0248] In this example, a chemical crosslinking agent such as glutaraldehyde, chloropropanol, boric acid and genipin is added to a PVA aqueous solution, and then the mixture is poured into a container to dry into a film, obtaining a chemically crosslinked PVA film which is then crushed into powder. However, it is found that the powder prepared by chemical crosslinking has poor swelling effect and cannot be extruded and fused into hydrogel in the subsequent swelling and extrusion process. The reason may be that the method of hydrogel relies on the diffusion, entanglement and crystallization of molecular chains, but chemical crosslinking restricts the movement of molecular chains, so that sufficient fusion between powder particles cannot be achieved, and thus the product cannot be shaped.

[0249] III. Preparation of prostheses, medical fillers and plastics

[0250] In this example, PVA powder prepared by the method of Example 1 is used to prepare PVA hydrogel, and then cartilage prostheses, medical fillers and PVA plastics are prepared, respectively. Different process parameters are used according to the mechanical property requirements of different products.

[0251] The soft tissues of the human movement system include tendons, ligaments, cartilage, meniscus, etc., which play the functions of shock absorption, buffering, load bearing and mechanical transmission. In order to perform normal physiological functions, these tissues have the characteristics of high strength, high toughness and fatigue resistance, which are derived from the large amount of extracellular matrix composed of water and fiber network in the tissues. However, due to the lack of cells in these tissues, they are difficult to regenerate after injury, and in clinical treatment, prosthetic materials are needed to reconstruct the functions of the soft tissues of the movement system. With the progress of social aging, the demand for high-performance prosthetic materials is increasing. In addition to ensuring biological safety, the prosthetic materials for the movement system soft tissues also need to match the mechanical characteristics of the corresponding tissues, i.e. high strength, high toughness and fatigue resistance, which are currently difficult to achieve in artificial synthetic materials.

[0252] The research team has successfully prepared meniscus, cartilage, trachea, blood vessels, nucleus pulposus, ligaments and other prostheses using the method provided by the present application. Among them, the photos of the prepared meniscus, cartilage, trachea / blood vessel and nucleus pulposus prostheses are shown in Figure 11, and the photo of the tendon prosthesis is shown in Figure 12.

[0253] 3.1 Cartilage prosthesis

[0254] The cartilage prosthesis must have high strength, high toughness, and fatigue resistance. In general, the compressive strength of the prosthesis product should be 6 MPa to 20 MPa, the compressive modulus should be more than 4 MPa, and the mechanical properties should be stable in a cyclic compression test simulating physiological stress.

[0255] Example 19, Preparation of a cartilage prosthesis

[0256] PVA powder (crystallinity 45%, particle size 100-150 um) obtained in Example 1 was mixed with water at a mass ratio of 2.5:1, and the water was at a temperature of 10°C. The mixture was stirred magnetically for 2 minutes, and the PVA microgel mixture was poured into a custom-made cylindrical mold having a diameter of 8 mm. After the mold was compressed, the mold was transferred to an oven at 40°C, and the mold was kept in the oven for 30 minutes. Subsequently, the mold was removed, and the PVA hydrogel obtained was air-dried and then fully rehydrated in water to obtain a cylindrical PVA hydrogel cartilage prosthesis. The solid content of the hydrogel was 40%, and the compressive strength was 12 MPa.

[0257] Example 20, Preparation of a cartilage prosthesis (increasing the water and powder ratio, and decreasing the temperature and reaction time)

[0258] PVA powder (crystallinity 45%, particle size 50-100 um) obtained in Example 1 was mixed with water at a mass ratio of 4:1, and the water was at a temperature of 1°C. The mixture was stirred magnetically for 0.5 minutes, and the PVA microgel mixture was poured into a custom-made cylindrical mold having a diameter of 8 mm. After the mold was compressed, the mold was transferred to an oven at 40°C, and the mold was kept in the oven for 30 minutes. Subsequently, the mold was removed, and the PVA hydrogel obtained was air-dried and then fully rehydrated in water to obtain a cylindrical PVA hydrogel cartilage prosthesis. The solid content of the hydrogel was 35%, and the compressive strength was 9 MPa.

[0259] Example 21, Preparation of a cartilage prosthesis (addition of a sodium chloride solution)

[0260] PVA powder (crystallinity 45%, particle size 150-200 um) obtained in Example 1 was mixed with a 1 M sodium chloride solution at a mass ratio of 2.5:1, and the water was at a temperature of 10°C. The mixture was stirred magnetically for 2 minutes, and the PVA microgel mixture was poured into a custom-made cylindrical mold having a diameter of 8 mm. After the mold was compressed, the mold was transferred to an oven at 40°C, and the mold was kept in the oven for 30 minutes. Subsequently, the mold was removed, and the PVA hydrogel obtained was air-dried and then fully rehydrated in water to obtain a cylindrical PVA hydrogel cartilage prosthesis. The solid content of the hydrogel was 39%, and the compressive strength was 10 MPa.

[0261] Example 22, Preparation of cartilage substitute (annealing after molding)

[0262] PVA powder material obtained in Example 1 (crystallinity 45%, particle size 100-150 um) was mixed with water at a mass ratio of water to PVA powder of 2.5:1, and the water was at a temperature of 10°C. The PVA microgel mixture was stirred magnetically for 2 minutes, poured into a custom-made cylindrical mold of 8 mm in diameter, and the mold was transferred to an oven at 40°C for 30 minutes after the mold was compacted. The mold was then removed, and the PVA hydrogel obtained was air-dried and then fully rehydrated and swollen in water to obtain a cylindrical PVA hydrogel cartilage substitute. The solid content of the hydrogel was 50%, and the compressive strength was 18 MPa.

[0263] Example 23, Preparation of cartilage substitute (tannic acid added to PVA aqueous solution during powder preparation, reduced crystallinity of powder)

[0264] PVA and tannic acid composite powder obtained in Example 2 (crystallinity 45%, particle size 100-150 um) was mixed with water at a mass ratio of water to PVA and tannic acid composite powder of 2.5:1, and the water was at a temperature of 10°C. The PVA and tannic acid composite microgel mixture was stirred magnetically for 2 minutes, poured into a custom-made cylindrical mold of 8 mm in diameter, and the mold was transferred to an oven at 40°C for 30 minutes after the mold was compacted. The mold was then removed, and the PVA and tannic acid composite hydrogel obtained was air-dried and then fully rehydrated and swollen in water to obtain a cylindrical PVA and tannic acid composite hydrogel cartilage substitute. The solid content of the hydrogel was 40%, and the compressive strength was 12 MPa.

[0265] Example 24, Preparation of cartilage substitute (reduced crystallinity of powder)

[0266] PVA powder material obtained in Example 3 (crystallinity 42%, particle size 100-150 um) was mixed with water at a mass ratio of water to PVA powder of 2.5:1, and the water was at a temperature of 5°C. The PVA microgel mixture was stirred magnetically for 1 minute, poured into a custom-made cylindrical mold of 8 mm in diameter, and the mold was transferred to an oven at 40°C for 30 minutes after the mold was compacted. The mold was then removed, and the PVA hydrogel obtained was air-dried and then fully rehydrated and swollen in water to obtain a cylindrical PVA hydrogel cartilage substitute. The solid content of the hydrogel was 37%, and the compressive strength was 8 MPa.

[0267] Example 25, Preparation of cartilage substitute (increased crystallinity of powder)

[0268] PVA powder (crystallinity 55%, particle size 100-150 um) obtained in Example 4 was mixed with water, the mass ratio of water to PVA powder was 2.5:1, the temperature of water was 40°C, and the mixture was stirred magnetically for 5 minutes. The PVA microgel mixture was poured into a custom-made cylindrical mold with a diameter of 8 mm, and the mold was transferred to a 65°C oven after the mold was compacted. The PVA hydrogel obtained was dried in air after demolding, and then was dried in a vacuum drying oven at 120°C for 1 hour. The cylindrical PVA hydrogel cartilage prosthesis was obtained after the PVA hydrogel was fully rehydrated and swelled in water. The solid content of the hydrogel was 35%, and the compressive strength was 8 MPa.

[0269] Example 26, Preparation of cartilage prosthesis (increasing crystallinity of powder)

[0270] PVA powder (crystallinity 51%, particle size 100-150 um) obtained in Example 5 was mixed with water, the mass ratio of water to PVA powder was 2.5:1, the temperature of water was 30°C, and the mixture was stirred magnetically for 5 minutes. The PVA microgel mixture was poured into a custom-made cylindrical mold with a diameter of 8 mm, and the mold was transferred to a 50°C oven after the mold was compacted. The PVA hydrogel obtained was dried in air after demolding, and then was dried in a vacuum drying oven at 120°C for 1 hour. The cylindrical PVA hydrogel cartilage prosthesis was obtained after the PVA hydrogel was fully rehydrated and swelled in water. The solid content of the hydrogel was 40%, and the compressive strength was 11 MPa.

[0271] Example 27, Preparation of cartilage prosthesis (changing source of raw material)

[0272] PVA powder (crystallinity 52%, particle size 100-150 um) obtained in Example 6 was mixed with water, the mass ratio of water to PVA powder was 4:1, the temperature of water was 30°C, and the mixture was stirred magnetically for 5 minutes. The PVA microgel mixture was poured into a custom-made cylindrical mold with a diameter of 8 mm, and the mold was transferred to a 50°C oven after the mold was compacted. The PVA hydrogel obtained was dried in air after demolding, and then was dried in a vacuum drying oven at 120°C for 1 hour. The cylindrical PVA hydrogel cartilage prosthesis was obtained after the PVA hydrogel was fully rehydrated and swelled in water. The solid content of the hydrogel was 40%, and the compressive strength was 11 MPa.

[0273] Example 28, Preparation of cartilage prosthesis (changing source of raw material)

[0274] PVA powder material obtained in Example 7 (crystallinity 40%, particle size 100-150 um) was mixed with water, the mass ratio of water to PVA powder was 4:1, the temperature of water was 1°C, and the mixture was stirred magnetically for 0.5 minutes. The PVA microgel mixture was poured into a custom-made cylindrical mold with a diameter of 8 mm, and the mold was transferred to a 40°C oven after the mold was compacted. The mold was kept in the oven for 30 minutes. Subsequently, the mold was removed, and the obtained PVA hydrogel was air-dried and then fully rehydrated and swelled in water to obtain a cylindrical PVA hydrogel cartilage prosthesis. The solid content of the hydrogel was 35%, and the compressive strength was 9 MPa.

[0275] Example 29, Preparation of a cartilage prosthesis (change in raw material source, water containing sodium sulfate)

[0276] PVA powder material obtained in Example 8 (crystallinity 35%, particle size 100-150 um) was mixed with a 1 M sodium sulfate solution, the mass ratio of the sodium sulfate solution to PVA powder was 4:1, the temperature of water was 1°C, and the mixture was stirred magnetically for 0.5 minutes. The PVA microgel mixture was poured into a custom-made cylindrical mold with a diameter of 8 mm, and the mold was transferred to a 40°C oven after the mold was compacted. The mold was kept in the oven for 30 minutes. Subsequently, the mold was removed, and the obtained PVA hydrogel was air-dried and then fully rehydrated and swelled in water to obtain a cylindrical PVA hydrogel cartilage prosthesis. The solid content of the hydrogel was 39%, and the compressive strength was 10 MPa.

[0277] Example 30, Preparation of a cartilage prosthesis (change in raw material source, process)

[0278] PVA powder material obtained in Example 9 (crystallinity 45%, particle size 100-150 um) was mixed with water, the mass ratio of water to PVA powder was 3:1, the temperature of water was 10°C, and the mixture was stirred magnetically for 2 minutes. The PVA microgel mixture was poured into a custom-made cylindrical mold with a diameter of 8 mm, and the mold was transferred to a 40°C oven after the mold was compacted. The mold was kept in the oven for 30 minutes. Subsequently, the mold was removed, and the obtained PVA hydrogel was air-dried and then fully rehydrated and swelled in water to obtain a cylindrical PVA hydrogel cartilage prosthesis. The solid content of the hydrogel was 40%, and the compressive strength was 10 MPa.

[0279] Example 31, Preparation of a cartilage prosthesis (cutting and reshaping after overmolding)

[0280] PVA powder (crystallinity 45%, particle size 100-150 um) obtained in Example 1 was mixed with water, the mass ratio of water to PVA powder was 2.5:1, the temperature of water was 10°C, and the mixture was stirred magnetically for 2 minutes. The PVA microgel mixture was poured into a customized 30 mm*30 mm square mold, and after the mold was compressed, the mold was transferred to a 40°C oven for 30 minutes. Subsequently, the mold was demolded, and the obtained PVA hydrogel was air-dried. Then, a cylindrical material was drilled out by a 5 mm diameter trephine, and the cylindrical PVA hydrogel cartilage prosthesis was obtained after the material was fully rehydrated and swelled in water. The solid content of the hydrogel was 40%, and the compressive strength was 12 MPa.

[0281] 3.2 Tendon prosthesis

[0282] The tendon prosthesis is characterized by obtaining a long strip-shaped hydrogel material in a mold, and the tensile strength is a key indicator, which should be more than 10 MPa, the stiffness should be more than 10 MPa, and the mechanical properties should be stable in the cyclic tensile test under simulated physiological stress and suture fixation. The performance of the ligament prosthesis product is similar to that of the tendon prosthesis product, except that other shaped molds are needed or machining is needed after molding. The tendon and ligament prosthesis products usually need to be annealed to improve the tensile strength of the material to meet the use requirements.

[0283] Example 32, preparation of a tendon prosthesis

[0284] PVA powder (crystallinity 45%, particle size 100-150 um) obtained in Example 1 was mixed with water, the mass ratio of water to PVA powder was 2.5:1, the temperature of water was 10°C, and the mixture was stirred magnetically for 2 minutes. The PVA microgel mixture was poured into a customized 30 mm*30 mm square mold, and after the mold was compressed, the mold was transferred to a 40°C oven for 30 minutes. Subsequently, the mold was demolded, and the obtained PVA hydrogel was air-dried. Then, a cylindrical material was drilled out by a 5 mm diameter trephine, and the cylindrical PVA hydrogel cartilage prosthesis was obtained after the material was fully rehydrated and swelled in water. The solid content of the hydrogel was 40%, and the compressive strength was 12 MPa.

[0285] 3.2 Medical aesthetic filling material

[0286] Breast cancer is one of the most common cancers in women, and its incidence has been increasing year by year due to changes in diet and lifestyle in recent years. In order to prevent the spread of cancer cells, some breast cancer patients may choose to undergo mastectomy. Once the lesion is large or the small lesion is large and multiple, it is likely that more tissue will be removed, resulting in a large local tissue defect after surgery. Not only is the tactile sensation obvious, but it can also be directly seen, which causes a great psychological burden to the patient (European Patent EP3679890B1, Chinese Patent CN201798826U). Therefore, the demand for breast reconstruction using breast prosthesis is increasing and is of great concern. On the other hand, with the development of economy and the opening of society, it is human nature to pursue beauty, and now people have higher requirements for their appearance than before. Therefore, plastic surgery such as breast augmentation, rhinoplasty, and forehead augmentation, which meets the individual aesthetic perspective, is becoming more common. When the nose is lowered, a certain thickness of filler needs to be embedded in the tissue of the nose. This filler is called a nasal prosthesis (Chinese Patent CN206491900U). When the forehead, eyebrow arch, and glabella are raised, a certain thickness of filler needs to be embedded in the tissue of the central forehead and the excessive area of the forehead-nose. This filler is called a forehead augmentation prosthesis (Chinese Patent CN204049933U). Whether it is a breast prosthesis, a nasal prosthesis, or a forehead augmentation prosthesis, it needs to be made of a certain material. The prosthesis material must be made of a material that is harmless to the human body, has no rejection reaction, does not deteriorate for a long time, has a certain softness, is easy to shape, and is easy to remove.

[0287] The medical aesthetic filling material is characterized by obtaining a shaped hydrogel material in a mold, or obtaining a standard-shaped material and then obtaining a shaped material through machining. Compression strength is a key indicator. Compared with the strong and soft tissues of the musculoskeletal system, the compression strength of medical aesthetic filling materials is relatively small, generally in the range of 3-8 MPa, but different strength is required for prosthesis products used in different parts.

[0288] Example 33, preparation of a breast prosthesis

[0289] PVA powder (crystallinity 45%, particle size 100-150 um) obtained in Example 1 was mixed with water, and the mass ratio of water to PVA powder was 2.5:1. The temperature of the water was 1°C, and the PVA microgel mixture was stirred magnetically for 2 minutes. The PVA microgel mixture was poured into a custom-made water droplet mold, the mold was pressed tightly, and then the mold was transferred to a constant temperature and humidity box at 15°C for 30 minutes. Subsequently, the mold was removed, the obtained PVA hydrogel was dried, and then fully rehydrated and swelled in water to obtain a PVA hydrogel breast prosthesis in the shape of a water droplet. The solid content of the hydrogel was 25%, and the compression strength was 3 MPa.

[0290] Example 34, preparation of a nasal prosthesis

[0291] PVA powder (crystallinity 45%, particle size 100-150 um) obtained in Example 1 was mixed with water, the mass ratio of water to PVA powder was 2.5:1, the temperature of water was 5°C, and the mixture was stirred magnetically for 2 minutes. The PVA microgel mixture was poured into a customized L-shaped mold, the mold was pressed tightly, and then the mold was transferred to a constant temperature and humidity box at 25°C for 30 minutes. Subsequently, the mold was demolded, the obtained PVA hydrogel was air-dried, and then was fully rehydrated and swelled in water to obtain a PVA hydrogel nasal prosthesis in the shape of L. The solid content of the hydrogel was 35%, and the compressive strength was 8 MPa.

[0292] Example 35, preparation of a nasal prosthesis

[0293] PVA powder (crystallinity 45%, particle size 100-150 um) obtained in Example 1 was mixed with water, the mass ratio of water to PVA powder was 2.5:1, the temperature of water was 5°C, and the mixture was stirred magnetically for 2 minutes. The PVA microgel mixture was poured into a customized 20 mm*60 mm square mold, the mold was pressed tightly, and then the mold was transferred to a constant temperature and humidity box at 25°C for 30 minutes. Subsequently, the mold was demolded, the obtained PVA hydrogel was air-dried, and then was fully rehydrated and swelled in water to obtain a PVA hydrogel material in the shape of a square, and then a nasal prosthesis in a special shape was cut out. The solid content of the hydrogel was 35%, and the compressive strength was 8 MPa.

[0294] Example 36, preparation of a forehead prosthesis

[0295] PVA powder (crystallinity 45%, particle size 100-150 um) obtained in Example 1 was mixed with water, the mass ratio of water to PVA powder was 2.5:1, the temperature of water was 10°C, and the mixture was stirred magnetically for 2 minutes. The PVA microgel mixture was poured into a customized square sheet mold, the mold was pressed tightly, and then the mold was transferred to a constant temperature and humidity box at 35°C for 30 minutes. Subsequently, the mold was demolded, the obtained PVA hydrogel was air-dried, and then was fully rehydrated and swelled in water to obtain a PVA hydrogel forehead prosthesis in the shape of a sheet. The solid content of the hydrogel was 40%, and the compressive strength was 10 MPa.

[0296] 3.3 Plastic

[0297] Polyvinyl alcohol (PVA) is a non-toxic, high-barrier, biodegradable water-soluble polymer material. PVA's excellent biodegradability has been recognized, and its final decomposition product is carbon dioxide and water, which is non-polluting to the environment, making it an excellent environmentally friendly material. PVA material has no irritation to biologically active substances, is inexpensive, and is a material that can be used in various fields such as the pharmaceutical industry, agricultural production, the food industry, environmental protection, etc. The hydrolysis liquid is harmless to the soil, and the appropriate adhesive property promotes the modification of soil clumping, improves the soil's permeability to plant growth and the activity of biological growth in the soil, and is a truly green and environmentally friendly polymer material with development potential.

[0298] PVA is a thermoplastic polymer, but its thermoplastic processing is recognized as a world problem. This is determined by the molecular structure of PVA. PVA is a crystalline polymer that contains a large number of intramolecular and intermolecular hydrogen bonds, making its melting point exceed 220°C. However, the decomposition temperature of PVA is relatively low, and it starts to dehydrate and etherize at 160°C and starts to decompose at 200°C. Therefore, the melting point and decomposition temperature of PVA overlap, making it difficult to obtain a sufficient thermoplastic processing window. For this reason, the commonly used forming methods for PVA are all solution methods, such as solution spinning, solution casting film, etc. However, PVA based on solution processing can only be prepared into low-dimensional products such as films and fibers, and cannot obtain three-dimensional PVA products.

[0299] In order to solve this problem, researchers have tried to modify the PVA raw material to improve the thermal processing performance of PVA, or to dope other plasticizers and thermal stabilizers in ordinary PVA, so as to prepare PVA modified materials by thermoplastic processing (Chinese patents CN103724899A, CN111303570A, http: / / www.newpva.com / article / detail / 232, PVA thermal degradation and thermoplastic modification research). However, these methods all involve complex processes and introduce other chemical components, affecting the green environmental properties of PVA. Currently, there is no method to prepare three-dimensional PVA plastics without any doping.

[0300] In view of the technical problem of processing three-dimensional PVA plastics, the present embodiment provides a new production process for polyvinyl alcohol plastics, which does not use any additives in the preparation process, ensuring the environmental properties of the product, and the obtained material has a three-dimensional structure and mechanical properties comparable to special engineering plastics (such as polyether ether ketone) or composite materials.

[0301] Example 37, preparation of three-dimensional PVA plastics

[0302] Using the PVA powder (crystallinity 45%, particle size 100-150 um) obtained in Example 1, and water were mixed, the mass ratio of water and PVA powder was 2.5:1, the temperature of water was 10℃, and the mixture was stirred by magnetic force for 2 minutes. The PVA microgel mixture was poured into a customized square mold with a side length of 3 cm*3 cm. After the mold was compacted, the mold was transferred to a 40℃ oven for 30 minutes. Subsequently, the mold was demolded, and the obtained PVA hydrogel was air-dried and annealed. The annealing conditions were heating at 160℃ for 6 hours, and a square PVA plastic was obtained. Through three-point bending test, the bending strength of the material was measured to be 120 MPa.

[0303] Example 38, in vitro cell safety verification of polyvinyl alcohol hydrogel prosthesis

[0304] In this example, 100% of the leaching solution of the polyvinyl alcohol hydrogel material prepared in Example 13 was used to culture C3H cells in vitro according to the national standard GB / T16886.5-2017, and the C3H cells cultured in complete medium were used for comparison. Cell live / dead staining and CCK8 test were performed, and the results are shown in Figure 13, where HF is the leaching solution of the polyvinyl alcohol hydrogel material, and control is the complete medium. As can be seen from Figure 13, cell live / dead staining and CCK8 test show good proliferation activity of the cells, proving that the polyvinyl alcohol hydrogel material prepared by the present application has very good safety.

[0305] Although the present application is disclosed as above, the present application is not limited thereto. As can be extended according to its application range in medicine. Any person skilled in the art, without departing from the spirit and scope of the present application, can make various changes and modifications, therefore the protection scope of the present application should be limited by the scope defined in the claims.

Claims

1. A method for preparing a polyvinyl alcohol powder for preparing a hydrogel, characterized by, The polyvinyl alcohol is used as raw material, and is prepared by any one of the following four methods: The first method is direct pulverization; The second method is to prepare a polyvinyl alcohol solution, then to perform physical crosslinking, dry, and then pulverize; The third method is to prepare a polyvinyl alcohol solution, then to perform flow casting and film pulverization; The fourth method is to perform hot melt extrusion flow casting of polyvinyl alcohol, and then to pulverize.

2. The production method according to claim 1, wherein Any one of the four methods is used to prepare the powder, and the powder with a particle size of 1-1000 μm is screened.

3. The production method according to claim 1, wherein The polyvinyl alcohol has a polymerization degree of 200-5000 and an alcoholysis degree of 80-100%.

4. The production method according to claim 1, wherein The polyvinyl alcohol solution of the second or third method comprises an aqueous solution of polyvinyl alcohol.

5. The production method according to claim 4, wherein The aqueous solution of polyvinyl alcohol consists of polyvinyl alcohol and water only, or further comprises polycarboxyl or polyhydroxyl compounds, which include but are not limited to any one or more of citric acid, ethylenediaminetetraacetic acid, tannic acid, gallic acid, catecholamine, and polyacrylic acid.

6. The production method according to claim 4, wherein The mass percentage of polyvinyl alcohol in the polyvinyl alcohol solution is 5-20%.

7. The production method according to claim 1, wherein The physical crosslinking of the second method comprises one or more of freeze-thaw, freeze-drying, solvent exchange, and directional freeze-salting.

8. The production method according to claim 1, wherein The third method is preferably used to prepare the polyvinyl alcohol powder.

9. The production method according to claim 8, wherein The flow casting refers to placing the polyvinyl alcohol solution in a container, and then condensing the solution into a film after the water content is reduced, so that the thickness of the film is 30-150 μm.

10. The production method according to claim 1, wherein The temperature of the hot melt extrusion of the fourth method is not higher than 180℃.

11. A polyvinyl alcohol powder, characterized in that, The crystallinity is 30-60%, and the polyvinyl alcohol has a polymerization degree of 200-5000 and an alcoholysis degree of 80-100%.

12. The polyvinyl alcohol powder according to claim 11, wherein The crystallinity is 40-48%, and the polyvinyl alcohol has a polymerization degree of 1500-2500 and an alcoholysis degree of 97-99%.

13. The polyvinyl alcohol powder according to claim 12, wherein The method is prepared according to any one of claims 1-10.

14. A polyvinyl alcohol hydrogel, characterized in that, The polyvinyl alcohol powder is swelled to connect with each other to form the polyvinyl alcohol hydrogel, which has a granular material structure and pores.

15. The polyvinyl alcohol hydrogel of claim 14, wherein, The polyvinyl alcohol powder has a crystallinity of 30-60%, and the polyvinyl alcohol has a polymerization degree of 200-5000 and an alcoholysis degree of 80-100%.

16. The polyvinyl alcohol hydrogel of claim 15, wherein, The polyvinyl alcohol powder has a particle size of 1-1000 μm, and the gap between the un-fused particles in the polyvinyl alcohol hydrogel is 1-400 μm.

17. A method of preparing a polyvinyl alcohol hydrogel, characterized by, The polyvinyl alcohol hydrogel is prepared by swelling the polyvinyl alcohol powder to connect with each other.

18. The production method according to claim 17, wherein The method comprises the following steps: (1) preparing the polyvinyl alcohol powder, which has a crystallinity of 30-60%, and the polyvinyl alcohol has a polymerization degree of 200-5000 and an alcoholysis degree of 80-100%; (2) mixing the polyvinyl alcohol powder with water, and stirring to make the polyvinyl alcohol powder start to swell to form micro-gel, and providing pressure during the swelling process to make the swelled particles of the polyvinyl alcohol powder connect with each other to form the hydrogel.

19. The production method according to claim 18, wherein The ratio of the polyvinyl alcohol powder to water in step (2) is 1:(0.5-9).

20. The production method according to claim 18, wherein The pressure is provided during the swelling process of the polyvinyl alcohol powder to form the micro-gel, and the pressure makes the micro-gel particles connect with each other to form the hydrogel; the un-completely swelled micro-gel has a water content of not more than 90%.

21. The production method according to claim 20, wherein The step (2) of providing pressure during the swelling of the polyvinyl alcohol powder comprises providing pressure when the water content of the microgel is between 10% and 85%.

22. The production method according to claim 18, wherein The pressure in step (2) is (10 3 ~ 10 8 ) Pa.

23. The production method according to claim 18, wherein The step (2) of mixing the polyvinyl alcohol powder with water comprises that the temperature of the water is between 0 and 40℃.

24. The production method according to claim 18, wherein The step (2) of stirring comprises magnetic stirring, and the stirring time is between 0.1 and 10 minutes.

25. The production method according to claim 18, wherein The step (2) of providing pressure during the swelling comprises that the microgel which has not been completely swollen is placed in a container and is compacted.

26. The production method according to claim 25, wherein The step (2) of providing pressure during the swelling comprises that the microgel which has not been completely swollen is placed in a container and is compacted, and then the container is placed in an oven for heat preservation, and the temperature of the oven is between 5 and 80℃.

27. The production method according to claim 26, wherein The heat preservation time is between 10 and 60 minutes, and then the hydrogel is taken out from the container.

28. The production method according to claim 18, wherein The water in the step (2) can contain hydrophilic ions and / or chaotropic ions.

29. The production method according to claim 28, wherein The hydrophilic ions include any one or more of sulfate, carbonate, citrate, acetate, nitrate, chloride, and iodide, and the chaotropic ions include any one or more of lithium ion, sodium ion, potassium ion, magnesium ion, calcium ion, and strontium ion.

30. The preparation method according to claim 18, characterized in that, The polyvinyl alcohol powder in the step (1) is prepared by any one of the following four methods: The first method is that polyvinyl alcohol is directly crushed, and the powder with a particle size of 1-1000 μm is screened out. The second method is that polyvinyl alcohol solution is prepared, and then is physically crosslinked, dried, crushed, and the powder with a particle size of 1-1000 μm is screened out. The third method is that polyvinyl alcohol solution is prepared, and then is cast into a film, crushed, and the powder with a particle size of 1-1000 μm is screened out. The fourth method is that polyvinyl alcohol is hot-melt extruded, cast into a film, crushed, and the powder with a particle size of 1-1000 μm is screened out.

31. The production method according to claim 30, wherein The polyvinyl alcohol solution consists of polyvinyl alcohol and water, or further contains polycarboxylic or polyhydroxy compounds, which include but are not limited to any one or more of citric acid, ethylenediaminetetraacetic acid, tannic acid, gallic acid, catecholamine, and polyacrylic acid.

32. A method of preserving a polyvinyl alcohol hydrogel, characterized by, The polyvinyl alcohol hydrogel is prepared by any one of the methods of claims 14-16 or any one of the methods of claims 18-31, and is dried, rehydrated in water, and then stored, or is directly stored in water.

33. Use of a polyvinyl alcohol powder for the preparation of a polyvinyl alcohol hydrogel, characterized in that, The polyvinyl alcohol powder is prepared by any one of the methods of claims 1-10.

34. The use of claim 33, wherein the compound is administered in a daily dose of about 0.1 to about 100 mg / kg. The polyvinyl alcohol hydrogel is formed by the swelling of the polyvinyl alcohol powder, and has a granular material structure.

35. Use of a polyvinyl alcohol powder as a raw material for the preparation of a polyvinyl alcohol hydrogel with tunable mechanical properties, characterized in that, The polyvinyl alcohol hydrogel has any one or more of adjustable strength, rigidity, toughness, and fatigue resistance, and the polyvinyl alcohol powder is prepared by any one of the methods of claims 1-10.

Images