A mold for preparing a polyvinyl alcohol hydrogel

Abstract

This invention provides a mold for preparing polyvinyl alcohol hydrogel, comprising a base, a shaping device, and a pressure device. The shaping device and the base are detachably assembled from top to bottom to form a groove with an opening. The groove is used to hold microgels, which are granular gels formed when polyvinyl alcohol powder is mixed with water and begins to swell but has not yet fully swelled. The pressure device is used to apply pressure to the microgels in the groove, causing the microgel particles to connect with each other to form polyvinyl alcohol hydrogel. The base is provided with protrusions and grooves. The protrusions match the dimensions of the lower bottom surface of the chamber in the shaping device, allowing the protrusions to enter the chamber and cover the lower bottom surface of the chamber. The grooves are arranged around the outer periphery of the protrusions to encourage the water flowing out of the microgels during the extrusion process to flow from the protrusions to the grooves, preventing the microgels from being soaked in the extruded water and improving the preparation efficiency and quality of the polyvinyl alcohol hydrogels.

Description

[0001] This application claims priority to the earlier Chinese application, application number 202421249832.2, filed on June 3, 2024; all its contents are part of this invention. Technical Field

[0002] This utility model relates to the field of polyvinyl alcohol material preparation technology, and more specifically, to a mold for preparing polyvinyl alcohol hydrogel. Background Technology

[0003] The soft tissues of the human musculoskeletal system, including tendons, ligaments, cartilage, and menisci, function to absorb shock, cushion, bear weight, and transmit mechanical forces. To perform their normal physiological functions, these tissues possess high strength, high toughness, and fatigue resistance. These mechanical properties originate from the abundant extracellular matrix composed of water and fibrous networks within these tissues. However, due to the lack of cells in these tissues, they are difficult to regenerate after injury. In clinical treatment, prosthetic materials are needed to reconstruct the function of the musculoskeletal soft tissues. With the aging of society, the demand for high-performance prosthetic materials is increasing. In addition to ensuring biocompatibility, musculoskeletal soft tissue prosthetic materials must also possess mechanical characteristics matching the corresponding tissues, namely high strength, high toughness, and fatigue resistance. These properties are difficult to achieve with synthetic materials. Hydrogels are a class of polymeric materials containing a large amount of water and possessing a three-dimensional network structure. Their structure is very similar to the extracellular matrix, making them ideal biomedical materials. However, traditional hydrogel materials have relatively low strength and cannot meet the requirements of biomedical materials in the fields of musculoskeletal soft tissue prosthetics and tissue engineering.

[0004] Breast implants are used for breast reconstruction, and fillers are also required in other plastic surgeries such as breast augmentation, rhinoplasty, and forehead augmentation. These implant materials must be made of materials that are harmless to the human body, do not cause rejection, do not deteriorate over a long period, have a certain degree of softness, are easy to shape, and are easy to remove. Silicone and expanded polytetrafluoroethylene (ePTFE) are currently commercially available medical aesthetic filler materials. However, silicone implants have the following problems. 1. Silicone rubber filler is a solid structure and cannot form a reliable biological fixation with surrounding tissues, making it prone to displacement if it remains in the body for a long time; 2. Because tissues cannot grow into the silicone implant, the immune response can cause a capsule to form on the implant surface, leading to capsular contracture, which will cause implant deformity in the long term and result in an unnatural appearance after surgery; 3. Under significant pressure, it may deform or even rupture. If the filler is silicone gel, silicone may leak into the lymphatic system or adjacent tissues, causing complications such as lymph node inflammation and mild swelling, silicone granulomas, muscle spasms and pain, rashes, hair loss, and joint swelling and pain (Chinese Patent CN210673507U, Patent WO2006079905A2, Chinese Patent CN107412873A). Compared to silicone, expanded polytetrafluoroethylene (ePTFE) has pores on its surface that allow tissue ingrowth, thus preventing capsular contracture. However, ePTFE has poor toughness and high hardness, which does not match the mechanical properties of natural tissue, affecting comfort and resulting in an unnatural appearance after implantation. Traditional hydrogel materials lack sufficient elasticity and toughness, and do not possess the soft and rapid rebound properties similar to human soft tissue, failing to meet the requirements for cosmetic filler materials.

[0005] Polyvinyl alcohol (PVA) hydrogel possesses excellent biocompatibility, does not degrade in vivo, and is chemically stable, and has been approved by the U.S. Food and Drug Administration (FDA) for use in implantable medical devices. Due to its unique crystalline structure, PVA hydrogel's strength, toughness, and fatigue resistance are expected to meet the requirements for use in various soft tissue prosthetic materials.

[0006] Traditional methods for preparing PVA hydrogels mainly include chemical crosslinking and physical crosslinking. However, these methods have potential drawbacks, including uncontrollable crosslinking structures, low strength, reduced biocompatibility due to the introduction of other chemical reagents, and complex operational procedures. Preparing strong, tough, and fatigue-resistant polyvinyl alcohol hydrogels remains a significant challenge.

[0007] Chemical crosslinking involves adding a chemical crosslinking agent to form a network structure of polyvinyl alcohol (PVA) macromolecules, thereby constructing a gel. Commonly used PVA crosslinking agents include glutaraldehyde, chloropropanol, boric acid, and genipin. While chemical crosslinking can improve the strength of PVA hydrogels, it also increases the material's brittleness, thus reducing its toughness. Furthermore, chemical crosslinking presents challenges such as complex preparation processes and difficulty in removing crosslinking agent residues, which can reduce biocompatibility.

[0008] Physical crosslinking, also known as the freeze-thaw cycle or repeated freeze-thaw process, is the most common method for preparing PVA hydrogels. First, the PVA aqueous solution is frozen at a low temperature (around -20°C). At this temperature, the water in the polyvinyl alcohol aqueous solution crystallizes (ice). Using the formed ice as a template, polyvinyl alcohol molecules approach each other, forming numerous hydrogen bonds, thus creating crystalline fragments within the polyvinyl alcohol molecular chain. Subsequently, the frozen PVA aqueous solution is restored to room temperature, and these crystalline fragments are retained. At this point, the PVA aqueous solution transforms into a PVA hydrogel, and the PVA molecular chains form a three-dimensional network structure through the aforementioned crystalline fragments. This process is called a freeze-thaw cycle. Typically, one cycle is sufficient to obtain a hydrogel. With each additional cycle, the number of crystalline fragments in the PVA hydrogel increases, thus increasing the strength of the PVA hydrogel.

[0009] Physical cross-linking is low-cost and has good biocompatibility. Theoretically, increasing the number of freeze-thaw cycles can control the mechanical properties of the final product, thus making its mechanical properties similar to those of various human soft tissues (including those for strengthening the musculoskeletal system and cosmetic fillers). Furthermore, the preparation process involves pouring a PVA aqueous solution into a mold, freezing and thawing it, and then demolding to obtain the product. Therefore, theoretically, products of various shapes can be prepared by designing molds. However, in reality, the only commercially available PVA hydrogel product prepared using this method is a cartilage prosthesis (trade name Cartiva, patent EP3277228B1, patent WO2012162552A1). No products with different mechanical properties or complex shapes have been developed. Therefore, based on the current development status of this preparation method (repeated freeze-thaw cycles) and our analysis and reasoning, we believe that this method has the following shortcomings. 1. During repeated freeze-thaw cycles, the material is heated unevenly, making it difficult to maintain its shape during processing. Prolonged freeze-thaw cycles can lead to water loss and shrinkage (doi.org / 10.1016 / j.ces.2022.118120); 2. During repeated freeze-thaw cycles, the material may interact with the container, making demolding difficult and resulting in complex shapes; 3. Repeated freeze-thaw cycles cause the formation of numerous crystalline fragments within the material. However, these fragments are randomly distributed, making it difficult to stably control the material's mechanical properties; 4. Although increasing the number of freeze-thaw cycles can improve the mechanical strength of PVA hydrogels, this process is very time-consuming and energy-intensive (doi.org / 10.3390 / polym15183782).

[0010] To improve the strength and toughness of polyvinyl alcohol (PVA) hydrogels, researchers have conducted extensive work. The vast majority of this work is based on physically cross-linked PVA hydrogels, aiming to improve the crystallinity of the hydrogel through various methods. For example, Lin et al. (DOI: 10.1126 / sciadv.aau8528) annealed physically cross-linked PVA hydrogels to improve crystallinity, obtaining fatigue-resistant PVA hydrogels; Lin et al. (DOI: 10.1073 / pnas.1903019116) improved the orientation of the hydrogel network by mechanically training physically cross-linked PVA hydrogels, obtaining PVA hydrogels with muscle-like mechanical properties; Chinese patent CN106432759A discloses a method for improving the strength of PVA hydrogels, which involves... PVA hydrogels obtained through freeze-thaw cycles were soaked in a saturated sodium chloride aqueous solution, which improved their strength. Hua et al. (DOI: 10.1038 / s41586-021-03212-z) obtained high-strength and high-toughness PVA hydrogels through directional freezing combined with salting out. Chinese patent CN110229374B describes a method for preparing high-strength oriented polyvinyl alcohol hydrogels, which involves pre-stretching, freeze-drying, and salting out physically cross-linked PVA hydrogels, further improving their strength and toughness. Although these methods have improved the mechanical properties of polyvinyl alcohol hydrogels to some extent, the materials obtained still cannot meet the requirements of soft tissue prostheses for sports systems. Specifically, firstly, although some methods have improved strength and toughness, the resulting hydrogels do not have sufficient stiffness, i.e., the elongation at break is relatively large (exceeding 200%), while the deformation range of human tissues (such as ligaments and cartilage) is usually no more than 20%. Secondly, the preparation process for high-strength, high-toughness materials typically involves a salting-out step, but high concentrations of ions can reduce the biocompatibility of PVA hydrogels. Furthermore, the fatigue resistance of materials obtained through these methods is unknown; that is, it cannot be confirmed whether the material can withstand prolonged mechanical stress in an in vivo environment, and the effectiveness of these materials has not been verified through in vivo experiments. Finally, some methods have overly complex preparation processes, making it difficult to control the morphology of the material and obtain PVA hydrogel materials with natural tissue morphology.

[0011] Furthermore, while PVA is a thermoplastic polymer, its thermoplastic processing remains a recognized global challenge. This is due to the molecular structure of PVA. PVA is a crystalline polymer containing numerous intramolecular and intermolecular hydrogen bonds, giving it a melting point exceeding 220°C. However, PVA has a relatively low decomposition temperature, beginning dehydration and etherification at 160°C and decomposition 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, commonly used molding methods for PVA are solution methods, such as solution spinning and solution casting. However, solution-processed PVA can only produce low-dimensional products such as films and fibers, and cannot produce three-dimensional PVA products.

[0012] Therefore, there is an urgent need to find a method for preparing polyvinyl alcohol hydrogels that can improve mechanical properties while taking into account biological safety, and whose tensile / compressive mechanical properties are closer to those of natural musculoskeletal soft tissues, and to develop related molds, so as to prepare various polyvinyl alcohol hydrogel products more efficiently and conveniently, such as cartilage prostheses, medical aesthetic filling materials, three-dimensional PVA plastics, etc. Utility Model Content

[0013] To address the aforementioned problems, this invention provides a mold for preparing polyvinyl alcohol hydrogel, comprising a base, a shaping device, and a pressure device. The shaping device and the base are detachably assembled from top to bottom to form a groove with an opening. The groove is used to hold microgels, which are granular gels formed when polyvinyl alcohol powder is mixed with water and begins to swell but has not yet fully swelled. The pressure device applies pressure to the microgels in the groove, causing the microgel particles to connect with each other to form a polyvinyl alcohol hydrogel. The base has protrusions and grooves. The protrusions match the dimensions of the lower bottom surface of the chamber in the shaping device, allowing the protrusions to enter the chamber and cover its lower bottom surface. The grooves surround the outer periphery of the protrusions, causing the water flowing out of the microgels during the extrusion process to flow from the protrusions to the grooves, preventing the microgels from being soaked in the extruded water and improving the preparation efficiency and quality of the polyvinyl alcohol hydrogels.

[0014] All existing techniques for preparing polyvinyl alcohol hydrogels involve cross-linking polyvinyl alcohol solutions, differing only in the cross-linking method and post-cross-linking reinforcement treatment. Chemically cross-linked hydrogels exhibit low toughness, complex processes, additive residues, and low safety. Hydrogels obtained through repeated freeze-thaw cycles have low strength. Hydrogels prepared by freeze-thaw + annealing or freeze-thaw + mechanical training are complex to handle, have moduli that are difficult to match with natural tissues, and cannot simulate natural tissue morphology. Hydrogels prepared by freeze-thaw + salting out or directional freeze-thaw + salting out are prone to residual ions, reducing safety, have low modulus, and are complex to handle.

[0015] This invention presents an original method for preparing polyvinyl alcohol hydrogels without the need for cross-linked polyvinyl alcohol solutions. This method can be called Hydrafusion.

[0016] To facilitate understanding, we will first introduce the origin of this definition: the name comes from the process of bonding thermoplastic polymer parts through thermal fusion. Specifically, when thermoplastic polymers are heated, the activity 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 drops, the diffused molecular chains stabilize through entanglement and crystallization, thereby achieving a strong connection between the two parts.

[0017] The principles of this invention's Hydrafusion and Thermal fusion are similar, but the specific steps differ. First, polyvinyl alcohol (PVA) raw material is dissolved and cast into a film, then air-dried to obtain a PVA film. Next, the PVA film is pulverized to obtain PVA powder particles. Subsequently, the PVA powder is mixed with water and swirled to obtain partially swollen microgel particles. Finally, the microgels are injected into a mold of a specific shape and held for a period of time, allowing the PVA molecular chains to diffuse between the microgel interfaces, forming entanglements and crystallization, thereby obtaining a PVA hydrogel with a stable shape and structure.

[0018] The polyvinyl alcohol hydrogel prepared by this invention does not use any additives during the preparation process, ensuring the biocompatibility of the product. The resulting hydrogel material has a typical granular structure and tensile / compression mechanical properties similar to those of natural musculoskeletal soft tissue. It can recover its initial properties after repeated long-term compression or stretching. Moreover, it can improve the mechanical properties of polyvinyl alcohol while taking into account biocompatibility. It can be used to develop corresponding prosthetic materials, medical aesthetic fillers, plastics, etc.

[0019] In view of the preparation method of polyvinyl alcohol hydrogel, the present invention designs a corresponding mold. The mold has a simple structure, low cost, and can prepare polyvinyl alcohol hydrogel more efficiently and conveniently.

[0020] On the one hand, this utility model provides a mold for preparing polyvinyl alcohol hydrogel, the mold including a base, a shaping device and a pressure device; the shaping device and the base are combined from top to bottom to form a groove with an opening; the contact part between the base and the shaping device is provided with a groove; the pressure device is used to apply pressure to the microgel in the groove.

[0021] The tank is used to hold microgels, which are granular gels formed when polyvinyl alcohol powder is mixed with water and begins to swell but has not yet fully swelled; the pressure device is used to apply pressure to the microgels in the tank, so that the microgel particles connect with each other to form polyvinyl alcohol hydrogels.

[0022] This invention has proven that polyvinyl alcohol hydrogels can be produced by applying pressure to the microgels during the swelling process of polyvinyl alcohol powder, causing the originally dispersed microgels to fuse together. The direction of the pressure—whether from top to bottom, bottom to top, left to right, right to left, or from all directions towards the center, or even from the center outwards to form a hollow ring—can all achieve the desired fusion of the microgels into a hydrogel. For ease of mold preparation and pressure application to the microgels, the mold provided by this invention uses an upward-opening groove, with the pressure device applying pressure directly downwards from the groove opening.

[0023] During the initial swelling process of polyvinyl alcohol (PVA) powder, the PVA molecular chains begin to diffuse and form microgels. Once the diffusion reaches a certain extent, extrusion is performed. During extrusion, the PVA molecular chains at the microgel interface continue to diffuse and entangle, subsequently forming stable bonds through crystallization, thus forming a hydrogel. It is important to note that the hydrogel must be prepared during the swelling process. Once the microgel is fully swollen, it is impossible to prepare a hydrogel by extrusion because the PVA molecular chains cannot continue to diffuse during extrusion and therefore cannot entangle and bond together.

[0024] The polyvinyl alcohol hydrogel prepared by this invention is closely related to the molecular chain diffusion effect between polyvinyl alcohol powder particles during the preparation and processing. The more molecular chain diffusion at the powder particle interface, the better the fusion, and the more crystals formed in the fused area or inside the powder, the better the strength, toughness, stiffness, and fatigue resistance of the hydrogel material, making it more suitable for strengthening soft tissues of the musculoskeletal system. Conversely, the material will be softer and suitable for certain medical aesthetic filler materials.

[0025] In some embodiments, the mold can be flexibly designed according to product needs and can be of any shape, as long as the microgel can be squeezed within it. It includes a mold base for placing the hydrogel and a pressing element for pressing the hydrogel. The pressing element can press the microgel from the outside to the inside or from the inside to the outside, and the shape of the pressing element can also be set arbitrarily as needed.

[0026] Microgels are injected into molds for molding: by controlling the molding temperature and time, the microgels can be fused together to obtain polyvinyl alcohol hydrogels. By controlling the shape of the mold, polyvinyl alcohol hydrogels of various shapes can be obtained.

[0027] Furthermore, the shaping device has a vertically penetrating chamber with open top and bottom surfaces. When the shaping device is combined with the base, the base covers the bottom surface of the chamber of the shaping device.

[0028] The chambers within the shaping device form the walls of the tank. These chambers are open at both the top and bottom and can be cylindrical, triangular prism, or any other shape.

[0029] Furthermore, the contact area between the base and the shaping device is provided with a groove, which can be provided on the base or on the shaping device.

[0030] Whether the undesirable groove is located on the base or on the shaping device, it is sufficient that the contact area between the base and the shaping device has a groove when they are combined.

[0031] In some configurations, the groove is positioned below the orientation device.

[0032] In some designs, the groove is positioned above the base.

[0033] Furthermore, the base is also provided with a protrusion that matches the size of the bottom surface of the chamber in the shaping device, so that the protrusion can enter the chamber and cover the bottom surface of the chamber.

[0034] In some embodiments, the chamber is cylindrical with a circular bottom surface, and the protrusion is also cylindrical and its size matches that of the chamber, allowing the protrusion to enter the chamber from the bottom surface and combine with the chamber to form a complete groove.

[0035] In some methods, micron-sized gaps can exist between the protrusions and the chamber walls. These gaps allow water squeezed out of the microgel to flow away without leaking out. This ensures the microgel can effectively expel water during extrusion, preventing it from being soaked in the squeezed-out water for extended periods. Since the properties of polyvinyl alcohol hydrogels are related to the bonding effect of the microgel molecules during extrusion, if the microgel is submerged in water, it will inevitably affect the bonding of the underlying microgel molecules, thus impacting the performance of the prepared polyvinyl alcohol hydrogel.

[0036] In some designs, the upper surface of the protrusion is a horizontal circle or a circle with its center slightly raised, making it more difficult for moisture to remain.

[0037] Furthermore, the groove is positioned around the outer periphery of the protrusion and below the protrusion to facilitate the flow of water squeezed out of the microgel from the protrusion to the groove.

[0038] In some configurations, the groove surrounds the periphery of the protrusion, thereby catching all the water that flows out from the small gap.

[0039] Furthermore, the groove may or may not be connected to the outside world. When connected to the outside world, the water squeezed out of the microgel can be drained out; when not connected to the outside world, the water squeezed out of the microgel can be stored.

[0040] Furthermore, the shape of the tank is defined by the chamber within the shaping device and the protrusion on the base, and the shape of the tank can be matched to the shape of the product to be prepared.

[0041] Furthermore, the pressure application device is equipped with a component that can extend into the tank from the tank opening, thereby applying pressure to the microgel inside the tank through the tank opening.

[0042] In some embodiments, the tank is cylindrical, and the component that can extend into the tank is also cylindrical, thereby allowing the microgel therein to be fully compacted.

[0043] Furthermore, the shaping device and the base are detachable.

[0044] The shaping device and the base are detachable. When combined, they can be used to prepare polyvinyl alcohol hydrogels. When separated, they can be used to remove the polyvinyl alcohol hydrogels from the mold.

[0045] Furthermore, when the shaping device is separated from the base, the tank has an upper opening and a lower opening, and the pressure device can extend into the tank from the upper or lower opening, thereby causing the prepared polyvinyl alcohol hydrogel to detach from the mold.

[0046] In some methods, after the microgel is extruded, the base can be separated from the shaping device, the shaping device can be inverted, and then a pressure device can be used to enter from the bottom surface of the inner cavity of the shaping device to press the polyvinyl alcohol hydrogel out of the tank.

[0047] In some methods, after the microgel is extruded, the base can be separated from the shaping device, and then the pressure device can be directly inserted from the top surface of the inner cavity of the shaping device to press the polyvinyl alcohol hydrogel out of the tank. Since the prepared polyvinyl alcohol hydrogel has a certain viscosity, it is more preferable to invert the shaping device, which provides more space for the pressure device to help the polyvinyl alcohol hydrogel detach from the inner wall of the chamber.

[0048] On the other hand, the method for preparing the above-mentioned polyvinyl alcohol hydrogel uses the mold described above.

[0049] Furthermore, the method includes the following steps:

[0050] (1) Prepare polyvinyl alcohol powder, wherein the crystallinity of the polyvinyl alcohol powder is 30-60%, and it is prepared from polyvinyl alcohol with a degree of polymerization of 200-5000 and a degree of alcoholysis of 80-100%;

[0051] (2) Mix polyvinyl alcohol powder with water and stir to make the polyvinyl alcohol powder begin to swell and form microgels. During the swelling process, transfer the microgels to the tank of the mold and apply pressure to the microgels in the tank with a pressure device to make the microgel particles connect with each other to form polyvinyl alcohol hydrogels.

[0052] In some methods, step (2) of applying pressure refers to placing the microgel, which has not yet fully swollen, in a container and then compressing it.

[0053] Furthermore, it also includes step (3): separating the mold shaping device from the base, and extending the pressure device into the tank from the upper or lower opening of the tank, so that the prepared polyvinyl alcohol hydrogel is removed from the mold.

[0054] In some embodiments, the polyvinyl alcohol powder of step (1) is obtained by any one of the following four methods:

[0055] The first method: using polyvinyl alcohol as raw material, directly crushing and screening to obtain powder with a particle size of 1~1000μm;

[0056] The second method involves first preparing a polyvinyl alcohol solution, then physically cross-linking it, drying it, pulverizing it, and screening it to obtain powder with a particle size of 1~1000μm.

[0057] The third method involves first preparing a polyvinyl alcohol solution, casting it into a film, pulverizing it, and then screening it to obtain powder with a particle size of 1~1000μm.

[0058] The fourth method involves using polyvinyl alcohol hot melt extrusion casting to form a film, followed by pulverization and screening to obtain powder with a particle size of 1~1000μm.

[0059] Preparation method of polyvinyl alcohol hydrogel: By adjusting the parameters of the preparation process and controlling the shape of the mold, a variety of different products can be prepared, including soft tissue prostheses for the sports system, medical aesthetic filling materials, and polyvinyl alcohol plastics with three-dimensional structures.

[0060] The preparation method of polyvinyl alcohol (PVA) hydrogel mainly involves two steps. The first step is to prepare PVA powder using commercially available PVA as a raw material. The second step is to prepare PVA hydrogel by molding the PVA powder through a mold during the swelling process. The PVA powder can be obtained by direct pulverization, physical cross-linking, or film casting. The third method (water solution film casting) is preferred for preparing PVA powder, as it yields the most suitable crystallinity and excellent consistency. It is also simple to operate, has more stable performance, and can be used to prepare PVA hydrogel products with superior performance.

[0061] Polyvinyl alcohol hydrogels prepared from polyvinyl alcohol powder exhibit a typical granular structure. Under an electron microscope, it can be clearly seen that they are prepared by the fusion of particles, and there are micron-sized pores between adjacent particles that are not fused together. In contrast, hydrogels prepared by other methods have a denser surface and do not exhibit granular structures or micron-sized pores. Therefore, the polyvinyl alcohol hydrogel prepared by this invention is a novel product.

[0062] The ability of polyvinyl alcohol (PVA) powder to fuse and form a hydrogel under pressure during swelling is likely related to the molecular chain structure of PVA. PVA has a linear chain structure and can diffuse during swelling. Attempts to process other natural or synthetic polymers using similar methods have failed to produce hydrogels.

[0063] The gap size between unfused adjacent particles in polyvinyl alcohol hydrogel is determined by the particle size of the polyvinyl alcohol powder. The presence of these gaps also enhances the fatigue resistance of the polyvinyl alcohol hydrogel. This is because the pore structure in porous materials can disperse stress and transfer loads, preventing stress concentration. Furthermore, the presence of these gaps facilitates cell ingrowth, improving the repair effect of bone defects. The polyvinyl alcohol hydrogel can recover to its initial state after repeated long-term compression or stretching, making it more suitable for preparing soft tissues of the human musculoskeletal system (including tendons, ligaments, cartilage, menisci, etc.), providing better shock absorption, cushioning, load-bearing, and mechanical transmission functions.

[0064] The method provided by this invention ultimately yields a polyvinyl alcohol hydrogel with a typical granular material structure. That is, the bulk hydrogel is assembled through strong connections between particles. Therefore, the mechanical properties of the hydrogel are determined by two factors: 1. the interparticle bonding force; 2. the properties of the particles themselves. Regarding the interparticle bonding force: During the molding process, polyvinyl alcohol molecular chains diffuse, entangle, and crystallize between the particles. Due to polyvinyl alcohol's unique hydroxyl-rich structure, the molecular chains recrystallize at the interface after entanglement, thus firmly connecting the particles together and preventing material failure under stress. For the polyvinyl alcohol hydrogel particles themselves, their load-bearing capacity is largely affected by the solid content. For any hydrogel, higher water content results in weaker mechanical properties, while lower water content results in stronger mechanical properties. Because the interconnection of polyvinyl alcohol microgels in this invention is completed during the swelling process of the microgels, meaning that the water content of the microgels is not high during molding, and the entanglement and crystallization at the interface further restrict the water absorption of the particles, the polyvinyl alcohol hydrogel prepared according to the process of this invention still has a high solid content, reaching up to 70%, even in a fully swollen state. By controlling the process parameters, it can usually be controlled at 40%-60%. Therefore, considering the above two aspects, this material has excellent mechanical properties.

[0065] This utility model has the following beneficial effects:

[0066] A novel method for preparing polyvinyl alcohol hydrogels has been developed. First, polyvinyl alcohol is processed into polyvinyl alcohol powder, then mixed with water and swirled to cause the powder to swell and form microgels. Pressure is then applied to cause the polyvinyl alcohol molecular chains at the microgel interfaces to diffuse, entangle, connect, and crystallize to obtain polyvinyl alcohol hydrogels. A corresponding preparation mold has also been designed for this method, which enables the preparation of polyvinyl alcohol hydrogels more conveniently and efficiently.

[0067] The mold consists of a shaping device and a base that can be detachably combined into an open groove, which facilitates both the extrusion of microgels and the demolding of the prepared polyvinyl alcohol hydrogels.

[0068] The base has protrusions and grooves, with the grooves surrounding the outer periphery of the protrusions. This is designed to encourage the water flowing out of the microgel during the extrusion process to flow from the protrusions to the grooves, thus preventing the microgel from being soaked in the extruded water and improving the preparation efficiency and quality of polyvinyl alcohol hydrogels.

[0069] It has a simple structure, low cost, and is suitable for large-scale production applications.

[0070] Detailed description

[0071] Shaping device

[0072] A shaping device is a device that allows microgels to be extruded and then extruded into polyvinyl alcohol hydrogel products of the same shape according to the shape of its internal tank. The key to a shaping device is that it provides shape constraints for its internal tank, while there are no requirements for its overall or external shape. The external shape of the shaping device can be designed based on factors such as ease of processing, placement, transportation, storage, and cost control.

[0073] base

[0074] The base is used to hold the shaping device. To facilitate the extrusion process of polyvinyl alcohol hydrogel and to facilitate demolding, the shaping device is designed with a vertically continuous cavity. When the shaping device is combined with the base, the bottom surface of the cavity is covered by the base, and it is no longer vertically continuous, thus forming a complete groove. Therefore, the base plays a crucial role in this invention. The structural design of the base is very important. By setting protrusions and grooves on the base, when the base is combined with the shaping device, it can ensure the integrity of the groove, allowing for smooth extrusion of microgels to form polyvinyl alcohol hydrogels, while also ensuring that the extruded water is discharged in time during the extrusion process, thereby preventing the bottom of the microgel from being soaked in water and affecting product quality.

[0075] The shape of the base is also unrestricted. It can be designed in any shape based on factors such as ease of processing, convenience of placement, transportation and storage, and cost control. However, it must be ensured that there is a protrusion that matches the bottom surface of the cavity of the shaping device, and that there is a groove near the protrusion to collect the water squeezed out by the microgel in time.

[0076] The volume of the groove inside the base should be no less than the volume of water squeezed out by the microgel, so as to ensure that all the water squeezed out by the microgel can be successfully removed.

[0077] When the groove is connected to the outside, one or more channels can be provided to allow water to drain out. Alternatively, some water can drain out of the groove while some remains inside, as long as water is not trapped at the microgel area.

[0078] Pressure device

[0079] The pressure application device needs to have a pressure-applying component in the shape of a rod, column, etc., so as to apply pressure to the microgel in the tank and compact it. For easy handling and operation, a handle can also be provided on the top of the pressure application device, and the pressure component can be used to apply force to the microgel in the tank by operating the handle.

[0080] The dimensions of the pressure-applying component must be controlled to allow it to smoothly enter the tank; for example, its cross-sectional area should be smaller than the cross-sectional area of ​​the opening in the tank or the interior of the tank. Simultaneously, the material of the pressure-applying component must be of a certain strength to prevent breakage or bending during the pressure-applying process. Attached Figure Description

[0081] Figure 1 This is a schematic diagram of the overall structure of the mold assembly used to prepare the polyvinyl alcohol hydrogel in Example 1.

[0082] Figure 2 This is a cross-sectional view of the mold assembly used to prepare the polyvinyl alcohol hydrogel in Example 1;

[0083] Figure 3 This is a cross-sectional view of the mold used to prepare the polyvinyl alcohol hydrogel in Example 1 after disassembly.

[0084] Figure 4 This is a schematic diagram of the shaping device in Example 1;

[0085] Figure 5 This is a bottom view of the shaping device in Example 1;

[0086] Figure 6 This is a schematic diagram of the base structure in Example 1;

[0087] Figure 7This is a schematic diagram of the overall structure of the tubular polyvinyl alcohol hydrogel mold used in Example 2;

[0088] Figure 8 This is an exploded view of the tubular polyvinyl alcohol hydrogel mold prepared in Example 2;

[0089] Figure 9 The cross-sectional view of the tubular polyvinyl alcohol hydrogel mold prepared in Example 2 is shown in (1) and (2) respectively.

[0090] Figure 10 This is a flowchart of the process for preparing PVA hydrogel by swelling PVA powder in Example 3. Detailed Implementation

[0091] The preferred embodiments of this utility model will be described in further detail below with reference to the accompanying drawings. It should be noted that the embodiments described below are intended to facilitate understanding of this utility model and are not intended to limit it in any way. The raw materials and equipment used in the specific embodiments of this utility model are all known products and were obtained by purchasing commercially available products.

[0092] Example 1: Mold for preparing polyvinyl alcohol hydrogel provided by this utility model

[0093] The mold for preparing polyvinyl alcohol hydrogel provided in this embodiment is as follows: Figures 1-6 As shown, where Figure 1 A schematic diagram of the overall structure after the mold assembly for preparing polyvinyl alcohol hydrogel; Figure 2 A cross-sectional view of the mold assembly for preparing polyvinyl alcohol hydrogel; Figure 3 A cross-sectional view of the mold used to prepare polyvinyl alcohol hydrogel after disassembly; Figure 4 This is a schematic diagram of the shaping device; Figure 5 This is a bottom view of the shaping device; Figure 6 This is a schematic diagram of the base structure.

[0094] This invention provides a novel method for preparing polyvinyl alcohol (PVA) hydrogels. During the initial swelling process of PVA powder, PVA molecular chains begin to diffuse and form microgels. Once the diffusion reaches a certain extent, extrusion is performed. During extrusion, the PVA molecular chains at the microgel interface continue to diffuse and entangle, subsequently forming stable connections through crystallization to form a hydrogel. It is important to note that the hydrogel must be prepared during the swelling process. Once the microgels are fully swollen, extrusion is not possible because the PVA molecular chains cannot continue to diffuse and thus cannot entangle and bond together. A mold specifically designed for this method is used to prepare the PVA hydrogel. The microgels are injected into the mold for molding. By controlling the molding temperature and time, the microgels fuse together to obtain the PVA hydrogel. By controlling the shape of the mold, PVA hydrogels of various shapes can be obtained.

[0095] like Figures 1-3 The mold 1 for preparing polyvinyl alcohol hydrogel provided in this embodiment includes a base 2, a shaping device 3, and a pressure device 4. The shaping device 3 and the base 2 are combined from top to bottom to form a tank 5 with an opening. The tank 5 is used to hold microgels. The microgels described in this embodiment are granular gels that have begun to swell after being mixed with water, but have not yet fully swelled. The pressure device 4 is used to apply pressure to the microgels in the tank 5 so that the microgel particles connect with each other to form polyvinyl alcohol hydrogels.

[0096] like Figure 4 and 5 The shaping device 3 has a vertically connected chamber 6. Both the upper bottom surface 7 and the lower bottom surface 8 of the chamber 6 are open. When the shaping device 3 is combined with the base 2, the base 2 covers the lower bottom surface 8 of the chamber 5 of the shaping device 3. The chamber 6 in the shaping device 3 forms the wall of the tank 5. The chamber 6 is vertically connected and can be cylindrical, triangular prism, or any other shape.

[0097] like Figure 1 The contact area 9 between the base 2 and the shaping device 3 is provided with a groove 10. The groove 10 can be located below the shaping device 3 at 11, above the base 2 at 12, or partially located at both the bottom 11 of the shaping device 3 and the top 12 of the base 2, forming a complete groove 10 when combined. In this embodiment, the groove is provided at the bottom 11 of the shaping device 3, which simplifies the manufacturing process.

[0098] like Figure 6The base 2 is also provided with a protrusion 13, which matches the size of the lower bottom surface 8 of the chamber 6 in the shaping device 3, so that the protrusion 13 can enter the chamber 6 and cover the lower bottom surface 8 of the chamber 6. In this embodiment, the chamber 6 is cylindrical, its lower bottom surface 8 is circular, and the protrusion 13 is also cylindrical and its size matches that of the chamber 6, so that the protrusion 13 can enter the chamber 6 from the lower bottom surface and combine with the chamber 6 to form a complete groove 5.

[0099] Preferably, a small gap, on the micrometer scale, can exist between the protrusion 13 and the inner wall 14 of the chamber 6. This gap allows water squeezed out of the microgel to flow away, but prevents the microgel from leaking out. This ensures that the microgel can effectively remove water during the extrusion process, preventing it from being soaked in the squeezed-out water for an extended period. Since the properties of polyvinyl alcohol hydrogels are related to the bonding effect of the microgel molecules during extrusion, if the microgel is submerged in water, it will inevitably affect the bonding of the lower microgel molecules, thus impacting the performance of the prepared polyvinyl alcohol hydrogel.

[0100] Preferably, the upper surface 15 of the protrusion 13 is a horizontal circle or a circle with its center slightly raised, making it more difficult for water to remain and easier for it to flow into the groove. Figure 5 The groove 10 is arranged around the outer periphery of the protrusion 13 to facilitate the flow of water squeezed out of the microgel from the protrusion 13 to the groove 10. Since the groove 10 surrounds the outer periphery of the protrusion 13, it can collect all the water flowing out from the small gap. The groove 10 can be connected to or not connected to the outside. When connected to the outside, the water squeezed out of the microgel can drain out; when not connected to the outside, it can store the water squeezed out of the microgel. Figure 1 The groove 10 is connected to the outside through the groove opening 16, so that the moisture generated by the squeezed microgel can be discharged to the outside in a timely manner.

[0101] Preferably, the shape of the tank 5 is defined by the chamber 6 in the shaping device 3 and the protrusion 13 on the base 2, and the shape of the tank 5 can be matched to the shape of the product to be prepared.

[0102] like Figure 2 The pressure device 4 is equipped with a component 18 that can extend into the tank 5 from the opening 17, thereby applying pressure to the microgel inside the tank 5 through the opening 17. In this embodiment, the tank 5 is cylindrical, and the component 18 that can extend into the tank 5 is also cylindrical, thereby ensuring that the microgel inside is fully compacted.

[0103] Preferably, the shaping device 3 and the base 2 are detachably combined. When combined, they can be used to prepare polyvinyl alcohol hydrogel; when separated, they can be used to detach the polyvinyl alcohol hydrogel from the mold 1. When the shaping device 3 is separated from the base 2, the tank 5 has an upper opening 19 and a lower opening 20. The pressure device 4 can extend into the tank 5 from the upper opening 19 or the lower opening 20, thereby detaching the prepared polyvinyl alcohol hydrogel from the mold 1.

[0104] Preferably, after the microgel is extruded, the base 2 can be separated from the shaping device 3, and the shaping device 3 can be inverted. Then, the pressure device 4 can be used to enter from the lower bottom surface 8 of the inner cavity 6 of the shaping device 3 to press the polyvinyl alcohol hydrogel out of the tank 5. Alternatively, the shaping device 3 can be inverted without inverting. After the microgel is extruded, the base 2 can be separated from the shaping device 3, and the pressure device 4 can be used directly from the upper bottom surface 7 of the inner cavity 6 of the shaping device 3 to press the polyvinyl alcohol hydrogel out of the tank 5. Since the prepared polyvinyl alcohol hydrogel has a certain viscosity, it is more preferable to invert the shaping device 3, which provides more space for the pressure device 4 to help the polyvinyl alcohol hydrogel detach from the inner wall 14 of the chamber 6.

[0105] Example 2: Another mold for polyvinyl alcohol hydrogel

[0106] This embodiment provides another mold 1 for preparing tubular polyvinyl alcohol hydrogels, such as... Figures 7-9 As shown, where Figure 7 A schematic diagram of the overall structure for preparing a tubular polyvinyl alcohol hydrogel mold; Figure 8 An exploded view of the preparation of a tubular polyvinyl alcohol hydrogel mold; Figure 9 A cross-sectional view for preparing a tubular polyvinyl alcohol hydrogel mold.

[0107] like Figures 7-9The mold 101 for preparing tubular polyvinyl alcohol hydrogel provided in this embodiment includes a base 102, a shaping device 103, and a pressure applying device 104. The shaping device 103 and the base 102 are combined from top to bottom to form a tank 105 with an opening. The tank 105 is used to hold microgels. The microgels described in this embodiment are granular gels formed when polyvinyl alcohol powder is mixed with water and begins to swell but has not yet fully swelled. The pressure applying device 104 is used to apply pressure to the microgels in the tank 105, so that the microgel particles connect with each other to form polyvinyl alcohol hydrogels. The shaping device 103 has a vertically penetrating chamber 106. The upper bottom surface 107 and the lower bottom surface 108 of the chamber 106 are both open. When the shaping device 103 is combined with the base 102, the base 102 covers the lower bottom surface 108 of the chamber 105 of the shaping device 103. The chamber 106 within the shaping device 103 forms the wall of the groove 105, and the chamber 106 is a cylindrical shape with openings at both the top and bottom. A groove 110 is provided at the contact point 109 between the base 102 and the shaping device 103. A protrusion 113 is also provided on the base 102. The cross-section of the protrusion 113 is smaller than the cross-section of the chamber 106 in the shaping device 103, but the cross-sections of the protrusion 113 and the chamber 106 are concentric circles, thus allowing the microgel to be located within the interlayer 121 between the protrusion 113 and the chamber 106. This allows the production of a tubular polyvinyl alcohol hydrogel material, the thickness of which is equivalent to the radius of the chamber 106 minus the radius of the protrusion 113.

[0108] like Figure 2 The groove 110 of the base 102 is also provided with a convex arc 122. When the shaping device 103 is combined with the base 102, the shaping device will not enter the groove 110 due to the obstruction of the convex arc 122, while the water squeezed out of the microgel will flow into the groove 110, which plays the role of storing the water squeezed out of the microgel.

[0109] The pressure applying device 104 is equipped with a component 118 that can extend into the tank 105 through the opening 117, thereby applying pressure to the microgel inside the tank 105 through the opening 117. In this embodiment, the tank 105 is cylindrical, and the component 118 that can extend into the tank 105 is also an annular cylinder with a hollow 123. The outer circumferential dimension of the annular cylinder matches the inner wall dimension of the tank 105, and the inner circumferential dimension matches the outer wall dimension of the protrusion 113, thereby fully compacting the tubular microgel inside. The shaping device 103 and the base 102 are detachably combined. When combined, it can be used to prepare polyvinyl alcohol hydrogel; after separation, it can be used to remove the polyvinyl alcohol hydrogel from the mold 101. When the shaping device 103 is separated from the base 102, the tank 105 has an upper opening 119 and a lower opening 120. The pressure device 104 can extend into the tank 105 from the upper opening 119 or the lower opening 120, thereby causing the prepared polyvinyl alcohol hydrogel to detach from the mold 101.

[0110] Preferably, after the microgel is extruded, the base 102 can be separated from the shaping device 103, and the shaping device 103 can be inverted. Then, the pressure device 104 enters from the lower bottom surface 108 of the inner cavity 106 of the shaping device 103 to press the polyvinyl alcohol hydrogel out of the tank 105. A funnel 124 is provided above the shaping device 103, which facilitates the loading of the microgel into the tank 105 and also facilitates the demolding of the tubular hydrogel inside when inverted.

[0111] Example 3: Method for preparing polyvinyl alcohol hydrogel using a mold

[0112] This embodiment uses mold 1 provided in Example 1 to prepare polyvinyl alcohol hydrogel, including the following steps:

[0113] (1) Preparation of polyvinyl alcohol powder

[0114] Polyvinyl alcohol powder can be prepared by various methods such as pulverization, physical crosslinking, and freeze drying. In this embodiment, the preferred method is casting film formation. The specific process is as follows: PVA of grade 1799 (degree of polymerization 1700, degree of hydrolysis 99%) is dissolved in water to prepare a 10% aqueous solution. The aqueous solution is cast into a film to obtain a PVA film with a thickness of about 50 μm. The film is pulverized to obtain PVA powder. Powder with a particle size of 100-150 μm is sieved out for use in the subsequent preparation of hydrogel materials.

[0115] (2) Preparation of polyvinyl alcohol hydrogel (see flowchart) Figure 10 )

[0116] The polyvinyl alcohol powder (45% crystallinity, 100-150 μm particle size) prepared in step (1) was mixed with water at a mass ratio of 2.5:1 and a water temperature of 10°C. The mixture was magnetically stirred for 2 minutes to obtain a microgel mixture. The microgel mixture was poured into the tank 5 of a cylindrical mold 1 with a diameter of 8 mm. The microgel in the tank 5 was pressed with a pressure device 4 to compress the microgel that had not yet fully swelled. The mold 1 was then transferred to a 40°C oven and kept warm for 30 minutes. Subsequently, the base 2 was separated from the shaping device 3, the shaping device 3 was inverted, and the pressure device 4 entered from the bottom surface 8 of the cavity 6 of the shaping device 3 to push out the polyvinyl alcohol hydrogel material. The obtained polyvinyl alcohol hydrogel material was placed in a constant temperature oven at 140°C for 2 hours and then fully rehydrated and swelled in water to obtain a cylindrical polyvinyl alcohol hydrogel material.

[0117] Our research team has successfully prepared polyvinyl alcohol hydrogel materials using the method provided in this invention, and has successfully completed the preparation of prostheses such as meniscus, cartilage, trachea, blood vessels, nucleus pulposus, and ligaments.

[0118] While the present invention has been disclosed above, it is not limited thereto. Its applications in medicine can be expanded accordingly. Any person skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention; therefore, the scope of protection of the present invention should be determined by the scope defined in the claims.

Claims

1. A mold for preparing polyvinyl alcohol hydrogel, characterized in that, It includes a base, a shaping device, and a pressure applying device; the shaping device and the base are combined from top to bottom to form a groove with an opening; the contact area between the base and the shaping device is provided with a groove.

2. The mold as described in claim 1, characterized in that, The shaping device has a through-cavity, with openings on both the top and bottom surfaces. When the shaping device is combined with the base, the base covers the bottom surface of the cavity of the shaping device.

3. The mold as described in claim 2, characterized in that, The groove can be set on the base or on the shaping device.

4. The mold as described in claim 3, characterized in that, The base is also provided with a protrusion that matches the size of the bottom surface of the chamber in the shaping device, so that the protrusion can enter the shaping device and cover the bottom surface of the chamber.

5. The mold as described in claim 4, characterized in that, The groove is positioned around the outer periphery of the protrusion and below the protrusion, and is used to facilitate the flow of moisture from the protrusion to the groove within the shaping device.

6. The mold as described in claim 5, characterized in that, The groove can be connected to or not connected to the outside. When connected to the outside, it allows moisture in the setting device to drain out; when not connected to the outside, it can be used to store moisture in the setting device.

7. The mold as described in claim 4, characterized in that, The shape of the tank is defined by the chamber inside the shaping device and the protrusion on the base. The shape of the tank can be matched to the shape of the product to be prepared.

8. The mold as described in claim 1, characterized in that, The pressure application device is equipped with a component that can extend into the tank from the opening of the tank, thereby enabling pressure to be applied into the tank through the opening of the tank.

9. The mold as described in claim 1, characterized in that, The shaping device and the base are detachable.

10. The mold as described in claim 9, characterized in that, When the shaping device separates from the base, the tank has an upper opening and a lower opening, and the pressure device can extend into the tank from the upper or lower opening, thereby causing the prepared polyvinyl alcohol hydrogel to detach from the mold.

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