A super-tough polyvinyl alcohol composite hydrogel with biological activity and a preparation method thereof

Abstract

The application discloses a kind of super tough polyvinyl alcohol composite hydrogel with biological activity and preparation method thereof.The polyvinyl alcohol composite hydrogel refers to that polyvinyl alcohol (PVA) is added into NaOH solution, heated to 90 DEG C, and stirred vigorously for 2 hours, after PVA is completely dissolved, a certain proportion of sodium lignosulfonate (LS) and rutin (RT) powder is added, after sodium lignosulfonate and rutin are completely dissolved, it is air-dried into 0.3~0.5 mm thick film at room temperature, then it is immersed in 20~30 mL 10 wt% NaCl solution and swells for 3~5 hours, to obtain PVA-LS-RT composite hydrogel.The polyvinyl alcohol composite hydrogel prepared by the application has super strong mechanical property, and has higher antibacterial, antioxidant and wound healing capacity, and has good application prospect in wound dressing, artificial cartilage and flexible electronics and other cutting-edge fields.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of super tough polyvinyl alcohol composite hydrogel with biological activity and its preparation method, belong to biomedical materials field. BACKGROUND

[0002] Hydrogel is a kind of polymer material with three-dimensional cross-linked network structure, due to its adjustable physical and chemical properties and excellent biocompatibility, it shows broad application prospects in biomedical (such as artificial cartilage, wound dressing) and flexible electronics (such as wearable sensors, supercapacitors) and other fields. Polyvinyl alcohol (PVA), polyacrylic acid, polyacrylamide and cellulose and other polymers have been used to prepare high-performance hydrogel. Among them, PVA hydrogel has become one of the hot research materials due to its excellent biocompatibility, chemical stability and the characteristics of forming crystalline region by physical cross-linking. However, traditional PVA hydrogel generally has insufficient mechanical properties, lacks biological activity and other problems, which seriously limits its practical application in load-bearing medical devices or high-durability flexible devices.

[0003] To overcome the above-mentioned defects, researchers have developed various enhancement strategies to improve the mechanical properties of hydrogel, including building double network structure, introducing nano-composite materials, designing biomimetic directional structure and using physical cross-linking mechanism (such as crystallization, multiple hydrogen bonds, etc.). Among them, lignin, as the second largest renewable natural polymer next to cellulose, has biological activities such as antioxidant, antibacterial and ultraviolet shielding due to its phenolic structure. In particular, lignosulfonate (LS) as a sulfonated derivative of lignin has good water solubility and biocompatibility. Some studies have introduced LS into PVA hydrogel, and through various post-processing techniques such as freeze-thaw cycle, multi-solvent induction, salting-out, annealing, pre-stretching and nano-composite doping, the tensile strength and toughness of some materials have been improved to a certain extent (Adv. Funct. Mater, 2025, 35: 2503023). However, the complex multi-step process they rely on often involves high energy consumption, high cost and low efficiency, which seriously restricts the large-scale preparation and clinical transformation of the material. It is worth noting that Darabi et al. (Adv Sci, 2020, 7: 1902740) soaked PVA film in a strong alkaline environment to induce high crystallization of its chain segments, thereby achieving a leap in mechanical properties. However, it is difficult to precisely control the crystallization of its chain segments in a simple alkaline environment, so its mechanical properties are limited, and it is necessary to explore the introduction of electrolytes to further promote the crystallization of PVA / LS composite hydrogel to obtain high strength and high toughness, so as to broaden its application in high-end biomedical field.

[0004] In addition, the weak biological activity of LS alone still cannot meet the requirements of cell affinity, antibacterial and antioxidant functions in complex biomedical environment applications. To overcome this problem, introducing natural bioactive components is an effective strategy. Rutin (RT) is a natural flavonoid compound with a wide range of pharmacological activities, including antioxidant, antibacterial, cell affinity, vascular protection, anticancer and heart protection, which can significantly enhance the biological functionality of hydrogel. Therefore, it is necessary to enhance the biological activity of PVA / LS composite hydrogel and explore a simple and efficient preparation method to obtain PVA composite hydrogel with high strength and biological activity, so as to have a greater application prospect in skin dressings and other load-bearing medical devices or high-durability flexible devices. SUMMARY

[0005] The application provides a preparation method of a super-strong and tough polyvinyl alcohol composite hydrogel with biological activity. The method aims to solve the three major bottlenecks of existing high-strength hydrogels, i.e. complex process, high energy consumption and insufficient biological activity. The method uses a strong alkaline solution as a solvent for PVA to precisely control the crystallization and orientation of PVA chain segments during the dissolution process, induce the formation of highly ordered crystal structures, and simultaneously achieve the complete dissolution and nanoscale dispersion of sodium lignosulfonate and rutin, so as to have multiple biological functions such as antioxidant, antibacterial, cell affinity and pro-angiogenic functions. The method provides a new idea for developing new high-strength hydrogels for skin dressings and has a good application prospect in high-end biomedical materials and flexible electronic devices.

[0006] The preparation method of the super-strong and tough polyvinyl alcohol composite hydrogel with biological activity comprises the following steps:

[0007] 0.8 g of PVA is added to 10 mL of NaOH solution with pH=13, heated to 90°C, and stirred vigorously for 2 hours. After the PVA is completely dissolved, a certain proportion of sodium lignosulfonate (LS) and rutin (RT) powder is added. After the sodium lignosulfonate and rutin are completely dissolved, the film is air-dried at room temperature to a thickness of 0.3-0.5 mm, and then immersed in 20-30 mL of 10 wt% NaCl solution for 3-5 hours to obtain a PVA-LS-RT composite hydrogel.

[0008] The application provides a polyvinyl alcohol composite hydrogel with excellent biological activity and super-strong mechanical properties and an efficient preparation method thereof. The core innovation and significant advantages are as follows:

[0009] (1) Hydrogel performance breakthrough and function integration: Based on a new solvation design strategy, the present application successfully introduces lignosulfonate and rutin, two natural active ingredients, while achieving a significant improvement in the mechanical properties of polyvinyl alcohol hydrogel. The composite hydrogel has excellent antioxidant, antibacterial and anti-inflammatory functions, and exhibits sustained drug release capacity. This comprehensive performance advantage greatly expands the application potential of the material in advanced wound dressings, artificial cartilage and flexible electronic devices, etc.

[0010] (2) Preparation process innovation: Abandoning the traditional multi-step complex process required for high-strength PVA hydrogel, the present application uses sodium hydroxide aqueous solution as the solvent, combined with the unique two-step "wet annealing-salting out" method, so that the "dissolution-recrystallization-orientation" process of PVA chain is precisely controlled. This process not only promotes PVA to form a highly crystalline dense network, but also realizes the uniform dispersion and stable compounding of sodium lignosulfonate and rutin in the gel, ultimately obtaining PVA composite hydrogel with ultra-high strength and biological activity. This method is simple and efficient, providing a new technical path for the preparation of high-performance PVA hydrogel.

[0011] (3) Raw material green economy: The selected sodium lignosulfonate and rutin are both natural products with wide sources and low cost, which not only endow the hydrogel with good biocompatibility and activity, but also greatly reduce the cost of raw materials, which is conducive to large-scale production and clinical application.

[0012] In summary, the present application realizes systematic full-chain innovation in material structure design, preparation process, function integration and performance verification, not only successfully develops a PVA composite hydrogel with excellent mechanical properties and multiple biological activities, suitable for high-demand scenarios such as biomedicine, but also builds a general technical platform for green, low-cost, large-scale manufacturing and clinical transformation of high-performance hydrogel. BRIEF DESCRIPTION OF DRAWINGS

[0013] Figure 1 is the tensile-strain graph of the hydrogel in the examples.

[0014] Figure 2 is the toughness strength graph of the hydrogel in the examples.

[0015] Figure 3 is the antibacterial performance graph of the hydrogel in the examples.

[0016] Figure 4 is the antioxidant capacity graph of the hydrogel in the examples.

[0017] Figure 5 is the wound healing capacity graph of the hydrogel in the examples. DETAILED DESCRIPTION

[0018] The following examples are prepared by using PVA of type 1799, adding PVA into NaOH solution (pH=13) with a concentration of 0.08 g / mL, the LS content is 25 wt%-50 wt% of PVA, the RT content is 5 wt%-25 wt% of PVA, air-drying at room temperature into a 0.3-0.5 mm thick film, and then immersing it into 20-30 mL 10 wt% NaCl solution for 3-5 hours to prepare the hydrogel. The preparation conditions beyond the above range will result in poor performance of the hydrogel, thus the present application only gives the experimental results of the examples meeting the above range.

[0019] Example 1: 0.8 g PVA is added into 10 mL NaOH solution (pH=13), heated to 90 ℃, and stirred vigorously for 2 hours. After PVA is completely dissolved, 0.4 g sodium lignosulfonate (LS) and 0.2 g rutin (RT) powder are added. After sodium lignosulfonate and rutin are completely dissolved, air-drying at room temperature into a 0.5 mm thick film, and then immersing it into 30 mL 10 wt% NaCl solution for 5 hours to obtain PVA-LS-RT composite hydrogel. Tensile stress: 21 MPa, toughness: 102 MJ / m 3 , antibacterial rate: 98.6%, free radical scavenging rate: more than 99%, 15-day wound healing rate: 97.4%.

[0020] Example 2: 0.8 g PVA is added into 10 mL NaOH solution (pH=13), heated to 90 ℃, and stirred vigorously for 2 hours. After PVA is completely dissolved, 0.4 g sodium lignosulfonate (LS) and 0.1 g rutin (RT) powder are added. After sodium lignosulfonate and rutin are completely dissolved, air-drying at room temperature into a 0.4 mm thick film, and then immersing it into 20 mL 10 wt% NaCl solution for 4 hours to obtain PVA-LS-RT composite hydrogel. Tensile stress: 27 MPa, toughness: 135 MJ / m 3 , antibacterial rate: 95.5%, free radical scavenging rate: more than 99%, 15-day wound healing rate: 92.9%.

[0021] Example 3: 0.8 g PVA was added into 10 mL NaOH solution (pH = 13), heated to 90 °C, and stirred vigorously for 2 hours. After PVA was completely dissolved, 0.2 g sodium lignosulfonate (LS) and 0.04 g rutin (RT) powder were added. After sodium lignosulfonate and rutin were completely dissolved, it was air-dried into a 0.3 mm thick film at room temperature, and then immersed into 20 mL 10 wt% NaCl solution for 3 hours to swell, obtaining PVA-LS-RT composite hydrogel. Tensile stress: 25 MPa, toughness: 152 MJ / m 3 , antibacterial rate: 92.6%, free radical scavenging rate: more than 99%, 15-day wound healing rate: 87.4%.

[0022] Comparative Example 1: 0.8 g PVA was added into 10 mL NaOH solution (pH = 13), heated to 90 °C, and stirred vigorously for 2 hours. After PVA was completely dissolved, 0.2 g sodium lignosulfonate (LS) and 0.04 g rutin (RT) powder were added. After sodium lignosulfonate and rutin were completely dissolved, it was air-dried into a 0.3 mm thick film at room temperature, and then immersed into 20 mL 10 wt% Na2SO4 solution for 3 hours to swell, obtaining PVA-LS-RT composite hydrogel. Tensile stress: 12 MPa, toughness: 63 MJ / m 3 , antibacterial rate: 92.6%, free radical scavenging rate: more than 99%, 15-day wound healing rate: 83.5%.

[0023] Comparative Example 2: 0.8 g PVA was added into 10 mL NaOH solution (pH = 11), heated to 90 °C, and stirred vigorously for 2 hours. After PVA was completely dissolved, 0.2 g sodium lignosulfonate (LS) and 0.04 g rutin (RT) powder were added. After sodium lignosulfonate and rutin were completely dissolved, it was air-dried into a 0.3 mm thick film at room temperature, and then immersed into 20 mL 10 wt% NaCl solution for 3 hours to swell, obtaining PVA-LS-RT composite hydrogel. Tensile stress: 6.3 MPa, toughness: 22.6 MJ / m 3 , antibacterial rate: 92.6%, free radical scavenging rate: more than 99%, 15-day wound healing rate: 73.8%.

[0024] Comparative Example 3: 0.8 g PVA was added into 10 mL NaOH solution (pH = 13), heated to 90 °C, and stirred vigorously for 2 hours. After PVA was completely dissolved, 0.6 g of sodium lignosulfonate (LS) powder was added. After sodium lignosulfonate was completely dissolved, it was air-dried into a 0.5 mm thick film at room temperature, and then immersed into 30 mL of 10 wt% NaCl solution for 3 hours to swell, obtaining a PVA-LS composite hydrogel. Tensile stress: 22 MPa, toughness: 146 MJ / m 3 , antibacterial rate: 94.6%, free radical scavenging rate: more than 99%, 15-day wound healing rate: 84.8%.

[0025] Comparative Example 4: 0.8 g PVA was added into 10 mL NaOH solution (pH = 13), heated to 90 °C, and stirred vigorously for 2 hours. After PVA was completely dissolved, it was air-dried into a 0.3 mm thick film at room temperature, and then immersed into 20 mL of 10 wt% NaCl solution for 4 hours to reswell, obtaining a PVA-salt hydrogel. Tensile stress: 42 MPa, toughness: 160 MJ / m 3 , antibacterial rate: 0%, free radical scavenging rate: 0%, 15-day wound healing rate: 75.6%.

[0026] Comparative Example 5: 0.8 g PVA was added into 10 mL NaOH solution (pH = 13), heated to 90 °C, and stirred vigorously for 2 hours. After PVA was completely dissolved, it was air-dried into a 0.3 mm thick film at room temperature, and then immersed into 20 mL of deionized water for 3 hours to reswell, obtaining a PVA-alkali hydrogel. Tensile stress: 22 MPa, toughness: 75.6 MJ / m 3 , antibacterial rate: 0%, free radical scavenging rate: 0%, 15-day wound healing rate: 72.7%.

[0027] Comparative Example 6: 0.8 g PVA was added into 10 mL deionized water, heated to 90 °C, and stirred vigorously for 2 hours. After PVA was completely dissolved, it was air-dried into a 0.3 mm thick film at room temperature, and then immersed into 20 mL of deionized water for 3 hours to reswell, obtaining a PVA-H2O hydrogel. Tensile stress: 0.43 MPa, toughness: 1.48 MJ / m 3 , antibacterial rate: 0%, free radical scavenging rate: 0%, 15-day wound healing rate: 57.4%.

[0028] Mechanical properties: dumbbell-shaped hydrogel specimens (width: 3 mm, thickness: 0.3 mm) were prepared using a standardized mold. After reaching equilibrium swelling in aqueous solution, uniaxial tensile tests were performed on a universal testing machine (ANS MT4503, SANS, China). The samples were stretched at a constant crosshead speed of 30 mm / min until failure. Cyclic tensile test: the hydrogels were subjected to 20 consecutive loading-unloading cycles at a speed of 30 mm / min. To prevent dehydration: the specimens were sprayed with deionized water between cycles. The residual strain and hysteresis energy for each cycle were quantified to assess elastic recovery and energy dissipation.

[0029] Antibacterial property: 1900 μL of lysogeny broth was added to the sample, after 24 h, 100 μL of S. aureus or E. coli suspension (1 x 10 5 CFU / mL) was added, the sample was placed in an incubator at 37 °C with constant shaking. After 12 h, 1000 μL of bacterial suspension was collected in a centrifuge tube. The optical density (OD) of the suspension was measured at 600 nm. The antibacterial rate was calculated according to the following formula, where OD Control is the absorbance of the control, and OD Sample is the absorbance of the sample.

[0030]

[0031] Antioxidant property: 50 mg of hydrogel was weighed at the bottom of a centrifuge tube, 4 mL of methanol was added, and it was soaked at ambient temperature for 12 h, 1 mL of supernatant extract was taken to evaluate the scavenging activity of DPPH: 1 mL of supernatant extract was mixed with 1 mL of DPPH methanol solution (50 mg / L) to obtain a 25 mg / L DPPH solution. The mixture was maintained at room temperature in the dark for 60 minutes. The absorbance was measured at 517 nm using a UV-visible spectrophotometer (UV-2600i, Japan). The mixture solution of methanol solution and DPPH methanol solution was used as a control. The DPPH radical scavenging activity was calculated using the following formula, where OD1 is the absorbance of the sample, and OD0 is the absorbance of the control.

[0032]

[0033] Wound healing: Four 7-week-old male SD mice (36 - 40 g) were anesthetized with 1 wt% sodium pentobarbital. After anesthesia, the mice were shaved on the back, and a full-thickness circular wound (wound diameter 8 mm) was created on the back of each mouse using an 8 mm skin biopsy punch. Sterilized hydrogel (1 cm long, 1 cm wide) was implanted into the wound site of the mice. The wound was observed daily, and the wound healing of the mice on day 5, day 10, and day 15 was recorded. The skin wound healing rate was calculated according to the following formula, where S 初始 is the area of the wound of the mouse on day 0, S 愈合 is the area of the wound of the mouse on the corresponding day.

[0034]

Claims

1. A method for preparing a bioactive, ultra-tough polyvinyl alcohol composite hydrogel, characterized in that: Polyvinyl alcohol was added to a NaOH solution with pH = 13, heated to 90 °C, and stirred vigorously for 2 hours. After PVA was completely dissolved, a certain proportion of sodium lignosulfonate and rutin powder was added. After sodium lignosulfonate and rutin were completely dissolved, the mixture was air-dried into a 0.3-0.5 mm thick film at room temperature. Then the film was immersed in 20-30 mL of 10 wt% NaCl solution for 3-5 hours to obtain a polyvinyl alcohol-sodium lignosulfonate-rutin composite hydrogel.

2. The method for preparing the super-tough polyvinyl alcohol composite hydrogel with biological activity according to claim 1, wherein the polyvinyl alcohol is type 1799, the concentration of polyvinyl alcohol added to the NaOH solution is 0.08 g / mL, the content of sodium lignosulfonate is 25 wt%-50 wt% of polyvinyl alcohol, and the content of rutin is 5 wt%-25 wt% of polyvinyl alcohol.

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