CN108715641B

CN108715641B - PVA hydrogel, composite material using same, method for producing same, and use thereof

Info

Publication number: CN108715641B
Application number: CN201810560799.8A
Authority: CN
Inventors: 邢孟秋; 吴军; 叶海雁; 刘抗; 邱佩琪
Original assignee: Huzhou Siman Biomaterial Co ltd
Current assignee: Huzhou Siman Biomaterial Co ltd
Priority date: 2018-05-25
Filing date: 2018-05-25
Publication date: 2022-05-03
Anticipated expiration: 2038-05-25
Also published as: CN108715641A; WO2019223189A1; CN108774327A; CN108774327B

Abstract

The invention provides a PVA hydrogel and a composite material based on the PVA hydrogel, wherein the PVA hydrogel not only has excellent mechanical property, shape memory property, hydrophilicity and biocompatibility, but also has 3D printability and injectability. The present invention also provides a novel method for producing a PVA hydrogel. The invention also provides applications of the PVA hydrogel in various fields such as catheters, 3D printable solutions, injectable electronic devices, microfluidic channels, bioabsorbable sensors, micro-robots, tissue engineering scaffolds, surgical sutures, medical gloves and condoms.

Description

PVA hydrogel, composite material using same, method for producing same, and use thereof

Technical Field

The present invention relates to a polyvinyl alcohol (PVA) hydrogel, to a composite material based on the PVA hydrogel, to a method for producing the PVA hydrogel and to the use of the PVA hydrogel.

Background

Polyvinyl alcohol (PVA) is one of the most important synthetic polymers consisting of carbon, oxygen and hydrogen atoms, and is biodegradable under both aerobic and anaerobic conditions, widely used in the commercial, industrial, medical and nutraceutical fields. PVA can be easily dissolved in water. Currently, PVA hydrogels are typically synthesized by two common mechanisms, including chemical bonding using cross-linking agents such as glutamate and/or physical means such as freezing and thawing. PVA is very important for biomedical, tissue engineering and soft robotic applications.

At present, the PVA hydrogel prepared by the conventional method (hereinafter, referred to as conventional PVA hydrogel for short) has the defects of relatively poor mechanical properties, complex preparation process and the like, and it is expected to develop a method for preparing the PVA hydrogel with excellent properties in a simple and convenient manner, so that the PVA hydrogel can be more suitably applied to the fields of implantable electronics, nano medicine, minimally invasive technology, biomedicine and the like.

Disclosure of Invention

The present inventors have unexpectedly found that a PVA hydrogel can be obtained in a simple manner by gelling PVA using an alkaline solution. By introducing such a novel gelation mechanism, PVA hydrogels having excellent properties that can be applied to various fields can be obtained.

The invention provides a PVA hydrogel which has an elastic modulus of 1MPa-20MPa and an ultimate strength of 10MPa-100 MPa.

Further, the PVA hydrogels of the present invention have a deformation recovery ratio of 65 to 95% when water is added. Preferably, the PVA hydrogels of the present invention have a deformation recovery of 70 to 92% upon addition of water. Here, the deformation recovery rate is calculated by the following formula: deformation recovery rate-the deformation recovery length of the PVA hydrogel upon addition of water/the tensile deformation length of the PVA hydrogel.

Further, the PVA hydrogels of the present invention have contact angles of 15 to 20 degrees.

The invention also relates to a composite material comprising the PVA hydrogel.

Preferably, the composite material comprises the PVA hydrogel and magnetic nanoparticles incorporated within the PVA hydrogel.

Preferably, the composite material comprises the PVA hydrogel and graphene incorporated within the PVA hydrogel.

Preferably, the composite material comprises the PVA hydrogel and carbon nanotubes incorporated within the PVA hydrogel.

Preferably, the composite material comprises the PVA hydrogel and urea incorporated within the PVA hydrogel.

Preferably, the composite material comprises a layer formed from the PVA hydrogel and polyaniline coated on the PVA hydrogel.

Preferably, the composite material includes a layer formed of a PVA hydrogel containing silver nanoparticles, a layer formed of a PVA hydrogel, and a layer formed of a PVA hydrogel containing carbon nanotubes, which are sequentially stacked.

The invention also relates to a novel method for preparing the PVA hydrogel, which comprises the steps of mixing the polyvinyl alcohol with the molecular weight of 100-1000K with water to obtain a PVA solution, then pouring the PVA solution into a culture dish, drying to obtain a PVA film, and then soaking the PVA film into an alkaline solution with the molar concentration of 1-10M to obtain the PVA hydrogel. The method of the present invention enables the production of a PVA hydrogel in a simpler manner than the conventional methods for producing PVA hydrogels.

In the method of the present invention, as examples of the alkaline solution, solutions of NaOH, KOH, LiOH, ammonia water, sodium carbonate, sodium bicarbonate, and the like are included.

In consideration of the mechanical property of the PVA hydrogel, the alkaline solution is preferably a NaOH solution or a KOH solution, and the molar concentration is 3-10M. More preferably, the alkaline solution is NaOH solution or KOH solution, and the molar concentration is 3-6M.

Preferably, the method of the present invention further comprises washing the PVA hydrogel with pure water.

Preferably, the method of the present invention further comprises subjecting the PVA hydrogel to a dehydration treatment. This dehydration treatment can further improve the mechanical strength of the PVA hydrogel.

Preferably, the dehydration treatment is air drying at room temperature for 2-8 hours.

Preferably, the dehydration treatment is dried at room temperature for 2-5 hours using a micro fan.

Preferably, in the method of the present invention, the polyvinyl alcohol and the water are mixed in a mass ratio of 1:5 to 1:30, and the mixture is placed in a shaking bath at 60 ℃ overnight to obtain a PVA solution.

Preferably, in the process of the present invention, the polyvinyl alcohol is mixed with water to obtain a PVA solution having a concentration of 10%, and the ratio between the PVA solution and the alkaline solution is 1:3 to 10 in parts by weight.

Preferably, the PVA solution is poured into a petri dish and dried at room temperature for 8-24 hours.

Preferably, the PVA film is immersed in the alkaline solution for 1 to 60 minutes; further preferably, the PVA film is immersed in the alkaline solution for 10 to 20 minutes.

The invention also relates to the PVA hydrogel prepared by the method, and the PVA hydrogel has excellent mechanical property, shape memory property, hydrophilicity, biocompatibility, 3D printability or injectability and the like.

The invention also relates to the use of PVA hydrogels for the manufacture of any of catheters, 3D printable solutions, injectable electronics, microfluidic channels, bioabsorbable sensors, micro-robots.

The invention also relates to the use of a PVA hydrogel for the manufacture of any of tissue engineering scaffolds, surgical sutures, medical gloves and condoms.

The present invention provides a multifunctional polyvinyl alcohol hydrogel having excellent mechanical properties, shape memory properties, hydrophilicity, biocompatibility, 3D printability or injectability, etc., by gelling PVA with an alkaline solution. By the novel gelation mechanism of the present invention, PVA can be combined with other materials to make new composite materials. The ability to benefit from 3D printing and microfluidic technologies offers great promise for commercialization of such new materials for different industrial areas. The present invention can provide a tough PVA hydrogel that can bear a weight 1500 times greater than its weight. The ease of manufacturing and biocompatibility of the PVA hydrogels may not only represent good candidates for next generation resistive catheters, but may also incorporate catheter-based monitoring systems. The thus-prepared PVA hydrogel can be used in the manufacture of tissue engineering scaffolds, surgical sutures, medical gloves and condoms, taking into account its good shape memory. The novel materials have proposed numerous applications in the fields of drug delivery, biomedical devices, bio-robotics and biomedicine.

Drawings

FIG. 1 shows a PVA hydrogel based composite material prepared by combining a 10% PVA solution with different nanomaterials by the method of the invention, where Panel A is the combination of PVA with MNP (magnetic nanoparticles); panel B is a combination of PVA and exfoliated graphene; FIG. C is a PVA ultrathin film containing CNTs (carbon nanotubes); FIG. D is PVA coated with PANI (polyaniline) after one and multiple coats; panel E is PH sensing of color change by PANI coated PVA.

FIG. 2A shows the chemical structure of fully hydrolyzed PVA, and FIG. 2B shows the chemical structure of partially hydrolyzed PVA.

FIG. 3A shows the chemical structure of an aqueous solution of partially hydrolyzed PVA, and FIG. 3B shows that the dry PVA film is cured by the addition of concentrated NaOH solution with strong hydrogen bonding.

FIG. 4A shows ATR-FTIR results for PVA hydrogels made with 6M NaOH molar concentration according to the present invention, and FIG. 4B shows ATR-FTIR results for dry pristine PVA films.

FIG. 5 is an SEM image (for determining the swelling ratio) of hydrogels obtained by mixing PVA and urea at different ratios according to the present invention, wherein the A image is a graph obtained by mixing PVA and urea at 90: 10, dried and gelled with sodium hydroxide, and figure B is a sample obtained by mixing 5ml of urea (8M molar concentration) with 5ml of PVA (0.4 gr PVA powder added), dried and gelled with sodium hydroxide.

FIG. 6 shows ATR-FTIR results for PVA hydrogels made with different concentrations of NaOH (1M, 3M, and 6M molar concentrations, respectively) according to the present invention.

FIGS. 7A, 7B and 7C are photographs of PVA hydrogels of the present invention prepared with NaOH at molar concentrations of 1M, 3M and 6M, respectively.

FIG. 8 is a graph showing the results of stretching 10% PVA hydrogels cured with different types and different concentrations of hydroxide according to the present invention, in which FIG. 8A is a photograph of the PVA hydrogels during the stretching test; FIG. 8B is a stress-strain curve and elastic modulus of PVA hydrogels prepared with different concentrations of NaOH (dimensions (length, width and thickness) of 15, 5, 0.1 (unit: mm) for samples prepared with NaOH concentrations of 3M, 5M and 6M, respectively, and dimensions (length, width and thickness) of 12, 5, 0.05 (unit: mm) for samples prepared with NaOH concentration of 1M, and a test speed of 10 mm/min); FIG. 8C is a graph showing stress-strain curves and elastic moduli of PVA hydrogels prepared with KOH, NaOH, and LiOH (dimensions (length, width, and thickness) of samples prepared with KOH and NaOH are 15, 5, 0.1 (unit: mm); dimensions (length, width, and thickness) of samples prepared with LiOH are 15, 3, 0.05 (unit: mm); test speed is 10 mm/min); FIG. 8D is the drawing result of the PVA hydrogel cured with NaOH (molarity 6M) and tested 3 times (sample size (length, width and thickness): 120, 10, 0.3 (unit: mm) (curve at the lowermost end): 118, 10, 0.3 (unit: mm) (curve at the middle end): 111, 10, 0.3 (unit: mm) (curve at the uppermost end) at a speed of 5 mm/min); FIG. 8E is a graph showing the tensile properties of PVA hydrogel strips air-dried for 2.5 hours (test speed of 5mm/min, sample size 111, 10, 0.3 (unit: mm) (curve at the upper end) (2 nd time); 94, 10, 0.3(mm) (curve at the lower end) (1 st time)); FIG. 8F is a cyclic tensile test under room conditions (PVA samples made by pouring 20ml of PVA were cut to dimensions of 17, 5 and 0.1 (unit: mm) in length, width and thickness, respectively); FIG. 8G is a cyclic tensile test of PVA hydrogels (hydrogels made with 20ml of PVA solution of length, width and

thickness

25, 5 and 0.1 (unit: mm), respectively, at a test speed of 20mm/min) when an external humidity-generating humidifier was used to avoid dehydration during the test), where the top left, top right and bottom left plots are cycling over the 12% -40%, 22% -70% and 25% -100% strain ranges, respectively, and the bottom right plot is the stress-strain curve of the same sample under humid conditions.

FIG. 9A shows the sharp object resistance of the PVA hydrogels of the present invention, and FIG. 9B shows the PVA-PANI coated tape bearing a weight of 15 Kg.

FIG. 10 is a graph showing degradation tests of PVA hydrogels under heat, wherein FIGS. 10A, 10B, and 10C are SEM observations of conventional PVA hydrogel films; 10D, 10E, and 10F are SEM images of PVA films heated at 70 ℃ for 30 minutes, with the samples of FIGS. 10A, 10B, 10D, and 10E gold plated before SEM, and the samples of FIGS. 10C and 10F not gold plated.

Fig. 11 shows the measured Contact Angle (CA), where fig. 11A shows that for PDMS, CA is 92.718 °; figure 11B shows CA 56.88 ° for the PVA hydrogel sample dried only; FIG. 11C shows that for the PVA hydrogel sample gelled with NaOH of the present invention (5 seconds after the drop was dropped), CA was 16.608 °.

FIG. 12 is a graph showing the shape memory property of the PVA hydrogel of the present invention, in which FIG. 12A shows that a PVA tape is immersed in a 6M NaOH solution and elongated from 13mm to 36mm, and then immersed in water to restore its original length after several seconds; FIG. 12B shows that the shrinkage force due to the addition of water can increase the 500gr weight to 3.5 cm; FIG. 12C shows that the contraction force due to the addition of water can lift the weight of 200gr to 10 cm; FIG. 12D shows the same samples as used for 12B, 12C, 12E, where L0 is the original length, L1 is the length when the sample was elongated to 32mm, and L2 is related to the time of immersion in water after the test; FIG. 12E shows the contractile force caused by the addition of water.

FIGS. 13A and 13B show SEM images of a PVA hydrogel of the invention immersed in a NaOH solution, and FIGS. 13C and 13D show SEM images of a PVA hydrogel of the invention first immersed in a NaOH solution and then fully stretched to a plastic region (arrows indicate stretching directions).

FIG. 14 shows the EDX results for a PVA hydrogel of the present invention, wherein FIG. 14A shows an SEM image of the PVA hydrogel immersed in a NaOH solution, with selected areas for EDX analysis; fig. 14B and 14C show atomic and weight percentages of elements in selected regions and quantitative results.

FIGS. 15A and 15B show SEM images of cross-sections of a composite of the present invention comprising three layers, wherein the left layer is PVA-CNT, the middle layer is PVA alone, and the right layer is PVA-silver nanoparticles; FIGS. 15C and 15D show the high resolution boundary between two layers with CNTs (left) and without CNTs (right); fig. 15E and 15F show the higher resolution of the PVA layer containing silver nanoparticles.

Fig. 16 shows EDX results for the CNT-PVA-silver nanoparticle composite of the present invention, where fig. 16A is an SEM image of a cross-section of the composite comprising three layers and three regions selected for EDX studies; 16B, 16C, and 16D are elemental percentages and quantitative results for each selected region.

FIG. 17A shows the synthesis of tubes of different diameters based on the PVA hydrogel of the present invention, FIG. 17B shows that the tubes behave like a balloon when high pressure air is applied, and FIG. 17C shows that the tubes are strong when dry, but the area in contact with water is elastic, so that the tubes will mimic a balloon when high pressure air is passed through the tubes.

Fig. 18 shows an injectable mesh electronic device with an open macroporous structure and mechanical properties similar to those of brain tissue, which provides a new minimally invasive approach to mapping and modulating brain activity.

Fig. 19A shows the PVA-CNT solution as printed during 3D printing, fig. 19B the cured 3D printing screen, and fig. 19C and 19D the 3D printing screen injected through a small pipette tip with a diameter of 400 μm.

FIG. 20 shows a PVA-CNT conductive ink printed on a thin PVA film.

Fig. 21A shows the synthesis of microfluidic channels on a PVA hydrogel film, and fig. 21B shows alginate printed on the PVA hydrogel film and layer-by-layer curing.

Fig. 22A and 22B show optical images of microfluidic channels fabricated on PVA tubes by using small rods for making tubes into which water containing dye is injected and the tubes are placed in water under UV to display fluid in the microfluidic system, and fig. 22B shows a large tube with multiple printed microchannels on the tube wall.

FIG. 23A is a schematic view of a Bioabsorbable Electronic Stent (BES) containing bioabsorbable temperature and flow sensors, memory modules and therapeutic nanoparticles, where NIR exposure can be used to initiate therapeutic functions; FIG. 23B shows the placement of the BES on a balloon catheter for in vivo delivery to the canine common carotid artery; FIG. 23C shows X-ray images of the balloon catheter and BES in a dog model before (left) and after (right) inflation of the balloon catheter; FIG. 23D shows a BES implanted in vivo in canine common carotid artery; fig. 23E shows a volume rendered CT image of the in vivo BES.

FIG. 24A is a photograph of a tube with a printed CNT mesh (used to record signal changes related to internal pressure); FIG. 24B shows a photograph of a catheter fitted with a sensor made of CNT/PVA connected to a tube through which a fluid can pass.

FIG. 25 shows a PVA-gelatin film obtained by: 5mL of the PVA solution was poured onto a petri dish and allowed to dry before standing in NaOH solution to form a gel.

Fig. 26 is a schematic diagram showing a hepatic lobule microstructure and a synthetic method of making a linear hepatic micro-organ, wherein fig. 26A shows a hepatic lobule microstructure: parenchymal Hepatocytes (PH) are detached from the blood sinuses and form a linear structure of a hepatocyte layer with a thickness of 1, in which hepatocyte cords are covered by an Endothelial Cell (EC) layer, and between PH and EC, there is a perisinus space (the space of space) in which stellate cells are arranged; figure 26B shows alginate hydrogel microfibers binding hepatocytes and 3T3 cells were fabricated with a microfluidic system, with the lower panel showing cross-sectional views of alginate threads encapsulating the cells before and after gelation.

Fig. 27 is a schematic diagram of a droplet focusing microfluidic channel for layer-by-layer microgel fabrication, where the light gray with black dots is a PVA hydrogel containing a drug and the dark color is another PVA solution as a second layer, and droplets thereof can be formed by using NaOH solution as the gel solution.

Detailed Description

The invention provides a method for preparing PVA hydrogel, which comprises the steps of shaping and drying a PVA solution in a mould, and then soaking the PVA solution in an alkaline solution to obtain the PVA hydrogel.

The present invention will be specifically described below with reference to examples and drawings, but the present invention is not limited thereto.

Example 1

A PVA viscous solution was formed by dissolving PVA with a molecular weight of 205,000 in distilled water to make 10% PVA (100 mg/mL; 10g PVA in 100mL distilled water) and standing overnight in a shaking bath heated at 60 ℃. Then, 20ml of 10% PVA solution was poured into a glass dish having a diameter of 10cm, dried overnight at room temperature, immersed in a 1M NaOH solution for 10 to 20 minutes, gelled, washed with pure water, washed, drained, and stored under sealed conditions.

Example 2

A PVA hydrogel was prepared in the same manner as in example 1, except that the concentration of NaOH was changed to 3M.

Example 3

A PVA hydrogel was prepared in the same manner as in example 1, except that the concentration of NaOH was changed to 5M.

Example 4

A PVA hydrogel was prepared in the same manner as in example 1, except that the concentration of NaOH was changed to 6M.

Example 5

A PVA hydrogel was prepared in the same manner as in example 4 except that NaOH was changed to LiOH.

Example 6

A PVA hydrogel was prepared in the same manner as in example 4 except that NaOH was changed to KOH.

Example 7

A PVA hydrogel was prepared in the same manner as in example 4, except that the PVA hydrogel obtained was air-dried at room temperature for 2.5 hours.

Comparative example 1

Mixing polyvinyl alcohol and water according to the mass ratio of 10:100, placing the mixture in a constant-temperature oil bath at 85-90 ℃ under the condition of stirring, and completely dissolving the mixture to obtain a PVA solution. And then, putting the PVA solution into a refrigerator, freezing the PVA solution for 18 hours at the temperature of-20 ℃, then unfreezing the PVA solution for 3 hours at room temperature, and carrying out freeze-thaw cycling for 3 times to obtain the conventional PVA hydrogel.

The PVA hydrogel designed by the invention has the capability of uniformly doping different nano materials. Here, various composite materials based on the PVA hydrogel of the present invention were prepared by using the above-described method of the present invention, a 10% PVA solution in combination with Magnetic Nanoparticles (MNPs), exfoliated graphene, Carbon Nanotubes (CNTs), and Polyaniline (PANI).

As can be seen from fig. 1A, combining PVA with MNPs results in a stretchable magnetic membrane that can be used as a magnetic actuator (0.1 gr of magnetic nanoparticles are added to 5mL of PVA solution and sonicated and stirred, then poured into a petri dish, dried and then gelled by immersion in sodium hydroxide solution, producing a PVA hydrogel membrane doped with MNPs). Fig. 1A shows how the magnetic film waves with the movement of the magnet. Figure 1B shows that the exfoliated graphene is perfectly embedded in the PVA network and made into a uniformly distributed film. FIG. 1C is a very thin nanomembrane made with PVA and CNT (10 mg/mL PVA and CNT) wherein the solution was poured onto a petri dish and dried overnight, then gelled by immersion in sodium hydroxide solution to produce a uniform PVA hydrogel film doped with CNT, and the image on the right shows the image when 10mL of the solution was left to dry on the petri dish. FIG. 1D shows a PVA film coated with PANI (polyaniline) after one or more coats, where it was observed that PANI can be well coated on PVA films, and can provide many applications in pH indicators or for supercapacitors. As shown in fig. 1D and 1E, the PANI-coated PVA film can effectively detect a change in PH by changing its color from green in an acidic environment to purple in an alkaline environment. The preparation method of the present invention provides for adjustable thickness production. As can be seen from FIGS. 1A to 1E, the PVA hydrogels of the present invention have excellent ability to bind various materials, and can be used to prepare various composite materials.

Characterization of

The PVA hydrogels of the present invention were characterized by EDX, Fourier transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM), and were investigated for their mechanical and chemical properties, swelling ratio, and degradability. Gel mechanism and FTIR analysis

The chemical structures of fully hydrolyzed and partially hydrolyzed PVA polymers are shown in fig. 2A and 2B, respectively. For partially hydrolyzed PVA polymers (PVA is referred to as partially hydrolyzed polymer), residual acetate molecules are present in the polymer. In the PVA solution, water molecules form hydrogen bonds with the adjacent PVA network (see fig. 2). When the PVA solution is dried, weak hydrogen bonds are formed between the hydroxyl groups of the PVA, while the remaining acetate blocks additional hydrogen bonds. After immersing the PVA film in a highly concentrated alkaline solution, the residual acetate will be removed, resulting in stronger hydrogen bonding of the hydrogel film (see fig. 3). As shown by EDX and FTIR analysis, water was used to wash the PVA hydrogel to remove sodium and hydroxyl ions and to adjust the pH of the synthesized material.

Fig. 4 provides FTIR spectra of various samples to aid in further discussion of the prepared composite films. FIG. 4A shows FTIR spectra of crosslinked PVA treated with NaOH; FIG. 4B shows FTIR spectra of pristine PVA, having a wavelength in the range of 3000-3600cm^-1(Wide-OH stretch), 2800-3000cm^-1(C-H alkyl stretched), 1733cm^-1(residue ofAcetate of CH₃CO₂C ═ O stretch of (C), 1300 to 1500cm^-1(C-H bend) and 1084cm^-1Typical peak of (C-O stretching).

FTIR spectra of crosslinked PVA show all expected characteristic peaks for PVA but at 1733cm^-1The peak at (a) shrinks significantly (or almost disappears), which demonstrates the successful removal of the acetate (see fig. 4A).

In the FTIR spectra of pristine PVA and crosslinked PVA, it was found to be 1084cm^-1(C-O stretching) and 1142cm^-1(C-O-C stretching). Crosslinked PVA at 1142cm^-1The peak intensity at (a) increases, indicating that the crystallinity of the crosslinked PVA increases.

The crosslinked PVA pad was soaked in water for several days to ensure a successful crosslinking procedure. To elucidate the mechanism, the PVA hydrogel was immersed in an 8M urea solution and held overnight, resulting in dissolution of the PVA hydrogel. This fact reveals an important role of hydrogen bonding. In addition, the PVA solution was mixed with urea at 90/10 weight percent (PVA/urea) to prepare a PVA-urea hydrogel. The SEM image in FIG. 5 reveals that the pore size increased, which may be due to the obstruction of hydrogen bonding in the PVA hydrogel.

FTIR results for the PVA hydrogels of examples 1, 2 and 4 prepared with NaOH molar concentrations of 1M, 3M and 6M, respectively, are shown in FIG. 6. With excess NaOH, the residual acetate pick-up (acetate pick) was reduced more. Considering the mechanical properties and gelation of PVA, it can be seen that the hydrogel of example 1 made with 1M NaOH is very weak. Thus, removal of residual acetate is not the primary cause of strong hydrogen bonding, and high concentrations of NaOH solution play a critical role. The optical photographs of the PVAs prepared with the above different concentrations of NaOH are shown in FIG. 7.

Mechanical properties

FIG. 8A shows a sample of PVA-NaOH (6M NaOH molar concentration) during the tensile test. When the PVA hydrogel reached high strain (about 300% strain), a color change from clear to white was observed for the sample, indicating that the interior PVA chains were aligned parallel and more ordered.

FIG. 8B is a graph investigating the tensile and mechanical properties of PVA hydrogels of examples 1-4 prepared from different concentrations of NaOH. The reported elastic modulus (at 50% strain) was obtained by averaging the results of three samples from each group. It can be seen that the sample gelled with 1M NaOH in example 1 has a very small elastic modulus of 0.04MPa and has a very weak film. However, when the concentration of NaOH was increased to 3M, 5M and 6M, then strong PVA hydrogel films were obtained, with elastic modulus increasing to the order of 1MPa and ultimate strength increasing significantly to the order of 10 MPa. Linear elastic behavior of all samples was observed when stretched to at least 100% strain. The film exhibits excellent stretchability, exceeding 350% of its original length. This elongation is affected by the performance of the stretcher, as most samples slide off the grips or cut at the edges due to the stress concentration the grips use to hold the sample. Thus, all data show minimal strength and elongation of the PVA hydrogel. To ensure the fastest gelation and robust performance, PVA hydrogels made with hydroxide concentrations of 6M were used in the experiments of the present invention. FIG. 8C compares the tensile properties of PVA hydrogels of examples 4-6 gelled with different types of hydroxides (including LiOH, NaOH, and KOH). The results show that the use of LiOH results in a weak PVA hydrogel, whereas the use of NaOH and KOH shows strong mechanical properties, with an ultimate strength of more than 10MPa and a Young's modulus of more than 1.3 MPa.

FIGS. 8D and 8E further investigate the effect of drying on the mechanical properties of PVA hydrogels. 30mL of 10% PVA was poured into a large petri dish, dried and gelled with 6M sodium hydroxide solution to form a 0.3mm thick PVA hydrogel film. The PVA hydrogel samples were stored in distilled water and, after wiping off water from the sample surface, the tensile properties of the PVA hydrogel were tested three times at a speed of 5mm/min, and the results are shown in FIG. 8D. Each time, the PVA hydrogel showed stronger behavior, and it is known that dehydration plays a key role in the mechanical strength of the PVA hydrogel. As can be seen from FIG. 8D, the ultimate strength and Young's modulus increased as the PVA hydrogel was drier.

The tensile test was repeated for the PVA hydrogel of example 7 dried for 2.5 hours, and the results are shown in FIG. 8E. The sample was tested 2 times at a speed of 5 mm/min. In the first test, it was stretched to 30% and slipped off the jig, and in the second test, the hydrogel followed exactly the same trend as the previous results shown after 2.5 hours, indicating that drying had a negligible effect on the mechanical properties during this test.

In FIG. 8F, after removing water from the surface of the PVA hydrogel sample, the hydrogel was used for tensile cycling tests and was tensile released between 30% and 58% strain for 10 cycles. It can be seen that during cyclic stretching the hydrogel was dried, affecting the mechanical properties, as seen in the tenth cycle, the maximum strength was increased by 14% compared to the first cycle (10 cycles took approximately 8 minutes).

The cyclic tensile test was repeated for the same PVA hydrogel samples of fig. 8G and to evaluate the drying effect, the hydrogel was exposed this time to a humidifier that generated water vapor to prevent evaporation of water during the cyclic test. The cyclic tests shown in fig. 8G indicate that the top left, top right, and bottom left represent cyclic stretch and relaxation results at 12% -40%, 22% -70%, and 25% -100% strain, respectively. Compared to fig. 8F, where the gel was tested under room conditions, there was only a difference between the first and last cycles, highlighting the effect of hydration on tensile behavior. The same samples were further tested and showed the presence of tensile behavior at humidity as shown in the upper left graph of fig. 8G.

A PVA hydrogel prepared by pouring 5mL of PVA solution, drying, and treating with NaOH is shown in FIG. 9. The film has excellent resistance to sharp metals, scrapers and gently pushing pins. FIG. 9B shows a photograph of a PANI coated PVA hydrogel used to carry a weight of 15 kg.

Degradability, morphology and swelling ratio

The degradability of the PVA hydrogels of the present invention was evaluated by placing the hydrogels in water for 1 year, and no degradation was observed. In order to improve the degree of degradation of PVA hydrogels, studies in combination with degradable materials can be performed. For example, urea can weaken the intramolecular interactions and hydrogen bonds of PVA, and alter lattice energy and crystallinity. When soaked in urea solution overnight, the PVA hydrogel was dissolved in urea solution (molar concentration 8M). For PVA hydrogels, a very stable chemistry is observed, since it retains its properties even when soaked in strong acids.

Heating a 0.5mm thick PVA hydrogel film; for temperatures below 50 ℃, the hydrogel is very stable, but around 70 ℃, the hydrogel starts to regenerate and disappear. The hydrogel film was heated at 70 ℃ for 30 minutes and collected and kept in water at room temperature overnight. This heat treatment substantially reduces its mechanical properties and increases the swelling ratio. The swelling ratio for this study was calculated according to the following formula: swelling ratio [ W ]_f-W₀/W₀](ii) a Wherein W_fWeight of hydrogel in the fully swollen state, W₀Is the weight in the dry state.

For the conventional PVA hydrogel in comparative example 1, the swelling ratio was about 0.8. However, when the hydrogel was heated and collected, the swelling ratio increased to 9.5. After freezing and drying, conventional PVA hydrogels (fig. 10A, B, C) and heated PVA hydrogels (fig. 10D, E, F) were used for SEM studies. As shown in fig. 10, the pore size increased significantly for the heated sample. The range of recyclable and reusable devices is introduced in view of thermal degradation.

Contact angle

The hydrophilic properties of the PVA hydrogels of the present invention were evaluated by measuring the Contact Angle (CA). Fig. 11A shows a drop of water on PDMS with a contact angle of 92.7 °. Fig. 11B shows that the dried PVA film had a CA of 56.88 ° before gelation. FIG. 11C shows that the PVA film of the invention gelled with NaOH has a CA of 16 °, indicating that the PVA hydrogel of the invention contains a hydrophilic-rich surface (contact angle is calculated after 5 seconds of droplet contact with the film).

Shape memory and artificial muscle

The shape memory property of the PVA hydrogel in example 4 of the present invention is shown in FIGS. 12A and 12B. The PVA tape was stretched from the original 13cm length to 36cm, which indicated that the tape extended to 300% of its original length after immersion in NaOH solution. After the addition of water, the strip retained its plastic deformation and recovered to 15cm in a short time (with a deformation recovery of about 91% (obtained by calculation as (36cm-15cm)/(36cm-13cm) ═ 91%); strain ratio recovered to 260%). This process is associated with a strong contractive force capable of moving 500gr weight (equivalent to 175mJ of energy).

In addition, samples air dried within 2 hours showed that they could recover more than 70% of their original length when water was added (samples with dimensions of 26, 8, 0.1(mm) were stretched to 100mm and placed in water for a few minutes, then removed and measured). The maximum length was 32.6mm, showing a recovery of 67.4mm plastic deformation (with a recovery of deformation of about 91%), and samples with the same properties and appearance could be reused.

20ml of PVA solution was poured into a petri dish, dried and immersed in NaOH solution for 5min to prepare PVA hydrogel strips for artificial muscle testing and measurement of contractility. The initial length of the strip is L₀12cm, moistened with NaOH and stretched to L₁Loading 500gr and then elongating to L₂43 cm. According to FIGS. 12B and 12C, the shrinkage force of the hydrogel due to the addition of water increased the weight of 0.2kg to 10cm and the weight of 0.5kg to 3.5 cm. The same samples were used for tensile testing to measure the shrinkage force. Similarly, the strip is elongated to L₁32cm and between the gripping surfaces (fig. 12D). After calibration, the strips were manually elongated to achieve a preload of 5N to simulate weight suspension. The force was measured while water was continuously added to both sides of the hydrogel strip. The retractive force increased to a maximum of 10N within 50 seconds (fig. 12E).

FIGS. 13A and 13B show SEM images of PVA hydrogels of the present invention immersed in NaOH solutions. FIGS. 13C and 13D show the PVA hydrogel stretched into its plastic region. Comparing the high resolution images (fig. 13B and 13D), it is apparent that when the hydrogel is fully stretched, the material web becomes a flat structure. Also, the cracks appearing in fig. 13D are perpendicular to the stretching direction. After the water has been added to the stretched strip, these cracks can be eliminated, corresponding to the restoration of the plastic deformation. Thus, the microscopic self-healing phenomenon is apparent.

The EDX results of the PVA hydrogel films of the present invention held in NaOH solution were studied in fig. 14. The oxygen percentage is higher for the present invention compared to conventional PVA hydrogel films. In addition, it was confirmed that the element Na could be removed with water.

Layer-by-layer manufacture and application

The ability to manufacture layer by layer of the present method makes it possible to design multifunctional composite materials with a variety of properties. A composite membrane of PVA with silver Nanoparticles (NPs), PVA alone and PVA with CNTs was prepared and its cross section was studied with SEM (fig. 15), showing a clear boundary of micrometer thickness. First solution: mixing 10% silver nanoparticles and 10% PVA; the second solution: 10% PVA; third solution: 8.8% CNT and 10% PVA were mixed. 0.5gr of each solution was poured onto small petri dishes in three steps. The first solution was poured and completely dried, then the second and third solutions were similarly poured and air dried. Thereafter, the dried PVA composite membrane was immersed by pouring 6M NaOH solution to complete gelation. The conductivities of the CNTs were 30-50Kohm/cm, the silver nanoparticles 400-600Kohm and the PVA 10Mohm measured with a two-point probe instrument.

Figure 16 shows the EDX results for each layer in the composite of the present invention. From the results, it was found that the PVA-CNT layer contained the highest amount of carbon element compared to the other two layers. Silver pick-up (Ag pick) also occurs in the third layer. Thus, the method of the present invention enables the synthesis of micro-scale and nano-scale membranes with different materials and properties.

Tube and catheter

Catheters are a very important tool in minimally invasive cardiac therapies. Currently, different types of polymers are available for manufacturing catheters, including silicon, nylon, polyurethane, polyethylene terephthalate (PET), latex, and thermoplastic elastomers. However, the current catheters have poor mechanical properties, and the comfort and safety still have to be improved

Strong elasticity and durable implants with rough surfaces are important factors in catheters. In view of the excellent surface roughness, the PVA hydrogels developed by the present invention are beneficial as permanent and temporary (biodegradable) catheter-based implants. Microtubes with adjustable mechanical properties and thickness can be manufactured by the method of the invention. To make the vials, metal rods were immersed in a 10% PVA solution and spun by a custom motor with an attached drying fan, for single layer coating (fig. 17A). As the speed is increased to higher frequencies, a uniform coating can be achieved. The coating process is repeated to achieve the desired thickness. Various PVA-based solutions can be used for coating to obtain different composite materials. After drying, the coated rods were soaked in NaOH solution for 10 minutes for gelation. They easily peel off the metal bar and are rinsed with water.

Air bag conduit (layer by layer manufacturing)

The developed tube may also be used as a balloon catheter. Due to its elasticity, the tube acts like a balloon and can be inflated when pressurized with a fluid. As can be seen from FIG. 14B below, when the hydrogel is dry, it is very resistant to the pressure applied when air is passed through it. Water is used to wet certain parts of the tube to restore its elastic properties, which blow like a balloon after applying pressure (fig. 14C).

3D printing production and application

The ability to mix PVA with different materials may result in a viscous printable solution. This may help to synthesize a different range of printing inks.

Injectable electronic device

Combining PVA hydrogels with flexible biodegradable, wireless and injectable electronics can provide a long-term monitoring system for minimally invasive surgery and brain activity. One challenge associated with the use of PVA hydrogels is the lack of controllable dosage for real-time interaction. This can be addressed by using layer-by-layer hydrogels, microfluidic techniques, or injectable electronics.

The use of a 10% PVA solution combined with a conductive agent (10% PVA solution with 10mg/ml CNTs) enables the preparation of a conductive ink that can be gelled using the mechanism of the present invention. PVA as a surfactant can help to effectively disperse the carbon nanotubes in solution without coagulation. First, 10mg/mL of CNT was dispersed in 2% (weight percent) PVA solution, sonicated and stirred for 1 hour. More PVA was added to reach 10 wt% PVA, the heating was maintained and the bath was moved overnight at 60 ℃. PVA-CNT ink was used as printing ink to print electronic grids on the back of the petri dish as shown in fig. 19A and 19B. When the print was dry, NaOH solution was added to coagulate the PVA and CNT network for curing. The resulting web can be easily peeled from the substrate to form a very strong and stretchable conductive web, providing countless applications in wearable sensors and printable electronics. Fig. 19B shows several printing screens in water. The ability to print very thin webs and high mechanical strength allows the development of injectable electronic webs; as can be seen in fig. 19, the strong gel maintains its integrity even after being pushed through the hollow narrow site of the small pipette tip (fig. 19C and 19D).

Stretchable electronic board with PVA film

Other conductive inks including PVA-Ag nanowires and PVA-graphene were also fabricated. Conductive particles comprising a PVA solution may also be printed on the dried PVA hydrogel, printed layer by layer and an electronic board may be printed on the PVA film. Fig. 20 shows a printed web on a PVA substrate that prints well and assembles with its substrate (fig. 20 shows the performance of the printed web on the PVA substrate). To prepare the substrate, 5ml of 10 wt% PVA was poured into a petri dish and dried overnight. Then, PVA-CNTs were printed on a dried PVA substrate, then dried for several minutes, followed by addition of NaOH for curing (fig. 20).

Microfluidic channel

The field of hydrodynamics relates to microfluidics, and channel sizes from 500 microns to 0.1 microns can be considered microfluidic channels. Microfluidic chips are typically made with PDMS membranes using different methods and processes and are typically associated with internal channel surface modifications to enhance hydrophilicity for microfluidic applications. The present invention introduces a new alternative to microfluidic channels that are typically fabricated from PDMS. The PVA hydrogels of the present invention have shown the ability to be used as an alternative method for the fabrication of microfluidic channels of various shapes and sizes, and the application of PVA hydrogels in new biomedical sensors and catheters is presented by combining PVA with conductive nanomaterials and is compatible with 3D printing fabrication, which provides a new solution for microfluidic lab-on-a-chip systems.

Synthesis of microfluidic channels on membranes

20ml of 10% PVA solution was poured into a large petri dish and dried overnight. Then, a 5% alginate solution was prepared for printing as a sacrificial material (sacrificial material) on the PVA film. After printing the different patterns, the dried PVA with the 3d printed alginate was covered with another 20mL PVA solution and dried overnight at room temperature. Then, the dried PVA film was immersed in the NaOH solution for 20 minutes (fig. 21A). After gelation, the membrane was washed with water and the alginate solution was removed from the edges of the pressed membrane. The channels were washed and water was passed through the channels of a tiny needle and syringe to remove the alginate. As shown in fig. 21B, a yellow dye traceable under UV light was injected into the channel.

Synthesis of 3d microfluidic channels on PVA tubes

The microfluidic channels can be printed on a non-planar surface following the same process used for the membrane. To demonstrate this ability, a metal rod was immersed in the PVA solution and rotated under a fan to obtain a uniform film covering the rod. This process was repeated three times. Then, alginate was printed on the PVA surface. Then, the alginate-printed PVA was again immersed in PVA and dried three times, and then the system was placed in a NaOH solution for 20 minutes. The sample was washed with water and easily removed from the rod. The samples were placed in water overnight to neutralize the PH. The printed alginate was then pushed out of the channel, resulting in the formation of a microfluidic channel on the PVA tube (fig. 22).

Thus, the PVA-based manufacturing process of the present invention provides new opportunities for developing novel microfluidic devices that exhibit higher mechanical properties, stretchability, ease of preparation, hydrophilic surface and biocompatibility than commonly used PDMS films. This design is beneficial to introduce the concept of lab-on-a-chip for novel applications.

The PVA hydrogel developed by the invention can be introduced into a biomedical sensor for measuring flow, pressure and bioactivity in different applications and environments, and has adjustable mechanical properties. Combining the PVA hydrogel of the present invention with recently developed inexpensive technical laboratories with wireless data communication may provide a new generation of health monitoring systems for different conditions and different organs. Importantly, this may lay the foundation for indiscernible real-time health monitoring. Figure 24 shows a catheter with a printed CNT-based conductive mesh for recording the resistance signal caused by internal flow.

Other potential applications

Cell culture, in vitro and in vivo applications

The elasticity and contractile properties of the hydrogel of the present invention can provide a novel culture medium to stimulate human muscles to have contractile motion like cardiac muscles. PVA can be mixed with cell attachment proteins such as gelatin and dopamine to improve cell compatibility and used for cell culture studies. After approaching the optimal mixture of PVA and gelatin with excellent cell viability characteristics, 3D printable cell culture media for different applications can be synthesized. Figure 25 shows PVA mixed with gelatin (10% PVA and 1% gelatin). Drug delivery

As explained, PVA hydrogels can be used to make new catheters. Catheters are one means of drug delivery that can deliver large volumes of target solution to a target site. On the other hand, the ability to design microfluidic channels on a tube allows drugs, cells or molecules to reach desired regions in controlled and continuous amounts.

Drug releasing microcapsules and microgels

Currently, a diverse range of biocompatible natural, synthetic polymers and proteins have been used for encapsulation and extended release of active agents. Microfluidic technology provides a way to obtain systems of controlled size and properties by encapsulating target molecules, drugs or particles in microgels. The scale-up capability allows thousands of microgels to be produced. The physical gelation of alginate and calcium makes them an interesting combination for encapsulating different agents, which are passed through two or more solutions flowing together at different speeds via microchannels with the help of microfluidic systems to prepare microgels with different sizes. Alginate-calcium has been widely used in tissue engineering, cell culture and drug delivery (FIG. 26)

Fig. 26 is a schematic diagram showing a hepatic lobular microstructure and a synthetic method of making a linear hepatic micro-organ. Fig. 26A shows liver lobular microstructure: the Parenchymal Hepatocytes (PH) are detached from the blood sinuses and form a linear structure of a hepatocyte layer with a thickness of 1. The hepatocyte cords are covered by a layer of Endothelial Cells (ECs), and between PH and EC there is a perisinus space (the space of dise) in which stellate cells are disposed. Figure 26B shows alginate hydrogel microfibers binding hepatocytes and 3T3 cells were fabricated with a microfluidic system, with the lower panel showing cross-sectional views of alginate threads encapsulating the cells before and after gelation.

The proposed mechanism of the present invention can provide a new method for preparing a range of different hydrogels. By increasing the degradability of the PVA of the present invention to the desired value and varying the concentration of NaOH, a new controlled release mechanism for drug delivery purposes can be provided.

When PVA solution is the mainstream, droplet focused microfluidic channels are designed and NaOH as a separator can produce size controlled PVA microgels that can be further washed in other parts of the microfluidic chip custom designed to wash NaOH from the microgels. Designing microfluidic systems with multiple co-flows can facilitate the production of layer-by-layer microgels for targeted applications (fig. 27). The elastic and rough surface and electrical resistance properties of PVA hydrogels may lead to a new family of microcapsules.

Micro robot

According to PVA hydrogels, by combining nanoparticles such as MNP and layer-by-layer fabrication, a magnetically controllable mechanism can be developed and a multifunctional micro-robot designed for monitoring and drug delivery systems.

Nano energy source and super capacitor

The combination of PVA with conductive materials such as graphene, CNT, PANI and the like can be beneficial to the application of nano energy. The PVA-CNTs and PVA-graphene hydrogels prepared in this study were electrodeposited and coated multiple times with PANI and could be used as supercapacitors. Bioabsorbable sensor

In view of the improvement of antibacterial properties and the adjustment of degradability, PVA hydrogels can be used to develop bioabsorbable sensors having strong stretchable rough hydrophilic surface properties.

PVA hydrogels and composites based thereon having various interesting properties have been developed. Strong stretchable PVA hydrogel films can be made with adjustable thickness as small as a few microns. Various nanomaterials, such as carbon nanotubes and graphene, can be incorporated into films for sensor applications. In addition, the PVA hydrogel film can recover large plastic deformation, and the shrinkage force can be increased by 500 gr. The materials designed by the present invention can be mechanically and chemically stable, have good properties and are compatible with the target application. Typically, films made with PVA are mechanically weak, and the present invention introduces a very strong PVA hydrogel with a low swelling ratio of about 1.5. The PVA hydrogels of the present invention have good contact angles and hydrophilicity, showing promising alternatives to microfluidic channels. The scalable process of the present invention can provide convenient commercialization for any application.

Claims

1. A PVA hydrogel having an elastic modulus of 1MPa to 20MPa and an ultimate strength of 10MPa to 100MPa, the PVA hydrogel being produced by a method comprising: mixing polyvinyl alcohol with the molecular weight of 100-1000K with water according to the mass ratio of 1: 5-1: 30 to obtain a PVA solution, then pouring the PVA solution into a culture dish, drying to obtain a PVA film, then immersing the PVA film into an alkaline solution with the molar concentration of 3-6M,

wherein the alkaline solution is NaOH solution or KOH solution, and the ratio of the PVA solution to the alkaline solution in parts by weight is 1: 3-10.

2. The PVA hydrogel of claim 1, wherein the PVA hydrogel has a deformation recovery rate of 65% to 95% when added with water.

3. The PVA hydrogel of claim 2, wherein the PVA hydrogel has a deformation recovery rate of 70% to 92% when water is added.

4. The PVA hydrogel of claim 1, wherein the PVA hydrogel has a contact angle of from 15 to 20 degrees.

5. A composite material comprising the PVA hydrogel of any one of claims 1 to 4.

6. The composite of claim 5, wherein the PVA hydrogel has incorporated therein magnetic nanoparticles.

7. The composite of claim 5, wherein the PVA hydrogel has incorporated therein graphene.

8. The composite of claim 5, wherein said PVA hydrogel has carbon nanotubes incorporated therein.

9. The composite of claim 5, wherein the PVA hydrogel has urea incorporated therein.

10. The composite of claim 5, comprising a layer formed from the PVA hydrogel, wherein the layer of PVA hydrogel is coated with polyaniline.

11. The composite material according to claim 5, comprising a layer formed of a PVA hydrogel containing silver nanoparticles, a layer formed of a PVA hydrogel, and a layer formed of a PVA hydrogel containing carbon nanotubes, which are stacked in this order.

12. A method for preparing the PVA hydrogel according to any one of claims 1 to 4, comprising mixing polyvinyl alcohol having a molecular weight of 100 to 1000K with water in a mass ratio of 1:5 to 1:30 to obtain a PVA solution, pouring the PVA solution into a culture dish, drying the PVA solution to obtain a PVA film, immersing the PVA film in an alkaline solution having a molar concentration of 3 to 6M to obtain the PVA hydrogel,

13. The method of claim 12, further comprising washing the PVA hydrogel with purified water.

14. The method of claim 12, further comprising dehydrating the PVA hydrogel.

15. The method according to claim 14, wherein the dehydration treatment is air drying at room temperature for 2-8 hours.

16. The method according to any one of claims 12 to 15, wherein the polyvinyl alcohol is mixed with water at a mass ratio of 1:5 to 1:30, and the mixture is left in a shaking bath at 60 ℃ overnight to obtain a PVA solution.

17. A method according to any of claims 12 to 15, characterised in that polyvinyl alcohol is mixed with water to obtain a PVA solution with a concentration of 10% by mass in volume.

18. The method according to any one of claims 12 to 15, wherein the drying is carried out at room temperature for 8 to 24 hours.

19. The method of any one of claims 12 to 15, wherein the PVA film is immersed in the alkaline solution for 1 to 60 minutes.

20. Use of a PVA hydrogel according to any one of claims 1 to 4 for the manufacture of any one of a catheter, a 3D printable solution, an injectable electronic device, a microfluidic channel, a bioabsorbable sensor, a micro-robot.

21. Use of a PVA hydrogel according to any one of claims 1 to 4 in the manufacture of any one of a tissue engineering scaffold, a surgical suture, a medical glove and a condom.