Polyethylene glycol gel as well as preparation method and application thereof

Abstract

The invention discloses polyethylene glycol gel as well as a preparation method and application thereof. The preparation method of the polyethylene glycol gel comprises the following steps: 1) uniformly mixing acrylic acid, active ester-polyethylene glycol-methacrylate, phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate and polyethylene glycol, and defoaming to obtain a gel pre-polymerized solution; and 2) injecting the gel prepolymerization liquid into a mold, and then carrying out ultraviolet curing to obtain the polyethylene glycol gel. The polyethylene glycol gel has the advantages of being adjustable in mechanical property, good in adhesion property, capable of achieving self-healing, good in biocompatibility, suitable for multiple types of base materials and the like, the preparation method is simple, raw materials are easy to obtain, the production cost is low, and the polyethylene glycol gel is suitable for large-scale industrial production and application.

Description

Technical Field

[0001] The present invention relates to the technical field of gel materials, and particularly relates to a polyethylene glycol gel, a preparation method thereof, and an application thereof. Background Art

[0002] Hydrogel adhesives have good mechanical flexibility and biocompatibility, and are widely used in fields such as tissue engineering and flexible electronics. However, there are significant differences in the mechanical strengths of different biological tissues, and it is difficult to easily adjust the mechanical properties of existing hydrogel adhesives. Therefore, they cannot well adapt to biological tissues with different mechanical strengths, and their practical applications are greatly limited. For a long time, researchers have been committed to developing tough gel adhesives that can be applied to multiple tissue interfaces and have multiple applications. However, it is still a huge challenge to simultaneously achieve convenient adjustment of gel mechanical properties and strong adhesion in a complex physiological environment.

[0003] Therefore, it is of great significance to develop a hydrogel adhesive with adjustable mechanical properties, good adhesion properties, self-healing ability, good biocompatibility, and a wide variety of applicable substrates. Summary of the Invention

[0004] The purpose of the present invention is to provide a polyethylene glycol gel, a preparation method thereof, and an application thereof.

[0005] The technical solution adopted by the present invention is as follows:

[0006] A preparation method of a polyethylene glycol gel includes the following steps:

[0007] 1) Mix acrylic acid, active ester-polyethylene glycol-methacrylate, lithium phenyl(2,4,6-trimethylbenzoyl)phosphate, and polyethylene glycol evenly, and then defoam to obtain a gel prepolymer solution;

[0008] 2) Inject the gel prepolymer solution into a mold, and then perform ultraviolet curing to obtain the polyethylene glycol gel.

[0009] Preferably, the mass ratio of acrylic acid (AA), active ester-polyethylene glycol-methacrylate (NHS-PEG-MA), lithium phenyl(2,4,6-trimethylbenzoyl)phosphate (LAP), and polyethylene glycol (PEG) in step 1) is 0.2-0.3:0.1-0.2:0.0005-0.002:1.

[0010] Preferably, the number average molecular weight of the active ester-polyethylene glycol-methacrylate in step 1) is 400 g / mol-800 g / mol.

[0011] Preferably, the number average molecular weight of the polyethylene glycol in step 1) is 400 g / mol-4000 g / mol.

[0012] Preferably, the mixing in step 1) is carried out at a temperature of 50°C to 80°C.

[0013] Preferably, the defoaming method in step 1) is ultrasonic defoaming.

[0014] Preferably, the ultraviolet curing in step 2) is carried out under the condition that the ultraviolet light intensity is 6 mW / cm 2 ~10 mW / cm 2 and the curing time is 1 min to 5 min.

[0015] A polyethylene glycol gel is prepared by the above preparation method.

[0016] An adhesive contains the above polyethylene glycol gel.

[0017] An application of the polyethylene glycol gel as described above in the field of tissue engineering or bioelectronics.

[0018] The beneficial effects of the present invention are as follows: The polyethylene glycol gel of the present invention has the advantages of adjustable mechanical properties, good adhesion performance, self-healing ability, good biocompatibility, and a wide variety of applicable substrate types (such as traditional substrates like glass, metal, rubber, hydrogel, etc.; biological tissues like pig skin, pork, heart, etc.), and its preparation method is simple, raw materials are easy to obtain, production cost is low, and it is suitable for large-scale industrial production and application. Description of the Drawings

[0019] Figure 1 FTIR diagram of the gel prepolymer solution and MAP in Example 1 400

[0020] Figure 2 XPS diagram of MAP in Example 1 400

[0021] Figure 3 Diagram of the gel-forming ability test results of the polyethylene glycol gel in Example 1

[0022] Figure 4 Stress-strain relationship curves of the polyethylene glycol gels in Examples 1 to 6

[0023] Figure 5 Physical display diagram of the tensile properties of MAP in Example 1 400

[0024] Figure 6 Test result diagram of the cyclic compression performance of MAP in Example 1 400

[0025] Figure 7 ​​​​For the MAP in Example 1 400 Graph of the adhesion performance test results for different substrates.

[0026] Figure 8 For the MAP in Example 1 400 Physical display graph of the adhesion performance for different substrates.

[0027] Figure 9 Graph showing the self-healing process of the polyethylene glycol gel.

[0028] Figure 10 Physical diagram of polyethylene glycol gel samples of different shapes formed by 3D printing.

[0029] Figure 11 SEM graph of the Janus gel.

[0030] Figure 12 The MAP in Example 1 400 Graph of the in vitro biocompatibility test results.

[0031] Figure 13 For the MAP 400 Physical diagram of the application of MAP, UV hydrogel, and Janus gel in the tendon adhesion model.

[0032] Figure 14 For the MAP 400 Graph of the H&E and Masson staining results of the application of MAP, UV hydrogel, and Janus gel in the tendon adhesion model.

[0033] Figure 15 For the MAP in Example 1 400 Graph of the H&E staining results of the biosafety.

[0034] Figure 16 For the MAP 400 Graph of the application of the adhesion of MAP and the flexible patch in finger bending and beating of an ex vivo heart.

[0035] Figure 17 For the MAP 400 Test graph of the adhesion of MAP and the flexible patch in finger bending and beating of an ex vivo heart. Detailed implementation method

[0036] The present invention will be further explained and described below in conjunction with specific embodiments.

[0037] Example 1:

[0038] A polyethylene glycol gel, and its preparation method is as follows:

[0039] 1) Add 200 mg of acrylic acid, 150 mg of active ester - polyethylene glycol - methacrylate (number - average molecular weight is 600 g / mol), 1 mg of lithium phenyl(2,4,6 - trimethylbenzoyl) phosphate, and 800 mg of polyethylene glycol (number - average molecular weight is 400 g / mol) into an EP tube with a volume of 5 mL. Then place it in a 70 °C water bath and stir magnetically for 10 min at a stirring rate of 600 rpm. Then ultrasonicate for 5 min to remove bubbles to obtain a gel prepolymer solution;

[0040] 2) Inject the gel prepolymer solution into a silica gel mold, and then place it under ultraviolet light for irradiation for 3 min. The ultraviolet light intensity is 6 mW / cm 2 , demold to obtain polyethylene glycol gel (denoted as MAP 400 ).

[0041] Example 2:

[0042] A polyethylene glycol gel (denoted as MAP 600 ), except that when preparing, replace the "polyethylene glycol with a number - average molecular weight of 400 g / mol" with an equal mass of "polyethylene glycol with a number - average molecular weight of 600 g / mol", and the rest is exactly the same as in Example 1.

[0043] Example 3:

[0044] A polyethylene glycol gel (denoted as MAP 800 ), except that when preparing, replace the "polyethylene glycol with a number - average molecular weight of 400 g / mol" with an equal mass of "polyethylene glycol with a number - average molecular weight of 800 g / mol", and the rest is exactly the same as in Example 1.

[0045] Example 4:

[0046] A polyethylene glycol gel (denoted as MAP 1000 ), except that when preparing, replace the "polyethylene glycol with a number - average molecular weight of 400 g / mol" with an equal mass of "polyethylene glycol with a number - average molecular weight of 1000 g / mol", and the rest is exactly the same as in Example 1.

[0047] Example 5:

[0048] A polyethylene glycol gel (denoted as MAP 4000 ), except that when preparing, replace the "polyethylene glycol with a number - average molecular weight of 400 g / mol" with an equal mass of "polyethylene glycol with a number - average molecular weight of 4000 g / mol", and the rest is exactly the same as in Example 1.

[0049] Example 6:

[0050] A polyethylene glycol gel (denoted as MAP 400 / 4000), except that during preparation, "polyethylene glycol with a number-average molecular weight of 400 g / mol" was replaced with an equal mass of "polyethylene glycol with a number-average molecular weight of 400 g / mol and polyethylene glycol with a number-average molecular weight of 4000 g / mol (the mass ratio of polyethylene glycol with a number-average molecular weight of 400 g / mol to polyethylene glycol with a number-average molecular weight of 4000 g / mol is 1:3)", and the rest is exactly the same as in Example 1.

[0051] Performance test:

[0052] 1) Structural characterization of polyethylene glycol gel:

[0053] The infrared spectroscopy (FTIR) diagrams of the gel prepolymer solution and polyethylene glycol gel (MAP 400 ) in Example 1 are as Figure 1 shown. The X-ray photoelectron spectroscopy (XPS) diagram of the polyethylene glycol gel (MAP 400 ) in Example 1 is as Figure 2 shown.

[0054] From Figure 1 and Figure 2 , it can be seen that: the carboxyl group in polyacrylic acid (PAA) shows a C=O peak at 288.5 eV in the C1s XPS spectrum and a C=O stretch at 1720 cm 400 in MAP -1 ; the NHS ester in active ester-polyethylene glycol-methacrylate shows a C-N peak at 285.9 eV in the C 1s XPS spectrum, a peak at 398.8 eV in the N1s XPS spectrum, an asymmetric C-N-C stretch at 1292 cm 400 and a symmetric C-N-C stretch at 1235 cm -1 in MAP -1 ; the polymerization process is characterized by a change in the C=C stretch related to AA and PAA in MAP -1 ~1640 cm -1 at 1618 cm 400 ; in summary, a polymer cross-linked network is formed inside MAP 400 and it contains NHS ester reactive groups.

[0055] 2) Gel-forming ability test of polyethylene glycol gel:

[0056] Use a pipette to aspirate 1 mL of the gel prepolymer solution in Example 1 and add it to a sample bottle. Place it under ultraviolet light irradiation with an ultraviolet light intensity of 6 mW / cm 2 , and start timing and taking pictures. Tilt the sample bottle and stop timing when the gel is formed. The gel-forming ability test results of the obtained polyethylene glycol gel are as Figure 3(As shown in (a), it is a physical diagram at the beginning of timing, not polymerized and solidified; (b) is a physical diagram when the gel is formed, already polymerized and solidified).

[0057] It can be seen from Figure 3 that the gel prepolymer can be quickly polymerized into a gel within 12 s, indicating that the polyethylene glycol gel of the present invention has the ability of rapid processing and forming.

[0058] 3) Mechanical property test of polyethylene glycol gel:

[0059] The tensile properties of the polyethylene glycol gel samples were tested using an AGS-X series universal electromechanical test stand (Shimadzu Corporation, Japan). For the tensile test, the test samples were molded into dumbbell shapes (length 35 mm, thickness 1 mm, length of the narrow neck region 10 mm, width 1 mm), and the tensile speed was set at 50 mm / min. The cyclic compression experiment was carried out using cylindrical specimens obtained from silicone molds. The total height of the specimens was 10 mm, the diameter was 12 mm, and the height-diameter ratio of the specimens was 1:1.2 (which can effectively prevent the bending effect caused by eccentric force), and the compression speed was set at 50 mm / min. During the test, all actual test dimensions were accurately measured with a vernier caliper. The stress-strain relationship curves of the polyethylene glycol gels in Examples 1 to 6 obtained from the test are as shown in Figure 4 and the physical diagram showing the tensile properties of the polyethylene glycol gel (MAP 400 ) in Example 1 is as shown in Figure 5 ((a) is a manual tensile test; (b) is a machine tensile test), and the test results of the cyclic compression performance (50% compression strain) of the polyethylene glycol gel (MAP 400 ) in Example 1 are as shown in Figure 6 .

[0060] It can be seen from Figure 4 and Figure 5 that as the molecular weight of PEG increases, the tensile strength of the obtained polyethylene glycol gel increases from 134 kPa (PEG 400 ) to 146 kPa (PEG 600 ), 177 kPa (PEG 800 ), 207 kPa (PEG 1000 ) to 1094 kPa (PEG 4000 ); however, the fracture strain of the polyethylene glycol gel changes from 1545% (PEG 400 ) to 2432% (PEG 600 ), 2653% (PEG 800 ), 1100% (PEG 1000 ) and 149% (PEG 4000) It shows that a higher molecular weight of PEG helps to increase the interaction between polymer chains within the poly(ethylene glycol) gel network, thereby effectively improving the tensile strength of the poly(ethylene glycol) gel. However, at room temperature, the state of PEG changes with the increase of M w When M w is below 1000, PEG mainly exists in a liquid state, thus showing good fluidity and dispersibility. When the molecular weight exceeds 1000, PEG transforms into a solid state, and the gap between molecular chains is very narrow, making it challenging to achieve effective entanglement, which results in the poly(ethylene glycol) gel being hard and brittle. In addition, by mixing PEG 400 (low molecular weight) and PEG 4000 (high molecular weight) in a 1:1 ratio to prepare the poly(ethylene glycol) gel, the obtained poly(ethylene glycol) gel has both good strength and good fracture strain. Therefore, a suitable poly(ethylene glycol) gel can be customized by adjusting the ratio of low molecular weight to high molecular weight PEG, indicating that the mechanical properties of PEG can be conveniently adjusted by regulating its molecular weight.

[0061] It can be seen from Figure 6 that the poly(ethylene glycol) gel can still provide a well-shaped compression profile under a large compression strain of 50% for up to 50 cycles. At the same time, an obvious hysteresis loop is observed in the loading-unloading curve, indicating that the poly(ethylene glycol) gel has a considerable energy dissipation capacity. The observed rapid recovery may be due to the reversible and dynamic hydrogen bonds between the P(MPN-co-AA) chains and PEG. This binding is temporarily broken during loading to dissipate energy and is rapidly reconstructed during unloading, indicating that the poly(ethylene glycol) gel has excellent fatigue resistance and durability.

[0062] 4) Adhesion performance test of the poly(ethylene glycol) gel:

[0063] The shear-adhesion test method was used to conduct the adhesion performance test. The specific operations are as follows: a) Prepare the cleaned pigskin and remove the cutin layer with a skin preparation knife; b) Apply the gel prepolymer solution in Example 1 to the surface of the pigskin, cover it with a piece of glass. The size specification of the area where the prepolymer solution is applied between the pigskin and the glass is 10 mm × 10 mm × 1 mm, and then place it under ultraviolet light with a wavelength of 365 nm for 3 min. The ultraviolet light intensity is 6 mW / cm 2 , then put it into a tensile machine and stretch it at a speed of 10 mm / s, and record the data. Each sample is tested 3 times and the average value is taken. Different substrates are tested according to the above method. The adhesion performance test results of the poly(ethylene glycol) gel on different substrates are as shown in Figure 7 (the substrates in a are glass, Al, PET, PDMS, and wood; the substrates in b are skin, muscle, intestine, and liver), and the physical display diagram of the adhesion performance is as shown in Figure 8As shown (the substrates in (a) are skin, rubber, Al, and PET; the substrates in (b) are heart, kidney, liver, and spleen).

[0064] It can be seen from Figure 7 that the polyethylene glycol gel has a strong adhesion to the glass substrate, and the bonding strength reaches 5.69 MPa. At room temperature, the average adhesion strengths of the polyethylene glycol gel to glass, aluminum (Al), polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), and wood are 5.69 MPa, 1.40 MPa, 1.75 MPa, 0.82 MPa, and 2.82 MPa respectively (the adhesion area is 1 cm 2 ). At room temperature, the average adhesion strengths of the polyethylene glycol gel to skin, muscle, intestine, and liver are 109.44 kPa, 79.31 kPa, 63.64 kPa, and 55.22 kPa respectively (the adhesion area is 1 cm 2 ). In summary, it can be seen that the polyethylene glycol gel shows excellent adhesion performance to various materials and tissues.

[0065] It can be seen from Figure 8 that the polyethylene glycol gel has a firm adhesion to various substrates, indicating that the polyethylene glycol gel shows excellent adhesion performance to various materials and tissues.

[0066] 5) Self-healing performance test of the polyethylene glycol gel:

[0067] Pour the gel prepolymer solution in Example 1 into a dumbbell-shaped tensile specimen mold, and then place it under ultraviolet light with a wavelength of 365 nm for 3 min. The ultraviolet light intensity is 6 mW / cm 2 . Then observe it under a stereomicroscope, cut it open at the neck with a blade, and observe and photograph the scratch healing situation at different times. The self-healing process display diagram of the polyethylene glycol gel obtained is as Figure 9 shown.

[0068] It can be seen from Figure 9 that at 1 min, the scratch starts to heal, and at 10 min, the scratch is almost completely healed, indicating that the physical cross-linking network and hydrogen bond interaction inside the polyethylene glycol gel endow it with good self-healing properties.

[0069] 6) 3D printing forming performance test of the polyethylene glycol gel:

[0070] The gel prepolymer solution in Example 1 was used as the ink for 3D printing by a digital light processing printer. Lithium phenyl(2,4,6-trimethylbenzoyl)phosphate was used as the photoinitiator with a concentration of 1 mg / mL. The curing time for each layer (with a thickness of 100 μm) was 30 s. The printing contour was designed using 3D Studio Max software and exported in STL format. The gel prepolymer solution was printed into the target shape through a needle (with a diameter of 600 μm) using an extrusion-based 3D printer. The physical pictures of the polyethylene glycol gel samples with different printed shapes are as Figure 10 shown.

[0071] It can be seen from Figure 10 that: Using the gel prepolymer solution as the raw material, three objects were printed by a 3D printer, and their internal pore size differences and hollow structures could be well displayed, indicating that the polyethylene glycol gel has the characteristics of rapid prototyping and can be 3D printed, and has broad application prospects in biomedical and irregular adhesion scenarios.

[0072] 7) Structural characterization of the Janus gel formed by adhesion of polyethylene glycol gel and GelMA hydrogel:

[0073] The Janus gel consists of two layers of ultraviolet-cured hydrogel layers and a polyethylene glycol gel layer. The UV-curable hydrogel prepolymer solution was prepared from 300 mg of acrylamide, 50 mg of GelMA, 1 mg of LAP, and 1 mL of PBS buffer solution, and stored in the dark after vortex mixing. The prepolymer solution of the MAP layer was prepared by mixing 200 mg of AA, 150 mg of MA-PEG-NHS, 1 mg of LAP, and 800 mg of PEG-400, stirring in a 75 °C water bath for 5 min, vortexing for 3 min, and storing in the dark. First, 300 mL of the MAP prepolymer and 300 mL of the UV hydrogel prepolymer were sequentially added into a cylindrical silicone mold using a syringe, allowed to stand for 30 s, and then irradiated with ultraviolet light at a wavelength of 365 nm for 3 min. The ultraviolet light intensity was 6 mW / cm 2 , and the Janus gel was prepared. The scanning electron microscope (SEM) images of the Janus gel are as Figure 11 (the GelMA hydrogel layer, the bonding interface, and the polyethylene glycol gel layer were tested separately) shown.

[0074] It can be seen from Figure 11 that: The GelMA hydrogel layer in the Janus gel is loose and porous, while the polyethylene glycol gel layer is uniform and dense. The two-phase interface penetrates and binds tightly, and at the same time, the regions outside the interface still maintain their own independent gel structures and are not affected by this adhesion. This structure endows the Janus gel with different adhesive properties on both sides. It can be seen that the polyethylene glycol gel can stably adhere to the photocurable hydrogel and can be used to design structural gels with different properties on both sides.

[0075] 8) In vitro biocompatibility test of polyethylene glycol gel:

[0076] The in vitro cytotoxicity of L929 cells was evaluated by the standard MTT method. L929 cells were seeded in 96-well plates at a density of 5×10 3 . After incubation for 12 h, conditioned media of polyethylene glycol gels at different concentrations and the original DMEM were added to the wells. After incubation for different times, MTT solution (10 μL, 5 mg / mL) was added to each well and incubated for 4 h. Then, the medium containing the MTT solution was discarded, and dimethyl sulfoxide (DMSO, 200 μL per well) was added to dissolve the formazan crystals for 10 min. The absorbance at 490 nm was measured using a microplate reader.

[0077] The blood compatibility of the polyethylene glycol gel was evaluated by a hemolysis test. First, 20 mg of the polyethylene glycol gel was incubated in 1 mL of saline at 37 °C. Fresh whole blood obtained from the orbital venous plexus of mice was collected in an anticoagulant tube. The supernatant was removed by centrifugation. The obtained red blood cells were washed 3 times with PBS buffer solution and then resuspended in saline with a hematocrit of 2%. Then, 10 μL of the red blood cell suspension was added to deionized water, and saline was used as the positive control and negative control, respectively. After incubation in a shaker at 37 °C for 4 h, photos were taken, and the absorbance of the supernatant was measured at 540 nm using a microplate reader.

[0078] The hemolysis rate was calculated by the following formula:

[0079] Hemolysis rate (%) = (A 样品 - A 阴性对照 ) / (A 阳性对照 - A 阴性对照 ) × 100%, where A 样品 represents the absorbance of the sample, and A 阳性对照 and A 阴性对照 represent the absorbances of the positive control and negative control, respectively.

[0080] The results of the in vitro biocompatibility test of the polyethylene glycol gel in Example 1 are shown as Figure 12 (a is the test result of the MTT method; b is the test result of the hemolysis test).

[0081] It can be seen from Figure 12 that in the cytotoxicity experiment, treatment with the polyethylene glycol gel for 12 h, 24 h, 36 h, 48 h, and 72 h had no significant effect on cell viability. In the hemolysis test, according to the standard protocol for evaluating the hemolytic properties of materials (ASTM F756-17), the hemolysis rate of the polyethylene glycol gel was within the acceptable range for biomaterials (<5%). It can be seen that the polyethylene glycol gel has good biocompatibility.

[0082] 9) Application characterization of the Janus gel formed by the adhesion of polyethylene glycol gel and GelMA hydrogel for tendon adhesion model:

[0083] The construction steps of the tendon adhesion model are as follows: Twenty-four female Sprague-Dawley (SD) rats, 8 weeks old and weighing 150 g to 200 g, were randomly divided into four groups (n = 6 in each group: control group (surgery untreated group), MAP hydrogel, UV hydrogel, and Janus gel). The rats were anesthetized by intravenous injection of 3% sodium pentobarbital at a dose of 30 mg / kg. After preparing and disinfecting the skin, a 2-cm incision was made along the midline at the tendon site of the rats. Next, the tendon was excised from the bony prominence of the joint of the bone, specifically about 5 mm away, and then sutured together with 4-0 silk thread using the modified Kessler method. Subsequently, these patches were surrounded in the surgical area. Then the incision was closed using sutures. Tissue specimens were preserved in 4% paraformaldehyde (PFA) solution, rinsed with running water, dried with a series of ethanol solutions with increasing concentrations, solidified with xylene, and embedded in paraffin. Sections with a thickness of 5 μm were made using a microtome for histological analysis. The physical pictures of the MAP hydrogel, UV hydrogel, and Janus gel applied in the tendon adhesion model are as Figure 13 shown, and the H&E and Masson staining results pictures are as Figure 14 shown.

[0084] It can be seen from Figure 13 and Figure 14 that: Through visual inspection, it was determined that no obvious ulcers or infections occurred in the wound areas of each group. However, in the control group, extensive fibrotic tissue appeared around the repaired tendon, which required the intervention of a scalpel to manually separate the sutured tendon from the adjacent tissue. Although compared with the control group, the MAP hydrogel and hydrogel groups showed a reduction in adhesion formation, the subcutaneous tissue and the tendon surface were still wrapped by densely intertwined fibrous tissue bundles. However, in the tendon surrounding area of the Janus gel group, the tendon was clearly visible, and there was almost no adhesion caused by being wrapped by fibrous bands. The H&E staining of the control group showed a large amount of adhesion tissue, resulting in the repaired tendon being trapped in the granulation tissue and attracting a large number of inflammatory cells. In the tendon surrounding area, the MAP hydrogel and hydrogel groups showed the formation of disordered fiber bundles, and the repaired tendon tissue showed the presence of inflammatory cells. On the contrary, the Janus gel group showed clear tendon boundaries, reduced granulation tissue development, and reduced inflammatory cell infiltration, indicating a stronger anti-adhesion effect in vivo. It can be seen that the Janus gel formed by the adhesion of MAP hydrogel and GelMA hydrogel with asymmetric adhesion has good application effects in preventing tendon adhesion.

[0085] 10) In vivo biosafety characterization of polyethylene glycol gel:

[0086] Three weeks after the surgery, the rats were euthanized with a lethal dose of anesthetic, and then their major organs (heart, liver, spleen, lung, and kidney) were excised and processed with hematoxylin and eosin (H&E) staining. The H&E staining results of the biosecurity of the polyethylene glycol gel in Example 1 were as Figure 15 shown.

[0087] It can be Figure 15 seen that: at the third week after the surgery, the H&E staining of the major organs showed no obvious damage in the gel implantation, indicating that the polyethylene glycol gel has good biosecurity in the application in rats.

[0088] 11) Characterization of the application of the polyethylene glycol gel bio- and strain-sensing patch adhesion device in the behavior monitoring model:

[0089] To evaluate the adhesion of the strain sensor, the MAP-strain sensor hybrid was adhered to the finger joint and abdomen. The strain sensor attached to the finger joint was kept at room temperature, bent at different angles, and then connected to a digital multimeter to monitor the deformation of the finger joint. To evaluate the adhesion of the strain sensor, the MAP-strain sensor hybrid was adhered to the beating pig heart. A pneumatic pump was used to simulate the beating of the pig heart. The strain sensor adhered to the beating heart was continuously beaten at room temperature for 3 min, and then connected to a digital multimeter to monitor the deformation of the beating heart. After rinsing the surface with PBS, all the devices were adhered to the beating heart and then pressed for 5 s. The application display diagrams of the adhesion of MAP and the flexible patch in finger bending and ex vivo heart beating are as Figure 16 (the test object in a is the finger; the test object in b is the heart) shown, and the test diagrams of the adhesion of MAP and the flexible patch in finger bending and ex vivo heart beating are as Figure 17 (the test object in a is the finger; the test object in b is the heart) shown.

[0090] It can be Figure 16 and Figure 17 seen that: in the experiment of monitoring finger bending behavior, when MAP was adhered to the finger joint, it was found that it could adhere well to the joint and could stretch and contract with the movement. The results showed that as the finger bent, the strain sensor could sensitively capture the change of the resistance signal. Then, when bent at 30°, 60°, and 90° respectively, the signal peak magnification increased by an equal multiple, indicating that the adhesion of MAP could ensure the sensitivity of motion sensing monitoring. In the experiment of detecting the beating of the ex vivo pig heart, each heartbeat could be monitored by the signal within 60 s after the test. It can be seen that the MAP strain sensor hydride showed strong adhesion and sensitive motion monitoring, indicating that it has great application potential in the field of flexible electronics.

[0091] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. A method for preparing a polyethylene glycol gel, characterized in that, It includes the following steps: 1) Mix acrylic acid, acrylate-polyethylene glycol-methacrylate, lithium phenyl(2,4,6-trimethylbenzoyl)phosphate and polyethylene glycol evenly, and then defoam to obtain a gel prepolymer solution; 2) Inject the gel prepolymer solution into a mold and then carry out ultraviolet curing to obtain polyethylene glycol gel.

2. The preparation method according to claim 1, wherein: The mass ratio of the acrylic acid, acrylate-polyethylene glycol-methacrylate, lithium phenyl(2,4,6-trimethylbenzoyl)phosphate, and polyethylene glycol in step 1) is 0.2-0.3:0.1-0.2:0.0005-0.002:

1.

3. The preparation method according to claim 1 or 2, characterized in that: The number-average molecular weight of the acrylate-polyethylene glycol-methacrylate in step 1) is 400 g / mol - 800 g / mol.

4. The preparation method according to claim 1 or 2, characterized in that: The number-average molecular weight of the polyethylene glycol in step 1) is 400 g / mol - 4000 g / mol.

5. The preparation method according to claim 1 or 2, characterized in that: The mixing in step 1) is carried out under the condition of a temperature of 50°C - 80°C.

6. The preparation method according to claim 1 or 2, characterized in that: The defoaming method in step 1) is ultrasonic defoaming.

7. The preparation method according to claim 1 or 2, characterized in that: Step 2) The ultraviolet curing is carried out under the condition that the ultraviolet light intensity is 6 mW / cm 2 ~10 mW / cm 2 , and the curing time is 1 min to 5 min.

8. A polyethylene glycol gel, characterized in that, It is made by the preparation method described in any one of claims 1-7.

9. An adhesive, characterized in that, It contains the polyethylene glycol gel described in claim 8.

10. An application of the polyethylene glycol gel as described in claim 8 in the field of tissue engineering or bioelectronics.

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