A hydrogel smart electronic ligament or tendon

Abstract

The invention discloses a hydrogel intelligent electronic ligament or tendon. The preparation method of the hydrogel intelligent electronic ligament or tendon comprises the following steps: mixing a polyvinyl alcohol solution and a sodium alginate solution, then adding calcium sulfate thereto and stirring uniformly to obtain a mixed liquid, wherein the mass ratio of polyvinyl alcohol, sodium alginate, calcium sulfate and water is 0.05-0.2:0.01-0.1:0.0005-0.02:1; subjecting the mixed liquid to a freeze-thaw cycle; pre-stretching the hydrogel obtained after the freeze-thaw cycle by 10-100%, coating the surface of the stretched hydrogel with polydimethylsiloxane to a thickness of 500-1000 μm, drying the hydrogel under the pre-stretching condition, and peeling off the surface polydimethylsiloxane after drying; and rehydrating the dried hydrogel in a lithium chloride solution to obtain a hydrogel, wherein the concentration of the lithium chloride solution is 0.5-2 M.

Description

Technical Field

[0001] The invention relates to a hydrogel intelligent electronic ligament or tendon, which can be used for ligament or tendon transplantation and strain characteristic monitoring. Background Art

[0002] The statements herein merely provide background information related to the present invention and do not necessarily constitute prior art.

[0003] Injury and disorder of connective tissues such as ligaments and tendons in the human body is an increasingly serious problem in all age groups. Especially in severe cases such as ligament or tendon rupture, due to the poor regeneration ability of autologous ligaments and tendons, artificial ligament or tendon transplantation is one of the most promising treatment methods in clinical practice. In transplant surgery, artificial ligaments or tendons are usually used to protect joints and prevent excessive movement, but their single function cannot achieve monitoring. In the personalized treatment and rehabilitation stage, it is crucial to quickly and directly monitor the strain characteristics of ligaments or tendons for patients undergoing ligament or tendon reconstruction and repair. Current clinical detection tools, such as ultrasound and magnetic resonance imaging technology, usually require bulky and power-intensive equipment, and their real-time monitoring capabilities are also limited.

[0004] Flexible materials, such as conductive elastomers or hydrogels, have attracted extensive research in implantable electronic devices, promoting the development of novel bioelectronics, soft robotics, and artificial biological tissues and organs. Hydrogels, in particular, are considered one of the best candidates for mimicking natural tissue in biomedical and bioengineering applications due to their excellent biocompatibility, high water content, and ionic conductivity. They also hold broad application prospects in areas such as tissue engineering, drug delivery, energy storage, and flexible electronics. For bioelectronics applications, especially to replace natural human tissues such as ligaments and tendons, hydrogels must not only be conductive but also possess excellent mechanical properties, including high strength and toughness. However, due to their uniform internal structure, high water content, and strength typically less than 1 MPa, these hydrogels generally lack sufficient strength and toughness, limiting their potential for tissue replacement. In particular, fabricating hydrogels with excellent mechanical properties to replace fibrous connective tissues such as ligaments and tendons, while also possessing good sensing capabilities to monitor the strain and mechanical properties of ligaments and tendons, is a particularly challenging task. Summary of the Invention

[0005] In response to the above-mentioned shortcomings of the existing technology, especially the poor mechanical strength of sensors based on traditional hydrogel materials and the lack of means to quickly and directly monitor the strain characteristics of ligaments or tendons in patients undergoing ligament or tendon reconstruction, the present invention provides a hydrogel smart electronic ligament and tendon.

[0006] In order to achieve the above object, the present invention is implemented through the following technical solutions:

[0007] A hydrogel smart electronic ligament or tendon, prepared by mixing a polyvinyl alcohol solution and a sodium alginate solution, then adding calcium sulfate and stirring uniformly to obtain a mixed liquid, wherein the mass ratio of polyvinyl alcohol, sodium alginate, calcium sulfate and water is 0.05-0.2:0.01-0.1:0.0005-0.02:1;

[0008] subjecting the mixed liquid to a freeze-thaw cycle;

[0009] The hydrogel obtained after the freeze-thaw cycle is pre-stretched by 10-100%, the ends of the stretched hydrogel are fixed with clamps, the surface is coated with polydimethylsiloxane to a thickness of 500-1000 μm, and the hydrogel is dried under the pre-stretching conditions. After drying, the surface polydimethylsiloxane is peeled off;

[0010] The dried hydrogel is rehydrated in a lithium chloride solution to obtain a hydrogel, wherein the concentration of the lithium chloride solution is 0.5-2M.

[0011] The sodium alginate hydrogel is further cross-linked by a method of sustained release of calcium ions through calcium sulfate. By controlling the relative content of slightly water-soluble calcium sulfate and slowly releasing calcium ions to cross-link the sodium alginate, it is possible to prevent the cross-linking speed from being too fast and causing uneven gel.

[0012] Freeze-thaw cycles allow the polyvinyl alcohol to achieve initial physical cross-linking.

[0013] Pre-stretching can cause the sodium alginate polymer to become fibrillated during the drying process, and the length restriction leads to the oriented arrangement of the fibers, further increasing the strength and toughness of the hydrogel.

[0014] Coating the hydrogel surface with polydimethylsiloxane controls the hydrogel's water content during the drying process, preventing it from completely losing water during drying. Uncoated hydrogels will completely lose water and plasticize during drying. Coating too thin or too thick can easily result in uneven coating.

[0015] Lithium chloride, a hygroscopic salt, not only imparts conductivity but also makes the hydrogel have good moisture retention properties. Too little lithium chloride can affect conductivity and thus sensing performance, while too much can affect the mechanical properties of the final hydrogel device, such as tensile strength.

[0016] In some embodiments, the mass of calcium sulfate is 5-20% of the dry weight of sodium alginate.

[0017] In some embodiments, the sodium alginate solution is prepared by dispersing sodium alginate powder in water and stirring at 45-85° C. for 1-6 hours.

[0018] Preferably, the final mass concentration of sodium alginate is 1-10%.

[0019] In some embodiments, the polyvinyl alcohol solution is prepared by dispersing polyvinyl alcohol powder in deionized water and stirring at 55-95° C. for 1-6 hours.

[0020] Preferably, the final mass fraction of polyvinyl alcohol is 5-20%.

[0021] In some embodiments, the freezing temperature of the freeze-thaw cycle is -20 to -5°C, and the freezing time is 1 to 5 hours.

[0022] Preferably, the thawing temperature is 20-30°C.

[0023] Preferably, the number of freeze-thaw cycles is 2-4 times.

[0024] In some embodiments, the drying temperature is 60-100° C., and the drying time is 2-4 hours.

[0025] The beneficial effects achieved by one or more embodiments of the present invention are as follows:

[0026] The hydrogel intelligent electronic ligament or tendon provided by the present invention adopts polyvinyl alcohol and sodium alginate as the polymer network of hydrogel, which has excellent characteristics such as low manufacturing cost, good biocompatibility, and easy control of mechanical properties; during the high-temperature drying process under pre-stretching, the hydrogel phase changes to form a directionally arranged fiber structure, while enhancing the crystallinity, so that the hydrogel has excellent tensile strength and mechanical fatigue resistance; different degrees of tensile strain affect the migration of internal conductive ions, thereby producing different resistance changes, and has high response sensitivity, and ultimately the strain characteristics of the hydrogel can be monitored according to the resistance change rate; it has good biocompatibility, can be implanted in the knee joint to complete the reconstruction of the ligament or tendon, can stabilize the knee joint and realize good sensing function in the body; it improves the problem of poor mechanical strength inherent in the hydrogel, plays a fixing role similar to that of natural ligaments or tendons, and can sense the strain characteristics of the ligament or tendon during exercise, and has important application prospects in guiding the postoperative rehabilitation of patients with ligament or tendon reconstruction. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The accompanying drawings, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0028] Figure 1 This is a schematic diagram of the process for preparing the hydrogel smart electronic ligament of the present invention;

[0029] Figure 2 This is an optical photograph of the hydrogel smart electronic ligament or tendon of Example 1;

[0030] Figure 3 This is a stress-strain curve diagram of the hydrogel smart electronic ligament or tendon in Example 2;

[0031] Figure 4 This is a graph showing the tensile fatigue resistance of the hydrogel smart electronic ligament or tendon in Example 2;

[0032] Figure 5 This is a graph showing the sensing performance of the hydrogel smart electronic ligament or tendon under different strains in Example 2;

[0033] Figure 6 This is a graph showing the long-cycle test of the sensing performance of the hydrogel smart electronic ligament or tendon in Example 2;

[0034] Figure 7 This is a graph showing the in vitro sensing performance of the anterior cruciate ligament of the knee joint model reconstructed with the hydrogel smart electronic ligament or tendon in Example 3;

[0035] Figure 8 This is a diagram of the in vivo sensing performance of the hydrogel smart electronic ligament or tendon reconstructed in the anterior cruciate ligament of the rabbit knee joint in Example 4. DETAILED DESCRIPTION

[0036] It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those skilled in the art to which the present invention belongs.

[0037] The following are four different examples based on hydrogel smart electronic ligaments and tendons of different specifications:

[0038] Example 1

[0039] The specific steps for preparing the hydrogel smart electronic ligament are as follows:

[0040] (1) Prepare 10 ml of polyvinyl alcohol (PVA) solution and 10 ml of sodium alginate (SA) solution, mix the two solutions and stir them evenly. The concentration of PVA is 10% and the concentration of SA is 2.5%.

[0041] (2) Add 0.075g of calcium sulfate (CaSO4) to the mixed solution and stir evenly;

[0042] (3) The mixed solution was transferred to a low temperature environment (-15°C) for freezing and thawed at room temperature, and the freeze-thaw cycle was repeated three times;

[0043] (4) drying the hydrogel obtained after freeze-thawing under pre-stretching conditions;

[0044] Drying involves the following steps:

[0045] Step 1: pre-stretching the hydrogel after freeze-thaw cycles by 50%;

[0046] Step 2, fixing the two ends of the pre-stretched hydrogel on a fixture;

[0047] Step 3: Coat the hydrogel with polydimethylsiloxane except the two ends fixed by the clamps, with a thickness of 800 μm.

[0048] Step 4: Place the fixed hydrogel together with the fixture in an oven at 80°C and dry for 3 hours;

[0049] Step 5: Peel off the polydimethylsiloxane on the outer surface to obtain a high-strength hydrogel.

[0050] (5) The dried hydrogel was rehydrated in 1 M lithium chloride (LiCl) solution to obtain a high-strength hydrogel.

[0051] like Figure 1 As shown in the figure, the process flow diagram of preparing the hydrogel electronic ligament shows that the preparation process is simple, has low requirements on experimental equipment, materials and environment, is cost-effective, has strong controllability, high repeatability and can be mass-produced. Figure 2 As shown, Figure 2 a and Figure 2 b are optical photos of the hydrogel before and after drying, Figure 2 c Optical photo of the final dumbbell-shaped hydrogel loaded with 4 kg. The size of the hydrogel electronic ligament before treatment is 50*10*3 mm 3 After treatment, the size of the hydrogel electronic ligament is 48.3*5.2*1.3mm 3 , indicating that the length of the hydrogel has almost no change before and after drying treatment, the thickness and width are reduced, and it has high mechanical strength.

[0052] Example 2

[0053] The specific steps for preparing the hydrogel smart electronic tendon are as follows:

[0054] (1) Prepare 10 ml of polyvinyl alcohol (PVA) solution and 10 ml of sodium alginate (SA) solution, mix the two solutions and stir them evenly. The concentration of PVA is 15% and the concentration of SA is 5%.

[0055] (2) Add 0.15g of calcium sulfate (CaSO4) to the mixed solution and stir evenly;

[0056] (3) The mixed solution was transferred to a low temperature environment of -15°C for freezing and thawed at room temperature, and the freeze-thaw cycle was repeated three times;

[0057] (4) drying the hydrogel obtained after freeze-thawing under pre-stretching conditions;

[0058] Drying involves the following steps:

[0059] Step 1: pre-stretching the hydrogel after freeze-thaw cycles by 50%;

[0060] Step 2, fixing the two ends of the pre-stretched hydrogel on a fixture;

[0061] Step 3: Coat the hydrogel with polydimethylsiloxane except the two ends fixed by the clamps, with a thickness of 800 μm.

[0062] Step 4: Place the fixed hydrogel together with the fixture in an oven at 80°C and dry for 3 hours;

[0063] Step 5: Peel off the polydimethylsiloxane on the outer surface to obtain a high-strength hydrogel.

[0064] (5) The dried hydrogel was rehydrated in 1 M lithium chloride (LiCl) solution to obtain a high-strength hydrogel.

[0065] The size is 30*8*1mm 3 Take hydrogel smart electronic tendon as an example:

[0066] like Figure 3 As shown in Figure 3, it shows that the prepared hydrogel smart electronic tendon has high breaking strength and breaking strain. Figure 4 As shown in the figure, it shows that it has good tensile stability under multiple cycles of stretching and has the potential to replace human tendons and other connective tissues. Figure 5 As shown in the figure, it shows that the prepared hydrogel smart electronic tendon has excellent sensing performance under different strains and can better meet the needs of implantable sensors. Figure 6 As shown, under long-cycle sensing performance tests, the hydrogel electronic tendon can maintain stable sensing signals, laying the foundation for its long-term implantation in the body.

[0067] Example 3

[0068] The specific steps for preparing the hydrogel smart electronic ligament are as follows:

[0069] (1) Prepare 30 ml of polyvinyl alcohol (PVA) solution and 30 ml of sodium alginate (SA) solution, mix the two solutions and stir them evenly. The concentration of PVA is 15% and the concentration of SA is 5%.

[0070] (2) Add 0.9 g of calcium sulfate (CaSO4) to the mixed solution and stir evenly;

[0071] (3) The mixed solution was transferred to a low temperature environment of -15°C for freezing and thawed at room temperature, and the freeze-thaw cycle was repeated three times;

[0072] (4) drying the hydrogel obtained after freeze-thawing under pre-stretching conditions;

[0073] Drying involves the following steps:

[0074] Step 1: pre-stretching the hydrogel after freeze-thaw cycles by 50%;

[0075] Step 2, fixing the two ends of the pre-stretched hydrogel on a fixture;

[0076] Step 3: Coat the hydrogel with polydimethylsiloxane except the two ends fixed by the clamps, with a thickness of 800 μm.

[0077] Step 4: Place the fixed hydrogel together with the fixture in an oven at 80°C and dry for 3 hours;

[0078] Step 5: Peel off the polydimethylsiloxane on the outer surface to obtain a high-strength hydrogel.

[0079] (5) The dried hydrogel was rehydrated in 1 M lithium chloride (LiCl) solution to obtain a high-strength hydrogel.

[0080] The size is 120*10*1mm 3 Take the hydrogel smart electronic ligament as an example:

[0081] like Figure 7 As shown, the hydrogel smart electronic ligament is used as the anterior cruciate ligament to replace the original anterior cruciate ligament in the knee joint model. The knee joint is bent to different angles and its sensing performance is tested. It is shown that when the knee joint model is bent to different angles, the hydrogel smart electronic ligament has different stretching degrees, and thus different resistance changes are obtained, which can realize the monitoring of the ligament strain state.

[0082] Example 4

[0083] The specific steps for preparing the hydrogel smart electronic tendon are as follows:

[0084] (1) Prepare 20 ml of polyvinyl alcohol (PVA) solution and 20 ml of sodium alginate (SA) solution, mix the two solutions and stir them evenly. The concentration of polyvinyl alcohol is 15% and the concentration of sodium alginate is 5%.

[0085] (2) Add 0.3g of calcium sulfate (CaSO4) to the mixed solution and stir evenly;

[0086] (3) The mixed solution was transferred to a low temperature environment of -15°C for freezing and thawed at room temperature, and the freeze-thaw cycle was repeated three times;

[0087] (4) drying the hydrogel obtained after freeze-thawing under pre-stretching conditions;

[0088] Drying involves the following steps:

[0089] Step 1: pre-stretching the hydrogel after freeze-thaw cycles by 50%;

[0090] Step 2, fixing the two ends of the pre-stretched hydrogel on a fixture;

[0091] Step 3: Coat the hydrogel with polydimethylsiloxane except the two ends fixed by the clamps, with a thickness of 800 μm.

[0092] Step 4: Place the fixed hydrogel together with the fixture in an oven at 80°C and dry for 3 hours;

[0093] Step 5: Peel off the polydimethylsiloxane on the outer surface to obtain a high-strength hydrogel.

[0094] (5) The dried hydrogel was rehydrated in 1 M lithium chloride (LiCl) solution to obtain a high-strength hydrogel.

[0095] The size is 80*1.5*0.8mm 3 Take the hydrogel smart electronic ligament as an example:

[0096] like Figure 8 As shown, the dumbbell-shaped hydrogel electronic ligament was cut into a suitable size, an animal model was established, and it was implanted into the rabbit's knee joint cavity as an electronic anterior cruciate ligament to replace the original anterior cruciate ligament. This shows that the high-strength hydrogel electronic ligament can stabilize the knee joint on the one hand, and on the other hand, it can obtain sensing signals according to the bending of the knee joint, and then directly feedback the strain state of the ligament.

[0097] The hydrogel smart electronic ligament or tendon provided in the above embodiments has a simple preparation process, excellent mechanical properties and sensing properties, and can be implanted into animals to reconstruct ligaments and play a role in fixed support. At the same time, the strain state of the ligament or tendon can be directly fed back through the sensing performance, which is conducive to formulating personalized rehabilitation plans for patients in the rehabilitation stage after ligament or tendon reconstruction.

[0098] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention are intended to be within the scope of protection of the present invention.

Claims

1. A hydrogel smart electronic ligament or tendon, characterized by: The preparation method comprises the following steps: mixing a polyvinyl alcohol solution and a sodium alginate solution, and then adding calcium sulfate thereto and stirring the mixture to obtain a mixed liquid, wherein the mass ratio of polyvinyl alcohol, sodium alginate, calcium sulfate and water is 0.05-0.2:0.01-0.1:0.0005-0.02:1; The mass fraction of the polyvinyl alcohol is 5-20%; subjecting the mixed liquid to a freeze-thaw cycle; Pre-stretching the hydrogel obtained after the freeze-thaw cycle by 10-100%, coating the surface of the stretched hydrogel with polydimethylsiloxane to a thickness of 500-1000 μm, drying under the pre-stretching condition, and peeling off the surface polydimethylsiloxane after drying; The drying temperature is 60-100°C and the drying time is 2-4 hours; The dried hydrogel is rehydrated in a lithium chloride solution to obtain a hydrogel, wherein the concentration of the lithium chloride solution is 0.5-2M.

2. The hydrogel smart electronic ligament or tendon according to claim 1, characterized in that: The mass of calcium sulfate is 5-20% of the dry weight of sodium alginate.

3. The hydrogel smart electronic ligament or tendon according to claim 1, characterized in that: The preparation method of sodium alginate solution is as follows: dispersing sodium alginate powder in water, stirring at 45-85° C. for 1-6 hours, and obtaining the solution.

4. The hydrogel smart electronic ligament or tendon according to claim 3, characterized in that: The mass concentration of sodium alginate is 1-5%.

5. The hydrogel smart electronic ligament or tendon according to claim 1, characterized in that: The preparation method of the polyvinyl alcohol solution is as follows: dispersing polyvinyl alcohol powder in deionized water and stirring at 55-95° C. for 1-6 hours.

6. The hydrogel smart electronic ligament or tendon according to claim 1, characterized in that: The freezing temperature of the freeze-thaw cycle is -20 to -5°C, and the freezing time is 1 to 5 hours.

7. The hydrogel smart electronic ligament or tendon according to claim 6, characterized in that: The thawing temperature is 20-30℃.

8. The hydrogel smart electronic ligament or tendon according to claim 7, characterized in that: The number of freeze-thaw cycles was 2-4 times.

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