A rapid method for preparing customizable hydrogel artificial ligaments

Abstract

This invention discloses a rapid preparation method for customizable hydrogel artificial ligaments. Step S1: Dissolve thickener A in solvent A to form a thickener solution; S2: Add an accelerator to the thickener solution to obtain mixture A; S3: Add a polymerizable monomer, a crosslinking agent, and thickener B to mixture A to obtain mixture B; the monomer is selected from one or more combinations of acrylic acid, acrylamide, sodium p-styrene sulfonate, and methyl methacrylate; S4: Use mixture B as printing ink, and directly extrude the ink into an aqueous solution containing an initiator via extrusion printing to obtain a tough hydrogel. The tough hydrogel is then rinsed with deionized water and post-crosslinked to obtain the artificial ligament. The preparation method of this invention allows control of different geometric dimensions of the tough hydrogel through extrusion printing, resulting in customized artificial ligaments that meet the needs of different age groups, genders, and body parts for artificial ligaments.

Description

Technical Field

[0001] This invention relates to the field of biomedical engineering technology, and in particular to a rapid method for preparing customizable hydrogel artificial ligaments. Background Technology

[0002] The anterior cruciate ligament (ACL) is the primary dynamic stabilizing structure of the knee joint during flexion and rotation, playing a crucial role in maintaining knee joint stability. In recent years, the incidence of ACL injuries has been increasing annually, and these injuries can lead to serious complications such as meniscus tears and traumatic osteoarthritis. The most common treatment is surgical reconstruction of the ACL to restore knee function and allow patients to resume normal activity. Currently, the most common ACL reconstruction grafts used clinically include autografts, allogeneic grafts, and artificial ligaments.

[0003] Autologous grafts are ligaments and tendons harvested from other parts of the patient's body during surgery, tailored to the length of ligament requiring reconstruction. They pose no risk of disease transmission, immune rejection, and offer excellent mechanical properties. However, they have drawbacks such as limited availability, secondary damage to the harvesting site, numerous complications, and a long recovery period. Allogeneic grafts, taken from the same tissue, avoid secondary trauma to the patient, but carry risks of disease transmission and immune rejection, and their quality varies, making them expensive. Artificial ligaments, characterized by high strength and low rejection rates, have gradually become the preferred choice for ACL reconstruction. They primarily consist of synthetic polymer fibers and carbon fibers. However, existing artificial ligaments cannot meet the needs of different age groups, genders, and body parts. Therefore, the rapid fabrication of customized artificial ligaments with adjustable mechanical properties and geometry is crucial. Summary of the Invention

[0004] To address the technological gap in existing technologies where artificial ligaments cannot be customized, this invention provides a rapid method for preparing customizable hydrogel artificial ligaments.

[0005] The present invention provides a rapid method for preparing customizable hydrogel artificial ligaments, comprising the following steps:

[0006] S1. Thickener A is added to solvent A to form a thickener dispersion. Solvent A is one of water, DMF, or NMP.

[0007] S2. Add the accelerator to the thickener dispersion and stir to mix evenly to obtain mixture A; the accelerator is selected from one or a combination of ascorbic acid, ferrous sulfate, ferrous chloride, and MXene.

[0008] S3. Add a polymerizable monomer, a crosslinking agent, and thickener B to mixture A, and stir to mix evenly to obtain mixture B. The monomer is selected from one or a combination of several of acrylic acid, acrylamide, sodium p-styrene sulfonate, and methyl methacrylate. The crosslinking agent is selected from N,N'-methylenebisacrylamide or polyethylene glycol acrylate. Thickener A and thickener B are both selected from one of hydroxypropyl methylcellulose, carboxymethyl cellulose, starch ether, polyvinyl alcohol, sodium polyacrylate, and polyacrylamide. Thickener A and thickener B can be the same or different.

[0009] S4. Using mixture B as printing ink, the ink is directly extruded into an aqueous solution containing an initiator through extrusion printing to obtain a tough hydrogel. The tough hydrogel is then rinsed with deionized water and post-crosslinked to obtain an artificial ligament. The different geometric dimensions of the tough hydrogel can be controlled by the extrusion printing method to obtain customized artificial ligaments.

[0010] The extrusion printing method can be one of pneumatic, piston, or screw type. During printing, the needle moves at a speed of 5-20 mm / s relative to the substrate, and the gap between the needle and the substrate is 50 μm-400 μm. The substrate can be made of quartz glass, plexiglass, or polytetrafluoroethylene. After printing, the reaction temperature is 30℃-90℃, and the reaction time is 30 min-120 min.

[0011] Preferably, in step S1, the mass percentage concentration of thickener A in the thickener dispersion is 2%-10%.

[0012] Preferably, the total amount of thickener A and thickener B accounts for 4%-7% of the total mass of the ink.

[0013] Preferably, the accelerator accounts for 1‰-5‰ of the total mass of the ink.

[0014] Preferably, the monomer accounts for 20%-90% of the total mass of the ink. The mass ratio of the crosslinking agent to the monomer is 1:(350-700).

[0015] Preferably, the initiator is ammonium persulfate, and the initiator has a mass percentage concentration of 6%-15% in aqueous solution.

[0016] Compared with the prior art, the advantages of the present invention are:

[0017] The method of this invention achieves rapid gelation of high-toughness hydrogels by using an accelerator to promote the rapid polymerization reaction of monomers under the action of an initiator. Combined with extrusion printing, it enables the preparation of high-toughness hydrogels with customized shapes and sizes. This customizable high-toughness hydrogel exhibits excellent mechanical properties in artificial ligament applications. It successfully solves the problem that existing artificial ligaments cannot meet the ligament needs of different genders, age groups, and different parts of the body.

[0018] Other advantages, objectives and features of the present invention will become apparent in part from the following description, and in part from those skilled in the art through study and practice of the invention. Attached Figure Description

[0019] Figure 1 The image shown is a photograph of the artificial ligament prepared in Example 1.

[0020] Figure 2 The tensile stress-strain curve of the artificial ligament prepared in Example 1.

[0021] Figure 3 The artificial ligament prepared in Example 1 is used for the repair of the anterior cruciate ligament in pigs.

[0022] Figure 4 This is a stress-strain curve of the joint after ACL repair. Detailed Implementation

[0023] The preferred embodiments of the present invention will be described below with reference to the accompanying drawings. It should be understood that the preferred embodiments described herein are for illustration and explanation only and are not intended to limit the present invention.

[0024] Example 1

[0025] Preparation and performance testing of polyacrylic acid high-toughness hydrogel artificial ligaments: The preparation steps are as follows:

[0026] S1: Disperse hydroxypropyl methylcellulose powder in water to form an aqueous dispersion with a hydroxypropyl methylcellulose mass concentration of 5%, i.e., a thickener dispersion;

[0027] S2. Take 2g of thickener dispersion, add 50mg of ferrous sulfate (accelerator) to it, and stir in a rotary mixer at 2000rpm for 1h to obtain mixture A.

[0028] S3. Add 20g of acrylic monomer, 5mg of N,N'-methylenebisacrylamide and 1g of hydroxypropyl methylcellulose powder to mixture A, and stir in a rotary mixer at 2000rpm for 2h to obtain mixture B.

[0029] S4. Using mixture B as printing ink, the ink was directly extruded into an aqueous solution containing ammonium persulfate using a pneumatic extrusion printing method to obtain a tough hydrogel. The printing air pressure was set to 200 kPa, the needle-to-substrate movement speed was 10 mm / s, the gap between the needle and the substrate was 200 μm, the substrate was plexiglass, and the mass percentage concentration of ammonium persulfate in the aqueous solution was 10%. After printing, the surface was rinsed with running deionized water for 5 min, then dried with absorbent paper, and crosslinked at 40℃ for 60 min to obtain the desired product. Figure 1 The hydrogel artificial ligament shown.

[0030] The artificial ligament was subjected to tensile stress-strain testing using a universal testing machine at a tensile rate of 50 mm / min. The test results are shown below. Figure 2 The intrinsic hydrogel artificial ligament has a maximum tensile deformation of 220%, a tensile strength of 1.48 MPa, and a modulus of approximately 0.67 MPa.

[0031] The anterior cruciate ligament of a pig leg was reconstructed using the artificial ligament prepared in Example 1: Figure 3 As shown, fresh pig legs were purchased from the market. First, the muscles, patella, infrapatellar fat, and joint capsule at the knee were removed, preserving the collateral ligaments, medial and lateral menisci, and two cruciate ligaments. The anterior cruciate ligament was shortened, and then two bone tunnels were created within the tibial and femoral footprints using a 5.0mm diameter twist drill. Two artificial ligaments (20cm long, 6mm wide, and 0.5mm thick) were passed through the bone tunnels to replace the anterior cruciate ligament and secured with two polyetherketone (PEK) interface screws. The stress-strain curve of the joint after anterior cruciate ligament repair is shown below. Figure 4 As shown. The repaired joint ligaments include the lateral collateral ligament and the hydrogel-replaced anterior cruciate ligament. With the assistance of these two ligaments, the repaired knee joint can withstand a force of 60 kg without being damaged.

[0032] Example 2

[0033] Preparation of polyacrylamide high-toughness hydrogel artificial ligaments:

[0034] S1: Disperse hydroxypropyl methylcellulose powder in water to form an aqueous dispersion with a hydroxypropyl methylcellulose mass concentration of 5%, i.e., a thickener dispersion;

[0035] S2. Take 2g of thickener dispersion, add 30mg of MXene (accelerator) to it, and stir in a rotary mixer at 2000rpm for 1h to obtain mixture A.

[0036] S3. Add 5g of acrylamide monomer, 10g of water, 5mg of N,N'-methylenebisacrylamide and 1g of hydroxypropyl methylcellulose powder to mixture A, and stir in a rotary mixer at 2000rpm for 2h to obtain mixture B.

[0037] S4. Using mixture B as printing ink, the ink is directly extruded into an aqueous solution containing ammonium persulfate using a pneumatic extrusion printing method to obtain a tough hydrogel. The printing air pressure is set to 300 kPa, the needle movement speed relative to the substrate is 5 mm / s, the gap between the needle and the substrate is 300 μm, and the substrate is made of plexiglass. The mass percentage concentration of ammonium persulfate in the aqueous solution is 6%. After printing, the surface is rinsed with flowing deionized water for 5 min, then the surface moisture is dried with absorbent paper, and the crosslinking reaction is carried out at 50℃ for 30 min to obtain a hydrogel artificial ligament.

[0038] Example 3

[0039] Preparation of high-toughness polyacrylic acid hydrogel artificial ligaments:

[0040] S1: Disperse polyvinyl alcohol in water to form an aqueous dispersion with a mass percentage concentration of 5%, i.e., a thickener dispersion;

[0041] S2. Take 2g of thickener dispersion, add 30mg of MXene (accelerator) to it, and stir in a rotary mixer at 2000rpm for 1h to obtain mixture A.

[0042] S3. Add 20g of acrylic monomer, 5mg of N,N'-methylenebisacrylamide and 1g of hydroxypropyl methylcellulose powder to mixture A, and stir in a rotary mixer at 2000rpm for 2h to obtain mixture B.

[0043] S4. Using mixture B as printing ink, the ink is directly extruded into an aqueous solution containing ammonium persulfate using a pneumatic extrusion printing method to obtain a tough hydrogel. The printing air pressure is set to 100 kPa, the needle movement speed relative to the substrate is 8 mm / s, the gap between the needle and the substrate is 300 μm, the substrate is made of plexiglass, and the mass percentage concentration of ammonium persulfate in the aqueous solution is 15%. After printing, the surface is rinsed with running deionized water for 5 min, then the surface moisture is dried with absorbent paper, and the crosslinking reaction is carried out at 50℃ for 40 min to obtain a hydrogel artificial ligament.

[0044] Comparative Example 1

[0045] Based on Example 1, the addition of ferrous sulfate (accelerator) was omitted, while other steps remained unchanged, resulting in an artificial ligament.

[0046] Comparative Example 2

[0047] The amounts of each raw material and reagent are exactly the same as in Example 1, and the preparation method is as follows:

[0048] Step S1: Add 50mg ferrous sulfate (accelerator), 20g acrylic acid monomer, 5mg N,N'-methylenebisacrylamide, and 1.1g hydroxypropyl methylcellulose powder to 1.9g water, and stir in a rotary mixer at 2000rpm for 2h to obtain a mixture.

[0049] Step S2: Using the mixture as printing ink, the ink is directly extruded into an aqueous solution containing ammonium persulfate using a pneumatic extrusion printing method to obtain a tough hydrogel. The printing air pressure is set to 200 kPa, the needle movement speed relative to the substrate is 10 mm / s, the gap between the needle and the substrate is 200 μm, the substrate is made of plexiglass, and the mass percentage concentration of ammonium persulfate in the aqueous solution is 10%. After printing, the surface is rinsed with flowing deionized water for 5 min, then the surface moisture is dried with absorbent paper, and the crosslinking reaction is carried out at 40°C for 60 min to obtain an artificial ligament.

[0050] Comparative Example 3

[0051] Based on Example 1, in step S4, the ink was directly extruded into pure water without an initiator using a pneumatic extrusion printing method. The results showed that, due to the lack of an initiator, the monomer could not undergo polymerization and could not form an artificial ligament.

[0052] The artificial ligaments prepared in Examples 1-3 and Comparative Examples 1 and 2 were tested for properties such as toughness, strength, and tensile strength. The results are shown in Table 1.

[0053] Table 1. Comparison of the performance of artificial ligaments prepared in Examples 1-3 and Comparative Examples 1 and 2.

[0054] <![CDATA[Toughness (kJ / m 2 )]]> Strength (MPa) Strength (%) Example 1 12.5 1.48 220 Example 2 75.2 2.35 2300 Example 3 6.72 0.53 725 Comparative Example 1 0.12 0.08 135 Comparative Example 2 0.04 0.03 526

[0055] The data in the table show that the artificial ligament preparation method of the present invention has universality and can be applied to the customized rapid preparation of artificial ligaments with different geometric dimensions and chemical compositions; moreover, the artificial ligaments prepared by the present invention have high and adjustable toughness. As can be seen from Comparative Example 1, if the accelerator is not added in the preparation method, the toughness, strength, and tensile strength of the obtained artificial ligament will be significantly reduced. This is because the accelerator in the preparation method of the present invention can promote and accelerate the polymerization reaction of monomers, thereby rapidly polymerizing to prepare a high-toughness hydrogel artificial ligament. As can be seen from Comparative Example 2, if the thickener is added all at once in the preparation method, the toughness, strength, and tensile strength of the prepared artificial ligament will also be significantly reduced. This indicates that in the preparation method of the present invention, adding the thickener in batches at different times is beneficial to improving the overall performance of the artificial ligament.

[0056] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A rapid method for preparing customizable hydrogel artificial ligaments, characterized in that, Includes the following steps: S1. Thickener A is added to solvent A to form a thickener dispersion; S2. Add the accelerator to the thickener dispersion and stir to mix evenly to obtain mixture A; the accelerator is selected from one or a combination of several of ascorbic acid, ferrous sulfate, ferrous chloride, and MXene; S3. Add polymerizable monomer, crosslinking agent and thickener B to mixture A, and stir to mix evenly to obtain mixture B; the monomer is selected from one or more of acrylic acid, acrylamide, sodium p-styrene sulfonate and methyl methacrylate, and the crosslinking agent is selected from N,N'-methylenebisacrylamide or polyethylene glycol acrylate. S4. Using mixture B as printing ink, the ink is directly extruded into an aqueous solution containing an initiator through extrusion printing to obtain a tough hydrogel. The tough hydrogel is then rinsed with deionized water and post-crosslinked to obtain an artificial ligament. The different geometric dimensions of the tough hydrogel can be controlled by the extrusion printing method to obtain customized artificial ligaments.

2. The rapid preparation method for customizable hydrogel artificial ligaments as described in claim 1, characterized in that, Both thickener A and thickener B are selected from one of hydroxypropyl methylcellulose, carboxymethyl cellulose, starch ether, polyvinyl alcohol, sodium polyacrylate, and polyacrylamide.

3. The rapid preparation method for customizable hydrogel artificial ligaments as described in claim 2, characterized in that, Solvent A is one of water, DMF, or NMP.

4. The rapid preparation method for customizable hydrogel artificial ligaments as described in claim 3, characterized in that, In step S1, the mass percentage concentration of thickener A in the thickener dispersion is 2%-10%.

5. The rapid preparation method for customizable hydrogel artificial ligaments as described in claim 1, characterized in that, The total amount of thickener A and thickener B accounts for 4%-7% of the total ink mass.

6. The rapid preparation method for customizable hydrogel artificial ligaments as described in claim 1, characterized in that, The accelerator is used at a rate of 1‰-5‰ of the total ink mass.

7. The rapid preparation method for customizable hydrogel artificial ligaments as described in claim 1, characterized in that, The monomer used accounts for 20%-90% of the total ink mass.

8. The rapid preparation method for customizable hydrogel artificial ligaments as described in claim 7, characterized in that, The mass ratio of the crosslinking agent to the monomer is 1:(350-700).

9. The rapid preparation method for customizable hydrogel artificial ligaments as described in claim 1, characterized in that, The extrusion printing method is one of pneumatic, piston, or screw type.

10. The rapid preparation method for customizable hydrogel artificial ligaments as described in claim 1, characterized in that, The initiator is ammonium persulfate, and the initiator has a mass percentage concentration of 6%-15% in aqueous solution.

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