CN112940294A

CN112940294A - PVA/HA double-network hydrogel and preparation method and application thereof

Info

Publication number: CN112940294A
Application number: CN202110289294.4A
Authority: CN
Inventors: 李巧玲; 韩昕; 张雨; 范泽文
Original assignee: North University of China
Current assignee: North University of China
Priority date: 2021-03-18
Filing date: 2021-03-18
Publication date: 2021-06-11

Abstract

The invention discloses a preparation method of a high-strength low-friction self-repairing artificial articular cartilage material, belonging to the technical field of medical soft materials. The preparation method specifically comprises the following steps: (1) dissolving polyvinyl alcohol (PVA) with alcoholysis degree of more than 98% in deionized water at 95 ℃ as a reaction raw material, and uniformly doping nano Hydroxyapatite (HA) into a PVA network to obtain a reactant 1; (2) mixing borax and boric acid as a cross-linking agent, adding the mixture into the modified product 1, and preparing milky white gel by a thermal cross-linking method; (4) and (3) taking out the milky white gel, putting the milky white gel into a mold for pressing, removing internal bubbles and microcracks to obtain a sample, and then obtaining the high-strength low-friction self-repairing artificial articular cartilage material by using a freezing and thawing method. The hydrogel has self-healing capability and good bearing mechanical property, friction property and the like, and can be used in the field of artificial cartilage materials.

Description

PVA/HA double-network hydrogel and preparation method and application thereof

Technical Field

The invention relates to a preparation method of a high-strength low-friction self-repairable artificial articular cartilage material, in particular to PVA/HA double-network hydrogel and a preparation method and application thereof, belonging to the technical field of artificial cartilage material preparation.

Background

Osteoarthritis caused by the wear of articular cartilage has become the first disabling disease in the world. Approximately 4 million people suffer from joint disease. Once damage or disease is caused, repair is impossible due to the limitation of self-repair ability. Replacement of the artificial joint is therefore set to reconstruct the joint characteristics. Artificial joint replacement has become an effective method for treating joint disease or trauma. However, the prosthetic interface is poorly compatible with living media due to the lack of natural metabolism of the artificial implant material. Moreover, the contact interface of a total joint replacement implant is a hard surface, and there is wear on the contact surface. Numerous clinical medical studies have demonstrated that wear of the prosthetic joint is a major cause of aseptic loosening in joint replacement procedures. The local osteolysis caused by the abrasive particles results in aseptic loosening. This is the primary reason for the failure of artificial joint replacement. Polyvinyl alcohol (PVA) hydrogel has a three-dimensional network structure, similar to natural articular cartilage; moreover, the composite material has the properties of solid and liquid, and also has good biocompatibility, mechanical property and biological tribological property. In recent years, PVA hydrogel is expected to become a cartilage repair material and replace biological materials.

Hydrogels have been extensively studied for use as articular cartilage, and PVA hydrogels have desirable properties for use as soft tissue substitutes. However, PVA hydrogels are not strong enough to withstand the demands of human weight-bearing environments.

In the prior art, research reports of PVA/HA double-network hydrogel exist, but the PVA/HA double-network hydrogel HAs no self-repairing capability, cannot face the problem of damage in a human body after being implanted, only can adopt a treatment mode of replacement, and is limited in application and popularization.

Disclosure of Invention

Aiming at the defects and shortcomings of the prior art, the invention provides PVA/HA double-network hydrogel and a preparation method and application thereof, and overcomes the defects that the hydrogel obtained by the double-network structure in the prior art still HAs self-healing and incompatibility among mechanical properties, poor functionality, complex preparation process and the like.

The invention adopts the macromolecule-micromolecule synergistic effect to prepare the high-strength low-friction self-healing PVA/HA composite hydrogel, and HA particles are distributed in a PVA matrix to play roles of dispersion strengthening and toughening; under the action of multiple hydrogen bonds, the network structure keeps high consistency and cooperativity under external force strain, the unique structural design mode enables the interior of the hydrogel grid to have high orderliness when dynamic change occurs, and the prepared PVA/HA composite hydrogel HAs excellent performance. Meanwhile, the polyvinyl alcohol and the boric acid are connected through the function of a boric ester bond, so that the networks have good cooperativity, and the mechanical strength and the self-repairing performance of the hydrogel are improved.

The invention provides a preparation method of PVA/HA double-network hydrogel, which comprises the following specific preparation scheme:

(1) preparing hydrogel by using a thermal crosslinking-freezing thawing method, dissolving polyvinyl alcohol (PVA) with alcoholysis degree of more than 98% in deionized water at 95 ℃ to serve as a reaction raw material, wherein the mass ratio of the deionized water to a polymerized monomer is 1: 0.1-0.2; adopting inert gas for protection; the stirring speed is 500-700 rpm; stirring for 1-4h to obtain a modified PVA solution 1;

(2) adding nano hydroxyapatite serving as a modifier of the system into the PVA solution 1 obtained in the step (1), wherein the mass fraction of the nano hydroxyapatite is 1-10 wt%; the stirring speed is 500-700 rpm; stirring for 2h to obtain a modified PVA solution 2;

(3) adding a mixed solution of sodium tetraborate decahydrate and boric acid as a cross-linking agent into the modified PVA solution 2, wherein the mass ratio of the sodium tetraborate decahydrate to the boric acid is 1: 0.1-0.5; carrying out thermal crosslinking, wherein the temperature of the system is 90-95 ℃, the stirring speed is 500-700 rpm, and the reaction time is 1-20 min, so as to prepare milky white gel;

(4) and taking out the milky white gel, putting the milky white gel into a mold, pressing for 1h, removing internal bubbles and microcracks to obtain a sample, freezing for 6-12h in a refrigerator at-20 to-40 ℃, then unfreezing for 6-12h at room temperature, and repeatedly freezing and unfreezing for 3-6 times to obtain the PVA/HA double-network hydrogel.

The alcoholysis degree of the polymer monomer PVA in the step (1) is more than 98 percent;

the inert atmosphere in the step (1) is nitrogen, argon or helium;

preferably, the mass ratio of the PVA solution to the modifier in the step (2) is 1:0.1 to 1;

preferably, the system temperature in the step (3) is 90-95 ℃, and the reaction time is 10-15 min;

preferably, in the step (4), the freezing temperature is-20 ℃, the freezing time is 6h, the unfreezing time at room temperature is 12h, and the cycle time is 3 times.

Preferably, according to the above steps: the prepared sample has high-efficiency repairing capability (the original tensile stress is 0.4-0.5MPa, and the tensile stress after repairing is 0.2-0.385 MPa); the friction coefficient is low and is 0.1-0.25.

The invention provides application of PVA/HA double-network hydrogel prepared by the method as a high-strength low-friction self-repairable artificial articular cartilage material.

The invention has the beneficial effects that:

(1) the invention provides a new synthesis way for the construction of self-healing, high-strength and low-friction hydrogel materials;

(2) the high-strength low-friction self-repairing hydrogel prepared by the invention has self-healing capability and excellent mechanical properties (compressive strength), and can be used for structural biomaterials, artificial cartilage materials and the like;

(3) the sodium tetraborate decahydrate and the boric acid mixed solution are very sensitive to the fracture combination of PVA, so that the formation of dynamic chemical bonds is promoted, the repair rate is improved, and a new thought is provided for the improvement of the self-repair efficiency;

(4) the invention provides an activation mechanism of a polymer-micromolecule synergistic system, and the polymer-micromolecule synergistic system can play a role in dispersion strengthening and toughening; under the action of multiple hydrogen bonds, the network structure keeps high consistency and cooperativity under the external force strain, thereby greatly improving the bearing capacity of the hydrogel.

Drawings

FIG. 1 is an infrared characterization of the hydrogel prepared in example 3 of the present invention.

FIG. 2 is a graph of the healing stress strain before and after self-healing for the hydrogels prepared in example 3 of the present invention and comparative example 1.

Fig. 3 is a friction performance graph of the self-healing hydrogel of example 2 of the present invention.

Detailed Description

The present invention is illustrated in detail by the following examples, which should be construed as limiting the scope of the invention and which are intended to be limited only by the appended claims.

Example 1

The high-strength low-friction self-repairing artificial articular cartilage material is prepared according to the following steps:

(1) 10g of polyvinyl alcohol (PVA) is weighed and dissolved in 40g of deionized water at 98 ℃, and the mixture is stirred for 2 hours at the water bath temperature of 95 ℃ and the nitrogen atmosphere and the stirring speed of 600 rpm to obtain a PVA solution 1.

(2) Adding 2.5g of nano hydroxyapatite into the PVA solution 1, stirring for 2 hours at the water bath temperature of 95 ℃ and the nitrogen atmosphere at the stirring speed of 600 rpm to obtain a modified PVA solution 2.

(3) A mixed solution of sodium tetraborate decahydrate (0.76 g) and boric acid (0.13 g) dissolved in 50mL of deionized water was added to the modified PVA solution 2, and the mixture was stirred in a water bath at 95 ℃ and a stirring speed of 600 rpm for 20min to obtain a milky white gel.

(4) And (3) taking out the milky white gel, putting the milky white gel into a mould, pressing for 1h, removing internal bubbles and microcracks to obtain a sample, then freezing for 12h at the temperature of-20 ℃ in a refrigerator, then thawing for 12h at room temperature, and repeatedly freezing and thawing for 3 times to obtain the high-strength low-friction self-repairing artificial articular cartilage material.

Example 2

(2) Adding 5.0g of nano hydroxyapatite into the PVA solution 1, stirring for 2 hours at the water bath temperature of 95 ℃ and the nitrogen atmosphere at the stirring speed of 600 rpm to obtain a modified PVA solution 2.

(4) And (3) taking out the milky white gel, putting the milky white gel into a mould, pressing for 1h, removing internal bubbles and microcracks to obtain a sample, then freezing for 6h at-30 ℃ in a refrigerator, then thawing for 6h at room temperature, and repeatedly freezing and thawing for 4 times to obtain the high-strength low-friction self-repairing artificial articular cartilage material.

Example 3

(2) Adding 7.5g of nano hydroxyapatite into the PVA solution 1, stirring for 2 hours at the water bath temperature of 95 ℃ and the nitrogen atmosphere at the stirring speed of 600 rpm to obtain a modified PVA solution 2.

(4) And (3) taking out the milky white gel, putting the milky white gel into a mould, pressing for 1h, removing internal bubbles and microcracks to obtain a sample, then freezing for 6h at the temperature of-40 ℃ in a refrigerator, then thawing for 6h at room temperature, and repeatedly freezing and thawing for 5 times to obtain the high-strength low-friction self-repairing artificial articular cartilage material.

Example 4

(2) Adding 10g of nano hydroxyapatite into the PVA solution 1, stirring for 2 hours at the water bath temperature of 95 ℃ and the nitrogen atmosphere at the stirring speed of 600 rpm to obtain a modified PVA solution 2.

(4) And (3) taking out the milky white gel, putting the milky white gel into a mold, pressing for 1h, removing internal bubbles and microcracks to obtain a sample, then freezing for 12h at the temperature of-40 ℃ in a refrigerator, then unfreezing for 12h at room temperature, and repeatedly freezing and unfreezing for 3 times to obtain the ultra-fast self-healing hydrogel.

Comparative example 1

A PVA-BB hydrogel was prepared as follows:

(2) A mixed solution of sodium tetraborate decahydrate (0.76 g) and boric acid (0.13 g) dissolved in 50mL of deionized water was added to the modified PVA solution 2, and the mixture was stirred in a water bath at 95 ℃ and a stirring speed of 600 rpm for 20min to obtain a milky white gel.

(3) And taking out the milky white gel, putting the milky white gel into a mold, pressing for 1h, removing internal bubbles and microcracks to obtain a sample, freezing for 6h at the temperature of minus 40 ℃ in a refrigerator, thawing for 6h at room temperature, and repeatedly freezing and thawing for 5 times to obtain the PVA-BB hydrogel.

Example 5: infrared spectrum characterization experiment of hydrogel

Infrared spectroscopy characterization experiments were performed on the hydrogels prepared in example 3. Fourier Transform Infrared (FTIR) characterization was performed on an FTIR spectrometer (IR-8400, Simadzu, Japan).

The infrared spectrogram of the hydrogel containing the high-molecular polymer with various groups can reflect the characteristic functional groups, the detection result is shown in the attached figure 1, and the attached figure 1 shows the infrared spectrogram of the hydrogel prepared in the embodiment 3. As shown in FIG. 1, at 1350 cm^-1The peak at (B) is attributed to the absorption peak of the dynamic boronic ester bond in the double-crosslinked system, 3190-3600 cm^-1The wide absorption band of (a) is due to a large number of hydrogen bonds and tensile vibrations of the amide I band. The hydrogel is successfully synthesized by analysis on an infrared spectrum.

Example 6: tensile Property test of hydrogel

Test standards tensile tests were carried out according to the test for tensile Properties of plastics of GB T1040.3-2006

The hydrogels prepared in example 3 and comparative example 1 were subjected to tensile test testing. In the figure, curve (I) is the original tensile diagram of example 3, curve (II) is the tensile diagram of example 3 after repair, and curve (III) is the tensile stress diagram of comparative example 1.

The samples were tested using a universal tensile tester (LEGEND 2345, streron) at a tensile rate of 20mm/min and the tensile stress and strain of the test samples were recorded, as well as the tensile stress and strain after a 5 s transient self-repair at room temperature after fracture.

The detection result is shown in figure 2, and it can be seen that the tensile strain and tensile stress of the hydrogel are improved by adding the nano hydroxyapatite, and the repairing effect of the borate bond on the hydrogel is improved

Example 7: the ionic hydrogel prepared in example 2 was subjected to a lubricating property test

The test mode is as follows: and (3) placing the ionic hydrogel on a block type bearing table, and performing a ring block type friction experiment test.

Attached figure 3 is a graph of hydrogel friction data.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims

1. A preparation method of PVA/HA double-network hydrogel is characterized by comprising the following steps:

(1) preparing hydrogel by using a thermal crosslinking-freezing thawing method, dissolving polyvinyl alcohol (PVA) with alcoholysis degree of more than 98% in deionized water at 95 ℃ to serve as a reaction raw material, wherein the mass ratio of the deionized water to a polymerized monomer is 1: 0.1-0.2; adopting inert gas for protection; the stirring speed is 500-700 rpm; obtaining a modified PVA solution 1;

(2) adding nano hydroxyapatite serving as a modifier of a system into the PVA solution 1 obtained in the step (1); the stirring speed is 500-700 rpm; stirring for 2h to obtain a modified PVA solution 2;

(3) adding a mixed solution of sodium tetraborate decahydrate and boric acid as a cross-linking agent into the modified PVA solution 2, wherein the mass ratio of the sodium tetraborate decahydrate to the boric acid is 1: 0.1-0.5; carrying out thermal crosslinking, wherein the temperature of the system is 90-95 ℃; preparing milk white gel;

2. The method for preparing PVA/HA double-network hydrogel according to claim 1, wherein: the alcoholysis degree of the polymer monomer PVA in the step (1) is more than 98%.

3. The method for preparing PVA/HA double-network hydrogel according to claim 1, wherein: and (2) the inert atmosphere in the step (1) is nitrogen, argon or helium.

4. The method for preparing PVA/HA double-network hydrogel according to claim 1, wherein: the stirring time in the step (1) is 1-4 h.

5. The method for preparing PVA/HA double-network hydrogel according to claim 1, wherein: the mass ratio of the PVA solution to the modifier in the step (2) is 1: 0.1-1.

6. The method for preparing PVA/HA double-network hydrogel according to claim 1, wherein: in the thermal crosslinking process in the step (3), the stirring speed is 500-700 rpm, the reaction time is 1-20 min, and the milky white gel is prepared.

7. The method for preparing PVA/HA double-network hydrogel according to claim 6, wherein: the reaction time is 10 min-15 min.

8. The method for preparing PVA/HA double-network hydrogel according to claim 1, wherein: in the step (4), the freezing temperature is-20 ℃, the freezing time is 6h, the unfreezing time at room temperature is 12h, and the cycle time is 3 times.

9. A PVA/HA double-network hydrogel prepared by the preparation method of any one of claims 1 to 8, which is characterized in that: the prepared sample has the original tensile stress of 0.3-0.5MPa and the tensile stress of 0.2-0.385MPa after restoration; the friction coefficient is 0.1-0.25.

10. The application of the PVA/HA double-network hydrogel of claim 9 as a high-strength low-friction self-repairing artificial articular cartilage material.