TWI813309B - Biphysical crosslinked hydrogel with tensile induced enhancement, preparation method thereof, and application thereof - Google Patents

Abstract

The present disclosure discloses a biphysical crosslinking hydrogel with tensile induced enhancement, and a preparation method and an application thereof. The hydrogel has a double physical crosslinking (DPC) structure of hydrophobic association (HA) crosslinking and ionic coordination (IC) crosslinking. The hydrogel can keep its complete shape after five continuous cycles of stretching with different strains (50% ~ 250%) or five continuous cycles of stretching with a same strain (200%). After five minutes of recovery at room temperature, the recovery rate of modulus and toughness exceeds 100%, and the hydrogel has ultra-high tensile elongation at break, anti-fatigue, rapid room temperature self-recovery and tensile induced reinforcement (SIS) effect similar to muscle. The HA/IC DPC hydrogel prepared by this disclosure has long service life, simple preparation process, low cost of raw material, and it is beneficial to industrial production and has a good application prospect in the field of biomedicine.

Description

Dual physically cross-linked hydrogel with stretch-induced reinforcement, its preparation, and its application

The present disclosure belongs to the technical field of high-performance hydrogel development, and specifically relates to a multifunctional dual-physical cross-linked hydrogel and its preparation method and application.

Hydrogel is a water-containing material composed of three-dimensional network polymers. Many living tissues in nature (such as cartilage and muscle) are also natural hydrogel materials. Therefore, hydrogel, as a biomimetic material, has attracted more and more attention from researchers in the fields of biomedicine, environmental protection, food and medicine. However, the traditional hydrogels developed in the early stage exhibited low mechanical strength (~10kPa), modulus, and toughness (~170kJ m ^-3 ), which greatly limited the practical application of hydrogel materials.

In order to improve the practical application value of hydrogels, researchers have used various methods to improve the mechanical and mechanical properties of hydrogels in recent years. The most representative ones are: double network (DN) hydrogel, double cross-linked (DC) hydrogel, nanocomposite hydrogel, sliding ring hydrogel, macromolecule microsphere hydrogel, dipole- Hydrogen bond enhanced hydrogel, hydrophobic association hydrogel. Among them, DN and DC hydrogels have attracted much attention due to their special energy dissipation mechanism. DN hydrogel is formed by interpenetrating two polymer networks with different chemical structures. DN hydrogels with excellent mechanical properties usually consist of a small amount of rigid and dense first polymer network and a large amount of soft and loose second highest polymer network. Molecular networks are interspersed with each other. When the hydrogel is subjected to external force, the rigid network is destroyed first, and a large amount of energy is dissipated because the cross-linking points in the rigid network are destroyed. At this time, the soft second polymer The network allows the hydrogel to maintain its intact shape by stretching the polymer chains. Therefore, compared with single-network hydrogels, DN hydrogels have higher mechanical strength, modulus, and toughness. However, both networks in the early developed DN hydrogel were formed through covalent bond cross-linking. Due to the irreversibility of the covalent bond, the covalent bond cannot be reconstructed after it is destroyed, resulting in the hydrogel not having good resistance. Fatigue and self-healing properties affect the service life of hydrogels. In view of this, covalent-physical hybrid double network (HDN) hydrogel and physical double network (PDN) hydrogel were designed and prepared. Due to the reversibility of physical cross-linking points, compared with covalent DN The anti-fatigue and self-healing properties of hydrogels, HDN hydrogels and PDN hydrogels have been significantly improved, especially PDN hydrogels. However, most PDN hydrogels developed so far exhibit low modulus and strength. It is worth mentioning that Professor Gong Jianping’s research group (H.J.Zhang, T.L.Sun, A.K.Zhang, Y.Ikura, T.Nakajima, T.Nonoyama, T.Kurokawa, O.Ito, H. .Ishitobi, J.P.Gong, Adv.Mater.2016,28,4884.) A hydrophobic association-hydrogen bond PDN hydrogel was prepared with amphiphilic triblocks cross-linked by hydrophobic association (HA) The copolymer is the first polymer network, and the polyacrylamide cross-linked by hydrogen bonds is the second polymer network. The HA-hydrogen bonded PDN hydrogel exhibits high modulus, high strength and fast self-healing properties. However, the preparation process of the hydrogel is relatively complex, and organic solvents are used in the preparation process, which is not conducive to environmental protection. Therefore, how to prepare hydrogel materials with high strength, high modulus, high toughness, excellent fatigue resistance and self-healing properties through a simple and environmentally friendly process has become the focus of researchers.

Compared with DN hydrogel, another hydrogel with similar energy dissipation mechanism and simpler preparation process is DC hydrogel. Different from the double network structure, DC hydrogel is solidified and formed by a polymer chain of a chemical structure through two different cross-linking reactions. Common DC hydrogels include covalent-physical hybrid double cross-linked (HDC) hydrogel and double physically cross-linked (DPC) hydrogel. Among them, DPC hydrogel theoretically has better comprehensive mechanical properties. (High strength, high modulus, high toughness, excellent fatigue resistance and self-healing properties) and have received close attention. Inspired by the strengthening and toughening mechanism of DN hydrogel, in DPC hydrogel, a hard and strong cross-linking effect is paired with another soft and weak cross-linking effect, which will help to improve the comprehensive performance of DPC hydrogel. mechanical properties. Ionic coordination (IC) and hydrophobic association (HA) are representatives of strong and weak physical cross-linking effects respectively. Research shows that HA/IC DPC hydrogel does have excellent comprehensive mechanical properties (high strength, high modulus, high toughness, excellent fatigue resistance and self-healing properties). However, according to current research, there is no IC/HA DPC hydrogel material whose mechanical properties can be restored to exceed those of the original spline in a short time at room temperature, that is, HA with a stretch-induced strengthening (SIS) effect. /IC DPC hydrogel material. The SIS effect is a property that is of great value in improving the fatigue resistance of hydrogels, extending the service life of hydrogels, and expanding the application fields of hydrogels.

In view of the above-mentioned deficiencies in the existing technology, the purpose of this disclosure is to provide a multifunctional dual-physical cross-linked hydrogel and its preparation method and application, which solves the problem that the existing DPC hydrogel does not have rapid self-recovery at room temperature and the short-term It exhibits the characteristics of SIS effect within a certain period of time and expands its scope of application.

In order to achieve the above purpose, this disclosure adopts the following technical solution: a preparation method of multifunctional dual physical cross-linked hydrogel, including the following steps:

1) Add semi-interpenetrating natural polymers and hydrophilic olefin monomers to deionized water, then add emulsifier, stir evenly, then add hydrophobic monomers, heat and stir to completely emulsify the system, and obtain solution A; the hydrophilic olefins The monomers include at least one anionic vinyl monomer and one nonionic vinyl monomer.

In this way, the anionic vinyl monomer enters the polymer chain through polymerization, providing a structural basis for subsequent binding of metal cations to form ionic cross-linking points. All anionic vinyl monomers cannot be used, otherwise when there are too many anionic groups in the hydrophilic polymer chain, too many ionic cross-linking points will be formed, causing the hydrogel to become brittle. Cationic olefinic monomers cannot be used, otherwise the cationic olefinic monomer will combine with the anions in the emulsifier, affecting the emulsification effect of the emulsifier. Furthermore, common cationic olefinic monomers are quaternary ammonium salt olefins. Monomers, while the quaternary ammonium salt structure has a certain inhibitory effect on free radical polymerization and is prone to side reactions. Therefore, nonionic vinyl monomers are selected to constitute the main material of the hydrophilic polymer of the hydrogel.

2) Add the initiator solution to the solution A obtained in step 1), stir evenly, and then slowly add it to the mold to perform the polymerization reaction. After the reaction is completed, a semi-interpenetrating network (sIPN) HA hydrogel is obtained;

3) Immerse the sIPN HA hydrogel obtained in step 2) into FeCl ₃ aqueous solution to fully react, take it out and then immerse it in deionized water. After taking it out, the multifunctional dual-physical cross-linked hydrogel is obtained.

In this way, the prepared hydrogel has a dual physical cross-linking (DPC) structure of hydrophobic association (HA) cross-linking and ionic coordination (IC) cross-linking. Among them, the HA cross-linked network is formed by the association of hydrophobic structural units on the amphiphilic copolymer polymer chain, and the semi-interpenetrating natural polymers present a semi-interpenetrating state in the HA cross-linked network. The IC cross-linked network is formed by the ion coordination between -COO ^- on the amphiphilic copolymer polymer chain, -COO ^- on the interpenetrating natural polymer and Fe ³⁺ . The amphiphilic copolymer is formed by free radical copolymerization of hydrophilic vinyl monomers and hydrophobic monomers.

Preferably, the semi-interpenetrating natural polymer is sodium alginate or carboxymethyl cellulose; the hydrophilic vinyl monomer is acrylamide and acrylic acid; the hydrophobic monomer is stearyl methacrylate ester.

Preferably, the emulsifier is sodium dodecylbenzene sulfonate; The initiators are potassium persulfate and sodium bisulfite.

Preferably, the total concentration of hydrophilic vinyl monomers and hydrophobic monomers in the solution A is 2.2~2.8 mol/L.

Preferably, the mass ratio of the anionic vinyl monomer to the nonionic vinyl monomer is 0.1 to 0.15:1.

Preferably, the mass ratio of the semi-interpenetrating natural polymer and the hydrophilic vinyl monomer is 0 to 0.1:1; the mass ratio of the emulsifier to the hydrophilic vinyl monomer is 0.3 to 0.6:1; The mass ratio of initiator to hydrophilic vinyl monomer is 0.005~0.008:1.

Preferably, the polymerization reaction is carried out at 40°C to 60°C for 22 hours (h) to 26 hours.

Preferably, the concentration of the FeCl ₃ aqueous solution is 0.1~0.2mol/L, and the immersion time is 22 hours~26 hours; the immersion time in deionized water is 22 hours~26 hours.

Another object of this disclosure is to also provide a multifunctional dual-physically cross-linked hydrogel prepared by the above method.

Another purpose of this disclosure is to also provide applications of multifunctional dual-physical cross-linked hydrogels in the field of biomedicine, wherein the applications in the field of biomedicine are used in biosensors and tissue engineering scaffolds. , biological material separation, or drug release carrier.

Compared with the existing technology, this disclosure has the following beneficial effects:

1. The hydrogel prepared by this disclosure has a dual physical cross-linking (DPC) structure of hydrophobic association (HA) cross-linking and ionic coordination (IC) cross-linking. Among them, HA is a weak interaction with lower binding energy, while IC is a strong interaction with higher binding energy. The two cross-linking effects work together to effectively improve the comprehensive mechanical and mechanical properties (strength, modulus) of the hydrogel. , elongation at break and toughness). In addition, the reversible characteristics of HA and IC and the compatibility of semi-interpenetrating natural polymers endow the DPC hydrogel with excellent fatigue resistance, rapid self-recovery at room temperature, and stretch-induced reinforcement (SIS) properties. The hydrogel can maintain its complete shape after being subjected to five consecutive cyclic stretches of different strains (50% to 250%) or five consecutive cyclic stretches of the same strain (200%), and recovers for 5 seconds at room temperature. After minutes, the modulus and toughness recovery rates exceeded 100%, showing a typical stretch-induced strengthening (SIS) effect. Expands the functionality and application scope of the hydrogel.

2. The dual physical cross-linked hydrogel disclosed in this disclosure not only has good comprehensive mechanical properties, but also has a muscle-like SIS effect, long service life, simple preparation process, low raw material cost, is conducive to industrial production, and can be used Used as biosensors, tissue engineering scaffolds, biological material separation, drug release carriers, etc. For example, when the dual-physical cross-linked hydrogel disclosed in this disclosure is used as a tissue engineering scaffold material, when the material undergoes multiple deformations on a large scale, the material will not only not break, but will also have improved modulus, toughness and strength. It has been improved with intelligent characteristics and has good application prospects in the field of biomedicine.

The present disclosure will be further described in detail below with reference to specific examples and drawings. The following experimental methods are conventional methods unless otherwise specified. In this article, tensile modulus = Young's modulus = stress/strain ratio. Therefore, the tensile modulus of each tested hydrogel can be obtained by converting the data of the tensile stress-strain curve in the figure.

In the following examples, the modulus, strength, elongation at break, toughness, self-recovery performance and fatigue resistance of DPC hydrogel were characterized by a microcomputer-controlled electronic universal testing machine. The tensile modulus is calculated based on the slope of the tensile stress-strain curve in the strain range of 0% to 20%. The internal energy dissipation is calculated based on the integral of the hysteresis loop area in loop stretching. The calculation formulas of the modulus recovery rate R _M and the internal energy recovery rate R _E are as shown in Equations 1 and 2 respectively.

After continuous loop stretching, the modulus recovery rate R _M after self-recovery for 5 minutes at room temperature is calculated using Equation 1:

In Formula 1, _MR represents the initial tensile modulus of the hydrogel in the first loop stretching after recovering for 5 minutes at room temperature, and M _O represents the initial tensile modulus of the hydrogel in the first loop stretching. Initial tensile modulus.

In Formula 2, S _R represents the integrated area of the stretch-retraction loop in the first loop stretch after the hydrogel has recovered for 5 minutes at room temperature, and S _O represents the stretch-retraction loop area in the first loop stretch of the hydrogel. The integrated area of the stretch-retraction loop.

Example 1

1. Preparation method of stretch-induced reinforced hydrogel

1) After adding 24mL of deionized water to a 100mL beaker, add 3.75g acrylamide (AM), 0.47g acrylic acid (AA), 2.52g sodium dodecylbenzene sulfonate (SDBS) and 0.31g methyl Stearyl acrylate (SMA), heated to 50°C and stirred to completely emulsify the system to obtain solution A.

2) Add 25 mg potassium persulfate and 5 mg sodium bisulfite to 1 mL of deionized water, stir and dissolve evenly to obtain an initiator solution, then add the initiator solution to the solution A obtained in step 1), stir evenly, and then mix the above The solution was poured into a glass sheet/silicone plate mold (10cm*10cm*3mm) made in the laboratory, and the mold was placed in a 50°C oven for 24 hours to carry out polymerization reaction. After the reaction, a semi-interpenetrating network HA hydrogel was obtained. Glue.

3) Use a dumbbell-shaped cutter (50mm*4mm) to cut the HA hydrogel into dumbbell-shaped splines, soak them in FeCl ₃ solutions with concentrations of 0.1M and 0.2M for 24h, and then transfer the hydrogel splines to Soak in deionized water for 24 hours and then take it out to obtain stretch-induced enhanced double physical cross-linking (DPC) hydrogels SA ₀ HA-Fe _0.1 and SA ₀ HA-Fe _0.2 respectively. The HA hydrogel prepared without soaking in FeCl ₃ solution was used as a control and named SA ₀ HA-Fe ₀ .

Hydrogel SA _x HA-Fe _y , where x represents the mass percentage (%) of sodium alginate in the hydrogel, and y represents the concentration of the FeCl ₃ solution (mol/L) in which the hydrogel is soaked (the same below) .

2. Performance verification

1. The tensile stress-strain curves of SA ₀ HA-Fe ₀ , SA ₀ HA-Fe _0.1 and SA ₀ HA-Fe _0.2 hydrogels prepared in this example are shown in Figure 1.

As shown in the figure, the tensile modulus of SA ₀ HA-Fe ₀ , SA ₀ HA-Fe _0.1 and SA ₀ HA-Fe _0.2 hydrogels are 0.012MPa, 0.65MPa and 0.75MPa respectively, and the elongation at break is 2841.6 respectively. %, 1228.6% and 1209.4%, and the fracture energies are 0.31MJ/m ³ , 19.11MJ/m ³ and 17.60MJ/m ³ respectively. It can be seen that the SA ₀ HA-Fe ₀ sIPN hydrogel exhibits soft and tough mechanical properties, and the SA ₀ HA-Fe _0.1 and SA ₀ HA-Fe _0.2 DPC hydrogels exhibit strong and tough mechanical properties.

2. The stress-strain curve of the SA ₀ HA-Fe _0.1 DPC hydrogel after five consecutive cyclic stretches and another cyclic stretch after recovery for 5 minutes at room temperature (fixed maximum strain is 200%) is as shown in Section 2 As shown in the figure.

As shown in the figure, the modulus of SA ₀ HA-Fe _0.1 DPC hydrogel after five cycles of stretching are 1.63MPa, 0.24MPa, 0.15MPa, 0.12MPa and 0.11MPa respectively, and the water solidifies after 5 minutes of recovery at room temperature. The modulus of the glue is 2.21MPa, and the modulus recovery rate is 135.6%. The internal energy consumption of SA0HA-Fe0.1 DPC hydrogel during five loop stretches is 1.36MJ/m ³ , 0.56MJ/m ³ , 0.45MJ/m ³ , 0.40MJ/m ³ and 0.36MJ/m ³ respectively. After 5 minutes of recovery at room temperature, the internal dissipation energy of the hydrogel was 1.86MJ/m ³ , and the internal dissipation energy recovery rate was 136.8%. It can be seen that the hydrogel exhibits excellent room temperature self-recovery ability and typical stretch-induced strengthening (SIS) effect.

3. The continuous loop stretching curves of SA ₀ HA-Fe _0.1 DPC hydrogel under different maximum strains (50% -250%) are shown in Figure 3.

As shown in the figure, the modulus of the SA ₀ HA-Fe _0.1 DPC hydrogel in five cycles of stretching are 2.11MPa, 1.87MPa, 1.24MPa, 0.44MPa and 0.19MPa respectively. It can be seen that the hydrogel The rubber can still maintain its complete shape after five cycles of gradually increasing strain, showing good fatigue resistance.

4. The stress-strain curve of SA ₀ HA-Fe _0.2 DPC hydrogel after five consecutive cyclic stretches and another cyclic stretch after recovery for 5 minutes at room temperature (fixed maximum strain is 200%) is as shown in Section 4 As shown in the figure.

As shown in the figure, the modulus of SA ₀ HA-Fe _0.2 DPC hydrogel after five cycles of stretching are 1.28MPa, 0.25MPa, 0.16MPa, 0.13MPa and 0.12MPa respectively, and the water solidifies after 5 minutes of recovery at room temperature. The modulus of the glue is 1.49MPa, and the modulus recovery rate is 116.4%. The internal energy consumption of SA ₀ HA-Fe _0.2 DPC hydrogel during five loop stretches is 1.06MJ/m ³ , 0.48MJ/m ³ , 0.39MJ/m ³ , 0.35MJ/m ³ and 0.32MJ/m respectively. ^3. After 5 minutes of recovery at room temperature, the internal dissipation energy of the hydrogel is 1.37MJ/m ³ , and the internal dissipation energy recovery rate is 129.2%. It can be seen that the hydrogel exhibits excellent room temperature self-recovery ability and typical stretch-induced strengthening (SIS) effect.

5. The continuous loop stretching curves of SA ₀ HA-Fe _0.2 DPC hydrogel under different maximum strains (50% -250%) are shown in Figure 5.

As shown in the figure, the modulus of the SA ₀ HA-Fe _0.2 DPC hydrogel in five cycles of stretching are 1.67MPa, 1.59MPa, 1.04MPa, 0.40MPa and 0.16MPa respectively. It can be seen that the hydrogel can still maintain its complete shape after five cycles of gradually increasing strain, showing good fatigue resistance.

Example 2

1. Preparation method of stretch-induced reinforced hydrogel

1) Add 24 mL deionized water and 0.2 g sodium alginate (SA) into a 100 mL beaker. After SA is completely dissolved and evenly distributed, add 3.75 g acrylamide (AM), 0.47 g acrylic acid (AA), and 2.52 g dodecylamine in sequence. Sodium alkyl benzene sulfonate (SDBS) and 0.31g stearyl methacrylate (SMA) were heated to 50°C and stirred to completely emulsify the system to obtain solution A.

2) Add 25 mg potassium persulfate and 5 mg sodium bisulfite to 1 mL of deionized water, stir and dissolve evenly to obtain an initiator solution, then add the initiator solution to the solution A obtained in step 1), stir evenly, and then mix the above The solution is poured into a glass sheet/silicone plate mold (10cm*10cm*3mm) made in the laboratory, and the mold is placed in a 50°C oven for 24 hours to carry out polymerization reaction. After the reaction is completed, a semi-interpenetrating network (sIPN) HA is obtained. hydrogel.

3) Use a dumbbell-shaped cutter (50mm*4mm) to cut the sIPN HA hydrogel obtained in step 2) into dumbbell-shaped splines, and then soak the hydrogel splines in FeCl ₃ at concentrations of 0.1M and 0.2M respectively. solution for 24h, and then the hydrogel splines were transferred to deionized water and soaked for 24h to obtain stretch-induced enhanced dual physical cross-linking (DPC) hydrogels SA _0.6 HA-Fe _0.1 and SA _0.6 HA-Fe respectively. _0.2 . The HA hydrogel prepared without soaking in FeCl ₃ solution was used as a control and named SA _0.6 HA-Fe ₀ .

2. Performance verification

1. The tensile stress-strain curves of SA _0.6 HA-Fe ₀ , SA _0.6 HA-Fe _0.1 and SA _0.6 HA-Fe _0.2 hydrogels prepared in this example are shown in Figure 6.

As shown in the figure, the tensile modulus of SA _0.6 HA-Fe ₀ , SA _0.6 HA-Fe _0.1 and SA _0.6 HA-Fe _0.2 hydrogels are 0.023MPa, 0.88MPa and 1.07MPa respectively, and the elongation at break is respectively 2603.2%, 869.1% and 950.8%, and the fracture energies are 1.59MJ/m ³ , 14.97MJ/m ³ and 18.02MJ/m ³ respectively. It can be seen that the SA _0.6 HA-Fe ₀ sIPN hydrogel exhibits soft and tough mechanical properties, and the SA _0.6 HA-Fe _0.1 and SA _0.6 HA-Fe _0.2 DPC hydrogels exhibit strong and tough mechanical properties.

2. The curve of five consecutive cyclic stretching tests of SA _0.6 HA-Fe _0.1 DPC hydrogel and another cyclic stretching after returning to room temperature for 5 minutes (fixed maximum strain is 200%) is shown in Figure 7.

As shown in the figure, the modulus of SA _0.6 HA-Fe _0.1 DPC hydrogel after five cycles of stretching are 1.70MPa, 0.28MPa, 0.17MPa, 0.14MPa and 0.12MPa respectively. The modulus after recovery for 5 minutes at room temperature is The amount is 2.14MPa, and the modulus recovery rate is 125.9%; the internal energy consumption of SA _0.6 HA-Fe _0.1 DPC hydrogel during five loop stretching is 1.63MJ/m ³ , 0.58MJ/m ³ , and 0.46MJ/m respectively. ³ , 0.40MJ/m ³ and 0.37MJ/m ³ , the internal consumption energy after 5 minutes of recovery at room temperature is 2.01MJ/m ³ , and the internal energy recovery rate is 123.3%. It can be seen that the hydrogel exhibits excellent self-healing properties and typical SIS effect.

3. The loop stretching curves of SA _0.6 HA-Fe _0.1 DPC hydrogel under different strains (50% - 250%) are shown in Figure 8.

As shown in the figure, the modulus of the SA _0.6 HA-Fe _0.1 DPC hydrogel in five consecutive cycles of stretching are 2.29MPa, 2.05MPa, 1.42MPa, 0.60MPa and 0.21MPa respectively. Five consecutive cycles of gradually increasing strain can still maintain the complete shape, showing good fatigue resistance.

4. The curve of five consecutive cyclic stretching tests of SA _0.6 HA-Fe _0.2 DPC hydrogel and cyclic stretching after returning to room temperature for 5 minutes (fixed maximum strain is 200%) is shown in Figure 9.

As shown in the figure, the modulus of SA _0.6 HA-Fe _0.2 DPC hydrogel after five cycles of stretching are 1.74MPa, 0.31MPa, 0.19MPa, 0.16MPa and 0.15MPa respectively. The modulus of the SA 0.6 HA-Fe 0.2 DPC hydrogel after recovery for 5 minutes at room temperature is The amount is 1.99MPa, and the modulus recovery rate is 114.4%; the internal energy consumption of five loop stretching is 1.50MJ/m ³ , 0.65MJ/m ³ , 0.50MJ/m ³ , 0.44MJ/m ³ and 0.40MJ respectively. /m ³ , the internal energy consumption after 5 minutes of recovery at room temperature is 1.78MJ/m ³ , and the internal energy recovery rate is 118.7%. It can be seen that the hydrogel exhibits excellent self-healing properties and typical SIS effect.

5. The loop stretching curves of SA _0.6 HA-Fe _0.2 DPC hydrogel under different strains (50% -250%) are shown in Figure 10.

As shown in the figure, the modulus of the SA _0.6 HA-Fe _0.2 DPC hydrogel in five consecutive cyclic stretches are 2.63MPa, 2.26MPa, 1.48MPa, 0.42MPa and 0.17MPa respectively. The hydrogel After five consecutive cycles of gradually increasing strain, it can still maintain its complete shape and exhibit good fatigue resistance.

Example 3

1. Preparation method of stretch-induced reinforced hydrogel

1) Add 24mL deionized water and 0.4g sodium alginate (SA) into a 100mL beaker. After SA is completely dissolved and evenly distributed, add 3.75g acrylamide (AM), 0.47g acrylic acid (AA), 2.52g ten Sodium dialkyl benzene sulfonate (SDBS) and 0.31g stearyl methacrylate (SMA) were heated to 50°C and stirred to completely emulsify the system to obtain solution A.

2) Add 25 mg potassium persulfate and 5 mg sodium bisulfite to 1 mL of deionized water. Stir and dissolve evenly to obtain an initiator solution. Add the initiator solution to solution A and stir evenly. Then pour the above mixed solution into the experiment. A self-made glass sheet/silicone plate mold (10cm*10cm*3mm) was placed in a 50°C oven for 24 hours to perform polymerization reaction. After the reaction, a semi-interpenetrating network (sIPN) HA hydrogel was obtained.

3) Use a dumbbell-shaped cutter (50mm*4mm) to cut the sIPN HA hydrogel into dumbbell-shaped splines. Soak the hydrogel splines in FeCl ₃ solutions with concentrations of 0.1M and 0.2M for 24h respectively, and then add water to them. After the gel strips were transferred to deionized water and soaked for 24 hours, stretch-induced enhanced double physical cross-linking (DPC) hydrogels SA _1.2 HA-Fe _0.1 and SA _1.2 HA-Fe _0.2 were obtained respectively. The HA hydrogel prepared without soaking in FeCl ₃ solution was used as a control and named SA _1.2 HA-Fe ₀ .

2. Performance verification

1. The tensile stress-strain curves of SA _1.2 HA-Fe ₀ , SA _1.2 HA-Fe _0.1 and SA _1.2 HA-Fe _0.2 hydrogels prepared in this example are shown in Figure 11.

As shown in the figure, the tensile modulus of SA _1.2 HA-Fe ₀ , SA _1.2 HA-Fe _0.1 and SA _1.2 HA-Fe _0.2 hydrogels are 0.027MPa, 0.99MPa and 1.18MPa respectively, and the elongation at break is 2658.1 respectively. %, 952.0% and 775.7%, and the fracture energies are 2.12MJ/m ³ , 16.04MJ/m ³ and 14.25MJ/m ³ respectively. It can be seen that the SA _1.2 HA-Fe ₀ sIPN hydrogel exhibits soft and tough mechanical properties, and the SA _1.2 HA-Fe _0.1 and SA _1.2 HA-Fe _0.2 DPC hydrogels exhibit strong and tough mechanical properties.

2. The curve of five consecutive loop stretching tests of SA _1.2 HA-Fe _0.1 DPC hydrogel and another loop stretching after recovery for 5 minutes (fixed maximum strain is 200%) is shown in Figure 12.

As shown in the figure, the modulus of the SA _1.2 HA-Fe _0.1 DPC hydrogel after five consecutive cyclic stretches are 1.65MPa, 0.32MPa, 0.21MPa, 0.18MPa and 0.16MPa respectively. After recovery for 5 minutes at room temperature The modulus is 2.27MPa, and the modulus recovery rate is 137.6%; the internal energy consumption of SA _1.2 HA-Fe _0.1 DPC hydrogel for five consecutive loop stretches is 1.48MJ/m ³ , 0.60MJ/m ³ , and 0.48MJ respectively. /m ³ , 0.43MJ/m ³ and 0.39MJ/m ³ , the internal energy consumption after 5 minutes of recovery at room temperature is 2.24MJ/m ³ , and the internal energy recovery rate is 151.4%. It can be seen that the hydrogel exhibits excellent self-healing ability.

3. The loop stretching curves of SA _1.2 HA-Fe _0.1 DPC hydrogel under different strains (50% -250%) are shown in Figure 13.

As shown in the figure, the modulus of SA _1.2 HA-Fe _0.1 DPC hydrogel after five consecutive cycles of stretching are 2.49MPa, 2.22MPa, 1.48MPa, 0.60MPa and 0.26MPa respectively. Cyclic stretching with increasing strain can still maintain the complete shape and exhibit good fatigue resistance.

4. The curve of five consecutive loop stretching tests of SA _1.2 HA-Fe _0.2 DPC hydrogel and another loop stretching test after recovery for 5 minutes (fixed maximum strain is 200%) is shown in Figure 14.

As shown in the figure, the modulus of SA _1.2 HA-Fe _0.2 DPC hydrogel after five consecutive cyclic stretches are 2.76MPa, 0.19MPa, 0.16MPa, 0.15MPa and 0.14MPa respectively. After recovery for 5 minutes at room temperature The modulus is 2.68MPa, and the modulus recovery rate is 97.1%; the internal energy consumption of SA _1.2 HA-Fe _0.2 DPC hydrogel for five consecutive loop stretches is 2.39MJ/m ³ , 0.83MJ/m ³ , and 0.65MJ respectively. /m ³ , 0.58MJ/m ³ and 0.52MJ/m ³ , the internal consumption energy after 5 minutes of recovery at room temperature is 2.81MJ/m ³ , and the internal energy recovery rate is 117.6%, showing excellent self-recovery ability.

5. The loop stretching curves of SA _1.2 HA-Fe _0.2 DPC hydrogel under different strains (50% -250%) are shown in Figure 15.

As shown in the figure, the modulus of the SA _1.2 HA-Fe _0.2 DPC hydrogel after five consecutive cycles of stretching are 2.80MPa, 2.45MPa, 1.62MPa, 0.68MPa and 0.25MPa respectively. It can still maintain its complete shape under large-strain cyclic stretching, showing good fatigue resistance.

In summary, when the hydrogel was subjected to five consecutive cyclic tensile tests with different strains (50% to 250%), when the maximum strain was between 50% and 200%, the modulus of the hydrogel decreased rapidly and significantly. , when the maximum strain reaches 200% and above, the decreasing trend of the hydrogel modulus becomes gentle, indicating that the rate of destruction and reconstruction of physical cross-linking points in the hydrogel has gradually reached a dynamic equilibrium, showing The DPC hydrogel has excellent anti-fatigue properties. During five consecutive cyclic stretching tests at the same strain (200%), the modulus of the hydrogel decreased significantly during the second 200% cyclic stretching test, while the modulus decreased significantly during the third to fifth 200% cyclic stretching tests. During the loop stretching, the modulus has been basically maintained constant. This result shows that during the first large strain loop stretching of the DPC hydrogel, part of the physical cross-linking points are destroyed, thereby effectively dissipating energy. During the subsequent large-strain loop stretching, the speed at which the physical cross-linking points are destroyed and the speed at which they are reconstructed have basically reached a dynamic balance, and the modulus and internal energy consumption have been basically maintained constant, demonstrating the excellent large-strain resistance of DPC hydrogel. Sub-cycle stretch and fatigue resistance properties.

After the hydrogel of the present disclosure is subjected to an external tensile force, the modulus and internal energy dissipation can be restored to more than 100% of the original spline after 5 minutes at room temperature, reflecting an obvious stretch-induced enhancement (SIS) effect. This is because when the hydrogel disclosed in this disclosure is subjected to an external tensile force, part of the physical cross-linking points are destroyed, and at the same time, the polymer chains are oriented along the stretching direction. After the external force is removed, the physical cross-linking points are rebuilt and the physical cross-linking points are re-established. The reconstruction of the junction limits the complete relaxation of the polymer chain, thereby locking the polymer chain in an oriented conformation, so that the modulus and internal energy consumption of the hydrogel can be restored to more than 100% of the original spline. It can be seen that the HA/IC DPC hydrogel of the present disclosure has rapid self-healing properties. After five cycles of HA/IC DPC hydrogel at 200% and recovery for 5 minutes, the cross-sectional area of the thin neck part of the dumbbell-shaped hydrogel decreased significantly, indicating that the polymer chains in the thin neck part of the hydrogel were more tightly packed. , the polymer chain gap is lower. This phenomenon confirms from another aspect that the polymer chains in the HA/IC DPC hydrogel are oriented and arranged regularly after stretching. The HA/IC DPC hydrogel has muscle-like stretch-induced strengthening behavior, giving the hydrogel excellent anti-fatigue properties and long service life.

Comparative example 1

In Example 2, 0.1g polyvinyl alcohol (PVA) was added to solution A for preparing semi-interpenetrating network (sIPN) HA hydrogel, and the prepared sIPN hydrogel was frozen in a -20°C freezer for 24 hours. , then take it out, place it at room temperature for 2 hours, cycle freeze and return to room temperature three times, and obtain hydrophobic association-microcrystalline double network hydrogel (HMDN). Then use a dumbbell-shaped cutter to cut the HMDN hydrogel into a dumbbell shape. The dumbbell-shaped spline is immersed in 0.1M FeCl ₃ solution for 24 hours. Then the spline is taken out and immersed in deionized water for 24 hours to obtain fully physical cross-linked triple interpenetration. Network hydrogel (same as CN110591121A).

Comparative example 2

0.2g polyvinyl alcohol (PVA) was added to solution A, and other steps were the same as in Comparative Example 1.

Comparative example 3

0.4g polyvinyl alcohol (PVA) was added to solution A, and other steps were the same as in Comparative Example 1.

The fully physically cross-linked triple interpenetrating network hydrogels prepared in Examples 1 to 3 were stretched in five consecutive cycles at 200% strain, then recovered at room temperature for 260 minutes, and then again subjected to 200% strain. The lower loop tensile stress-strain curves are shown in Figures 16 to 18 respectively.

As shown in the figure, the fully physically cross-linked triple interpenetrating network hydrogel prepared in Comparative Example 1 has a modulus of 86.4KPa and an internal consumption energy of 69KJ/m ³ at the first loop stretch under 200% strain. The modulus during the fifth loop stretching under 200% strain is 54.3KPa, and the internal dissipation energy is 14KJ/m ³ . After recovery at room temperature for 260 minutes, the modulus during loop stretching under 200% strain is 73.9KPa, the internal dissipation energy is 46KJ/m ³ , the modulus recovery rate is 85.5%, and the internal dissipation energy recovery rate is 66.7%. The fully physically cross-linked triple interpenetrating network hydrogel prepared in Comparative Example 2 has a modulus of 104.5KPa and an internal consumption energy of 73KJ/m ³ at the first loop stretch under 200% strain. The modulus during the fifth loop stretching is 59.8KPa, and the internal energy consumption is 14KJ/m ³ . After recovery at room temperature for 260 minutes, the modulus during loop stretching under 200% strain is 86.1KPa, and the internal energy consumption is 86.1KPa. It is 49KJ/m ³ , the modulus recovery rate is 82.4%, and the internal energy consumption recovery rate is 67.1%. The fully physically cross-linked triple interpenetrating network hydrogel prepared in Comparative Example 3 has a modulus of 94.8KPa and an internal consumption energy of 73KJ/m ³ at the first loop stretch under 200% strain. The modulus during the fifth loop stretching is 56.8KPa, and the internal energy consumption is 13KJ/m ³ . After recovery at room temperature for 260 minutes, the modulus during loop stretching under 200% strain is 85.9KPa, and the internal energy consumption is 85.9KPa. It is 51KJ/m ³ , the modulus recovery rate is 90.6%, and the internal energy consumption recovery rate is 69.9%.

In summary, although the fully physically cross-linked triple interpenetrating network hydrogel prepared in the comparative example contains hydrophobic association and ionic cross-linking methods, it does not have rapid self-recovery properties at room temperature and muscle-like stretch-induced enhancement ( SIS) effect. This may be because there are three cross-linking modes: hydrophobic association, microcrystalline and ionic cross-linking in fully physically cross-linked triple interpenetrating network hydrogel. Compared with double physical cross-linking hydrogel, triple interpenetrating network hydrogel has The high density of physical cross-linking points in the gel restricts the movement of polymer chains, thereby reducing the reconstruction rate of physical cross-linking points, thereby weakening the room temperature self-recovery performance of the hydrogel.

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present disclosure and are not limiting. Although the present disclosure has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the present disclosure can be modified. If the technical solution is modified or equivalently substituted without departing from the purpose and scope of the technical solution disclosed in this disclosure, they shall all be covered by the scope of the claims of the present invention.

without

Figure 1 is the tensile stress-strain curve of SA ₀ HA-Fe ₀ , SA ₀ HA-Fe _0.1 and SA ₀ HA-Fe _0.2 hydrogels prepared in Example 1 of the present disclosure. Figure 2 shows the stress-strain curve of the SA ₀ HA-Fe _0.1 DPC hydrogel prepared in Example 1 of the disclosure after five consecutive cyclic stretches and another cyclic stretch after recovery for 5 minutes at room temperature (fixed maximum strain to 200%). Figure 3 shows the continuous loop stretching curves of the SA ₀ HA-Fe _0.1 DPC hydrogel prepared in Example 1 of the present disclosure under different maximum strains (50% - 250%). Figure 4 shows the stress-strain curve of SA ₀ HA-Fe _0.2 DPC prepared in Example 1 of the present disclosure after five consecutive loop stretches and another loop stretch after recovery for 5 minutes at room temperature (the maximum strain is fixed at 200 %). Figure 5 shows the continuous loop stretching curves of the SA ₀ HA-Fe _0.2 DPC hydrogel prepared in Example 1 of the present disclosure under different maximum strains (50% - 250%). Figure 6 shows the tensile stress-strain curves of SA _0.6 HA-Fe ₀ , SA _0.6 HA-Fe _0.1 and SA _0.6 HA-Fe _0.2 hydrogels prepared in Example 2 of the present disclosure. Figure 7 shows the stress-strain curve of the SA _0.6 HA-Fe _0.1 DPC hydrogel prepared in Example 2 of the present disclosure after five consecutive cyclic stretches and another cyclic stretch after recovery for 5 minutes at room temperature (fixed maximum strain to 200%). Figure 8 shows the continuous loop stretching curves of the SA _0.6 HA-Fe _0.1 DPC hydrogel prepared in Example 2 of the disclosure under different maximum strains (50% -250%). Figure 9 shows the stress-strain curve of the SA _0.6 HA-Fe _0.2 DPC hydrogel prepared in Example 2 of the disclosure after five consecutive cyclic stretches and another cyclic stretch after recovery for 5 minutes at room temperature (fixed maximum The strain is 200%); Figure 10 shows the continuous loop stretching curves of the SA _0.6 HA-Fe _0.2 DPC hydrogel prepared in Example 2 of the present disclosure under different maximum strains (50% - 250%). Figure 11 shows the tensile stress-strain curves of SA _1.2 HA-Fe ₀ , SA _1.2 HA-Fe _0.1 and SA _1.2 HA-Fe _0.2 hydrogels prepared in Example 3 of the present disclosure. Figure 12 shows the stress-strain curve of the SA _1.2 HA-Fe _0.1 DPC hydrogel prepared in Example 3 of the disclosure after five consecutive cyclic stretches and another cyclic stretch after recovery for 5 minutes at room temperature (fixed maximum strain to 200%). Figure 13 shows the continuous loop stretching curves of the SA _1.2 HA-Fe _0.1 DPC hydrogel prepared in Example 3 of the present disclosure under different maximum strains (50% - 250%). Figure 14 shows the stress-strain curve of the SA _1.2 HA-Fe _0.2 DPC hydrogel prepared in Example 3 of the disclosure after five consecutive cyclic stretches and another cyclic stretch after recovery for 5 minutes at room temperature (fixed maximum strain to 200%). Figure 15 shows the continuous loop stretching curves of the SA _1.2 HA-Fe _0.2 DPC hydrogel prepared in Example 3 of the disclosure under different maximum strains (50% - 250%). Figure 16 shows the stress-strain curve of the hydrogel prepared in Comparative Example 1 after five consecutive cyclic stretches, then recovered at room temperature for 260 minutes and then cyclically stretched again (the fixed maximum strain is 200%). Figure 17 shows the stress-strain curve of the hydrogel prepared in Comparative Example 2 after five consecutive cyclic stretches, and then recovered at room temperature for 260 minutes and then cyclically stretched again (the maximum strain is fixed at 200%). Figure 18 shows the stress-strain curve of the hydrogel prepared in Comparative Example 3 after five consecutive cyclic stretches, and then recovered at room temperature for 260 minutes and then cyclically stretched again (the maximum strain is fixed at 200%).

Domestic storage information (please note in order of storage institution, date and number) without Overseas storage information (please note in order of storage country, institution, date, and number) without

Claims (5)

A method for preparing dual physical cross-linked hydrogels, including the following steps: 1) Add semi-interpenetrating natural polymers and hydrophilic vinyl monomers to deionized water, then add emulsifier, stir evenly, and then add hydrophobic monomers , heat and stir to completely emulsify the system, and obtain solution A, in which the hydrophilic olefinic monomer includes at least one anionic olefinic monomer and a nonionic olefinic monomer, and the semi-interpenetrating natural polymer is alginic acid Sodium, carboxymethyl cellulose or carrageenan, the non-ionic vinyl monomer is acrylamide or methacrylamide, the anionic vinyl monomer is acrylic acid, methacrylic acid, p-phenylene Sodium ethylene sulfonate or 2-acrylamide-2-methylpropanesulfonic acid, the hydrophobic monomer is stearyl methacrylate, cetyl methacrylate, stearyl acrylate Or cetyl acrylate, the emulsifier is sodium dodecylbenzene sulfonate or sodium dodecyl sulfonate, the initiator is potassium persulfate or sodium bisulfite, and the solution A is hydrophilic The total concentration of the olefinic monomer and the hydrophobic monomer is 2.2~2.8mol/L, the mass ratio of the anionic olefinic monomer and the nonionic olefinic monomer is 0.1~0.15:1, and the semi-interpenetrating The mass ratio of natural polymers to hydrophilic vinyl monomers is 0.047~0.1:1; the mass ratio of the emulsifier to hydrophilic vinyl monomers is 0.3~0.6:1; the mass ratio of the initiator to hydrophilic vinyl monomers The mass ratio is 0.005~0.008:1; 2) Add the initiator solution to the solution A obtained in step 1), stir evenly, and then slowly add it to the mold to perform the polymerization reaction. When the reaction is completed, a semi-interpenetrating network is obtained Hydrophobic association hydrogel; and 3) immerse the semi-interpenetrating network hydrophobic association hydrogel obtained in step 2) in FeCl ₃ aqueous solution to fully react, take it out and then immerse it in deionized water, and after taking it out, obtain The double physically cross-linked hydrogel. The method for preparing double physically cross-linked hydrogel according to claim 1, wherein the polymerization reaction is carried out at 40°C to 60°C for 22 hours to 26 hours. The preparation method of double physical cross-linked hydrogel according to claim 1, wherein the concentration of the FeCl ₃ aqueous solution is 0.1~0.2mol/L, and the immersion time is 22 hours~26 hours; the immersion in the deionized water The time is 22 hours to 26 hours. A double physically cross-linked hydrogel prepared by the method for preparing double physically cross-linked hydrogel according to any one of claims 1 to 3. An application of the dual physical cross-linked hydrogel as described in claim 4 in the field of biomedicine, wherein the application in the field of biomedicine is for biosensors, tissue engineering scaffolds, biological material separation, or drug release carrier.