CN116396426A

CN116396426A - Shape memory hydrogel and application thereof

Info

Publication number: CN116396426A
Application number: CN202310368521.1A
Authority: CN
Inventors: 杨小牛; 杨磊; 吕红英; 李硕; 赵梓健
Original assignee: Changchun Institute of Applied Chemistry of CAS
Current assignee: Changchun Institute of Applied Chemistry of CAS
Priority date: 2023-04-07
Filing date: 2023-04-07
Publication date: 2023-07-07

Abstract

The invention provides a shape memory hydrogel and application thereof. The shape memory hydrogel is obtained by cross-linking polymerization of a hydrophobic monomer and a hydrophilic monomer, wherein the hydrophobic monomer comprises 2-methacrylic acid amino ethyl carbamate isopropyl ester, and the hydrophilic monomer comprises methacrylic acid sulfobetaine. The invention can regulate and control the hydrogel with shape transition near body temperature by polymerizing IMA with excellent mechanical property and multiple hydrophobic aggregation crosslinking points and SBMA with lower highest critical dissolution temperature. Meanwhile, ionic bonds are formed between sulfobetaine groups in SBMA, so that the mechanical property of the shape memory hydrogel is further enhanced. In addition, the SBMA can lead the prepared shape memory hydrogel to have wider shape transition temperature, so that the shape memory hydrogel can have more complex triple memory capability, and has wider future practical application prospect.

Description

Shape memory hydrogel and application thereof

Technical Field

The invention belongs to the technical field of high polymer materials, and particularly relates to a shape memory hydrogel and application thereof.

Background

Shape Memory Hydrogels (SMHs) are smart materials that have great potential for advanced materials because they can memorize one or more temporary shapes and recover their shape upon external stimuli such as light, heat, water, etc. Shape memory hydrogels have received increasing attention in the fields of sensors, actuators, artificial muscles, soft robots, drug delivery, and the like over the last decade. In particular, SMHs have 3D structures and tissue-like aqueous environments and play a critical role in biomedical applications (e.g., as implantable materials for use in the human body).

In general, suitable trigger temperatures and strong mechanical strength are two basic requirements that must be met by thermally responsive SMHs for use as biomedical materials. On the one hand, too high trigger temperatures are not suitable for in vivo applications, as temperatures exceeding 50 ℃ may cause irreversible damage to the tissue. Therefore, thermally responsive SMHs with low deformation trigger temperature and approximately 37 ℃ are more suitable for application in the biomedical field. On the other hand, reversible weak interactions and repeated force-induced cracking lead to poor mechanical properties of SMHs, and low mechanical strength cannot meet the bearing performance, thereby limiting the application of the SMHs. In addition, the wider the glass transition temperature range of the shape memory hydrogel, the more transition temperatures of the gel are indicated, which is beneficial to the gel to memorize more shapes and generate more complex shape memory behaviors, and the practical application prospect is wider. However, it remains a challenge to produce thermally responsive SMHs that trigger temperatures near body temperature, have excellent mechanical strength and broad transition temperatures.

Disclosure of Invention

In view of the above, the present invention is directed to a shape memory hydrogel and its application. The glass transition temperature of the shape memory hydrogel is near the body temperature, and the shape memory hydrogel has excellent mechanical strength and wider shape transition temperature.

In order to achieve the purpose, the invention adopts the following technical scheme:

in a first aspect, the present invention provides a shape memory hydrogel, obtained by cross-linking polymerization of a hydrophobic monomer and a hydrophilic monomer;

the hydrophobic monomer comprises 2-methacrylic acid amino ethyl carbamate isopropyl ester;

the hydrophilic monomer includes sulfobetaine methacrylate.

Preferably, the molar ratio of the hydrophobic monomer to the hydrophilic monomer is (1-12): 1.

In a second aspect, the present invention provides a method for preparing the shape memory hydrogel, comprising the following steps:

(1) Mixing a hydrophobic monomer, a hydrophilic monomer, a chemical cross-linking agent, an initiator and a solvent, and performing polymerization reaction under an anaerobic condition to obtain organogel;

the solvent is a mixed solution of an organic solvent and water;

(2) Immersing the organogel in water to exchange the organogel out of the organic solvent until equilibrium is reached, thereby obtaining the shape memory hydrogel.

Preferably, the ratio of the total mole number of the hydrophobic monomer and the hydrophilic monomer to the mole number of the chemical crosslinking agent is 1 (0.005 to 0.1).

Preferably, the ratio of the total mole number of the hydrophobic monomer and the hydrophilic monomer to the mole number of the initiator is 1 (0.002 to 0.005).

Preferably, the chemical crosslinking agent comprises any one or more of N, N-methylene acrylamide, N-methylene acrylamide derivatives, ethylene glycol dimethacrylate or ethylene glycol dimethacrylate derivatives.

Preferably, the free radical initiator comprises a photoinitiator and/or a thermal initiator.

Preferably, the organic solvent comprises any one or more of dimethyl sulfoxide, dichloromethane, tetrahydrofuran or N, N-dimethylformamide.

Preferably, the temperature of the polymerization reaction is 50-80 ℃ and the time is 6-14 h.

In a third aspect, the present invention provides an implantable medical device material comprising a shape memory hydrogel as referred to in the above technical solutions.

Compared with the prior art, the invention has the beneficial effects that:

the invention provides a shape memory hydrogel which is obtained by polymerizing hydrophobic monomers of 2-methyl ethyl amino ethyl carbamate (IMA) and zwitterionic methyl acrylic Sulfobetaine (SBMA), and has good biocompatibility. The invention can regulate and control the hydrogel suitable for shape transformation near the body temperature by introducing SBMA with lower highest critical dissolution temperature (17-22 ℃). Meanwhile, the SBMA is a hydrophilic monomer, small and uniform hydrophobic aggregation crosslinking points are regulated by utilizing the hydrophilism of the SBMA, and ionic bonds are formed between sulfobetaine groups in the SBMA, so that the mechanical property of the shape memory hydrogel is further enhanced. In addition, the SBMA can lead the prepared shape memory hydrogel to have wider shape transition temperature, so that the shape memory hydrogel can have more complex triple memory capability, and has wider future practical application prospect.

Drawings

FIG. 1 is a macroscopic view of the hydrogels obtained in examples 1 to 5;

FIG. 2 is a graph showing the tensile stress-strain curves of the hydrogels obtained in examples 1 to 5;

FIG. 3 is a graph of storage modulus/loss factor versus temperature for the hydrogels obtained in example 1;

FIG. 4 is a graph showing cyclic compressive stress-strain curves of the hydrogels obtained in example 1;

FIG. 5 is a graph showing the compression modulus and the compression strength of the hydrogel obtained in example 1 at various cycle times;

FIG. 6 is a graph showing the shape retention and shape recovery of the hydrogels obtained in examples 1 to 5;

FIG. 7 is a graph showing the results of the triple memory test of the hydrogel obtained in example 1;

FIG. 8 is a graph showing the macroscopic shape change of the hydrogel obtained in example 1 at various temperatures.

Detailed Description

The technical solutions of the present invention will be clearly and completely described in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

Aiming at the problem that the shape memory hydrogel in the prior art cannot simultaneously meet the trigger temperature near the body temperature, excellent mechanical strength and wider transition temperature, the invention provides the shape memory hydrogel which is obtained by cross-linking polymerization of a hydrophobic monomer and a hydrophilic monomer. Wherein the hydrophobic monomer comprises isopropyl 2-methacrylate (IMA) and the hydrophilic monomer comprises sulfobetaine methacrylate (SBMA). According to researches, if the molar ratio of IMA to SBMA is more than 12:1, the obtained gel is brittle, has high strength, but poor toughness, and is similar to plastics; if the molar ratio of IMA to SBMA is less than 1:1, the obtained gel has good toughness but low strength, and is similar to rubber. Thus, in some embodiments of the invention, the molar ratio of IMA to SBMA is controlled to be (1-12): 1, specifically 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1 or 12:1, etc., preferably (3-10): 1, more preferably (5-8): 1, and other values within this range of values are equally applicable and will not be described here.

Because IMA mainly provides excellent mechanical properties, the shape triggering temperature of a single IMA gel is far higher than the body temperature, and in order to ensure that the transition temperature of the shape memory hydrogel can be near the body temperature, materials with glass transition temperature lower than the body temperature need to be introduced, so that SBMA with the highest critical dissolution temperature of 17-22 ℃ is preferably adopted to carry out cross-linking polymerization with IMA, and the shape transition hydrogel near the body temperature can be conveniently regulated and controlled.

In the invention, the IMA is used as a hydrophobic aggregation crosslinking point enhanced by hydrogen bonds and has a strong energy dissipation structure, so that excellent mechanical properties of far beyond human tissues can be provided, but a single IMA is prepared into gel, the gel is high in strength but fragile and has a shape transition temperature far higher than the body temperature. According to the test, the gel is softened and fixed into a spiral shape at 50 ℃, then fixed into a straight shape at room temperature, and then the gel is put into water at 37 ℃ to observe the shape change. The gel was found to change from a straight bar to a spiral, indicating excellent shape memory. The hydrophilic monomers mentioned above may also be other common hydrophilic monomers that lower the glass transition temperature, for example: acrylic acid, acrylamide, and the like.

Meanwhile, the invention utilizes the hydrophilism of SBMA to adjust out small and uniform hydrophobic aggregation crosslinking points, and forms ionic bonds among sulfobetaine groups in SBMA, which is beneficial to further enhancing the mechanical property of shape memory hydrogel, and has tensile strength up to 2.0MPa and Young modulus of 20.49MPa, and gradually decreases along with the increase of SBMA. And, the shape memory hydrogel has a slow rise in compressive strength with an increase in the number of cyclic compressions, which is very advantageous for its repeated use.

In addition, the invention discovers that the SBMA can lead the prepared shape memory hydrogel to have wider shape transition temperature, thereby leading the shape memory hydrogel to have more complex triple memory capability and having wider future practical application prospect.

In some embodiments of the invention, the shape memory hydrogel is obtained from a hydrophobic monomer, a hydrophilic monomer, and a chemical cross-linking agent and an initiator. Wherein the chemical cross-linking agent is any one or more of N, N-methylene acrylamide, N-methylene acrylamide derivatives, ethylene glycol dimethacrylate or ethylene glycol dimethacrylate derivatives. The free radical initiator comprises a photoinitiator and/or a thermal initiator, preferably a thermal initiator of the present invention, which may be any one or more of Azobisisobutyronitrile (AIBN), dibenzoyl peroxide or potassium persulfate. When the initiator is selected from a photoinitiator or other initiators, the initiation conditions are changed, and the initiator needs to be initiated by corresponding means such as light, radiation or microwaves with specific wavelengths.

In some embodiments of the invention, the ratio of the total moles of hydrophobic monomer and hydrophilic monomer to the moles of chemical cross-linking agent is 1 (0.005-0.1), which may be 1:0.005, 1:0.01, 1:0.02, 1:0.03, 1:0.04, 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09, or 1:0.1, etc., and other values within this range are applicable and are not repeated herein. The ratio of the total mole number of the hydrophobic monomer and the hydrophilic monomer to the mole number of the initiator is 1 (0.002-0.005), and may be 1:0.002, 1:0.0025, 1:0.003, 1:0.0035, 1:0.004, 1:0.0045, or 1:0.005, etc., and other values in the range are applicable and are not described herein. In some embodiments of the invention, the polymerization is preferably carried out under anaerobic conditions to prevent oxygen radical quenching reactions.

In some embodiments of the invention, the shape memory hydrogel is prepared specifically according to the following method:

(1) Mixing a hydrophobic monomer, a hydrophilic monomer, a chemical cross-linking agent, an initiator and a solvent, and then carrying out polymerization reaction under an anaerobic condition to obtain organogel;

the hydrophilic monomer comprises sulfobetaine methacrylate;

the solvent is a mixed solution of an organic solvent and water;

According to the invention, firstly, hydrophobic monomer, hydrophilic monomer, chemical cross-linking agent, initiator and solvent are mixed and then undergo free radical polymerization reaction under the anaerobic condition to obtain organogel. Wherein, the hydrophobic monomer and the hydrophilic monomer can be directly purchased from the market or prepared according to a preparation method well known to a person skilled in the art, the IMA is prepared by referring to a CN115873268A method in the invention, and SBMA is a general commercial product. The specific selection of the chemical crosslinking agent and the initiator is described in the relevant content in the technical scheme, and is not repeated here. The amounts and proportions of the hydrophobic monomer, the hydrophilic monomer, the chemical crosslinking agent and the initiator are referred to in the above technical solutions, and will not be described in detail herein. The solvent is a mixed solvent of organic solvent and water, the organic solvent comprises one or more of dimethyl sulfoxide (DMSO), dichloromethane, tetrahydrofuran or N, N-dimethylformamide, and the preferred solvent is DMSO/H ₂ O，DMSO、H ₂ The volume ratio of O is preferably 10 (0.5-2), more preferably 10:1. In the present invention, the above polymerization reaction needs to be carried out under an oxygen-free condition to prevent free radicals generated by oxygen quenching during the polymerization. The anaerobic condition can be realized by any one of the following modes: 1) Filling inert gas into the system, wherein the inert gas is well known by the person skilled in the art; 2) Performing freeze-induced oxygen removal on the mixture obtained after mixing in liquid nitrogen, wherein the freeze-induced oxygen removal is performed according to means well known to a person skilled in the art; 3) Oxygen is consumed or converted using chemical reagents which are common reagents well known to those skilled in the art, such as sodium sulfite, dimethyl ketoxime,Sodium ascorbate, sodium (or calcium) dithiotetraoxide, ferrous hydroxide, and the like. The invention adopts the mode 2) preferably, the frozen extraction deoxidization does not need other special equipment reagents, the operation is simple, the use is flexible, and the deoxidization efficiency is high and thorough. In some embodiments of the present invention, it is preferable to mix a hydrophobic monomer, a hydrophilic monomer, a chemical crosslinking agent, an initiator and a solvent in the molar ratio referred to in the above technical scheme and perform a freeze-induced oxygen removal treatment in liquid nitrogen, and then transfer the resulting solution into a glass mold of a specific shape, which may be selected as required, for example, rectangular or circular, and so on, and polymerize at 50 to 80 ℃ for 6 to 14 hours to obtain an organogel. Wherein the temperature and time of the polymerization can be adjusted in a matching manner, the polymerization temperature can be a little higher, and the time can be relatively shorter, and vice versa. The polymerization is preferably carried out at 60℃for 10 hours.

After the organogel is obtained, the organogel is immersed in water and exchanged out of the organic solvent until equilibrium is reached, in accordance with the present invention, to obtain the shape memory hydrogel. The organogel may be cut into a predetermined shape in advance before being immersed in water, and cut according to actual needs. In some embodiments of the invention, the frequency of water exchange during immersion of the organogel in water may be suitably high to speed up the progress of the organic solvent exchange during the first day, and may be selected as desired, such as 4, 5, 6 or more times, after which water is exchanged once a day until equilibrium is reached.

The preparation method of the shape memory hydrogel provided by the invention is simple and convenient, is convenient to realize, and is beneficial to realizing large-scale production.

It should be noted that the hydrogel provided by the present invention has a shape memory function, so as to be different from other common hydrogels, because of the structure of the hydrogel formed by polymerizing the preparation raw materials, i.e., the hydrophobic monomer and the hydrophilic monomer. In the invention, the hydrogel formed after polymerization of IMA and SBMA has reversible physical crosslinking points such as strong hydrophobic aggregation crosslinking, weak ionic bonds and the like in the internal structure, and a small amount of chemical crosslinking exists to maintain the shape of the gel. The hydrophobic aggregate crosslinks and ionic bonds have different association energies, dissociation occurs at different temperatures, and the strength of the hydrophobic aggregate is greater than that of the ionic bond, so that the hydrophobic aggregate needs a higher temperature to be destroyed. If at 60 ℃, part of weak hydrophobic aggregation and ionic bonds in the gel network can be destroyed, and the hydrophobic aggregation is reformed when the temperature is reduced to 40 ℃, but the ionic bonds also need to be recovered at a lower temperature, so that the internal cross-linked structure of the hydrogel is destroyed to different degrees at different temperatures, and different shapes are given and fixed by different types of cross-links, namely the gel can memorize different shapes at different temperatures. In general, when the gel is subjected to external loading (e.g., water, temperature), the "weak switch" inside the network will open, the ionic bonds and some hydrophobic aggregates will be destroyed, and the gel will remain in a temporary shape. When we unload this "external force", the weak interactions inside the gel start to form again and the gel starts to recover. This disruption-formation process gives the gel good shape memory.

The hydrogel provided by the invention has excellent shape memory capability, and can be used in the field of biomedical devices, for example, the hydrogel can be used for preparing implantable medical device materials which can be used as a spring ring or a bracket for treating aneurysms, and the like.

In order to further illustrate the present invention, the following examples are provided. The experimental materials used in the following examples of the present invention are commercially available or prepared according to conventional preparation methods well known to those skilled in the art. SBMA was purchased from ampoul gecko, model a 01473.

Preparation example 1

The preparation example provides a hydrophobic monomer IMA, and the reaction route is as follows:

the preparation method comprises the following steps:

2-Isocyanate methacrylate (25 g,161.1 mmol) and anhydrous isopropanol (12 g,199.6 mmol) were charged into a flask, dissolved in 20mL of dry dichloromethane, added with one drop of dibutyltin dilaurate DBTD as catalyst, stirred and mixed well, and heated under nitrogen protection at 70℃under reflux overnight. DCM and unreacted isopropanol were removed by rotary evaporation and dried in a vacuum oven to finally give white solid IMA (34.4 g).

Example 1

The present example provides a shape memory hydrogel (abbreviated as P (IMA-co-SBMA), which is prepared by the following steps:

the hydrophobic monomer IMA (1.60 g,7.43 mmol) obtained in preparation example 1 and the hydrophilic monomer SBMA (0.34 g,1.22 mmol) were taken and fed in a molar ratio of 6:1, and N, N-methyleneacrylamide MBAA (26.5 mg), the initiator azobisisobutyronitrile AIBN (3.9 mg) was added and dissolved in the mixed solvent DMSO/H ₂ O (11 mL,10/1, v/v), oxygen was frozen in liquid nitrogen. And then transferring and injecting the mixed solution into a self-made rectangular glass mold, and polymerizing for 10 hours at 60 ℃ to obtain the organogel. After polymerization, the gel is cut into cylinders or strips, immersed in a large amount of water and exchanged for the organic solvent DMSO until equilibrium is reached to obtain the hydrogel. During the soaking process, the water was changed six times a first day, after which the water was changed once a day.

Examples 2 to 5

According to the method of example 1, P (IMA-co-SBMA) gels were prepared by feeding monomer IMA and SBMA in a molar ratio of 10:1, 7:1, 5:1 and 3:1, respectively.

Notably, the resulting P (IMA-co-SBMA) gel was very temperature sensitive, and to ensure reproducibility of the experiment, the solvent exchange process in the above examples was performed at a constant temperature of 25 ℃.

The macroscopic graphs of the hydrogels obtained in examples 1 to 5 are shown in FIG. 1, and it can be seen that the gel becomes gradually transparent as the SBMA content increases, because the size of the hydrophobic aggregates inside the gel becomes gradually smaller, resulting in a gradual weakening of the diffuse reflection of light at the interface. This demonstrates that the hydrophilic monomer SBMA in the bulk system is able to adjust the size of the aggregates in the hydrophobic gel, thus producing a high strength gel.

Performance testing

Tensile Property test

The cylindrical or long-strip gel samples of examples 1 to 5 were taken, and compression test and uniaxial tensile test were performed in a universal tensile tester, compressing the samples to a strain of 85% at a speed of 10mm/min or stretching until the samples were broken.

The resulting tensile stress-strain plot is shown in FIG. 2, and it can be seen that the tensile strength and Young's modulus of the gel are both significantly reduced with increasing zwitterionic SBMA. But the elongation at break increases with increasing SBMA. P (IMA) ₁₀ -co-SBMA ₁ ) The gel has a tensile strength of up to 2.0MPa, a Young's modulus of 20.49MPa, but an elongation at break of only 47%. P (IMA) ₃ -co-SBMA ₁ ) The tensile strength and Young's modulus of the gel were reduced to 1.3MPa and 1.84MPa, respectively, but the elongation thereof was increased to 418%. The trend in the mechanical properties of hydrogels is due to the increase in zwitterionic SBMA, which forms ionic crosslinks that limit the movement of the copolymer chains, so that the hydrophobic aggregation in the gel network is gradually reduced. While hydrophobic aggregation is a strong energy dissipation structure, its reduction entails a decrease in strength and modulus, while a weak ionic bond increase is beneficial in increasing the elongation at break of the gel. In addition, P (IMA) ₆ -co-SBMA ₁ ) The gel has a tensile strength of up to 2.67MPa, with a young's modulus of 20MPa, and also an elongation at break of around 200%, which may be related to its maximum crosslink density.

Dynamic mechanical test

Dynamic mechanical analysis Using DMA-850 (TA Instruments) versus P (IMA) ₆ -co-SBMA ₁ ) The gel was tested at a heating rate of 2 ℃/min, a temperature range of 10 ℃ to 60 ℃, and a frequency of 1Hz. The amplitude was set to 10 μm.

The storage modulus/loss factor-temperature diagram of the resulting gel is shown in FIG. 3, P (IMA ₆ -co-SBMA ₁ ) The storage modulus (G ') of the gel was always higher than the corresponding loss modulus (G') at temperatures ranging from 15 to 50℃indicating P (IMA) ₆ -co-SBMA ₁ ) The hydrogel has elasticity. With increasing temperature, the gel G 'and G' drop greatly, which should be due to physical damage such as ionic bonding, hydrophobic aggregation, etc. in the network. The loss factor (tan delta) peaks at 35℃which is P (IMA) ₆ -co-SBMA ₁ ) Glass transition temperature Tg of the gel.

Hydrogel self-enhancement experimental verification

Referring to the procedure of example 1, a 10mm thick mold was replaced, and other procedures were consistent with example 1 to prepare a cylindrical compressed sample-P (IMA ₆ -co-SBMA ₁ ) And (5) gel. The prepared compressed sample is taken to carry out cyclic compression test in a universal tensile tester, the sample is compressed to be 60% in strain at the speed of 10mm/min, the test is repeated for 10 times, and meanwhile, each interval is soaked in warm water at 37 ℃ to recover for 10min.

The obtained P (IMA) ₆ -co-SBMA ₁ ) The cyclic compressive stress-strain curves of the gel are shown in fig. 4 and 5, fig. 4 being P (IMA ₆ -co-SBMA ₁ ) The cyclic compressive stress-strain curve of the gel is shown in fig. 5 as P (IMA ₆ -co-SBMA ₁ ) Compression modulus and compression strength profiles of the gel at different cycles. It can be seen that the gel had about 5% residual strain from the start of the second cycle compression in the course of 10 cycles of compression, and could not be completely recovered. At the same time, the modulus of the second cycle compression increases from 19MPa to 38MPa compared to the first, after which a slow rise trend is exhibited, but the compressive strength of the gel (60%) remains almost unchanged, presumably the temperature causes the formation of a large number of hydrophobic aggregates in the network, and the change in the type of crosslinking causes the rise of the gel modulus, which is advantageous for the repeated use of the shape memory gel.

Bending recovery test

The hydrogels obtained in examples 1 to 5 were softened and deformed into a "U" shape in water at 50℃and their angle (. Theta. _i ) Recorded 180 °. Thereafter, the hydrogel of the given shape was immersed in water at 25℃to fix the temporary shape, and the temporary fixing angle (θ _t ). The hydrogel sample is then immersed in 37℃water or heated toThe set temperature induces its shape recovery, and the final angle (θ _f ). Shape fixation ratio (R) _f ) And shape recovery rate (R) _r ) Defined by the following formula:

the shape retention and shape recovery of the resulting different gels are shown in FIG. 6 (wherein gray columns correspond to shape retention R _f Shape recovery rate R corresponding to black column _r ) It can be seen that as IMA decreases, P (IMA ₁₀ -co-SBMA ₁ )、P(IMA ₇ -co-SBMA ₁ ) And P (IMA) ₆ -co-SBMA ₁ ) The gel had a similar shape retention of 95%, P (IMA ₅ -co-SBMA ₁ ) The gel had the highest 100% shape retention, P (IMA) ₃ -co-SBMA ₁ ) The shape retention of the gel was reduced to 84%. This is due to the fact that the shape retention is related to hydrophobic aggregation, ionic crosslinking present in the gel, deformation of the physically crosslinked gel is destroyed at high temperature, physical crosslinking resumes after transfer, P (IMA) ₅ -co-SBMA ₁ ) The gel has a higher degree of crosslinking and thus a high shape retention, P (IMA) ₃ -co-SBMA ₁ ) The gel has little hydrophobic aggregation and therefore the shape fixation rate decreases dramatically. At the same time, the shape recovery rate of the gel gradually increases with decreasing IMA, due to the decrease in hydrophobic aggregation, resulting in a faster gel recovery time, so P (IMA) ₃ -co-SBMA ₁ ) The gel has a higher shape recovery rate instead.

P(IMA ₆ -co-SBMA ₁ ) Gel triple shape memory capability test

The gel triple shape memory effect was characterized by DMA-850 quantification. Selecting P (IMA) ₆ -co-SBMA ₁ ) The gel samples were tested for a fixed length of 15mm. First, the sample was heated to 60℃under a preload of 0.002N and held for 8min,obtaining a temporary shape A, marked epsilon _A . Then stretching the sample under the stress of about 0.006MPa, cooling to 40 ℃ at the speed of 2 ℃/min, and keeping the temperature of 40 ℃ under the stress for 10min to obtain the maximum tensile strain epsilon _B Load. After stress relief, the sample was incubated at 40℃for a further 2min to give its temporary shape B, designated ε _B . Secondly, stretching the sample under the stress condition of about 0.025MPa, cooling to 20 ℃, and keeping the temperature of 20 ℃ for 10min under the stress condition to obtain another maximum tensile strain epsilon _C Load. Then stress is released and the mixture is kept at 20 ℃ for 2min to obtain a temporary shape C, which is marked as epsilon _C . Finally, the sample is heated back to 40 ℃ at the speed of 5 ℃/min, the isothermal holding is carried out for 5min, and the strain is marked as epsilon _B,rec Heating to 60 ℃ at the same rate to recover the original shape A, marked as epsilon _A,rec . Shape memory fixed ratio (R) _f,1→2 ) And recovery ratio (R _r,1→2 ) The calculations are as follows (where 1 or 2 corresponds to A, B or C as needed at the time of calculation):

R _f，1→2 ＝(ε ₂ -ε ₁ )/(ε _2，load -ε ₁ )

R _r，2→1 ＝(ε ₂ -ε _1，rec )/(ε ₂ -ε ₁ )

the test results are shown in FIG. 7, and the shape B (R _f,A→B ) And shape C (R) _f,B→C ) The shape fixation ratio of (2) was 71.91% and 97.4%, respectively. In the subsequent recovery process, R _r,C→B And R is _r,B→A 93.5% and 101%, respectively. Physical crosslinks including ionic bonds and partially hydrophobic aggregates are broken due to high temperature. The hydrophobic aggregation is re-aggregated with the decrease of the temperature, but the temperature has larger influence on the ionic bond, and the ionic bond cannot be recovered at 40 ℃, so that the crosslinking density in the gel network is low, more space can be freely moved in the copolymer chain, and finally R is presented _f,A→B Only 71.91% results. As the temperature is further cooled to 20deg.C, ionic bonds are also reformed, limiting the free movement of the molecular chains, thus R _f,B→C Up to 97.4%. The above results indicate that the gel has more complex triple memory capacity and phaseThe method lays a foundation for the excellent shape fixation rate and recovery rate, and the use of the method in more complex application environments.

P(IMA ₆ -co-SBMA ₁ ) Gel shape memory capability test

The gel bars of example 2 were fixed in a spiral shape at a softening temperature of 50℃and at 37℃and then in a straight shape at room temperature, and then the samples were put into water at 37℃to observe the shape change. The results are shown in FIG. 8, and it can be seen that the gel changed from a straight bar shape to a spiral shape, indicating excellent shape memory.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A shape memory hydrogel, which is characterized by being obtained by cross-linking polymerization of a hydrophobic monomer and a hydrophilic monomer;

the hydrophilic monomer includes sulfobetaine methacrylate.

2. The shape memory hydrogel of claim 1, wherein the molar ratio of hydrophobic monomer to hydrophilic monomer is (1-12): 1.

3. The method for preparing the shape memory hydrogel according to claim 1 or 2, comprising the steps of:

the solvent is a mixed solution of an organic solvent and water;

4. The method according to claim 3, wherein the ratio of the total mole number of the hydrophobic monomer and the hydrophilic monomer to the mole number of the chemical crosslinking agent is 1 (0.005 to 0.1).

5. The process according to claim 3, wherein the ratio of the total mole number of the hydrophobic monomer and the hydrophilic monomer to the mole number of the initiator is 1 (0.002 to 0.005).

6. The method of claim 3, wherein the chemical cross-linking agent comprises any one or more of N, N-methyleneacrylamide, N-methyleneacrylamide derivatives, ethylene glycol dimethacrylate, or ethylene glycol dimethacrylate derivatives.

7. A method of preparation according to claim 3, wherein the free radical initiator comprises a photoinitiator and/or a thermal initiator.

8. A method of preparation according to claim 3, wherein the organic solvent comprises any one or more of dimethyl sulfoxide, dichloromethane, tetrahydrofuran or N, N-dimethylformamide.

9. The process according to claim 3, wherein the polymerization reaction is carried out at a temperature of 50 to 80℃for a period of 6 to 14 hours.

10. An implantable medical device material comprising the shape memory hydrogel of claim 1 or 2 or a shape memory hydrogel prepared according to the method of any one of claims 3-9.