阅读说明：本技术 一种复合水凝胶及其制备方法和应用 (Composite hydrogel and preparation method and application thereof ) 是由 耿志杰 于珊 裴大婷 国翠平 鲁道欢 于 2020-12-22 设计创作，主要内容包括：本发明公开了一种复合水凝胶及其制备方法和应用。这种复合水凝胶包括第一网络和第二网络；其中,第二网络半互穿第一网络；第一网络包括异丙基丙烯酰胺基单体和纳米颗粒形成的水凝胶；第二网络包括高分子聚合物。这种复合水凝胶可以应用在生物和/或医药领域。本发明提供的复合水凝胶具有双重网络结构,具有温度响应性和超高机械性能。这种高弹性水凝胶的制备采用廉价易得的原料和温和的制备工艺,使得水凝胶的制备容易放大生产,拓展了其应用范围。(The invention discloses a composite hydrogel and a preparation method and application thereof. The composite hydrogel comprises a first network and a second network; wherein the second network semi-interpenetrates the first network; the first network comprises a hydrogel formed from isopropyl acrylamide-based monomers and nanoparticles; the second network comprises a high molecular weight polymer. The composite hydrogel can be applied to the biological and/or medical fields. The composite hydrogel provided by the invention has a dual network structure, and has temperature responsiveness and ultrahigh mechanical properties. The preparation of the high-elasticity hydrogel adopts cheap and easily-obtained raw materials and a mild preparation process, so that the preparation of the hydrogel is easy to enlarge production, and the application range of the hydrogel is expanded.)

1. A composite hydrogel, characterized by: the composite hydrogel comprises a first network and a second network;

the second network semi-interpenetrating the first network;

the first network comprises a hydrogel formed from isopropyl acrylamide-based monomers and nanoparticles;

the second network includes a high molecular weight polymer.

2. A composite hydrogel according to claim 1, wherein: the isopropyl acrylamide based monomer comprises at least one of N-isopropyl acrylamide, propenyl-N-isopropyl acrylamide, glucosyl-N-isopropyl acrylamide and chitosan-N-isopropyl acrylamide.

3. A composite hydrogel according to claim 1, wherein: the nano particles comprise at least one of nano graphene oxide, nano clay and carbon nano tubes.

4. A composite hydrogel according to claim 1, wherein: the high molecular polymer comprises at least one of polyethylene glycol, polyvinyl alcohol, polyethylene glycol methacrylate, polyvinylpyrrolidone, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose and methyl cellulose.

5. A composite hydrogel according to any one of claims 1 to 4, wherein: the phase transition temperature of the composite hydrogel is 34-40 ℃.

6. A composite hydrogel according to any one of claims 1 to 4, wherein: the tensile elongation at break of the composite hydrogel is 900-1200%.

7. A preparation method of composite hydrogel is characterized by comprising the following steps: the method comprises the following steps:

1) dissolving a high molecular polymer in a solvent to obtain a high molecular polymer solution;

2) mixing the high molecular polymer solution, the isopropyl acrylamide monomer and the nano particles to obtain a mixed solution;

3) mixing the mixed solution with an initiator, and reacting to obtain the composite hydrogel according to any one of claims 1 to 6.

8. The method of claim 7, wherein: in the step 2), the mass ratio of the high molecular polymer, the isopropyl acrylamide based monomer and the nanoparticles is (3-80): 100: (0.3-40).

9. The method of claim 7, wherein: in the step 3), the reaction temperature is 50-80 ℃; the reaction time is 2 to 10 hours.

10. The application of the composite hydrogel in the biological and/or medical field is characterized in that: the composite hydrogel is the composite hydrogel described in any one of claims 1 to 6, or is prepared by the preparation method described in any one of claims 7 to 9.

Technical Field

The invention relates to the technical field of hydrogel, and particularly relates to composite hydrogel and a preparation method and application thereof.

Background

The hydrogel contains a large amount of water and has a three-dimensional network structure, so that the hydrogel has more and more obvious application value in the field of biomedicine and can be used as a biosensor, a tissue engineering scaffold, a biological separation carrier, a drug release carrier and the like. The application fields have certain requirements on the biocompatibility and the mechanical property of the hydrogel, particularly the tensile strength, but the traditional chemical crosslinking hydrogel has irregular crosslinking points and uneven length distribution of polymer molecular chains, so that the mechanical property of the hydrogel is poor and the application requirement on high mechanical property can not be met. The traditional chemical crosslinking hydrogel often needs to add a small molecular chemical crosslinking agent, and has a great negative effect on the biocompatibility of the hydrogel.

Patent document CN107840926A discloses a fast-response high-strength hydrogel, the gel preparation method disclosed by the invention firstly prepares double-bond functionalized N-isopropylacrylamide microgel as a cross-linking agent to prepare the hydrogel, the reaction steps of the technical scheme are more, the preparation method is tedious, and the operation difficulty of the preparation process and the control difficulty of the preparation result are increased.

The preparation method of the hydrogel in the prior art is complex, the number of intermediate reaction steps is large, the reaction result is not easy to control, the reports of the ultrahigh-strength hydrogel with temperature responsiveness are few, the technical problem of poor mechanical strength generally exists, and further improvement is needed.

Disclosure of Invention

The present invention is directed to solving at least one of the above-mentioned problems associated with hydrogels of the prior art. Accordingly, an object of the present invention is to provide a highly elastic composite hydrogel having temperature responsiveness, a second object of the present invention is to provide a method for producing the composite hydrogel, and a third object of the present invention is to provide applications of the composite hydrogel.

The invention concept of the invention is as follows: according to the invention, by designing the composite hydrogel with the double-network structure, the mechanical property of the hydrogel can be improved, so that the hydrogel has ultrahigh elasticity. Specifically, the preparation of the composite hydrogel selects isopropyl acrylamide and derivatives thereof as basic monomers, adopts inorganic nanoparticles as a gel reinforcing agent and plays a role of a cross-linking agent, avoids adding a micromolecule cross-linking agent additionally in the system to improve the biocompatibility of the hydrogel, adopts a free radical solution polymerization method to prepare a first layer of gel network structure, and then forms a second network structure of the gel system by adding the reinforcing agent to form a semi-interpenetrating network.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows:

a first aspect of the present invention provides a composite hydrogel comprising a first network and a second network;

the second network semi-interpenetrating the first network;

the first network comprises a hydrogel formed from isopropyl acrylamide-based monomers and nanoparticles;

the second network includes a high molecular weight polymer.

Preferably, in the composite hydrogel, the isopropyl acrylamide-based monomer comprises at least one of N-isopropyl acrylamide, propenyl-N-isopropyl acrylamide, glucosyl-N-isopropyl acrylamide and chitosan-based-N-isopropyl acrylamide. In some embodiments of the present invention, N-isopropylacrylamide is selected as the isopropylacrylamide-based monomer.

Preferably, in the composite hydrogel, the nanoparticles comprise at least one of nano graphene oxide, nano clay and carbon nanotubes.

Preferably, in the composite hydrogel, the high molecular polymer comprises at least one of polyethylene glycol, polyvinyl alcohol, polyethylene glycol methacrylate, polyvinylpyrrolidone, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose and methyl cellulose; further preferably, the high molecular polymer includes at least one of polyethylene glycol, polyethylene glycol methacrylate, and hydroxyethyl cellulose.

Preferably, the phase transition temperature of the composite hydrogel is 34-40 ℃; further preferably, the phase transition temperature of the composite hydrogel is 35-39 ℃.

Preferably, the tensile elongation at break of the composite hydrogel is 900-1200%.

The second aspect of the present invention provides a method for preparing a composite hydrogel, comprising the following steps:

1) dissolving a high molecular polymer in a solvent to obtain a high molecular polymer solution;

2) mixing the high molecular polymer solution, the isopropyl acrylamide monomer and the nano particles to obtain a mixed solution;

3) and mixing the mixed solution with an initiator, and reacting to obtain the composite hydrogel.

In a second aspect, the invention provides a composite hydrogel prepared according to the first aspect of the invention.

Preferably, in step 1) of the preparation method, the mass concentration of the high molecular polymer solution is 1-10%; more preferably, the mass concentration of the high molecular polymer solution is 2% to 8%.

Preferably, in step 1) of the preparation method, the solvent is water.

Preferably, in step 2) of the preparation method, the mass ratio of the high molecular polymer, the isopropyl acrylamide-based monomer and the nanoparticles is (3-80): 100: (0.3-40); further preferably, the mass ratio of the high molecular polymer, the isopropyl acrylamide based monomer and the nanoparticles is (5-50): 100: (0.5 to 4); still further preferably, the mass ratio of the high molecular polymer, the isopropyl acrylamide-based monomer and the nanoparticles is (10-40): 100: (1-2.5).

Preferably, in step 2) of the preparation method, the mixing manner includes stirring; further preferably, the means of mixing comprises magnetic stirring.

Preferably, in step 2) of the preparation method, the mixing manner further comprises ultrasonic mixing.

Preferably, in step 3) of the preparation method, the initiator is selected from at least one of azo compounds, peroxides and persulfates; more preferably, the initiator is at least one selected from the group consisting of azobisisobutyronitrile, azobisisoheptonitrile, hydrogen peroxide, tert-butyl hydroperoxide, sodium persulfate, potassium persulfate, and ammonium persulfate; still more preferably, the initiator is at least one selected from the group consisting of sodium persulfate, potassium persulfate, and ammonium persulfate.

Preferably, in the step 3) of the preparation method, the amount of the initiator is 1-30% of the mass of the isopropyl acrylamide-based monomer; further preferably, the using amount of the initiator is 5 to 28 percent of the mass of the isopropyl acrylamide-based monomer; still more preferably, the amount of the initiator is 12.5 to 25 percent of the mass of the isopropyl acrylamide-based monomer.

Preferably, in step 3) of the preparation method, the reaction mixture obtained by mixing the mixed solution and the initiator is reacted in a mold.

Preferably, in the step 3) of the preparation method, the reaction temperature is 50-80 ℃; the reaction time is 2 to 10 hours.

Preferably, in step 3) of the preparation method, the reaction is a water bath reaction.

The third aspect of the present invention provides a use of a composite hydrogel in the biological and/or medical fields, wherein the composite hydrogel is the composite hydrogel according to the first aspect of the present invention, or is prepared by the preparation method according to the second aspect of the present invention.

Preferably, the composite hydrogel is applied to biosensors, tissue engineering scaffolds, bioseparations, gel bandages or drug release carriers.

The invention has the beneficial effects that:

the composite hydrogel provided by the invention has a dual network structure, and has temperature responsiveness and ultrahigh mechanical properties. The preparation of the high-elasticity hydrogel adopts cheap and easily-obtained raw materials and a mild preparation process, so that the preparation of the hydrogel is easy to enlarge production, and the application range of the hydrogel is expanded.

Specifically, compared with the prior art, the invention has the following advantages:

according to the hydrogel system disclosed by the invention, inorganic nanoparticles capable of enhancing the mechanical property of the hydrogel are introduced as crosslinking agent molecules, so that the influence of an additionally added small-molecule chemical crosslinking agent on the biocompatibility of the hydrogel is avoided, and meanwhile, a high-molecular polymer with good biocompatibility is introduced into the system as a second network of the composite hydrogel to improve the mechanical strength of the hydrogel.

The dual-network high-strength hydrogel prepared by the invention has temperature responsiveness, the phase transition temperature of the hydrogel can be adjusted by adjusting the dosage of the temperature-sensitive monomer and the reinforcing agent, and the functionality and the application range of the composite hydrogel are expanded.

The composite hydrogel has ultrahigh tensile elongation at break and wide application prospect, and can be used as a biosensor, a tissue engineering bracket, a biological separation carrier, a drug release carrier and the like if being applied to the field of biological medicines.

Detailed Description

The present invention will be described in further detail with reference to specific examples. The starting materials, reagents or equipment used in the examples are, unless otherwise specified, either conventionally commercially available or may be obtained by methods known in the art. Unless otherwise indicated, the testing or testing methods are conventional in the art.

Example 1

The preparation method of the composite hydrogel with the double-network structure comprises the following steps:

weighing 0.2g of polyethylene glycol methacrylate, dissolving in 10mL of pure water to prepare an aqueous solution, then weighing 2g N-isopropylacrylamide and 0.02g of graphene oxide respectively, adding into the solution, magnetically stirring for 4 hours, ultrasonically mixing uniformly to form a uniform mixed solution, adding 0.3g of ammonium persulfate into the mixed solution, magnetically stirring to form a uniform reaction mixed solution, finally pouring the reaction mixed solution into a mold, and placing in a water bath at 50 ℃ for reaction for 3 hours to obtain the high-elasticity hydrogel with temperature responsiveness.

Detection shows that in the hydrogel prepared in the embodiment, the polyethylene glycol methacrylate semi-interpenetrating poly-N-isopropylacrylamide hydrogel forms a double-network structure.

The hydrogel of this example was tested to have a phase transition temperature of 35 ℃ and a tensile elongation at break of 1200%.

Example 2

The preparation method of the composite hydrogel with the double-network structure comprises the following steps:

weighing 0.5g of hydroxyethyl cellulose, dissolving the hydroxyethyl cellulose in 10mL of pure water to prepare an aqueous solution, then respectively weighing 2g N-isopropylacrylamide and 0.02g of graphene oxide, adding the obtained mixture into the solution, magnetically stirring the obtained mixture for 4 hours, ultrasonically mixing the obtained mixture uniformly to form a uniform mixed solution, adding 0.5g of ammonium persulfate into the mixed solution, magnetically stirring the obtained mixture to form a uniform reaction mixed solution, finally pouring the reaction mixed solution into a mold, and placing the mold in a water bath at 50 ℃ for reaction for 3 hours to obtain the high-elasticity hydrogel with temperature responsiveness.

According to detection, in the hydrogel prepared in the embodiment, hydroxyethyl cellulose semi-interpenetrating poly N-isopropyl acrylamide hydrogel forms a double-network structure.

The hydrogel of this example was tested to have a phase transition temperature of 37 ℃ and a tensile elongation at break of 1160%.

Example 3

The preparation method of the composite hydrogel with the double-network structure comprises the following steps:

weighing 0.8g of hydroxyethyl cellulose, dissolving in 10mL of pure water to prepare an aqueous solution, then respectively weighing 2g N-isopropyl acrylamide and 0.05g of nano clay, adding into the solution, magnetically stirring for 2 hours, ultrasonically mixing uniformly to form a uniform mixed solution, then adding 0.25g of ammonium persulfate into the mixed solution, magnetically stirring to form a uniform reaction mixed solution, finally pouring the reaction mixed solution into a mold, and placing in a water bath at 50 ℃ for reaction for 3 hours to obtain the high-elasticity hydrogel with temperature responsiveness.

According to detection, in the hydrogel prepared in the embodiment, hydroxyethyl cellulose semi-interpenetrating poly N-isopropyl acrylamide hydrogel forms a double-network structure.

The hydrogel of this example was tested to have a phase transition temperature of 39 ℃ and a tensile elongation at break of 900%.

The microstructure of the composite hydrogel prepared by the embodiment of the invention is a dual network structure, and the composite hydrogel has temperature responsiveness and ultrahigh mechanical property.

The composite hydrogel provided by the invention can be widely applied to the fields of biology and medicine, such as biosensors, tissue engineering scaffolds, biological separation, gel bandages or drug release carriers, and the like, and has wide application prospects.

The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.