CN109970999A - A kind of chitosan/polysulfobetaine ion supply double network hydrogel and preparation method thereof - Google Patents

Abstract

The invention relates to the technical field of polymer hydrogels, in particular to a chitosan/polysulfobetaine ion-donating double network hydrogel and a preparation method thereof. The chitosan/polysulfobetaine ion supply double network hydrogel is a double network structure, which is formed by the mutual penetration of a first heavy network and a second heavy network, and the first heavy network is composed of chitosan. The physical cross-linked network formed by the coordination of sugar and multivalent negative ions, the second heavy network is a chemical cross-linked network formed by polysulfobetaine, and the first heavy network is interspersed in the second heavy network. The double-network hydrogel prepared by the invention has excellent toughness and elasticity, and also has good antibacterial, anti-nonspecific protein adsorption and anti-cell adhesion properties, and has broad application prospects in the field of biomedicine; the preparation method is simple, Efficient and environmentally friendly, it is environmentally friendly.

Description

A chitosan/polysulfobetaine ion-donating double network hydrogel and its preparation backup method

technical field

The invention relates to the technical field of polymer hydrogels, in particular to a chitosan/polysulfobetaine ion-donating double network hydrogel and a preparation method thereof.

Background technique

Hydrogels composed of polymer networks and water are similar in composition to biological tissues, thus, hydrogels have received high attention as equivalents for various applications in synthetic biological systems. However, the practical application of traditional hydrogels is limited by their poor mechanical properties (Advanced Materials, 2016, 28(24): 4884-4890.). To date, many methods have been developed to fabricate hydrogels with excellent mechanical properties, the most typical being dual-network hydrogels (DN gels) consisting of a brittle first network and a flexible second network.

As a natural polymer, chitosan (CS) has excellent biological functionality and compatibility, blood compatibility, safety, and microbial degradability, and has received extensive attention from various industries. The chitosan molecular chain contains amino groups. These amino groups inhibit bacteria by combining negative electrons. The good antibacterial properties make them widely used in medicine, textile and food fields. The long-chain CS chain is rigid, but its low solubility leads to weak mechanical properties of the hydrogel; compared with the long-chain CS, the rigid short-chain CS has higher solubility in water and has good solubility, but the rigid short-chain CS network is prone to The energy dissipates and ruptures.

Preventing the attachment of nonspecific biomolecules and microorganisms to surfaces is a huge challenge in many applications, from biomedical devices to ship hulls. For example, nonspecific protein adsorption reduces the performance of surface-based diagnostic devices and adversely affects the healing process of implantable biomaterials. Polysulfobetaine is one of the representatives of zwitterionic polymers, and its monomer, sulfobetaine (SBMA), is similar in structure to taurine. Taurine is a sulfur-containing non-protein amino acid that is widely found in many animals. Because the zwitterionic part contains one cationic group and one anionic group, which makes the part electrically neutral as a whole, it can strongly bind water molecules through electrostatically induced hydration, so it has excellent hydrophilicity and can Effective against bacterial adhesion to avoid long-term bacterial biofilm formation.

Similar to taurine, sulfobetaine is also a monomer of a zwitterionic polymer, and the polysulfobetaine (PSBMA) formed by its polymerization is different from the more common chitosan, polyacrylamide, etc. Different from zwitterionic polymers, the resulting electrostatic induction effect is very strong, and the binding force to water molecules is strong, and it is an electrically neutral zwitterion. When forming a double network structure, it basically does not interact with another heavy network. The occurrence of fixed-point connection leads to the double network becoming a hybrid single network structure, resulting in the degradation of the performance of the double network hydrogel. Therefore, PSBMA-based materials can be widely used in many fields such as biomedicine and industrial production. Its potential The application prospect is very broad.

However, the existing dual-network hydrogels have obvious contradictions in many aspects such as good mechanical properties, good antifouling and antibacterial properties, and biocompatibility. Those with good mechanical properties usually have poor antifouling and antibacterial properties and biocompatibility; those with good antifouling and antibacterial properties and biocompatibility have poor mechanical properties. Various reasons limit the application of existing dual network hydrogels in real life. Therefore, it is of far-reaching significance to develop a dual-network hydrogel with a simple preparation method and good mechanical properties, antifouling and antibacterial properties, and biocompatibility, which will expand its application fields.

On May 31, 2017, the Chinese Patent Office disclosed the invention patent authorization of a graphene oxide/chitosan grafted double network hydrogel and its preparation method. The authorization publication number is CN104140631B, and its first network is oxidation Graphene/chitosan grafted hydrogel, the graphene oxide/chitosan grafted hydrogel is grafted by graphene oxide solution, chitosan solution, initiator, first monomer and crosslinking agent The second network is interspersed in the interior of the first network, and the second network is a hydrogel formed by the polymerization of the second monomer, the crosslinking agent and the photoinitiator under the irradiation of ultraviolet light. The hydrogel has high compressive strength and tensile strength, and the technical solution enhances the mechanical properties of the double network hydrogel by introducing graphene oxide; the Chinese Patent Office also disclosed a kind of The invention patent application of chitosan/acrylamide sticky and tough double network hydrogel and its preparation method, the application publication number is CN108178838A, it uses FeCl ₃ solution to dissolve chitosan, and this method not only provides a good solution for the dissolution of chitosan. In acidic conditions, at the same time, Fe ³⁺ and chitosan form physical cross-linking through coordination interaction, and then realize one-step dissolution and cross-linking of chitosan to form the first network, which makes the hydrogel have good biocompatibility and A certain viscosity, and chemical cross-linking of acrylamide is introduced as the second network, so that the hydrogel has good biocompatibility and viscosity, and also has excellent mechanical properties. Sugar forms coordination, cross-links with multivalent metal cations as ligands, improves the viscosity of hydrogels, and introduces acrylamide to improve the mechanical properties of hydrogels; China Patent Office also published a report on November 2, 2018. An invention patent application for a double network hydrogel with high strength, shape memory and self-healing properties and a preparation method thereof, the application publication number is CN108727610A, the first weight of which is chitosan and polyethylene glycol with aldehyde groups at both ends Alcohols form a network of dynamic imine bonds through Schiff base reactions, the second is a polyacrylamide cross-linked network; and a high-strength, frost-resistant, conductive shell disclosed by the Chinese Patent Office on January 4, 2019 The invention patent application for polysaccharide/acrylamide double network hydrogel and its preparation method, the application publication number is CN109134762A, which is formed by the interpenetration of the first network and the second network. The first network is a hydrogel formed by physical entanglement or physical cross-linking of chitosan molecular chains under the action of inorganic salts of different valences; the second network is a hydrogel formed by chemical cross-linking of acrylamide. In terms of zwitterionic double network hydrogels, the Chinese Patent Office also disclosed an invention patent application for an amphoteric polysaccharide/cross-linked graphene oxide double network composite hydrogel adsorption material and its preparation method on January 12, 2018 , the application publication number is CN107570121A, after it mixes graphene oxide with polysaccharides and zwitterionic monomers (or mixtures of cationic monomers and anionic monomers), single-network composite hydrogels are prepared by microwave-assisted graft copolymerization. Then the single-network composite hydrogel is cross-linked with graphene oxide in an aqueous solution of polyamine or amino-terminated polymer to obtain a double-network composite hydrogel adsorption material. But first of all, its double network is a chemically cross-linked network, which has poor stability, resulting in poor mechanical properties, easy to break or rupture, and its own chemical cross-linked structure is easily damaged, resulting in a rapid decline in performance. Preparation of double network hydrogels with graphene oxide has poor biocompatibility, and also fails to make good use of the antifouling and antibacterial properties of polysaccharides and zwitterionic polymers. It has practical value when used in biomedical technology and other fields. Low.

In the above technical solutions, the chitosan in the hydrogel is only a relatively simple cross-linking to form a network or cross-linking with a cation, and the cation is used as the central ion. After the coordination bond is broken, the overall structure will be greatly formed. loose and less stable.

SUMMARY OF THE INVENTION

In order to solve the obvious contradictions in the existing double-network hydrogels in terms of good mechanical properties, good antifouling and antibacterial properties, and biocompatibility, and most chitosan-based double-network hydrogels. The chitosan network is loose and the stability is poor. The present invention provides a chitosan/polysulfobetaine ion-donating double network hydrogel and a preparation method thereof.

The goals to be achieved include: first, to make the double network hydrogel have excellent mechanical properties, good antifouling and antibacterial properties and biocompatibility; second, to improve the stability of the chitosan network and make its network structure more efficient. High strength and toughness and make it have a certain self-healing ability; three, simplify the preparation process, make the preparation more convenient and efficient.

In order to achieve the above objects, the present invention adopts the following technical solutions.

A chitosan/polysulfobetaine ion supply double network hydrogel, the chitosan/polysulfobetaine ion supply double network hydrogel is a double network structure, which is composed of a first The heavy network and the second heavy network are formed by interpenetrating each other, the first heavy network is a physical cross-linked network formed by the coordination of chitosan and multivalent negative ions, and the second heavy network is formed by polysulfobetaine chemically cross-linked network, the first heavy network is interspersed within the second heavy network.

In the chitosan/polysulfobetaine ion-donating double-network hydrogel of the present invention: first, the second network is a polysulfobetaine chemically cross-linked network, and the chemical cross-linked network is usually obtained by polymerization, polycondensation It has the advantages of high stability and high order. First, it ensures that the overall hydrogel has good basic mechanical properties to a certain extent, and it is used as the second heavy network to achieve elasticity and increase. Toughness and other purposes, the network structure is more stable, and its water absorption and water retention properties are balanced. On the other hand, polysulfobetaine is a very typical zwitterionic polymer, and its zwitterionic part contains a cationic group. group and anion group, making it electrically neutral as a whole, and its surface can capture water molecules through electrostatic induction, form a strong bond with water molecules, exhibit excellent hydrophilicity, and form a strong hydration film The existence of the hydrated membrane layer can make it difficult for non-specific proteins and bacteria to adhere, so that the double network hydrogel has good anti-non-specific protein and anti-bacterial adhesion effects.

In addition, the first heavy network is the physical cross-linked network formed by the coordination of chitosan and multivalent negative ions, while the existing physical cross-linked network of chitosan is formed by the coordination of chitosan and cations. When chitosan is coordinated with a cation, the cation is used as the center and the chitosan is used as the ligand, that is, it can almost be regarded as a dispersed cation connected by chitosan. In this coordination and cross-linking method, a single cation is connected. The number of chitosan and/or the cations connected by a single chitosan molecule is highly restricted, the coordination connection position is relatively fixed, and mostly only amino groups can coordinately connect with cations, and the usually formed cross-linked network is a kind of The partial linear cross-linked network is interspersed in the second network, the degree of improvement of mechanical properties is low and insignificant, and it can only provide a certain rigidity. Its properties and its rigidity are well utilized, and the way of its physical cross-linking to form a network is also significantly different from the existing chitosan network.

In the technical solution of the present invention, chitosan forms physical cross-linking by coordinating with multivalent negative ions (ie, A ^N- , where N>1), with chitosan as the center and multivalent negative ions as ligands In this connection method, due to the existence of a large number of oxygen atoms in the chitosan molecule, most of its carbon atoms have a certain positive charge, which can coordinate with multivalent negative ions, and can be ionized in water. The generated hydrogen ion will combine with the amino group to form NH ₃ ⁺ , which can also further combine with the multivalent negative ion, so when it is coordinated with the multivalent negative ion, there are more connection points. When the first network is physically cross-linked through the coordination of chitosan and multivalent negative ions, it is more likely to generate a complex network structure, while the traditional chitosan network simply makes the linear network interspersed in the second network. Among them, the first heavy network is formed. In the present invention, the first heavy network formed by chitosan and multivalent negative ions is intertwined and entangled with the second heavy network, so the generated double network hydrogel has Better mechanical properties. On the other hand, after the chitosan network is broken in the present invention, since there are more coordination points between multivalent negative ions and chitosan, it is easier to form a connection again and achieve a certain degree of self-repair. After long-term use Still able to maintain good mechanical properties.

Moreover, in the double network hydrogel of the present invention, since the polysulfobetaine itself has cationic groups and anionic groups, but itself is electrically neutral, although the first heavy network chitosan network does not directly interact with the chitosan network. The second network polysulfobetaine network is combined, but under the electrostatic induction, the entanglement of the two will be more tightly, and then the protection of the second network by the first network can be achieved, that is, the double network can be ensured. When the network hydrogel is stretched or even damaged, the first heavy network chitosan network is sacrificed first, so that it can still maintain or maintain a good antibacterial and antifouling effect for a period of time. Better use effect can avoid the problem of breakage or failure.

A preparation method of chitosan/polysulfobetaine ion-supplied double network hydrogel, the preparation method comprises the following preparation steps:

1) prepare a mixed solution of chitosan, sulfobetaine, initiator and crosslinking agent;

2) placing the mixed solution in a mold, irradiating the reaction with ultraviolet light under a protective atmosphere, and obtaining a pregel after the reaction;

3) Immerse the pregel in a multivalent negative ion solution to obtain the chitosan/polysulfobetaine ion-donating double network hydrogel.

The preparation method of the invention is simple and efficient, and after compounding, reacting and dipping, the chitosan/polysulfobetaine ion-donating double network hydrogel can be quickly and efficiently prepared.

Preferably, in the mixed solution prepared in step 1): the concentration of chitosan is 0.02～0.12g/mL, the concentration of sulfobetaine is 0.14～0.84g/mL, the concentration of initiator is 0.76～3.0mg/mL, The concentration of the cross-linking agent is 0.16-0.96 mg/mL; the preparation process is to first dissolve the sulfobetaine, the initiator and the cross-linking agent in a solvent, and then add chitosan to dissolve after stirring evenly; the solvent includes water .

In the technical scheme of the present invention, the concentration ratio and addition order of the four raw materials are controlled to ensure that the chitosan will not have a negative impact on the second heavy network during the production process, and to ensure that the initiator and cross-linking agent are sufficient to initiate the reaction, Good formation of the second heavy network is promoted without leaving a large amount of impurities.

Preferably, the sulfobetaine in step 1) is 3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium]propane-1 - Sulfonate.

3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium]propane-1-sulfonic acid inner salt is a functional monomer, which It has abundant cationic groups and anionic groups, and is electrically neutral as a whole, and it can strongly bind water molecules through electrostatic-induced hydration and generate more hydrogen ions, making the amino groups on chitosan more It has positive charge in many places, and also has a positive promotion effect on chitosan network formation.

Preferably, in step 1) the molecular weight of the chitosan is less than 10000 Da; the degree of deacetylation of the chitosan is more than 90%.

Molecular weight chitosan has good water solubility, and its solubility in water is higher. Compared with large molecular weight chitosan, it has shorter chain length and better mechanical properties in water, and has better mechanical properties of hydrogels. Significantly. And compared with the long-chain high-molecular-weight chitosan, it is easier to form a complex first-heavy network, reducing its linearity.

Preferably, the initiator in step 1) is α-ketoglutaric acid; the cross-linking agent is N,N-methylenebisacrylamide.

α-Ketoglutaric acid and N,N-methylenebisacrylamide have good initiating and promoting effects on the cross-linking reaction of sulfobetaine, and can form a good cross-linking network of sulfobetaine.

Preferably, the mold in step 2) includes a silicone rubber sheet with pores; the thickness of the silicone rubber sheet is less than or equal to 2 mm.

Preferably, the ultraviolet light with a wavelength of 340 to 400 nm is selected for the ultraviolet light irradiation reaction in step 2); the ultraviolet light irradiation reaction time is 5 to 9 hours.

Preferably, in step 3) the multivalent negative ion solution includes multivalent acid ions; the multivalent acid ions include citrate ions.

The beneficial effects of the present invention are:

1) Anion and chitosan are selected to form the first network, so that the hydrogel has good antibacterial properties and biocompatibility, which further improves the mechanical properties of the double network hydrogel, and also has a certain degree of mechanical properties. Self-healing ability, and the first network and the second network are intertwined rather than simply interspersed, and the dual network stability is higher;

2) The prepared double network hydrogel has excellent toughness and elasticity, and also has good antibacterial, anti-nonspecific protein adsorption and anti-cell adhesion properties, and has broad application prospects in the field of biomedicine;

3) The preparation method is simple, efficient and environmentally friendly, and is environmentally friendly.

Description of drawings

Fig. 1 is the tensile stress-strain curve of the chitosan/polysulfobetaine ion-donating double network hydrogel prepared in Example 1 and Example 2;

Fig. 2 is the tensile stress-strain curve of the chitosan/polysulfobetaine ion-donating double network hydrogel prepared in Example 3 and Example 4;

Fig. 3 is the tensile stress-strain curve of the chitosan/polysulfobetaine ion-donating double network hydrogel prepared in Example 5 and Example 6;

4 is the compressive stress-strain curve of the chitosan/polysulfobetaine ion-donating double network hydrogel prepared in Example 1;

Fig. 5 is the antibacterial effect diagram of the prepared chitosan/polysulfobetaine ion-supplied double network hydrogel on Escherichia coli prepared in Example 1;

Fig. 6 is the antibacterial effect diagram of the prepared chitosan/polysulfobetaine ion-supplied double network hydrogel on Staphylococcus aureus prepared in Example 1;

7 is a graph showing the anti-nonspecific protein adsorption effect of the chitosan/polysulfobetaine ion-donating double network hydrogel prepared in Example 1.

Detailed ways

The present invention will be further described and described in detail below with reference to specific embodiments and accompanying drawings. Those of ordinary skill in the art will be able to implement the present invention based on these descriptions. In addition, the embodiments of the present invention referred to in the following description are generally only some embodiments of the present invention, not all of the embodiments. Therefore, based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without creative work shall fall within the protection scope of the present invention.

Unless otherwise specified, the raw materials used in the examples of the present invention are commercially available or available to those skilled in the art; unless otherwise specified, the methods used in the embodiments of the present invention are all methods mastered by those skilled in the art.

Example 1

A preparation method of chitosan/polysulfobetaine ion-supplied double network hydrogel, the preparation method comprises the following preparation steps:

1) Dissolve 2.8g of sulfobetaine, 15mg of initiator and 3mg of cross-linking agent in 5mL of water, add 0.5g of chitosan after stirring for 10min and dissolve with ultrasonic vibration for 30min to prepare chitosan, sulfobetaine, initiator Mixed solution of agent and crosslinking agent;

2) The mixed solution is placed in a mold, and the mold is composed of a silicon rubber sheet with pores and a thickness of 2 mm indirectly arranged between two glass sheets. The mixed solution is placed in the mold and sealed. The reaction was irradiated with ultraviolet light for 6h, and the pre-gel was obtained after the reaction;

3) Immerse the pregel in a saturated trisodium citrate solution for 30 minutes to obtain the chitosan/polysulfobetaine ion-donating double network hydrogel.

Wherein, sulfobetaine is 3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium]propane-1-sulfonic acid inner salt; The molecular weight of chitosan is less than 10000Da, the degree of deacetylation is more than 90%; the initiator is α-ketoglutaric acid; the cross-linking agent is N,N-methylenebisacrylamide.

The tensile stress-strain curve results of the chitosan/polysulfobetaine ion-donating double network hydrogel prepared in this example are shown in the E curve in Figure 1, and the tensile strength is 1.95MPa , the elongation at break is 417%; its compressive stress-strain curve is shown in Figure 4, and its compressive strength is as high as 119MPa; its antibacterial effect is shown in Figures 5 and 6, and its anti-nonspecific protein adsorption effect is shown in Figure 4 As shown in Figure 7, it can be clearly seen from the figure that the chitosan/polysulfobetaine ion-donating double network hydrogel of this example has excellent antibacterial and anti-nonspecific protein adsorption effects.

Example 2

The difference between this example and Example 1 is that the chitosan added in step 1) is 0.1g, 0.2g, 0.3g, 0.4g and 0.6, respectively; the rest are exactly the same as Example 1.

The tensile stress-strain curves of the chitosan/polysulfobetaine ion-donating double-network hydrogel prepared in this example are shown as curve A, curve B, curve C, curve D and curve F in order in Figure 1. As shown, its tensile strength is 0.34MPa, 1.01MPa, 1.61MPa, 1.63MPa and 1.14MPa, and its elongation at break is 782%, 727%, 681%, 531% and 292%.

Example 3

A preparation method of chitosan/polysulfobetaine ion-supplied double network hydrogel, the preparation method comprises the following preparation steps:

1) Dissolve 0.7g of sulfobetaine, 3.8mg of initiator and 0.8mg of cross-linking agent in 5mL of water, add 0.2g of chitosan after stirring for 10min and dissolve with ultrasonic vibration for 30min to prepare chitosan and sulfobetaine , mixed solution of initiator and crosslinking agent;

2) The mixed solution is placed in a mold, and the mold is composed of a silicon rubber sheet with pores and a thickness of 2 mm indirectly arranged between two glass sheets. The mixed solution is placed in the mold and sealed. The reaction was irradiated with ultraviolet light for 6h, and the pre-gel was obtained after the reaction;

3) Immerse the pregel in a saturated trisodium citrate solution for 30 minutes to obtain the chitosan/polysulfobetaine ion-donating double network hydrogel.

Wherein, sulfobetaine is 3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium]propane-1-sulfonic acid inner salt; The molecular weight of chitosan is less than 10000Da, the degree of deacetylation is more than 90%; the initiator is α-ketoglutaric acid; the cross-linking agent is N,N-methylenebisacrylamide.

The tensile stress-strain curve of the chitosan/polysulfobetaine ion-donating double network hydrogel prepared in this example is shown in the curve A in Figure 2. The tensile strength is 0.10 MPa, and the fracture The elongation is 171%.

Example 4

The difference between this example and Example 3 is: the added sulfobetaines in step 1) are respectively 1.4g, 2.1g, 2.8g, 3.5g and 4.2g respectively; the rest are the same as in Example 3.

The tensile stress-strain curves of the chitosan/polysulfobetaine ion-donating double network hydrogel prepared in this example are shown in Figure 2 as B curve, C curve, D curve, E curve and As shown by the F curve, the tensile strengths are 0.69MPa, 0.91MPa, 1.01MPa, 0.94MPa and 0.56MPa respectively, and the elongation at break are 558%, 723%, 727%, 646% and 578% respectively.

Example 5

A preparation method of chitosan/polysulfobetaine ion-supplied double network hydrogel, the preparation method comprises the following preparation steps:

1) Dissolve 2.8g of sulfobetaine, 15mg of initiator and 0.8mg of cross-linking agent in 5mL of water, add 0.2g of chitosan after stirring for 10min and dissolve with ultrasonic vibration for 30min to prepare chitosan, sulfobetaine, Mixed solution of initiator and crosslinking agent;

2) The mixed solution is placed in a mold, and the mold is composed of a silicon rubber sheet with pores and a thickness of 2 mm indirectly arranged between two glass sheets. The mixed solution is placed in the mold and sealed. The reaction was irradiated with ultraviolet light for 6h, and the pre-gel was obtained after the reaction;

3) Immerse the pregel in a saturated trisodium citrate solution for 30 minutes to obtain the chitosan/polysulfobetaine ion-donating double network hydrogel.

Wherein, sulfobetaine is 3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium]propane-1-sulfonic acid inner salt; The molecular weight of chitosan is less than 10000Da, the degree of deacetylation is more than 90%; the initiator is α-ketoglutaric acid; the cross-linking agent is N,N-methylenebisacrylamide.

The tensile stress-strain curve of the chitosan/polysulfobetaine ion-donating double network hydrogel prepared in this example is shown in the curve A in Fig. 3, the tensile strength is 0.44MPa, the fracture The elongation is 592%.

Example 6

The difference between this example and Example 5 is that the amount of crosslinking agent used in step 1) is 1.6g, 2.4g, 3.2g, 4.0g and 4.8g respectively; the rest is the same as Example 5.

The tensile stress-strain curves of the chitosan/polysulfobetaine ion-donating double network hydrogel prepared in this example are shown in Figure 3 as B curve, C curve, D curve, E curve and F curve shown. The tensile strengths were 0.82MPa, 0.85MPa, 1.01MPa, 0.82MPa and 0.68MPa, respectively, and the elongation at break were 847%, 572%, 727%, 631% and 620%, respectively.

Example 7

The difference between this example and Example 1 is that: in step 2), the conditions of the ultraviolet light irradiation reaction are respectively 340nm wavelength ultraviolet light irradiation for 5h, 355nm wavelength ultraviolet light irradiation for 5.5h, 370nm wavelength ultraviolet light irradiation for 7h, 385nm wavelength ultraviolet light irradiation for 7h, and 385nm wavelength ultraviolet light irradiation respectively Irradiate for 8h and 400nm wavelength ultraviolet light for 9h; the rest is the same as in Example 1.

The tensile strengths of the chitosan/polysulfobetaine ion-donating double network hydrogels prepared in this example are 1.87MPa, 1.84MPa, 1.82MPa, 1.83MPa and 1.87MPa respectively, and the elongation at break They are 452%, 511%, 534%, 526% and 471%, respectively.

In the embodiment of the present invention, the performance detection is all carried out according to the following standards:

(1) Tensile mechanical property test: Using a glass mold with a thickness of 1 mm, a hydrogel spline with a length of 40 mm and a width of 10 mm was prepared. 1mm hydrogel splines. Take 3 splines to carry out mechanical tensile test on Instron5966 universal material testing machine, the tensile speed is 100mm/min, and the mechanical properties are measured;

(2) Compression mechanical performance test: A cylindrical hydrogel sample with a height of 8 mm was prepared with a glass mold with a diameter of 8 mm, and 3 splines were taken to perform a mechanical tensile test on an Instron 5966 universal material testing machine at a compression speed of 2 mm/min. , to measure its mechanical properties;

(3) Antibacterial experiment: prepare a 10×10×1mm cuboid hydrogel sample, soak it in 75% ethanol for 30min to sterilize, then soak it in PBS buffer solution for 30min, put the hydrogel into a 12-well plate, add the OD value 0.1 Escherichia coli strain/1 mL of Staphylococcus aureus was co-cultured for 24 hours at 37°C, 120 rpm shaker. After culturing, react with dyes under dark conditions for 15 min, and take fluorescence photos with a fluorescence microscope;

(4) Anti-non-specific protein adsorption experiment: prepare a 5×5×1mm cuboid hydrogel sample, soak it in 75% ethanol for 30min to sterilize, then soak it in PBS buffer solution for 30min, and put the hydrogel into a 24-well plate , add 1 mL of 1 μg/mL HRP-IgG protease solution, and transfer the hydrogel to 1 mL of PBS buffer solution after soaking for 1.5 h. After soaking in PBS solution for 0.5 and 3 h, transfer the hydrogel to 1 mL of citric acid-phosphate buffer solution ( containing 0.03% H ₂ O ₂ , 20 μg/mL o-phenylenediamine), the enzymatic reaction was terminated with 2M H ₂ SO ₄ after the reaction for 15 min, and the enzyme reaction was tested with a microplate reader at 492 nm.

To sum up, it can be clearly seen that the chitosan/polysulfobetaine ion-donating double network hydrogel of the present invention has good mechanical properties, and also has good antibacterial and anti-nonspecific protein adsorption properties. , has broad application prospects in the field of biomedical materials.

Claims (9)

1. a kind of chitosan/polysulfonate acidic group beet basic ion is for valence double-network hydrogel, which is characterized in that the chitosan/poly- Sulfonic group beet basic ion is dual network structure for valence double-network hydrogel, is mutually passed through by the first weight network and the second weight network It wears to be formed, the first weight network is the physical cross-linked network formed by chitosan and multivalent state anion by coordination, Second weight network is the chemical crosslinking network that polysulfonate acidic group glycine betaine is formed, and the first weight network is interspersed in the second weight network.

2. a kind of chitosan as described in claim 1/polysulfonate acidic group beet basic ion is for the preparation method of valence double-network hydrogel, It is characterized in that, the preparation method includes following preparation step:

1) mixed solution of chitosan, sulfonic group glycine betaine, initiator and crosslinking agent is prepared；

2) mixed solution is placed in mold, ultraviolet light is reacted under the conditions of protective atmosphere, obtains pregel after reaction；

3) pregel is placed in multivalent state negative solution and is impregnated to get the chitosan/polysulfonate acidic group beet basic ion is arrived For valence double-network hydrogel.

3. a kind of chitosan according to claim 2/polysulfonate acidic group beet basic ion is for the preparation of valence double-network hydrogel Method, which is characterized in that in the prepared mixed solution of step 1): chitosan concentration is 0.02~0.12g/mL, sulfonic group sweet tea Dish alkali concentration is 0.14~0.84g/mL, initiator concentration is 0.76~3.0mg/mL, crosslinker concentration is 0.16~0.96mg/ mL；The process for preparation is that first sulfonic group glycine betaine, initiator and crosslinking agent are dissolved in solvent, and it is poly- to be stirring evenly and then adding into shell Sugar dissolution；The solvent includes water.

4. a kind of chitosan according to claim 2 or 3/polysulfonate acidic group beet basic ion is for the system of valence double-network hydrogel Preparation Method, which is characterized in that step 1) the sulfonic group glycine betaine is 3- [N, N- dimethyl-[2- (2- methyl propyl- 2- alkene acyl-oxygen Base) ethyl] ammonium] propane -1- acid inner salt.

5. a kind of chitosan according to claim 2 or 3/polysulfonate acidic group beet basic ion is for the system of valence double-network hydrogel Preparation Method, which is characterized in that step 1) the molecular weight of chitosan < 10000Da；The deacetylation > 90% of the chitosan.

6. a kind of chitosan according to claim 2 or 3/polysulfonate acidic group beet basic ion is for the system of valence double-network hydrogel Preparation Method, which is characterized in that the step 1) initiator is α-ketoglutaric acid；The crosslinking agent is N, N- methylene bisacrylamide acyl Amine.

7. a kind of chitosan according to claim 2/polysulfonate acidic group beet basic ion is for the preparation of valence double-network hydrogel Method, which is characterized in that the step 2) mold be include the silicone rubber plate with hole；Silicone rubber plate thickness≤the 2mm.

8. a kind of chitosan according to claim 2/polysulfonate acidic group beet basic ion is for the preparation of valence double-network hydrogel Method, which is characterized in that the step 2) ultraviolet light selects wavelength when reacting be the ultraviolet light of 340~400nm；The purple A length of 5~9h when outer photo-irradiation reaction.

9. a kind of chitosan according to claim 2/polysulfonate acidic group beet basic ion is for the preparation of valence double-network hydrogel Method, which is characterized in that step 3) the multivalent state negative solution includes multivalent state acid ion；The multivalent state acid group from Attached bag includes citrate ion.