CN104845382A - Silk protein/cellulose derivative blending hydrogel and preparation method thereof - Google Patents

Abstract

The invention belongs to the technical field of natural polymer materials and biomedical materials, and specifically relates to a blended hydrogel of silk protein/cellulose derivatives and a preparation method thereof. In the invention, the high-strength hydrogel with a solid content of 4-20% is prepared by heating the aqueous solution of silk protein and hydroxypropyl methylcellulose or the blended aqueous solution of methylcellulose or hydroxypropyl cellulose. The preparation process of the present invention is simple, green and mild, energy-saving and efficient, and low in cost, and the mechanical properties of the final hydrogel can be controlled by simply changing the solid content; the prepared high-strength hydrogel based on natural macromolecules can be applied to Biomedical field.

Description

A kind of silk protein/cellulose derivative blended hydrogel and preparation method thereof

technical field

The invention belongs to the technical field of natural polymer materials and biomedical materials, and in particular relates to a high-strength natural biomacromolecule hydrogel and a preparation method thereof.

Background technique

Polymer hydrogel is a three-dimensional network with a water content of up to 90%, in which the polymer is in a swollen but insoluble state in water. Generally, hydrogels are divided into two types: chemically crosslinked hydrogels and physically crosslinked hydrogels. The advantage of ordinary chemically cross-linked hydrogels is that the mechanical properties of the final hydrogel can be controlled by changing the chemical structure, but the disadvantages are poor biocompatibility and the need to introduce chemical cross-linking agents. The advantage of physically cross-linked hydrogels is that they are often three-dimensional networks formed by natural polymers or FDA-approved synthetic polymers such as PVA, which have better biocompatibility than chemical gels. The disadvantage is that it is difficult to control the mechanical properties of the final hydrogel by changing the chemical structure, or it is difficult to artificially control the mechanical properties of the final hydrogel. In addition, the mechanical properties of physically crosslinked hydrogels are much worse than those of chemical hydrogels. However, traditional chemical hydrogels and physical hydrogels are at a relatively low level in terms of tensile and compressive modulus and ductility, which is far from the requirements of practical applications. . Therefore, how to improve the mechanical properties of hydrogels has always been a research hotspot in recent years. The preparation of double network hydrogels, nanocomposite hydrogels and topological gels are three commonly used methods to improve the mechanical properties of hydrogels, but The above three methods for preparing hydrogels have limited applicability to natural biomacromolecules.

Silk is an ancient natural protein material. Due to its inherent excellent mechanical properties and biocompatibility as well as a wide range of sources, silk and silk protein-based materials have broad application prospects in the biomedical field. The use of regenerated silk protein solutions to prepare hydrogels has been reported many times, but its mechanical properties cannot meet the mechanical properties of artificially synthesized chemical hydrogels or the requirements of tissues with high mechanical properties, such as ligaments or cartilage. Water-soluble cellulose derivatives such as hydroxypropylmethylcellulose, methylcellulose and hydroxypropylcellulose are all derivatives of natural polysaccharide-cellulose, and the hydrophobic groups on their side chains make them thermosensitive. For example, the aqueous solution of hydroxypropyl methylcellulose or aqueous methylcellulose can change from a transparent solution to a gel after heating, and return to a solution state after cooling down to room temperature; while heating an aqueous solution of hydroxypropyl cellulose can cause precipitation , but still becomes a solution after cooling down. At the same time, like silk protein, these three cellulose derivatives have good biocompatibility.

The present invention obtains a class of hydrogels with high modulus, strong toughness and good biocompatibility by heating the blended aqueous solution of mulberry silk protein and cellulose derivatives. This type of hydrogel can be controlled by controlling the solid content To adjust the final mechanical properties, it overcomes a major shortcoming of traditional physical gels. In addition, compared with the preparation of chemical gels, its preparation method is more convenient and mild, green and environmentally friendly, and also avoids the use of chemical cross-linking agents, and its biocompatibility is well maintained. This simple and rapid preparation method also provides feasibility for its future industrialized large-scale production.

Contents of the invention

The object of the present invention is to provide a hydrogel with good biocompatibility and excellent mechanical properties and a preparation method thereof.

The hydrogel provided by the present invention is a blended hydrogel of mulberry silk protein and cellulose derivatives. The aqueous solution of mulberry silk protein and the aqueous solution of cellulose derivatives with a mass concentration of 4 to 20% are mixed according to a certain volume. It is made by mixing, and the mass fraction of mulberry silk protein accounting for the overall solid in the final blended hydrogel is 30% ~ 90%; the cellulose derivative is hydroxypropyl methylcellulose or methylcellulose or hydroxypropyl cellulose.

The preparation method of the blended hydrogel of mulberry silk protein/cellulose derivative provided by the invention, the specific steps are:

(1) Prepare an aqueous solution of regenerated mulberry silk protein so that its final concentration is 4% to 20%;

(2) Under stirring, dissolve hydroxypropylmethylcellulose or methylcellulose or hydroxypropylcellulose aqueous solution powder in deionized water to make the final concentration 4%~20%;

(3) Mix the two solutions obtained in step (1) and step (2) evenly, and heat in a water bath.

In step (3), the volume ratio of mulberry silk protein aqueous solution: cellulose derivative aqueous solution is 3:7 ~ 9:1.

In step (3), the heating temperature of the water bath is 65°C to 90°C.

In step (3), the heating time of the water bath is 2 hours to 24 hours.

The hydrogel preparation method of the present invention is simple, efficient, green and environmentally friendly, and does not involve any chemical cross-linking agent or biological cross-linking agent in the preparation process. are preserved in the process.

The biocompatibility and biodegradability of the hydrogel of the present invention are much higher than those of the synthetic polymer hydrogel.

Advantages of the present invention:

(1) Compared with the preparation method of chemical gel, the preparation method of the hydrogel of the present invention is simpler and more efficient, the preparation conditions are mild, green and environmentally friendly, and it is beneficial to realize large-scale industrial production;

(2) The source of raw materials of the hydrogel of the present invention is more extensive than that of chemical gels, and the cost is lower;

(3) The hydrogel of the present invention has excellent biocompatibility while having excellent mechanical properties.

Description of drawings

Fig. 1 is a flow diagram of the method of the present invention.

Figure 2 shows the mechanical properties of the high-strength hydrogel of the present invention. The arrow points to the hydrogel prepared in the present invention. The volume is about 1 cm ³ , the height is about 10 mm, and the diameter is about 9 mm. The hydrogel is solid The content is 10%.

Detailed ways

Below in conjunction with specific embodiment, further illustrate the present invention. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Example 1

Prepare regenerated silk protein and hydroxypropyl methylcellulose aqueous solutions with concentrations of 6%, 8% and 10%, respectively, and mix the same concentration of silk protein aqueous solution and hydroxypropyl methylcellulose aqueous solution at a volume ratio of 9:1, Ensure that the final mixed solution concentration (that is, the following solid content value) is 6%, 8% or 10%, and heat in a 65 ^o C water bath for 2 hours to form a hydrogel. The mechanical properties test shows that the tensile modulus of the hydrogel with a solid content of 6% is 0.37 MPa, the elongation at break is 120%, and the compressive modulus is 0.47 MPa; the tensile modulus of the hydrogel with a solid content of 8% is 0.75 MPa, The elongation at break was 116%, and the compressive modulus was 0.75 MPa; the tensile modulus was 1.23 MPa, the elongation at break was 108%, and the compressive modulus was 1.45 MPa.

Example 2

Prepare a 10% regenerated silk protein aqueous solution and a 10% hydroxypropyl methylcellulose aqueous solution, mix the silk protein aqueous solution and the hydroxypropyl methylcellulose aqueous solution at a volume ratio of 9:1, and ensure that the final mixed solution concentration is 10%. After heating in a water bath at 65 ^o C for 2 hours, a cylindrical sample was finally obtained. The tensile modulus was 1.40 MPa, the elongation at break was 105%, and the compressive modulus was 1.34 MPa.

Example 3

Prepare a 10% regenerated silk protein aqueous solution and a 10% hydroxypropyl methylcellulose aqueous solution, mix the silk protein aqueous solution and the hydroxypropyl methylcellulose aqueous solution at a volume ratio of 9:1, and ensure that the final mixed solution concentration is 10%. After heating in a water bath at 90 ^o C for 2 hours, a cylindrical sample was finally obtained. The tensile modulus was 1.28 MPa, the elongation at break was 117%, and the compressive modulus was 1.34 MPa.

Example 4

Prepare a 10% regenerated silk protein aqueous solution and a 10% hydroxypropyl methylcellulose aqueous solution, and mix the silk protein aqueous solution and the hydroxypropyl methylcellulose aqueous solution at a volume ratio of 5:5 or 7:3 to ensure that the final The concentration of the mixed solution is 10%. Hydrogels were obtained by heating in a water bath at 65 ^o C for 2 h, and the compressive moduli were 0.34 MPa (5:5) and 0.92 MPa (7:3); however, the hydrogels prepared at this ratio were not strong enough to conduct tensile tests , and the gel is not uniform.

Example 5

Prepare a 10% regenerated silk protein aqueous solution and a 10% methylcellulose aqueous solution, mix the silk protein aqueous solution and methylcellulose aqueous solution at a volume ratio of 9:1, and ensure that the final mixed solution concentration is 10%. After heating in a water bath at 65 ^o C for 2 hours, a cylindrical sample was finally obtained, and its compressive modulus was found to be 0.58 MPa through mechanical property tests.

Example 6

Prepare a 10% regenerated silk protein aqueous solution and a 10% hydroxypropyl cellulose aqueous solution, mix the silk protein aqueous solution and hydroxypropyl cellulose aqueous solution at a volume ratio of 9:1, and ensure that the final mixed solution concentration is 10%. After heating in a water bath at 65 ^o C for 2 hours, a cylindrical sample was finally obtained, and its compressive modulus was found to be 0.27 MPa through mechanical property tests.

Example 7

Prepare a 10% regenerated silk protein aqueous solution and a 10% hydroxypropyl methylcellulose aqueous solution, mix the silk protein aqueous solution and the hydroxypropyl methylcellulose aqueous solution at a volume ratio of 9:1, and ensure that the final mixed solution concentration is 10%. Heated in a water bath at 65 ^o C for 2 hours to obtain a high-strength hydrogel. After sterilization, its biocompatibility was tested with L929 cells. After three days, the cell survival rate reached 93.9±6.29%, which proved that it had no cytotoxicity, so it has the potential to be used as a biomedical gel. material potential.

Claims (3)

1. A blended hydrogel of silk protein/cellulose derivative is characterized in that it is made by mixing an aqueous solution of mulberry silk protein with a mass concentration of 4 to 20% and an aqueous solution of cellulose derivatives in a certain volume ratio, The mass fraction of mulberry silk protein accounting for the overall solid in the final blended hydrogel is 30% ~ 90%; the cellulose derivative is hydroxypropyl methylcellulose or methylcellulose or hydroxypropyl fiber white. 2. a preparation method of the blended hydrogel of silk protein/cellulose derivative as claimed in claim 1, is characterized in that concrete steps are: (1) Prepare an aqueous solution of regenerated mulberry silk protein so that its final concentration is 4% to 20%; (2) Under stirring, dissolve hydroxypropylmethylcellulose or methylcellulose or hydroxypropylcellulose aqueous solution powder in deionized water to make the final concentration 4%~20%; (3) Mix the two solutions obtained in step (1) and step (2) evenly, and heat in a water bath. 3. The preparation method according to claim 2, characterized in that: in step (3), the volume ratio of silkworm silk protein aqueous solution: cellulose derivative aqueous solution is 3:7 ~ 9:1; the heating temperature of the water bath is 65°C to 90°C; the heating time in the water bath is 2 hours to 24 hours.