Collagen-based composite material and preparation method thereof

Abstract

The invention discloses a collagen-based composite material and a preparation method thereof. The invention belongs to the technical field of composite materials. The collagen-based composite material comprises the following components in parts by weight: 50-60 parts of collagen; 10 to 20 parts of nano cellulose; 20 to 30 parts of a reinforcing component; 1-3 parts of a cross-linking agent; and 0.5-2 parts of a functional additive. By adding the reinforcing component, the mechanical strength of the collagen-based composite material is remarkably improved, and meanwhile, the non-toxic cross-linking agent and the natural reinforcing component are adopted, so that the material has good biocompatibility and does not generate toxic or adverse reaction on cells and tissues; according to the present invention, the porous three-dimensional network structure is provided, the pore size is 50-300 [mu] m, the porosity is more than or equal to 80%, the cell adhesion, the proliferation and the nutrient substance transmission are easily achieved, and the method is suitable for tissue engineering and wound repair; according to the collagen-based composite material disclosed by the invention, through reasonable raw material formula design, the collagen, the nano cellulose and the natural polysaccharide are compounded, the advantages of all the components are fully exerted, and the comprehensive performance of the composite material is further improved.

Description

Technical Field

[0001] The invention belongs to the technical field of composite materials, and specifically refers to a collagen-based composite material and a preparation method thereof. Background Art

[0002] As a natural high molecular weight protein, collagen is widely found in animal skin, bones, tendons and other tissues. Its unique triple helix structure gives it good biocompatibility, which makes it show great application potential in the biomedical field, such as wound dressings, tissue engineering scaffolds, and drug sustained-release carriers. In the process of wound healing, collagen materials can provide a suitable microenvironment for cell adhesion, proliferation and differentiation, and promote rapid wound healing; in tissue engineering, it can be used as a basic material for constructing tissues and organs, guiding cell growth and tissue regeneration.

[0003] However, pure collagen materials have many limitations. From the perspective of mechanical properties, their strength and toughness are relatively low, making it difficult to meet the requirements of some application scenarios with high mechanical properties, such as load-bearing tissue repair. Under the physiological environment in the body, pure collagen materials are easily degraded by enzymatic hydrolysis and have poor stability, which limits their application in long-term implant materials. At the same time, their processing performance is not ideal, and it is difficult to obtain precise shapes and sizes during the molding process.

[0004] To overcome these shortcomings, researchers have tried to compound collagen with other materials to prepare collagen-based composite materials with better performance. Currently, common composite methods include composite with synthetic polymer materials, such as polylactic acid (PLA), polycaprolactone (PCL), etc., and composite with inorganic materials, such as hydroxyapatite (HA), nano-titanium dioxide (TiO2), etc. However, synthetic polymer materials often have poor biocompatibility and may induce immune responses; there are compatibility issues at the interface between inorganic materials and collagen, resulting in unstable overall performance of the composite materials. Moreover, most of the existing preparation processes are relatively complicated, requiring the use of a large amount of organic solvents and complex equipment, which not only increases production costs, but also causes certain pollution to the environment. For example, in some composite processes, toxic organic solvents are needed to dissolve synthetic polymer materials. These solvents are difficult to completely remove in subsequent processing, and residual solvents may affect the biosafety of the materials. In addition, the existing processes have difficulties in achieving uniform dispersion and effective combination of collagen and other materials, resulting in poor uniformity and repeatability of composite material performance. Therefore, it is urgent to develop a collagen-based composite material and its preparation method with excellent performance, simple preparation process and green environmental protection. Summary of the invention

[0005] The purpose of the present invention is to provide a collagen-based composite material and a preparation method thereof. The present invention significantly improves the mechanical strength of the collagen-based composite material by adding a reinforcing component, and adopts a non-toxic cross-linking agent and a natural reinforcing component to ensure that the material has good biocompatibility and will not produce toxicity or adverse reactions to cells and tissues; the present invention has a porous three-dimensional network structure, a pore size of 50-300 μm, a porosity of ≥80%, is conducive to cell adhesion, proliferation and nutrient transmission, and is suitable for tissue engineering and wound repair; the collagen-based composite material of the present invention is compounded by a reasonable raw material formula design, collagen, nanocellulose and natural polysaccharide, giving full play to the advantages of each component. Nanocellulose has high strength and modulus, and can effectively enhance the mechanical properties of the collagen-based composite material; natural polysaccharides have good biocompatibility and biological activity, further improving the comprehensive performance of the composite material.

[0006] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present invention is as follows: a collagen-based composite material and a preparation method thereof, wherein the collagen-based composite material comprises the following components in parts by weight: 30-90 parts of collagen; 10-50 parts of nanocellulose; 10-40 parts of reinforcing component; 0.5-10 parts of cross-linking agent; and 0.1-10 parts of functional additives.

[0007] Preferably, the collagen-based composite material comprises the following components in parts by weight: 40-80 parts of collagen; 10-30 parts of nanocellulose; 20-40 parts of reinforcing component; 1-7 parts of cross-linking agent; and 0.2-5 parts of functional additives.

[0008] Preferably, the collagen-based composite material comprises the following components in parts by weight: 50-60 parts of collagen; 10-20 parts of nanocellulose; 20-30 parts of reinforcing component; 1-3 parts of cross-linking agent; and 0.5-2 parts of functional additives.

[0009] Preferably, the collagen is bovine skin collagen or fish skin collagen.

[0010] Preferably, the reinforcing component consists of one or more of chitosan and sodium alginate.

[0011] Preferably, the cross-linking agent is composed of one or more of genipin and glutaraldehyde.

[0012] Preferably, the functional additives consist of one or more of growth factors, antimicrobial agents and drug-loaded microparticles.

[0013] The present invention also provides a method for preparing a collagen-based composite material, the preparation method comprising the following steps:

[0014] (1) Collagen extraction and purification: Collagen is extracted from animal tissues by acid-enzymatic hydrolysis, and purified collagen sponge is obtained by dialysis and freeze-drying;

[0015] (2) Preparation of composite solution: dissolving collagen in a weak acid solution, mixing with the reinforcing component and nanocellulose in proportion, and ultrasonically dispersing; adding a crosslinking agent, adjusting the pH to 7-8, and reacting at low temperature with stirring for 6-24 hours to obtain a mixed solution;

[0016] (3) Molding and post-processing: injecting the mixed solution in step (2) into a mold, freeze-drying to form a porous scaffold; performing secondary cross-linking by ultraviolet irradiation or low-temperature plasma treatment; and packaging and storing after sterilization.

[0017] Furthermore, the weak acid solution in step (2) is 0.5 M acetic acid.

[0018] Furthermore, the sterilization method in step (3) is γ-ray irradiation.

[0019] The beneficial effects achieved by the present invention using the above structure are as follows: (1) The present invention significantly improves the mechanical strength of the collagen-based composite material by adding reinforcing components, and at the same time uses non-toxic cross-linking agents and natural reinforcing components to ensure that the material has good biocompatibility and will not cause toxicity or adverse reactions to cells and tissues; (2) The present invention has a porous three-dimensional network structure with a pore size of 50-300 μm and a porosity of ≥80%, which is conducive to cell adhesion, proliferation and nutrient transmission, and is suitable for tissue engineering and wound repair; (3) The collagen-based composite material of the present invention is compounded with collagen, nanocellulose and natural polysaccharides through a reasonable raw material formula design, giving full play to the advantages of each component and further improving the comprehensive performance of the composite material. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 Tensile strength of collagen-based composites.

[0021] The accompanying drawings are used to provide further understanding of the present invention and constitute a part of the specification. They are used to explain the present invention together with the embodiments of the present invention and do not constitute a limitation of the present invention. DETAILED DESCRIPTION

[0022] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments; based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0023] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein may be applied to the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only and are not intended to limit the content of this application.

[0024] The experimental methods in the following examples are conventional methods unless otherwise specified; the experimental materials and test strains used in the following examples are purchased from commercial channels unless otherwise specified.

[0025] Example 1

[0026] A collagen-based composite material and a preparation method thereof

[0027] The collagen-based composite material comprises the following components in parts by weight: 50 parts of collagen; 20 parts of nanocellulose; 20 parts of reinforcing components; 3 parts of cross-linking agents; and 0.5 parts of functional additives.

[0028] Wherein, the collagen is fish skin collagen; the reinforcing component is composed of chitosan and sodium alginate; the cross-linking agent is genipin; and the functional additive is composed of growth factors and antibacterial agents.

[0029] The present invention also provides a method for preparing a collagen-based composite material, the preparation method comprising the following steps:

[0030] (1) Collagen extraction and purification: Collagen is extracted from fish skin by acid-enzymatic hydrolysis, and purified collagen sponge is obtained by dialysis and freeze-drying;

[0031] (2) Preparation of composite solution: Dissolve collagen in 0.5 M acetic acid solution, mix with reinforcing component and nanocellulose in proportion, and disperse by ultrasonication; add crosslinking agent, adjust pH to 7-8, and react at low temperature with stirring for 6-24 hours to obtain a mixed solution;

[0032] (3) Molding and post-processing: injecting the mixed solution in step (2) into a mold, freeze-drying to form a porous scaffold; performing secondary cross-linking by ultraviolet irradiation; sterilizing by γ-ray irradiation, and then packaging for storage.

[0033] Example 2

[0034] A collagen-based composite material and a preparation method thereof

[0035] The collagen-based composite material comprises the following components in parts by weight: 60 parts of collagen; 10 parts of nanocellulose; 30 parts of reinforcing components; 1 part of a cross-linking agent; and 2 parts of a functional additive.

[0036] Wherein, the collagen is fish skin collagen; the reinforcing component is composed of chitosan and sodium alginate; the cross-linking agent is genipin; and the functional additive is composed of growth factors and antibacterial agents.

[0037] The present invention also provides a method for preparing a collagen-based composite material, and the preparation method is carried out with reference to Example 1.

[0038] Example 3

[0039] A collagen-based composite material and a preparation method thereof

[0040] The collagen-based composite material comprises the following components in parts by weight: 55 parts of collagen; 15 parts of nanocellulose; 25 parts of reinforcing components; 2 parts of cross-linking agents; and 1.2 parts of functional additives.

[0041] Wherein, the collagen is fish skin collagen; the reinforcing component is composed of chitosan and sodium alginate; the cross-linking agent is genipin; and the functional additive is composed of growth factors and antibacterial agents.

[0042] The present invention also provides a method for preparing a collagen-based composite material, and the preparation method is carried out with reference to Example 1.

[0043] Experimental Example 1

[0044] Mechanical properties test

[0045] The collagen-based composite materials prepared in Example 1, Example 2 and Example 3 were used as test samples and marked as Example 1 group to Example 3 group, with three replicates in each group. The tensile strength of the samples was tested using a universal material testing machine.

[0046] Result analysis: Figure 1 As shown, the collagen-based composite materials of Examples 1-3 all have relatively high tensile strengths, among which the tensile strength of Example 3 is the highest.

[0047] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

[0048] The present invention and its embodiments are described above, and such description is not restrictive. The drawings show only one embodiment of the present invention, and the actual structure is not limited thereto. In short, if ordinary technicians in the field are inspired by it, without departing from the purpose of the invention, they can design a structure and embodiment similar to the technical solution without creativity, which should belong to the protection scope of the present invention.

Claims

1. A collagen-based composite material, characterized in that: The collagen-based composite material comprises the following components in parts by weight: 30-90 parts of collagen; 10-50 parts of nanocellulose; 10-40 parts of reinforcing components; 0.5-10 parts of cross-linking agents; and 0.1-10 parts of functional additives.

2. The collagen-based composite material according to claim 1, characterized in that: The collagen-based composite material comprises the following components in parts by weight: 40-80 parts of collagen; 10-30 parts of nanocellulose; 20-40 parts of reinforcing components; 1-7 parts of cross-linking agents; and 0.2-5 parts of functional additives.

3. The collagen-based composite material according to claim 2, characterized in that: The collagen-based composite material comprises the following components in parts by weight: 50-60 parts of collagen; 10-20 parts of nanocellulose; 20-30 parts of reinforcing components; 1-3 parts of cross-linking agents; and 0.5-2 parts of functional additives.

4. The collagen-based composite material according to claim 3, characterized in that: The collagen is cow skin collagen or fish skin collagen.

5. The collagen-based composite material according to claim 4, characterized in that: The reinforcing component is composed of one or more of chitosan and sodium alginate.

6. The collagen-based composite material according to claim 5, characterized in that: The cross-linking agent is composed of one or more of genipin and glutaraldehyde.

7. The collagen-based composite material according to claim 6, characterized in that: The functional additives consist of one or more of growth factors, antimicrobial agents and drug-loaded microparticles.

8. A method for preparing the collagen-based composite material according to claim 7, characterized in that: The preparation method comprises the following steps: (1) Collagen extraction and purification: Collagen is extracted from animal tissues by acid-enzymatic hydrolysis, and purified collagen sponge is obtained by dialysis and freeze-drying; (2) Preparation of composite solution: dissolving collagen in a weak acid solution, mixing with the reinforcing component and nanocellulose in proportion, and ultrasonically dispersing; adding a crosslinking agent, adjusting the pH to 7-8, and reacting at low temperature with stirring for 6-24 hours to obtain a mixed solution; (3) Molding and post-processing: injecting the mixed solution in step (2) into a mold, freeze-drying to form a porous scaffold; performing secondary cross-linking by ultraviolet irradiation or low-temperature plasma treatment; and packaging and storing after sterilization.

9. The method for preparing a collagen-based composite material according to claim 8, characterized in that: The weak acid solution in step (2) is 0.5 M acetic acid.

10. The method for preparing a collagen-based composite material according to claim 9, characterized in that: The sterilization method in step (3) is gamma ray irradiation.

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