Organic-inorganic composite medical material and preparation method therefor

Abstract

The present invention is applied to the technical field of composite medical materials. Disclosed is an organic-inorganic composite medical material, the material consisting of organic components and inorganic components, the organic components comprising collagen, hyaluronic acid and chitosan, and the inorganic components being nano-hydroxyapatite and silica nanoparticles. Among the inorganic components of the organic-inorganic composite medical material, the nano-hydroxyapatite has the characteristics of good biocompatibility and osteoconductivity and thus enables the composite material to integrate with human bones; and the silica nanoparticles which have the characteristics of enhancing the strength and stability of materials improve the stability of the composite material. Among the organic components, proteins which are natively present in the human body and mainly comprise collagen can improve the biological activity and flexibility of the composite material, and promote cell growth and tissue regeneration; the collagen provides an attachment and growth environment for cells; and the hyaluronic acid is used for moisturizing and has an effect of promoting cell growth.

Description

An organic-inorganic composite medical material and its preparation method Technical Field

[0001] This invention relates to the field of composite medical materials technology, specifically to an organic-inorganic composite medical material and its preparation method. Background Technology

[0002] With the continuous advancement of medical technology, the performance requirements for medical materials are becoming increasingly stringent. Organic-inorganic composite medical materials, as a new type of material with great potential, are gradually becoming the focus of research. Traditional medical materials mainly include metal materials, polymer materials, and ceramic materials. Metal materials such as stainless steel and titanium alloys have high mechanical strength, but they have problems such as poor biocompatibility and easy corrosion. After long-term implantation in the human body, they may cause adverse consequences such as inflammatory reactions and allergic reactions. In addition, the elastic modulus of metal materials is much different from that of human bones, which can easily lead to stress shielding effect and affect the normal growth and repair of bone tissue. Polymer materials such as polyethylene and polylactic acid have good flexibility and processability, but their mechanical strength is relatively low, making it difficult to meet some high-strength medical needs. Moreover, some polymer materials may produce harmful substances during the degradation process in the body, posing a potential threat to human health. Ceramic materials such as alumina and zirconium oxide have excellent mechanical strength and chemical stability, but they are brittle and lack flexibility, making it difficult to adapt to the complex physiological environment of the human body.

[0003] However, existing organic-inorganic composite medical materials and their preparation methods still have some shortcomings. First, the preparation process is complex and costly. Currently, most methods for preparing organic-inorganic composite medical materials require complex chemical synthesis or physical processing techniques. These methods not only require expensive equipment and reagents, but also involve cumbersome operations, low production efficiency, and difficulty in large-scale production. Second, the material performance stability is insufficient. Due to the significant differences in properties between organic and inorganic materials, phase separation and poor interfacial bonding are prone to occur during the composite process, leading to unstable material performance. For example, during long-term use, the material may degrade, age, and experience a decrease in mechanical strength, affecting its service life and therapeutic effect. Finally, the bioactivity is not ideal. Although organic-inorganic composite medical materials have certain bioactivity, it is still far from comparable to that of human tissues. For example, in the process of bone repair, the material needs to effectively promote the growth, differentiation, and mineralization of osteoblasts, accelerating bone tissue regeneration and repair. However, the performance of existing materials in this regard is not ideal and needs further improvement.

[0004] Summary of the Invention

[0005] The purpose of this invention is to provide an organic-inorganic composite medical material and its preparation method, so as to solve the problems of poor material strength, stability and bioactivity mentioned in the background art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: an organic-inorganic composite medical material, which is composed of organic components and inorganic components, wherein the organic components include collagen, hyaluronic acid and chitosan, and the inorganic components are nano-hydroxyapatite and silica nanoparticles.

[0007] The proportions of the organic components, by mass percentage, are as follows:

[0008] Collagen 25%-35%

[0009] Hyaluronic acid 10%-15%

[0010] Chitosan 10%-15%

[0011] The inorganic components are proportioned as follows by mass percentage:

[0012] Nano-hydroxyapatite 20%-30%

[0013] 10%-20% silica nanoparticles

[0014] The total mass percentage of the organic and inorganic components is 100%.

[0015] Compared with the prior art, the beneficial effects of the present invention are: the organic-inorganic composite medical material:

[0016] 1. In inorganic materials, the excellent biocompatibility and osteoconductivity of nano-hydroxyapatite enable the composite material to integrate with human bone, while the strength and stability of silica nanoparticles enhance the stability of the composite material.

[0017] 2. In organic materials, collagen, a naturally occurring protein in the human body, can enhance the bioactivity and flexibility of composite materials, promote cell growth and tissue regeneration. Collagen provides an environment for cell attachment and growth, while hyaluronic acid moisturizes and promotes cell growth, and chitosan's antibacterial properties promote wound healing and prevent wound infection. Detailed Implementation

[0018] This invention provides a technical solution: an organic-inorganic composite medical material, which is composed of organic components and inorganic components. The organic components include collagen, hyaluronic acid and chitosan, and the inorganic components are nano-hydroxyapatite and silica nanoparticles.

[0019] The proportions of the organic components, by mass percentage, are as follows:

[0020] Collagen 25%-35%

[0021] Hyaluronic acid 10%-15%

[0022] Chitosan 10%-15%

[0023] The inorganic components are proportioned as follows by mass percentage:

[0024] Nano-hydroxyapatite 20%-30%

[0025] 10%-20% silica nanoparticles

[0026] The total mass percentage of the organic and inorganic components is 100%.

[0027] Experimental verification process for each embodiment:

[0028] I. Experimental Preparation

[0029] 1. Material preparation:

[0030] Accurately weigh nano-hydroxyapatite, silica nanoparticles, collagen, hyaluronic acid, and chitosan according to different proportions, prepare multiple combinations with different proportions, and prepare the solvents, stirring equipment, molds, drying equipment, sterilization equipment, etc. required for the experiment.

[0031] 2. Preparation of testing equipment:

[0032] Scanning electron microscope (SEM): Used to observe the microstructure of materials;

[0033] Universal testing machine: Used to test the mechanical properties of materials, such as tensile strength and compressive strength;

[0034] Cell culture equipment includes incubators, culture media, cell lines, etc., used to evaluate the biocompatibility of materials and their ability to promote cell growth;

[0035] Antimicrobial performance testing equipment: such as petri dishes and bacterial strains required for the inhibition zone method;

[0036] II. Experimental Procedure

[0037] 1. Material preparation:

[0038] Add the components in different proportions to the solvent in sequence, stir thoroughly to ensure that the components are well dispersed;

[0039] According to the experimental design, the mixed solution was prepared into a solid material by freeze-drying or other suitable drying methods.

[0040] The prepared materials are then sterilized.

[0041] 2. Mechanical performance testing:

[0042] Cut standard-shaped specimens from each group of materials, such as strips for tensile testing and cylinders for compression testing;

[0043] The specimens were tested using a universal testing machine, and data such as tensile strength and compressive strength were recorded.

[0044] Analyze the effects of different ratio combinations on the mechanical properties of the material.

[0045] 3. Biocompatibility testing:

[0046] The material is shaped to suit cell culture, such as in sheets or blocks;

[0047] Inoculate the surface of the material with specific cell lines, such as osteoblasts and skin cells;

[0048] Cells are cultured in a culture system containing the material and cultured for a period of time under certain conditions (such as temperature, humidity, CO2 concentration, etc.).

[0049] The growth of cells on the material surface is observed under a microscope, such as cell morphology and proliferation rate; cell activity is assessed using specific detection methods, such as the MTT assay.

[0050] 4. Antibacterial performance test:

[0051] The material is made into a circular sheet and placed in a petri dish containing bacterial strains;

[0052] After a period of cultivation, observe whether an inhibition zone appears around the material;

[0053] Measure the size of the inhibition zone to evaluate the antibacterial properties of the material.

[0054] III. Data Analysis and Conclusions

[0055] 1. Analyze the mechanical performance test data, compare the strength, toughness and other indicators of the materials under different ratio combinations, and determine the ratio range that meets medical requirements;

[0056] 2. Analyze the biocompatibility test results, observe the growth and activity of cells on the material, determine the degree of cell affinity of the material, and select a ratio combination that is conducive to cell growth and tissue regeneration;

[0057] 3. Based on the antibacterial performance test results, determine the proportions of ingredients that have good antibacterial effects;

[0058] 4. Taking into account factors such as mechanical properties, biocompatibility, and antibacterial properties, determine the optimal combination of material components.

[0059] Example 1, this example discloses:

[0060] The proportions of the organic components, by mass percentage, are as follows:

[0061] 35% collagen

[0062] 15% hyaluronic acid

[0063] Chitosan 15%

[0064] The inorganic components are proportioned as follows by mass percentage:

[0065] 20% Nano-hydroxyapatite

[0066] 15% silica nanoparticles

[0067] The total mass percentage of the organic and inorganic components is 100%.

[0068] Example 2: This example discloses:

[0069] The proportions of the organic components, by mass percentage, are as follows:

[0070] 30% collagen

[0071] 10% hyaluronic acid

[0072] Chitosan 20%

[0073] The inorganic components are proportioned as follows by mass percentage:

[0074] Nano-hydroxyapatite 25%

[0075] 15% silica nanoparticles

[0076] The total mass percentage of the organic and inorganic components is 100%.

[0077] Example 3: This example discloses:

[0078] The proportions of the organic components, by mass percentage, are as follows:

[0079] 25% collagen

[0080] 10% hyaluronic acid

[0081] Chitosan 15%

[0082] The inorganic components are proportioned as follows by mass percentage:

[0083] 30% Nano-hydroxyapatite

[0084] 20% silica nanoparticles

[0085] The total mass percentage of the organic and inorganic components is 100%.

[0086] The table below shows the strength test data for each embodiment.

[0087] Analysis: As the proportion of nano-hydroxyapatite and silica nanoparticles increases, the tensile strength does indeed tend to increase gradually. However, in terms of data stability, Example 2 has better stability while ensuring high tensile strength. When the proportion is too high, such as in Example 3, although the tensile strength value is high, the stability is insufficient, which may affect the reliability of the material in practical applications. Considering all factors, Example 2 is more suitable, as it can meet certain strength requirements without being too rigid.

[0088] The table below shows the biocompatibility test data for each embodiment.

[0089] Analysis: The material in Example 2 has the best affinity for cells, providing a good growth environment for cells and promoting cell growth and proliferation. The higher the cell activity, the better the biocompatibility of the material. Example 2 has the highest cell activity, indicating that the material at this ratio has low toxicity to cells and can promote normal cell metabolism and growth.

[0090] The table below shows the antibacterial performance test data for each embodiment.

[0091] Analysis: The larger the inhibition zone, the stronger the antibacterial performance of the material. The inhibition zone of Example 3 is the largest. However, considering that its performance in terms of mechanical properties and biocompatibility is not as good as that of Example 2, the antibacterial performance of Example 2 can meet the requirements.

[0092] The mechanical properties, biocompatibility, and antibacterial properties of organic-inorganic composite medical materials with different component ratios were tested, and the following conclusions were drawn:

[0093] Example 2 demonstrates a balanced performance across various indicators. The material with this composition ratio exhibits a tensile strength of 32 MPa and a compressive strength of 52 MPa, possessing moderate mechanical strength that meets medical requirements. It also exhibits a high proportion of regular cell morphology (95%) and cell viability (90%), demonstrating good biocompatibility and promoting cell growth and tissue regeneration. Furthermore, it possesses an inhibition zone diameter of 10 mm and exhibits certain antibacterial properties, reducing the risk of infection. Therefore, Example 2 can be considered a preferred proportion for this organic-inorganic composite medical material.

Claims

1. An organic-inorganic composite medical material, characterized in that, The material is composed of organic and inorganic components. The organic components include collagen, hyaluronic acid and chitosan, and the inorganic components are nano-hydroxyapatite and silica nanoparticles. The proportions of the organic components, by mass percentage, are as follows: Collagen 25%-35% Hyaluronic acid 10%-15% Chitosan 10%-15% The inorganic components are proportioned as follows by mass percentage: Nano-hydroxyapatite 20%-30% 10%-20% silica nanoparticles The total mass percentage of the organic and inorganic components is 100%.

2. The method for preparing an organic-inorganic composite medical material according to claim 1, characterized in that: The preparation method of this composite medical material includes the following steps: S1. Collagen Extraction: Clean the animal tissue to remove impurities and fat, and cut it into pieces for later use. Soak the cut animal tissue in an acidic solution, keep it warm and soak it to dissolve the collagen. Centrifuge the soaked solution to remove insoluble matter. Dialyze the centrifuged solution using a dialysis bag to remove small molecule impurities and acid. Freeze-dry the dialyzed solution to obtain collagen powder. S2. Hyaluronic acid extraction: Clean the animal tissue to remove impurities, treat the tissue with protease, keep warm and stir to decompose the protein, centrifuge the treated solution to remove insoluble matter, precipitate hyaluronic acid with organic solvent and collect the precipitate, then dissolve the precipitate with deionized water, dialyze and freeze dry to obtain hyaluronic acid powder. S3. Extraction of chitosan: Clean the shells of crustaceans and remove impurities. After drying, crush them into powder. Soak the powder in sodium hydroxide solution, heat and stir to react and deacetylate chitin into chitosan. Centrifuge the solution after reaction to remove insoluble matter. Wash the precipitate repeatedly with deionized water to remove sodium hydroxide. Dry the washed product to obtain chitosan powder. S4. Preparation of nano-hydroxyapatite: Prepare appropriate amounts of calcium chloride and sodium dihydrogen phosphate, and prepare calcium chloride solution and sodium dihydrogen phosphate solution respectively. Under stirring conditions, slowly add sodium dihydrogen phosphate solution to calcium chloride solution, add acid and base to adjust pH value to 7-8, and continue stirring for 0.5h-1h after the reaction is complete to allow the product to fully precipitate. Centrifuge the precipitate to remove the supernatant, wash the precipitate repeatedly with deionized water to remove impurity ions, put the washed product into a low temperature oven to dry, and grind the dried product to obtain nano-hydroxyapatite powder. S5. Preparation of silica nanoparticles: Prepare appropriate amounts of tetraethyl orthosilicate, ethanol, water and catalyst. Add tetraethyl orthosilicate to ethanol and stir evenly to obtain solution A. Mix water and catalyst and stir evenly to obtain solution B. Under stirring conditions, slowly add solution B to solution A and continue stirring for 2-4 hours to allow tetraethyl orthosilicate to hydrolyze and condense. After the reaction is complete, a sol is obtained. After a period of aging, it is converted into a gel. The gel is dried under normal or reduced pressure. The dried product is ground to obtain silica nanoparticles. S6. Weigh a certain amount of nano-hydroxyapatite powder, silica nanoparticle powder, collagen powder, hyaluronic acid powder, and chitosan powder and prepare an appropriate amount of phosphate buffer solution. S7. Add collagen powder, hyaluronic acid powder and chitosan powder to phosphate buffer solution and stir to dissolve to obtain an organic solution; S8. Slowly add nano-hydroxyapatite powder and silica nanoparticle powder to the organic solution while stirring to ensure uniform dispersion of the particles and obtain a mixed solution; S9. Using the freeze-drying method, the mixed solution is poured into a mold and frozen at -50℃ to -80℃ for a period of time. Then, it is dried under vacuum to sublimate the solvent, resulting in a porous composite medical material. The prepared composite medical material is sterilized by ethylene oxide sterilization and irradiation sterilization.

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