A biocompatible bioaerogel material and a preparation method thereof

Abstract

The application provides a biocompatible biological aerogel material and a preparation method thereof, and the method comprises the following steps: cleaning and roughening pretreatment of a substrate; dissolving polyvinyl alcohol to prepare a precursor solution; introducing wear-resistant reinforcing materials into the precursor solution and uniformly dispersing the wear-resistant reinforcing materials; adding a crosslinking agent, glutaraldehyde, to perform a crosslinking reaction and construct a three-dimensional network structure; coating the system in the initial stage of crosslinking on the substrate, and performing low-temperature or freeze-drying and subsequent heat treatment to form a stable coating. The obtained material takes polyvinyl alcohol as a biocompatible skeleton, and has excellent porous structure, mechanical properties and wet stability through chemical crosslinking and reinforcing phase compounding. In-vitro cell experiments show that the material has no obvious toxicity to cells, and the cells adhere and spread well. The application solves the problem that the existing biological aerogel material is difficult to consider the biocompatibility, structural stability and process friendliness, and is suitable for the biomedical field such as tissue engineering scaffolds and wound dressings.

Description

Technical Field

[0001] This invention belongs to the field of new coating materials technology, and relates to a biocompatible bioaerogel material and its preparation method. Background Technology

[0002] Aerogel materials are porous materials with ultra-high porosity, low density, high specific surface area, and tunable pore structure. Initially, they were mainly used in industrial fields such as thermal insulation, adsorption, and catalysis. In recent years, with the rapid development of biomedical engineering, tissue engineering, and regenerative medicine, aerogels, due to their unique structural properties, have shown promising applications in biomedical fields such as drug delivery, tissue scaffolds, wound dressings, and biosensing. The porous structure not only facilitates cell adhesion, growth, and migration but also provides channels for the transport of nutrients and metabolites, thus being considered a promising biomaterial.

[0003] Currently, common aerogel materials mainly include inorganic aerogels (such as silica and carbon-based aerogels) and synthetic polymer aerogels. These materials have certain advantages in terms of mechanical properties, thermal stability, and structural controllability, but their biocompatibility is generally poor, easily causing cytotoxicity, inflammatory responses, or immune rejection, limiting their long-term or direct contact application in the human body. The compatibility issue between the material and biological tissue is particularly prominent when used in implantable devices or tissue engineering scaffolds.

[0004] To improve biocompatibility, researchers are increasingly turning to the use of natural polymers or bio-based materials to prepare aerogels, such as collagen, chitosan, and hyaluronic acid. These materials are bio-friendly and have good cell affinity, but they often face problems such as poor mechanical properties, structural instability, and a tendency to soften or collapse in humid environments. Especially when supporting tissues or in dynamic physiological environments, the structural integrity and durability of these materials are difficult to guarantee.

[0005] Furthermore, existing aerogel preparation processes often involve high temperatures, high pressures, toxic organic solvents, or complex post-processing, which may introduce harmful biological residues and affect the biosafety of the final product. At the same time, most preparation methods have limited precision in controlling the pore structure, making it difficult to achieve a balanced design of pore size, pore distribution, and connectivity, thereby affecting cell behavior and tissue integration.

[0006] Therefore, there is still a lack of bioaerogel materials in the existing technology that have good biocompatibility, suitable mechanical strength, stable porous structure, and mild and safe preparation process. Summary of the Invention

[0007] The purpose of this invention is to provide a biocompatible bioaerogel material and its preparation method, aiming to solve the problems of existing bioaerogel materials, such as difficulty in balancing biocompatibility and mechanical properties, poor structural stability, unfriendly preparation processes for biological applications, and insufficient controllability of pore structure.

[0008] To address the aforementioned technical problems, this invention provides a method for preparing a biocompatible bioaerogel material, comprising the following steps:

[0009] S1. Substrate pretreatment: The surface of the metal or non-metal substrate is cleaned and roughened to form a micro-rough structure, and then dried.

[0010] S2. Preparation of polyvinyl alcohol precursor solution: Dissolve polyvinyl alcohol in deionized water, heat and stir at 80℃~95℃ to fully dissolve it, and obtain a polyvinyl alcohol solution with a mass fraction of 3%~12%.

[0011] S3. Introducing reinforcing materials: Adding wear-resistant reinforcing materials to the polyvinyl alcohol precursor solution and dispersing them uniformly by high-speed stirring or ultrasonic dispersion to form a polyvinyl alcohol-reinforcing phase composite system;

[0012] S4. Crosslinking reaction: Glutaraldehyde, a crosslinking agent, is added to the composite system, and a crosslinking reaction is carried out under weakly acidic conditions to construct a three-dimensional porous aerogel network structure.

[0013] S5. Film formation and drying: The aerogel system before or at the initial stage of crosslinking is coated onto the surface of the pretreated substrate, and the moisture is removed by low-temperature drying or freeze-drying to form a stable bioaerogel coating.

[0014] S6. Curing treatment: The dried coating is heat-treated at 40℃~80℃ to further stabilize the aerogel structure.

[0015] More preferably, the cleaning and roughening treatment in step S1 includes: first using ethanol or acetone for degreasing treatment, and then roughening the surface by at least one of mechanical grinding, sandblasting or chemical etching.

[0016] More preferably, the polyvinyl alcohol is a medium-to-high molecular weight polyvinyl alcohol with a degree of alcoholysis greater than 85%.

[0017] More preferably, the wear-resistant reinforcing material is selected from at least one of silica, acrylic materials, layered inorganic materials, hollow microspheres, or nanofiber materials.

[0018] More preferably, the layered inorganic material includes graphene oxide, montmorillonite, or MXene; the hollow microspheres include hollow silica microspheres or hollow polymer microspheres; and the nanofiber material includes aramid nanofibers or cellulose nanofibers.

[0019] More preferably, the coating method in step S5 is spraying, scraping, or spin coating.

[0020] This invention provides a biocompatible bioaerogel material prepared by the above-described method. The material consists of a substrate and a coating. The coating has a polyvinyl alcohol skeleton, contains uniformly dispersed wear-resistant reinforcing materials, and has a three-dimensional porous network structure.

[0021] The bioaerogel material of the present invention has good biocompatibility and structural stability, and is suitable for use in tissue engineering scaffolds, wound dressings, drug delivery systems or biosensors.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. Excellent biocompatibility: Using polyvinyl alcohol, which has good biocompatibility, as the main material avoids the cytotoxic risks of inorganic or partially synthetic polymer materials, making it more suitable for applications that come into direct contact with biological tissues.

[0024] 2. Good mechanical properties and structural stability: A stable three-dimensional network is constructed through chemical cross-linking of glutaraldehyde, and a wear-resistant reinforcing phase is introduced, which significantly improves the mechanical strength, water resistance and anti-collapse ability of the material in a humid environment.

[0025] 3. Mild and controllable process: The in-situ film formation and mild drying (low temperature or freeze drying) technology effectively avoids the damage to the biocompatibility of the material caused by harsh conditions such as high temperature and high pressure, while maintaining the integrity of the porous structure of the aerogel and enhancing the adhesion between the coating and the substrate.

[0026] 4. High designability of structure and performance: By adjusting the concentration of polyvinyl alcohol, the amount of crosslinking agent, the type and content of reinforcing phase, and the drying process, the pore size, porosity, mechanical properties and degradation behavior of aerogel can be effectively controlled to meet the needs of different biomedical applications. Attached Figure Description

[0027] Figure 1 These are fluorescence microscopy images of bioaerogel materials after in vitro cell culture.

[0028] Figure 2 This is a statistical chart of the results of cell viability detection using the CCK-8 assay. Detailed Implementation

[0029] The following detailed description, in conjunction with the accompanying drawings and specific embodiments, provides a more detailed account of the biocompatible bioaerogel material and its preparation method proposed in this invention. The advantages and features of this invention will become clearer from the following description. It should be noted that the accompanying drawings are all in a very simplified form and use non-precise proportions, used only to facilitate and clarify the illustration of the embodiments of this invention. The same or similar reference numerals in the drawings represent the same or similar parts.

[0030] Example: Preparation and performance evaluation of a biocompatible polyvinyl alcohol-based bioaerogel material

[0031] This embodiment provides a method for preparing the bioaerogel material and evaluates its microstructure and biocompatibility.

[0032] 1. Material preparation process

[0033] (1) Preparation of coating substrate:

[0034] Titanium sheets are selected as the substrate, but non-metallic materials can also be used. First, the surface of the titanium sheet is ultrasonically cleaned with ethanol for 15 minutes to remove oil and impurities. Then, a sandblasting process is used to roughen the cleaned surface, creating a uniform micro-rough structure. The treated substrate is then placed in a clean environment at 20℃~30℃ and relative humidity below 50% to dry completely before use.

[0035] Residual oil and impurities on the substrate surface can significantly weaken the interfacial adhesion between the polyvinyl alcohol aerogel coating and the substrate. Surface roughening treatment can increase the surface energy of the substrate and increase the actual contact area, thereby enhancing the mechanical interlocking and interfacial adhesion stability between the coating and the substrate. Substrate drying and surface stabilization treatment can completely remove residual moisture or organic solvents from the substrate surface, avoiding uneven coating structure or decreased interfacial adhesion due to moisture interference during the subsequent polyvinyl alcohol aerogel coating film formation process.

[0036] (2) Preparation of polyvinyl alcohol precursor solution:

[0037] Polyvinyl alcohol (PVA) particles with a degree of hydrolysis greater than 85% and an average molecular weight of 89,000-98,000 were selected. The PVA molecular chain contains a large number of hydroxyl groups, exhibiting good film-forming properties and reactivity, making it suitable for constructing stable three-dimensional porous aerogel structures through chemical crosslinking. This provides a continuous polymeric framework and good mechanical support for the coating.

[0038] PVA was added to deionized water to prepare a mixture with a target concentration of 3%–12%. The mixture was placed in a water bath at 80℃–95℃ and mechanically stirred continuously for 3 hours until the PVA was completely dissolved, resulting in a homogeneous and transparent PVA precursor solution. By controlling the concentration and dissolution state of the polyvinyl alcohol solution, the pore structure and mechanical properties of the subsequent aerogel network can be effectively adjusted, avoiding discontinuous aerogel structure or unstable performance due to insufficient dissolution of polyvinyl alcohol.

[0039] (3) Introduction and dispersion of wear-resistant reinforcing phase:

[0040] Nano-sized silica particles are added to the above-mentioned PVA precursor solution as a wear-resistant reinforcing material. The wear-resistant reinforcing material includes silica and acrylic materials, and may also be selected from at least one of layered inorganic materials, hollow microspheres, or nanofiber materials. The layered inorganic materials include graphene oxide, montmorillonite, or MXene; the hollow microspheres include hollow silica microspheres or hollow polymer microspheres; and the nanofiber materials include aramid nanofibers or cellulose nanofibers. The addition amount is 10% of the PVA mass. Subsequently, the mixture is placed in an ice-water bath and ultrasonically dispersed for 30 minutes using an ultrasonic cell disruptor at 400W power to ensure uniform dispersion of the nano-silica in the PVA solution, forming a stable PVA-silica composite dispersion system.

[0041] The wear-resistant reinforcing phase can play a role in load transfer and stress dispersion in the aerogel structure, effectively inhibiting the wear and deformation of the polyvinyl alcohol matrix during friction, thereby significantly improving the wear resistance and service life of the coating.

[0042] (4) Crosslinking and structural construction of polyvinyl alcohol aerogel system:

[0043] Under continuous low-speed stirring, glutaraldehyde aqueous solution was slowly added dropwise to the composite dispersion system as a crosslinking agent, while dilute hydrochloric acid was added dropwise to adjust the pH of the system to 4.5. The amount of glutaraldehyde added was controlled to be 5% of the mass of PVA. The reaction was carried out by continuous stirring at room temperature to carry out pre-crosslinking. The system gradually changed from a solution to a sol state and began to build a three-dimensional network structure.

[0044] Glutaraldehyde can undergo an acetal reaction with the hydroxyl groups on the polyvinyl alcohol molecular chain to form a stable chemical cross-linking structure, thereby significantly improving the structural stability and mechanical strength of the aerogel network and giving the coating good water resistance and durability.

[0045] (5) Film formation and drying of aerogel coating:

[0046] The sol system in the pre-crosslinking stage is uniformly coated onto the surface of the pretreated titanium sheet substrate by a blade coating method. Alternatively, a blade coating or spin coating method can be used, with the wet film thickness controlled at approximately 500 μm.

[0047] Applying the coating before the polyvinyl alcohol crosslinking reaction is completely finished allows the aerogel network to be built in situ on the substrate surface, thereby enhancing the interfacial bonding strength between the coating and the substrate.

[0048] The coated samples underwent a staged drying process using low-temperature drying or freeze-drying methods. The coated samples were rapidly transferred to a -20°C freezer for pre-freezing for 4 hours. Subsequently, the samples were placed in a freeze dryer and freeze-dried at -50°C and a vacuum degree below 10 Pa for 24 hours to remove all moisture and form a porous aerogel coating.

[0049] A gentle drying method can effectively prevent the collapse of the aerogel pore structure or cracking of the coating, ensuring the integrity of the aerogel porous structure and the overall performance of the coating.

[0050] (6) Coating curing and performance stabilization treatment:

[0051] The freeze-dried sample was placed in a vacuum drying oven and heat-treated at 40℃~80℃. This step aims to further promote the complete cross-linking reaction, stabilize the three-dimensional network structure, and improve the mechanical properties and long-term stability of the coating. After treatment, the polyvinyl alcohol-based bioaerogel material is obtained.

[0052] 2. Material Characterization and Performance Evaluation

[0053] (1) Structural morphology observation:

[0054] The surface and cross-sectional morphology of the obtained material were observed using scanning electron microscopy (SEM). The results showed that the material has a continuous and interconnected three-dimensional porous network structure, with pore sizes mainly distributed in the range of 50-200 μm. The pore walls are clear, the structure is intact, and there is no obvious collapse (refer to the porous features shown in the schematic diagram in the original document).

[0055] (2) In vitro biocompatibility evaluation:

[0056] In vitro cell experiments were conducted to assess the biosafety of the material.

[0057] Cell culture and morphological observation: Mouse fibroblasts (L929) were seeded onto the material surface and cultured. After 48 hours of culture, live cells were stained with calcein-AM and observed under a fluorescence microscope. Figure 1 As shown, green fluorescence represents surviving cells. Compared with the control group, the experimental group cells adhered well to the material surface, with a relaxed cell morphology and a typical spindle-shaped spreading state. The cell density was high, and no obvious abnormal morphology such as cell shrinkage or death was observed.

[0058] Quantitative assay of cell viability: Cell viability was quantitatively analyzed using the CCK-8 assay. Absorbance (OD value) was measured after 24 hours and 48 hours of culture. Results are as follows: Figure 2 As shown in the figure (corresponding to the CCK-8 detection results statistics in the original file), there was no significant difference in cell viability between the experimental group and the control group at any time point (P > 0.05). Quantitative data indicate that this bioaerogel material has no significant toxicity to L929 cells and exhibits good in vitro biocompatibility.

[0059] Conclusion: This embodiment successfully prepared a bioaerogel material with polyvinyl alcohol as the backbone, nano-silica as the reinforcing phase, and cross-linked with glutaraldehyde. This material possesses an ideal three-dimensional porous structure, and in vitro cell experiments confirmed its excellent biocompatibility, meeting the basic safety requirements of biomedical materials. It has application potential in tissue engineering scaffolds, wound dressings, and other fields.

[0060] This invention incorporates three core technologies, and its specific advantages compared to existing technologies are described below:

[0061] Core Technology 1: Biocompatible Aerogel Framework Construction Technology Based on Polyvinyl Alcohol

[0062] Current technological status:

[0063] Most existing bioaerogel materials use inorganic materials or non-biological synthetic polymers as the framework structure. These materials have certain advantages in terms of mechanical properties or structural stability, but they often have problems such as insufficient biocompatibility, inflammatory response, or poor cell adhesion when in long-term contact with biological tissues or body fluids, which limits their application in biomedical fields.

[0064] The technical solution and advantages of this invention:

[0065] This invention uses polyvinyl alcohol (PVA) as the main gelling and film-forming matrix for aerogel materials, utilizing the abundant hydroxyl structures on its molecular chains to construct a continuous and stable polymeric network framework. PVA possesses excellent biocompatibility and film-forming properties, forming a porous aerogel structure without significantly irritating the biological environment. Compared to existing aerogel materials primarily composed of inorganic or non-biological polymers, this invention significantly improves the biosafety and biocompatibility of the material while maintaining the porous characteristics of the aerogel, making it more suitable for applications involving direct contact with biological tissues or long-term use.

[0066] Core Technology 2: Glutaraldehyde Chemical Crosslinking-Regulated Polyvinyl Alcohol Three-Dimensional Porous Network Structure Technology

[0067] Current technological status:

[0068] Most existing bioaerogel materials are constructed using physical crosslinking or weak chemical crosslinking. Although the preparation process is relatively simple, the materials are prone to swelling, structural collapse, or rapid decline in mechanical properties under aqueous or physiological conditions, making it difficult to meet the requirements of structural stability and durability for practical applications.

[0069] The technical solution and advantages of this invention:

[0070] This invention introduces glutaraldehyde as a crosslinking agent in the polyvinyl alcohol (PVA) aerogel system. A stable three-dimensional chemically crosslinked network structure is constructed through the acetal reaction between glutaraldehyde and the hydroxyl groups of the PVA molecular chain. This crosslinking method can be carried out under mild conditions, and the degree of crosslinking is controllable, ensuring the porous structure of the aerogel while significantly improving the material's mechanical strength and water resistance. Compared with existing aerogel materials that mainly rely on physical crosslinking or weak crosslinking, the PVA aerogel of this invention maintains good structural integrity and stability in humid environments.

[0071] Core Technology 3: Aerogel Coating Construction Technology with Synergistic Control of In-situ Film Formation and Mild Drying

[0072] Current technological status:

[0073] In the preparation and application of existing aerogel materials, the method of first preparing bulk materials and then coating or attaching them is often adopted, or a rapid evaporation process is used in the drying stage. This can easily lead to insufficient adhesion between the coating and the substrate, collapse of the pore structure or cracking of the material, thus affecting the actual performance of the aerogel material.

[0074] The technical solution and advantages of this invention:

[0075] This invention involves directly coating the system onto the substrate surface before or at the initial stage of the polyvinyl alcohol aerogel crosslinking reaction, allowing the aerogel network to form in situ on the substrate surface. Combined with gentle drying methods such as low-temperature drying or freeze-drying, this effectively avoids pore structure collapse and interfacial defects. Compared to existing technologies, this method significantly improves the interfacial bonding strength between the aerogel coating and the substrate while maintaining the integrity of the aerogel's porous structure, resulting in better structural stability and performance consistency in practical applications.

[0076] The above description is merely a description of preferred embodiments of the present invention and is not intended to limit the scope of the present invention in any way. Any changes or modifications made by those skilled in the art based on the above disclosure shall fall within the protection scope of the claims.

Claims

1. A method for preparing a biocompatible bioaerogel material, characterized in that, Includes the following steps: S1. Substrate pretreatment: The surface of the metal or non-metal substrate is cleaned and roughened to form a micro-rough structure, and then dried. S2. Preparation of polyvinyl alcohol precursor solution: Dissolve polyvinyl alcohol in deionized water, heat and stir at 80℃~95℃ to fully dissolve it, and obtain a polyvinyl alcohol solution with a mass fraction of 3%~12%. S3. Introducing reinforcing materials: Adding wear-resistant reinforcing materials to the polyvinyl alcohol precursor solution and dispersing them uniformly by high-speed stirring or ultrasonic dispersion to form a polyvinyl alcohol-reinforcing phase composite system; S4. Crosslinking reaction: Glutaraldehyde, a crosslinking agent, is added to the composite system, and a crosslinking reaction is carried out under weakly acidic conditions to construct a three-dimensional porous aerogel network structure. S5. Film formation and drying: The aerogel system before or at the initial stage of crosslinking is coated onto the surface of the pretreated substrate, and the moisture is removed by low-temperature drying or freeze-drying to form a stable bioaerogel coating. S6. Curing treatment: The dried coating is heat-treated at 40℃~80℃ to further stabilize the aerogel structure.

2. The method for preparing a biocompatible bioaerogel material according to claim 1, characterized in that, The cleaning and roughening process described in step S1 includes: first, degreasing with ethanol or acetone, and then roughening the surface by at least one of mechanical grinding, sandblasting or chemical etching.

3. The method for preparing a biocompatible bioaerogel material according to claim 1, characterized in that, The polyvinyl alcohol is a medium-to-high molecular weight polyvinyl alcohol with a degree of alcoholysis greater than 85%.

4. The method for preparing a biocompatible bioaerogel material according to claim 1, characterized in that, The wear-resistant reinforcing material is selected from at least one of silica, acrylic materials, layered inorganic materials, hollow microspheres, or nanofiber materials.

5. The method for preparing a biocompatible bioaerogel material according to claim 4, characterized in that, The layered inorganic material includes graphene oxide, montmorillonite, or MXene; the hollow microspheres include hollow silica microspheres or hollow polymer microspheres; and the nanofiber material includes aramid nanofibers or cellulose nanofibers.

6. The method for preparing a biocompatible bioaerogel material according to claim 1, characterized in that, The coating method described in step S5 is spraying, scraping, or spin coating.

7. A biocompatible bioaerogel material prepared by the preparation method according to any one of claims 1 to 6, characterized in that, The material consists of a substrate and a coating. The coating has a polyvinyl alcohol skeleton, contains uniformly dispersed wear-resistant reinforcing materials, and has a three-dimensional porous network structure.

8. The bioaerogel material according to claim 7, characterized in that, The material exhibits good biocompatibility and structural stability, making it suitable for applications such as tissue engineering scaffolds, wound dressings, drug delivery systems, and biosensors.

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