Cellulose-based composite materials and their research progress in medical field

Biomass resources mainly include agricultural biomass, forestry biomass, animal manure, and municipal waste. China is a large agricultural country that produces large amounts of waste every year after harvesting crops. In addition, China's forest area ranks fifth in the world, and it also has abundant forestry biomass resources.

Agroforestry biomass is produced by plants through photosynthesis, has a regenerable and short regeneration cycle, and is biodegradable.

The comprehensive development and utilization of agricultural and forestry biomass is conducive to the sustainable development of modern agriculture. In the medium and long-term development plan (2006-2020), the government has listed “agricultural and forestry biomass engineering” as one of the major projects, including the conversion of agricultural and forestry biomass into gas. , liquids, solid energy, and bio-based materials and chemicals.

The agriculture and forestry biomass is mainly composed of cellulose, hemicellulose and lignin, and the content of the three accounts for more than 90% of the total. Using modern science and technology to effectively separate and transform the components of agricultural and forestry biomass, a series of high value-added products such as new powder materials, membrane materials, gel materials, semiconductor materials and biological materials can be obtained.

Cellulose

Cellulose is the most abundant natural renewable polysaccharide in nature. It has many sources, low price, renewable, degradable, non-toxic and derivatizable. It is one of the important biomass materials. Cellulose-based functional composites can be widely used in textile, catalysis, food packaging, biomedical, water treatment and other fields.

The conversion of cellulose into functional composites is conducive to opening up new ways of utilizing agricultural and forestry biomass, which is of great significance for achieving sustainable economic development.

Cellulose composite

Composite material refers to a material that has new properties by combining two or more different properties by physical or chemical means. The prepared composite material can not only maintain the partial characteristics of the original single component, but also can improve the overall performance due to the interaction between the components, and can obtain the characteristics that the original component does not have, that is, the "composite effect. ".

In recent years, research on functional composites based on cellulose has received extensive attention.

Professor Ma Mingguo from Beijing Forestry University introduced three preparation methods such as hydrothermal (solvent heat) method, microwave assisted method and ultrasonic method for composite materials. The development history of cellulose functional composites was briefly reviewed, and the cellulose-based biomedical treatment was highlighted. The latest research progress of composite materials, and finally combined with its own experience, explored the development direction of cellulose-based biomedical composite materials, in order to resource, functionalization, high value and recycling of biomass materials represented by cellulose. for reference.

1 composite material preparation method

There are many preparation methods for composite materials, such as coprecipitation, blending, template, vapor deposition, and biomimetic mineralization. These methods have their own characteristics and are widely used in the preparation of composite materials, which greatly promotes the development of composite materials. The characteristics and limitations of hydrothermal (solvent heat), microwave assisted, and ultrasonic methods applied in the preparation of cellulose functional composites will be highlighted here.

1.1 Hydrothermal (solvent heat) method

1.2 microwave assisted method

1.3 Ultrasonic method

2 The rise of cellulose-based composites

Cellulose is an important biomass material with superior performance and wide application. However, cellulose also has shortcomings such as chemical resistance and limited strength, which limits its application range. The combination of cellulose and other organic or inorganic materials to prepare composite materials not only retains the original properties of cellulose, but also imparts new properties and greatly expands the application of cellulose. In recent years, cellulose functional composites have received extensive attention due to their good biocompatibility, biodegradability, low toxicity, magnetic/optical/mechanical properties, etc. in fiber, catalysis, textile, water treatment, biomedical Other fields have potential application prospects. The molecular chain of cellulose contains a large amount of -OH, which can adsorb metal ions through electrostatic interaction, and then prepare cellulose-based metal nanocomposites by in-situ reduction. Cellulose can also be combined with oxides such as Fe2O3, TiO2, ZnO, CuO, Mn3O4 to prepare cellulose functional composites.

In addition, cellulose can also be combined with a variety of metals or inorganic materials to prepare a multi-component composite. For example, nanocellulose can also be used as a template and a reducing agent to prepare a Fe3O4/Ag/nanocellulose ternary composite, and the material has excellent catalytic reduction performance for 4 nitrophenol, and 7 times of 4 nitrophenol is recovered. The conversion rate can still reach 81.8%. In addition, the prepared material has strong antibacterial activity against Staphylococcus aureus, and is expected to be used as a catalyst and an antibacterial agent for recycling in medical or environmental fields.

3Development of cellulose-based biomedical composites

In recent years, the preparation of biomedical composites by combining cellulose with inorganic materials (such as Ca5 (PO(3), CaCO3, CaSiO3, Ag/AgCI, etc.) has attracted extensive attention. The combination of cellulose and inorganic materials has been prepared into composite materials. It can be applied to biomedical fields such as protein adsorption, tissue engineering, antibacterial, etc. The use of cellulose as a matrix material has many advantages: based on the structural characteristics of cellulose macromolecular chains, it has strong reactivity and interaction properties, so The material has low cost and simple processing technology; cellulose itself has good biocompatibility and biodegradability, so it is an environment-friendly material; compared with polymer materials such as collagen, cellulose has excellent properties. The mechanical properties can effectively overcome the defects of insufficient mechanical properties of polymers such as collagen. The cellulose raw materials used in such materials are widely used, low in price, green and environmentally friendly , low in production cost and have good biological activity, so they are developed and applied. It will have good social and economic benefits in the field of biomedicine.

3.1 cellulose / hydroxyapatite nanocomposites

Hydroxyapatite (HA) is often present in non-stoichiometric, ion-substituted or calcium-deficient forms in hard tissues such as bones and teeth of vertebrates and imparts the necessary mechanical properties (such as strength, Hardness, toughness and stability, etc., and HA is also the most stable crystalline phase of many calcium and phosphorus salts under physiological conditions. Synthetic HA is widely used in tissue engineering fields such as bone repair and bone replacement, gene transfection, and drug/protein transport because of its good biological activity, biodegradability and osteoconductivity. However, as a biomaterial, synthetic HA also has many defects such as insufficient bending strength and fracture toughness to limit its application. Bone or other calcified tissue can be thought of as a natural anisotropic composite of biominerals (one or more calcium phosphate salts, 65% to 70% of the total bone mass) embedded in the protein matrix. Contains other organic matter and moisture. The researchers were inspired to develop a series of HA⁃ polymer composites based on high molecular polymers to improve their mechanical and biological properties. Among them, cellulose has received extensive attention due to its excellent mechanical properties, good biocompatibility, derivatization and low cost. In recent years, researchers have made a lot of research in the field of biomedical research by using cellulose (or its derivatives) as a matrix and preparing cellulose/HA composites by different methods. The CTA⁃HA composite fiber showed good adsorption performance to Hb, and its maximum adsorption amount was 176.04 mg/g, which was much higher than 18.39 mg/g of CTA nanofiber. In the previous research work of Professor Ma Mingguo, cellulose/carbonate-containing HA nanocomposites were prepared by hydrothermal method in NaOH/urea solution by using lignocellulose as the matrix; N,N⁃ dimethylacetamide was used. For the solvent, the cellulose/HA nanocomposites were prepared by microwave rapid heating technology; the loose porous wood fiber/HA nanocomposites were prepared by microwave hydrothermal method. In addition, using NaOH/urea as solvent, phosphorus-containing biomolecules (adenosine triphosphate, creatine phosphate and fructose diphosphate) were used as phosphorus sources to rapidly prepare cellulose/HA nanocomposites by microwave hydrothermal method. By changing phosphorus source and microwave heating Time and temperature can be used to control the phase, size and morphology of mineral crystals in cellulose/HA nanocomposites, so as to obtain HA nanostructures with different morphologies.

3.2 cellulose / calcium carbonate nanocomposites

Calcium carbonate (CaCO3) is not only widely found in rocks such as marble, limestone, and chalk, but also the main inorganic component of vertebrate bones and teeth, corals, eggshells, pearls, sea urchins, and crustacean exoskeletons. In addition, CaCO3 is also a general-purpose filler with abundant sources, low price and good color. It is widely used in coatings, plastics and papermaking industries. Natural CaCO3 has three anhydrous crystalline phases, namely calcite, aragonite and vaterite. The thermodynamic stability of calcite is highest under room temperature and atmospheric conditions, while vaterite is metastable phase CaCO3, which has the lowest thermodynamic stability. Two aqueous phases and one amorphous phase CaCO3. In addition to industrial applications, CaCO3 is also widely used in the study of mineralization in vivo, and CaCO3 has good biological activity, protein adhesion, cell compatibility, hard tissue compatibility, etc., and has a wide application in the medical field. prospect.

In recent years, cellulose/CaCO3 composites prepared with cellulose as the matrix phase and CaCO3 as the reinforcing phase have also attracted attention. The prepared cellulose/CaCO3 composites can be used not only as paper reinforcing agents or adsorbents, but also in biomedical fields. It also has potential application prospects. From the fluorescence micrograph after drug loading, it can be observed that Dox is uniformly dispersed on the BQ film (Fig. 2a); when the BQ film is immersed in the Carr and then loaded with the drug Dox, some fluorescent spots can be observed from the figure due to the presence of Carr. (Fig. 2b); a similar phenomenon is observed in Fig. 2c, but due to the presence of CaCO3, the Dox loaded on the BC film is less; when Carr and CaCO3 are present in the BC film, Dox is mainly loaded in the spot (Fig. 2d). Infrared, confocal and scanning electron microscopy analysis showed that Dox was mainly embedded in Carr⁃CaCO3 composite microspheres when loaded with bc/car⁃CaCO3 composite membrane. The Dox loading rate was about 80% and showed pH response. Sex release performance. When the pH was lowered from 7.4 to 5.8 at 37 ° C, the amount of release increased from 1.50 μg / d to 1.70 μg / d.

Liu et al. studied the mineralization behavior of CaCO3 on electrospun cellulose acetate (CA) in the presence of polyacrylic acid (PAA). It can be observed from the SEM photograph that PAA has an important influence on the nucleation and growth of CaCO3 crystals, and the morphology of CaCO3 is significantly different when PAA is added or not (Fig. 3). When the solution contained no PAA, the resulting CaCO3 was rhombohedral calcite, and some CA fibers were observed to be embedded in the calcite (Fig. 3a, b). When the CaCI2 solution contained PAA, the surface of the fiber became rough, and the surface of the CA fiber was completely coated with a CaCO3 coating formed by nanoneedle polymerization (Fig. 3c, d). It can be observed from the enlarged view in Fig. 3c that the CaCO3 coated CA fiber has a diameter of 1 to 2 μm and the CaCO3 coating has a thickness of about 400 nm. In the presence of PAA, the CaCO3 coating formed does not affect the original morphology of the CA fiber, and the CA fiber can be removed by acetone dissolution treatment to obtain a calcite CaCO3 microtube.

In the previous work of Professor Ma Mingguo, the effects of ultrasonic and microwave methods on the CaCO3 crystals in the preparation of cellulose/CaCO3 composites were studied. It was found that the preparation method has an influence on the phase, microstructure, morphology, thermal stability and biological activity of CaCO3 crystal. For example, pure phase vaterite microspheres having a size of 320 to 600 nm can be obtained by ultrasonic method, and calcite and vaterite type CaCO having a size of 0.82 to 1.24 μm can be obtained by a microwave method. In addition, Prof. Ma Mingguo used ionic liquid [Bmim]CI as a solvent and microwave absorber for cellulose to prepare cellulose/CaCO3 nanocomposites by microwave rapid heating technology, and prepared polyhedral or cubic structure by changing the cellulose concentration. CaCO3 crystal. After the prepared composite material was co-cultured with human gastric cancer cells (SGC⁃7901) for 48 hours, most of the cells still maintained normal spindle morphology, and the prepared cellulose/CaCO3 composite material had good cytocompatibility in biomedicine. The field has potential application value.

3.3 cellulose / silver antibacterial material

Numerous antibacterial materials can kill harmful bacteria in vitro and in vivo, including metal oxides (such as ZnO, TiO2, CuO, etc.), metal sulfides, halides, and precious metals such as Ag, Pd, Au, and Pt. Among these antibacterial materials, metallic silver nanoparticles (Silvernanoparticles, AgNPs) have a large specific surface area, excellent antibacterial properties and are non-toxic to human cells, and thus are considered to be the most promising antibacterial materials. Silver and its compounds have been found to exhibit excellent antimicrobial activity against more than 650 bacteria. Cellulose has good biocompatibility, biodegradability and non-toxicity, and the surface of cellulose-OH forms intramolecular and intermolecular hydrogen bond network structure, which can effectively control the growth of AgNPs and realize the shape and particle size of AgNPs. Regulation. The large amount of -OH contained in the cellulose structure makes it negatively charged on the surface of the aqueous solution and has an adsorption property to metal ions. In addition, the reducing terminal group of the cellulose molecular chain can also serve as a reducing agent for metal ions. Therefore, cellulose can be used as a matrix of AgNPs, a stabilizer and/or a reducing agent for Ag+ ions. The prepared cellulose/Ag nanocomposites can be applied to many fields such as textile, medical, food packaging, water treatment and the like.

Recently, Ye et al. prepared a cellulose hydrogel using NaOH/urea as a solvent and epichlorohydrin as a crosslinking agent, and then obtained a cellulose/Ag sponge material by hydrothermal and freeze-drying treatment (Fig. 4). The results of antibacterial research showed that the prepared sponge had excellent antibacterial properties against Staphylococcus aureus and Escherichia coli, and the diameter of the inhibition ring was 15.5-26.8 mm and 17.4-23.6 mm, respectively. In vivo tests have found that the sponge accelerates the healing of infected wounds. The porous structure of the cellulose sponge allows sufficient air to permeate, and the sponge can effectively absorb the wound exudate, while the AgNPs in the sponge can effectively kill harmful bacteria, so the prepared cellulose/Ag sponge can be used as a wound dressing for infection. The healing of the wound. In the preliminary work of Professor Ma Mingguo, the hemicellulose was used as the matrix of AgNPs and the reducing agent of Ag+ ions, and the hemicellulose/Ag nanocomposites were synthesized by hydrothermal method. The AgNPs in the prepared composite have a spherical structure, and by controlling the reaction conditions, hemicellulose/Ag nanocomposites of different sizes can be prepared (Fig. 5). The composite material showed high antimicrobial activity against Staphylococcus aureus and Escherichia coli, and the size of the inhibition ring was 13.0-16.0 mm and 7.5-12.0 mm, respectively.

It has been reported in the literature that the bactericidal mechanism of AgNPs in cellulose matrix is: the surface of bacteria is usually negatively charged, AgNPs can adhere to the surface of bacterial cell membrane by electrostatic action, blocking cell permeability and respiratory function; AgNPs release Ag+ ions, Ag+ Ions can penetrate the cell membrane and enter the bacteria, and interact with the S and P compounds in the bacterial cell wall and cytoplasm to affect the cell's penetration and division, leading to bacterial death; Ag+ ions penetrate into the bacteria and interact with the thiol protein in the DNA. Deformation of DNA inhibits bacterial growth and ultimately leads to bacterial death. The cellulose macromolecular chain contains a large amount of -OH. These -OH can not only adsorb Ag+ ions through electrostatic action, but also form intramolecular and intermolecular hydrogen bond network structures. AgNPs are bound in the cellulose network structure to control Ag+. The release of ions, in turn, achieves sustained antibacterial action.

in conclusion

At present, cellulose functional composites are widely used in the fields of pulp and paper, fine chemicals, food packaging and the like. In summary, cellulose-based biomedical composites combine the advantages of cellulosic materials and biomaterials, and have potential applications in tissue engineering, biomedicine, gene carriers, and protein adsorption. In recent years, the resource utilization, functionalization, high value and recycling of agricultural and forestry biomass have become an important research direction. Cellulose functional composite materials, especially cellulose-based biomedical composite materials, must closely surround these research directions and meet the major national needs. Oriented, facing the world's frontiers of science and technology, solving the bottleneck problem that restricts the development of the industry, opening up new ways and providing new ideas for its application. In the future research, in addition to continuing the traditional modification of cellulose esterification and etherification, and expanding its synthesis methods and material types, it is necessary to further explore the universal preparation strategy suitable for industrial production, study its synthesis mechanism, and reveal The composite effect, the intrinsic organic relationship between preparation methods, properties and mechanisms, the method, material, mechanism, performance and application of cellulose-based biomedical composites, provide industrial application of cellulose functional composites Theoretical basis and experimental basis. Biomass represented by cellulose is stable in performance and difficult to dissolve in common solvents. Finding a suitable solvent is a prerequisite for application. Nanocellulose has been widely used for its excellent performance. It is recommended to use nanocellulose in the choice of cellulose type to apply the characteristics and advantages of nanocellulose to functional composites. Cellulose-based multifunctional composite materials are an important development direction in the field of biomass. It is recommended to carry out multi-functional special composite materials with new high-efficiency antibacterial, flame retardant, adsorption, waterproof, fireproof, anti-counterfeiting, rapid analysis and testing. Using cellulose functional materials as precursors, it can be converted into carbon-based functional materials for environmental restoration, soil improvement, and supercapacitors. Cellulose hydrogels can be applied to wearable strain sensors for real-time health monitoring. The design of integrated flexible hydrogel sensors that are conductive, highly elastic, self-healing and strain sensitive is expected to achieve new breakthroughs.