Application of carboxymethyl chitosan in oral tissue engineering

Many oral diseases can lead to jaw bone defects and permanent loss of periodontal tissue, such as periodontal disease, jaw osteomyelitis, jaw tumors, etc., and tissue engineering is considered an effective method to solve this problem. Today, tissue engineering applied in the oral cavity is mainly guided tissue regeneration and guided bone regeneration. Biofilms made of biomaterials are used to artificially erect a biological barrier between the gingival soft tissue and the bone defect to hinder the migration of epithelial cells. This leaves space around the bone defect for osteoblast proliferation and new bone formation. The development of three-dimensional biomaterial scaffolds that are highly similar to the physical and chemical structures of bone tissue at the nanoscale remains a major challenge in tissue engineering. The key to the success of tissue engineering is to form regenerative tissue on a biodegradable scaffold. As a transitional structure for cell attachment, proliferation and differentiation, the scaffold material must have good biocompatibility, degradability, non-toxicity, and can imitate natural The biological and physical properties of the extracellular matrix regulate tissue regeneration. Natural biomaterials are the preferred materials for providing scaffold materials. Currently, chitosan, as a natural biomaterial, meets the basic requirements and characteristics of tissue engineering scaffolds. Once new target tissue is formed, chitosan can be degraded by lysosomes into natural metabolites without producing toxic substances, and chitosan will not stimulate the human immune system.

Due to its rigid crystal structure, chitosan has poor solubility in water, which limits its effective application in tissue engineering. Carboxymethylation, as a hydrophilic modification method, can improve the solubility of chitosan and generate carboxymethyl chitosan. Carboxymethyl occurs on the H, C3 and C6 hydroxyl groups on the C2 amino group in the chitosan molecule, and three products can be obtained depending on the substitution position. Carboxymethyl chitosan is very different from chitosan in that it has zwitterionic properties, is more water-soluble than chitosan, and provides more surface modification through additional carboxyl groups. possible. In addition, compared with the positive charge of chitosan itself, carboxymethyl chitosan can compete with mineral anions for protons, deprotonating mineral anions to a certain extent, and promoting the deposition of mineral cations and anions. This shows that carboxymethyl chitosan has a stronger chelating ability for metal cations such as Ca2+, and carboxymethyl chitosan is composed of long chains containing carboxymethyl groups. These carboxymethyl groups protect calcium ions from being carried away by the tissue. Effect of negatively charged phosphate ions. As a biomaterial with excellent properties, carboxymethyl chitosan has been widely used in wound healing, bioimaging, tissue engineering, and drug/gene delivery. Although carboxymethyl chitosan meets the characteristics of good membranes and scaffolds, it relatively lacks the mechanical properties and bioactivity necessary in oral tissue engineering. To achieve this goal, it is considered to combine carboxymethyl chitosan scaffolds with synthetic polymers, bioactive ingredients, and growth factors to prepare composites with enhanced mechanical properties and tissue regeneration.

Advantages of carboxymethyl chitosan in oral tissue construction

1. Antibacterial properties of carboxymethyl chitosan

Carboxymethyl chitosan has natural antibacterial activity and a broad antibacterial spectrum. It has an antibacterial effect on oral cariogenic bacteria such as Streptococcus mutans. It also has the advantage of inhibiting the growth of important anaerobic bacteria in the oral cavity. Its antibacterial mechanism may be carboxymethyl chitosan. Chitosan enters the cell through the cell wall and disrupts bacterial synthesis and metabolism, thereby exerting a certain antibacterial effect. Further research suggests that it may be carboxymethyl chitosan. The effective group NH3+ is alkaline. After carboxymethyl chitosan is degraded, the degradation products react with the lipid and protein complexes on the bacterial cell membrane, denaturing the protein, changing the permeability of the cell membrane, and causing the bacteria to dissolve and rupture. It may also form a negative charge environment with the bacterial cell wall, damaging the integrity of the cell wall, or causing the cell wall to dissolve until the cell dies. The antibacterial activity of carboxymethyl chitosan is affected by the amount of NH2, degree of deacetylation, solution concentration, relative molecular mass, pH value and NH3+ concentration in the solution. Therefore, it can be seen that the antibacterial mechanism of carboxymethyl chitosan is not clear yet and is one of the topics for future research.

2. Remineralization properties of carboxymethyl chitosan

At present, amorphous calcium phosphate is considered to be the best choice for remineralization of tooth enamel or dentin. However, due to its thermodynamic instability, it is easy to quickly transform into a stable hydroxyapatite crystalline phase in aqueous media in vitro. , unable to controllably release amorphous calcium phosphate or mineral ions. Based on carboxymethyl chitosan, a carboxyl-rich chitosan derivative that can isolate cationic. It can effectively inhibit the combination of metal ions such as calcium and magnesium with anions such as carbonate and phosphate to form precipitates, balancing the interaction between carboxymethyl chitosan, mineral cations and acid radicals, thereby making amorphous minerals The solution of nanoparticles remains emulsified at pH=2, thus appropriately suppressing this sedimentation tendency. Researchers used chimeric peptide-mediated carboxymethyl chitosan/amorphous calcium phosphate nanocomposites to simulate amelogenin in enamel biomineralization, inducing the mineralization process of directional assembly of amorphous calcium phosphate, seeking to establish a rapid An effective method for remineralizing human carious tooth enamel. This study proves that carboxymethyl chitosan is rich in carboxyl groups and can be used to improve the stability of calcium and phosphorus after deposition. It is a good stabilizer for amorphous calcium phosphate nanoparticles. The tooth tissue acts as a remineralizer. The combined application of carboxymethyl chitosan and remineralization drugs will be a research hotspot in oral tissue construction in the future. Due to the complexity of the human oral environment, research on the effects of factors such as oral temperature, pH value, and bacterial ecology on carboxymethyl chitosan composites should be conducted simultaneously.

3. Osteogenic properties of carboxymethyl chitosan

Carboxymethyl chitosan has been widely used in the field of tissue engineering. Tissue engineering typically incorporates cells into three-dimensional porous scaffolds to prepare composite materials. On the one hand, scaffolds prepared from carboxymethyl chitosan have a porous structure and can be degraded when new tissues are formed, and the degradation products are non-toxic or cause minimal inflammatory reactions; on the other hand, compared to chitosan, carboxymethyl chitosan The osteogenic effect of methyl chitosan as a scaffold material is more obvious.

4. Wound-healing properties of carboxymethyl chitosan

Traditional wound dressings have structural and functional defects and cannot effectively promote wound healing. In the future, the development of dressings will tend to have multiple functions, which can accelerate blood coagulation, inhibit bacterial infection, and trigger the regeneration process of full-thickness wounds. Carboxymethyl chitosan is a chitosan derivative that not only maintains its excellent properties but also has good water solubility, fiber, film-forming, and hydrogel capabilities. It has been widely used in oral surgery. in wound dressings. On the one hand, it is because carboxymethyl chitosan can promote the growth of skin keratinocytes and fibroblasts and is a good wound dressing material; on the other hand, it is because carboxymethyl chitosan can increase the number of red blood cells. The aggregation and platelet adhesion can shorten the coagulation time.

Application of carboxymethyl chitosan in oral tissue regeneration

1. Bone tissue regeneration

Jaw disease, maxillofacial trauma, and advanced periodontitis are all oral diseases that lead to maxillofacial bone loss. In order to repair bone defects and restore facial fullness, it is currently a research hotspot in oral bone tissue engineering. Carboxymethyl chitosan plays an important role as a bioactive scaffold or hydrogel material in the construction and repair of oral bone tissue. Some studies have used carboxymethyl chitosan and amorphous calcium phosphate to enhance the mechanical strength of biomimetic mineralized collagen scaffolds, while reducing the degradation rate of collagen scaffolds, so that biomimetic mineralized collagen scaffolds can better promote the regeneration of defective bone tissue. , which shows that carboxymethyl chitosan is an ideal choice as a scaffold material or a modified scaffold material.

2. Dental tissue regeneration

Caries are the main cause of dental tissue loss and are a dynamic process caused by an imbalance in demineralization and remineralization. Without timely treatment (including remineralization therapy and plaque control) to restore this balance, dental caries is likely to gradually progress from the enamel to the dentin, leading to deep caries and ultimately tooth loss. Researchers prepared carboxymethyl chitosan and lysozyme nanogels and wrapped amorphous calcium phosphate to achieve controlled release, which improved the stability of amorphous calcium phosphate in a water environment and restored its original appearance on the surface of demineralized tooth enamel. A layer of enamel-like layer without prisms is formed. By synthesizing experimental resin doped with carboxymethyl chitosan and calcium phosphate micro fillers to achieve remineralization of artificial dentin and improve the durability of resin-dentin bonding, the results show that carboxymethyl chitosan can effectively Geographically guide the biomimetic mineralization of collagen fibers. In addition, some scholars have used carboxymethyl chitosan/amorphous calcium phosphate nanocomposites to remineralize demineralized dentin in deep caries tooth models. These studies indicate that the carboxymethyl chitosan complex shows a good remineralization effect and is expected to become a potential material for dentin regeneration.

3. Periodontal tissue regeneration

Periodontitis is the most common disease in the oral cavity. It can destroy the supporting tissues of teeth, causing a large amount of periodontal tissue loss, causing periodontal pus and loose teeth. Periodontitis begins with the formation of periodontal pockets and worsens with the development of bone defects. In advanced cases of deep periodontal pockets, irreversible loss of alveolar bone and periodontal tissue is often seen. In this case, surgical regenerative treatment is more clinically considered. Carboxymethyl chitosan has broad application prospects in periodontal tissue regeneration due to its good affinity for cells, non-toxicity, non-immunogenicity and ability to inhibit oral calcium and phosphorus ion binding. Studies have found that culturing human gingival fibroblasts on a degradable scaffold made of carboxymethyl chitosan has good effects on promoting proliferation and differentiation.

As a kind of chitosan derivative, carboxymethyl chitosan inherits the advantages of chitosan and also shows its unique advantages, such as water solubility, film-forming property, ion chelating ability, collagen-promoting ability, etc. In terms of mineralization, many studies have confirmed its important role in oral tissue regeneration, including bone tissue regeneration, dental tissue regeneration, periodontal tissue regeneration, etc. On the one hand, carboxymethyl chitosan not only has good antibacterial properties as a scaffold material or gel material, but also has excellent sustained release effect and ideal pore size, and can be used in combination with a variety of bioactive macromolecules, metal compounds, etc. Create synergy. On the other hand, carboxymethyl chitosan can be used as a modified material to give composite materials better performance, biological activity, and service life.

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