Natural polymers are widely used in food, medicine and other related industries due to their safety, non-toxicity, low cost, environmental friendliness, abundant sources, good biocompatibility and degradability in the human body. Among them, natural polysaccharides, as one of the major types of natural polymers, are a type of polymer that medical researchers focus on. Natural polysaccharides are widely available and can be obtained from various sources, such as extraction from seaweed, crustaceans, etc. Carrageenan is a linear anionic polysaccharide with sulfated galactose as the sugar unit extracted from marine red algae. Since its discovery in the 20th century, carrageenan polysaccharides have been widely used as thickeners and gelling components in the food industry. Because its structure is similar to that of natural glycosaminoglycans, carrageenan is also widely used in the medical field. At present, carrageenan has been included in the United States Pharmacopoeia and the European Pharmacopoeia, and its safety has been widely recognized worldwide.
Figure 1. Molecular structure of the polymers and the photographic images of the obtained hydrogels. (Croitoru C, et al.; 2020)
Carrageenan is a natural polysaccharide whose skeleton is formed by alternating D-galactose in α-(1-3) or β-(1-4) bonds. It can be classified according to the presence of 3,6-anhydro-D-galactose at the 1-4 bond and the position and content of its sulfate group. According to the connection form of its sugar units and the number of sulfate groups, it is divided into three types: κ (kappa) carrageenan, ι (iota) carrageenan and λ (lambda) carrageenan. Among them, κ-carrageenan is composed of galactose and 3,6-anhydrogalactose containing 4-sulfate ester groups connected by alternating 1,3-α- and 1,4-β-glycosidic bonds, and each disaccharide repeating unit carries a negative charge. ι hydrocarrageenan carries two negative charges. κ-carrageenan and ι-carrageenan have similar properties. Under high temperature conditions, both will undergo thermally reversible conformational arrangements and their gelling properties are excellent. Temperature, ion species and concentration will affect their gelling properties. The molecular chain of λ-carrageenan is in a random curled conformation at any temperature, so λ-carrageenan does not have the ability to form gels. However, under the action of trivalent iron ions, λ-carrageenan can also form gels
As a natural polysaccharide, carrageenan has excellent biocompatibility and thermal responsiveness. κ-carrageenan has the ability to form a fibril network and can form hydrogels of different shapes and adjustable mechanical strength. Researchers used nanosilicate to enhance the mechanical strength of κ-carrageenan, making it shear-thinning, and prepared a nanosilicate/κ-carrageenan bio-ink, which can be used to print a tissue structure with controllable mechanical strength and material shape. In addition, the shear-thinning properties of the bio-ink enable mouse preosteoblasts to be effectively mixed without forming cell aggregates. These enhanced bio-inks have broad application prospects in the design of large human tissue structures in tissue engineering and regenerative medicine. In addition, the study found that when κ-carrageenan is combined with functional bioactive ingredients, an apatite layer can be quickly formed on the surface of κ-carrageenan with a better structure. After researchers incorporated κ-carrageenan into hydroxyapatite/collagen composite hydrogels, their compressive strength increased significantly. The enhancement of mechanical properties proves that κ-carrageenan can be used as an effective enhancer for bone repair materials. By coating the surface of polyhydroxybutyric acid (PHB) and polyhydroxybutyric acid valerate (PHBV) nanofibers with κ-carrageenan, the mechanical strength and degradation rate of the nanofibers can be adjusted, and the differentiation and biomineralization of osteoblasts can be promoted. Compared with the control polyester fibers, the surface of the κ-carrageenan-coated fibers has micron- to nanometer-scale apatite crystals. After being cultured with osteosarcoma cells, the biomineralization of the fibers coated with κ-carrageenan is improved, giving the fiber material the potential for osteogenic differentiation. In addition to its application in bone tissue engineering, κ-carrageenan is also used in the field of wound healing. In order to overcome the disadvantage of poor mechanical strength of κ-carrageenan, some researchers have incorporated silk into γ-ray irradiated cross-linked PVA/PVP/κ-carrageenan hydrogels. Compared with commercially available wound dressings, PVP/κ-CRG/polyethylene glycol hydrogel dressings have a long shelf life, good effects, and high tensile strength. κ-carrageenan-enhanced 2D nanosilicates were developed by simply mixing two components in different ratios. The incorporation of nanosilicates not only enhances the mechanical properties, injectability, and stability of the hydrogel, but also provides space for the continuous delivery of therapeutic drugs, with better protein adsorption, cell adhesion, migration, and platelet binding capabilities, which not only play a hemostatic role but also promote wound healing. The shortcomings of insufficient antibacterial properties of dressings can be improved by incorporating nanosilver ions into hydrogels. These nanosilver ions incorporated into κ-CRG hydrogels have a significant inhibitory effect on both Gram-positive and Gram-negative bacteria. More importantly, κ-carrageenan also has important applications in the field of drug delivery. The thermoreversible gelation, biocompatibility, adjustable viscoelasticity, and simple gelation mechanism of κ-carrageenan make κ-carrageenan an ideal polymer for drug transport applications. The researchers synthesized κ-carrageenan beads cross-linked with KCl for the continuous delivery of angiogenic growth factors, thereby promoting vascularization in the defect area. The introduction of nanosilver ions increased the elastic modulus of κ-CRG hydrogels because the negative surface charge of AuNPs attracted K+ ions to the surface, resulting in an increase in counterions around the nanocarriers. The release of AuNPs due to surface chemical adsorption resulted in the release of methylene blue (MB) from AuNPs incorporated into κ-hydrogels. In the past few years, there has been an emerging trend in the use of carbon nanotubes (CNTs) in the field of nanomedicine and biotechnology. Near-infrared light (NIR) and temperature-responsive multilayer CNTs-reinforced κ-hydrogel composites for controlled drug release have been developed. The mechanical strength increases with concentration. After NIR exposure, faster release of methylene blue was observed due to the transition of MWCNTs-κ-hydrogel from gel to sol. Compared with the control hydrogel without MWCNTs, the drug release was slow and sustained at physiological temperature without NIR exposure.
Alternate Names:
Kappa-carrageenan sulfate
K-carrageenan
Carrageenan K
Kappa-carrageenan gum
References:
1. Croitoru C, et al.; Physically Crosslinked Poly (Vinyl Alcohol)/Kappa-Carrageenan Hydrogels: Structure and Applications. Polymers (Basel) . 2020, 12(3):560.
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