Alginic acid, or more commonly known as alginate, is probably one of the most commonly used and versatile hydrogel for cell encapsulation, cell culture, and tissue engineering. Its biocompatibility and simple cross-linking / gelation chemistry makes it ideal for encapsulating cells. In addition, chemical modifications can be made on the polymer chain to promote cell adhesion and cell growth. In this blog, we will discuss how alginate has been used for bioprinting.
What is alginate?
Alginate is an anionic polysaccharide derived from brown seaweed and basically made up of two polymer blocks, (1-4)-linked β-D-mannuronate (M) and its C-5 epimer α-L-guluronate (G) residues (Figure 1), that are covalently linked together. The important component in the alginic acid polymer chain are the carboxylic acid groups which permits cross-linking. This transforms alginate from its liquid state to a semi-solid gel state.
How does it cross-link?
The most common form used for cell culture and tissue engineering is sodium alginate, this is the sodium salt of alginic acid (Figure 1). In the presence of calcium ions, ionic interactions between Ca2+ and COO- occur and cross-linking of alginate polymers results (Figure 2). Ionic crosslinking is a gentle procedure for cells causing minimal damage. The crosslinking process occurs fairly quickly.
Due to its structural similarity to natural extracellular matrices, alginate has been used extensively in many biomedical applications including wound healing and delivery of bioactive agents.
Alginate hydrogels are traditionally used for cell encapsulation. This is done by mixing cells in alginate solution then dropping the alginate-cell mixture into a bath of calcium chloride solution. At low concentrations (1-2%), the alginate solution is low in viscosity and will not be printable. But it can be mixed with other materials such as gelatin or methylcellulose to make it more viscous and more printable.
How is it used in bioprinting?
The structural similarity of alginate to extracellular matrices make it an ideal biomaterial. Matrix stiffness is a key determinant of stem cell differentiation and alginate presents a promising material to promote control stem cell growth. Alginate supports cell growth and possesses high versatility, extending to both in vitro and vivo differentiation.
Bioprinting applications, such as extrusion, require fast gelation. Alginate offers high gelation processes when mixed with a multivalent cation, allowing gels to develop and set at constant temperature. It is also used to encapsulate cells. This allows it to be an effective tool in varying the release rate of drug and growth factor delivery. While alginate degradation rate can be somewhat controlled by altering the MW of the alginate, it is still slow and difficult to control. The stiffness and composition properties of alginate bioink can be tuned to direct the differentiation of stem cells.