Beginners Guide to Bioprinting: Alginate as a Biomaterial

Here is the 2nd blog to our series of beginners guide to bioprinting. The purpose of this guide is to provide basic knowledge in a topic of interest in the field of bioprinting. This blog will feature the use of alginate as a biomaterial for bioprinting.

Alginic acid, or more commonly known as alginate, is probably one of the most commonly used and versatile hydrogels 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.
Stay tuned to more educational beginners guides to bioprinting featuring other biomaterials like collagen and pluronic. To view or participate in our webinar series, click here.

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. 

Figure 1. Alginate polymer consisting of G and M-residues

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 the calcium ions and cationic carboxylic group 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.

Figure 2. Crosslinking of alginate polymer chains in the presence of calcium ions

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. After printing, the alginate-gelatin or alginate-methylcellulose gel can be crosslinked in calcium chloride solution. Due to its simple chemistry, alginate is an easy-to-use material for many

beginners. You can find a variety of alginate based biomaterials for bioprinting here.

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 in 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 molecular weight of the alginate, it is still slow and difficult to control. Alginate based hydrogels has been used extensively for growing adult and embryonic stem cells in vitro. The stiffness and composition properties of alginate bioink can be tuned to direct the differentiation of stem cells.

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