**2.1 Brown algae source**

Contributing up to 40% of the dry matter, a major raw source of alginic acid is derived from marine algae and kelp-like brown seaweed [3, 4]. There are several species of brown algae from which alginate can be derived; however, two species, namely *Macrocystis porifera* and *Ascophyllum nodosum*, account for most of the world's supply of alginate [5]. These species of seaweed are members of a class of seaweed that are both large and lengthy, making these plants ideal for alginic acid harvesting [5]. Unlike eukaryotic animal cells, plant cells are known to contain a rigid cell wall composed mainly of carbohydrate polysaccharide like cellulose and pectin [6]. Marine plants, such as algae, contain cell walls which are maintained by hydrocolloid polysaccharides such as alginate, carrageen, and agar which differentiate aquatic vegetation from land plants [6, 7]. These precursors can be used to cultivate alginic acid for market production.

## **2.2 Bacterial exopolysaccharide alginate source**

Two types of gram-negative bacteria genera, namely *Pseudomonas* and *Azotobacter*, can produce alginate in the form of exopolysaccharides which constitute bacterial biofilm [8, 9]. For example, *Pseudomonas aeruginosa* can synthesize alginate which contributes to the mucosal buildup of biofilms along the respiratory tract of patients with the disease cystic fibrosis [10–12]. The biosynthesis of alginate in these bacteria genera are conducted through genetic expression of alginate substrate producing genes (alg), the products of which are exported to the cell exterior [9]. The isolation of marginally pure alginate from immobilized bacterial cell extracts has been reported, but the progress of advanced bacterial alginate isolation techniques has been slow overall [13, 14]. Although these bacteria can be utilized as a source of alginate, the main commercially available form of alginate is derived from brown algae sources.

### **2.3 Alginate extraction**

Alginate exists *in vivo* as a mixture of different alginate salts including magnesium, strontium, or calcium within the intracellular matrix of brown algae tissue [4, 15]. Alginate is the conjugate base of the alginic acid and is formed upon treatment with alkaline medium [4, 16]. The primary extraction of alginic acids from brown seaweed is performed using an alkaline ion exchange treatment method which can extract and separate each of the major carbohydrate constituents of the brown algae [8, 17]. The initial extraction of algal particles from brown algae results in semi-pure fractions of differing polysaccharides which include the salt form of alginate [18, 19]. A chemical purification process, usually CaCl2 purification, involves treatment of algal particles with a mineral acid followed by neutralization with strong base (**Figure 1**). Alginate precipitates are formed via further ion transfer acid-base reaction which results in a product of mainly sodium alginate [4, 8, 18]. The sodium alginate form of alginic acid is the most favored form produced after extraction which is mainly due to cold water solubility [16]. Current techniques examine the quality and purity of extracted alginate during extraction and purification processes through several chemistry-based analytical assays including nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy [16, 20]. Recent advances in computational modeling have allowed

**39**

*Current Perspective and Advancements of Alginate-Based Transplantation Technologies*

researchers to construct models of precipitation stages which has allowed for

*Extraction of sodium alginate from brown seaweed followed by sodium alginate purification via CaCl2*

Alginate is an unbranched copolymer of β-d-mannuronic acid (M group) and α-l-guluronic acid (G group) commercially derived from algae [8]. Hydroxyl and carboxyl groups are abundantly distributed across the polymer, giving rise to a plethora of chemically modifiable sites [21]. Commercially, alginate is blocked in either consecutive M, consecutive G, or alternating M & G [22]. Given that it is a polymer with versatile properties, alginate can be easily changed to exhibit a variety of properties tailored to the individual needs of an implant. Pre-existing properties of alginate are able to be chemically enhanced through manipulating the percentage of M and G in the material, adding immunoprotective layers that impede diffusion, as well as divalent cation crosslinking. Under dicationic conditions, viscous alginate transforms

optimization of the extraction and purification process overall [20].

**3. Composition of alginate**

**Figure 1.**

*purification.*

**3.1 Types of alginate polymers**

*DOI: http://dx.doi.org/10.5772/intechopen.87120*

## *Current Perspective and Advancements of Alginate-Based Transplantation Technologies DOI: http://dx.doi.org/10.5772/intechopen.87120*

#### **Figure 1.**

*Alginates - Recent Uses of This Natural Polymer*

cultivate alginic acid for market production.

derived from brown algae sources.

**2.3 Alginate extraction**

**2.2 Bacterial exopolysaccharide alginate source**

Contributing up to 40% of the dry matter, a major raw source of alginic acid is derived from marine algae and kelp-like brown seaweed [3, 4]. There are several species of brown algae from which alginate can be derived; however, two species, namely *Macrocystis porifera* and *Ascophyllum nodosum*, account for most of the world's supply of alginate [5]. These species of seaweed are members of a class of seaweed that are both large and lengthy, making these plants ideal for alginic acid harvesting [5]. Unlike eukaryotic animal cells, plant cells are known to contain a rigid cell wall composed mainly of carbohydrate polysaccharide like cellulose and pectin [6]. Marine plants, such as algae, contain cell walls which are maintained by hydrocolloid polysaccharides such as alginate, carrageen, and agar which differentiate aquatic vegetation from land plants [6, 7]. These precursors can be used to

Two types of gram-negative bacteria genera, namely *Pseudomonas* and *Azotobacter*, can produce alginate in the form of exopolysaccharides which constitute bacterial biofilm [8, 9]. For example, *Pseudomonas aeruginosa* can synthesize alginate which contributes to the mucosal buildup of biofilms along the respiratory tract of patients with the disease cystic fibrosis [10–12]. The biosynthesis of alginate in these bacteria genera are conducted through genetic expression of alginate substrate producing genes (alg), the products of which are exported to the cell exterior [9]. The isolation of marginally pure alginate from immobilized bacterial cell extracts has been reported, but the progress of advanced bacterial alginate isolation techniques has been slow overall [13, 14]. Although these bacteria can be utilized as a source of alginate, the main commercially available form of alginate is

Alginate exists *in vivo* as a mixture of different alginate salts including magnesium, strontium, or calcium within the intracellular matrix of brown algae tissue [4, 15]. Alginate is the conjugate base of the alginic acid and is formed upon treatment with alkaline medium [4, 16]. The primary extraction of alginic acids from brown seaweed is performed using an alkaline ion exchange treatment method which can extract and separate each of the major carbohydrate constituents of the brown algae [8, 17]. The initial extraction of algal particles from brown algae results in semi-pure fractions of differing polysaccharides which include the salt form of alginate [18, 19]. A chemical purification process, usually CaCl2 purification, involves treatment of algal particles with a mineral acid followed by neutralization with strong base (**Figure 1**). Alginate precipitates are formed via further ion transfer acid-base reaction which results in a product of mainly sodium alginate [4, 8, 18]. The sodium alginate form of alginic acid is the most favored form produced after extraction which is mainly due to cold water solubility [16]. Current techniques examine the quality and purity of extracted alginate during extraction and purification processes through several chemistry-based analytical assays including nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy [16, 20]. Recent advances in computational modeling have allowed

**2. Sources of alginate**

**2.1 Brown algae source**

**38**

*Extraction of sodium alginate from brown seaweed followed by sodium alginate purification via CaCl2 purification.*

researchers to construct models of precipitation stages which has allowed for optimization of the extraction and purification process overall [20].
