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Among various physical structures such as films, fibers, and beads, microbial polysaccharides are biopolymers suitable to fabricate a half liquid‐like and half solid‐like material, known as hydrogel [137,139]. Hydrogel is a 3D crosslinked polymeric network capable of absorbing and retaining large amounts of water, commonly used in a wide range of applications in the most diversified fields [140,141].

Over recent decades, several polysaccharides including alginate, gellan gum, cellulose, dextran, hyaluronic acid, xanthan, and chitin/chitosan, either alone or in blends, all attainable through microbial production, have been used for the design and fabrication of hydrogels.

According to their preparation method and physical structure, hydrogels can be produced by physical or chemical crosslinking (Figure 2.1) [138,141]. Physically crosslinked hydrogels are reversible under specific conditions, and polymer chains are weakly stabilized by secondary forces such as ionic interactions, hydrogen bonding, or hydrophobic interactions. Despite their shape instability due to the reversibility of the formed bonds, physical hydrogels are generally harder than the chemical hydrogels [138]. A well‐known example of hydrogels formed by ionic interaction is the crosslinking of alginate using divalent cations as Ca²⁺ [143]. On the other hand, chemically crosslinked hydrogels are irreversible and stable, with strong covalent bonds involving reactions of polymeric backbone with a crosslinking agent. Chemical hydrogels can be produced by different techniques such as radiation and graft copolymerization or in the presence of a crosslinking agent. In the case of polysaccharides, the most common technique is the use of a crosslinking agent involving active reaction sites as –OH groups on its backbone [141].

Figure 2.1 Schematic representation of the fabrication of chemically and physically crosslinked hydrogels.

Source: Hoffman 2012 [142]. Reprinted with permission of Elsevier.

Depending on the types of monomers involved, hydrogels can be classified as homopolymer hydrogels, if composed by one single monomer unit; copolymer hydrogels, if constituted by two or more monomeric units, one of which must be hydrophilic; and interpenetrating polymeric network (IPN) hydrogels when two independent crosslinked networks intermesh each other in the presence of crosslinker. Therefore, hydrogels can be semi‐IPN if one of the components is a non‐crosslinked polymer [140].

Additionally, polysaccharide hydrogels can also be categorized on the basis of ionic charges as non‐anionic (neutral), ionic (cationic or anionic), and ampholytic hydrogels. Such classification refers to the overall charge, namely, no charge groups are present in neutral hydrogels, and cationic and anionic hydrogels are characterized by the presence of positively and negatively charged groups, respectively. In the presence of both negatively and positively charged groups, ampholytic hydrogels are produced [141,144]. Ionic and ampholytic hydrogels are also known as polyelectrolytes.

Considering their final application, hydrogels can be designed to be stimulus sensitive, responding distinctively toward the external condition such as temperature, pH, ionic strength, and magnetic or electric field [140,145]. In fact, the ability to respond to external stimuli makes them usually called “smart” or “stimuli‐sensitive” hydrogels. Moreover, exhibiting “smart” characteristics is an advantage to be useful in biomedical applications such as controlled drug delivery [146,147] or agricultural applications [148].

An example of naturally thermoresponsive microbial polysaccharide is gellan gum. As earlier mentioned, gellan is an anionic extracellular bacterial polysaccharide with the ability to fabricate thermoreversible gels that can have distinct mechanical properties depending on their composition. Therefore, while acetylated form of gellan produces soft and elastic gels, with deacetylated gellan hard and brittle gels are produced [144,149]. Generally, gellan has an upper critical solution temperature (UCST), which means that at a high temperature a polymer solution is obtained and the gel is produced upon cooling the solution. In particular, the temperature of gelation for gellan is within a range from 35 to 42 °C, varying with molecular weight, processing conditions, and the presence of cations [150]. Although the most common application of gellan gels is in food industry as food additive and as thickener or gelling agent [151], their potential to be applied in some biomedical applications including drug delivery and tissue engineering approaches has been investigated [149,152]. Due to their properties, gellan hydrogels are suitable to be used as injectable system for long‐term cartilage regeneration, as reported by Gong et al. [153].

The fabrication of hydrogels based on microbial polysaccharides is emerging mainly due to their less toxicity, biocompatibility, and biodegradability properties ally to acceptable mechanical strength [141]. One of the main polysaccharides studied to be used in hydrogel design and production is chitosan. Microbial chitosan is a semicrystalline cationic polysaccharide obtained by deacetylation of chitin present in yeasts and fungi cell wall. Chitosan‐based hydrogels have been prepared either by physically or chemically crosslinked methods to develop materials suitable to be applied in biomedical field as drug delivery systems or wound healing dressing [154,155]. It is well known that chitosan has low water solubility and can be maintained in solution under acid conditions. Consequently, the neutralization of a chitosan solution to a pH above 6.2 (amine pK_a) displays the gelation phenomenon [156]. This behavior allows the utilization of chitosan to produce pH‐sensitive hydrogels [154]. In fact, chitosan pH‐responsive hydrogels can be transformed into thermosensitive by the incorporation of polyol‐ or sugar‐phosphate salts such as glycerophosphate [156]. Contrary to gellan hydrogels, chitosan‐based thermoreversible hydrogels have a low critical solution temperature (LCST), which means that at room temperature a polymer solution presents low viscosity and above an LCST a gel is obtained [154]. Chenite et al. reported the production of an injectable hydrogel by physical mixture of glycerophosphate and chitosan for tissue engineering application. Neutralization of ammonium groups of chitosan by the phosphates enables the hydrophobic and hydrogen bonding between chitosan chains at high temperatures. By that way, mixture remains liquid at room temperature and forms a gel at 37 °C [157]. Similar hydrogels were fabricated by Cao et al. for the treatment of chronic rhinosinusitis (Figure 2.2) [158].

Figure 2.2 Macroscopic aspect of injectable chitosan‐based hydrogels at (a) 4 °C and (b) 37 °C.

Source: From Cao et al. 2015 [158].

Another microbial polysaccharide used to fabricate hydrogels is dextran. As previously mentioned, dextran is a water‐soluble bacterial EPS [159]. Similar to other polysaccharides, dextran has hydroxyl groups that allow derivatization and, consequently, chemical and physical crosslinking. Various authors have reported the synthesis of dextran‐based hydrogels mainly for drug delivery and tissue engineering applications [144,159]. The utilization of poly(ethylene glycol)‐grafted dextran and α‐cyclodextrins for the fabrication of thermoresponsive hydrogels was reported by Huh et al. [160]. Results showed that polyethylene glycol (PEG) grafts form inclusion complexes with α‐cyclodextrin molecules through hydrophobic interactions and thermoreversible gelation occurs through supramolecular assembly and dissociation. Similarly, Pescosolido et al. [161] have synthesized biodegradable dextran‐based hydrogels via UV polymerization of hydroxyethyl‐methacrylate‐derivatized dextran (Dex‐HEMA) and hyaluronic acid for bioprinting applications (Figure 2.3).

Figure 2.3 Top view of 3D printed hyaluronic acid (6% w/v) and Dex‐HEMA (10% w/v) hydrogel. The scale bar represents 25 mm.

Source: Reprinted with permission from Pescosolido et al. [161]. Copyright 2011, American Chemical Society.

Xanthan gum is other polyanionic polysaccharide often used as an attractive material for the fabrication of hydrogels. Generally, xanthan is combined with other polysaccharides to improve gelation characteristics since by itself xanthan is only able to produce transient weak gels. Recently, a hydrogel made from xanthan and galactomannan from the seeds of the Brazilian native tree Schizolobium parahyba was reported by Koop et al. [162]. The binary hydrogel was loaded with curcumin for topical and cutaneous wound applications. The results revealed that such hydrogels allowed prolonged exposure to the skin without any irritation and the possibility to treat skin diseases such as psoriasis. In other study, xanthan was chemically crosslinked with starch to perform hydrogels for drug delivery applications [163]. Starch–xanthan gum hydrogels exhibited selective permeability depending on drug charges and revealed to be a promising material for controlled release of several drugs.

As described, a wide and diverse range of polysaccharides have been used as attractive materials to design and fabrication of hydrogels [139,141]. Among others, remarkable properties of microbial polysaccharides make them promising materials for different biomedical applications including tissue engineering, drug delivery, and cell therapies.