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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 pKa) 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.
2.5 Bionanocomposites Based on Microbial Polysaccharides
MNPs are valuable nanostructures with proven applicability in areas such as molecular diagnostics and biomedicine [164,165]. Their unique physical properties can be tailored based on the size and composition of the inorganic material that can include noble metals (e.g. gold, silver), magnetic elements (e.g. iron, cobalt), or semiconductors (e.g. carbon nanotubes) [164]. The encapsulation of such MNPs in an inorganic (e.g. ceramic) or organic (e.g. biopolymeric) matrix generates multiphase materials (nanocomposites), wherein the synergetic effect between the components adds novel features to this material. Over the past years, the interest in the study and development of nanocomposites has grown considerably due to their valuable physical properties and countless applications that range from packaging to biomedicine [166].
Nanocomposites can have different types of matrices: ceramic, metallic, or polymeric. The properties and functionalities of these matrices can be enhanced by using diverse nanostructures such as ceramics, carbon nanotubes, metal nanoparticles, or even active biological substances [166]. Giving this, nowadays it is possible to produce nanocomposites for all sorts of applications. One good example is the production of a biocompatible hydrogel with conductive properties to be used in biomedicine. By using a polymer‐based matrix (e.g. chitosan) incorporated with a conductor inorganic material (e.g. carbon nanotubes), it is possible to produce a nanocomposite with potential use in the design of electrochemical biosensors [82,167]. Another great example is the nanocomposites produced with magnetic nanoparticles. These MNPs have their potentialities well established in the medical field. Usually, these applications take advantage of three unique features inherent to magnetic nanoparticles. These properties are the field‐induced mobility (for the development of drug delivery systems), their ability to modify magnetic relaxation times of surrounding molecules (for magnetic resonance imaging [MRI] applications), and