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عنوان فارسی مقاله:

ژل آلژینات با ترکیبی از کلسیم و چندپار کیتوزان مخلوط به عنوان کراس لینکر


عنوان انگلیسی مقاله:

Alginate gels with a combination of calcium and chitosan oligomer mixtures as crosslinkers


سال انتشار : 2016



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مقدمه انگلیسی مقاله:

1. Introduction

Chitosans form a family of linear polysaccharides consisting of (1→4)--linked 2-acetamido-2-deoxy-d-glucopyranose (GlcNAc or A-unit) and its de-N-acetylated analogue (GlcN or D-unit). These polycationic derivatives of one of Nature’s most abundant biopolymers (chitin) can be prepared with varying degree of polymerization (DP) and degree of acetylation (FA) (Vårum & Smidsrød, 2005). The amine-group of the D-unit has a pKa-value of ca. 6.5 (Anthonsen & Smidsrød, 1995; Strand, Tømmeraas, Vårum, & Østgaard, 2001; Tsukada & Inoue, 1981) and therefore the amount of charges also influences properties as their water-solubility as a function of pH (Vårum, Ottøy, & Smidsrød, 1994). Chito-oligosaccharides (CHOS), i.e. shorter fragments of chitosans composed of the same building units and glycosidic linkages, can be prepared using both chemical and enzymaticmethods. CHOS have attracted much attention in recent years as they have been suggested to exhibit numerous biological effects (Aam et al., 2010; Nilsen-Nygaard, Strand, Vårum, Draget, & Nordgård, 2015). Alginates form a polysaccharide family (occurring in brown algae and bacteria) comprised of (1→4)-linked -d-mannuronic acid (M-unit) in the 4C1 conformation and its C5-epimer, -l- ∗guluronic acid (G-unit) in the 1C4 conformation with a pKa-value of ca. 3.5. These linear polyanionic block copolymers are composed of homopolymeric regions of M-units (M-blocks) or G-units (Gblocks), interspaced by regions of alternating epimers (MG-blocks) of different length (Draget, Moe, Skjåk-Bræk, & Smidsrød, 2006). Hydrogels are cross-linked hydrophilic polymer chains able to capture large amounts water, defined by specific properties regarding their dynamic (Ross-Murphy, 1984). The cross-links in hydrogels can be established through covalent linkages (Desai, Koshy, Hilderbrand, Mooney, & Joshi, 2015; Li, 2010) or through ionic linkages (Mi et al., 1999). Ionically crosslinked hydrogels generally feature a higher swelling sensitivity to pH changes than their covalently crosslinked counterparts, which extends their potential applications since a further tuning of the hydrogel to their specific environment becomes possible (Cuan et al., 1996). Chitosan is known for its high biocompatibility, biodegradability (Nordtveit, Vårum, & Smidsrød, 1996; Vårum, Myhr, Hjerde, & Smidsrød, 1997) and low toxicity (Köping-Höggård et al., 2001; Strand, Danielsen, Christensen, & Vårum, 2005). Moreover, antimicrobial effects (Dutta, Tripathi, Mehrotra, & Dutta, 2009; Felt, Carrel, Baehni, Buri, & Gurny, 2000; Liu, Guan, Yang, Li, & Yao, 2000; Mellegård, Strand, Christensen, Granum, & Hardy, 2011) have been shown, which are beneficial for applications such as drug delivery, implants (Xia, Liu, Zhang, & Chen, 2011) and wound healing (Ong, Wu, Moochhala, Tan, & Lu, 2008; Ueno, Mori, & Fujinaga, 2001). Tailoring of chitosans with respect to DP, polydispersity, FA andacetyl distribution is providing tools for controlling their function and properties in relation to their biological effects. Alginates are able to form ionically crosslinked hydrogels in the presence of multivalent cations (e.g. Ca2+, Sr2+ and Ba2+). Calcium-alginate gels are intensively studied and widely used for cell immobilization and protection of the cells from the host’s immune system (Draget & SkjåK-Braek, 2011; Leong et al., 2015; Strand, Mørch, & Skjåk-Bræk, 2000). These gels can be prepared through internal gelation or a diffusion method (Draget et al., 2006). The internal gelation provides a mechanism where insoluble calcium carbonate is mixed with an alginate solution, followed by a controlled lowering ofthe pH through a proton-donator such as the slowly hydrolyzing D-glucono--lactone (GDL), causing a homogeneous release of the calcium ions and subsequent gel formation. The calcium ions show specific interactions with the G-units and form junctions zones specifically between G-blocks (Sikorski, Mo, Skjåk-Bræk, & Stokke, 2007). Khong, Aarstad, Skjåk-Bræk, Draget, and Vårum (2013) has shown the possibility of forming junction zones between consecutive M-units (using polymannuronic acid) crosslinked with fully deacetylated chitosan oligomers, and it was found that at the same conditions only very weak gels were formed using polyguluronic acid (poly-G). This new gelling system, also induced by the homogeneous lowering of the pH thereby charging the chitosan oligomers using the slowly hydrolyzing proton-donator GDL, provides a new possibility of crosslinking alginates. The suggested reason for this difference in the gelling properties between alginate composed of poly-M and poly-G is the match in charge distance between the chitosan and poly-M (4C1 conformation, diequatorial glycosidic linkage) of about 10.4Å (Minke & Blackwell, 1978; Sørbotten, Horn, Eijsink, & Vårum, 2005) whereas the G-blocks (1C4 conformation, diaxial glycosidic linkage) exhibits a shorter charge distance of only 8.7Å (Atkins, Mackie, & Smolko, 1970). It seems then that Ca2+ and chitosan oligomers can provide crosslinkers for alginates where calcium ions are crosslinking through the G-blocks and the chitosan oligomers most effectively through the M-blocks. For certain cell lines immobilized in calcium alginate gels it has been found that the calcium ions can have negative effects (Chan & Mooney, 2013). Here we have undertaken a study of gelling properties of two different alginates of different composition using combinations of the two crosslinkers, where we have applied the internal gelation method (see Scheme 1) with the two different crosslinkers and measured the gel strength (Young’s modulus) and syneresis as well as the gelling kinetics of the new gels.



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کلمات کلیدی:

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