Gellan gum, a microbial exopolysaccharide fermentation product of Pseudomonas elodea, is a natural biomaterial that has shown promise for tissue engineering and regenerative medicine applications. Although this exopolysaccharide possesses many advantages, such interesting physicochemical properties and non-cytotoxicity, the mechanical properties and processability of gellan gum are not totally satisfactory in different tissue engineering contexts, i.e. gellan gum hydrogels are mechanically weak and the high gelling temperature is also unfavourable. An additional critical limitation is the lack of specific attachment sites for anchorage-dependent cells. However, the multiple hydroxyl groups and the free carboxyl per repeating unit of gellan gum can be used for chemical modification and functionalization in order to optimize its physicochemical and biological properties. A number of physical modification approaches have also been employed. This review outlines the recent progresses for gellan gum hydrogels and derivatives, and identifies the new challenges in tissue engineering, provided by blending and/or chemical modifications. Figure 2 -(A) Gradual transformation of gellan gum in aqueous solutions: (1) due to a change in temperature, the transition of a thermally reversible coil to double-helix chain occurs (coil-helix transition). Then, the helices self-assemble in clusters joined together by the untwined polysaccharide regions; (2) ionic-crosslinking: polymer backbone carrying the charge bind with cations (blue circles); (3) chemical crosslinking: covalent bond between polymer chains. (B) Photographs of 2% (w/v) HAGG and LAGG hydrogels.The described properties have been supporting the exploitation of gellan gum for different tissue engineering (TE) and regenerative medicine applications 13,16 . Both acellular and cellular strategies using GG were successfully proposed for drug delivery 17-20 , cartilage 21, 22 and intervertebral disc repair 23,24 . Further attractive characteristics of gellan for TE are its biocompatibility, non-cytotoxicity, mild conditions of processing, structural similarity with native glycosaminoglycans (due to the presence of glucuronic bioprinted structures that consist of discrete layers of primary cortical neurons encapsulated in GG-RGD hydrogels. These gellan gum-based brain-like structures provide an opportunity to mimic more accurately in in vitro studies the 3D microstructure of neuronal tissues.The permeability of cells from GG hydrogels is crucial for cell culture and for cell survival. GG-based hydrogels present different permeability to cells. The chick embryo chorioallantoic membrane (CAM) assay performed by in GG, iGG-MA and phGG-MA hydrogels showed that the hydrogels present different permeability to cells. iGG-MA and phGG-MA hydrogels are non-permissive to endothelial cells ingrowth, behaviour not observed in the unmodified GG hydrogels. The results showed that the methacrylation of GG allowed tuning the hydrogel permeability to cells. Conclusions and final remarksGellan ...

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