4 drug delivery (17) and tissue engineering (e.g. bone (18), cartilage (18,19) or neural (20) tissue regenerations). From the structural point of view, CS is a linear polysaccharide made of randomly distributed mixtures of deacetylated residues (β-(14)-linked-D-glucosamine) and acetylated residues (N-acetyl-Dglucosamine). This polysaccharide is commercially produced by deacetylation of chitin ( Figure 1A). The percentage of deacetylated and acetylated residues (so-called degree of deacetylation, DA) in CS determines its physicochemical properties as well as solubility (21), biodegradability and biological activity (22).The protonation of the amino groups on the CS backbone under acidic conditions permits the biopolymer solubility before reaching pH values that can range from 6.2 and 6.5. As a consequence, the amino groups of the Dgalactosamine units are predominantly positively charged at pH values below 6.2 (23, 24). The development of physical entanglements in CS hydrogels is governed by reversible non-covalent forces such as hydrogen, ionic and/or hydrophobic intermolecular interactions that depend on the pH, temperature, chemical composition and polymer chain length (24,25,26). Importantly, the robustness of CS-based hydrogels permits the incorporation of small molecules during the gelation process under mild conditions. In this regard, β-glycerophosphate (GP) has been described as an efficient catalyst to trigger the CS sol-to-gel transition at physiological pH. This process has led to transparent physically cross-linked hydrogels with potential use as injectable biomaterials (24) ( Figure 1B). Other small anionic molecules have also been described as effective ionic cross-linking agents including a) citrate and sulphates, b) transition metal ions like Pt (II) (27) or Mo (IV) (28), and c) the use