The production of injectable hydrazone crosslinked gellan gum-hyaluronan-hydrogels with tunable mechanical and physical properties

Gellan gum (GG) has been proposed for use in tissue engineering (TE) due to its structural and functional similarities with alginate. The most traditional crosslinking methods of GG, ionical and photocrosslinking, have downsides such as loss of stability or phototoxicity, which can limit their use in certain applications. In this study, an alternative hydrazone crosslinking method is introduced. Hydrazone crosslinking is a simple method that produces no toxic reagents or side-products. The method enables the fabrication of injectable hydrogels. GG was combined with hyaluronan (HA) to improve some properties such as cell attachment. The mechanical and physical properties of GG-HA hydrogels were controlled by changing the molecular weight, the degree of modification, and the ratio of polymer components. GG-HA hydrogels showed ionic nature of deswelling in the presence of cations enabling the control of physical properties in different solution environments. Due to the non-linear elastic behavior of hydrogels and tissues, the stiffness as a function of strain was represented instead of solely giving the second-order elastic constants. The stiffness of GG-HA hydrogels was similar to that of soft tissues at small strains.