Gellan gum based thiol-ene hydrogels with tunable properties for use as tissue engineering scaffolds

Gellan gum is a naturally occurring polymer that can crosslink in the presence of divalent cations to form biocompatible hydrogels. However, physically crosslinked gellan gum hydrogels lose stability under physiological conditions, which substantially limits the applications of these hydrogels in vivo. In order to improve the mechanical strength, we incorporated methacrylate into gellan gum and chemically crosslinked the hydrogel through three polymerization methods: step growth through thiol-ene photoclick chemistry, chain growth via photopolymerization, and mixed model in which both mechanisms were employed. Methacrylation was confirmed and quantified by proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FTIR). The mechanical property and chemistry of the crosslinked gels were systematically explored by varying the reaction conditions. The swelling ratios of the hydrogels were correlated with the compression moduli and affected by the addition of calcium. In vitro enzymatic degradation rate was found dependent on the degree of methacrylation. NIH/3T3 fibroblast cell proliferation and morphology were related to substrate stiffness with high stiffness leading generally to higher proliferation. The proliferation is further affected by the thiol-ene ratios. We then further modified methacrylate Gellan gum with alkane bromide to increase hydrophobicity. Cell attachment on resultant hydrogels were assessed and imaged. Cytokine release was also measured with comparison to pristine methacrylated Gellan gum based hydrogels. The results suggest that a hydrogel platform based on gellan gum can offer versatile chemical modifications and tunable mechanical properties for a variety of biomaterials applications, such as the wound healing scaffold