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

Abstract

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 physically 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 stability, 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 properties including modulus and cytocompatibility of the crosslinked gels were systematically explored by varying the reaction conditions. We then modified methacrylate Gellan gum with alkane bromide to increase hydrophobicity and assessed macrophages attachment and cytokine release on hydrogels. We further hybridized hydrogels with viscoelastic gelatin to dissipate traction force exerted by fibroblasts, thus promote the myofibroblast activation at low compressive modulus. In the end, we functionalized hydrogels with arginine and dopamine groups. We systematically investigated how fibroblasts respond to functional groups and paracrine signals on hydrogels. The results suggested that our 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.