Fabrication of cell-compatible hyaluronan hydrogels with a wide range of biophysical properties through high tyramine functionalization.

Abstract

Enzymatically mediated crosslinked hyaluronan-tyramine hydrogels (HA-Tyr) are promising matrices for tissue engineering and regenerative medicine. However, due to relatively low tyramine modifications of the hyaluronan backbone achieved, HA-Tyr matrices have a weak and narrow range of mechanical properties. The iterative use of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as a coupling agent increased the yields of tyramine functionalization, which was reflected by a two-fold increase in Young's modulus of HA-Tyr hydrogels. The accurate control over hydrogel degradation was also facilitated. Viable encapsulation of human mesenchymal stem cells, with 85-98% over 6 days, was achieved in all hydrogels and distinct cellular spreading was observed in the absence of additional binding cues. The biophysical properties of the tunable HA-Tyr hydrogels are improved to study a wide range of cellular behaviors.