Synthesis and Characteristic of Cross-linked Hyaluronic Acid Hydrogels with Putrescine under the Neutral pH Condition

This study is to fabricate hyaluronic acid (HyA) hydrogels under the neutral pH condition in order to minimize the degradation of HyA during the cross-linking reaction. Two kinds of HyA hydrogels (HPDM or HPEN), were prepared with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM) or 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) as cross-linking agents, respectively, in the presence of putrescine as a diamine. Amide bond formation of hydrogels in the presence of putrescine was confirmed by FT-IR analysis. The morphology and rheological property of the hydrogels were studied through a scanning electron microscope and a rheometer, respectively. The swelling property and the degradation behavior of the hydrogels were affected by the two kinds of cross-linking agents and the molar ratio of the putrescine/cross-linking agents. Cytocompatibility of these hydrogels on human dermal fibroblast was confirmed by MTT assay. In conclusion, the cross-linking efficiency and the bio-compatibility of HPDM cross-linked by DMTMM were better than those of HPEN cross-linked by EDC/NHS.