A composite hydrogel was fabricated by introducing hyaluronic acid (HA) into gelatin (Gel) using 1-ethyl-(3-3-dimethylaminopropyl) carbodiimide (EDC) as a cross-linker. The effects of cross-linking, including cross-linker content and cross-linking time, on the morphology, swelling ratio, compressive strength and cytotoxicity in vitro of the Gel/HA hydrogel were investigated. The results showed that the pore size of the Gel/HA hydrogel decreased with increasing cross-linker content. Further, the swelling ratio of the Gel/HA hydrogel also decreased with increasing cross-linker content and cross-linking time. However, the compressive strength increased with increasing EDC content and cross-linking time. The hydrogel extracts with various contents of EDC were not toxic, due to easy removal of excess EDC by washing with dilute acid or water.
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Zhou et al. (2013) studied this question.
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