A Facile Crosslinked Hyaluronic Acid Hydrogel Strategy: Elution Conditions Adjustment

Abstract Due to its remarkable biocompatibility and biodegradability, hyaluronic acid (HA) is widely applied to increase the volume of soft tissue. However, many side effects appeared along with the residual chemical crosslinking agents. A more efficient elution process was investigated to reduce butanediol diglycidyl ether(BDDE) residue and improve the physical and biological properties of hyaluronic acid hydrogels. The effect of BDDE concentration on different properties of gels was explored under two different elution conditions. The crosslinking agent is removed more thoroughly under a high‐temperature and weakly alkaline elution condition. As the elution temperature increased and the elution solution became weakly basic, the formed HA hydrogel structure became denser with smaller pores. Moreover, changes in elution conditions significantly optimized several other important performance parameters of the gels, including their rheological properties and biocompatibility. These results indicate that the performance of HA hydrogels can be markedly enhanced without further additives or modifications, which is expected to contribute to industrial synthesis processes.