In vitro evaluation of hyaluronic acid gels crosslinked with 1,4-butanediol diglycidyl ether and poly(ethylene glycol) diglycidyl ether for soft-tissue augmentation
Abstract
Unmodified sodium hyaluronate is highly susceptible to degradation in vivo, which limits its residence time and mechanical integrity for soft-tissue augmentation. To address these limitations, various chemical crosslinking strategies have been systematically investigated. 1,4-Butanediol diglycidyl ether (BDDE) remains one of the most widely used cross-linking agents. Recently, poly(propylene glycol) diglycidyl ether (PEGDE) has also gained increasing attention due to its superior biocompatibility. In this study, hyaluronic acid hydrogels (HA-BDDE and HA-PEGDE) were prepared with BDDE and PEGDE, respectively. The residual epoxy group content of both gels was below 1 ppm, meeting the safety requirements for injectable fillers. Compared with HA-BDDE, HA-PEGDE exhibited a lower swelling ratio (Q = 68 ± 5 vs. 45 ± 3), a more compact crosslinked network, and a firmer texture, contributing to the longer chain structure of PEGDE. In enzymatic degradation tests (12 U mL-1 hyaluronidase), HA-PEGDE displayed a slower initial degradation rate than HA-BDDE (23% vs. 36% at 15 min) but a faster later-stage degradation after 30 min. After 4 h of degradation, the degradation fractions reached 79% for HA-BDDE and 85% for HA-PEGDE. Cytotoxicity assays revealed higher cell viability for HA-PEGDE than HA-BDDE (99 ± 4% versus 94 ± 3%). Both hydrogels can be manufactured using analogous processes and exhibit good biocompatibility. This study provides an in vitro comparative analysis to elucidate…
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