In vitro evaluation of hyaluronic acid gels crosslinked with 1,4-butanediol diglycidyl ether and poly(ethylene...

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 the reasons for the widespread clinical use of HA-BDDE, and further delineates the distinct properties of HA-PEGDE along with its potential applications in soft-tissue augmentation.