Effect of cross-linker chain length on biophysical property of hyaluronic acid hydrogel dermal filler

Hyaluronic acid (HA) hydrogels have been widely harnessed for tissue augmentation in plastic surgery, lubrication in knee joint, ocular surgery, and other biomedical applications. The biophysical features of the HA hydrogels are highly depending on the cross-linking agents, which is especially important for the applications to dermal fillers. Here, we investigated the effect of cross-linking chain length of divinyl sulfone (DVS) and 1,4-butanediol diglycidyl ether (BDDE) on the viscoelasticity and retention time of HA hydrogel dermal fillers. After subcutaneous injection of HA-DVS hydrogel dermal filler to rabbits, the safety and stability assessment for a period of 12 weeks revealed that the statistically significant amount of HA-DVS hydrogels remained without any observable change and toxicity. Furthermore, the clinical evaluation demonstrated the equivalence of HA-DVS hydrogels comparable to HA-BDDE hydrogels. There were no clinical abnormal reaction and safety issues. Taken together, we could confirm the clinical feasibility of HA-DVS hydrogel dermal filler with high stability and safety for further clinical applications. Graphical abstract Hyaluronic acid (HA) hydrogels have been widely used for various biomedical applications. Here, we investigated the effect of cross-linking chain length of divinyl sulfone (DVS) and 1,4-butanediol diglycidyl ether (BDDE) on the viscoelasticity and retention time of HA hydrogel dermal fillers. From the results, we could confirm the feasibility of HA-DVS hydrogel dermal fillers with high stability and safety for further clinical applications.