Comparative toxicity study of hyaluronic acid fillers crosslinked with 1,4-butanediol diglycidyl ether or poly (ethylene glycol) diglycidyl ether.
Do Hyun Kim, Chang Hee Jeong, Jong Hyeon Han, Su Jin Lim, Hyuk Cheol Kwon, Yea Ji Kim, Dong Hyun Keum, Keyong Ho Lee, Sung Gu Han
Author Information
Do Hyun Kim: Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea.
Chang Hee Jeong: Technology Innovation Research Division, World Institute of Kimchi, Gwangju 61755, Republic of Korea.
Jong Hyeon Han: Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea.
Su Jin Lim: Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea.
Hyuk Cheol Kwon: Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea.
Yea Ji Kim: Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea.
Dong Hyun Keum: Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea.
Keyong Ho Lee: R&D Department, Organoflora, Chuncheon 42237, Republic of Korea.
Sung Gu Han: Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea. Electronic address: hansg@konkuk.ac.kr.
Dermal fillers comprising injectable hyaluronic acid (HA) are widely used for soft tissue augmentation, often using crosslinking agents such as 1,4-butanediol diglycidyl ether (BDDE) or poly (ethylene glycol) diglycidyl ether (PEGDE). Here, we assessed the physical properties, toxicity, and inflammatory reactions of HA fillers crosslinked with either BDDE (HA-BDDE filler) or PEGDE (HA-PEGDE filler) in in vitro and in vivo investigations. The HA-PEGDE filler exhibited higher G', tan δ, G*, and complex viscosity values compared to the HA-BDDE filler, while maintaining similar cohesivity. The filler extracts were used to evaluate cytotoxicity. HA-PEGDE filler extracts exhibited reduced cytotoxicity, oxidative stress, and inflammation in human keratinocytes (HaCaTs) and fibroblasts (HDFs) than that of HA-BDDE filler extracts. In animal studies, SKH1-hairless mice were injected subcutaneously with varying volumes of fillers and euthanized at 1- and 4-weeks post-injection. Compared with the HA-BDDE filler, the HA-PEGDE filler displayed favorable biocompatibility, decreased tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression and reduced inflammatory cell infiltration. Our results demonstrate that the HA-PEGDE filler has comparable rheological properties and lower toxicity than the HA-BDDE filler, suggesting its suitability as an alternative in applications where minimal inflammatory response is crucial.
