A Review of the Metabolism of 1,4-Butanediol Diglycidyl Ether-Crosslinked Hyaluronic Acid Dermal Fillers

Abstract

BackgroundCosmetic procedures are growing ever more common, and the use of soft tissue fillers is increasing. Practicing physicians need to be aware of the biological behavior of these products in tissue to enable them to respond to any safety concerns that their patients raise.ObjectivesTo provide an overview of the metabolism of 1,4-butanediol diglycidyl ether (BDDE)-crosslinked hyaluronic acid (HA) dermal fillers and to examine the safety of the resulting byproducts.MethodsA review of available evidence was conducted.ResultsAfter reaction with HA, the epoxide groups of BDDE are neutralized, and only trace amounts of unreacted BDDE remain in the product (<2 parts per million). When crosslinked HA, uncrosslinked HA, and unreacted BDDE degrade, they break down into harmless byproducts or into byproducts that are identical to substances already found in the skin.ConclusionClinical and biocompatibility data from longer than 15 years support the favorable clinical safety profile of BDDE-crosslinked HA and its degradation products. Given the strength of the empirical evidence, physicians should be confident in offering these products to their patients.

Global Aesthetics Consensus: Avoidance and Management of Complications from Hyaluronic Acid Fillers—Evidence- and Opinion-Based Review and Consensus Recommendations

“…12 Biocompatibility data provide some reassurance regarding long-term exposure to the cross-linker 4-butanedioldiglycidyl ether in some hyaluronic acid filler products. 13,14 …”

Study of the effect of mixing approach on cross-linking efficiency of hyaluronic acid-based hydrogel cross-linked with 1,4-butanediol diglycidyl ether

“…The reaction between HA and BDDE was performed in strong alkaline conditions to form a stable covalent ether bond (De Boulle et al, 2013). At a very high pH range, the epoxide groups of BDDE preferentially react with the hydroxyl groups of HA, because the deprotonated hydroxyls are much stronger nucleophiles than both the anionic carboxylic group and the amide (Kenne et al, 2013).…”

Regeneration of dentin–pulp-like tissue using an injectable tissue engineering technique

“…Generally, scaffolds oen used for so tissue regeneration, such as polyglycolic acid (PGA) and collagen, are difficult to use for hard tissue engineering, whereas scaffolds such as b-tricalcium phosphate (b-TCP) and bioceramics, are mainly used for hard tissue regeneration, e.g. 28 Hence, BDDE-crosslinked HA gels (HAGs) in the form of microparticles are proposed to be used as an injectable scaffold to regenerate dentin-pulp complex in this work. 9,[12][13][14][15][16][17] Therefore, it is of great necessity to develop a suitable and injectable scaffold that can penetrate the entire root canal space 1,4,5,8,[18][19][20][21][22] and is also suitable for clinical application.…”