Are We Overlooking Harms of BDDE-Cross-Linked Dermal Fillers? A Scoping Review

Relatively higher-quality human studies compared with other topics in this database, e.g. multiple RCTs or systematic reviews. This does not mean it is standard or approved care.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

1,4-Butanediol ether (BDDE) is widely used as a cross-linker for hyaluronic acid in dermal fillers. The purpose of this scoping review was to determine the state of knowledge about the behaviour of cross-linked substances and safety of BDDE application. The rationale behind the review came from the clinical experience of one of the authors (KS), who noticed adverse reactions after BDDE-linked hyaluronan application. The scoping review was conducted according to PRISMA-ScR guidelines. Out of 399 articles, 52 met the inclusion criteria. Data on study design, sample/population, aims, methodology, outcomes and funding were extracted. Results were charted according to 6 subtopics: rheological properties, hydrogel stability, BDDE toxicity, immunogenicity, tissue interactions and clinical studies. In vitro, cross-linked hydrogels were characterized as effective fillers in terms of viscosity and elasticity; however, previously uncharacterized by-products of the cross-linking reaction were found. Most in vivo studies reported increased dermis regeneration, vascularization and anti-inflammatory cytokine release after implantation of BDDE-cross-linked substances. In clinical studies, BDDE was shown to sensitize subjects to 1,6-hexanediol ether and other substances found in epoxy resin systems. Occupational dermatitis and hypersensitivity reactions were documented. Our review shows that BD

Evidence level

Relatively higher-quality human studies compared with other topics in this database, e.g. multiple RCTs or systematic reviews. This does not mean it is standard or approved care.

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