Decomposition and Changes in In Vivo Post-HA Filler Injection: A Review.

Background: Hyaluronic acid (HA) fillers are widely used in aesthetic medicine, but their in vivo behavior and long-term effects are not fully understood.

Aims: To review the decomposition and changes occurring in the body following HA filler injections, focusing on crosslinking agents, degradation processes, and tissue responses.

Methods: This review analyzed oxidative and enzymatic degradation processes of HA fillers, evaluated the impact of 1,4-Butanediol Diglycidyl Ether (BDDE) crosslinking, and examined histological changes post-injection.

Results: Uncrosslinked HA degrades rapidly due to endogenous hyaluronidase, while crosslinked HA undergoes slower degradation via free radicals and hyaluronidase. Complete cross-linking (C-MoD) showed better durability compared to partially cross-linked BDDE (P-MoD). The concept of modification efficiency (MoE) was proposed to optimize filler safety and viscoelastic properties. Histological analysis revealed collagen capsule formation and autologous tissue replacement, affecting long-term outcomes. The degree of chemical modification (MoD) influences filler durability and safety, with concerns raised about potential delayed immune reactions from accumulated pendent BDDE.

Conclusions: Clinicians should consider injection site, tissue conditions, and filler properties for safe and effective HA filler use. Emphasizing thorough BDDE removal and optimal crosslinking can enhance treatment safety and efficacy. The balance between achieving desired viscoelastic properties and minimizing potential risks is crucial. Future studies should include diverse ethnic groups to validate findings and further explore long-term tissue responses to HA fillers.