Structural Analysis of Hyaluronic Acid Fillers Using Nuclear Magnetic Resonance: Implications for Quality Control and Clinical Performance

Potential disruptions in the biocompatibility of hyaluronic acid (HA) fillers can arise with mono-linked 1,4-butanediol diglycidyl ether (BDDE) or unreacted (pendant) 1,4-butanediol di-(propan-2,3-diolyl) ether. Assessing the filler's degree of modification involves evaluating improperly cross-linked BDDE. This study analyzed commercially available HA fillers using nuclear magnetic resonance (NMR), focusing on key parameters, such as the degree of modification (MoD), the cross-linker ratio (CrR), and the degree of cross-linking. We assessed thirteen commercially available HA fillers using NMR. The samples were placed in an NMR instrument, and each sample was analyzed for 26 h, including MoD and CrR assessments. MoD ¹H ranged from 17.065% to 2.239%, MoD ¹³C ranged from 12.567% to 1.947%, and CrR ¹³C ranged from 0.394 to 0.014. Significant distinctions were observed in the CrR ¹³C values when the MoD values of the products were similar. This study underscores the importance of considering the MoD and the CrR together to ensure optimal cross-linking and minimize the risks associated with residual BDDE impurities. Utilizing NMR for HA gel characterization provides valuable insights regarding product quality control, safety assessments, and clinical performance evaluations for esthetic interventions, contributing to filler product improvements. Further studies correlating NMR findings with real-world outcomes are essential for ensuring safety and efficacy.