Chemical Characterization of Hydrogels Crosslinked with Polyethylene Glycol for Soft Tissue Augmentation

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Dermal Fillers

Background:

• Hyaluronic acid (HA) hydrogels are widely used in esthetic applications.
• Crosslinking is essential for HA hydrogels to achieve desired viscoelastic properties and resist degradation by hyaluronidase.
• Polyethylene glycol diglycidyl ether (PEGDE) is a newer crosslinker offering improved viscoelasticity and reduced biodegradation.

Purpose of the Study:

• To develop and validate a method for determining crosslinking properties in PEGDE-crosslinked HA dermal fillers.
• To quantify the percentage of crosslinker and the fraction of effectively crosslinked PEGDE.
• To address the current lack of standardized methods for analyzing these fillers.

Main Methods:

• Proton Nuclear Magnetic Resonance (1H NMR) was used to determine the percentage of crosslinker.
• Carbon-13 Nuclear Magnetic Resonance (13C NMR) was employed to determine the fraction of effectively crosslinked PEGDE.
• Samples were pre-treated with acetonitrile to remove residual PEG and then digested enzymatically with hyaluronidase for NMR analysis. Acidic hydrolysis was also tested as an alternative digestion method.

Main Results:

• The crosslinking parameters were successfully determined in four NEAUVIA PEG-crosslinked dermal filler samples.
• The percentage of crosslinker ranged from 2.8% to 6.2% of HA.
• The effective crosslinker ratios (moles of effectively crosslinked PEG to total moles of PEG) ranged from 0.07 to 0.16.

Conclusions:

• The proposed NMR-based method accurately quantifies crosslinking in PEGDE-crosslinked HA dermal fillers.
• The determined crosslinker percentages are comparable to those reported for other crosslinking agents.
• PEG crosslinked hydrogels exhibit a lower effective crosslinker ratio compared to other crosslinked HA fillers.