Modulating Rheological Properties via Non-Cross-Linked Phase in Biphasic Hyaluronic Acid Fillers

Area of Science:

• Biomaterials Science
• Dermal Fillers
• Tissue Engineering

Background:

• Hyaluronic acid (HA) based soft tissue augmentation materials are widely used for cosmetic and reconstructive purposes.
• Current HA fillers often utilize cross-linkers that can pose toxicity risks.
• There is a need for safer, effective dermal filler materials with tunable mechanical properties.

Purpose of the Study:

• To synthesize novel biphasic hyaluronic acid (HA) dermal fillers using citric acid (CA) as a green cross-linker.
• To evaluate the mechanical, rheological, and biocompatibility properties of the developed HA fillers.
• To identify an optimal HA filler formulation for soft tissue augmentation.

Main Methods:

• Biphasic HA fillers were prepared by combining non-cross-linked HA with varying concentrations of CA (4-12% w/w) and a cross-linked HA phase synthesized using 1,4-Butanediol diglycidyl ether (BDDE).
• Steam sterilization was employed, and its effect on physical properties was assessed.
• Rheological properties (G', G″, η*, phase angle) were measured, and cell viability was assessed using MTT assays with L929 cells.
• In vivo biocompatibility was evaluated according to ISO 10993 standards, including histopathological assessments.

Main Results:

• The BP-E-10-S sample, containing 10% CA, was identified as the optimal formulation.
• This optimal sample exhibited favorable rheological properties: elastic modulus (G') of 388.76 ± 13.91 Pa, loss modulus (G″) of 88.89 ± 6.22 Pa, complex viscosity (η*) of 12.69 ± 0.47 Pa·s, and phase angle of 12.86 ± 0.45°.
• Steam sterilization did not generate toxic waste.
• In vivo studies confirmed the BP-E-10-S formulation is non-irritant and biocompatible (ISO 10993-6:2016, score 1.92).
• A patent was secured for the developed formulations.

Conclusions:

• Citric acid (CA) serves as an effective and safer green cross-linker for synthesizing biphasic hyaluronic acid (HA) dermal fillers.
• The developed biphasic HA fillers possess tunable mechanical properties and demonstrate excellent biocompatibility, making them suitable for soft tissue augmentation.
• The optimal BP-E-10-S formulation represents a promising advancement in the field of dermal fillers, offering enhanced safety and efficacy.