Hyaluronic Acid Dermal Fillers

Hyaluronic acid fillers are composed of long chains of hyaluronic acid (HA). Most of them contain HA that has been cross-linked with chemicals such as 1,2,7,8-diepoxyoctane (DEO), divinyl sulfone (DVX), and 1,4-butanedioldiglycidyl ether (BDDE). In some formulations, hyaluronic acid is suspended in a phosphate-buffered or physiological solution. These products are then processed as a suspension of particles in gel carriers or a homogeneous gel. Due to the different manufacturing methods, hyaluronic acid fillers vary greatly in their properties, such as concentration, the size of particle, and degree of cross linking. Ultimately, these properties will influence the performance and effectiveness of the dermal filler. Hyaluronic acid chains are linked together by hydrogen bonds, forming highly stable complexes. The minimal use of chemicals in the manufacturing process helps to reduce the risk of allergy.

Based on their particulate forms, hyaluronic acid can be classified as either monophasic of biphasic. As implied by its name, monophasic HA gels contain a single phase of hyaluronic acid. These gels can be either mono-densified (in which hyaluronic acid is cross-linked and mixed in just 1 step) or poly-densified. In contrast, biphasic HA gels (e.g. Restylane) contain 2 phases of hyaluronic acid. Non-crosslinked hyaluronic acid acts as a carrier, in which cross-linked hyaluronic acid is suspended.

It is unclear which type of gels is more effective. This is still being debated and studied. In reality, there really is no “1 size fits all” product. Rather, the fillers are meant for different indications due to their difference in physical properties.

The Rheology of Hyaluronic Acid Dermal Fillers

Rheology is the branch of physics dealing with the flow of matter. It involves the study of physical characteristics that affect the behavior of materials under deforming forces. Once administered, dermal fillers are subject to stretch, vertical compression, and shearing resulting from the movements of muscle, gravity, and compression. In order to select the most suitable filler, doctors should have a good understanding of how dermal fillers behave in a particular skin layer or treatment area. Fillers differ greatly in terms of desirable qualities depending on the location of the treatment site.

For instance, when injecting into the deep subdermal skin layer, the filler should be able to give good volume and projection. At the same time, it should not spread too easily through the tissue. In contrast, when treating the superficial skin layers, the filler should spread through the tight connective tissues easily so that it can sit smoothly on the upper skin layer. There are many factors that can influence the physical characteristics of hyaluronic acid fillers, including:

  • Viscous modulus G”, which refers to the inability of the material to recover and revert into its original shape after shear deformation.
  • Elastic modulus or G’, which is the ability to recover and return to the original shape after shear deformation.
  • Cohesivity, which refers to the strength of the cross-linking adhesive forces that connect individual hyaluronic acid units. It is determined by the degree of cross-linking and the concentration of hyaluronic acid. High cohesivity can help the dermal filler to maintain vertical projection.
  • Complex modulus or G*, which is the total ability of the material to withstand deformation. It is calculated by adding viscous modulus (G”) to elastic modulus (G’).

The following table outlines the rheological properties and desirable physical characteristics of fillers based on the treatment areas.

Area Purpose Rheological Properties Desirable Properties
Fine lines and lips
  • To restore volume in sub-dermal and intradermal planes
  • Low cohesivity (e.g. Juvederm Volbella, Belotero Balance, Restylane Refyne, Restylane Kysse, Teosyal Global Action and Teosyal RHA 2)
  • Low-medium elasticity
  • Low viscosity (for ease of injection)
  • Easy molding and spread of product
  • Non-bulking
  • To achieve projection
  • To restore volume
  • Deep dermal or subdermal injection
  • Medium to high cohesivity (e.g. Juvederm Voluma, Belotero Volume, Teosyal Ultimate, Restylane Lyft and Teosyal Ultra Deep)
  • High elasticity
  • Low viscosity (for ease of injection)
  • Maintain shape
  • Minimal displacement
  • Withstand compression
  • Withstand shear deformation
Chin and Nose
  • For chin and nasal projection
  • High cohesivity (e.g. Juvederm Voluma, Belotero Volume, Teosyal Ultimate and Restylane Lyft)
  • High elasticity
  • Low viscosity (for ease of injection)
  • Maximal vertical projection
  • Minimal lateral spread
Lower Face 
  • To restore volume in subdermal planes or deep dermal
  • Low-medium cohesivity (e.g. Juvederm Volift, Belotero Intense, Teosyal Global Action, Restylane Refyne and Teosyal RHA 3)
  • Moderate elasticity
  • Low viscosity (for ease of injection)
  • Non-palpable
  • Minimal projection
  • Easily moldable