Primary Rheological Characteristics of a Novel Agarose Gel Filler Versus a Deep Volumizing HA Filler, Relevance to Clinical Behavior and Potential Considerations for Injectable Safety
Hyaluronic acid (HA) soft-tissue fillers are the most popular degradable injectable products used for facial volumization. Their viscoelastic properties under shear-stress conditions have been characterized by rheological testing, and the data have been applied to product selection and indications. The purpose of these studies was to determine key rheological properties of a novel purified agarose gel filler derived from an algal source that is CE-marked for use in Europe and for which North American clinical studies are anticipated. Like HA, agarose is a biodegradable polysaccharide that gives immediate and durable clinical results. It differs from HA in that it is stable in vivo and provides durable results after tissue implantation without the need for crosslinking chemicals or other additives.
Methods/Technique
:Rheologic testing was performed on agarose gel filler and on a crosslinked HA comparator that is CE-marked and US FDA approved for deep (subcutaneous and/or supraperiosteal) injection for cheek augmentation to correct age-related volume deficit. Testing was performed in an independent laboratory, using a parallel plate-to-plate rheometer at fixed ambient temperature and humidity. Oscillatory shear deformation testing comprised shear rate sweeps (0.1 to 100 s-1 range), time sweeps (1 s-1 shear rate) and frequency sweeps in shear. This measured elastic modulus (G’) and viscous modulus (G”); how the gels thinned out as applied force was increased (Eta*); and changes in rheological properties after agarose gel was mixed 1:1 by volume with normal (0.9%) saline and HA filler was mixed 1:1 with hyaluronidase. Static compression testing was also performed to provide a measure of each filler’s resistance to constant deformation (at a rate of 0.1 mm/s).
Results/Complications
:Rheometric testing showed that agarose gel filler had a significantly higher elastic modulus (G’) and viscosity (G”) than the crosslinked HA comparator. Both agarose gel filler and the crosslinked HA comparator demonstrated a decrease in viscosity that was proportional to applied force – a phenomenon known as shear thinning. Agarose gel filler diluted 1:1 with normal saline showed a greater decrease in viscosity than the crosslinked HA filler diluted 1:1 with hyaluronidase. Viscosity decreased rapidly / almost instantaneously for both fillers and was maintained at the same low level over the ensuing 30-minute observation period. Agarose gel filler and the crosslinked HA comparator had qualitatively similar responses to static compression testing.
Mathematical calculations of tan delta (G’ / G”) showed that both agarose gel filler and the crosslinked HA comparator had a predominance of solid over fluid behavior within the frequency range of testing.
Conclusion
:Based on these studies, agarose gel filler was found to have a rheological profile compatible with clinical behavior as a deep volumizer suitable for implantation in the subcutaneous or supraperiosteal tissue planes. Higher elasticity (G’) indicates potential for greater tissue volumizing capacity and more volume-efficient filling. Higher viscosity indicates potential for greater contour stability and less spread of the filler after implantation. The shear thinning behavior demonstrated by agarose gel filler is typical also of crosslinked HA fillers, representing a controlled and predictable thinning of the gel associated with maintenance of its elastic properties within a physiologically relevant range of testing (linear viscoelastic range). Static compression testing is especially relevant for deep volumizers which are exposed to the weight of overlying tissues.
The rapid dispersal of agarose gel filler on mixing with saline, as evinced by instantaneous decrease in viscosity, correlates with in vitro testing showing dispersal of agarose gel filler with saline and gentle agitation. In contrast, HA filler under the same testing conditions takes up water hygroscopically and is not dispersed. (Videos will be shown to demonstrate this). Water uptake within the blood vessel lumen is understood to play a significant role in the occlusive potential of HA filler. This suggests that, under the right conditions, saline may be effective to disperse agarose gel filler without the need for enzymes or other additives. Further studies must be conducted to define the relevance of these findings to in vivo behavior during and after tissue implantation. While rapid dispersal by saline may be a promising property if a filler is inadvertently injected into a blood vessel, the effects of blood components that are not present in saline such as plasma proteins must also be taken into consideration in order to accurately define whether agarose gel filler has lower occlusive or embolic tendencies. Further studies are now in progress with a particular focus on injectable safety.