Rheologic and Physicochemical Properties Used to Differentiate Injectable Hyaluronic Acid Filler Products

Abstract

Background: Injectable hyaluronic acid fillers are routinely used for correction of soft-tissue volume loss and facial rejuvenation. Product differentiation has primarily been based on the rheologic parameter known as elastic modulus (G'), although other physicochemical properties are being explored to characterize potential product performance. As clinical data regarding product performance are lacking, the practical experience of injectors provides a valuable bridge in the knowledge gap between product rheologic data and product use.

Methods: Rheologic and physicochemical measurements (swelling factor and cohesion) were collected for 18 products. To observe the impact of G' and hyaluronic acid concentration on swelling factor and cohesion, proportional relationships were evaluated. Contributing authors were queried regarding their G'-based selection of products when considering skin quality, degree of correction, injection depth, and anatomical location.

Results: Relationships were observable between G' and swelling factor and G' and cohesion only when limited to products manufactured by the same crosslinking technology and the same concentration. No relationship between isolated hyaluronic acid concentration and swelling factor or cohesion was apparent. Although rheological parameters and the assumptions of ex vivo data translating to in vivo performance are oftentimes not completely aligned, in the clinical experience of the authors, in general, higher G' products are better suited for thicker skin and deeper injection planes, whereas lower G' products are better for more superficial planes, although exceptions to these trends are also made based on technical experience.

Conclusions: While rheologic and physicochemical characteristics can vary widely between products and the methods and measurements of these parameters are often difficult to correlate, G' represents a useful and consistent parameter for product differentiation. Understanding how to select products based on G' is valuable knowledge for customizing injection plans and contributes to an optimal aesthetic outcome.

Fig. 1.

Schematic depicting rebound effect of elastic, viscous, and viscoelastic materials following deformation.

Fig. 2.

The relationship between G′ and swelling factor (SwF) appeared most consistent only when evaluating products of the same hyaluronic acid concentration and manufacturing process, which showed that a higher swelling factor was associated with lower G′ and a lower swelling factor was associated with higher G′. Rheologic measurements were performed in a sequence that included a relaxation time of 30 minutes, a frequency sweep from 10 to 0.1 Hz at 0.1 percent strain, followed by an amplitude sweep from 0.1 to 10,000 percent (0.001 to 100) strain at 1 Hz. The gap was 1 mm using a PP25 measuring system at 25°C. Swelling factor was determined by dispersing 0.5 g of gel in saline by thorough mixing with 10 ml of 0.9% sodium chloride. The sample was shaken until dispersed and swollen to equilibrium. Swelling factor was calculated as the swollen volume (in milliliters) divided by tested weight of product (in grams).

Fig. 3.

The relationship between isolated product hyaluronic acid (HA) concentration and swelling factor (SwF) was not demonstrated. Hyaluronic acid concentration was calculated from a standard curve with the absorbance of known amounts of glucuronic acid. Product was degraded to monosaccharides with acid and the concentration of one of the disaccharide units, glucuronic acid, was measured using spectrophotometry. Swelling factor was determined by dispersing 0.5 g of gel in saline by thorough mixing with 10 ml of 0.9% sodium chloride. The sample was shaken until dispersed and swollen to equilibrium. Swelling factor was calculated as the swollen volume (in milliliters) divided by tested weight of product (in grams).

Fig. 4.

In general, as G′ decreases, the product may exhibit more cohesive properties (higher drop weight). Rheologic measurements were performed in a sequence that included a relaxation time of 30 minutes, a frequency sweep from 10 to 0.1 Hz at 0.1 percent strain, followed by an amplitude sweep from 0.1 to 10,000 percent (0.001 to 100) strain at 1 Hz. The gap was 1 mm using a PP25 measuring system at 25°C. Cohesion was measured as drop weight of the samples. Gel was extruded at a constant speed (7.5 mm/minute) from an 18-gauge cannula. Once a constant force was achieved, at least 10 fragments (drops) were collected, and average drop weight (in milligrams) was calculated.

Fig. 5.

The relationship between isolated product hyaluronic acid concentration and cohesion (drop weight method) was not demonstrated. Hyaluronic acid concentration was calculated from a standard curve with the absorbance of known amounts of glucuronic acid. Product was degraded to monosaccharides with acid and the concentration of one of the disaccharide units, glucuronic acid, is measured using spectrophotometry. Cohesion was measured as drop weight of the samples. Gel was extruded at a constant speed (7.5 mm/minute) from an 18-gauge cannula. Once a constant force was achieved, at least 10 fragments (drops) were collected, and average drop weight (in milligrams) was calculated.

Fig. 6.

Dynamic forces that contribute to deformation of hyaluronic acid filler products implanted in the superficial (dermis) and deep planes (deep fat pad and supraperiosteal) of soft tissues.