Article by Dr. Paula Pifarré
Injectable dermal fillers are currently the most widely used products to treat the signs of facial aging and improve the face.
Hyaluronic acid (HA) in particular, is the most common since they are safe, effective and reversible treatments that provide long-term natural results. (Pierre 2015; Fagien 2019; Faivre 2022; Fundarò 2022)
HA fillers are a hydrogel composed of cross-linked HA, suspended in physiological or phosphate-buffered solution, that are made by joining chains of HA. The most commonly used crosslinker or crosslinker to produce these networks and junctions is 1,4-butandioldiglicidyl ether (BDDE), which binds covalently and irreversibly to HA molecules.
This binding results in a crosslinked HA compound, which can be processed in different ways to produce homogeneous gels or particle suspensions.
Each HA filler has different amounts of crosslinker, HA concentrations and is processed in a different way, so each commercial house and product has unique properties that must be taken into account when applying an HA filler.
Understanding the properties will allow injectors to select the ideal and safest product for the treatment of each area of the face. Fillers placed superficially on the face to correct small wrinkles must have different properties from those used at deep levels to recover volume. This is because facial regions are layered, subjected to stresses of varying frequency and intensity due to underlying skin tension, muscle activity, and fat volume. These stresses will cause a deformation of the HA filling in different proportions.
Fillers for deep injections are colloquially defined as “harder” and fillers for fine lines as “softer.” Soft fillers are considered to have lower viscosity and elasticity and tend to spread or expand into soft tissue (i.e., they are ideal for fine lines and wrinkles). Hard fillers, on the other hand, have higher viscosity and elasticity and provide lift and support, with negligible product migration (ie, they are ideal for restoring volume).
Most modern AHs are obtained from bacterial fermentation due to their reduced allergenic and immunogenic potential (AH of animal origin can retain impurities that could cause adverse reactions).
Rheology is a branch of physics that deals with the deformation and flow of liquid, gaseous, and soft solid (such as gel) matter. It studies the behavior of materials when subjected to deforming forces and is applied to substances that have a complex microstructure, such as mud, suspensions, topical medicines, paints, body fluids (for example, blood) etc.
HA rheology refers to the study of its behavior and physicochemical properties when subjected to mechanical stress such as flow, deformation or viscosity.
The rheological behavior of HA is especially relevant in the field of medicine and cosmetics. The gelatinous consistency of HA gives it its unique characteristics, allowing it to be injected and molded in different areas of the body.
In rheological terms, HA can exhibit both elastic and viscous properties. This means that it can behave like an elastic solid when subjected to small deformations, but also like a viscous liquid when subjected to shear forces (shear internal force that is tangential to the surface on which it acts).
Injectors are advised to be familiar with the rheological and physicochemical properties of filler materials to facilitate selection and avoid adverse effects.
Recently, Fundarò et al. (2022), identified nine important characteristics with clinical implications related to the application of HA dermal fillers (Table 1).
Table 1. Summary of rheological and physicochemical characteristics and their clinical implications (adapted from Fundarò et al. 2022).
It is essential to understand these parameters in order to select the most appropriate and safest among the different products available on the market.
It is important to note that many of these parameters are used to determine what the behavior of the fill will be in situ. For example, when G´´> G’ the filling will behave like a viscous material, while G”< G’ will behave like an elastic material; or for example, as the crosslinker increases, so does the G’ but the swelling coefficient decreases (Fallacara A. 2017; Fagien 2019).
The rheological and physicochemical properties will be affected by multiple factors, such as the crosslinker used, the HA concentration, the molecular weight, or the formation process of the injectable solution or gel. (Fagen 2019).(Fagien 2019).
No filler is appropriate or indicated for all possible treatments in the field of facial aesthetic medicine. The interaction between all its rheological and physicochemical properties should allow us to understand how the filler will behave in situ and will allow a correct selection of the product based on the area to be treated.
Depending on the manufacturing procedure, two large families of HA fillers have been described: “monophasic” and “biphasic” (also known as “cohesive” and “granular”). The monophasic filler is a homogeneous mixture of high or low molecular weight crosslinked HA chains and the biphasic type contains crosslinked HA particles dispersed in a carrier (non-crosslinked or very low crosslinked HA) that act as a fluid matrix (Figure 1, adapted from Fundarò 2022). These two types of filler have different production modalities that lead to different rheological and physical characteristics although they share the same indications. In general, single-phase fillers have less elasticity and higher viscosity than two-phase fillers.
Figure 1: Differences between single-phase and two-phase fillers (adapted Fundarò 2022).
In the body, the natural linear shape of HA molecules is rapidly broken down by the enzyme hyaluronidase. For the application as fillers, it is necessary to modify the physical properties to increase the resistance of the HA molecules to reabsorption. The polymerization of HA modifies its properties and facilitates the permanence of the product in the tissue. Crosslinked HA, for example, is less susceptible to chemical and enzymatic hydrolysis and shows prolonged persistence, becoming less viscous when transformed into a viscoelastic gel. This creates a steric “barrier” that reduces penetration and mobility of hyaluronidase within the gel, thereby increasing the longevity of the filler in soft tissue.
The degree of crosslinking contributes indirectly to the “hardness” of the gel. This process makes it possible to increase the rigidity of the gel until it becomes a solid material. For this reason, the crosslinking process greatly influences the physical and rheological characteristics of HA fillers.
They can also be divided into two types based on whether or not the fillers are biodegradable. In biodegradable fillers, it must be considered that its application must be repeated at regular intervals. With the exception of fillers with autologous fat, biodegradable fillers of long duration (15 to 24 months, polylactic acid or calcium hydroxyapatite) or moderate duration (3 to 12 months such as HA or collagen) can be differentiated (Fallacara 2017 )
Knowledge and understanding of the rheological properties of HA can help physicians select products and identify the most appropriate for each indication, facial region, and anatomical layer. The tension of the soft tissues, the muscular movements, gravity and the pressure on external surfaces (a pillow when sleeping, a motorcycle helmet, etc.) apply different forces to the HA fillings that determine a shear deformation, the vertical compression and stretching. Each of these forces varies depending on the depth where the injection has been made, the area of the face and the types of mimetic movements of the patient.
In conclusion, it must be borne in mind that the rheological and physicochemical characteristics influence the integration between the filler and the surrounding soft tissue and determine the capacity of the filler to modify the volume of the injected anatomical layer.
Knowledge allows professionals in the field of aesthetic medicine to be able to select the filler with the appropriate characteristics to achieve the desired results. There is a consensus in the medical community attributing the greatest importance to the G’ parameter within the rheological parameters, however it is essential to combine it with the physicochemical parameters when selecting a product to be injected.
When making a selection of filler, the following must be taken into account: the anatomy of the injected area, the consistency of the tissue, the thickness of the tissue, the tensing of the retention areas, the intensity and strength of the mimetic muscles and external forces. that act on that facial area, as well as the properties of the product. This selection will determine the “aesthetic footprint” that the product will leave on patients. Recently, the Spanish Society of Aesthetic Medicine (SEME) has published an article regarding the problems and misuse of facial fillers, with the consequent negative aesthetic traces, versus the “positive aesthetic traces” when all these points are taken into account.
It is important to highlight that the degradation of fillers using hyaluronidase is a fundamental aspect of safety in HA treatments. It must be kept in mind that the degree of crosslinking can, for example, alter the exposure of the molecules and hinder enzymatic degradation. In this sense, the rheology and physicochemical properties must also be known in order to apply the appropriate protocols in the presence of adverse effects. (Wong Prasert 2022).
MASTERCLASS: Importance of product choice for optimal results.
Bibliographic references
1-Fundarò, S. P., Salti, G., Malgapo, D. M. H., & Innocenti, S. (2022). The Rheology and Physicochemical Characteristics of Hyaluronic Acid Fillers: Their Clinical Implications. International journal of molecular sciences, 23(18), 10518. https://doi.org/10.3390/ijms231810518
2-Wongprasert, P., Dreiss, C. A., & Murray, G. (2022). Evaluating hyaluronic acid dermal fillers: A critique of current characterization methods. Dermatologic therapy, 35(6), e15453. https://doi.org/10.1111/dth.15453
3-de la Guardia, C., Virno, A., Musumeci, M., Bernardin, A., & Silberberg, M. B. (2022). Rheologic and Physicochemical Characteristics of Hyaluronic Acid Fillers: Overview and Relationship to Product Performance. Facial plastic surgery : FPS, 38(2), 116–123. https://doi.org/10.1055/s-0041-1741560
4-Faivre, J., Gallet, M., Tremblais, E., Trévidic, P., & Bourdon, F. (2021). Advanced Concepts in Rheology for the Evaluation of Hyaluronic Acid-Based Soft Tissue Fillers. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.], 47(5), e159–e167. https://doi.org/10.1097/DSS.0000000000002916
5-Fagien, S., Bertucci, V., von Grote, E., & Mashburn, J. H. (2019). Rheologic and Physicochemical Properties Used to Differentiate Injectable Hyaluronic Acid Filler Products. Plastic and reconstructive surgery, 143(4), 707e–720e. https://doi.org/10.1097/PRS.0000000000005429
6-Fallacara, A., Manfredini, S., Durini, E., & Vertuani, S. (2017). Hyaluronic Acid Fillers in Soft Tissue Regeneration. Facial plastic surgery : FPS, 33(1), 87–96. https://doi.org/10.1055/s-0036-1597685
7-Pierre, S., Liew, S., & Bernardin, A. (2015). Basics of dermal filler rheology. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.], 41 Suppl 1, S120–S126. https://doi.org/10.1097/DSS.0000000000000334
