Adilson Costa1, Lívia Carolina Della Coletta1, Aline Siqueira Talarico1, Maria Carolina Fidelis1, Ellem Tatiani de Souza Weimann1
Keywords: HYALURONIC ACID, ESTHETICS
Dermal fillers, which are capable of increasing cutaneous volume and restoring facial contours, are an integral part of the armamentarium used in skin rejuvenation.1,2 Among them, hyaluronic acid (HA) based substances are, without doubt, the most frequently used due to their clinical efficacy and safety of use.
There are currently a number of these filler brands available on the market, which differ in several aspects: purity of raw material, manufacturing process, HA concentration, presence and degree of crosslinking and ability to provide volume and resistance to degradation (enzymes and free radicals).2 These aspects can play an important role in the behavior of the materials during and after injection.3
Rheology is the branch of physics that studies how materials behave in response to forces, when applied to them. 4 Based on such studies, a HA-based filler can be proven to have good rheological stability, remaining intact when passing through a needle or syringe.
Hyaluronidase is an enzyme that acts on the hyaluronic acid present in the extracellular matrix, by breaking the links1-4 between glucuronic acid and N-acetylglucosamine.
HA-based fillers can be classified into: those that have crosslinking, those that contain intermolecular bond-generator substances (which increase the stability and durability of the medical implant),and those which do not have crosslinking, i.e. without those stabilizing substances.6
There are two types of reticulated HA, which have distinctive characteristics: monophasic and biphasic. The monophasic type consists of a homogeneous blend of high and low molecular weight Ahs that are easy to inject and can be sub-classified into monodensified (blending of AHs and reticulation in a single step) or polydensified (cross-linked HA with an increase of crosslinking in a second stage). The biphasic HA are heterogeneous because they contain reticulated HA particles dispersed in the vehicle (non-cross-linked HA) that act as a lubricant, allowing the suspension to pass through a fine needle.2,7
A filler''''''''s physicochemical structure and rheological properties are important because they can help determine how these substances behave during and after their respective application. 8Two important rheological properties that can be quantified are: complex viscosity (*) and elastic modulus (G'''''''').8
During the injection process, * refers to the way the filler flows from the needle, i.e. the ability of the fluid phase to resist shear forces, whereas G'''''''' relates to the ability to resist deformation while being injected.8 Once injected, * and G'''''''' influence how the filler resists the skin''''''''s tensile forces caused by movement of the face.8
A filler with a high G'''''''' value has a greater ability to resist changes in shape.4 A filler''''''''s modulus (G'''''''') is influenced by its degree of crosslinking and its concentration – the greater the crosslinking and concentration, the greater the value of G''''''''.6 The crosslinking creates intermolecular carbon bridges to hinder the action of endogenous hyaluronidase, which then produces a material with greater longevity and viscoelastic properties.1,2,6,7
Fillers with higher concentrations also have a higher volume expansion capacity and may be associated with the increased duration of their effect. Concentrations equal to or greater than 20mg/mL are deemed ideal.9
The present study was aimed at identifying alterations in the rheological properties of different kinds of HA-based dermal fillers before and after their passage through their respective needles and, in the latter situation, when in contact or not with hyaluronidase.
HA-based fillers—and their respective characteristics— used in the present study are shown in Table 1, whose summary is based on information obtained from the currently available literature and advertisements.7,10,11 Three syringes of each commercially available brand were used. The first (Syringe A) contained the material in its pure state, as found commercially; the second (Syringe B) contained the filler after passing through the needle available in its commercial form, and being returned to its standard syringe; the third (Syringe C) contained the filler after passing through its commercial needle, being returned to its standard syringe through the top brim, and being finally added with 40IU hyaluronidase (Hyalozima® - Apsen Farmacêutica S/A - São Paulo, Brazil).
After being fixed to a flat surface, the syringes were then left upright (at a right angle) for 24 hours. Due to the loss of contents during the replacement of the products to their syringes, and also in consideration of the appropriateness of the photographic images to be obtained, it was decided that only the upper 0.5 mL of each product—measured from the top brim (the tip of the syringe when in the upright, right angle position)—would be evaluated. After this period, toluidine blue (three drops) was put in all syringes through their tips. The toluidine blue remained in contact with the product at its top. Photographs of the syringes were taken at the time intervals D0 (30'''''''' and 2h30''''''''), D1 (24h), D2 (48h), D3 (72h), D4 (96h) and D7 (168h), for macroscopic visualization. At the same time intervals, photographs of the syringes were taken with a Sony CyberShot® DSC-X1 camera (Sony Corporation - Tokyo, Japan) in order to obtain a photographic record of the possible temporal changes.
As can be seen from the images obtained with the evaluation of the toluidine blue''''''''s gravimetric migration in the craniocaudal direction of the syringes (Figure 1), it is possible to note that regardless of the HA''''''''s concentration and type, the simple fact of the material passing through the needles (Syringe B) alters its state of rheological equilibrium. That situation is accelerated when the products come into contact with hyaluronidase (Syringe C).
In spite of this being an isolated study that evaluated a single syringe of a single specific commercial batch of each product, it is possible to conclude that the products that do not contain crosslinking and are monophasic have an earlier occurrence (D0 – 30'''''''') of the bluish stain gravimetry when coming in contact with hyaluronidase (Syringe C). Biphasic products are apparently the ones that have higher rheological stability when in contact with hyaluronidase after passing through the needle. Nevertheless, further studies with a greater number of syringes, obtained from different batches of biphasic and monophasic AH types, from several brands (especially those who claim to be of the monophasic type, given that they are the most commonly found in the market), should be performed with an aim of determining the actual differences among them, proving the robustness of the findings verified in the present pilot evaluation.
In general, therefore, it was verified that regardless of having crosslinking or not, or a more or less dense HA concentration, the features of HA are influenced by its rheological characteristics due to its passage through the needle, and are intensified when the AH comes into contact with hyaluronidase.
We would like to thank the dermatologists Emerson Vasconcelos de Andrade Lima, Márcio Soares Serra, Maria Helena Lesqueves Sandoval and Rosemarie Mazzuco, and the plastic surgeons Henrique Cardoso Tardelli and Henrique Lopes Arantes, who supported the authors by providing scientific information, which allowed the design of this study and the interpretation of the results.
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