Fillers based on hyaluronic acid – the gold standard in aesthetic medicine for the correction of wrinkles and restoration of facial volumes. Cosmetologists who have been using fillers for more than a year are well aware of how much the needs and requirements for this type of product have changed. Accordingly, since the invention of dermal fillers, indicators of their effectiveness and safety have increased. Read more about the technological evolution of hyaluronic acid fillers on estet-portal.com right now.
History of hyaluronic acid fillers
Hyaluronic acid fillers have a rich history. In 1934 Mayer and Palmer discovered hyaluronic acid. One of the first branches of medicine in which it began to be applied is ophthalmology.
In the nineties, thanks to Dr. Balazs, the first hydrogels for nourishing the skin (hylan B) were obtained.
At first, hyaluronic acid of animal origin was used in preparations. HA was obtained from crushed parts of animals (for example, cartilage, intra-articular fluid). Often, as a result of the use of the acid thus obtained, patients developed inflammatory and allergic reactions to animal protein.
In order to solve this problem, HAs of bacterial origin have been used (for the first time – in NASHA gel). Until recently, its most popular source was bacterium streptococcus. The production process of HA requires the destruction of the bacterial cell membrane using chemical solvents. Therefore, endotoxins, bacterial particles and solvent residues are present in the finished product. Unfortunately, the cleaning process does not completely eliminate these impurities, which negatively affects the safety of the filler.
Progress is not worth it place, therefore, in the search for an ideal solution, for the first time in injectable preparations, HA synthesized by the non-pathogenic bacterium Bacillus Subtilis (Hay bacillus) was used. This innovative patented technology, used by Novozymes (Denmark) and certified GRAS (absolutely harmless) in the USA, eliminates the use of chemical solvents and allows you to get the purest hyaluronic acid!
Hyaluronic acid fillers:
- substances for cross-linking hyaluronic acid in fillers;
- PEG characteristics for hyaluronic acid fillers;
- calcium hydroxyapatite microspheres in hyaluronic acid fillers;
- rheological properties and binding abilities of HA gels.
Substances for crosslinking hyaluronic acid in fillers
The safety and effectiveness of fillers also depends on the method of HA stabilization. The substance that is used for cross-linking (“adhesion”) allows holding long chains of HA molecules. With an increase in the concentration of the cross-linking agent, the clinical effect increases, but the risk of developing allergic reactions to the injected filler increases.
As the industry has evolved, ever less toxic crosslinkers have been used: from divinyl sulfate (lethal dose, DL50 32mg/kg) to the use of BDDE (DL50 1134mg/kg ). Given the toxicity of these substances and their ability to accumulate in tissues, many manufacturers seek to reduce its content in their products. But this negatively affects the duration of the effect and the volumizing ability of fillers.
Deciding to go the other way, the developers of NEAUVIA ORGANIC fillers pioneered the technology of HA reticulation using PEG(polyethylene glycol, DL50 30200mg/kg).
Today, a polymer called polyethylene glycol (PEG) has been used in aesthetic medicine for stitching.
Crosslinking with polyethylene glycol is called pegylation in pharmacology. This technology provides significant safety and performance benefits for hyaluronic acid fillers used in aesthetic applications.
Both PEG and hyaluronic acid – these are polymers. Their combination ensures the formation of the most suitable filler structure for its integration in tissues.
Main advantages of PEG for crosslinking HA-based fillers:
- low toxicity (30 times less than BDDE) and the ability to be completely eliminated from the body without accumulating in tissues;
- reduces the activity of proteolytic enzymes (hyaluronidase), significantly slowing down the destruction and biological absorption of implants;
- masks the substance with which it is crosslinked from the host organism, thereby reducing the risk of an immunological reaction, preventing inflammation and the formation of granulomas;
- high biomechanical compatibility and physiological integration of the gel into tissues.
Due to the properties of PEG described above, it is possible to achieve:
- better results of correction with hyaluronic acid fillers;
- a longer correction effect due to the resistance of the drug to stress (thermal and mechanical).
By PEGylating hyaluronic acid produced with Bacillus Subtilis, the chemical and physical properties of hyaluronic acid filters have been improved.
The pegylation technology makes it possible to improve the fillers, giving them additional properties and capabilities. For example, calcium hydroxyapatite (CaHA), as well as essential & nbsp; amino acids L-proline and glycine. Thanks to these substances, two important points are ensured:
- revitalizing effect action on the skin;
- stimulation of cells responsible for the synthesis of collagen and elastin, – fibroblasts.
Accordingly, such gels activate the processes of skin rejuvenation, thereby increasing the effectiveness of the use of fillers based on hyaluronic acid.
Calcium hydroxyapatite microspheres in hyaluronic acid fillers
Calcium hydroxyapatite – this is not a novelty in the field of aesthetic medicine, however, for the first time such a unique combination in dermal fillers has been used in NEAUVIA ORGANIC preparations. They combine the advantages of the biological activity and biocompatibility of hyaluronic acid with the stimulating properties of hydroxyapatite, thereby increasing the effect of tissue filling and increasing resistance to biodegradation.
An important role in the effectiveness of fillers is played by the size and number of CaHA microspheres used. Clinical studies have shown that in the presence of microspheres smaller than 20 microns, a significantly larger number of cells participate in the cellular response than in the presence of larger microspheres (40-80 / 80-200 microns in other preparations).
And this means that they provide longer lasting cellular stimulation, and therefore a long-term rejuvenating effect.
It should also be noted that the CaHA microspheres are evenly distributed and fixed (sewn) in the HA gel with the help of PEG. This prevents their aggregation and the formation of macromolecules larger than phagocytes, which in turn prevents the formation of granulomas and significantly increases the safety of drugs.
Calcium hydroxyapatite microspheres in HA-based fillers provide a longer lasting anti-aging effect.
Rheological properties and binding abilities of HA gels
PEG provides unique rheological characteristics of the gel - combination of cohesiveness, viscoelasticity and plasticity.
High cohesiveness allows the filler to retain for a long time form and, most importantly, prevents fragmentation and migration of gels from the injection site under the action of dynamic muscle contractions.
Polyethylene glycol creates a unique matrix with HA, bringing the elasticity modulus of the hydrogel closer to that of the dermis tissues. This ensures high elasticity and resistance of the preparation to deformation even in areas with high mimic activity.
At the same time, due to their plasticity, fillers have a unique adaptive ability. They are very uniformly integrated into the surrounding tissues, thereby strengthening the amorphous extracellular matrix, filling it through the diffusion process and restoring its former shape.
The proper balance between viscosity/elasticity and plasticity, as well as the degree of bonding power, allows correction without the risk of visible/tangible changes or displacement of the implant.
PEGylation allows you to create a dynamic and at the same time resistant to mechanical stress and thermal effects of the filler structure.
This structure of NEAUVIA ORGANIC fillers not only promotes better adaptation to tissues of different densities, but also reduces the risk of rejection, as in the case of using too dense gels. Result – excellent aesthetic effect, long-term effect and minimal risk of adverse reactions.
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