When considering the performance of hyaluronic acid injectables, it is very important to understand the concept of rheology .
Rheology is a field of physics that aims to analyze and study the properties of matter in the applied and compressed states. In other words, we are trying to study the behavior of substances under stress and deformation.
In clinical applications, it is very important to understand the rheological properties of hyaluronic acid injectables, as it helps physicians choose the right product for the right indication.
Rheological properties have four main parameters: viscosity η, normal force FN, elastic G'(shear stress), and elastic E'(dynamic compression) .
Elastic G'(shear stress) is often talked about as an important parameter in the rheological properties of hyaluronic acid injections.
Shear stress is the force that is generated inside an object and causes it to shift. For example, when you make a smile, shear stress acts on the tissue. The movement of one of the overlapping skin tissues to slide over the other is called shear stress.
Elastic G'(shear stress) basically represents the hardness of the hyaluronic acid injection. The higher the elastic G'(shear stress), the less likely the gel will be deformed.
According to Baste Ajab, Ph.D. in Pharmacy and Mechanical Engineering, one of the developers of Kaisense, Kaisense didn't want the elastic G'(shear stress) to be too high . If it is too high, the patient can feel the filler .
Kaisense is said to have increased the value of the normal force FN, another very important parameter, while finding the proper balance of elastic G'(shear stress), which represents hardness.
Normal force FN is the force with which the gel repels pressure . In the clinical setting, it means the force with which the gel raises the skin tissue. High uplift (ability to lift tissue) is the most important characteristic of the Kaisense series.
Of the Kaisense series, "Volume" and "Extreme" are said to have extremely high ability to raise the tissue, and are excellent in volume-up effect and sustainability.
Here, Dr. Tinson Lim, a well-known Asian physician and a leading opinion leader in the clinical application of filler rheology, summarizes the results of a study comparing the uplifting power of Kaisense® Extreme and Juviderm Vista® Voluma XC. Introducing the papers.
Source: Projection capacity assessment of hyaluronic acid fillers
Jérémie Bon Betemps1, Francesco Marchetti2, Tingsong Lim3, Basste Hadjab1, Patrick Micheels4, Denis Salomon5, Samuel Gavard Molliard1
1. Research and Development Department, Kylane Laboratoires SA, Plan-les-Ouates 1228, Switzerland.
2.Surgeon Roma Plastic Surgery Center Private Practice, Roma 00199, Italy.
3.Clique Clinic Private Practice, Petaling Jaya 46300, Malaysia.
4. Dr. Patrick Micheels Private Practice, Genève 1206, Switzerland.
5. Clinique Internationale de Dermatologie Genève SA Private Practice, Genève 1201, Switzerland.
Correspondence to: Dr. Samuel Gavard Molliard, Research and Development Department, Kylane Laboratoires SA, Plan-les- Ouates 1228, Switzerland. E-mail: email@example.com
How to cite this article: Bon Betemps J, Marchetti F, Lim T, Hadjab B, Micheels P, Salomon D, Gavard Molliard S. Projection capacity assessment of hyaluronic acid fillers. Plast Aesthet Res 2018; 5:19. Http: // dx.doi.org/10.20517/2347-9264.2018.24
Received: 17 Apr 2018 First Decision: 18 May 2018 Revised: 11 Jun 2018 Accepted: 11 Jun 2018 Published: 28 Jun 2018
Science Editor: Raúl González-García Copy Editor: Jun-Yao Li Production Editor: Cai-Hong Wang
Objective: Hyaluronic acid (HA) is considered the gold standard for biomaterials used in the correction of facial soft tissues. For the last eight years, doctors have sought a highly bulging HA product that restores a face with reduced volume on the cheeks, cheekbones, chin, outer corners of the eyes and lower chin. Therefore, bulging ability is an essential property of HA injectables, especially products that specialize in facial volume recovery.
METHODS: This article presents, applies and examines a new skin model assay for assessing the uplifting ability of HA injectables.
Results: This skin model assay can efficiently evaluate the uplifting ability of HA injectables. A comparative evaluation of the benefits of Juvéderm Voluma with products benefiting from the new OXIFREE technology revealed that OXIFREE products have higher uplift capabilities than Juvéderm Voluma.
CONCLUSIONS: This test demonstrates that it is an important tool to guide physicians in choosing products that are effective in thickening tissues in order to optimize cosmetic outcomes aimed at facial volume formation. Was done.
Keywords: hyaluronic acid injection, bulging ability, skin model test, facial volume
Hyaluronic acid (HA) infusions are the gold standard in cosmetic medicine for treating signs of facial aging, such as infusion into wrinkled and depressed skin and facial volume formation . According to the American Society for Aesthetic Plastic Surgery (ASAPS), 2.49 million cases of HA infusion therapy were performed in the United States alone in 2016, a high increase of 16.1% compared to the previous year  2].
Juvéderm Voluma (Allergan, France), the first HA volume agent and still leading the global market in this area, was launched in 2010.
Since then, doctors have become more and more interested in HA injectables, which are highly effective in thickening the skin tissue .
The Juvé derm Voluma is manufactured with the patented technology VYCROSS . This technique enhances the action of chemical reactions by using a combination of high molecular weight and low molecular weight HA in the process of cross-linking.
In recent years, unprecedented exclusive manufacturing technology has been found for the production of innovative HA injectables. It is OXIFREE technology (Kylane Laboratoires, Geneva, Switzerland), which is characterized by the removal of harmful oxygen in production processes such as the cross-linking stage.
As a result, the inherent property of the HA chain, which has a large molecular weight, is considerably maintained. This new technology has created an HA injectable with advanced rheological properties that has a high uplift effect and is therefore capable of exhibiting high resilience to the volume of facial skin tissue.
Volume agents such as Juvéderm Voluma and HA injections that benefit from OXIFREE technology are designed to be injected into the subcutaneous tissue and the band above the periosteum. Such products are required to have a high bulging ability to efficiently treat each area of the face that requires volume formation, such as the cheek, cheekbone, chin tip, outer corner of the eye and the contour of the lower chin.
Since rheological properties have very important implications for the mechanical behavior of HA gels in tissues, these functions are of course taken into account in the design [5-7].
Many papers have been published on this subject in recent years, some highlighting the important role of normal force FN on tissue uplift of HA injectables [8-11]. This document proposes a new skin model assay for assessing the uplifting ability of HA injectables.
This assay will be applied to the market-leading Juvéderm Voluma in the area of volumetric agents and new HA injectables benefiting from OXIFREE technology to compare the uplifting effects of these products. The results obtained by the skin model assay will then be examined with particular attention to the key rheological features of these two products.
Two HA injectables for facial injection in aesthetic medicine were subjected to flow tests, vibration shear stress tests and compression tests using a DHR-1 rheometer (viscoelasticity measuring device) (TA Instruments, Newcastle, USA). ..
Of the two HA injectables shown in Table 1, one is manufactured with the new OXIFREE technology and the other is Juvéderm Voluma (Allergan, France) with the VYCROSS technology.
Table 1: Description of the HA Volumizer benefiting from Juvéderm Voluma and OXIFREE technology
|product name||Manufacturer||Manufacturing technology||HA concentration (mg / mL)||Clinical indication||comment|
|Gel D||Kylane Laboratoires (Geneva, Switzerland)||OXI FREE||twenty four||Injection into adipose tissue or intraepithelial zone, restoration of facial volume||The product with the highest raising ability among HA fillers that restores facial volume|
|Juvéderm Voluma||Allergan (Pringy, France)||VYCROSS||20||Injection into adipose tissue or intraepithelial zone, restoration of facial volume||/|
The two HA injectables were investigated in terms of rheological properties and also using a new skin model test.
In the flow test, the viscosity η of the gel can be measured. The implementation environment was a cone / flat aluminum geometry with a temperature of 25 ° C, a shear modulus of 0.001 to 1000 s-1, 40 mm and 2 degrees, and a gap between the rheometer cone and flat plate of 50-µm. The value of viscosity η is evaluated at a shear modulus of 1 s-1.
In the vibration shear stress test, the elastic modulus G'(G prime) can be measured. The implementation environment was a shear stress vibration mode with a temperature of 25 ° C and a strain of 1.0%, a linear viscoelastic region, a cone / flat plate aluminum geometry of 2 degrees at 40 mm, and a gap between the rheometer cone and flat plate of 50-µm.
The measurements were performed at frequencies in the range of 0.1-5 Hz. The modulus of elasticity G'was measured at the physiological vibration frequency of 1 Hz.
In the compression test in static mode, the normal force FN can be measured. The implementation environment was a cone / flat plate aluminum geometry of 2 degrees at a temperature of 25 ° C, normal force mode, and 40 mm. After placing 1.0 g of gel between the cone and the flat plate, the cone set in contact with the gel was placed in the direction of the bottom plate. I lowered it and pressed the gel. The normal force (FN) was measured at a gap of 1.11 mm (inverse gap = 0.9 mm-1) between the cone and the flat plate.
In the compression test in the dynamic mode, the elastic modulus E'(E prime) can be measured. The implementation environment was a compression vibration mode with a temperature of 25 ° C. and a strain of 1.0%, a linear viscoelastic region, a 40 mm flat plate / flat plate aluminum geometry, and a gap between parallel rheometer flat plates of 0.5-µm. The measurement was carried out at a frequency in the range of 0.1 to 5 Hz. The modulus of elasticity E'was measured at the physiological vibration frequency of 1 Hz.
All measurements were performed 3 times each. The data are expressed as mean ± standard deviation. A coefficient of variation of less than 10% was considered good. The results were statistically evaluated by Student's t-test with the significance level fixed at α = 0.05.
The skin model "Injection trainer" (Limbs & Things, Bristol, UK) used to assess uplift ability is a multi-layered structure consisting of epidermal, dermis, adipose and muscle tissues. This artificial skin model may also be used for training to practice injection into intradermal, subcutaneous and intramuscular tissues. You can also strip off the layers of skin.
To evaluate the uplifting ability of the two HA injectables, Juvéderm Voluma and OXIFREE product (Gel D), the following protocol is applied and an artificial skin model such as the following is used.
-After stripping the upper layer of skin, pipette exactly 0.80 g of each HA gel onto the surface of the middle layer of skin.
-Cover the upper layer of skin with two HA gels.
Take a standard image from a distance of -30 cm (front view, camera used is Nikon D5000, lens is Nikon AF-S DX VR II 18-200 mm f / 3.5 --5.6 ED).
-Measure the height of the ridge created by each HA gel administration in millimeters [difference between the apex of the ellipse and the basal line (the basal line is the section connecting the two inflection points of the ellipse)].
One of the tests is performed with Juvéderm Voluma on the left side on the skin and Gel D on the right side, and the other side on the skin with Juvéderm Voluma on the right side and Gel D on the left side.
Each measurement was performed in 3 sets. The data (elevation height) are expressed as mean ± standard deviation.
A statistical test is used to compare the average of the six ridges of Juvéderm Voluma with the average of the six ridges of Gel D (OXIFREE technique).
In this bilateral study (comparing two means at a given value), the difference between the means (Juvéderm Voluma and Gel D) is compared to the D0 value. The D0 value is fixed as equivalent to zero so that the equivalence of the two average values can be verified.
In the novel HA injectable (Gel D) benefiting from Juvéderm Voluma and OXIFREE technology, important rheological properties are viscosity η, static compression FN, G prime in dynamic shear stress and E prime in dynamic compression. Was measured. The results are shown in Table 2.
Table 2: Key rheological characteristics of the two HA volumeizers
|product name||Viscosity η (Pa.s) at 1 second-1||Normal force FN of compression at 0.9mm-1 (cN)||Elastic modulus G'at shear stress at 1Hz (Pa)||Elastic modulus E'in compression at 1Hz (Pa)|
|Gel D||204 ± 12||71 ± 7||310 ± 4||85,765 ± 1701|
|Juvéderm Voluma||65 ± 1||15 ± 2||318 ± 3||59,000 ± 1440|
The height of the ridge measured by the skin model test is shown in Fig. 1, and the overall findings are summarized in Table 3.
Figure 1: Figure of ridge height measured by skin model assay
Step 1: Accumulation of tested HA gel Step 2: HA gel is covered with an upper skin layer Step 3: Measurement of ridge height induced by each HA gel
Table 3: Height of ridges of two HA volumeizers obtained in skin model assay
|product name||Height of ridge (mm)|
|Gel D||2.38 ± 0.07|
|Juvéderm Voluma||1.77 ± 0.08|
Statistical comparison of the mean values of each of the six uplift heights of Juvéderm Voluma and Gel D (OXIFREE technology) revealed a statistical difference between the two mean values (Juvéderm Voluma and Gel D). Be done.
The new OXIFREE product, Gel D, shows a 34% higher elevation than the Juvéderm Voluma.
In this article, a new skin model assay was presented and applied to two HA volume agents, including the market-leading Juvéderm Voluma, with reproducible uplift and significant differences between the two products tested. Is recognized.
Therefore, this new assay can be said to be effective and reliable for assessing the ability of HA injectables to thicken and form volume.
The height of the ridge measured by this test method can be considered to be the same as the ability of the gel under test to push up the skin tissue to make it thicker and restore the volume of the face.
Therefore, this assay method is very convenient for comparing the uplifting ability of HA injection agents, especially HA volume agents.
For the two HA volume agents examined in this document, the ridge height measured by the skin model assay is significantly and statistically higher in the new OXIFREE product than in the Juvéderm Voluma. The uplift capability obtained with OXI FREE products is thus higher than that of Juvéderm Voluma.
This finding is consistent and correlated with the rheological properties of the two HA volume agents tested. As mentioned in the previous literature on the important rheological features of HA injectables, the normal force FN of compression plays a key role in the uplifting capacity of HA injectables.
That is, the higher the FN, the higher the ability of HA products to raise skin tissue. In this regard, the normal force FN of compression could be called the projection force to emphasize the significance of its ability for tissue uplift and volume formation.
In the case of the product and Juvéderm Voluma, as shown in Fig. 2, the uplift force FN and uplift height of the OXIFREE product are considerably higher than those of Juvéderm Voluma. This explains the considerable height of the uplifting ability of OXIFREE products observed in the skin model test.
Therefore, skin model assay is a new and valid tool for the medical community to evaluate and compare the uplifting ability of HA injectables, which reinforces the rheological property FN and correlates with FN. ..
This measurement method allows physicians to select HA volume agents with maximum bulging capacity for the treatment of facial signs that require significant volume recovery in the cheeks, cheekbones, chin tips, corners of the eyes and lower chin contours. Will be.
This choice leads to optimized beauty outcomes and improved patient satisfaction.
This new skin model assay is not only capable of demonstrating the uplifting ability of HA injectables, but also has the convenience and speed of visually observing the uplifting ability of the product-attached model.
Figure 2: Rheological properties and ridge height of the two HA volumeizers
A: Graph of uplift force of two HA gels
B: Photograph of ridge height using two HA gels
C: Graph of ridge height of two HA gels
In conclusion, volume agents play an increasingly important role in minimally invasive cosmetological procedures and contribute significantly to the global growth of the HA infusion market.
HA volume agent is an important clinical effect for facial rejuvenation such as treatment of cheek, cheekbone, chin and lower jaw contours, and is a liquid agent gold for recovering facial volume loss, especially for correcting the central part of the face. It is clear that it is a standard.
Rheological property analysis has demonstrated to be very useful for physicians to guide in selecting and using the optimal product for the intended treatment, administration technique and infusion depth.
This document proposes a new skin model assay for assessing the uplifting ability of HA injectables. This skin model assay has proven reliable and reproducible using two HA volume agents, including the market-leading Juvéderm Voluma.
This makes it easier to recognize the ability of HA injectables to raise tissue and form volume. It is also possible to compare the level of ridge capacity of various volume forming HA products.
Therefore, this model is considered to be a new important tool for complementing the rheological properties of the uplifting force FN and evaluating the uplifting ability of HA injectables.
Further insights from this new skin model assay will better elucidate the characteristics of HA injectables that will be selected and used by physicians seeking optimization of cosmetological outcomes as well as patient safety and satisfaction. It will be a boost for.
 Bui P, Pons Guiraud A, Lepage C. Benefits of volumetric to facial rejuvenation. Part 2: Dermal fillers. Ann Chir Plast Esthet 2017; 62: 550-9. (In French)
 American Society of Plastic Surgeons. 2016 Plastic Surgery Statistics Report. Avaiable from: https://www.plasticsurgery.org/news/ plastic-surgery-statistics? Sub = 2016 + Plastic + Surgery + Statistics [Last accessed on 26] Jun 2018]
 De Maio M, DeBoulle K, Braz A, Rohrich RJ; Alliance for the Future of Aesthetics Consensus Committee. Facial assessment and injection guide for botulinum toxin and injectable hyaluronic acid fillers: focus on the midface. Plast Reconstr Surg 2017; 140 : e540-50.
 Goodman GJ, Swift A, Remington BK. Current concepts in the use of Voluma, Volift and Volbella. Plast Reconstr Surg 2015; 136: S139-48.
 Sundaram H, Rohrich RJ, Liew S, Sattler G, Talarico S, Trévidic P, Molliard SG. Cohesivity of hyaluronic acid fillers: development and clinical implications of a novel assay, pilot validation with a five-point grading scale, and evaluation of six US Food and Drug Administration-approved fillers. Plast Reconstr Surg 2015; 136: 678-86.
 Tran C, Carraux P, Micheels P, Kaya G, Salomon D. In vivo bio-integration of three hyaluronic acid fillers in human skin: a histological study. Dermatology 2014; 228: 47-54.
 Sundaram H, Cassuto D. Biophysical characteristics of hyaluronic acid soft-tissue fillers and their relevance to aesthetic applications
 Billon R, Hersant B, Meningaud JP. Hyaluronic acid rheology: Basics and clinical applications in facial rejuvenation. Ann Chir Plast Esthet 2017; 62: 261-7. (In French)
 Gavard Molliard S, Albert S, Mondon K. Key importance of compression properties in the biophysical characteristics of hyaluronic acid soft-tissues fillers. J Mech Behav Biomed Mater 2016; 61: 290-8.
 Gavard Molliard S, Bon Bétemps J, Hadjab B, Topchian D, Micheels P, Salomon D. Key rheological properties of hyaluronic acid fillers: from tissue integration to product degradation. Plast Aesthet Res 2018; 5:17.
 Pierre S, Liew S, Bernardin A. Basics of dermal filler rheology. Dermatol Surg 2015; 41 Suppl 1: S120-6