Comparison of Two Swiss-Designed Hyaluronic Acid Gels: Six-Month Clinical Follow-Up.

The aim of this paper is to compare 2 hyaluronic acid gel fillers from the same Swiss manufacturer and with the same indications: filling of line wrinkles and folds. The products differ by their cross-linking process. With very simple easy-to-reproduce tests, cohesivity and resistance to traction forces were examined. Also, both gels were injected under ultrasound control in the mid reticular dermis of three subjects. The papules were controlled under ultrasound and biopsies at D0 and D15. Results showed significant differences between the 2 gels in all the tests. The new gel, manufactured with a lower-crosslinking density, seems to benefit from better integration in the tissue of the mid reticular dermis and to have a more cohesive nature than its comparator from a previous crosslinking technology. Under clinical observation, the range of new products present excellent tissue integration properties.

J Drugs Dermatol. 2017;16(2):154-161.

Effect of Different Crosslinking Technologies on Hyaluronic Acid Behavior: A Visual and Microscopic Study of Seven Hyaluronic Acid Gels.

BACKGROUND: The mechanical, rheological, and pharmacological properties of hyaluronic acid (HA) gels differ by their proprietary crosslinking technologies.
OBJECTIVE: To examine the different properties of a range of HA gels using simple and easily reproducible laboratory tests to better understand their suitability for particular indications.
METHODS AND MATERIALS: Hyaluronic acid gels produced by one of 7 different crosslinking technologies were subjected to tests for cohesivity, resistance to stretch, and microscopic examination. These 7 gels were: non-animal stabilized HA (NASHA® [Restylane®]), 3D Matrix (Surgiderm® 24 XP), cohesive polydensified matrix (CPM® [Belotero® Balance]), interpenetrating network-like (IPN-like [Stylage® M]), Vycross® (Juvéderm Volbella®), optimal balance technology (OBT® [Emervel Classic]), and resilient HA (RHA® [Teosyal Global Action]).
RESULTS: Cohesivity varied for the 7 gels, with NASHA being the least cohesive and CPM the most cohesive. The remaining gels could be described as partially cohesive. The resistance to stretch test confirmed the cohesivity findings, with CPM having the greatest resistance. Light microscopy of the 7 gels revealed HA particles of varying size and distribution. CPM was the only gel to have no particles visible at a microscopic level.
CONCLUSION: Hyaluronic acid gels are produced with a range of different crosslinking technologies. Simple laboratory tests show how these can influence a gel's behavior, and can help physicians select the optimal product for a specific treatment indication.

Versions of this paper have been previously published in French and in Dutch in the Belgian journal Dermatologie Actualité. Micheels P, Sarazin D, Tran C, Salomon D. Un gel d'acide hyaluronique est-il semblable à son concurrent? Derm-Actu. 2015;14:38-43.

J Drugs Dermatol. 2016;15(5):600-606..

Quantifying Depth of Injection of Hyaluronic Acid in the Dermis: Data from Clinical, Laboratory, and Ultrasound Settings.

Although manufacturers' instructions for use of dermal fillers ordinarily direct injection in the superficial, mid or deep dermis, or, in some cases, the hypodermis (subcutis), the precise depth of injection may not always be for injectors. In this article, investigators report findings gathered from histopathology, ultrasound, "live" one on one training injections, as well as application of a mathematical formula for depth calculation of the various layers within the dermis. Areas of particular interest are the superficial reticular dermis and the mid dermis. Following the depth measurements detailed by Della Volpe et al in 2012, investigators compare and contrast their own depth findings of the various layers, arriving at the conclusion that the depth of the dermis is not as deep as had been previously assumed. The investigators also develop an argument for the appropriate angles of injection for placement of dermal filler into the various layers, demonstrating that the heretofore widely used angles of 30˚ and 45˚ are far more acute than required.

Superficial dermal injection of hyaluronic acid soft tissue fillers: comparative ultrasound study.

BACKGROUND: Superficial dermal injection of hyaluronic acids (HAs) has not been well studied. OBJECTIVES: To study HAs injected into the superficial dermis using ultrasound examination and measurements, to evaluate induration and pain, and to examine histology. MATERIALS AND METHODS: Three commercial HAs were injected into the superficial dermis (0.2 mL). The HAs used were a biphasic gel, a monophasic monodensified gel, and a monophasic polydensified gel. Ultrasound measurements and images were obtained, pain assessed, and biopsies performed at 7 days. RESULTS: Participants experienced pain from the HAs that did not contain lidocaine. After 8 days, the biphasic HA papules appeared erythematous, with two-thirds reporting the biphasic HA papules as tender. Ultrasound demonstrated superficial placement of HA gels in the upper dermis. The gels each exhibited unique characteristic patterns on ultrasound. Skin biopsies of the superficial dermal placement confirmed earlier patterns. Superficial placement of the biphasic product is associated with tenderness and an eosinophilic inflammatory infiltrate. CONCLUSION: Superficial placement of HAs is possible, as demonstrated by ultrasonography. Gels that do not have lidocaine within them are more painful. Injection of biphasic HA gels superficially in the dermis is associated with clinical erythema and tenderness and histology showing an eosinophilic infiltrate.

Comparative histology of intradermal implantation of mono and biphasic hyaluronic acid fillers.

BACKGROUND: Hyaluronic acid (HA) gels have been used as filler material in the aesthetic field. Although the native HA molecule is without specificity of species and organs, synthetic cross-linked gels have differences in chemical composition and three-dimensional structure. Different technologies are employed in cross-linking, and the products have varying rheological properties. OBJECTIVE: To determine whether the gels with differing chemical composition have differing histologic behavior when injected into human skin to determine if the histology changes after 14 days of implantation. MATERIALS AND METHODS: Human volunteers consented to having controlled placement of HA intradermally into forearm or buttock skin. The trials were conducted in a single clinic in association with the Hôpitaux Universitaires de Genève, Geneva, Switzerland. The biopsies were taken immediately after implantation of the product and at day 14. Standard paraffin sections were prepared and stained with hematoxylin and eosin and Alcian blue and examined by an independent pathologist. RESULTS: Results show that each type of HA has a predictable histologic behavior in the skin. Biphasic gel has demonstrated deposition in big pools, often deep in the reticular dermis. The pools compress the collagen fibers. The papillary dermis and superficial reticular dermis are free of HA. Monophasic monodensified gels show large pools of hyaluronans throughout all the thickness of the reticular dermis. This material breaks up the collagen fibers of most of the dermal plane. The papillary dermis is free of exogenous hyaluronans. Monophasic polydensified cohesive gel penetrates into the dermis in a diffuse, evenly distributed manner, except in the papillary dermis, which remains free of exogenous material. CONCLUSION: The different types of cross-linked HA have different behaviors in the dermis immediately after their injection. The patterns are consistent between patients and are predictable. These histologic patterns do not change when biopsies are examined at 2 weeks.

Hyaluronic acid gel based on CPM® technology with and without lidocaine: Is there a difference?

BACKGROUND: In 2011, a cohesive polydensified matrix (CPM® ) hyaluronic acid (HA) gel filler was approved by the USA Food and Drug Administration. In 2014, lidocaine was added to the gel during its manufacturing process. OBJECTIVES: To compare the behavior and rheological properties of a CPM® HA gel with and without lidocaine. METHODS: In our office, we performed simple tests to document the cohesiveness and resistance to traction force of both gels. In two different laboratories, the rheological properties of both gels were measured. We used comparative data of the gel without lidocaine collected from over 6 years. We also observed the gels' behavior when injected into the superficial and mid-reticular dermis, comparing their distribution using both ultrasonography and histology. RESULTS: Over more than 10 years, we observed no difference between both gels, even if clinically we felt a difference in the gels' viscosity upon injection. Their behaviors during injection were similar. Using more sophisticated tests measuring the gels' rheological properties with different techniques, namely sheer sweeps, a difference was, however, noted between the two gels. CONCLUSIONS: Adding lidocaine to CPM® HA gel renders it more viscous. Whether this means a difference in the clinical results, however, would require a comparative clinical study over an extended time period.

Two Crosslinking Technologies for Superficial Reticular Dermis Injection: A Comparative Ultrasound and Histologic Study.

Background: Few hyaluronic acid fillers have been developed for superficial injection. Objective: To compare the diffusion and integration properties of cohesive polydensified matrix and Vycross® technology hyaluronic acid fillers with lidocaine following injection into the superficial reticular dermis. Methods and materials: Two subjects received two injections each of cohesive polydensified matrix and Vycross® hyaluronic acid (0.2mL/site) in the superficial reticular dermis of the buttock under ultrasound control. Biopsies were obtained at Days 0, 15, and/or 90. Ultrasound and histologic analyses were performed, plus a series of simple rheological tests. Results: Day 0 ultrasound images showed cohesive polydensified matrix hyaluronic acid homogeneous with the surrounding dermis. Vycross® hyaluronic acid showed more heterogeneity and some leakage into the hypodermis. Day 15 and Day 90 images were similar to Day 0. Histologic examination of biopsy tissue showed cohesive polydensified matrix hyaluronic acid homogeneously distributed among collagen fibrils with no visible particles. Vycross® hyaluronic acid appeared as variable-sized pools with a particulate appearance. Neither gel was associated with an inflammatory reaction. Laboratory tests showed cohesive polydensified matrix hyaluronic acid to have greater cohesivity and resistance to traction forces than Vycross®. Conclusion: cohesive polydensified matrix gel with lidocaine is homogeneously distributed following injection in the superficial reticular dermis and may be particularly suited for aesthetic indications requiring superficial injection.

Ultrasound and Histologic Examination after Subcutaneous Injection of Two Volumizing Hyaluronic Acid Fillers: A Preliminary Study.

BACKGROUND: This study examined the influence of hyaluronic acid (HA) crosslinking technology on the ultrasound and histologic behavior of HA fillers designed for subcutaneous injection. METHODS: One subject received subcutaneous injections of 0.25 ml Cohesive Polydensified Matrix (CPM) and Vycross volumizing HA in tissue scheduled for abdominoplasty by bolus and retrograde fanning techniques. Ultrasound analyses were performed on days 0 and 8 and histologic analyses on days 0 and 21 after injection. A series of simple rheologic tests was also performed. RESULTS: Day 0 ultrasound images after bolus injection showed CPM and Vycross as hypoechogenic papules in the hypodermis. CPM appeared little changed after gentle massage, whereas Vycross appeared more hyperechogenic and diminished in size. Ultrasound images at day 8 were similar. On day 0, both gels appeared less hypoechogenic after retrograde fanning than after bolus injection. Vycross was interspersed with hyperechogenic areas (fibrous septa from the fat network structure) and unlike CPM became almost completely invisible after gentle massage. On day 8, CPM appeared as a hypoechogenic pool and Vycross as a long, thin rod. Day 0 histologic findings confirmed ultrasound results. Day 21 CPM histologic findings showed a discrete inflammatory reaction along the injection row after retrograde fanning. Vycross had a more pronounced inflammatory reaction, particularly after retrograde fanning, with macrophages and giant cells surrounding the implant. Rheologic tests showed CPM to have greater cohesivity and resistance to traction forces than Vycross. CONCLUSIONS: CPM HA volumizer appears to maintain greater tissue integrity than Vycross after subcutaneous injection with less inflammatory activity.

A blanching technique for intradermal injection of the hyaluronic acid Belotero.

With the proliferation of dermal fillers in the aesthetic workplace have come instructions from various manufacturers regarding dermal placement. Determination of injection needle location in the dermis has in large part been based on physician expertise, product and needle familiarity, and patient-specific skin characteristics. An understanding of the precise depth of dermal structures may help practitioners improve injection specificity. Unlike other dermal fillers that suggest intradermal and deep dermal injection planes, a new hyaluronic acid with a cohesive polydensified matrix may be more appropriate for the superficial dermis because of its structure and its high degree of integration into the dermis. To that end, the authors designed a small study to quantify the depth of the superficial dermis by means of ultrasound and histology. Using ultrasound resources, the authors determined the depths of the epidermis, the dermis, and the reticular dermis in the buttocks of six patients; the authors then extrapolated the depth of the superficial reticular dermis. Histologic studies of two of the patients showed full integration of the product in the reticular dermis. Following determination of injection depths and filler integration, the authors describe a technique ("blanching") for injection of the cohesive polydensified matrix hyaluronic acid into the superficial dermis. At this time, blanching is appropriate only for injection of the cohesive polydensified matrix hyaluronic acid known as Belotero Balance in the United States, although it may have applications for other hyaluronic acid products outside of the United States.