Hyaluronic acid fillers with cohesive polydensified matrix for soft-tissue augmentation and rejuvenation: a literature review

Abstract

Background: Cohesive monophasic polydensified fillers show unique viscoelastic properties and variable density of hyaluronic acid, allowing for a homogeneous tissue integration and distribution of the material.

Objective: The aim of this paper was to review the clinical data regarding the performance, tolerability, and safety of the Belotero(®) fillers for soft-tissue augmentation and rejuvenation.

Methods: A literature search was performed up until May 31, 2015 to identify all relevant articles on Belotero(®) fillers (Basic/Balance, Hydro, Soft, Intense, Volume) and equivalent products (Esthélis(®), Mesolis(®), Fortélis(®), Modélis(®)).

Results: This comprehensive review included 26 papers. Findings from three randomized controlled trials showed a greater reduction in nasolabial fold severity with Belotero(®) Basic/Balance than with collagen (at 8, 12, 16, and 24 weeks, n=118) and Restylane(®) (at 4 weeks, n=40), and higher patient satisfaction with Belotero(®) Intense than with Perlane(®) (at 2 weeks, n=20). With Belotero(®) Basic/Balance, an improvement of at least 1 point on the severity scale can be expected in ~80% of patients 1-6 months after injection, with an effect still visible at 8-12 months. Positive findings were also reported with Belotero(®) Volume (no reduction in hyaluronic acid volume at 12 months, as demonstrated by magnetic resonance imaging), Soft (improvement in the esthetic outcomes when used in a sequential approach), and Hydro (improvement in skin appearance in all patients). The most common adverse effects were mild-to-moderate erythema, edema, and hematoma, most of which were temporary. There were no reports of Tyndall effect, nodules, granulomas, or tissue necrosis.

Conclusion: Clinical evidence indicates sustainable esthetic effects, good safety profile, and long-term tolerability of the Belotero(®) fillers, particularly Belotero(®) Basic/Balance and Intense.

Keywords: CPM®; dermal filler; facial lines; filling; nasolabial fold; wrinkle.

Figure 1

Two-dimensional surface profiles before (black lines) and 4 weeks after treatment (gray lines) with Belotero^® Basic and Restylane^®. Notes: Height (µm) on the vertical axis corresponds to wrinkle depth. It was calculated as the mean of 50 profile lines across the wrinkles of the target area, using the phase-shift rapid in vivo measurement of skin system. Adapted from Prager W, Steinkraus V. A prospective, rater-blind, randomized comparison of the effectiveness and tolerability of Belotero^® Basic versus Restylane^® for correction of nasolabial folds. Eur J Dermatol. 2010;20(6):748–752.

Figure 2

Change in nasolabial fold severity with Belotero^® Basic/Balance treatment, re-treatment, and optional touch-ups. Notes: In Prager et al’s study, fold severity was rated using the Merz Aesthetics Scales at baseline and at 1, 6, 9, and 12 months. In Narins et al’s study,, fold severity was rated using the Wrinkle Severity Rating Scale at baseline and at 24, 32, 48, 72, and 96 weeks. Baseline is before the injection. Data from Narins et al, Narins et al, and Prager et al. Abbreviation: t-u, touch-up allowed.

Figure 3

Esthetic effect of Belotero^® Soft. Notes: A 30-year-old female patient with congenital unilateral (left) upper eyelid hollowness received 0.2 mL of Belotero^® Soft in the suborbicularis fibroadipose tissue (pre-septal) layer using a blunt tip cannula to prevent bruising and intravascular injection. The product was spread as a thin layer to avoid swelling and lumps. Photo courtesy of AD Prasetyo.

Figure 4

Long-term change in nasolabial fold severity with Belotero^® Intense treatment based on the investigators’ rating on the Wrinkle Severity Rating Scale. Notes: The difference from baseline was statistically significant at each time point, in both studies (P<0.001). The mean trend shows the average scores when pooling data from the two studies. In Buntrock et al’s study, the ratings were performed by a blinded investigator at baseline (ie, before injection) and at 2, 24, and 48 weeks. In Pavicic’s study, the ratings were performed by an unblinded investigator at baseline, immediately post-injection, and then at 2 and 12 weeks. In both studies, touch-ups were not allowed. Data from Buntrock et al. Adapted from Pavicic T. Efficacy and tolerability of a new monophasic, double-crosslinked hyaluronic acid filler for correction of deep lines and wrinkles. J Drugs Dermatol. 2011;10(2):134–139. Abbreviation: WSRS, Wrinkle Severity Rating Scale.

Figure 5

Long-term change in facial volume loss (cheeks) with Belotero^® Volume treatment based on the investigators’ rating on the Facial Volume Loss Scale. Notes: The difference from baseline was tested by Micheels et al and was statistically significant at each time point (P<0.0001). The mean trend shows the average scores when pooling data from the two studies. In Micheels et al’s study, other facial areas than the cheeks were assessed. Only results for cheeks are presented here for comparison with Micheels et al. Assessments were performed at baseline, the day following the injection (ie, post-injection), and then at 1, 3, and 6 months. Touch-up at 1 month was performed in two out of 56 patients (3.6%). In Micheels et al’s study, assessments were performed at baseline, immediately post-injection, and then at 1, 3, 6, 9, and 12 months, with an optional follow-up at 18 months (n=11). Touch-up was performed in two out of 20 patients (10%, timing not provided). Baseline is before the injection. Reproduced from Micheels P, Ascher B, Beilin G, Elias B, Rummaneethorn P, Sattler G. Evaluation clinique de l’efficacité et l’innocuité d’un acide hyaluronique volumateur de technologie CPM^® pour le traitement de multiples zones du visage [Clinical evaluation of the efficacy and safety of a hyaluronic acid volumizer with CPM^® technology for the treatment of multiple facial areas]. Réal Thér Dermato-Vénérol. 2014;235(3):2–8. French. Micheels P, Vandeputte J, Kravtsov M. Treatment of age-related midface atrophy by injection of cohesive polydensified matrix hyaluronic acid volumizer. J Clin Aesthet Dermatol. 2015;8(3):28–34.46 Copyright ©2015 Matrix Medical Communications. All rights reserved. Abbreviations: FVLS, Facial Volume Loss Scale; t-u, touch-up allowed.