Hyaluronic Acid Filler Products Research Articles

"Cohesiveness of Hyaluronic Acid Fillers": Evaluation Using Multiple Cohesion Tests.

Background Hyaluronic acid fillers can be manufactured using various processes. They have multiple properties, including their concentration, degree of modification, and rheological data. Cohesion is one such property to evaluate gel integrity; however, there is no standardized method for calculating this parameter. This study aimed to evaluate different tests for calculating hyaluronic acid cohesion and discuss the importance of hyaluronic acid cohesion as a consideration when selecting fillers. Methods The cohesion levels of five different hyaluronic acid fillers with different rheological properties were evaluated and compared using the drop weight, compression, tack, and dispersion time tests. Results The cohesion tests yielded different results in the samples. Samples 2 and 4 showed approximately two times the number of droplets when compared with Sample 5 in drop weight test. Samples 1, 2, 3, and 4 were superior to Sample 5 in tack test. Samples 1, 2, and 3 showed cohesive appearances at 95 seconds in most cases in dispersion test. Rheological test results did not reflect the measures of cohesion. Conclusion Although there are no definite standardized tests to evaluate the cohesion of hyaluronic acid fillers, our proposed tests showed similar results for different hyaluronic acid filler products. Further studies are needed to evaluate the cohesion of hyaluronic acid fillers and determine the clinical use of this distinguishing characteristic for clinicians selecting the product of choice. Level of evidence statement: These data are Level IV evidence.

In Vitro Comparison Between Ovine and Human Recombinant Hyaluronidase on Hyaluronic Acid Fillers.

Introduction: Injectable hyaluronic acid (HA) fillers are commonly used to provide tissue augmentation and combat the effects of facial aging. Ovine and human recombinant formulations of the enzyme hyaluronidase (HAse) are used interchangeably; however, it is unknown if there exists a difference in their ability to degrade HA. Objective: To compare rates at which ovine and human recombinant forms of HAse degrade various HA fillers in vitro. Methods: Increasing amounts of either ovine or human recombinant HAse were added to fixed amounts of nine unique HA filler products. Degradation rates were then analyzed using a colorimetric method by measuring absorbance levels of degraded product. Results: Human recombinant HAse degraded more HA when compared with ovine HAse overall (p = 0.014, confidence interval [-0.015 to -0.0018]). Conclusions: Human recombinant HAse was found to be more effective on average in degrading HA fillers when compared with ovine HAse in vitro.

A Single-Center, Randomized, Double-Blind Clinical Trial to Compare the Efficacy and Safety of a New Monophasic Hyaluronic Acid Filler and Biphasic Filler in Correcting Nasolabial Fold.

Hyaluronic acid (HA) fillers have been widely used in humans since 1958 because of their biomedical safety. Restylane® was introduced in the1990s as a favorable temporary filler option for facial augmentation. Subsequently, many new HA filler products, including the Sardenyashape®, have been introduced, but comparative studies of these products are limited. Here, we compared tolerability (wrinkle severity rating scale, WSRS), pain (visual analog scale, VAS score), satisfaction (global esthetic improvement scale, GAIS), and safety of a new monophasic HA (MHA) filler (Sardenyashape®) containing lidocaine, used to correct nasolabial folds (NLFs), with those of biphasic HA (BHA) filler (Restylane LYFT®) containing lidocaine. We enrolled 96 participants with visible NLFs in this randomized, double-blind, single-center clinical study. Participants were injected with a new MHA filler in one NLF and a BHA filler and were reassessed for cosmetic changes at 8 and 24 weeks. Wrinkle severity was assessed using the 5-point WSRS. At week 24, the mean improvement in WSRS compared to baseline was 1.92 ± 0.75 and 2.24 ± 0.66 for MHA and BHA fillers, respectively, and corresponding average pain values using the VAS score 30min after the procedure were 0.04 ± 0.25 and 0.02 ± 0.15, respectively, showing no significant difference. Average GAIS values 8 weeks after the procedure with MHA and BHA fillers were 1.89 ± 0.77 and 1.40 ± 0.82, respectively (p < 0.001). Both fillers were well tolerated, with mild adverse reactions. The evaluation of the effect of Sardenyashape® with lidocaine on NLF in this study proved its effectiveness and safety for use in correcting NLF. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A comparison of the safety, efficacy, and longevity of two different hyaluronic acid fillers in filler rhinoplasty: A multicenter study.

Filler rhinoplasty is a popular procedure in Asia, and it is of great importance to understand the clinical efficacy and durability of the different filler products that serve this purpose. Here, we aimed to evaluate and compare the safety, efficacy, and longevity of two different hyaluronic acid (HA) fillers in improving the nasal profile in Asians. A multicenter comparative trial was performed for 48 weeks after a single injection of a popular monophasic monodensified, and a newly developed biphasic HA filler. Assessments including patient satisfaction and three-dimensional (3D) imaging analysis were performed before, immediately after, 2 weeks, 12 weeks, 24 weeks, and 48 weeks after filler rhinoplasty. Twenty-eight Korean women underwent structured rhinoplasty were divided into monophasic monodensified (n = 14) and biphasic (n = 14) groups. There were significant changes in the facial profile following filler rhinoplasty throughout the study period. Overall, an increase of 1.75 mm in nose height, increase of 3.66° in the nasofrontal angle and 2.77° in the nasolabial angle, and radix elevation of 1.24 mm was noted at week 48 which was statistically different from the baseline values (P < .05). Between the different filler types, statistical difference was only noted in radix elevation (per milliliter of filler material) immediately after filler injection. No serious adverse event occurred during treatment or follow-up. Nonsurgical rhinoplasty with the specific HA filler products led to significant changes in the facial profile which persisted for 48 weeks. Overall, the clinical efficacy and safety were comparable between the two filler types except for radix elevation which was more prominent with C-C immediately after filler injection. J-V was superior to C-C in maintaining the radix elevation long term.

Needle Manufacturing, Quality Control, and Optimization for Patient Comfort.

There is an increasing rise of cosmetic injectables. We sought to understand the manufacturing, quality control process, and needle selection of hypodermic needles for fillers. To understand the process of manufacturing and quality control of hypodermic needles and the relevance to an aesthetic clinician. We conducted a search of the internet and contacted medical device companies to understand the manufacturing process. We then collaborated with the Executive director of global pharmaceutical technology from Abbvie as well as the packaging and device engineer at Galderma and summarized our findings. Finally, we reviewed the literature and summarized existing recommendations on techniques to minimize pain related to injection. Hypodermic needles undergo an extensive manufacturing and regulatory process. Many considerations are taken into account in needle manufacturing as well as the selection process with commercially available hyaluronic acid filler products. Needle manufacturers are held to universal standards though the International Organization for Standardization (ISO). Filler companies perform their own testing to evaluate suitability of needles for their product including leakage force, penetration force, extrusion force, etc. Finally, parameters such as needle length, needle diameter, and wall thickness are considered for selection of needle/hub with individual filler viscosity. There is extensive consideration that goes into needle manufacturing, quality control, and optimization for hyaluronic acid filler. Understanding the technical process helps inform the clinician and guide patient care for maximum comfort. J Drugs Dermatol. 2021;20(1):44-48. doi:10.36849/JDD.5591.

A Multicenter, Randomized, Double-Blinded, Comparative Study of Two Hyaluronic Acid Filler Products for the Correction of Nasolabial Folds

A Multicenter, Randomized, Double-Blinded, Comparative Study of Two Hyaluronic Acid Filler Products for the Correction of Nasolabial Folds

Superficial Dermal Fillers with Hyaluronic Acid.

Minimally invasive aesthetic procedures with hyaluronic acid filler have increased drastically since their development in 1989. Patients' desires to avoid surgery and achieve rapid results with minimal recovery led to a transformation in facial plastic surgery, demanding that aesthetic surgeons become proficient in nonsurgical augmentation. Over the years, new hyaluronic acid filler products were developed with different intrinsic properties, allowing clinicians to better treat different deficiencies of the face, reduce postprocedural pain, and optimize outcomes. The purpose of this article is to review the current state of nonsurgical facial plastic surgery with the superficial dermal filler, hyaluronic acid.

Rheologic and Physicochemical Properties Used to Differentiate Injectable Hyaluronic Acid Filler Products.

Background:Injectable hyaluronic acid fillers are routinely used for correction of soft-tissue volume loss and facial rejuvenation. Product differentiation has primarily been based on the rheologic parameter known as elastic modulus (G′), although other physicochemical properties are being explored to characterize potential product performance. As clinical data regarding product performance are lacking, the practical experience of injectors provides a valuable bridge in the knowledge gap between product rheologic data and product use.Methods:Rheologic and physicochemical measurements (swelling factor and cohesion) were collected for 18 products. To observe the impact of G′ and hyaluronic acid concentration on swelling factor and cohesion, proportional relationships were evaluated. Contributing authors were queried regarding their G′-based selection of products when considering skin quality, degree of correction, injection depth, and anatomical location.Results:Relationships were observable between G′ and swelling factor and G′ and cohesion only when limited to products manufactured by the same crosslinking technology and the same concentration. No relationship between isolated hyaluronic acid concentration and swelling factor or cohesion was apparent. Although rheological parameters and the assumptions of ex vivo data translating to in vivo performance are oftentimes not completely aligned, in the clinical experience of the authors, in general, higher G′ products are better suited for thicker skin and deeper injection planes, whereas lower G′ products are better for more superficial planes, although exceptions to these trends are also made based on technical experience.Conclusions:While rheologic and physicochemical characteristics can vary widely between products and the methods and measurements of these parameters are often difficult to correlate, G′ represents a useful and consistent parameter for product differentiation. Understanding how to select products based on G′ is valuable knowledge for customizing injection plans and contributes to an optimal aesthetic outcome.

Filler frontier: what's new and heading West to the US market.

The amount of fillers approved by the United States Food and Drug Administration (FDA) for use in facial volume augmentation is diminutive in comparison to filler products employed worldwide. In the near future, several new hyaluronic acid filler products will be available to the United States market. Already approved fillers include Belotero Balance for fine lines, Juvéderm Voluma XC for midfacial volume loss replacement, and Restylane Silk for perioral lines and lip augmentation. Volbella, currently under FDA evaluation, will be used for fine-line correction and lip augmentation. The physiochemical properties, best practices, clinical uses, and side effects of these fillers are discussed. Additionally, evolving techniques such as the use of blunt-tipped microcannulas are explained.

Investigation of the degradation-retarding effect caused by the low swelling capacity of a novel hyaluronic Acid filler developed by solid-phase crosslinking technology.

BackgroundA variety of hyaluronic acid (HA) fillers demonstrate unique physical characteristics, which affect the quality of the HA filler products. The critical factors that affect the degradation of HA gels have not yet been determined.ObjectiveOur objective was to determine the characteristics of HA gels that affect their resistance to the degradation caused by radicals and enzymes.MethodsThree types of HA fillers for repairing deep wrinkles, Juvederm Ultra Plus (J-U), Restylane Perlane (Perlane), and Cleviel, were tested in this study. The resistance of these HA fillers to enzymatic degradation was measured by carbazole and displacement assays using hyaluronidase as the enzyme. The resistance of these fillers to radical degradation was measured by the displacement assay using H2O2.ResultsDifferent tests for evaluating the degradation resistance of HA gels can yield different results. The filler most susceptible to enzymatic degradation was J-U, followed by Perlane and Cleviel. The HA filler showing the highest degree of degradation caused by H2O2 treatment was Perlane, followed by J-U, and then Cleviel. Cleviel showed higher enzymatic and radical resistances than J-U and Perlane did. Furthermore, it exhibited the highest resistance to heat and the lowest swelling ratio among all the fillers that were examined.ConclusionThe main factor determining the degradation of HA particles is the gel swelling ratio, which is related to the particle structure of the gel. Our in vitro assays suggest that the decrease in the swelling ratio will lead to a retarding effect on the degradation of HA fillers.

Biophysical Characteristics of Hyaluronic Acid Soft-Tissue Fillers and Their Relevance to Aesthetic Applications

The purpose of this study was to present new rheologic data for hyaluronic acid filler products, correlate them with recent tissue integration studies, and provide a scientific rationale for selecting appropriate products for volume replacement within different tissue levels and anatomical zones. A brief overview of the methodology of filler rheology studies and data analysis is provided. Six U.S. Food and Drug Administration–approved, cross-linked, nonanimal-derived hyaluronic acid filler products and one hyaluronic acid product approved in Europe and elsewhere were studied: one cohesive polydensifiedmatrix hyaluronic acid (Belotero Balance, also known as Belotero Basic), two Hylacross hyaluronicacids (Juvéderm Ultra and Juvéderm Ultra Plus), one Vycross hyaluronic acid (Juvéderm Voluma), and three nonanimal stabilized hyaluronic acids (Perlane, Restylane and Restylane SubQ) [corrected].The elastic modulus, complex viscosity, and viscous modulus of each filler gel were quantified. Tan delta for each filler gel and also for calcium hydroxylapatite filler (Radiesse) was calculated at 0.7 Hz. Cohesive polydensified matrix hyaluronic acid (Belotero Balance) has the lowest elasticity and viscosity and the highest tan delta. This predicts its soft, flowing qualities and correlates with its homogeneous pattern of tissue integration after intradermal implantation. Nonanimal stabilized hyaluronic acid (Perlane and Restylane) has the highest elasticity and viscosity and low tan delta. This predicts its firm, less flowing qualities and correlates with a bolus-like pattern of tissue integration. Hylacross hyaluronic acid (Juvéderm) has intermediate elasticity, viscosity, and tan delta, correlating with its intermediate pattern of tissue integration. Rheologic evaluation reliably predicts tissue integration patterns and appropriate clinical applications of the studied fillers. Paradigms of layered filler placement can be designed to optimally address individual patient need.

The potpourri approach to hyaluronic acid filler injections

There is an ever-expanding range of hyaluronic acid fillers with varying physical characteristics available to cosmetic dermatologists. These fillers are commercially packaged in syringes of approximately 1 mL (range 0.5-2 mL) volume. Filler injectors are currently qualitatively and quantitatively restricted to fillers packaged in ready-to-go syringes. Patients often present for pan-facial rejuvenation requiring varying amounts of fillers as well as more than one type/subtype of filler for optimum correction. The potpourri approach allows access to a range of prepared hyaluronic acid filler subtypes that can be used on the same patient in the one session. The potpourri method centres on the use of multiple 31-gauge insulin syringes prepared with a range of different hyaluronic acid filler products that are ready for use. This increases flexibility with filler selection and has the potential to provide better filler-to-tissue match for patients.

Hyaluronic acid gel (Juvéderm) preparations in the treatment of facial wrinkles and folds.

Soft tissue augmentation with temporary dermal fillers is a continuously growing field, supported by the ongoing development and advances in technology and biocompatibility of the products marketed. The longer lasting, less immunogenic and thus more convenient hyaluronic acid (HA) fillers are encompassing by far the biggest share of the temporary dermal filler market. Since the approval of the first HA filler, Restylane, there are at least 10 HA fillers that have been approved by the FDA. Not all of the approved HA fillers are available on the market, and many more are coming. The Juvéderm product line (Allergan, Irvine, CA), consisting of Juvéderm Plus and Juvéderm Ultra Plus, was approved by the FDA in 2006. Juvéderm is a bacterium-derived nonanimal stabilized HA. Juvéderm Ultra and Ultra Plus are smooth, malleable gels with a homologous consistency that use a new technology called "Hylacross technology". They have a high concentration of cross-linked HAs, which accounts for its longevity. Juvéderm Ultra Plus is used for volumizing and correcting deeper folds, whereas Juvéderm Ultra is best for contouring and volumizing medium depth facial wrinkles and lip augmentation. Various studies have shown the superiority of the HA filler products compared with collagen fillers for duration, volume needed, and patient satisfaction. Restylane, Perlane, and Juvéderm are currently the most popular dermal fillers used in the United States.

Anatomic Location of Hyaluronic Acid Filler Material Injected into Nasolabial Fold: A Histologic Study

BACKGROUND Products instilled within or beneath the skin to improve its physical features are known as fillers. The position of the filler within the skin is one determinant of the end cosmetic result. OBJECTIVE The objective was to histologically determine the anatomic location of injected hyaluronic acid (HA) filler within nasolabial fold (NLF) skin. METHODS AND MATERIALS Sixteen patients (12 females, 4 males; median age, 59 years) undergoing Mohs micrographic surgery for basal cell carcinoma of the NLF area consented to injection of Burow's triangle or dog-ear redundant skin with HA gel (Juvederm), ex vivo, in vivo, or in vivo with delayed (1-4 weeks) removal. Sections of alcohol-fixed, paraffin-embedded tissue specimens were stained with hematoxylin and eosin and with Hale's colloidal iron for detection of acid mucins. Dermal thickness was measured and HA distribution assessed. RESULTS NLF dermal thickness was 1.37+/-0.27 mm (mean+/-SD), with a range of 1.04 to 1.86 mm. All 16 patients showed HA filler localized to the subcutis. In 9/16 tissue samples, some HA was present in the deep dermis, but filler was only observed in more superficial dermis in 1 patient. The thickness of injected filler was 2.11+/-0.63 mm, but filler was often transected at the specimen base. CONCLUSION The predominant localization of injected HA filler is within the subcutis. A relatively thin NLF dermal thickness, typically <1.50 mm, likely precludes accurate injection of filler into dermal collagen. The results suggest that dermal localization of HA filler products is not required for an excellent cosmetic result.

Anatomic Location of Hyaluronic Acid Filler Material Injected into Nasolabial Fold

BACKGROUND Products instilled within or beneath the skin to improve its physical features are known as fillers. The position of the filler within the skin is one determinant of the end cosmetic result. OBJECTIVE The objective was to histologically determine the anatomic location of injected hyaluronic acid (HA) filler within nasolabial fold (NLF) skin. METHODS AND MATERIALS Sixteen patients (12 females, 4 males; median age, 59 years) undergoing Mohs micrographic surgery for basal cell carcinoma of the NLF area consented to injection of Burow's triangle or dog-ear redundant skin with HA gel (Juvederm), ex vivo, in vivo, or in vivo with delayed (1–4 weeks) removal. Sections of alcohol-fixed, paraffin-embedded tissue specimens were stained with hematoxylin and eosin and with Hale's colloidal iron for detection of acid mucins. Dermal thickness was measured and HA distribution assessed. RESULTS NLF dermal thickness was 1.37±0.27 mm (mean±SD), with a range of 1.04 to 1.86 mm. All 16 patients showed HA filler localized to the subcutis. In 9/16 tissue samples, some HA was present in the deep dermis, but filler was only observed in more superficial dermis in 1 patient. The thickness of injected filler was 2.11±0.63 mm, but filler was often transected at the specimen base. CONCLUSION The predominant localization of injected HA filler is within the subcutis. A relatively thin NLF dermal thickness, typically <1.50 mm, likely precludes accurate injection of filler into dermal collagen. The results suggest that dermal localization of HA filler products is not required for an excellent cosmetic result.

Persistent delayed‐type hypersensitivity reaction to injectable non‐animal‐stabilized hyaluronic acid

Injectable hyaluronic acid is a glycosaminoglycan used for soft-tissue augmentation. A number of products that are not Food and Drug Administration (FDA) approved for use in the United States are used commonly in Europe. We report a case of persistent delayed-type hypersensitivity to injected non-animal-stabilized hyaluronic acid. The patient was initially injected in Europe with a non-FDA-approved filler but traveled to the United States for evaluation of this adverse reaction. A case of adverse reaction to non-animal-stabilized hyaluronic acid is described. An overview of selected hyaluronic acid filler products is provided. The patient developed persistent facial edema after injection of hyaluronic acid filler to the melolabial folds, glabella, lips, and perioral rhytids. Injectable hyaluronic acid can be associated with a variety of complications including immediate and delayed-type hypersensitivity reactions. Physicians should be familiar with products used in other countries, as patients may present for evaluation following adverse reaction to fillers obtained abroad or from American physicians using non-FDA-approved products.