A Novel Hybrid Injectable for Soft-tissue Augmentation: Analysis of Data and Practical Experience

Abstract

Background:

HA/CaHa (HArmonyCa, Allergan Aesthetics, an AbbVie Company) is a hybrid injectable filler developed for aesthetic purposes that contains calcium hydroxyapatite microspheres suspended in a hyaluronic acid gel. This review describes preclinical and clinical data, recommendations for use based on the primary author’s clinical experience, and case studies that illustrate implementation of product use recommendations and patient outcomes.

Methods:

Preclinical data on the lift capacity and tissue integration of the HA/CaHa hybrid injectable and clinical data on its safety, efficacy, and real-world use were extracted from poster presentations, published literature, manufacturer instructions for use, and proprietary data files. Case studies were presented based on clinical experience.

Results:

The HA component of HA/CaHa provides an immediate and noticeable filling and lifting effect, whereas CaHa microspheres result in neocollagenesis. In preclinical studies, HA/CaHa demonstrated higher lift capacity (P < 0.05) and faster tissue integration than a CaHa filler and led to collagen I gene and protein expression. Clinical studies showed clinical safety and effectiveness with high patient satisfaction. The most common adverse event was injection-site response. Clinician recommendations for achieving desired aesthetic results while minimizing or preventing adverse events are reviewed, including patient selection and assessment, treatment approaches based on face shape, injection technique, and postprocedure care.

Conclusion:

The novel hybrid injectable consisting of HA with incorporated CaHa microspheres in a single marketed product may help achieve aesthetic goals by immediately restoring volume and potentially improving skin architecture and soft-tissue quality over time.

Takeaways

Question: Is a single nonsurgical treatment available for patients whose aesthetic goals are improvements in facial volume, contour, skin architecture, and soft-tissue quality?

Findings: Preclinical and clinical data and patient case studies demonstrate the effectiveness and safety of a novel hybrid injectable—a formulated matrix of hyaluronic acid gel crosslinked with calcium hydroxyapatite—both in providing immediate volume and in increasing collagen production to help improve skin architecture and soft-tissue quality over time.

Meaning: A novel hybrid injectable matrix of components provides a treatment option for patients to achieve facial aesthetic goals concerning facial deflation and soft-tissue quality using a single product.

INTRODUCTION

Facial aging is a complex process affected by environmental, genetic, biologic, and cultural factors.^1–3 Changes in all layers of the face, including changes to fat compartments, loss of contour or volume, bony structure remodeling, and decreases in skin quality, contribute to an aged appearance; these changes and how they are perceived vary from person to person. Individuals pursuing rejuvenation treatments may desire facial volume restoration or lifting in addition to beautification.^4,5 Aesthetic approaches to treatment also aim to achieve attractive facial proportions.⁶ Achieving natural-looking results requires a tailored approach, with treatments chosen to address patient-specific concerns.

Numerous injectable fillers varying in composition, mechanism of action, host tissue interactions, and product characteristics are available for facial rejuvenation, with durations of effect ranging from months to years.^7–11 The most commonly used injectable fillers contain hyaluronic acid (HA), which provides immediate and sustained lift and volume that generally last 6 months to 2 years.^11,12 Biostimulatory fillers consisting of poly-L lactic acid, polycaprolactone, polymethylmethacrylate, or calcium hydroxyapatite (CaHa) act by stimulating new collagen in the skin for gradual and long-term (up to 1–4 y) restoration of volume loss without an immediate lift effect.^7,11,13–16

HA/CaHa (HArmonyCa; Allergan Aesthetics; an AbbVie company, Irvine, Calif.) is a hybrid injectable facial filler developed for aesthetic purposes that comprises a formulated matrix of HA gel crosslinked with CaHa microspheres to both provide immediate volume and lift and promote neocollagenesis for improved skin architecture and firmness.^17–19 Here, we provide an in-depth review of the HA/CaHa hybrid injectable, including supporting preclinical and clinical data, with cases to illustrate product use recommendations and optimal treatment outcomes.

Hybrid Injectable Description

HA/CaHa consists of 20-mg/mL crosslinked sodium hyaluronate gel with embedded synthetic CaHa microspheres (25–45 µm; 55.7% wt/wt concentration; Fig. 1) plus lidocaine hydrochloride (0.3% wt/vol) to reduce injection pain, provided in a prefilled sterile syringe.^17,20 The composite HA/CaHa gel has high elasticity, making it a suitable facial filler for providing improved facial structure and contour.^4,19 The matrix of HA and CaHa provides structural support for facial soft-tissue augmentation and also supports fibroblast proliferation.^{15,17,21–23} Neocollagenesis leads to tissue thickening and improved skin architecture, which increases skin firmness and soft-tissue quality and results in a sustained lifting effect over time.^15,22,23

Fig. 1.

HA/CaHa hybrid injectable filler consisting of crosslinked sodium hyaluronate gel with embedded synthetic calcium hydroxyapatite microspheres, as viewed on electron microscopy, showing a smooth consistency of the microspheres.

METHODS

The authors completed a literature review on the topic of the HA/CaHa hybrid injectable, including poster presentations, published medical literature, manufacturer directions for use, and proprietary data files. From these sources, the authors synthesized and summarized preclinical data and tissue integration characteristics of the HA/CaHa hybrid injectable as well as clinical data on its safety, efficacy, and real-world use. The authors then identified and described case studies from their clinical practice that demonstrated use of the HA/CaHa hybrid injectable to improve facial volume, contour, skin architecture, and soft-tissue quality.

RESULTS

Preclinical Data

As first presented at the 2022 Annual Aesthetic and Anti-Aging Medicine World Congress, a series of rodent experiments demonstrated statistically significantly higher sustained lift with subcutaneous injection of a 125-μL bolus of HA/CaHa filler compared with an equal volume of 55.7% wt/wt CaHa-based filler (Radiesse Volume Advantage; Merz North America, Franksville, Wis.) from weeks 2 to 12 after injection (P < 0.05 at weeks 2, 4, 8, and 12); HA/CaHa was also associated with statistically significantly higher lift at weeks 1, 2, 4, 8, and 12 compared with 30% vol/vol polycaprolactone-based filler (Ellansé M; Sinclair Pharma, London, United Kingdom).²⁰ The CaHa and polycaprolactone fillers exhibited similar lift profiles (Fig. 2A).²⁰ Histologic analysis demonstrated deeper and more rapid tissue integration of HA/CaHa compared with CaHa and polycaprolactone from weeks 1 to 8, at which point tissue integration was comparable across products (Fig. 2B).²⁰ Collagen I gene expression and protein production were observed with all three soft-tissue fillers at 1 and 8 weeks after injection.²⁰ Organized collagen I fibers were detected at 8 weeks with all three products (Fig. 2C).²⁰ These preclinical study results may not necessarily extrapolate to clinical effects.

Fig. 2.

Preclinical study results. A, Lift capacity and (B) tissue integration of facial fillers and (C) collagen deposition (collagen I fibers) in a preclinical model of HA/CaHa, a CaHa filler, and a polycaprolactone filler.²⁰ *P < 0.05 vs polycaprolactone. **P < 0.05 vs CaHa and polycaprolactone. Panels B and C are copyright Allergan Aesthetics. Collagen I fibers (second-harmonic generation imaging) were observed at 8 weeks in all products.

Clinical Data

A retrospective study evaluated the safety and performance of HA/CaHa in 162 participants [mean age, 52.4 (SD 9.6) y; women, 94%] treated at nine medical centers (data on file, Allergan Aesthetics, an AbbVie Company). With a median injected volume of 2.5 mL per participant (n = 116), HA/CaHa was effective in improving the aesthetic appearance of many areas of the face, including the cheeks, nasolabial folds, marionette lines, and jawline. Participants used a five-point Likert scale (1 = strongly disagree, 5 = strongly agree) to report their level of agreement with statements indicating treatment satisfaction, and the overall range of mean scores (3.60–4.29) demonstrated high rates and sustained levels of satisfaction with HA/CaHa. Based on mean scores of ≥4, participants agreed or strongly agreed that they were satisfied with treatment, treatment was beneficial, and they would likely return for additional treatment and would recommend HA/CaHa treatment to others. The high patient satisfaction levels are consistent with those reported in published studies on HA as a monotherapy.²⁴ Among 48 participants with pretreatment and posttreatment photographs available (the performance cohort), by 5 months, more than 90% showed improvement in Global Aesthetic Improvement Scale scores and more than 85% of treated regions exhibited at least a one-point improvement on the Lemperle Rating Scale,²⁵ which grades facial wrinkles on a six-point scale from 0 (no wrinkles) to 5 (very deep wrinkle, redundant fold).

In a case series, HA/CaHa was used to improve chin projection and jawline contour.¹⁹ Reshaping of the jawline via injections into the prejowl region, the mandibular line, and the mandibular angle and ramus improved the facial contour by producing a lifting effect of the cheek and neck. In another review, HA/CaHa was recommended for facial rejuvenation as part of a technique (described under “Recommendations for Clinical Use”) that tailors treatment to a patient’s face shape.⁴

Safety

The most common adverse events include redness, swelling, pain, tenderness, and itching. Most are mild injection-site responses comparable with those seen in single-component HA and CaHa products.^17,26–28 Injection-site responses occurring with HA/CaHa typically resolve within 24–48 hours, and swelling typically resolves within 1 week.¹⁷

A retrospective study assessed the long-term safety of HA/CaHa in 104 participants [mean (SD) age, 52 (9.6) y; women, 97%] treated at least 18 months before evaluation.²⁹ The study included patients who, based on a retrospective chart review, had received subdermal or deep dermal injections of HA/CaHa to treat multiple facial areas, including cheeks, nasolabial folds, marionette lines, jaw line, and chin. Participants reported no adverse events overall in at least 18 months of follow-up. In a subset of 87 participants who underwent additional safety evaluations, no signs of skin irregularities (eg, nodules/lumps, erythema, hematoma, necrosis) were observed by visual examination or dermatoscopic photography. High-frequency ultrasonography, performed in 64 participants, found no evidence of treatment-related inflammation, granulomas, or other adverse events, and imaging detected filler only in recently injected (4–11 mo before imaging) subjects acting as controls and in three subjects who had received repeat injections within 18 months of evaluation (7–16 mo). HA/CaHa filler was not detected by ultrasonography in participants treated 18 months or more before evaluation. Because this study involved a retrospective chart review, variables such as incomplete and/or inaccurate recordkeeping, adverse event reporting, and patient follow-up may limit the interpretation of results.

DISCUSSION

Recommendations for Clinical Use

A comprehensive aesthetic approach to addressing signs of facial aging may necessitate use of different categories of products. Guiding principles and recommendations for use of the HA/CaHa hybrid injectable based on the clinical practice experience of the lead author are discussed here.

Whether HA/CaHa is used alone or as a component of multimodal treatment, good aesthetic results may be achieved while minimizing or preventing adverse events. Meeting this goal requires knowledge of facial anatomy as well as patient-, product-, and procedure-related factors such as careful patient assessment, selection, and preparation; appropriate amount of filler; correct technique; and optimal postprocedural care.^{4,17,19,30–34}

Patient Selection

HA/CaHa is designed to provide facial soft-tissue augmentation.¹⁷ Candidates for treatment with HA/CaHa may include patients with facial laxity, sagginess, and light-to-moderate loss of facial contour or volume.¹⁹ Patients with severe laxity, loss of contour, and volume deficiencies may require surgery, additional treatment modalities (eg, HA fillers, laser devices, microfocused ultrasonography, radiofrequency), or combined approaches to achieve optimal results.^19,35–37 Although treatment with HA/CaHa is not contraindicated in cases of severe laxity, aesthetic results may be limited as with other injectable procedures, and patients could require more treatments over time. HA/CaHa should not be injected into the lips, perioral region, periocular region, or glabella.¹⁷ Caution is recommended in areas or patients with thin skin, where the HA/CaHa hybrid injectable could be visible, and in more dynamic areas of the face that could be more prone to filler accumulation.¹⁹

Patient Assessment

Understanding of facial anatomy, including aspects that contribute to a beautiful face, and thorough facial assessment are essential to deliver effective, safe results.^19,36,38,39 The patient’s face should be assessed in an upright position, both at rest and in animation.^19,37 Photographs should be taken in frontal, lateral, and oblique positions to facilitate assessment. The authors consider tilting the face and the pinch test to be useful in identifying signs of laxity and sagginess during pretreatment and posttreatment evaluation with HA/CaHa. Clinical signs indicating facial laxity can include marked nasolabial or mentolabial folds, the presence of prejowls (jowling), “accordion lines,” and loss of contour in the lower third of the face.^6,40,41 The pinch test performed in the buccal or lateral area of the face can help demonstrate soft-tissue laxity based on the degree of distensibility of the skin, skin thickness, and detachment from deeper planes of tissue.^42,43 In addition, careful clinical examination includes palpation of bone prominences to assess facial structure and evaluation of the teeth to identify dental problems that may interfere with treatment results and should be addressed before treatment.¹⁹ Injections should be postponed if dental problems or procedures occurred within the previous 15 days.¹⁹

Patient assessment should consider not only baseline facial features but also the patient’s self-perceptions and concerns.^4,5,19,44 Discussing the patient’s preferences, goals, and expectations of treatment is a fundamental part of treatment planning.^4,45,46 Effective communication is necessary to establish the patient’s underlying motivations, differentiate between preferences and needs, and set realistic treatment expectations.³³ Obtaining signed informed consent before the injection procedure is recommended to help ensure that the patient has realistic expectations and understands the potential complication risks.^4,33

General Approach Based on Facial Shape

Identification of the patient’s basic face shape as a starting point can help define the priorities of the aesthetic approach and determine facial areas requiring treatment to achieve desired outcomes.^4,47 Braz and de Paula Eduardo⁴ have adopted classification of four face shape models: oval, heart, round, and angular.

Injections placed in the posterior part of the face can lift the entire face.^19,48,49 Accordingly, we recommend performing midface volume correction or restoration, if needed, before treatment of the lower face because this helps to reposition and pull the soft tissue upward, affecting the approach to subsequent treatment of the lower face.¹⁹ However, the lower third of the face should also be evaluated in patients desiring midface treatment to optimize facial proportions.¹⁹

As described by Braz and de Paula Eduardo,⁴ the “anatomy of beauty” face technique approaches aesthetic treatment with injectable fillers based on the strengths and weaknesses of different facial shapes (oval, heart, round, and angular). Treatment priorities may vary based on face shape, with the lower face being prioritized in the heart shape and the midface in the angular shape. Volume and placement of filler will depend on the severity of the attribute to be corrected and the facial shape/structure. This approach can be used with the hybrid injectable and is the basis of the injection pattern described in the next section.

Injection Considerations

The hybrid matrix of HA with CaHa results in a gel with a smooth consistency that is malleable and easy to inject.⁵⁰ The product package contains two prefilled syringes of 1.25 mL each.¹⁷ It is recommended that HA/CaHa be homogenously distributed in the area of treatment with small volumes to avoid overcorrection. In the clinical experience of the lead author, using a blunt cannula versus a needle is an option for treating larger areas while reducing the risk of vascular adverse events and minimizing bruising and swelling.^4,19,51 The product can be delivered using retrograde fanning, retrograde linear threading, and retrograde short linear threading (described as “brush strokes”).⁵² The primary author recommends that if using a cannula, it is important to stop the injection before removing the cannula from the entry point to avoid superficial injection of the product in the skin.¹⁷ When using the fanning technique, it is recommended to inject smaller amounts when approaching the entry point to avoid product accumulation in the treated area. A video example of HA/CaHa injection into the mandibular line is shown in the Video.⁵³ [See Video (online), which displays an injection of HA/CaHa into the mandibular line. Video case example of a 50-year-old woman treated for aesthetic concerns of facial contour loss, skin thinning, and skin laxity. Treatment received was 1.25 mL of HA/CaHa in each side of the face. Use of a cannula with HA/CaHa has been reported in the literature^4,19; it is not included in the instructions for use. Video courtesy of André Braz, MD.]

Video 1. displays an injection of HA/CaHa into the mandibular line. Video case example of a 50-year-old woman treated for aesthetic concerns of facial contour loss, skin thinning, and skin laxity. Treatment received was 1.25 mL of HA/CaHa in each side of the face. Use of a cannula with HA/CaHa has been reported in the literature; it is not included in the instructions for use. Video courtesy of André Braz, MD.

Download video file ^{(35.4MB, mp4)}

Knowledge of regional anatomy and proper injection technique is critical to provide safe and effective treatment.^{4,19,33,54,55} Certain areas of the face are at a higher risk of complications due to the vasculature and nerves that lie beneath the skin.^33,53 The authors do not recommend injections with a needle in the deep plane onto the bone of the temporal fossa (Table 1). Figure 3A identifies potential treatment areas for HA/CaHa, and Figure 3B identifies the subcutaneous plane for HA/CaHa injection along the mandible. Notably, skin/facial aging and prior surgery or dermal filler injections may potentially influence the vascular anatomy.⁵³ When treating the lower face, it is also important to respect the proper plane of injection in the subcutaneous compartment and avoid injecting filler into the parotid gland, which could result in infection and parotiditis.^19,56 See Table 1 for additional HA/CaHa injection guiding principles and recommendations.

Table 1.

Guiding Principles and Recommendations for Injection of HA/CaHa^4,17,19

HA/CaHa injection depth is into the superficial fat compartments. Depending on the anatomical area being treated with HA/CaHa, these compartments can be deep subcutaneous or supraperiosteal

HA/CaHa is intended for injection into subdermal layers and should not be injected into the epidermis or superficial dermis, the glabellar or periocular areas, the lips and perioral region, frontal areas, regions containing foreign bodies, or blood vessels/highly vascularized areas

Injection into areas with frequent movement (eg, lips, perioral/periorbital regions) may lead to product accumulation and an increased risk of nodules

The authors do not recommend use in the temporal region, where the thin skin could cause the product to be visible when injected in the subcutaneous plane

HA/CaHa should be injected in small volumes and distributed homogenously in the area of treatment. Boluses/large volumes are not recommended. Instead of a needle, consider use of a 22G cannula. Use of a blunt cannula is especially recommended when injecting into higher risk facial regions (eg, vascularized areas)

Aspirate for several seconds before injection to ensure that the needle tip is not in a blood vessel; if blood enters syringe, interrupt injection and withdraw needle from skin

Stop HA/CaHa before withdrawing the cannula from the skin to prevent leakage into superficial skin layers

If signs of local ischemia (eg, pain, blanching) appear, stop the injection immediately and take appropriate measures, including massaging the area (in the case of blanching); applying warm compresses; injecting hyaluronidase; and consideration of aspirin, topical nitroglycerin, and low-molecular weight heparins

Gently massage and mold the product in the treated area to ensure even distribution of filler and to mold the gel to the tissue contour

Following treatment with HA/CaHa, apply an ice pack or cold compress to the treated area for 24 h to reduce redness, swelling, and irritation

Fig. 3.

Treatment considerations when injecting HA/CaHa. A, Illustration showing the potential treatment areas for HA/CaHa using the C-Plus Approach. B, Anatomical presentation of the subcutaneous plane for HA/CaHa deposition along the mandible line and mandibular ramus. Image courtesy of Andre Braz, MD.

Patient Cases

Case 1

A 56-year-old woman presented with concerns of facial contour loss and skin thinning and laxity. The pretreatment assessment showed overall good facial structure and signs of facial laxity, including marked nasolabial folds and mild jowls (Fig. 4). The patient was treated with HA/CaHa in the zygomatic arch, mandibular ramus/preparotid area, and mandibular line to improve facial contours and soft-tissue firmness. HA/CaHa was injected at the depth of the subcutaneous plane (superficial fat compartments) using a 22G blunt cannula. The filler product was distributed evenly with a fanning technique into the zygomatic arch and the mandibular ramus/preparotid area and via linear retrograde injection into the mandibular line. Immediately postinjection, the filler product was gently molded in treated areas. The total volume used was 2.5 mL (two HA/CaHa syringes; Table 2). The patient also received botulinum toxin treatment in the upper third of the face and mentalis muscle.

Fig. 4.

HA/CaHa treatment of a 53-year-old woman concerned with facial contour loss, skin thinning, and skin laxity. Treatment received: 2.5 mL of HA/CaHa; 1.25 mL per side of face. Individual results may vary. Images courtesy of Andre Braz, MD.

Table 2.

Case 1: HA/CaHa Injection Volumes

Treatment Area	Treatment Volume, mL
Zygomatic arch	0.5 (left + right: 0.25 mL each side)
Mandible ramus	1.0 (left + right: 0.5 mL each side)
Mandible body	1.0 (left + right: 0.5 mL each side)
Total volume	2.5 (left + right: 1.25 mL each side)

Satisfactory results were apparent immediately after treatment (Fig. 4), with visible improvement in the nasolabial folds and marionette lines, a more-defined mandibular line, and less-marked accordion lines when smiling. Effects were sustained at a 3-month follow-up visit.

Case 2

A 50-year-old woman presented with concerns of facial contour loss and skin thinning and laxity. In the pretreatment assessment, she exhibited very good facial structure and a heart-shaped face with prominent zygomas, presenting signs of facial laxity including buccal lines, accordion lines, and mild jowls (Figs. 5, 6). Skin laxity was also assessed by the pinch test. She was treated with HA/CaHa in the submalar and infrazygomatic regions, mandibular ramus/preparotid area, and mandibular line to improve lower face contour and soft-tissue firmness and reduce accordion lines. HA/CaHa was injected in the submalar and infrazygomatic regions and the mandibular ramus/preparotid area in the subcutaneous plane using a 22G blunt cannula, with the product distributed evenly using a fanning technique. For the mandibular line, HA/CaHa was delivered via linear retrograde injection to a similar depth. The product was molded gently in the treated areas immediately postinjection. At the 1-month evaluation, the patient continued to show soft-tissue laxity and loss of volume in the infrazygomatic areas; therefore, she elected to receive a second treatment session. The total volume of HA/CaHa was 3.8 mL in the first session and 2.3 mL in the second session (total volume, 6.1 mL; Table 3).

Fig. 5.

HA/CaHa treatment of a 50-year-old woman with concerns about facial contour loss, skin thinning, and skin laxity. Patient is shown with her face at rest before treatment and 1 year after the second treatment session; improvements in the jawline are evident. Individual results may vary. Images courtesy of André Braz, MD.

Fig. 6.

HA/CaHa treatment of a 50-year-old woman with concerns about facial contour loss, skin thinning, and skin laxity. When the patient is smiling, improvements are seen in the accordion lines, jawline, and midface. Treatment received: 6.1 mL of HA/CaHa in two separate sessions; results shown from second session. Individual results may vary. Images courtesy of André Braz, MD.

Table 3.

Case 2: HA/CaHa Injection Volumes

Area	Session 1: IZL + IZM + Submalar + Lower Face (3.8 mL), mL	Session 2: 1 Mo after First Session (2.3 mL), mL
Submalar	0.4 (left + right: 0.2 mL each side)	0.3 (left + right: 0.15 mL each side)
IZM	0.4 (left + right: 0.2 mL each side)	0.2 (left + right: 0.1 mL each side)
IZL	0.4 (left + right: 0.2 mL each side)	0.2 (left + right: 0.1 mL each side)
Jawline	1.3 (left + right: 0.65 mL each side)	0.8 (left + right: 0.4 mL each side)
Jaw ramus	1.3 (left + right: 0.65 mL each side)	0.8 (left + right: 0.4 mL each side)

IZL, infrazygoma lateral; IZM, infrazygoma medial.

Results were satisfactory at 1 month after the second treatment session (Figs. 5, 6), with visible improvement in the accordion lines and better jawline definition. Improvement was sustained for at least 1 year.

CONCLUSIONS

HA/CaHa, a novel hybrid injectable containing CaHa microspheres suspended in an HA gel, is designed to immediately restore volume and increase collagen production to improve skin architecture and soft-tissue quality over time, for an enduring effect in individuals with signs of facial aging. Preclinical data support the neocollagenesis effect of the hybrid injectable, and initial results from clinical studies support its long-term safety and suggest that treatment can result in positive outcomes and high levels of patient satisfaction. HA/CaHa offers a hybrid injectable matrix of components in a single product that can be used either alone or as part of a multimodal approach to achieve aesthetic goals.

DISCLOSURES

Dr. Braz is a speaker, advisor and investigator for Allergan Aesthetics, an AbbVie Company. Drs. Cazerta de Paula Eduardo, Pierce, Grond, Kutikov, and Nakab are full-time employees of AbbVie. Allergan Aesthetics, an AbbVie Company, funded this work and participated in the design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided to the authors by Adrienne Drinkwater, PhD, and Regina Kelly, MA, of Peloton Advantage LLC, an OPEN Health Company, Parsippany, NJ, and funded by Allergan Aesthetics, an AbbVie company.