Facial Soft Tissue Augmentation With Bellafill: A Review of 4 Years of Clinical Experience in 212 Patients

Abstract

Introduction:

Bellafill (Suneva Medical Inc) is a semipermanent injectable soft tissue filler composed of smooth and uniform polymethylmetacrylate (PMMA) microspheres suspended in a bovine collagen gel. It is a third generation PMMA filler, with more uniform shapes and sizes of the PMMA microspheres, which has been purported to decrease the incidence of granuloma formation.

Methods:

We performed a retrospective review of our clinical experience from 2014 to 2017 with Bellafill as a soft tissue injectable filler in the following clinical scenarios: deep nasolabial folds, depressed facial acne scars, malar volume loss, temporal wasting, tear trough deformity, chin augmentation, angle of jaw augmentation, and lip augmentation. The primary outcome is the rate of adverse events, and the secondary outcome is subjective patient satisfaction.

Results:

From 2014 to 2017, 842 syringes of Bellafill were administered to 212 patients, for a total of 417 procedures. Of the 417 procedures, 96 (23.0%) were for acne scars, 82 (19.7%) malar volume restorations, 65 (15.6%) nasolabial fold augmentations, 45 (10.8%) chin augmentations, 42 (10.1%) tear trough volume restorations, 28 (6.7%) temple volume restorations, 25 (6.0%) rhinoplasty touch-ups for small areas of nasal depression, 22 (5.3%) lip augmentations, and 12 (2.9%) jaw angle augmentations were performed. A range of 1 to 12 syringes were injected into each patient, over 1 to 3 sessions; 6 cases of adverse events occurred (1.4%). There were 4 cases of solitary nodules in the injection site, 1 case of lower eyelid oedema which persisted for 3 months and 1 case of lower lip oedema which resolved within hours. Patient satisfaction rates ranged from 83.3% for angle of jaw augmentation to 99.0% for improvement of acne scars.

Conclusion:

Bellafill is a safe and effective option for a semipermanent soft tissue filler, with high patient satisfaction and a good safety profile.

Introduction

Injectable fillers have become increasingly popular for soft-tissue augmentation, with temporary fillers such as hyaluronic acid being the most widely used due to their excellent safety profile and low complication rates. The disadvantage of temporary fillers is the need for repeat injections every few months, with the attendant discomfort and financial cost. Permanent fillers last much longer but has a higher propensity to induce foreign body reactions leading to permanent lumpiness, granulomas, infections, and adverse scarring.¹ One of the oldest permanent injectable fillers, liquid silicone, is only Food and Drug Administration (FDA)-approved for ophthalmic use and not for soft-tissue augmentation, though the FDA Modernization Act of 1997 allows the flexibility of off-label use of FDA-approved products with certain restrictions.² Polymethylmetacrylate (PMMA) is a permanent injectable filler that is FDA-approved for soft tissue augmentation.³

Polymethylmetacrylate is a biocompatible polymer that has been used in bone cement and cranial plates for decades,² and more recently in medialization laryngoplasty,³ with an excellent safety profile. Polymethylmetacrylate had been used for soft-tissue augmentation previously as Arteplast and Artecoll⁴ (Suneva Medical Inc). Bellafill is the third generation PMMA from Suneva Medical Inc, developed to avert complications from previous PMMA products such as granuloma formation. It is FDA-approved for correction of nasolabial folds and acne scars. Bellafill comes as a gel in pre-filled 0.8 mL syringes. It is comprised of 20% PMMA microspheres (approximately 6 million microspheres) suspended in 80% bovine collagen gel and 0.3% lidocaine. The PMMA microspheres in Bellafill are produced in a process that generates round, smooth, and relatively uniform microspheres of 30 to 50 microns. Polymethylmetacrylate above 20 microns are protected from phagocytosis by macrophages, while the lack of irregular surfaces mitigates inflammatory foreign body reaction.^5-7 Aggregation of microspheres is prevented by fixation in a suspension of viscous collagen, allowing for even collagenesis around the microspheres.^5,8 Bellafill provides an immediate volumizing effect due to the bovine collagen which will be absorbed over a month. This is followed by permanent volumization through collagenesis induced by the PMMA microspheres. Histological analysis at 3 months reveals encapsulation of PMMA microspheres by collagen fibers and fibroblasts. At 10 years, PMMA microspheres were seen integrated within vascularized mature collagen fibers.⁵

We performed a retrospective review of our clinical experience with Bellafill as a soft tissue injectable implant in the following clinical scenarios: deep nasolabial folds, depressed facial acne scars, cheek volume restoration, temporal wasting, tear trough deformity, chin augmentation and lip augmentation.

Methods

A retrospective review on the Bellafill injections performed by the senior author (P.S.) from 2014 to 2017 was performed. The primary outcome measured was the complication rate and the secondary objective were subjective patient satisfaction feedback and objective findings noted by the senior author. Patients were asked if they were “satisfied” or “not satisfied” with the improvement of the treatment at the end of 2 years. Patients who sought treatment that lasted longer than temporary fillers for deep nasolabial folds, depressed facial acne scars, cheek volume restoration, temporal wasting, tear trough deformity, chin augmentation, and lip augmentation were offered treatment with Bellafill. Information on previous injectable filler use, medical history, and history of reaction to collagen products or bovine allergies were obtained from all patients prior to treatment.

Patients without a history of collagen use or bovine allergies were offered an optional intradermal skin test in accordance with the Bellafill Instructions For Use document. This was performed on the volar aspect of their arm. Patients were informed to inspect the test site daily and return if any adverse reaction occurs. An inspection was performed at 4 weeks to assess for evidence of allergic reaction. Eight patients in the study group elected to undergo bovine collagen allergy testing, with none testing positive. We do not perform Bellafill injections in patients with a history of collagen or bovine allergies. All risks of allergy were disclosed and the patient’s informed consent was obtained. All study patients met the following inclusion criteria: no history of injection with semipermanent or permanent filler before Bellafill treatment and not having received any adjunctive therapy except botulinum toxin injection. The following patients were excluded: patients with history of collagen allergy, collagen and vascular disorders, pregnant or lactating women, immunocompromized patients, and patients with history of hypertrophic or keloid scars.

Our technique of injection is similar to that which we have previously described.⁶ The Bellafill syringe was thawed before injection. Ice was applied to facial injection sites for numbing effect. For lip augmentation, Xylocaine 1% was injected sublabially for an infraorbital or mental nerve block. Injections were performed with the needle bevelled downward. Steady pressure was applied to the syringe during injection, placing small droplets in appropriate locations to achieve volumizing effect. The filler was injected in small tunnels in the deep dermis, or in a fanning configuration. Gentle massage was then performed to mould and smoothen the product. For treatment of depressed acne scars, a small amount of Belafill was injected into the depression, elevating the depression. Bellafill used in isolation or in conjunction with subcision or laser resurfacing for acne scars.

We follow patients up in the office at 1 month, 2 months, 4 months, 1 year, and 2 years after injection unless otherwise required. At 4 months, an assessment of whether further injection would be made. All patients were followed for a minimum of 2 years.

Results

From 2014 to 2017, 842 syringes of Bellafill were administered to 212 patients, for a total of 417 procedures. Of the 417 procedures, 96 (23.0%) were for acne scars, 82 (19.7%) malar volume restorations, 65 (15.6%) nasolabial fold augmentations, 45 (10.8%) chin augmentations, 42 (10.1%) tear trough volume restorations, 28 (6.7%) temple volume restorations, 25 (6.0%) rhinoplasty touch-ups for small areas of nasal depression, 22 (5.3%) lip augmentations, 12 (2.9%) jaw angle augmentations were performed. A range of 1 to 12 syringes were injected into each patient, over 1 to 3 sessions. Table 1 illustrate the sites of injection and percentage of patients satisfied with the improvement.

Table 1.

Sites of injection and patient satisfaction data.

Site of injection	No. of sites injected (n = 417)	Average No. of vials per site	Percentage of patients satisfied with improvement (%)
Acne scars	96 (23.0%)	2	99.0
Malar	82 (19.7%)	3	91.5
Nasolabial fold	65 (15.6%)	2	87.7
Chin	45 (10.8%)	1	93.3
Tear trough	42 (10.1%)	1	90.5
Temple	28 (6.7%)	2	85.7
Rhinoplasty touch-ups	25 (6.0%)	0.2	96.0
Lips	22 (5.3%)	1	90.9
Jaw angles	12 (2.9%)	2	83.3

Of the 417 procedures performed, 6 (1.4%) cases of adverse events occurred. There were 4 cases of solitary nodules in the injection site, which were palpable but not visible to both the patients and the senior author; 3 of the nodules developed in the nasolabial folds and 1 in a cheek acne scar. Intralesional triamcinolone acetate was injected serially over 2 years to these nodules with mild improvement in all 4 cases but compete resolution did not occur. Surgical removal of the palpable nodules was not requested by the patients and was not performed. There was 1 case of prolonged lower eyelid oedema that persisted for 3 months after injection into the malar region for cheek volume restoration. The oedema resolved after 3 months with daily periorbital massages by the patient. There was 1 case of significant lower lip edema that occurred immediately after lower lip injection. The patient was observed in the office and did not develop signs of oral or airway edema, signs of infection, or systemic symptoms. The edema improved over 4 hours and was discharged uneventfully. Complete resolution of the edema was noted when the patient was reviewed the following day.

Discussion

Injectable fillers are among the most common cosmetic procedures today. The majority of injectable fillers are temporary and lasts several months to a year, resulting in the need for recurrent injections with its attendant costs, discomfort, and risks of adverse events. Previous PMMA fillers have demonstrated good safety profiles and longer-lasting results. However, the problem of granuloma formation needs to be solved. Bellafill, being a third generation PMMA filler following Artefill and Artecol, was developed to avert the complication of granuloma formation, with 3 major improvements, namely (i) uniform microspheres sized above 20 microns, thereby preventing them from being phagocytosed by macrophages,^5-8 (ii) lack of irregular surfaces mitigates inflammatory foreign body reaction, (iii) clumping of microspheres is prevented by fixation in a suspension of viscous collagen, allowing for even collagenesis. A 5-year study on the safety of Bellafill in nasolabial fold augmentation showed a 1.7% incidence of granuloma formation.⁹ A recent histological study in human skin found that Bellafill stimulated the formation of collagen-3 and procollagen-1 when injected into human skin and postulated that the combination of neocollagenesis followed by microencapsulation of PMMA microspheres in the new tissue provides for long-lasting results.¹⁰

The viscosity and elasticity of Bellafill is very high compared to other fillers. Viscosity measures the ability of the filler to withstand a force that is applied to it and not spread into surrounding tissues. Elasticity measures the ability of a filler to push back against a force applied to it and provide lift. The high viscosity enables Bellafill to remain where it is injected and enables the suspension of PMMA microspheres to remain in situ. The high elasticity implies that a lower volume is required to provide lifting and support. The ability of Bellafill to lift and provide volume has been noted by the authors. In the senior author’s experience, this lifting and volumizing effect follows a temporal pattern that evolves over several months. It is immediate following injection due to the collagen component. Over the next few weeks, the volumizing effect decreases following the dissolution of the collagen component. Over the following 4 to 12 weeks, the volumizing effect increases as collagenesis continues. Counselling of patients on the anticipated temporal sequence of effects is advised.

In our practice, the commonest indications for injection were acne scars, followed by volumization of malar regions and effacement of nasolabial folds. While Bellafill was FDA-approved for acne scars and nasolabial folds, we found that its use in other facial areas on an off-label basis for soft tissue augmentation were efficacious, with a good safety profile. This is in line with our previous study, in which off-label use of Artecoll in other facial sites have demonstrated good patient satisfaction rates and good safety profile.¹¹ Other studies on PMMA fillers in malar augmentation infraorbital rhytids and for primary non-surgical rhinoplasty have been demonstrated efficacy and safety.^12-14 Dermal fillers such as hyaluronic acid fillers have commonly been used in off-label sites. Many fillers are FDA-approved for facial wrinkles and folds, but have been used off-label for soft tissue augmentation such as in the jaw lines, post-rhinoplasty, or post-rhytidectomy depressions. It is our hope that by reporting on the senior author (P.S.)’s experience on the use of Bellafill over the years, the current clinical applications of this product can be reflected.

The highest patient satisfaction rate was for acne scars (99.0%), followed by rhinoplasty touch ups (96.0%) and chin augmentation (93.3%). The lowest patient satisfaction rate was for angle of jaw augmentation (83.3%), temple volumization (85.7%), and effacement of nasolabial folds 87.7%. A recent article on microneedling followed by Bellafill injection demonstrated significant improvement over microneedling alone.¹⁵ As this product is more costly per unit volume compared to other temporary fillers, it is less recommended for areas that require larger quantities of the product such as for angle of jaw augmentation. Filling in these areas with a small amount of Bellafill may not produce a significant enough augmentation and may decrease patient satisfaction. Patient satisfaction is highest in areas in which a small localized volume of Bellafill is adequate to produce a significant improvement, such as effacement of acne scars and post-rhinoplasty touch ups.

Of the 4 cases with persistent solitary nodules, 3 developed in the nasolabial folds and 1 in a cheek acne scar. In these 4 cases, 3 occurred in first year of the introduction of Bellafill into our practice (2014) and 1 in the second year (2015). This may suggest a learning curve, in which complications occur in the early stages of adoption of a new product or technology, though it is difficult to determine the effect of this quantitatively due to the small numbers of complications. This is in line with previous studies suggesting that the experience of the injector in administering a new product is related to the possibility to the formation of nodule or ridges.¹⁶ There were no cases of granulomas in our series. Clinically, granulomas are visible or palpable nodules that involves a delayed inflammatory response such as erythema, warmth, pain, and discharge. Granulomas may require excision and histology characteristically demonstrates giant cell foreign body reaction and can be classified histologically as cystic, edematous, or sclerosing.¹⁷ It is worth noting that granulomas can occur in temporary fillers including hyaluronic acid as well.^18,19

Our experience in administering Bellafill informs us that injecting multiple small aliquots of the product is preferable to injecting a larger volume in one localized site, particularly for superficial injections. The nasolabial folds can be a difficult area to inject as it requires a larger amount of filler to efface, which can lead to larger aliquots of fillers being administered in one spot and thus may explain the higher incidence of nodules in this area in our study. This technique lowers the risk of forming palpable clumps and allows for a more even distribution of the filler. If a palpable clump is formed immediately after injection, massaging of the clump can aid in evening the product out, as with other fillers.

While our primary outcome (adverse events) was clear and objective, the secondary outcome (patient satisfaction) was subjective and can be better assessed using subjective questionnaires and objective rating scores. We will incorporate more comprehensive outcomes measures into our subsequent studies.

Conclusion

The ideal filler should be non-immunogenic, biocompatible, technically easy to admininster, long-lasting, affordable, and predictable in behaviour. The wide variety of fillers in the market is a testament that no ideal filler has been identified. The results of our study has demonstrated that Bellafill is a safe and viable option for a semipermanent soft tissue filler, combining high patient satisfaction and a good safety profile.