Filler Dissolution Research Articles

In Vitro Analysis of Dissolution of 18 HA-based Dermal Fillers with Tailored Hyaluronidase Dosing to Achieve Urgent Reversal of Vascular Complications

Introduction: Hyaluronidase (HYAL), a hyaluronic acid-degrading enzyme, is commonly used “off-label” as part of the gold standard management of hyaluronic acid (HA) dermal filler complications. It is paramount that injectors be cognizant to diagnose and treat filler complications, particularly vascular emboli, where there may be a narrow window for timely treatment. There is a paucity of studies, however, that provide HYAL dosage guidelines in the setting of acute vascular obstruction that are specific to each of the 18 reversible HA-based dermal fillers commercially available on the current US market. Differences in resistance to HYAL degradation is based on variation in cross-linking technique, concentration of HA, and cohesive properties that each filler may possess. This in vitro study investigates optimal dosage parameters of HYAL to achieve gross dissolution of every reversible HA-based filler commercially available to better improve outcomes after filler-induced vascular complications. Methods: Standardized in vitro analysis using 0.5-mL aliquots of all 18 commercially available HA-based fillers included all Restylane products (Lyft, Restylane-L, Silk, Refyne, Defyne, Kysse, Contour), Juvederm products (Volbella, Vollure, Voluma, Ultra XC, Ultra Plus XC), Revanesse products (Versa+, Lips+), Teoxane products (RHA 2, RHA 3, RHA 4), and Belotero. Hylenex, recombinant human HYAL, was used in 150 IU increments for total quantities of either 300, 450, 600, or 750 IU to achieve timed assessment of the gross dissolution of filler using photographic and videographic documentation. Inert dye was used to improve filler visibility against the HYAL. Mechanical integration of HYAL into the filler mimicked massage technique commonly implemented to incorporate HYAL into the perivascular soft tissue to help relieve a filler-induced vascular obstruction. Results: The cross-linking technology utilized by each HA-filler manufacturer played a significant role in the readiness of filler dissolution with HYAL. Fastest dissolution times ranged from 11 seconds to approximately 32 minutes, with a strong correlation with Restylane products dissolving the fastest, followed by Juvederm & Revanesse products. The slowest to achieve gross dissolution were Belotero and the RHA series. Discussion: All 18 HA-based fillers achieved complete gross dissolution within the first 32 minutes, however, due to differences in cross-linking technology and molecular properties, there was large variation in in vitro HYAL-induced degradation that can be extrapolated clinically to help reverse urgent vascular obstruction. This may also help beginner injectors strategically choose the HA-based dermal fillers that have the fastest degradation response to HYAL. Further in vivo studies are necessary to integrate these into clinical practice.

Personalization of Minimally-Invasive Aesthetic Procedures with the Use of Ultrasound Compared to Alternative Imaging Modalities

Ultrasonography is a well-tolerated procedure that aids in the targeted esthetic therapies of special cutaneous regions, as well as in the prevention (vascular mapping, identification of previous filler, and others) and management of potential complications (vascular occlusion, external vascular compression, product misplacement or migration, inflammatory reactions, and others). It has lately been promoted as the first-line imaging tool to address injectables. In this article, we aim to review the evolving role of ultrasonography in cosmetic filler procedures, from the fundamental ultrasound characterization of cosmetic fillers to the ultrasound-enhanced detection and management of cosmetic filler complications, including ultrasound’s role in hyaluronidase-guided injections for cosmetic filler dissolution. Furthermore, the paper explores the integral role played by ultrasound in enhancing the precision, efficacy, and safety of additional minimally invasive aesthetic techniques such as mesotherapy, radiofrequency, cryolipolysis, and polydioxanone procedures.

Delayed infectious reactions of dermal filler injections in the face: Causes and management

ObjectiveNowadays, dermal filler injections in the face, are widespread. However, late complications are rarely reported and misunderstood. Moreover, they could be potentially severe, particularly cellulitis which is life-threatening. Reactivation of the biofilm and the hypersensitivity reaction are the main etiopathogenic factors of such unpredictable infections and granuloma reactions. Through four cases of foreign-body cellulitis, this article aims to explain the causality of filler material, and trigger conditions while emphasizes the prompt and adequate solution. Material and methodsThis work is a retrospective study and chart review which was granted an exemption by the author's institutional review board (IRB). Four women ranging from 27 to 55 years old, presented with onset symptoms of cellulitis of the face and inflammatory swelling of the lip. The hyaluronic acid filler was injected a long date prior. Trigger conditions caused the hatching of such complications which were solved with medical treatment without any filler dissolution or removal. ResultsImprovement of the symptoms was remarkable within the three and fifth days of antibiotic therapy. There was no abscess formation or, recurrence for more than one-year follow-up. ConclusionThe screening for dermal filler deposits must be considered for any inflammatory reaction of the face. Their causality should be discussed as well as the infectious and/or immunologic etiology, ensuring prompt and adequate medical treatment. Thus abscess formation could then not happen, and the resolution of the inflammatory reaction will be obtained. The extraction of filler material or the use of hyaluronidase should not be mandatory and will be done on a case-by-case basis.

Infraorbital Hyaluronic Acid Filler: Common Aesthetic Side Effects With Treatment and Prevention Options.

BackgroundInfraorbital hollows can give a fatigued or aged appearance, which can be treated by volumizing the segmented transition from the tear trough to the cheek with hyaluronic acid filler. Due to thin skin and the complex anatomy of the infraorbital area, both short- and long-term side effects (SEs) from this treatment are very common. While some patients are clear surgical candidates vs filler candidates, in real-world practice, many, if not most, patients are on a continuum where either procedure is appropriate, and the treatment decision is individualized based on each person’s risk vs benefit profile.ObjectivesCommon aesthetic SEs from hyaluronic acid filler treatment in the infraorbital area will be reviewed, including their etiology, prevention, detection, and treatment.MethodsThe author’s experience from injecting the infraorbital areas of more than 800 patients in private clinical practice and observations from both short- and long-term follow-ups over 8 years is leveraged to provide detailed guidance.ResultsRecommendations on injection techniques, patient selection, and patient education are presented along with algorithms for the prevention and management of bruising, short- and long-term swelling, bumps, and blue discoloration (which is usually secondary to swelling from the filler rather than just the filler alone placed or migrating too superficially).ConclusionsFor nearly all patients, complete dissolution of filler with hyaluronidase is not required to address the issue, and the guidelines provided here will assist clinicians in the management of SEs to increase patient satisfaction with their treatment and aesthetic outcome.Level of Evidence: 5

Rehabilitation of the Dysmorphic Lower Eyelid From Hyaluronic Acid Filler: What to Do After a Good Periocular Treatment Goes Bad.

Chronic, long-lasting edema accompanied by the Tyndall effect as a delayed reaction to hyaluronic acid (HA) filler injection seems to occur exclusively in the eyelids. The authors sought to present a treatment algorithm for management of patients with chronic lower eyelid edema as a delayed complication of HA filler injection. Retrospective study including 61 patients with delayed-onset chronic periocular edema following uneventful HA filler injection in the lower eyelids or cheeks. All patients underwent hyaluronidase enzyme dissolution followed by secondary treatment. Three retreatment options were presented: (1) observation, (2) secondary treatment with HA filler, and (3) lower eyelid blepharoplasty. All patients underwent filler dissolution using hyaluronidase. The mean age was 48 years and 97% of the patients were female. Single treatment was effective in 92% of patients with 8% requiring another hyaluronidase injection to completely eradicate residual edema. Six patients (10%) were satisfied after hyaluronidase only and 6 patients (10%) underwent lower eyelid blepharoplasty. Secondary treatment with HA filler was performed in 48 patients (80%). All were satisfied with final results without further edema in the follow-up period. Delayed-onset chronic lower eyelid edema is a frequent HA-related complication and cause of concern when considering periocular HA treatment. Previous treatment has been limited to either hyaluronidase only or blepharoplasty as a secondary solution after hyaluronidase, with only a minority of patients satisfied. Hyaluronidase, shortly followed by HA filler retreatment, is a safe and effective solution.

Deep Orbital Sub-Q Hyaluronic Acid Filler Injection for Enophthalmic Sighted Eyes in Parry-Romberg Syndrome.

The authors present a consecutive series of deep orbital Sub-Q injections to treat enophthalmic sighted eyes in Parry-Romberg syndrome patients. Retrospective, interventional case series in 2 centers. Data were collected on patient demographics, Parry-Romberg syndrome onset age, previous orbital and eyelid surgeries, diplopia, ocular movement restriction before and after the injection, number of injections, interval between injections, indication for any top-up or dissolution of filler, and any other complications. In all cases, the hyaluronic acid gel used was Restylane Sub-Q + Lidocaine. A total of 8 injections on 3 patients with Parry-Romberg syndrome, and significant enophthalmos is reported. All injections were with deep orbital Sub-Q filler. All patients were females, aged 32, 24, and 52 years old while their symptoms started at 15, 16, and 30 years old, respectively. None had orbital surgery prior to the injection. Follow up period was 2, 7, and 5 years respectively. All presented a significant enophthalmos of 4 mm which reduced to 1 mm after the injection, and duration effect was 18, 24, and 20 months, respectively. We observed a significant improvement in enophthalmos, lagophthalmos, exposure keratopathy, and even ocular motility. Lagophthalmos improved from 1, 4, and 7 mm to 0, 1, and 2 mm post injection. Ocular motility improved with no onset of new limitation or diplopia. Lower eyelid retraction increased in 1 patient after orbital injection. No other complications occurred. Deep orbital Sub-Q hyaluronic injection for treatment of enophthalmos in Parry-Romberg syndrome is an useful option in sighted eyes.

VOLUMIZING HYALURONIC ACID FILLER AS TEMPORARY TISSUE EXPANDER IN LOWER EYELID CICATRICIAL ECTROPION

We describe the treatment of lower eyelid cicatricial ectropion in a 24 year old male using volumizing hyaluronic acid (HA) filler. One milliliter of Juvederm Voluma was injected directly under the skin in each lower eyelid to create a large bubble. The filler was dissolved with hyaluronidase (750 I.U. / side) 5 months later, achieving an excellent and stable functional and cosmetic result. There was a 2.4 mm improvement in MRD-2 with the filler in place which decreased to 1.72 mm at 6 months after filler dissolution with hyaluronidase. This resulted in complete resolution of the signs and symptoms of corneal exposure. To date, there have been reports of low density HA injection for the treatment of cicatricial ectropion in elderly patients as well as infants with lamellar ichthyosis. In these cases the HA was injected and left in place to dissolve itself. Our case is the first report of a HA with high G’ properties injected directly under the skin followed by complete dissolution with hyaluronidase once the tissue expansion took place.

The Kinetics of Reversible Hyaluronic Acid Filler Injection Treated With Hyaluronidase.

Hyaluronidase is an enzyme capable of dissolution of hyaluronic acid (HA). There is a lack of evidence-based research defining time- and concentration-dependent reversal of HA filler using hyaluronidase. To explore the efficacy of different concentrations of hyaluronidase in digesting commercially available HA-based reversible fillers-Belotero Balance (BEL), Juvederm Ultra XC (JUVXC), Juvederm Ultra Plus (JUVX+), Juvederm Voluma XC (JUVV), Restylane-L (RESL), Restylane Silk (RESS), and Perlane/Restylane Lyft (RESLYFT). This was a blinded randomized study involving 15 participants. Participants received HA filler injection into their back, followed by no secondary injection, or injection with normal saline, 20 or 40 units of hyaluronidase. Using a 5-point palpation scale, the degradation of HA filler was monitored over 14 days. In the authors' study, there is a significant decrease in HA filler degradation using 20 and 40 units of hyaluronidase compared with no secondary injection or normal saline. There is no significant difference in HA filler dissolution when comparing 20 to 40 units of hyaluronidase. Lower concentrations of hyaluronidase may be just as effective as higher concentrations to degrade HA filler in situations where the reversal of cutaneous augmentation with HA filler arises.

The roughness, microhardness, and surface analysis of nanocomposites after application of topical fluoride gels

Objectives Application of acidulated phosphate fluoride (APF) gels has long been considered to cause deterioration of composite surfaces. The aims of this study were to demonstrate that nanocomposite surfaces were not affected by some APF gels and to investigate the possible underlying mechanisms. Methods The elemental composition and viscosity of 3 acidulated phosphate fluoride (APF) agents (60 Second Taste Gel, Topex, and Zap) and 1 neutral fluoride agent (pH7 Gel) were analyzed. Subsequently, 320 specimens of 3 nanocomposites (Premisa, Filtek Z350, and Grandio) and a microhybrid composite (Estelite Sigma) with 80 specimens for each composite were randomly divided into 5 groups ( n = 16) and treated with 4 fluoride gels as well as distilled water which served as the control. Fluoride gels were applied on composite resin surfaces 4 times, 30 min each time. The roughness and microhardness were measured after treatments. Qualitative examination of the surface degradation of the composites was carried out with Fourier transforming infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Results Topex and Zap did not cause surface changes of composite resins, the possible reason being ascribed to the presence of magnesium aluminum silicate (MAS) clays. In contrast, 60 Second Taste Gel treatments caused significant roughness increase, microhardness decrease, more prominent filler dissolution, and IR spectral changes of Premisa, Filtek Z350, and Grandio. Estelite Sigma was less affected by the 4 fluoride gels. Significance The composite surfaces were not affected by Topex or Zap even after extended treatments. These two APF gels may be more suitable for clinical applications.

Corrosive effect of topical fluoride agents on surfaces of five composite resins

To evaluate the potential corrosive effect of topical fluoride agents used for professional treatments at dental prophylaxis on the polished surfaces of five composite resins. A total of 125 specimens were fabricated from micro hybrid composite, nano-combined composite, nanocomposite, compomer and ormocer in a phi 6 mm x 3 mm cavity with 25 specimens for each composite group. The flat surfaces of the specimens were smoothed and polished, then applied respectively with four topical fluoride agents and distilled water, and stored at 37 degrees C 100% relative humidity for 30 min. The changes in morphologic features of the surfaces were assessed by scanning electron microscopy (SEM). The disintegrated surface was further analysed under a confocal laser scanning microscope (CLSM). All fluorides showed reaction to all composites except nanocomposite. The aggressiveness of the fluorides arranged sequentially as F (Elmex fluid) > G (Elmex gelée) > D (Duraphat) > B (Bifluorid 12). The treated surfaces were generally rough. F and G caused the overall surface corrosion, whereas etching on the surface by D and B was sporadic confined. The destructive effects demonstrated a large number of craters on the surface somewhat like an atoll owing to filler dissolution. Crack formation resulted in destruction of the filler-matrix interface was observed. Ormocer was severely affected after F and G treatment. Instead of crater glass filler protruding from the bumpy surface indicated the excessively disintegrated matrix of ormocer. Topography under CLSM exhibited the roughening of the composite surface, roughness parameters for profile (Sa, Sz, Smax) increased when the surface was treated. Surface change in nanocomposite specimens was neither visually nor numerically discerned. Topical application of highly concentrated fluoride prophylactic agents leaded to surface degradation and porosity of composite, nanocomposite was, however, chemically resistant. Isolation of the composite surface should be considered in clinical application of topical fluoride.

Effect of Physicochemical Aging Conditions on the Composite-Composite Repair Bond Strength

This study evaluated the effect of different physicochemical aging methods and surface conditioning techniques on the repair bond strength of composite. It was hypothesized that the aging conditions would decrease the repair bond strength and surface conditioning methods would perform similarly for the repair of resin composites. Disk-shaped resin composite specimens (Clearfil Photo Bright, Kuraray) were randomly assigned to one of the three aging conditions (N=120, n = 12/per group): (1) immersion in deionized water (37 degrees C, 1 week), (2) immersion in citric acid (pH: 3.0, 1 week), (3) boiling in water (8 h), (4) thermocycling (5000 times, 5 degrees C to 55 degreesC), (5) immersion in water (37 degrees C, 2 months). After aging procedures, the specimens were subjected to one of the following surface conditioning methods: (1) chairside silica coating (30-microm SiOx) (CoJet, 3M ESPE) + silane (ESPE-Sil) (SC method), (2) silane (Clearfil SE Bond Primer and Clearfil Porcelain Bond Activator) + bonding agent (Clearfil SE Bond) (SB method). The fresh and aged composite surfaces were also examined using SEM (n=6, 1/group). Resin composite (Quadrant Anterior Shine) was bonded to the conditioned substrates using polyethylene molds and then light polymerized. Shear force was applied to the adhesive interface in a universal testing machine (1 mm/min). The failure types were categorized as: (A) cohesive in the substrate, (B) adhesive at the interface, or C) cohesive in the adherend. Bond strength values were statistically analyzed using two-way ANOVA and Tukey's test (alpha < 0.05). A significant influence of the conditioning method (p < 0.0001) and aging method was observed (p < 0.01) (two-way ANOVA, Tukey-Kramer). The SC method showed significantly higher bond values (7.8 +/- 1.2 to 11.6 +/- 5 MPa) than those of SB method (4.6 +/- 2.3 to 7.6 +/- 3.9 MPa) in all groups (p < 0.0001). While the SC method showed 96% cohesive (A type), the SB method demonstrated 92% adhesive failures (B type). SEM images showed distinct pattern of microcracks in the boiled specimens and filler dissolution with disorganized matrix resin in the other aged specimens. Aging the composite substrates through water storage for 2 months produced significantly lower bond strengths than those of water or acid storage for 1 week (p = 0.011). Chairside silica coating and silanization provided the highest bond strength values with almost exclusively cohesive failures on aged composites. Aging methods showed significant differences on the composite-composite repair strength.

Internal corrosion in dental composite wear.

The internal corrosion of dental resin composites is associated with water-sorption and leads to (1) interfacial debonding, (2) filler dissolution, (3) matrix cracking, and (4) subsurface damage. The last factor creates a condition for "corrosive-wear" in which the damaged layer is worn with ease exposing a new surface and perpetuating the cycle of corrosion and wear. Central to the simulation of in vivo corrosive-wear is the recreation of the subsurface damage layer. To produce this layer in water, artificial saliva, and in media of low pH is time-consuming, because the degradation process in these environments is extremely slow. In laboratory wear tests using aqueous environments, the contact time of resin composites with water is too short to cause significant internal degradation. Thus, data obtained from such tests represent abrasive and not corrosive-wear, and do not correlate well with in vivo wear data. In considering this limitation of the above media for accelerated wear tests, an alkaline medium has been used in this study to simulate corrosive-wear of eleven commercial composites. The procedure consists of exposing each material to 0.1 N NaOH at 60 degrees C for 2 weeks followed by abrasion in a tooth brushing machine. The medium choice is based on the rationale that in vivo degradation arises from reaction with the OH(-), and this reaction can be enhanced by raising the pH and the temperature of the medium. The warm NaOH solution satisfies both these conditions. Parameters examined to evaluate the resistance of each composite to corrosion and wear were (1) mass loss, (2) Si-loss, (3) degradation depth, and (4) wear depth, respectively. A highly significant correlation has been observed among various corrosion and wear parameters. SEM examination indicated degradation to be associated with interfacial separation, filler dissolution, matrix cracking, and subsurface damage. These features are characteristics of in vivo worn composite restorations. Time is of utmost importance in laboratory evaluation of restorative materials. The ability of NaOH to meet this expediency and to mimic the in vivo degradation process makes it a useful medium for corrosive-wear studies of dental composites.

Effect of topical fluoride agents on the morphologic characteristics and composition of resin composite restorative materials

Statement of problem. The high reactivity of fluoride agents used in topical fluoride treatments have raised important questions on their potential adverse effects on restorative materials. Purpose. The purpose of this study was to evaluate the effect of topical fluoride agents used for office or home treatments on the surface morphologic characteristics and composition of composite restoratives. Material and methods. The fluorides used were Act, Phosflur, Gel II, Prevident, Stop, Butler APF, Nupro, and Omni Gel & Rinse. The composites tested were Brilliant DI, Heliomolar Ro, Herculite XRV, and P-50. The pH of the fluorides was measured as received and after dilution with water at a 1:3 volume ratio. The composites were subjected to the fluoride treatments until the total number of applications simulated the equivalent of 4 years under treatment. The changes induced on the surface morphologic features and composition of the restoratives were assessed by multiple internal reflectance Fourier transform infrared spectroscopy, scanning electron microscopy, and x-ray microanalysis. Results. All fluorides showed an acidic pH that was not significantly changed after dilution, except Stop, which exhibited a significant pH reduction. All fluorides increased the amount of loosely bound water in the composite matrix. Butler APF gel was the most aggressive for Brilliant DI and Herculite XRV, leading to excessive surface degradation, porosity, destruction of the filler-matrix interface, filler dissolution, and debonding. A reduction in the extent of remaining C = C bonds was observed in Herculite XRV after Butler APF treatment; Phosflur, Gel II, and Prevident had a milder effect. Treatment of Brilliant Dl and Herculite XRV with Omni Gel & Rinse resulted in the formation of a stable precipitation layer rich in barium, phosphorus, tin, oxygen, and fluoride. P-50 was severely affected at the resin-matrix interface after Stop treatment, whereas Omni Gel & Rinse induced fewer surface changes. Heliomolar Ro was the least affected restorative regardless of the type of fluoride used. (J Prosthet Dent 1997;77:405-13.)