Non-animal Stabilized Hyaluronic Acid Research Articles

Simplifying the injector's armamentarium: An international consensus regarding the use of gel science to differentiate hyaluronic acid fillers and guide treatment recommendations.

The Restylane portfolio of soft tissue fillers spans a wide range of indications, due in part to their complementary manufacturing technologies [non-animal stabilized hyaluronic acid (NASHA) and Optimal Balance Technology (OBT/XpresHAn)]. Using an array of products, injectors can achieve a holistic, natural looking effect for their patients. However, with a wide range of products it may be difficult to choose an optimal combination. Simplify and align global use recommendations for NASHA versus OBT products. Two pre-meeting surveys were completed by 11 key opinion leaders with international representation, with the goal of collecting information regarding their current injection practices for various anatomical regions of the face (i.e., temporal region, forehead, tear trough, lateral zygoma, anteromedial cheek, nose, pyriform aperture, nasolabial fold, perioral area, lips, labiomental crease, marionette lines, chin, and jawline). The data collected from these surveys was subsequently discussed in a consensus group meeting involving 11 voting members and 3 nonvoting members. Top product recommendations were identified for each anatomical area, along with secondary and tertiary recommendations that can also be used under defined circumstances. Recommendations were provided based on a consideration of elements such as patient features (e.g., skin thickness, bone structure), the desired aesthetic outcome, experience of the injector, and the preferred injection technique. A majority consensus regarding the top NASHA versus OBT product choice for each anatomical region of the face was reached. These recommendations represent international agreement regarding the use of Restylane products.

Evaluation of the Hydrophilic, Cohesive, and Physical Properties of Eight Hyaluronic Acid Fillers: Clinical Implications of Gel Differentiation.

Hyaluronic acid (HA) fillers are used to treat an array of aesthetic indications. Proper filler selection is paramount for successful patient outcomes. However, many important physiochemical and physical properties that impact HA gel behavior remain undefined. To evaluate the hydrophilicity, cohesivity and particle size of eight commercial HA fillers manufactured by either Non-Animal Stabilized Hyaluronic Acid (NASHA) or Optimal Balance Technology (OBT) techniques. Three individual in vitro experiments were performed to assess HA swelling capacity, cohesion, and particle size. Image analyses, blinded evaluation using the Gavard-Sundaram Cohesivity Scale, and laser diffraction technology were utilized, respectively. Compared to fillers manufactured with NASHA technology, OBT products demonstrated greater swelling capacity, cohesion, and wider particle size distributions. Strong positive correlations between swelling factor, degree of cohesivity, and increasing widths of the particle size distributions were observed. The hydrophilicity, cohesivity and particle size distributions vary among HA fillers manufactured with different techniques. The creation of new labels identifying products based on their unique combination of physiochemical and physical characteristics may help guide appropriate selection of HA fillers to optimize patient outcomes.

Non-Animal Stabilized Hyaluronic Acid (NASHA) Gel Marker vs. Surgical Clips for Tumor Bed Delineation in Breast Cancer Using MR-Simulation

Consistent delineation of the tumor bed (TB) after breast conserving surgery (BCS) is critical and remains a challenge with increasing prevalence of oncoplastic surgeries. Clips are generally used to help TB identification on CT-simulation but they are not well identified on MR-simulation. The aim of this study is to assess whether the use of NASHA gel with MR-simulation yields similar interobserver variability (inter-OV) compared to clips with CT-simulation. This prospective single arm feasibility study included patients eligible for BCS. After lumpectomy, the surgeon placed both clips (>5) and NASHA gel drops as markers to define the TB. Patients underwent CT and MRI simulation scans. Five radiation oncologists and one radiologist delineated the TB aided by clips on CT, and gel on MRI. The observers also assessed the visibility and utility of the gel (scale from 1 to 10), as well as the cavity visualization score (CVS, scale from 1 to 5). The primary endpoint was the inter-OV of the delineated TB using the overlap difference of contours using clips and CT versus gel and MRI, with the conformity index measured according to the pair definition of the Dice Similarity Coefficient (DSC). Of the 35 patients recruited, 30 were eligible for inter-OV analysis of TB delineation and 5 patients required further breast surgery for positive margins. One third of the eligible patients underwent an oncoplastic procedure. There were no significant differences between inter-OV of delineated TB using clips and CT versus gel and T2-weighted MRI with the mean DSC (0.60 vs 0.62, p = 0.364). The observers reported higher usefulness of gel in patients with an oncoplastic procedure than not (median US 8.2 vs 6.6, p = 0.024), and higher visibility of gel in patients who had their scans within 6 weeks than beyond post-op (median VS 8.1 vs 6.1, p = 0.013). When the CVS was higher (3-5), the median US of gel was lower (5.9 vs 7.8, p = 0.004), and the conformity index of clip and CT delineated TB was higher (median DSC 0.72 vs 0.53, p <0.001). Interestingly, a higher CVS did not lead to significantly higher conformity index of gel and T2-weighted MR delineated TB (mean DSC 0.67 vs 0.58, p = 0.073). NASHA gel injection added a median of 3 minutes to the operating theatre (OT) time and was rated as 'easy' in 89% of cases by surgeons. There were no immediate adverse events (AE) in OT, while 2 of 35 patients later experienced a grade 3 AE - hematoma which required evacuation in OT day 1 post-BCS, and infected seroma which required drainage and washout in OT 2 months post-BCS and axillary dissection. These reflect common risks with standard BCS and are not clearly attributed to gel injection alone. Use of NASHA gel leads to similar inter-OV of BC TB delineation compared to >5 clips. NASHA gel is hence a reliable alternative to clips when MR-simulation is used.

PP10 Presentation Time: 11:00 AM: Assessment of NASHA Spacer Symmetry for Prostate Radiation Therapy

<h3>Purpose</h3> NASHA (non-animal stabilized hyaluronic acid) is a spacer that can increase the separation between the prostate and anterior rectal wall prior to prostate radiation therapy (RT). Since there is no pre-defined time limit for NASHA spacer injection, physicians can precisely distribute the product within the peri-rectal space. Furthermore, the spacer is highly visible on T2-weighted MR, and generally visible on CT with optimized view settings. We conducted a randomized controlled trial evaluating whether a NASHA spacer improves rectal dosimetry among patients receiving hypofractionated RT (NCT 04189913). The purpose of the study is to evaluate the symmetry of a NASHA spacer among all patients who received the device on that study. <h3>Materials and Methods</h3> We analyzed data for 131 of 136 patients, who were randomized to and received a NASHA spacer on trial (5 datasets were unavailable at the time of analysis). All patients had pre-implant and post-implant CT/MR simulation. We developed an automated system for evaluating symmetry based on a previously published method (Fischer-Valuck, PRO, 2017). Briefly, prostate, rectum and spacer contours that had been prospectively validated by a core laboratory were downloaded. From the prostate center-of-mass, we defined axial slices at mid-gland, 1-cm superior, and 1-cm inferior. For each axial slice, we calculated the center of the spacer (spacer width center) along the transverse axis. Axial slice symmetry scores were assigned based on the distance between the spacer width center and the prostate midline (1 = distance within 1 cm of midline (symmetric), 2L/2R = distance between 1-2 cm from midline, 3L/3R = distance more than 2 cm from midline). Patient-level symmetry scores were assigned based on the number of slices with an asymmetric distribution (1 = none, 2 = 1 of 3 slices with axial score of 2L/2R, 3 = 2 of 3 slices with axial score of 2L/2R, 4 = all 3 slices with axial score of 2L/2R). <h3>Results</h3> The percentages of patients with an axial slice symmetry score of 1 (symmetric) at mid-gland, superior, and inferior planes, were 97%, 98%, and 98%, respectively (see Figure). Following the Fischer rubric, planes without gel were omitted (N=2 mid-gland, N=2 superior and N=9 inferior planes). The percentage of patients with patient-level symmetry scores of 1, 2, 3 and 4, were 95.4%, 2.3%, 1.5%, and 0.8% respectively. <h3>Conclusions</h3> Over 95% of NASHA spacers placed in this prospective trial demonstrated patient-level symmetry. These results suggest that NASHA may also improve rectal dosimetry for prostate brachytherapy. Further study is ongoing to correlate the dosimetry and clinical outcomes to implant quality for these patients.

Anti‑inflammatory and anti‑catabolic effect of non‑animal stabilized hyaluronic acid and mesenchymal stem cell‑conditioned medium in an osteoarthritis coculture model.

Previous clinical studies have reported the clinical effectiveness of non‑animal stabilized hyaluronic acid (NASHA) and adipose‑derived mesenchymal stromal/stem cells (MSC) in the treatment of knee osteoarthritis (OA). Unlike MSC secreted mediators, invitro anti‑inflammatory effects of NASHA have not been evaluated. We aimed to evaluate and compare the anti‑inflammatory effect of NASHA and MSC conditioned medium (stem cell‑conditioned medium; SC‑CM), in an explant‑based coculture model of OA. Cartilage and synovial membrane from seven patients undergoing total knee arthroplasty were used to create a coculture system. Recombinant IL‑1β was added to the cocultures to induce inflammation. Four experimental groups were generated: i)Basal; ii)IL‑1β; iii)NASHA (NASHA+IL‑1β); and iv)SC‑CM (SC‑CM+IL‑1β). Glycosaminoglycans (GAG) released in the culture medium and of nitric oxide (NO) production were quantified. Gene expression in cartilage and synovium of IL‑1β, matrix metallopeptidase13 (MMP13), ADAM metallopeptidase with thrombospondin type1 motif5 (ADAMTS5) and tissue inhibitor of metalloproteinases1 (TIMP1) was measured by reverse transcription‑quantitative PCR. Media GAG concentration was decreased in cocultures with NASHA and SC‑CM (48h, P<0.05; 72h, P<0.01) compared with IL‑1β. Production of NO was significantly lower only in SC‑CM after72h (P<0.01). In cartilage, SC‑CM inhibited the expression of IL‑1β, MMP13 and ADAMTS5, while NASHA had this effect only in MMP13 and ADAMTS5. In synovium, SC‑CM decreased the expression level of MMP13 and ADAMTS5, while NASHA only decreased ADAMTS5 expression. Both NASHA and SC‑CM increased TIMP1 expression in cartilage and synovium. Treatments with NASHA and SC‑CM were shown to be a therapeutic option that may help counteract the catabolism produced by the inflammatory state in knee OA. The anti‑inflammatory mediators produced by MSC promote a lower expression of inflammatory targets in our study model.

Changes in biomarkers in equine synovial fluid two weeks after intra-articular hyaluronan treatment: a randomised double-blind clinical trial

BackgroundInflammatory and degenerative activity inside the joint can be studied in vivo via analysis of synovial fluid (SF) biomarkers, which are molecular markers of inflammatory processes and tissue turnover. The aim of this study was to investigate the response of selected biomarkers in the SF after an intra-articular (IA) high-molecular-weight non-animal stabilized hyaluronic acid (NASHA) treatment. Our hypothesis was that prostaglandin E2 (PGE2), substance P, aggrecan chondroitin sulfate 846 epitope (CS846), and carboxypeptide of type II collagen (CPII) concentrations in SF would decrease more in the NASHA than in the placebo group. Twenty-eight clinically lame horses with positive responses to diagnostic IA anaesthesia of the metacarpophalangeal or metatarsophalangeal joints were randomized into treatment (n = 15) and control (n = 13) groups. After collection of baseline SF samples followed by IA diagnostic anaesthesia, horses in the treatment group received 3 ml of a NASHA product IA. Those in the placebo group received an equivalent volume of sterile 0.9% saline solution. The horses were re-evaluated and a second SF sample was obtained after a 2-week period.ResultsCS846 concentration decreased in the NASHA group only (P = 0.010). Both PGE2 and CPII concentrations decreased within the groups (PGE2, P = 0.010 for the NASHA group; P = 0.027 for the placebo group; CPII, P < 0.001 for NASHA group; P = 0.009 for placebo group). No significant treatment effect for any biomarker was found between groups. NASHA induced an increase in white blood cell count; this was significant compared with baseline (P = 0.021) and the placebo group (P = 0.045).ConclusionsAlthough the SF concentration of the cartilage-derived biomarker CS846 decreased in the NASHA group, no statistically significant treatment effect of any of the biomarkers were observed between treatment groups. The significant increase in SF white blood cell count after IA NASHA may indicate a mild inflammatory response. However, as no clinical adverse effects were observed, we conclude that IA NASHA was well tolerated.

Post-Maxillectomy Orbital Volume Augmentation Using Non- Animal Stabilized Hyaluronic Acid (NASHA) Injection: A Temporary Solution to Complex Reconstruction in Selected Cases

Post-Maxillectomy Orbital Volume Augmentation Using Non- Animal Stabilized Hyaluronic Acid (NASHA) Injection: A Temporary Solution to Complex Reconstruction in Selected Cases

A randomised, double-blinded, placebo-controlled clinical study on intra-articular hyaluronan treatment in equine lameness originating from the metacarpophalangeal joint.

BackgroundIntra-articular inflammation resulting in lameness is a common health problem in horses. Exogenous intra-articular hyaluronic acid has been shown to provide an analgesic effect and reduce pain in equine and human osteoarthritis. High molecular weight non-animal stabilized hyaluronic acid (NASHA) has gained popularity in the treatment of human arthritic conditions due to its long-acting pain-relieving effects. The aim of this study was to compare the response to treatment of lameness localized in the equine metacarpophalangeal joint injected with non-animal stabilized hyaluronic acid (NASHA) and placebo (saline). Twenty-seven clinically lame horses with a positive response to diagnostic intra-articular anaesthesia of the metacarpophalangeal joint and with no, or at most mild, radiographic changes in this joint were included in the study. Horses in the treatment group (n = 14) received 3 mL of a NASHA product intra-articularly, and those in the placebo group (n = 13) received an equivalent volume of sterile 0.9 % saline solution.ResultsThe change in the lameness score did not significantly differ between NASHA and placebo groups (P = 0.94). Scores in the flexion test improved more in the NASHA group compared with placebo (P = 0.01). The changes in effusion and pain in flexion were similar (P = 0.94 and P = 0.27, respectively) when NASHA and placebo groups were compared. A telephone interview follow-up of the owners three months post-treatment revealed that 14 of the 21 horses (67 %) were able to perform at their previous level of exercise.ConclusionsIn the present study, a single IA NASHA injection was not better than a single saline injection for reducing lameness in horses with synovitis or mild osteoarthritis. However, the results of this study indicate that IA NASHA may have some beneficial effects in modifying mild clinical signs but more research is needed to evaluate whether the positive effect documented ie. reduced response in the flexion test is a true treatment effect.

A randomized, prospective, blinded, split-face, single-center study comparing polycaprolactone to hyaluronic acid for treatment of nasolabial folds.

Dermal fillers have continuingly been under development to increase safety, efficacy, and longevity. Biostimulatory dermal fillers, such as calcium hydroxylapatite fillers, have already been shown to be superior in efficacy compared to nonanimal stabilized hyaluronic acid (NASHA)-based fillers. In this randomized split-face study, we compared a novel biostimulatory polycaprolactone (PCL)-based dermal filler with a NASHA-based dermal filler, for safety, efficacy, and duration of cosmetic correction for the treatment of nasolabial folds (NLFs). Forty subjects received a PCL-based dermal filler in one of their NLFs, and a NASHA-based dermal filler on the contralateral side. Efficacy was evaluated based on the Wrinkle Severity Rating Scale and Global Aesthetic Improvement Scale. After 6, 9, and 12months post-treatment, NLFs treated with the PCL-based dermal filler showed statistically significant improvements on the Wrinkle Severity Rating Scale and greater improvements on the GAIS compared to NLFs treated with the NASHA-based dermal filler. Both products were found to be equally safe and well tolerated. Our results suggest that PCL-based dermal fillers offer longer-lasting performance over NASHA-based dermal fillers in NLFs treatment.

Efficacy, Safety, and Patient Satisfaction of a Monophasic Cohesive Polydensified Matrix Versus a Biphasic Nonanimal Stabilized Hyaluronic Acid Filler After Single Injection in Nasolabial Folds

Intradermal injection of hyaluronic acid (HA) is currently the criterion standard to reduce the appearance of nasolabial folds (NLF). Effects of a monophasic HA filler using cohesive polydensified matrix (CPM) technology were compared with those of nonanimal stabilized HA (NASHA). In a double-blind, half-side comparison, 20 subjects (ages 35-65, mean 52±5.6) with symmetric NLF grade 3 to 4 were randomized to contralateral treatment with a monophasic polydensified filler (CPM) and a biphasic HA filler (NASHA). Efficacy was assessed at baseline and after 2, 24, and 48weeks using a wrinkle severity rating scale (WSRS) for NLF, subject questionnaire, and biophysical in vivo methods. All subjects showed significant improvements with both fillers up to day 365. Subject questionnaires confirmed significantly less injection pain for the CPMHA, significantly greater patient satisfaction after 2weeks with both fillers, and after 24 and 48weeks significantly greater improvement with the CPMHA compared to baseline. WSRS and skin surface topography parameters improved significantly up to 48weeks with both fillers. A single intradermal injection of a monophasic CPMHA and a biphasic NASHA filler showed significant improvements in WSRS and measured wrinkle depth up to 48weeks for both fillers and significant differences in injection comfort and patient satisfaction in favor of CPMHA.

Delayed Hypersensitivity Reaction to Restylane® SubQ

Purpose: To report on 4 patients who developed delayed hypersensitivity reactions to Restylane® SubQ and their management. To our knowledge, no cases of delayed hypersensitivity to Restylane® SubQ have been previously reported.Methods: A retrospective case series of 4 patients who were treated with preperiosteal Restylane® SubQ to their cheeks, for facial volume augmentation. All 4 patients were subsequently referred with delayed hypersensitivity reactions over a 4-month period.Results: The hypersensitivity reactions occurred from 1 week to 4 months’ post-cheek augmentation using Restylane® SubQ. All patients had previously (and some since) been treated with other non-animal stabilized hyaluronic acid (NASHA) products without adverse effect. Hyaluronidase led to fast and effective resolution in all cases, although 2 of the patients required repeat treatment.Conclusion: Hyaluronidase was effective at treating the inflammatory reaction and breaking up the retained Restylane® SubQ in all patients. Although Restylane® SubQ should be avoided in these patients, in our experience this does not preclude them from using other similar NASHA products.

Novel Hyaluronic Acid Dermal Filler: Dermal Gel Extra Physical Properties and Clinical Outcomes

Dermal gel extra (DGE) is a new, tightly cross-linked hyaluronic acid (HA)-based dermal filler containing lidocaine engineered to resist gel deformation and degradation. To develop a firmer gel product (DGE) and compare the efficacy and safety of DGE with nonanimal stabilized HA (NASHA) for correction of nasolabial folds (NLFs). DGE physical properties were characterized, and 140 subjects with moderate to deep NLFs were treated with DGE and NASHA in a randomized, multicenter, split-face design study. Efficacy, pain, and satisfaction were measured using appropriate standard instruments. Adverse events were monitored throughout the study. DGE has a higher modulus and a higher gel:fluid ratio than other HA fillers. Similar optimal correction was observed with DGE and NASHA through 36 weeks (9 months). Study subjects required less volume (p<.001) and fewer touch-ups (p=.005) and reported less injection pain (p<.001) with DGE treatment. Most adverse events were mild to moderate skin reactions. DGE is a firm HA gel that required significantly less volume and fewer touch-ups to provide equivalent efficacy to NASHA for NLF correction; both dermal gels were well tolerated. DGE will provide a comfortable and cost-effective dermal filler option for clinicians and patients.

12-Month Controlled Study in the United States of the Safety and Efficacy of a Permanent 2.5% Polyacrylamide Hydrogel Soft-Tissue Filler

To evaluate the safety and efficacy of a 2.5% polyacrylamide hydrogel in the aesthetic enhancement of nasolabial folds. The safety and efficacy of a polyacrylamide hydrogel were compared with those of nonanimal stabilized hyaluronic acid (NASHA) in 315 subjects in a double-blind, randomized, multicenter, noninferiority trial with a 12-month follow-up. The primary efficacy end point was mean change in Wrinkle Assessment Scale (WAS) scores at 6 months. The primary safety end point was rate of serious adverse events (AEs) through 12 months after treatment. Polyacrylamide hydrogel was as effective as NASHA, and effectiveness persisted throughout the 12-month follow-up. Treatment-related AEs occurred with equal incidence; most were mild to moderate, transient, and related to injection procedure. One serious AE (infection) was thought to be related to treatment with polyacrylamide hydrogel; it resolved within 5 days after appropriate treatment. This 2.5% polyacrylamide hydrogel offers promise as a long-lasting soft tissue filler. It is well tolerated, as effective as NASHA in correction of nasolabial folds, and persistent. Longer evaluation is required to evaluate longer-term safety and demonstrate duration of effect beyond 12 months. This

Orbitofacial Rejuvenation of Temple Hollowing With Perlane Injectable Filler

Temple hollowing with soft tissue volume loss is well recognized in HIV lipoatrophy. Similar changes occur as part of aging, with skeletalization of the orbital rim and clipping of the eyebrow tail. The authors report their initial experience treating temple volume loss and orbitofacial asymmetry with nonanimal stabilized hyaluronic acid (NASHA). This study was a retrospective, interventional case series with a patient satisfaction questionnaire and independent physician grading of results. Patients initially received approximately 1 mL of Perlane (Q-Med, Uppsala, Sweden; Medicis, Inc., Scottsdale, Arizona) injected into the superficial fascia of each temple. The filler was placed behind the frontozygomatic process to soften the bony contour of the lateral orbital rim. Outcome measures included satisfaction with injection procedure, fulfillment of expectations, satisfaction with appearance, change in self-confidence, the need for retreatment, and complications. Twenty patients were treated, for a total of 39 temples. Mean follow-up was nine months (range, four to 14 months). Patients were primarily female (90%), all were Caucasian, and their ages ranged from 20 to 60 years. Eighteen patients had age-related temple hollowing, one had dysthyroid volume loss, and one had hollowing due to orbitotemporal neurofibromatosis. The majority had 1-mL injections to each side (range, 0.3-3 mL). One patient received 3 mL to correct asymmetry. The procedure was well tolerated with ice pack cooling and no local anesthesia. Of 16 patients who replied to the questionnaire, 13 were very or moderately satisfied and requested repeat treatment, whereas three were only mildly satisfied or ambivalent. Side effects included transient mild or moderate discomfort, superficial vein prominence, and localized bruising. This series suggests the effective and safe application of Perlane in temple hollow rejuvenation and correction of asymmetry. It offers tolerability, high patient satisfaction, few complications, and the option of reversibility.

Brand-new Hydrobalance technology on the basis of stabilized hyaluronic acid for long-term skin hydration

The goal of this prospective clinical and instrumental study was to evaluate the efficacy and tolerability of Restylane Vital Light, a non-animal stabilized hyaluronic acid (NASHA), for rejuvenation of the periorbital and perioral facial and neck area in women aged 40-65. According to the study results, a triple injection of NASHA (Hydrobalance procedure) produces a visible esthetic result (smoothing wrinkles) and has a positive effect on the skin biomechanical properties improving its moisture level and elasticity (there were statistically significant changes in the cutometry and corneometry indices, р

Safety of Nonanimal Stabilized Hyaluronic Acid Dermal Fillers in Patients with Skin of Color

Nonanimal stabilized hyaluronic acid (NASHA) dermal fillers have been used in the United States since 2003 for the treatment of moderate to severe facial wrinkles and folds, such as nasolabial folds. Previous trials with NASHA dermal fillers have included small numbers of patients with pigmented skin. This randomized, evaluator-blinded, split-face trial compared the safety and efficacy of two variable-particle NASHA fillers in the correction of nasolabial folds in patients with Fitzpatrick skin types IV, V, and VI. One hundred fifty patients (predominantly African American) were enrolled at 10 sites. Patients received one treatment (with an optional touch-up treatment at week 2) with small- and large-particle NASHA gel randomized to the left or right side of the face. Safety was evaluated through patient diaries for the first 2 weeks and physician assessments at 3 days and 2, 6, 12, and 24 weeks after treatment for adverse events (AEs), skin pigmentation changes, and keloid formation. All related AEs were mild or moderate and of limited duration. They included bruising, tenderness, edema, redness, itching, pain, and changes in pigmentation. The incidence of AEs was not different between the 2 preparations, and no patient developed a keloid. There were 3 reported mass formations, 2 of which were infectious in nature. In patients with skin of color, NASHA dermal fillers are safe for the correction of moderate to severe facial folds and wrinkles, with no immunogenicity or keloid formation and only mild to moderate AEs occurring around the injection site.

Microbiologic Assessment of Multidose Restylane for Facial Augmentation

Microbiologic Assessment of Multidose Restylane for Facial Augmentation

Foreign Body Granuloma Due to Matridex Injection for Cosmetic Purposes

A new resorbable filler, Matridex, became commercially available during the last years with scarce evidence regarding side effects. A 43-year-old woman complained of multiple, painful, reddish, nonulcerated, hard nodules on both cheeks and periocular regions. Four weeks before, she had been injected by a general practitioner with Matridex for aesthetic purposes to correct wrinkles in the same areas of the nodular eruption. Histopathology showed a diffuse suppurative granulomatous reaction with the presence of multinucleate giant cells and many neutrophils involving the entire dermis. No areas of caseation were observed. The inflammatory granulomatous reaction surrounded 2 different types of nonpolarizing, bluish, exogenous material: one arranged in filamentous structures and the second composed by large spherical particles. All nodules were incised and drained; the patient received systemic antibiotic treatment for 2 consecutive weeks. The nodules progressively regressed and almost complete resolution was seen after 6 months. Matridex is a new resorbable filler constituted by a mixture of nonanimal-stabilized hyaluronic acid (HA), cross-linked HA, and dextranomer microspheres. Foreign body reactions have been described in association with other HA fillers, but a granulomatous reaction after the injection of Matridex has not been reported yet. Interestingly, in our patient, we were able to identify both fragments of HA: the filamentous particles and the spherical particles of dextranomer microspheres within the infiltrate, these last giving a characteristic and recognizable appearance to the histopathological picture.

Review of the Efficacy, Durability, and Safety Data of Two Nonanimal Stabilized Hyaluronic Acid Fillers from a Prospective, Randomized, Comparative, Multicenter Study

Nonanimal stabilized hyaluronic acid (NASHA)-based fillers are currently the criterion standard for cosmetic soft tissue augmentation. To report the efficacy, durability, and safety data of a large-particle NASHA filler and a small-particle NASHA filler. A blinded, prospective, randomized subject and evaluator study was conducted at 17 sites in the United States with 248 subjects enrolled. One of the two products was injected into both nasolabial folds and, if deemed necessary, the oral commissures of each subject. A 2-week touch-up injection was provided if necessary. Subjects returned for follow-up visits 2, 6, 12, and 24 weeks after receiving their last injection. Assessments were done using a subject diary, blinded investigator's Wrinkle Severity Rating Score (WSRS), and palpability of product. Both products demonstrated similar efficacy, durability, and safety profiles. Although both NASHA fillers demonstrated similar efficacy, durability, and safety, the fanning injection technique, and a faster rate of injection played a key role in the increase in incidence of adverse experiences. Furthermore, the safety of each NASHA product was demonstrated at volumes well beyond the volume range listed on the product inserts.

The Long-Term Efficacy and Safety of a Subcutaneously Injected Large-Particle Stabilized Hyaluronic Acid–Based Gel of NonAnimal Origin in Esthetic Facial Contouring

Nonanimal stabilized hyaluronic acid (NASHA) offers longer-lasting correction than many other injectable products and is associated with low risk of immunogenic and hypersensitivity reactions. A new large-particle stabilized hyaluronic acid-based gel has been developed to restore facial volume and define facial contours. This study was conducted to assess the long-term efficacy and safety of a large-particle stabilized hyaluronic acid-based gel in patients seeking facial contouring. Fifty-seven adult patients seeking esthetic cheek or chin augmentation or both received subcutaneous or supraperiosteal injections or both of large-particle stabilized hyaluronic acid-based gel (20 mg/mL). Efficacy was assessed subjectively using the Global Aesthetic Improvement Scale at intervals up to 12 months after treatment. After treatment, patients and investigators independently considered treatment sites to be at least somewhat improved in 91% and 96% (6 months), 68% and 77% (9 months), and 58% and 52% (12 months) of cases, respectively. Patient- and investigator-assessed treatment response rates (the proportion of patients showing at least moderate improvement) were 72% and 81% (6 months), 42% and 40% (9 months), and 21% and 15% (12 months), respectively. Most commonly reported adverse events were local injection-site reactions, skin induration, and implant mobility. This large-particle stabilized hyaluronic acid-based gel is well tolerated and provides relatively long-lasting esthetic correction of the cheeks and chin after subcutaneous or supraperiosteal injection.