Calcium Hydroxylapatite Microspheres Research Articles

Intradermal Delivery of Calcium Hydroxylapatite With Fractionated Ablation.

The absorption of biostimulatory particulate matter following its application to fractional skin defects remains poorly understood, and even less is known about its in vivo impact in terms of tissue integration. The objectives of this study are twofold: (1) to evaluate the potential of calcium hydroxylapatite (CaHA) to penetrate through skin treated with a fractional laser; and (2) to assess the effectiveness of clinical laser scanning microscopy technologies in monitoring the effects of such treatment over time. One area on a volunteer's arm was treated with a fractional erbium laser (Sciton Inc., Palo Alto, CA), while a second area received the same laser treatment followed by CaHA topical application. We used reflectance confocal microscopy (RCM) and multiphoton microscopy (MPM) to noninvasively image beneath the surface of the treated skin to study and monitor the effects of these treatments within 1 h of treatment and at four additional time points over a 6-week period. One hour posttreatment, at different depths beneath the skin surface, MPM and RCM provided similar visualizations of laser-induced channels. In skin treated by both laser and CaHA, these two imaging methods provided complementary information. RCM captured the lateral and depth distribution of CaHA microspheres and were seen as bright spheres as they became incorporated into the healing tissue. MPM, meanwhile, visualized the CaHA microparticles as dark shadow spheres within the laser-induced channels and encroaching healing tissue. Furthermore, MPM provided critical information about collagen regeneration around the microspheres, with the collagen visually marked by its distinct second harmonic generation (SHG) signal. This observational pilot study demonstrates that CaHA, a collagen stimulator used as a dermal filler, can not only be inserted into the dermis after fractional laser treatment but remains in the healing skin for at least 6 weeks posttreatment. The noninvasive imaging techniques RCM and MPM successfully captured the presence of CaHA microspheres mid-dermis during the healing phase. They also demonstrated new collagen production around the microspheres, highlighting the effectiveness of these imaging approaches in monitoring such treatment over time.

Optimizing Skin Regenerative Response to Calcium Hydroxylapatite Microspheres Via Poly-Micronutrient Priming.

Regenerative aesthetics aims to restore the structure and function of aging skin. Two products, Radiesse (CaHA) and NCTF 135 HA (micronutrient mesotherapy) have been established as minimally invasive treatments that restore the structure and function of various skin components. It has been anecdotally observed by the authors, however, that some patients respond suboptimally to regenerative treatments without a clear indication as to why. It was hypothesized that micronutrient deficiencies in some patients may contribute to their lack of responsiveness and that a concurrent delivery of amino acids and co-enzymes may create a nutritional reservoir necessary for optimal protein synthesis. Noting that CaHA is known to drive the regeneration of extracellular matrix proteins, the aim of this case series was to investigate if “priming” the skin with NCTF 135 HA could lead to enhanced clinical effects of CaHA. The combination treatment resulted in improvements in panfacial aesthetics, skin laxity, wrinkle severity, skin luminosity, hyperpigmentation, and in skin and subcutis thicknesses in 100% of patients following a single treatment. This study is the first to introduce skin priming via diluting a regenerative biostimulator treatment with an amino acid-based diluent.  Citation: Theodorakopoulou  E, McCarthy A, Perico V, et al. Optimizing skin regenerative response to calcium hydroxylapatite microspheres via poly-micronutrient priming. J Drugs Dermatol. 2023;22(9):925-934. doi:10.36849/JDD.7405.

The histologic reaction and permanence of hyaluronic acid gel, calcium hydroxylapatite microspheres, and extracellular matrix bio gel.

The filling materials on the beauty market can be classified into three types: natural biological materials, synthetic polymer materials, and composites containing bioactive substances. However, comparative experimental data is lacking to compare their biological responses and permanence. The main object of this study was to evaluate the biological response of these three types of fillers to provide a theoretical basis for clinical application. Six-week-old female mice were injected subcutaneously with hyaluronic acid (HA) gel, calcium hydroxylapatite (CaHA) microspheres, and extracellular matrix (ECM) bio gel to observe the body reaction and permanence. At 1, 4, 8, and 16 weeks, the test sites were excised and analyzed by histopathology and proteomics. Extracellular matrix had a minimal foreign body response. HA had a good volume effect at the early stage but the volume retention rate was lower than CaHA in the long term. CaHA could stimulate neo-collagen formation. This study has proven the effectiveness and safety of these fillers and could provide clinical guidance for the plastic surgeon.

Calcium hydroxylapatite microspheres activate fibroblasts through direct contact to stimulate neocollagenesis

Calcium hydroxylapatite (CaHA; Radiesse, Merz North America) restores volume and stimulates collagen production. The aim of this research was to explore the role of dilution and diffusion in microsphere distribution and the effect of CaHA concentration on activation of fibroblasts to produce collagen. Ex vivo: Tissue dispersion of CaHA was assessed in abdominal tissue segments obtained from patients which were subsequently injected with CaHA diluted to 1:1 and hyperdiluted to 1:2. In vitro: Collagen type III (COLIII) and type I (COLI) expression of fibroblasts was evaluated after 24 and 72 h of incubation with CaHA concentrations of 1.5 (high dilution), 3.0, and 4.5mg/ml (low dilution). Ex vivo: The 1:2 CaHA hyperdilution increased dispersion and decreased concentration of CaHA microspheres compared with the 1:1 dilution. In vitro: CaHA incubation resulted in an increased mean COLIII expression of 123% at 24 h. COLI synthesis did not change after 24 h but increased up to 124% at 72 h. Only fibroblasts in direct contact with CaHA increased COLIII expression. COLIII high-expressing cells were fully activated by CaHA and resulted in the same level of COLIII expression per cell independent of the CaHA dilution. A 1:2 hyperdilution of CaHA increased tissue dispersion of CaHA microspheres. Direct contact of CaHA with fibroblasts was a key factor for inducing neocollagenesis. COLIII high-expressing cells were fully activated by CaHA and resulted in the same expression level of COLIII per cell independent of the CaHA amount in each dilution. This indicates that increased collagen expression was due to the activation of more fibroblasts.

LB984 Intralesional sodium thiosulfate as a reversal agent for calcium hydroxylapatite soft tissue filler: An in vitro and ex vivo comparison

CaHA microspheres are the active component of an injectable filler material commonly used to correct fat and dermal atrophy. While use of CaHA in soft tissue augmentation is generally safe and well-tolerated, dissolution may be required for unwanted nodule formation or, rarely, for vascular occlusion. Though there is no approved reversal agent, preliminary reports have suggested STS may be considered. In this translational study, we sought to understand the effect of sodium thiosulfate (STS) on calcium hydroxylapatite (CaHA) microsphere size and dispersion.

Bilateral Gluteal Augmentation With Hyperdilute Calcium Hydroxylapatite Microspheres Performed Using the Bella Vida Instant Brazilian Butt Lift (BBL)™.

For decades, aesthetic medical procedures have sought to improve patient appearance, comfort, and self-confidence. In more recent years, a growing interest in body contouring cosmetic procedures has emerged, in large part due to increased transparency in procedures and improved outcomes with minimally invasive procedures. Notably, several biostimulatory fillers have emerged as a suitable treatment modality due to their relatively low cost, low pain, short downtime, high tunability, and sustained biostimulatory effect. One volumizing biostimulatory filler, Radiesse® (Merz Aesthetics, Frankfurt, Germany), consists of calcium hydroxylapatite microspheres suspended in a carboxymethyl cellulose gel. When injected, Radiesse immediately volumizes the injection site and initiates neocollagenesis and neoelastogenesis. One technique, the Bella Vida Instant Brazilian Butt Lift (BBL)™, is a fast, safe, and minimally invasive alternative to surgical gluteal augmentation that accomplishes morphological remodeling, increases volumization, and improves shape and patient satisfaction. This technical report provides the clinical basis, materials, and methods for implementing the Bella Vida Instant BBL™ in aesthetic practices.

Can Sodium Thiosulfate Act as a Reversal Agent for Calcium Hydroxylapatite Filler? Results of a Preclinical Study.

IntroductionCalcium hydroxylapatite microspheres suspended in a gel carrier of sodium carboxymethylcellulose (CaHA; Radiesse®) has demonstrated safe and effective restoration of facial volume in clinical trials, as well as collagen biostimulation leading to skin quality improvement. The potential with CaHA, as with any filler, to produce overcorrection and subsequent complications has led to the search for a reversal agent. Sodium thiosulfate (STS) was proposed based on experience with it as a chelating agent to treat calciphylaxis. Previous pilot studies with small sample sizes have suggested its efficacy in the reduction of CaHA volume and nodule formation. The present study focuses on the verification of this effect using various readout methods in preclinical experiments.MethodsWe use both in vitro (co-incubation of STS with CaHA) and in vivo (injections in farm pig) methods with readout techniques such as 3D camera analysis, micro-computed tomography ex vivo (µCT), computed tomography in vivo (CT), histopathology and scanning electron microscopy.ResultsWe did not obtain any indications of CaHA degradation by STS, either in vitro or in vivo. 3D-camera analysis also did not show any decreasing effect of STS on CaHA. However, histology, µCT ex vivo, and CT in vivo indicated a decrease of Radiesse amount/volume after STS treatment, which could be attributed to dispersion effect. It should be noted that necrosis and haemorrhages were observed after STS treatment.DiscussionResults suggest no indication of CaHA microspheres degradation with STS and that the STS mechanism of action on CaHA is consistent with a dispersion effect. Observed necrosis is a further obstacle in the use of STS.

Human Histology and Persistence of Various Injectable Filler Substances for Soft Tissue Augmentation.

An increasing number of soft tissue filler substances have been introduced to the beauty market outside the U.S. which lackexperimental and clinical data in support of their claim. Ten commercially available filler substances were examined for biocompatibility and durability: 0.1 cc of each substance was injected deep intradermally into the volar forearm of one of the authors and observed for clinical reaction and permanence. At 1, 3, 6, and 9 months the test sites were excised, histologically examined, and graded according to foreign body reactions classification. Collagen (Zyplast) was phagocytosed at 6 months and hyaluronic acid (Restylane) at 9 months. PMMA microspheres (Artecoll) had encapsulated with connective tissue, macrophages, and sporadic giant cells. Silicone oil (PMS 350) was clinically inconspicuous but dissipated into the tissue, causing a chronic foreign body reaction. Polylactic acid microspheres (New-Fill) induced a mild inflammatory response and had disappeared clinically at 4 months. Dextran microspheres (Reviderm intra) induced a pronounced foreign body reaction and had disappeared at 6 months. Polymethylacrylate particles (Dermalive) induced the lowest cellular reaction but had disappeared clinically at 6 months. Polyacrylamide (Aquamid) was well tolerated and remained palpable to a lessening degree over the entire testing period. Histologically, it dissipated more slowly and was kept in place through fine fibrous capsules. Polyvinylhydroxide microspheres suspended in acrylamide (Evolution) were well tolerated, slowly diminishing over 9 months. Calcium hydroxylapatite microspheres (Radiance FN) induced almost no foreign body reaction but were absorbed by the skin at 12 months.Host defense mechanisms react differently to the various filler materials, but all substances- resorbable or nonresorbable-appeared to be clinically and histologically safe, although all exhibit undesirable side effects. Since the mechanism of late inflammation or granuloma formation is still unknown, early histological findings are not useful in predicting possible late reactions to filler substances.

Ophthalmic Artery Occlusion and Subsequent Retinal Fibrosis From a Calcium Hydroxylapatite Filler Injection.

We report a case of otherwise healthy 48-year-old woman presenting with acute vision loss after injection of a soft tissue filler injection in the glabellar region with calcium hydroxylapatite microspheres (Radiesse®) with 9 months of follow-up. Fundus photographs and spectral domain optical coherence tomography (SD-OCT) were obtained at presentation, 4 months of follow-up, and 9 months of follow-up. Acutely, the retina was characterized by significant pallor and thickening but evolved into diffuse retinal fibrosis and atrophy. The patient was no light perception at presentation, and did not recover any visual function. Few case reports have described calcium hydroxylapatite filler injections leading to orbital and ocular complications. This is the first case report illustrating dense fibrotic and atrophic retinal changes on both fundus photography, fluorescein angiography, and SD-OCT. While various facial fillers have been reported to have serious ocular consequences, we illustrate the acute and subsequent sequelae of an ophthalmic artery occlusion from calcium hydroxylapatite microspheres (Radiesse®).

Calcium Hydroxylapatite Dermal Filler for Treatment of Dorsal Hand Volume Loss: Results From a 12-Month, Multicenter, Randomized, Blinded Trial.

Calcium hydroxylapatite (CaHA) microspheres suspended in a carrier gel is an opaque dermal filler that has been used to provide immediate volume correction in the dorsal hands. To assess the safety and effectiveness of CaHA for the correction of volume loss in the hands up to 12 months. This multicenter, controlled, single-blind study (NCT01832090) included 114 subjects randomized 3:1 to CaHA treatment and untreated control groups. Effectiveness was assessed by blinded investigators using the validated Merz Hand Grading Scale (MHGS). Subject-reported improvement was assessed using the Global Aesthetic Improvement Scale. Effects of treatment on hand function were also assessed. A total of 75% of subjects achieved ≥1-point improvement on the MHGS (p < .0001) at 3 months (primary end point); this response was generally maintained through 12 months. Proportions of subjects reporting improvement ranged from 98% (3 months) to 86% (12 months). There were no clinically significant differences between control and CaHA-treated subjects in any hand function measure. Adverse events were generally expected, minor, short-lived, injection-related, and similar to those observed in previous CaHA clinical studies. Treatment with CaHA results in significant improvement in the appearance of the dorsal hand and is well tolerated.

片側性声帯麻痺に対するdouble-bent Cathelin needleを用いた声帯内カルシウムハイドロキシアパタイト注入術の臨床的検討

片側性声帯麻痺に対するdouble-bent Cathelin needleを用いた声帯内カルシウムハイドロキシアパタイト注入術の臨床的検討

The use of injectable calcium hydroxylapatite in the surgically pretreated larynx with glottal insufficiency.

To evaluate the efficacy of vocal fold (VF) augmentation with calcium hydroxylapatite (CaHA) microspheres in the surgically pretreated larynx with glottal insufficiency. Prospective clinical pilot study. After several prior reconstructive attempts (following tumor resection, VF paralysis, in sulcus vocalis, and VF scarring), CaHA was injected under general anaesthesia using a transoral microlaryngoscopic approach in 10 patients with residual glottal insufficiency ≤1.5 mm. The postinterventional result was assessed after 1 day, and 1 and 3 months. Evaluation of augmentation comprised intraoperative video/photo documentation, pre-/postoperative videolaryngostroboscopy, as well as established subjective and objective voice function diagnostics (Grade, Roughness, Breathiness [GRB] Scale; Voice Handicap Index; voice range profile; and acoustic-aerodynamic analysis). In the pretreated VF with no or minimal lamina propria remaining, the exact placement of CaHA was not possible due to unpredictable propagation into the scarred tissue. The results showed an insufficient postoperative augmentation. Accordingly, the voice function did not improve. However, a significant increase of the vocal range from 6.2 ± 3.2 to 8.7 ± 3.9 semitones was observed in the speaking voice profile (P =.02). All other acoustic and aerodynamic parameters remained on the whole unchanged; the slight differences between pre- and postoperative findings were not significant. The application of CaHA in the surgically pretreated scarred larynx is not reliable to achieve a sufficient glottal closure and a satisfactory improvement of voice. Though CaHA is a welcome addition to our armamentarium against glottal insufficiency, the suitability for augmentation of scar tissue in the larynx must be considered carefully in each individual case. 4 Laryngoscope, 127:1125-1130, 2017.

Foreign Body Reaction to Radiesse

We report 2 cases of a foreign body reaction to Radiesse, a semipermanent soft-tissue filler consisting of 30% calcium hydroxylapatite microspheres and 70% carboxymethyl cellulose gel carrier. In one case, injection of this filler provoked a nodule on the columella, which was discovered during rhinoplasty. In the second case, the reaction was revealed during histopathologic examination of the deep section of a surgically removed basal-cell carcinoma. Histopathology showed a foreign body reaction with numerous giant cells and histiocytes, some plasma cells, and lymphocytes. Within this inflammatory reaction, a nonpolarizing exogenous material was identified consisting of numerous, round, uniformly sized, yellowish, extracellular deposits with a crackled appearance. Although many authors claim that Radiesse does not induce any foreign body reactions, we found a number of similar histopathologic pictures in studies describing animal or human auricular area test sites or even in reports of lip nodules, which are a well-known adverse effect after injection of this filler into this site. The histopathologic appearance of Radiesse is particularly distinctive and easily recognizable by dermatologists and dermatopathologists.

Vocal fold insufficiency: medialization laryngoplasty vs calcium hydroxylapatite microspheres (Radiesse Voice®)

Conclusion: The choice of technique will depend on the glottic gap observed by stroboscopy, the alteration of the Voice Handicap Index (VHI) and the recorded values of harmonics-to-noise ratio (HNR), jitter and shimmer, and the general health, age and underlying pathology. There are statistically significant differences between the values of VHI, shimmer and jitter in favour of those cases operated on within 6 months of diagnosis. Alternatives are discussed. Objectives: This study analysed and compared the functional, morphological and acoustic results, after surgery, through the techniques of medialization thyroplasty and infiltration of biomaterials to correct incomplete closure of the glottis. Methods: A total of 21 patients with dysphonia due to vocal fold insufficiency (13 women and 8 men) and ages ranging between 30 and 65 years (mean age 40.84, SD 12.5) were evaluated. The material used for augmentation surgery consisted of calcium hydroxylapatite microspheres. Measurements (VHI, jitter, shimmer and HNR) were performed before surgery and at 6 and 24 months post-intervention. Results: Overall, statistically significant differences were observed relating to measurements (p < 0.01) and surgical techniques (p < 0.05) analyzed. In particular, these differences were located in pairs pre-surgery – 6 months post-surgery and pre-surgery – post 24 months, in the four variables, and between the two techniques used in jitter (p = 0.008), HNR (p = 0.045) and VHI (p = 0.035).

Intense Focal F-18 FDG Uptake in Vocal Cord Associated with Injection of Calcium Hydroxylapatite Microspheres

Lower F-18 fluorodeoxyglucose (FDG) uptake on PET/CT is generally expected on the side of a paralyzed vocal cord (VC). The contrary pattern of increased uptake can raise concern for metastasis or a primary VC malignancy. We present a case showing paradoxical development of intense FDG uptake in the paralyzed VC, unrelated to malignancy. History revealed injection of calcium hydroxylapatite microspheres for treatment of VC paralysis. This new synthetic material can stimulate local fibroblast activity and macrophage accumulation, leading to increased FDG uptake. The case illustrates the importance of obtaining accurate history before interpreting intense FDG uptake in a paralyzed VC.

Comparison of the Rheological Properties of Viscosity and Elasticity in Two Categories of Soft Tissue Fillers: Calcium Hydroxylapatite and Hyaluronic Acid

Two types of soft tissue filler that are in common use are those formulated primarily with calcium hydroxylapatite (CaHA) and those with cross-linked hyaluronic acid (cross-linked HA). To provide physicians with a scientific rationale for determining which soft tissue fillers are most appropriate for volume replacement. Six cross-linked HA soft tissue fillers (Restylane and Perlane from Medicis, Scottsdale, AZ; Restylane SubQ from Q-Med, Uppsala, Sweden; and Juvéderm Ultra, Juvéderm Ultra Plus, and Juvéderm Voluma from Allergan, Pringy, France) and a soft tissue filler consisting of CaHA microspheres in a carrier gel containing carboxymethyl cellulose (Radiesse, BioForm Medical, Inc., San Mateo, CA). METHODS The viscosity and elasticity of each filler gel were quantified according to deformation oscillation measurements conducted using a Thermo Haake RS600 Rheometer (Newington, NH) using a plate and plate geometry with a 1.2-mm gap. All measurements were performed using a 35-mm titanium sensor at 30°C. Oscillation measurements were taken at 5 pascal tau (τ) over a frequency range of 0.1 to 10 Hz (interpolated at 0.7 Hz). Researchers chose the 0.7-Hz frequency because it elicited the most reproducible results and was considered physiologically relevant for stresses that are common to the skin. RESULTS The rheological measurements in this study support the concept that soft tissue fillers that are currently used can be divided into three groups. CONCLUSION Rheological evaluation enables the clinician to objectively classify soft tissue fillers, to select specific filler products based on scientific principles, and to reliably predict how these products will perform--lifting, supporting, and sculpting--after they are appropriately injected.

Calcium Hydroxylapatite Tissue Filler Discovered 6 Years after Implantation into the Nasolabial Fold

Injectable calcium hydroxylapatite is becoming increasingly popular as a facial soft tissue filler, due in part to its purported longevity of esthetic correction compared with other materials, but little is known about its long-term histologic appearance and persistence in facial skin. We recently encountered calcium hydroxylapatite microspheres incidentally during Mohs surgery of the nasolabial fold 6 years after implantation. To describe the long-term histologic appearance of calcium hydroxylapatite microspheres in human facial skin and review the relevant literature with a consideration of clinical implications. Routine hematoxylin and eosin staining was performed on frozen and fixed excised tissue containing calcium hydroxylapatite microspheres. Additional fixed sections were stained using Movat's pentachrome method. Numerous 4- to 20-mum round vacuoles were present throughout the reticular dermis associated with focal fibrosis, interstitial mucin, and little surrounding inflammation. Calcium hydroxylapatite microspheres and associated fibrosis may persist in facial dermis at least 6 years after implantation, long after its clinical effects are thought to subside. Dermatologists and dermatopathologists must be mindful of dermal implants because it is likely that incidental encounters will be an increasingly common occurrence.

Evaluation of Injectable Calcium Hydroxylapatite for the Treatment of Facial Lipoatrophy Associated with Human Immunodeficiency Virus

To evaluate the safety and effectiveness of soft tissue augmentation with calcium hydroxylapatite (CaHA) microspheres in an aqueous gel in patients with facial lipoatrophy (FLA) secondary to human immunodeficiency virus (HIV) disease. This 12-month open-label, prospective study enrolled 30 subjects (29 men and 1 woman) with HIV-associated FLA. After the initial treatment phase (up to 2 injections, 30 days apart), patients were followed up at 3, 6, and 12 months. Patients were offered touch-up injections at 6 and 12 months. Measurements included confirmed changes in the Global Aesthetic Improvement Scale and in cheek thickness. Average initial treatment volume was 9.5 mL per patient (both sides); total volumes per patient after 12 months averaged 16.1 mL. At all time points, all patients were rated as improved or better and responded affirmatively to satisfaction questions. Cheek thickness measurements increased substantially over baseline (p<.001). Most commonly reported adverse events were edema (93%), ecchymosis (83%), and erythema (77%). CaHA is an appropriate and well-tolerated treatment for patients with HIV-associated FLA. With an excellent safety profile, CaHA provides immediate correction of FLA and appears to provide lasting improvement in appearance.

Use of calcium hydroxylapatite (Radiesse&lt;sup&gt;&amp;reg;&lt;/sup&gt;) for facial augmentation

Radiesse (Bioform Inc, USA) is a sterile, latex-free, non-pyrogenic, semi-solid, cohesive subdermal, injectable implant, whose principal component is synthetic calcium hydroxylapatite, a biocompatible material with over 20 years of use in medicine. The semi-solid nature of the product is created by suspending calcium hydroxylapatite microspheres of 25-45 microns diameter in a gel carrier of carboxymethylcellulose. The product has FDA approval for esthetic facial augmentation in the US. Such approval includes the long-lasting correction of moderate to severe facial wrinkles and folds and the treatment of facial fat loss due to immunodeficiency virus infection. Diverse facial regions can be injected in order to ameliorate or enhance some features: glabellar lines, subdermal support of the brows, malar and buccal fat pads, tear troughs, nasolabial folds, nose, lips, perioral region, marionette lines, oral commisures and chin among others, as well as saucerized acne scars. Other medical indications include nipple projection for nipple areolar reconstruction, urinary incontinence, vesicoureteral reflux, vocal cord augmentation, and use as a radiographic tissue marker. The average lasting result is from 12 to 18 months. Radiesse can be considered an effective soft-tissue filler for overall longevity, biocompatibility, and low rate of side effects.

A Randomized, Bilateral, Prospective Comparison of Calcium Hydroxylapatite Microspheres versus Human-Based Collagen for the Correction of Nasolabial Folds

Current soft tissue fillers are a compromise between ease of use, duration of correction, reactivity, and cost. A product utilizing calcium hydroxylapatite (CaHA) is currently being used as a soft tissue filler. The objective was to compare the efficacy and safety of CaHA microspheres versus human-based collagen for the correction of nasolabial folds. Four centers enrolled 117 subjects with moderate to deep nasolabial folds. Subjects received CaHA on one side of the face and human collagen on the other. Up to two touch-ups were allowed. A blinded panel of experts evaluated subject photographs from initial and follow-up visits. Seventy-nine percent of subjects had superior improvement on the CaHA side through 6 months (p<.0001). For optimal correction, significantly less volume and fewer injections were needed for CaHA than for collagen (p<.0001). Adverse event rates were comparable, with some increase in bruising and edema for CaHA-treated sides. Adverse event duration was similar for both groups and generally resolved within 14 to 21 days. This CaHA-based product gives significantly longer-lasting correction of nasolabial folds compared to human collagen. Less total material and fewer injections are required. The adverse event profile of the product is similar to the collagen-based product.