Calcium Hydroxylapatite Filler Research Articles

The Hybrid Filler Technique: A 5-Year Retrospective Analysis.

The combination of calcium hydroxylapatite (CaHA) and hyaluronic acid fillers (CPM-HA, cohesive polydensified matrix-based hyaluronic acid fillers, Belotero® range, Merz Pharmaceuticals GmbH, Frankfurt, Germany), known as hybrid fillers, has emerged as a popular approach in aesthetic medicine. Premixed CaHA with CPM-HA offers several advantages, including enhanced tissue elevation and reduced early volume loss after injection. The objective of the present study is to assess the safety of premixing CaHA and CPM-HA fillers for rejuvenation purposes or as an aesthetic harmonization treatment. This retrospective study presents the clinical experience of two expert injectors who consistently used premixed CaHA and CPM-HA fillers for aesthetic treatments between March 2018 and December 2023. The premixed hybrid formulation was standardized and administered following a published protocol. A total of 2112 patients were treated, with meticulous follow-up over a minimum of one year. In the 2112 patients treated, only 5 minor adverse events (0.24%) were reported. The adverse events consisted of 4 non-inflammatory nodules of which 2 completely resolved with hyaluronidase, and 1 case of transient edema. Secondary findings consist of the treated areas, type of CPM-HA used and mixing ratios that were applied. The results from the current retrospective study, with the largest published cohort so far, are consistent with prior publications and strongly support a good safety profile of the CaHA:CPM-HA hybrid blend. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Blending Hyaluronic Acid and Calcium Hydroxylapatite for Injectable Facial Dermal Fillers: A Clinical and Ultrasonography Assessment

Both hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers have well-established indications in cosmetic medicine. Nevertheless, limited data are available on the effectiveness of combining CaHA and HA. The purpose of this report was to demonstrate the safety, tolerability, and clinical and ultrasonographic improvement of facial skin laxity using a blending technique that admixes HA and CaHA. Fifteen regular patients, including three men, between 25 and 71 years of age were reported. The participants were subjects who came regularly to the dermatologic office seeking a lifting effect without surgery. They were submitted to injection of an admixture of HA and CaHA and followed for 180 days. The clinical assessment consisted of photographic evaluation by two blind investigators, and a consensual subjective evaluation was performed by the physicians (PGAIS) using the five-point Global Aesthetic Improvement Scale. Dermal thickness was analyzed in jaw areas using high-frequency ultrasound. Subjects completed a satisfaction questionnaire with responses scored according to the five-point Global Aesthetic Improvement Scale (GAIS) to evaluate patient satisfaction. After 180 days of follow-up, clinical assessments by blinded physicians found that all patients improved. All the participants were highly satisfied with the results and reported exceptional improvement. Dermal thickness increased by 9.4% (8.2–10.8%), 14.0% (12.2–15.9%), and 18.8% (16.2–21.9%) at D90, D120, and D180, respectively, by ultrasonography. In conclusion, an injection technique using an admixture of CaHA and HA fillers was well tolerated, offering high satisfaction and long-lasting progressive benefits. The authors believe that this procedure optimizes the treatment time and results because HA promotes early volume restoration and CaHA stimulates long-term dermal remodeling through the synthesis of collagen and elastin.

Biostimulating fillers and induction of inflammatory pathways: A preclinical investigation of macrophage response to calcium hydroxylapatite and poly-L lactic acid.

Initial macrophage response to biostimulatory substances is key in determining the subsequent behavior of fibroblasts and the organization of newly synthesized collagen. Though histological studies suggest that calcium hydroxylapatite (CaHA) filler initiates a regenerative healing response with collagen and elastin deposition similar to natural, healthy tissue rather than an inflammatory response with fibrosis, the relative activity of macrophages stimulated by CaHA, as well as how this activity compares to that induced by other biostimulatory fillers, has not been explored. The aim of the study is to characterize the in vitro macrophage response to two biostimulory fillers, CaHA and PLLA (poly-L lactic acid), and to evaluate their inflammatory potential. Primary human macrophages were incubated with two dilutions (1:50 and 1:100) of commercially available CaHA or PLLA. After 24 h incubation, an inflammation array was used to screen for the expression of 40 cytokines, released by macrophages. ELISA was used to confirm array results. Four cytokines were significantly upregulated in M1 macrophages incubated with PLLA compared to both unstimulated controls and CaHA: CCL1 (p < 0.001), TNFRII (p < 0.01), MIP-1α (p < 0.05), and IL-8 (p < 0.001). In M2 macrophages, MIP-1α (p < 0.01) and MIP-1β (p < 0.01) were significantly upregulated by PLLA compared to CaHA and unstimulated controls. Together, these findings indicate that the CaHA mode of action is a non-inflammatory response while PLLA initiates expression of several cytokines known to play a role in inflammation. Our study supports the concept that these two "biostimulatory" fillers follow distinct pathways and should be considered individually with regard to mechanism of action.

Radiesse: State of the Art and Dilute Radiesse

AbstractBackgroundRadiesse is a calcium hydroxylapatite (CaHA)‐based filler first FDA‐approved in 2006 for the treatment of human immunodeficiency virus‐associated lipodystrophy and moderate to severe facial wrinkles, particularly the nasolabial folds. It has since expanded into new formulations and has been approved for jawline contouring and treatment of dorsal hand volume loss. CaHAs provide the basis of the filler's appeal, inducing biostimulation of stromal components including collagen, elastin, and vasculature. The carboxymethylcellulose gel carrier gives the filler its notoriously stiff volumizing effects, intended for deeper placement, typically in the subdermal and supraperiosteal planes. Since its inception, innovative efforts have been ongoing to take advantage of the filler's biostimulatory effects without its volumization.ObjectivesTo describe novel uses of dilute, hyperdilute, and HA‐mixed CaHA filler.MethodsA review was performed on current available literature and consensus guidelines.ConclusionsDiluted and hyperdiluted Radiesse allow for widespread treatment, providing patients the dermal rejuvenation they desire, without the firm volumizing effects seen with undiluted product. This has led to an explosion in off‐label use including treatment of skin laxity of the face, neck and decolletage, arms, abdomen, buttocks, and thighs. Clinicians have also begun combining the CaHA filler with hyaluronic acid‐based fillers to induce skin regeneration while providing a more flexible and softer volume replacement. Radiesse' uses continue to evolve with alterations in the original formula, allowing for increasingly customized product to meet each patient's individual needs.

Introducing aesthetic regenerative scaffolds: An immunological perspective.

Skin aging arises from immunological responses to tissue deterioration and damage. Tissue repair processes encompass the regeneration of original tissue and 'scarless' wound healing seen in foetuses, and the extreme fibrotic responses and scarring seen in adults. Anti-aging aesthetic medicine uses interventions like biomaterial-based fillers to influence these immunological responses and renew aged tissue structure and function. At filler injection sites, an inflammatory response occurs that causes a spectrum of outcomes, ranging from tissue regeneration to fibrosis and filler encapsulation. Importantly, the resulting inflammatory pathway can be predetermined by the biomaterial injected. By understanding this immunological process, we can develop Aesthetic Regenerative Scaffolds (ARS) - aesthetic injectable biomaterials - to direct inflammatory wound healing away from chronic, fibrotic responses, and towards physiological tissue regeneration. We identified and reviewed literature on the immunological and cellular responses to injected dermal fillers, whereby the wound healing response to the injection was moderated under the influence of an injected biomaterial. We described the mechanisms of dermal wound healing and the use of ARS to direct healing towards tissue regeneration instead of scarring. We also summarised studies on extracellular matrix remodeling by calcium hydroxylapatite. We found that Calcium hydroxylapatite fillers produce collagen as they gradually degrade and their spherical structures serve as a scaffold for tissue regeneration. Furthermore, CaHA improved fibroblast contractility, collagen type III and elastin production, proliferation and angiogenesis with less inflammation than hyaluronic acid fillers. Regneration pathways can be influenced at specific points between a facial filler biomaterial and the wound healingmechanisms at its site of implantaion. Physicians can select scaffolds that direct the immune response away from a fibrotic chronic inflammatory pathway and towards regeneration to enable true repair of the aging skin.

Improvement of Facial Skin Laxity by a Combined Technique With Hyaluronic Acid and Calcium Hydroxylapatite Fillers: A Clinical and Ultrasonography Analysis.

Facial aging involves skeletal changes, loss of volume in the fat compartment, and skin component changes. The current objective of cosmetic facial filling is to reestablish the overall aspect that was lost during the aging process. Hyaluronic acid (HA) and calcium hydroxyapatite (CaHA) fillers are indicated for facial rejuvenation, and these agents promote dissimilar effects regarding volume restoration and dermal biostimulation. This study aimed to assess clinical and ultrasonographic improvements in facial skin laxity using a technique that combines the injection of HA and CaHA. A 120-day follow-up, quasi-experimental study was conducted based on the enrollment of fifteen women (36&ndash;47 years old) with mild face flaccidity scores who underwent subcutaneous injection of up to 3 mL of HA (zygomatic-malar region, pyriform aperture, temporal region, and jaw) followed by 3 mL of 1:1 diluted CaHA using a fan technique (temporal, zygomatic-malar, and jaw regions). Adverse effects were registered, and the monthly assessed outcomes included clinical improvement, satisfaction, and high-frequency ultrasonography (dermal thickness) parameters. At 120 days of follow-up, clinical assessment by blinded physicians yielded six (40%) very improved patients and nine (60%) exceptionally improved patients. All the participants were highly satisfied with the results and reported exceptional improvement. Dermal thickness increased 11.1% (8.8&ndash;13.4%), and augmented dermal homogeneity was evidenced by ultrasonography. Local adverse effects were mild and transient. In conclusion, the combined technique with HA and CaHA fillers was well-tolerated and yielded high satisfaction and safe improve in facial skin laxity and dermal thickness in women with mild midface aging. J Drugs Dermatol. 2022;21(1): 102-106. doi:10.36849/JDD.633.

Management of vascular complications following calcium hydroxylapatite filler injections: a systemic review of cases and experimental studies

Aim: Dermal fillers are increasingly popular procedures. Inadvertent intraarterial injection of fillers, particularly with calcium hydroxylapatite (CaHA), can result in devastating consequences. A systemic review was performed to summarize management strategies to treat CaHA-associated vascular complications. Methods: The methodology of this review was derived from The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). In addition, this paper presents a previously unreported case of a CaHA-associated vascular complication. Results: There were 32 articles describing 42 cases, plus our case included in this review. There were 15 cases of vision complications, 23 cases of non-vision complications, and 5 experimental studies. The most common injection sites reported were nasal region for vision complications (45%) and nasolabial folds for non-vision complications (40%). Of the 38 human cases, the most prevalent treatment choice was steroids (24 cases, 63%). Complete or near complete improvement was reported in 83% of non-vision complications and 40% of vision complications. There was no noticeable homogeneity in the management strategies and outcomes of the patients. Of the 5 experimental studies, no clear consensus on treatments was found. Conclusion: Vascular complications of CaHA are seemingly uncommon, but it is widely suspected that this is due to underreporting. While best management is prevention, preparation for a potential complication is equally important. Derived from CaHA literature, hyaluronic acid filler complication protocols, findings of this review, and personal experiences, this report proposes management strategies for CaHA-associated vascular complications. We hope these strategies provide a much-needed framework for injectors to refer to and utilize as needed.

Improvement of Facial Skin Laxity by a Combined Technique With Hyaluronic Acid and Calcium Hydroxylapatite Fillers: A Clinical and Ultrasonography Analysis

Background: Facial aging involves skeletal changes, loss of volume in the fat compartment, and skin component changes. The current objective of cosmetic facial filling is to reestablish the overall aspect that was lost during the aging process. Hyaluronic acid (HA) and calcium hydroxyapatite (CaHA) fillers are indicated for facial rejuvenation, and these agents promote dissimilar effects regarding volume restoration and dermal biostimulation. Objective: This study aimed to assess clinical and ultrasonographic improvements in facial skin laxity using a technique that combines the injection of HA and CaHA. Methods: A 120-day follow-up, quasi-experimental study was conducted based on the enrollment of fifteen women (36–47 years old) with mild face flaccidity scores who underwent subcutaneous injection of up to 3 mL of HA (zygomatic-malar region, pyriform aperture, temporal region, and jaw) followed by 3 mL of 1:1 diluted CaHA using a fan technique (temporal, zygomatic-malar, and jaw regions). Objective: Adverse effects were registered, and the monthly assessed outcomes included clinical improvement, satisfaction, and high-frequency ultrasonography (dermal thickness) parameters. Results: At 120 days of follow-up, clinical assessment by blinded physicians yielded six (40%) very improved patients and nine (60%) exceptionally improved patients. All the participants were highly satisfied with the results and reported exceptional improvement. Dermal thickness increased 11.1% (8.8–13.4%), and augmented dermal homogeneity was evidenced by ultrasonography. Local adverse effects were mild and transient. Conclusion: In conclusion, the combined technique with HA and CaHA fillers was well-tolerated and yielded high satisfaction and safe improve in facial skin laxity and dermal thickness in women with mild midface aging. J Drugs Dermatol. 2022;21(1): 102-106. doi:10.36849/JDD.633Hyaluronic Acid and Calcium Hydroxylapatite Fillers

Combining Calcium Hydroxylapatite and Hyaluronic Acid Fillers for Aesthetic Indications: Efficacy of an Innovative Hybrid Filler

BackgroundLimited data are available describing effectiveness of combining the use of calcium hydroxylapatite (CaHA) and hyaluronic acid (HA).MethodsThe authors performed a retrospective chart review of patients injected with a premixed combination of CaHA and a cohesive polydensified matrix (CPM®) HA (CaHA:CPM-HA ) in the authors’ aesthetic practices. The midface and lower face were injected. Patients’ records were evaluated, and treatment results were scored using the Merz Aesthetics Scale for the jawline® (clinician rated, CR-MASJ). Adverse events were recorded.ResultsA total of 41 patients were included, all females with a mean age of 47.5 years (range 21–63 years). The mean CR-MASJ score improved from 2.12 at baseline to 0.68 at t = 3 months (SD = 0.69, 95% CI 1.28–1.60) and 1.27 at t = 12 months (SD = 0.74, 95% CI 0.43–0.74). 100% of the subjects had experienced a ≥1-point improvement in CR-MASJ score at t = 3 months, versus 85% at t = 12 months. No adverse events were reported.ConclusionThe results of this study support the volumizing and lifting potential of the hybrid mix CaHA:CPM-HA for treatment of cheeks and jawline.Level of Evidence IVThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

A Hybrid Filler: Combining Calcium Hydroxylapatite and Hyaluronic Acid Fillers for Aesthetic Indications

Limited data are available describing the use of calcium hydroxylapatite (CaHA) and hyaluronic acid (HA) in combination. The aim of this study is to investigate the safety of premixing CaHA and HA fillers before injection. The authors performed a retrospective chart review of patients injected with a premixed combination of CaHA and a cohesive polydensified matrix (CPM®) HA in the authors’ aesthetic practices. Patients records were evaluated for adverse events at 1-3 month, 5-7 month and &gt;12-month posttreatment follow-up visits. The retrospective chart review identified 134 patients who had been treated with premixed CaHA: HA, most of whom were female (95%). Most patients were treated for multiple facial areas. Injections were subcutaneous and performed with 25G 38- or 50-mm cannulas, using a fanning injection technique. Injection volumes and product ratios depended on the number of areas being treated and severity of the aesthetic defect. Only 2 adverse events were reported which comprised slight cases of overcorrection at 1-3 months, both of which resolved with hyaluronidase. No other adverse events were reported. This combined evaluation of the published literature and retrospective examination of case reports raised no concerns about the use of premixed CaHA and CPM-HA (Hybrid) fillers for the treatment of a range of facial aesthetic indications.

Comparison of polycaprolactone and calcium hydroxylapatite dermal fillers in a rat model.

Polycaprolactone (PCL) and calcium hydroxylapatite (CaHA) are semipermanent dermal fillers that are frequently preferred in the last decade. This study aims to compare the effects of these two fillers in the rat skin. A total of 30 female rats were divided into; control, PCL, and CaHA group. Tissue samples taken at the second and fourth month were stained with hematoxylin-eosin, Masson trichrome, collagen type 1, and 3 immunohistochemical antibodies. Collagen density was quantitatively compared using the Image J computer program. At 2 and 4 months, the density of collagen increased in both filler groups compared to the control group. There was no significant difference between collagen density or type 1 and type 3 collagen H scores in the filler groups. The number of fibroblast nuclei was significantly higher in the PCL group at 4 months compared to the other two groups. Dermis thickness was found to be superior in both filler groups compared to the control group at the fourth month, there was no significant difference between the filler groups. We compared the effect of CaHA and PCL filler on collagenization histologically and immunohistochemically. We found that PCL and CaHA fillers are effective in increasing dermal collagen density, type 1 and type 3 collagen amount, and preventing dermis atrophy and showed that they have no advantage over each other in this respect. We have shown that PCL filler provides more fibroblast increase compared to CaHA filler and the effect of stimulating fibroblast proliferation takes longer.

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.

Generation of Filler Emboli as a Mechanism for Filler-Related Blindness.

Intra-arterial injection of fillers can lead to occlusion of the ophthalmic artery or its branches supplying the retina or the optic nerve. The mechanism through which this occurs is incompletely understood. We investigated the possibility of generating microparticles after injecting commercially available fillers into a flowing system in vitro. Three hyaluronic acid fillers and one calcium hydroxylapatite filler were injected into an artificial saline flow system mimicking arterial systolic blood pressure and corresponding to the diameter of the facial artery. All the saline at the end of the tube was collected, centrifuged, and inspected for filler particles. After injection into the system, all fillers immediately disintegrated into small particles that were carried downstream with the flow of the saline. The saline at the end of the tube contained collections of filler. Hyaluronic acid and hydroxylapatite fillers break up into small particles immediately after injection into a flowing system, generating emboli rather than a column of filler. The results of this study lead us to hypothesize another potential mechanism leading to filler-related blindness.

Rheology of Polymethylmethacrylate-Collagen Gel Filler: Physiochemical Properties and Clinical Applications.

Soft tissue fillers are comprised of a range of materials with differing physiochemical and rheologic (ie, flow) properties. These properties can inform treatment selection for specific anatomic areas, planes of injection, and clinical applications. The aim of this study was to characterize the rheologic properties of polymethylmethacrylate (PMMA)-collagen gel for comparison with other available fillers. Commercially available PMMA-collagen gel, hyaluronic acid (HA), and calcium hydroxylapatite (CaHA) fillers were obtained from their respective manufacturers. Measures of complex viscosity (η*) and elastic modulus (G') for each filler were collected at 0.7 Hz in triplicate according to standard procedures on a rotational rheometer fitted with a 40-mm steel plate at 25°C on a Peltier plate (500-μm gap). The measured η* and G' values for HA and CaHA fillers were in agreement with previously published data. The difference in η* between CaHA (mean [standard deviation], 358.9 [21.56] Pa-s) and PMMA-collagen gel (656.41 [68.03] Pa-s) was statistically significant (P < 0.0001), as was the difference between the G' of CaHA (1424.8 [83.3] Pa) and the G' of PMMA-collagen gel (2815.27 [304.07] Pa; P < 0.0001). PMMA-collagen gel exhibited the highest η* and G' of all tested fillers. These properties likely underpin an increased capacity for lifting and support in areas where long-lasting revolumization is appropriate. In practice, PMMA-collagen gel is well suited for treatment of acne scars, as well as injection into the supraperiosteal plane in the temple, chin, mandible, and piriform by a retrograde linear threading technique. Additional clinical considerations are discussed.

Identification of a suitable layer for injecting calcium hydroxylapatite fillers in the hands

Hand rejuvenation has become increasingly popular in esthetic medicine. Hand rejuvenation with injectables remains challenging, and there are no established practice guidelines. The calcium hydroxylapatite (CaHA) filler injection is currently one of the most common procedures. This study aimed to identify the layer of the hand dorsum that is lifted by skin pinching and to identify the layer where an injectable filler would be placed based on the anatomical study and ultrasound findings. The anatomic layers of the cadaveric hands were examined using the skin pinching method. Anatomic dissections and histological examinations were performed on four fixed and five fresh cadaveric hands to reveal the anatomical layers in which the CaHA filler was administered. Furthermore, 20 patients were treated with the CaHA filler, and the Doppler ultrasound was used to reveal the proper anatomical layers for filler placement. The study of the cadaveric hands showed that skin pinching can ensure safe entry points and can guide the cannula into safe planes without compromising the large superficial veins. A filler injection with skin pinching in cadaveric hands demonstrated that the filler was introduced primarily in the dorsal intermediate lamina where the veins are present. This was further confirmed by ultrasound findings. The dorsal intermediate lamina, which has the veins is a relatively loose structure, and the cannula was moved along this space. When the layer is stretched by skin pinching, the veins run underneath. The dorsal intermediate lamina is the appropriate layer to inject the filler.

Management of periorbital hyperpigmentation: An overview of nature-based agents and alternative approaches.

Periorbital hyperpigmentation (POH) is a common dermatological condition that presents as dark periorbital area beneath the lower eyelids, and it is commonly found in females belonging to the age group of 16 to 45 years. The data presented in this review include studies conducted on patients with a clinical/histological diagnosis of POH or melasma. Many diverse topical depigmenting agents comprising an array of naturally obtained actives such as arabinoxylans, α-arbutin, asiaticoside, azelaic acid, beta-carotene, boswellic acid, caffeine, chrysin, curcumin, cyanidin-3-glucoside, d-glucoronic acid, dihydrochalcone, dipalmitoyl-hydroxyprolene, fucoxanthin, genistein, glabridin, b-glucogallin, hyaluronic acid, lactic acid, lycopene, niacinamide, pycnogenol, retinol, salidroside, and xymenynic acid demonstrated significant benefits in the management of POH. An exhaustive literature search revealed that other techniques such as blepharoplasty, carboxytherapy, calcium hydroxylapatite fillers, tear trough implant, Q-switched ruby laser, medicated tattoo, fat transfer, micro-needling, chemical peels, nitrogen plasma skin regeneration, intense pulsed light, and radiofrequency have been evaluated and reported to be beneficial in the treatment of POH. The use of topical depigmenting agents is the most widely reported method in the clinical management of POH. Of these, α-arbutin, caffeine, cyanidin-3-glucoside, and dihydrochalcone are reported to exhibit significant benefits. Combination products containing a blend of actives are reported to be better than single active containing products. This review aims to provide a comprehensive perspective on the role of several topical actives in the modulation of melanin and tyrosinase biosynthesis pathway involved in the complex pathophysiology of POH. It also presents the advantages of combination products and other alternative therapies used in the management of POH.

Combination of Calcium Hydroxylapatite Diluted With Normal Saline and Microfocused Ultrasound With Visualization for Skin Tightening.

Background/Objectives: Treatment options for the correction of age-related changes in skin include the use of energy-based devices and dermal fillers. In this study, we evaluate the clinical efficacy and tolerability of microfocused ultrasound with visualization (MFU-V) and injectable calcium hydroxylapatite (CaHA) filler diluted with normal saline, for the correction of age-related changes and to assess patients' satisfaction with this combination therapy. Methods: This was a randomized, split-face, comparative clinical study and immunohistochemical analysis in 20 subjects with indications for lower face, neck and décolleté lifting. Over five visits, CaHA diluted with normal saline (1:2) was injected subdermally in the lower third of the face, neck and décolleté, and lower abdominal quadrant. MFU-V was performed on the lower third of the face, neck, and décolleté, and the right lower abdominal quadrant. Results: Upon baseline examination, the age-related changes were quantified as follows: marionette lines score 2.47 ± 0.8, jawline contour score 2.2 ± 0.7 and neck score 2.1 ± 0.7 points; and after 15 months, they changed to 1.8 ± 0.7 (P≤0.00003), 1.89 ± 0.56 (P≤0.005), and 1.7 ± 0.6 (P≤0.005) points, respectively. The procedures were well tolerated, and subject satisfaction was high. Conclusions: The injections of CaHA in combination with MFU-V treatment stimulated neoangiogenesis, led to the increased synthetic activity of cells, a marked increase in collagen and elastin fibers, and remodeling of both the superficial and deep layers of the dermis. An improvement in the severity of age-related changes was observed in all areas studied. J Drugs Dermatol. 2020;19(4):405-411. doi:10.36849/JDD.2020.4625.

Facial Rejuvenation Using a Mixture of Calcium Hydroxylapatite Filler and Hyaluronic Acid Filler.

Calcium hydroxylapatite filler is a popular dermal filler, as it provides long-lasting results. However, it sometimes undergoes unexpected early volume loss, due to rapid gel absorption before neocollagenesis. To compensate for this phenomenon, hyaluronic acid filler was added to calcium hydroxylapatite filler for injection as a mixture. Twenty-five patients who scored 1 or 2 on the Merz 5-point scale for the nasolabial fold and jawline were injected with 3.0 mL of the mixture. The mixture was prepared with 1.0 mL of hyaluronic acid filler, 0.5 mL of lidocaine, and 1.5 mL of calcium hydroxylapatite filler. A visual analog scale (VAS) and the 5-point global satisfaction scale (GSS) were used for objective and subjective assessments. In a subset of patients, for histologic analysis, 0.1 mL of the mixture and 0.1 mL of only calcium hydroxylapatite filler were injected into the right and left postauricular areas, respectively. The histologic analysis was performed 6 months after implantation. The mean VAS and GSS scores for both sets of wrinkles were above "fair" at every follow-up, including at short-term and long-term periods. The skin biopsies from both postauricular areas from selected patients showed increased dermal collagen bundles without inflammation. The mixture of calcium hydroxylapatite filler and hyaluronic acid filler maintained constant volume with high satisfaction, as hyaluronic acid filler compensated for the unexpected early volume loss of calcium hydroxylapatite filler. This procedure can be applied safely, and it is also convenient, because no retouching procedure is needed.

Multilayered injection of calcium hydroxylapatite filler on ischial soft tissue to rejuvenate the previous phase of chronic sitting pressure sore.

IntroductionDuring a sitting position, the pressure distribution is located below the ischial tuberosity. Many women have skin atrophy on the ischial area. To treat atrophic changes on the skin above the ischium, volumization and improving skin texture are acquired simultaneously. Two methods of automatic and manual injections using a hard filler with a stitmulating effect were administered respectively to both the dermis and subdermis layers. A biopsy study using various straining evaluated histological tissue reactions after the filler injections.MethodsThis study focused on rejuvenating soft tissue on the atrophic ischeal areas, as described by the author as the previous phase of chronic sitting pressure sore, by using the multi-layered injection of calcium-hydroxylapatite (CaHA) filler. Sixteen women (mean, 38.5 years) were treated from 2012 January to 2019 April. Prior to the injection, 1.5cc of Radiesse® (calcium hydroxylapatite filler; Merz, Germany) was diluted with 1cc of normal saline and 0.5cc of lidocaine, and 3cc of filler mixture (1:1 dilution) was made. All subjects received the intradermal injection and multi layered subdermal injection with 2.5cc of diluted CaHA filler. A second session for booster treatment was performed at 6 months using the same method. Photography was taken by a camera and a dermascope observation before and 7 months after. Before and 7 months after the first injection, soft tissue depression, skin discoloration, and roughness were assessed. Standard deviations and coefficients of variation were also calculated for changes in depression, discoloration and roughness after the treatment. Biopsy specimens (3×5 mm) were taken from three patients 7 months after the first session. The specimens were analyzed using various stainins.ResultsThe improvements of skin quality, skin fold, and roughness were visible at physical examination, medical photography and also at high-resolution dermascope examination in all patients. Post-treatment the depressed amounts on the ischial areas reduced with increased volume.ConclusionDepressed soft tissue and skin folds on ischial areas were significantly improved by volumization of subdermal filler injection. The skin quality, roughness, and pigmentation on ischial areas improved, and these improvements may be caused by intradermal micro-droplet injections of CaHA filler which may be influenced by neocollagenesis by numerous fibroblasts and increased micro-blood circulation (neovascularization). This is the first article to show the scientific evidence of neocollagenesis and tissue reaction after an injection of CaHA filler in the dermis, especially using various histological staining and to show various stages of inflammation and foreign body reaction around CaHA particles. Numerous fibroblasts were present around CaHA particles, but plasma cells were not found. Interestingly a few eosinophils were found around CaHA filler. After a significant period of time, multi-layered injections of diluted CaHA tightened and remodeled atrophic ischial skin. The multi layered injection approach was safe and effectively treated ischial soft tissue atrophy without significant side effects, such as infection or delayed swelling or lumps.

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®).