Search

Background: Injectable biostimulators are widely used to improve facial aging signs. This study was performed to compare the genetic pathways affected by 2 different injectable biostimulators., Methods: Randomized 13-week study (n = 21) comparing gene expression after poly l-lactic acid (PLLA-SCA) and calcium hydroxylapatite (CaHA-R) injections (baseline [BL] and Day 28) as treatment of nasolabial fold wrinkles. Punch biopsy was performed at BL and day 90; RNA was isolated, gene expression was analyzed, and bulk RNA sequencing performed. Data from both pathways were studied using the Search Tool for Retrieval of Interacting Genes/Proteins and Reactome databases., Results: Analysis at Day 0 and Day 90 showed differing gene regulation for PLLA-SCA and CaHA-R (after accounting for minor differences at BL, p < .05 at Day 90 for 9-12 genes). PLLA-SCA uniquely correlates with genes involved in adipocyte regeneration, while CaHA-R did not affect these genes. Clinically, this could translate to healthy fat replacement with an enhanced effect beyond the improvement of the collagen structure and a longer-lasting effect with PLLA-SCA. Furthermore, the adipokines that appear to be upregulated are regenerative with a positive impact on skin health., Conclusion: PLLA-SCA has a novel and unique signature, which supports a potential regenerative mechanism of action through its role in the modulation of adipocyte function., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Calcium hydroxyapatite (CaHA) dermal filler has been increasingly used in facial aesthetic procedures., Objective: To investigate clinical and histological changes associated with calcium hydroxyapatite (CaHA) dermal filler in the orofacial region., Materials and Methods: Forty-eight female Wistar rats were divided into CaHA and control groups. The material was applied in the ventral tongue and the submandibular region; the animals were euthanized after 7, 30, and 90 days., Results: After 7 days, yellowish nodules with a firm consistency were observed on the tongue. In 2 animals, the material migrated to the base of the tongue. Histopathological examination revealed CaHA spheres surrounded by an infiltrate, predominantly composed of macrophages. In the CaHA group, the percentage of collagen in the tongue and dermis was higher compared with the control group ( p < .05) at both 30 and 90 days. The thickness of the epidermis/dermis was also higher in the CaHA group ( p < .05). In 5 submandibular glands containing material, areas of edema and hyperemia were observed, along with infiltrates of neutrophils, lymphocytes, and plasma cells. Changes in the morphology of ducts and acini in adjacent regions were evident., Conclusion: CaHA exhibits satisfactory properties for filling and collagen biostimulation in the tested regions. Further studies are required to explore the potential for migration and the glandular alterations., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

To realize high-quality vascularized bone regeneration, we developed a multifunctional hydrogel (SHPP-ZB) by incorporating BMP-2@ZIF-8/PEG-NH 2 nanoparticles (NPs) into a sodium alginate/hydroxyapatite/polyvinyl alcohol hydrogel loaded with PDGF-BB, allowing for the sequential release of angiogenic and osteogenic growth factors (GFs) during bone repair. ZIF-8 served as a protective host for BMP-2 from degradation, ensuring high encapsulation efficiency and long-term bioactivity. The SHPP-ZB hydrogel exhibited enhanced mechanical strength and injectability, making it suitable for complex bone defects. It provided a swelling interface for tissue interlocking and the early release of Zn 2+ and tannin acid (TA) to exert antioxidant and antibacterial effects, followed by the sequential release of angiogenic and osteogenic GFs to promote high-quality vascularized bone regeneration. In vitro experiments demonstrated the superior angiogenic and osteogenic properties of SHPP-ZB compared to other groups. In vivo experiments indicated that the sequential delivery of GFs via SHPP-ZB hydrogel could improve vascularized bone regeneration. Further, RNA sequencing analysis of regenerative bone tissue revealed that SHPP-ZB hydrogel promoted vascularized bone regeneration by regulating JUN, MAPK, Wnt, and calcium signaling pathways in vivo. This study presented a promising approach for efficient vascularized bone regeneration in large-scale bone defects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Calcium hydroxyapatite (CaHA)-carboxymethylcellulose (CMC)+ has unique properties that make it optimal for lifting, contouring, and defining the jawline. This long-term follow-up of a randomized, multicenter, rater-blinded trial reports efficacy and safety of CaHA-CMC(+) through 48 and up to 60 weeks post-treatment., Methods: Eligible patients were randomized (2:1) to the treatment or the control/delayed treatment group to receive CaHA-CMC(+) injections in both jawlines. While touch-ups were permitted 4 weeks post-treatment for both groups, only the treatment group was eligible for optional retreatment after 48 weeks. The primary outcome was ≥1-point improvement on both jawlines on the Merz Jawline Assessment Scale (MJAS); secondary endpoints included the Subject Global Aesthetic Improvement Scale (SGAIS) among others. Post hoc analysis included pooling up to 48-week data from the combined treatment and control/delayed groups and 60-week data for the treatment group., Results: Overall, 175 received treatment. MJAS responder rates were 77.9%, 78.7%, and 62.9% at 12, 24, and 48 weeks post-treatment, respectively. Responder rate on the MJAS at 60 weeks was 74.6% for those who received retreatment and 43.5% for those patients who received only the initial and touchup treatments. SGAIS scores demonstrated 93.4%, 85.6%, and 68.5% of patients rated themselves very much improved after 12, 24, and 48 weeks, respectively. Adverse events consisted of procedure or CaHA-CMC(+)-related events that were mostly resolved and overwhelmingly mild., Conclusions: CaHA-CMC(+) produced clinically meaningful and long-lasting improvements in jawline contour and was well tolerated in patients through 60 weeks., Trial Registration: ClinicalTrials.gov Identifier: NCT03583359., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

In this study, we developed scaffolds materials with microspheres to form a double sustained release system.Chitosan/nano-hydroxyapatite (CS-HA) was used as a drug carrier to construct a sustained-release system for Bone morphogenetic protein-2(BMP-2) and Vancomycin (VAN). Furthermore, VAN and BMP-2 loaded microspheres (Ms) were prepared by the emulsion ultrasonic method.The resultant composites were characterized by Scanning electron microscope (SEM), compressive strength, porosity, and biodegradation. The characterization results showed uniform porous and rough surface, enhanced thermal stability, and highest compressive strength ((1.912 ± 0.012) Kpa, the surface of the two microspheres was slightly folded and showed a regular spherical shape.The loading rate of BMP-2 was (59.611 × 10 -4  ± 0.023 × 10 -4 )% and the encapsulation rate was (6.022 ± 0.005)%. The release rate of vancomycin and BMP-2 was 57.194% and 12.968% respectively. Osteogenic differentiation of Bone marrow mesenchymal stem cells (BMSCs) was confirmed by alkaline phosphatase quantification. The deposition of late osteogenic markers (calcium phosphates) detected by Alizarin red, which indicated extracellular matrix mineralization. The results showed that BMP-2/VAN in CS-HA hydrogel successfully achieved the sequential release of the double drugs, which could benefit bone regeneration., (© 2024. The Author(s).)

Background: Treating signs of aging requires skeletal restructuring, facial contour redefinition, and sagging skin treatment. Hence, HarmonyCa® was recently introduced in the market, combining hyaluronic acid and hydroxyapatite. However, there are no studies evaluating the physicochemical properties of this material., Purpose: To analyze the morphology, rheology, and clinical applicability of HarmonyCa® over a 180-day follow-up., Methods: A morphological analysis with scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) and rheology measurement with a rheometer. The clinical applicability analysis included a tissue ptosis patient who received the product and was reassessed 30 and 180 days after applying HarmonyCa®., Results: SEM and EDS analyses showed two distinct morphologies related to hydroxyapatite and hyaluronic acid. The rheological measurements of HarmonyCa® showed G' and G″ of 51.56 and 44.01 Pa, respectively. The tan δ value was 0.8503, and G* was 108.1 Pa. The clinical outcomes were satisfactory., Conclusion: HarmonyCa® presents a good synergy between hyaluronic acid and hydroxyapatite. Also, the rheological analysis showed moderate viscosity for the product, with a clinical indication for subcutaneous application., Level of Evidence Iv: 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 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: Vascular adverse events (VAEs) occurring during injections of soft-tissue fillers are still considered a challenging issue for both patients and practitioners. Hyaluronidase can dissolve hyaluronic acid (HA)-based soft-tissue fillers during a VAE. For VAEs induced by non-HA fillers, the absence of an "antidote" is regarded as exceptionally challenging., Methods: This multicenter study describes a case series of three VAEs induced by non-HA fillers, for which ultrasound-guided hyaluronidase injections were incorporated into the treatment approach., Results: Two cases of calcium hydroxylapatite and one case of poly-L-lactic acid-induced VAEs are described, all of which were resolved without necrosis or scarring using a treatment approach with ultrasound-guided hyaluronidase injections., Conclusions: Unlike the mechanical hypothesis, which assumes filler particles travel antegrade to block arterioles in a large skin area, we hypothesize vasoconstriction as the pivot in VAEs. Filler injection-induced spasms could lead to long-lasting vasoconstriction of the perforator arteries stemming from the central facial arteries. Our results underscore that perforasome vasoconstriction might be the leading cause of the ischemia and subsequent necrosis in VAEs and that relaxation of these perforasomes, rather than dissolving the filler material, resolves the clinical symptoms associated with VAEs., (© 2024 the International Society of Dermatology.)

Filler-induced alopecia is a transient alopecia characterized by localized hair loss and often attributed to vascular compromise following dermal filler injections in facial regions. Although an uncommon phenomenon, the rising incidence of filler-induced alopecia underscores the importance of understanding and managing this condition. We performed an extensive PubMed review of articles reporting filler-induced alopecia and summarizing the implicated filler types, injection areas, hair loss patterns, symptom onset, course progression, treatments, and prognosis. Hyaluronic acid injections were the most implicated in filler-induced alopecia cases, with calcium hydroxylapatite and autologous fat less frequently associated. No cases involved other dermal filler types. Although recovery times varied depending on the treatment, hyaluronidase (HAase) injections rapidly restored near-normal hair density within 3-4 months. Minoxidil and platelet-rich plasma play a more minor role in restoring hair growth but may be used as adjuncts with HAase to facilitate hair growth. Finally, alternative interventions like intralesional triamcinolone, warm compresses, and nitroglycerin warrant exploration, given limited robust clinical data. Our study promotes awareness of filler-induced alopecia's rising incidence and offers practical insights and evidence-based recommendations for effective management. By equipping dermatologists with this knowledge, our aim is to improve patient outcomes and reduce adverse events in filler-based procedures., (© 2024 the International Society of Dermatology.)

Background: The facial aging process entails alterations in the volume, shape, and texture of all skin layers over time. Calcium hydroxyapatite (CaHA) is a well-established safe skin filler with unique properties to resolve some skin alterations by stimulating neocollagenesis. The vectoral-lift (V-lift) technique targets the global repositioning of facial structures by addressing distinct anatomical injection planes. It includes deep facial augmentation with Radiesse Plus TM to retain ligament restructuring and superficial subcutaneous enhancement with diluted Radiesse Duo TM . Herein, we present cases that illustrate the use of this approach., Methods: This pilot study enrolled 36 participants (33 women and three men; ages 37-68 years) in a Brazilian clinical setting, and all patients underwent a single treatment. Photographs were taken at rest, in frontal and oblique views, before injection, and 90 days after treatment., Results: Treatment resulted in elevation of the upper and middle face, notable improvements in the infraorbital hollow, and adjustment of the mean facial volume., Conclusions: The V-lift technique is a three-dimensional pan-facial treatment that relies on ligament support and face vectoring to obtain a lifting effect and facial contour restoration. It encompasses deep facial augmentation involving the use of Radiesse Plus TM for restructuring and retaining ligaments and Radiesse Duo TM for superficial subcutaneous enhancement. This approach targets a global repositioning of the facial structures by addressing distinct anatomical injection planes. It achieves a repositioning of the overall facial anatomy without requiring a substantial volumetric expansion., Level of Evidence Iv: 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 ., (© 2024. The Authors.)

Objective: The aim of the present study is to evaluate the efficacy of phonosurgical corrective approaches based on injection laryngoplasties and pharyngoplasties followed by speech therapy for voice restoration after unsatisfactory phonatory results of open partial horizontal laryngectomies., Methods: Ten patients with not satisfying phonatory results despite speech therapy after type II or type III open partial horizontal laryngectomies (OPHLs) were included. Each patient underwent a voice restoration program based on phonosurgery (injection laryngoplasty and/or injection pharyngoplasty) with hyaluronic acid and/or calcium hydroxyapatite, followed by post-surgical voice rehabilitation. Voices were recorded and analysed through spectrographic, aerodynamic, perceptual, laryngoscopic and self-assessment evaluations before the treatment (T0), after 1 month (T1) and after three months (T2)., Results: Significant improvements in the patients voices were found between T0, T1 and T2 concerning acoustic, perceptual, aerodynamic, laryngoscopic and self assessment evaluations., Conclusions: The results of the present study support phonosurgical injection procedures followed by speech therapy as an effective strategy for voice restoration after type II or type III OPHLs in selected patients., (Copyright © 2022 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Microneedling is used to enhance transcutaneous drug delivery. However, the extent to which microneedling devices impact filler delivery and whether this varies by filler type, microneedling device type, and treatment sequence is not known., Objective: To histologically assess and quantify the delivery of commonly used fillers through microneedling, using both a microneedling pen and a microneedling roller. In addition, the authors investigated whether there is a variation in filler delivery based on the sequence of microneedling in relation to topical filler application., Methods: Ex vivo human abdominal skin samples were subjected to microneedling pen or microneedling roller treatment. Black tissue marking ink, hyaluronic acid, poly- l -lactic acid, or undiluted calcium hydroxyapatite was topically applied before or immediately after microneedling treatment., Results: Histological evaluation revealed a notable presence of black ink within channels formed by both microneedling treatments (15.5%-98.1%), whereas there was limited presence of the various filler types tested (0%-6.6%) in all settings. Topical application before microneedling treatment led to relatively higher filler/ink deposition within the channels formed by the microneedling treatments compared with topical application after microneedling., Conclusion: Transcutaneous delivery of fillers was not significantly helped by microneedling treatment, whereas the microneedling devices demonstrated effective delivery of an aqueous solution., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Complications of temporary and permanent fillers have been extensively studied. However, there is a lack of comparative data regarding poly-L-lactic acid (PLLA), calcium hydroxyapatite (CaHA), and polycaprolactone (PCL) known as collagen biostimulators., Aims: This study addressed the complications of collagen biostimulators concerning their diagnosis, type of product, treatment, and monitoring., Patients/methods: An electronic questionnaire was sent to Brazilian dermatologic ultrasound experts to identify complications related to biostimulators. The type of biostimulator, location of application, number of vials injected, application plan, time between injection treatment and complication, injector profile, treatment, and prognosis were assessed., Results: Fifty-five cases were identified, of which 49.1% were caused by PLLA-Elleva®, 23.6% by CaHA (alone or combined with hyaluronic acid), 20.0% by PLLA-Sculptra®, and 7.3% by PCL. The most affected area was the face (72.7%), with nodules being the most common clinical form (89.1%), generally occurring late (60.0%) (>1 month). Only one case was injected at an incorrect depth (musculoaponeurotic system-SMAS). Despite several treatments, including saline (45.5%), hyaluronidase (25.5%), diluted corticosteroids (23.6%), and energy-based devices (10.9%), only five cases showed complete resolution. Hyaluronidase was beneficial in complications related to fillers when there was an association of calcium hydroxyapatite with hyaluronic acid (p < 0.01)., Conclusions: Complications from collagen biostimulators were more common on the face, typically manifesting about 1 month after treatment. These issues seemed to be related more to the properties of the products rather than inadequate technique. Furthermore, hyaluronidase demonstrated efficacy only in cases where there was an association with HA., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Carbon dots (CDs) are the research hotspots in antimicrobial applications. Also, due to the importance of calcium ions in skin regeneration, mesoporous hydroxyapatite nanoparticles (mHAP NPs) were prepared. This study aimed to evaluate the wound healing efficiency of both CD and mHAP NPs simultaneously., Methods: We doped Fluorine (F) and Copper (Cu) in CDs to prepare Cu*F-doped CDs (Cu.CDs). For the rapid release of calcium ions, a novel double-surfactant system (CTAB/F-127) was used for the synthesis of mHAP NPs. Then, we loaded both Cu.CDs and mHAP NPs simultaneously into the chitosan (CTS) gel., Results: The released calcium for mHAP NPs prepared using CTAB/F-127 was proved about 30 % higher than that prepared using only CTAB, after one day. The BET-specific surface area for mHAP NPs prepared using CTAB/F-127 was 23.17 % more than that prepared using only CTAB. This high porosity improves wound exudate absorption. Rheological analysis showed that the addition of both mHAP NPs and Cu.CD decreases the viscosity of CTS gel and thereby makes it suitable for topical applications. CTS gel containing mHAP + Cu.CDs indicated exceptional antibacterial properties even without light and/or H 2 O 2 with an inhibition zone diameter of 35 and 17 mm for E. coli and S. aureus species, respectively. CTS gel containing mHAP + Cu.CDs also showed significantly higher wound closure efficacy, greater inflammation inhibition, and better re-epithelialization than the other groups in rats with full-thickness skin wounds., Conclusion: The CTS gel containing both Cu.CD and mHAP NPs can be proposed as a new therapeutic gel for wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Summary What is this article about? A study (ClinicalTrials.gov identifier: NCT03583359) that tested whether an injectable filler treatment called calcium hydroxylapatite with lidocaine, or CaHA (+), could improve the shape of the jawline. How was the study in this summary conducted? Loss of jawline shape is a change to jawline appearance, like sagging or deflating, that occurs as people get older. A total of 123 participants received CaHA (+) injections on day 1 of the study (immediate treatment). Fifty-seven participants did not receive CaHA (+) until week 12 (delayed treatment). Jawline shape at week 12 was rated on a five-point scale (0 = no loss of shape or volume; 4 = extreme loss). Researchers also looked at participants' satisfaction and self-reported improvement, ratings of how old participants thought they looked, and side effects. What were the results of the study? In the immediate treatment group, 76% of participants had improvement in jawline shape at week 12 (compared with 9% of participants in the delayed treatment group), which typically lasted approximately 8 months, and 94% self-reported improvement in jawline appearance. The participants were more satisfied with their jawlines and reported looking approximately 3 years younger at week 12 compared with before treatment. Regardless of sex or skin tone, side effects were categorized as mostly mild or moderate reactions, like lumps or bruising, at the site where CaHA (+) was injected. What do the results of this study mean? The results showed that CaHA (+) injections improved jawline shape in most participants and caused only mild or moderate side effects regardless of sex or skin tone, suggesting that CaHA (+) is safe and works well for diverse groups of patients. Who should read this article? This summary is for patients and others interested in learning about how CaHA (+) works, its safety, and its ability to improve jawline shape. Who sponsored this study? The study was sponsored by Merz North America, Inc.

Background: Dermal fillers are widely used for facial rejuvenation and esthetic enhancement, offering temporary solutions for aging and volume loss. Despite their general safety, a rare but severe complication associated with these fillers is visual impairment, including blindness. This underscores the need for a thorough understanding of risks associated with various filler materials. Historical cases of blindness following filler injections date back to 1963, with increasing reports linked to the expansion of the cosmetic filler industry. While hyaluronic acid (HA) and autologous fat have been extensively studied, other fillers such as calcium hydroxylapatite and poly-l-lactic acid (PLLA) are less understood., Objective: This systematic review aims to address gaps in the literature by providing a comprehensive overview of visual impairment caused by fillers other than HA and autologous fat. We systematically examine the prevalence, causes, clinical features, and treatment outcomes associated with these less common fillers., Materials and Methods: A comprehensive literature search was conducted across databases including PubMed, Scopus, and Google Scholar using terms related to visual impairment and dermal fillers. Studies published between 2014 and 2021, including observational studies and case reports, were included. Studies were selected based on predefined inclusion and exclusion criteria, and a PRISMA flow diagram was used to illustrate the study selection process., Results: The review identifies and summarizes cases of visual impairment associated with calcium hydroxylapatite, poly-d,l-lactic acid (PDLLA), and PLLA fillers. Key findings reveal that visual impairment following these fillers is rare but can occur suddenly or within a few days of the procedure. Cases of delayed onset up to two weeks are also noted, emphasizing the need for extended post-procedure monitoring., Discussion: The review highlights unique insights into the risks associated with non-HA fillers, such as the heightened risk in the periorbital region and other facial areas. It explores mechanisms of complications, including retrograde flow of emboli leading to retinal ischemia. The discussion also covers emergency protocols and preventative measures, providing valuable guidance for managing and mitigating risks., Conclusions: Visual impairment caused by fillers other than HA and autologous fat, while rare, represents a serious complication that requires careful attention. This review contributes new perspectives on the differential risks of various fillers, symptom onset variability, and anatomical risk factors. Emphasizing the importance of proper patient selection, technique, and monitoring, it calls for further research to better understand and prevent these complications, ultimately aiming for safer and more effective use of soft-tissue fillers.

Osteoporosis, a prevalent systemic bone metabolic disorder, primarily affects postmenopausal women and is characterized by increased bone fragility and a heightened risk of fractures. The efficacy of current osteoporosis treatments is often limited by non-specific drug targeting and undesirable off-target skeletal side effects. To address this challenge, we have developed a novel hydroxyapatite-responsive drug delivery system. This system utilizes a self-assembled p-phosphonatocalix[4]arene tetradodecyl ether (PC4A12C), engineered to specifically target and sustain the release of osteoporosis medication at sites of bone remodeling. Our focus centers on icariin (ICA), a drug known for its potent osteogenic properties and minimal adverse effects. In vitro, ICA-loaded PC4A12C (ICA@PC4A12C) demonstrated enhanced proliferation, differentiation, and mineralization in bone marrow mesenchymal stem cells (BMSCs). In vivo, ICA@PC4A12C exhibited superior efficacy in specifically targeting bone tissue, ensuring a controlled and slow release of icariin directly within the bone environment. In an osteoporosis mouse model, treatment with ICA@PC4A12C showed notable enhancement in osteogenic activity and a significant increase in bone density compared to ICA alone. These results demonstrate the potential of PC4A12C as an effective drug carrier in the development of advanced antiosteoporotic drug delivery systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Hand aging is a prevalent concern characterized by the atrophy of local soft tissues and increased visibility of vessels and tendons. Hyaluronic acid (HA) and calcium hydroxyapatite (CaHA) are well-established treatments for addressing this issue. While hybrid filler containing HA and CaHA has been proposed for facial rejuvenation, studies investigating its efficacy for hand rejuvenation are lacking., Objective: This study aims to assess the safety and efficacy of a premixed hybrid filler containing calcium hydroxyapatite (CaHA) and hyaluronic acid (HA) for hand rejuvenation., Methods: A prospective, double-blind, controlled trial was conducted. The control arm (CA) received conventional subdermal treatment with CaHA at a 1:1 dilution. The intervention arm (IA) underwent hybrid treatment, consisting of CaHA at a 1:1 dilution combined with 1 ml of low-density HA. Evaluation was performed subjectively using the Global Aesthetic Improvement Scale (GAIS) and the Manchester Hand Grading System (MHGS), and objectively using cutometry, corneometry, and ultrasound., Results: Both the CA and the IA exhibited high rates of patient satisfaction and satisfaction as assessed by blinded evaluators. Although numerical superiority was observed in the IA, no statistical difference was found between the two groups. Significant improvements in hydration, elasticity, and skin thickness were observed in both arms, with no discernible difference between them. Greater ultrasound echogenicity was noted in the IA, which, as indicated by existing literature, may suggest enhanced biostimulation. No adverse effects were reported in either arm., Conclusion: Premixed filler containing HA and CaHA for hand rejuvenation appears to be a safe and effective approach., Level of Evidence I: 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 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: Radiesse, a widely utilized calcium hydroxylapatite (CaHA) dermal filler, has shown effectiveness in soft tissue augmentation and regeneration. As with all dermal fillers, the potential for nodules may arise. Understanding the pathogenesis of these nodules and exploring effective treatment methodologies are crucial for optimizing patient outcomes., Objectives: A literature search was carried out to identify published literature documenting reversal of CaHA nodules. After identification, a consensus panel developed a structured approach, denoted by levels, for applying such reversal methods., Methods: This concise review presents an algorithmic approach to addressing CaHA focal accumulations (noninflammatory nodules) based on invasiveness, cost, and potential risks based on published literature., Results: Level 0 involves no intervention, relying on natural degradation for asymptomatic nodules. Level 1 interventions utilize mechanical dispersion techniques, including massage and in situ dispersion, which have demonstrated high success rates, cost effectiveness, and minimal invasiveness. Level 2 introduces alternative modalities such as pharmacological treatments with 5-fluorouracil and corticosteroids, lasers, and experimental approaches. Level 3 represents last-resort options, including calcium-chelating agents, manual removal, and surgical excision., Conclusions: The article offers a structured approach to managing CaHA focal accumulations., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society.)

Background and Objectives : The facial skin defects associated with aging are common concerns in the aging population. Hyaluronic-acid-based intradermal gels have established themselves as safe and effective treatments for addressing these concerns. Recently developed enriched products aim to enhance the efficacy of these gels, yet their effectiveness lacks thorough validation in the existing literature. Materials and Methods : In this retrospective analysis, we investigated the outcomes of intradermal gel treatments in 103 patients with soft tissue defects. This study included three groups: 35 patients received amino-acid-enriched hyaluronic acid gel, another 35 were treated with hydroxyapatite-enriched hyaluronic acid gel, and the remaining 33 underwent hyaluronic acid treatment only. The efficacy of the treatments was assessed using the Global Aesthetic Improvement Scale (GAIS) score, while patient satisfaction was gauged through a detailed questionnaire. Any adverse event was monitored. Results : The treatments demonstrated remarkable efficacy, as evidenced by mean GAIS scores of 1.714 points for those treated with amino acid-enriched hyaluronic acid gel, 1.886 points for individuals receiving hydroxyapatite-enriched hyaluronic acid gel, and 1.697 for those treated with hyaluronic acid alone, all showing statistical significance ( p < 0.0001). Patient satisfaction was very high. Significantly, there were no recorded instances of major adverse events. Conclusions : Hyaluronic gels, particularly those enriched with amino acids and hydroxyapatite, are effective and safe interventions for addressing facial skin aging defects. They serve as valuable tools in mitigating age-related blemishes and contribute to the overall improvement of skin aesthetics.

Competing Interests: The authors have no financial or conflicts of interest to disclose.

A filler composed of calcium hydroxylapatite and carboxymethylcellulose gel (CaHA/CMC) has been shown to possess biostimulatory and skin-tightening properties that have been applied not just to the face but also to the body to boost rejuvenation. Recently, evidence and recommendations for CaHA/CMC treatment of the face have been provided, but they are still lacking in terms of body treatment. This article aims to perform a systematic review of the literature on CaHA/CMC applications on the body and provide evidence from the literature. Currently, the only FDA-approved indication on the body is treating the hands and a recent European Union Medical Device Regulation approval has been released for decolletage treatment. The application of hyperdilutions on the neck, feet, arms, thighs, abdomen, and other body parts has been proven to provide a skin-tightening effect. However, despite their wide use with a good safety profile in clinical practice, recent trends and guidelines of diluted and hyperdiluted CaHA/CMC have yet to be supported by randomized controlled trials., (© 2024 the International Society of Dermatology.)

Background: The signs of aging seem to be more visible on the neck compared to other locations, especially if a patient has already gone through facial rejuvenation procedures. Treatment of the aging neck imposes a challenge to the clinician, since one single approach is usually not enough to achieve the desired result, requiring multiple injections and sessions, which apart from being painful for the patients, is time-consuming for the clinician., Aim: To describe the use of calcium hydroxyapatite, incobotulinum toxin type A and Cohesive poly-densified matrix hyaluronic acid diluted in the same syringe and injected in the same session for neck rejuvenation., Patients and Methods: Fifteen women, older than 18 years, with cervical skin flaccidity grade 1-4 in a previously validated 5-point rating scale (Dermatologic Surg, 2016; 42, S94), who sought neck rejuvenation were injected in this pilot study with a single session with a combined hybrid mixture of calcium hydroxyapatite, incobotulinum toxin type A, and Cohesive poly-densified matrix hyaluronic acid and followed up for 90-180 days., Results: At the 4-month post injection evaluation, 93.3% of the patients presented at least 1-grade improvement in the 5-point scale as evaluated by the investigator. No serious adverse events were reported, being most mild and transient in nature., Conclusion: CaHA, incoBonTA, and CPM-HA have complementary mechanisms of action and may be injected from the same syringe in the same session, boosting the final outcome, with high patient satisfaction, and ease of process for both patients and clinicians., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: The search for minimally invasive treatments for areas not covered by clothing, such as the arms, has increased, particularly to combat flaccidity resulting from factors such as aging and weight loss. This study evaluated the efficacy of calcium hydroxyapatite (CaHA), an injectable biostimulator, in improving flaccidity and hydration of the skin of the arms., Materials and Methods: Six women between 40 and 50 years old with visible signs of brachial flaccidity were selected. Calcium hydroxyapatite was injected into the arms in a 1:4 dilution (1.5 mL per side), with subjective evaluation based on the GAIS score and objective hydration analysis using corneometry., Results: After a single application of CaHA, there was a significant increase in skin hydration (12.2%), objectively assessed by corneometry. Patient and physician satisfaction was high, evidenced by visible improvements in photographs and by the GAIS score. No significant adverse events were reported, demonstrating the safety of the procedure., Discussion: Our clinical observations confirm the ability of CaHA to visibly improve arm flaccidity. In addition, hydration measures support previous histological studies demonstrating increases in dermal proteoglycans. Compared to other studies, the increase in skin hydration with CaHA was similar to those obtained with hyaluronic acid, suggesting comparable results with a more comfortable and less invasive technique., Conclusion: This study demonstrates the efficacy of CaHA in improving hydration of brachial skin after a single treatment. Despite the limitations of the sample size, the research contributes to the medical literature, highlighting the utility of the 3 mL CaHA presentation for brachial treatment with objective results in skin hydration., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: Calcium hydroxylapatite (CaHA) dermal filler is used for a variety of aesthetic treatments; however, the safety and effectiveness of diluted CaHA for the treatment of d&eacute;collet&eacute; wrinkles have not been established., Objective: To demonstrate the effectiveness and safety of diluted CaHA (Radiesse; 1:2 CaHA:saline) injection for the improvement of d&eacute;collet&eacute; wrinkles in females., Methods: Eligible females with moderate or severe ratings on the Merz Aesthetic Scale (MAS) Decollete Wrinkles - At Rest received up to 3 injection cycles of diluted CaHA either 8 weeks apart (3 injection cycles) or 16 weeks apart (2 injection cycles). Effectiveness was evaluated by improvement on the MAS. Adverse events were recorded over a 52 week period., Results: Sixteen weeks after the last treatment, the response rate (1-point improvement or greater) on the MAS Decollete Wrinkles - At Rest was 73.5% (P&lt;0.0001; pooled sample) for all patients. The use of diluted CaHA in the decollete also demonstrated a favorable safety profile., Conclusions: Diluted CaHA is a safe and effective treatment for the improvement of decollete wrinkles in females.J Drugs Dermatol. 2024;23(7):551-556.&nbsp; doi:10.36849/JDD.8261.

Background: Calcium hydroxylapatite-carboxymethylcellulose (CaHA-CMC) injectables have emerged as dual-purpose fillers with bioregenerative and direct filling capabilities., Aims: This study investigates the rheological properties of CaHA-CMC and its CMC carrier gel at various dilutions., Methods: The storage modulus (G'), loss modulus (G″), complex viscosity (η*), loss factor (tan δ), cohesivity, and extrusion force were evaluated for a range of CaHA-CMC aqueous dilutions with an oscillatory rheometer, drop weight testing, and force analysis, respectively., Results: Results revealed a significant decrease in G', η*, and increase in tan(δ) with increasing dilution, indicating a decline in the product's direct filling capabilities. Cohesivity decreased dramatically with dilution, potentially enhancing tissue biointegration and the product's biostimulatory effects. The CMC gel carrier displayed inelastic and non-resilient properties, with rheological changes differing from CaHA-CMC. Dilutional rheology was also correlated with previously published dilution-dependent biostimulatory data where hyperdiluted CaHA-CMC (>1:2) demonstrated a regenerative profile and diluted or hypodiluted mixtures retained meaningful filling properties and increased regeneration., Conclusions: These findings offer a continuum for tailoring the product's rheological profile to match specific tissue requirements. Customizable rheology allows CaHA-CMC to be tuned for either filling and contouring or optimal regenerative effects. Importantly, safety implications related to vascular occlusion suggest that dilutional rheomodulation decreases the risk of vascular events. In conclusion, this study highlights the significant impact of aqueous dilution on the rheological properties of CaHA-CMC and its carrier gel. The findings support the clinical application of tailored dilutions to achieve desired outcomes, providing versatility and safety for aesthetic applications., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Cellulite is a condition characterized by dimpling and contour irregularities in the gluteal and thigh regions, affecting an estimated 80-98% of postpubertal women. Innovative treatments for cellulite dimpling in the buttocks have gained popularity in recent years, seeking new solutions for a historically challenging condition. In this open-label, investigator-initiated, single-center, prospective clinical study, the authors sought to evaluate the safety and efficacy of diluted calcium hydroxylapatite (CaHA; Radiesse®, Merz Aesthetics, Raleigh, NC) for the treatment of cellulite dimpling in the buttocks of adult women., Methods: Subjects underwent three treatment sessions, receiving a total of 12 syringes of 1:1 diluted CaHA administered using a cannula-based subcision technique. Endpoints included the cellulite severity scale (CSS), the global aesthetic improvement scale (GAIS), subject satisfaction measured on a 5-point scale, and three-dimensional imaging analysis via the Quantificare 3D Track®., Results: Twenty-four subjects completed the study (mean age, 35 years; mean BMI, 26.88 kg/m 2 ; mean body fat percentage, 31.29%), and no serious complications were reported. Quantitative analysis at week 14 revealed a mean reduction of 54.0% in the number of visible dimples and 50.09% in dimple depth compared to baseline. The mean CSS score decreased by 4.29 points, representing a 43.92% improvement in cellulite severity from baseline (p < 0.0001). Both physician-assessed and subject-assessed GAIS ratings also demonstrated significant improvement, with 91.6% of subjects rating their cellulite appearance as "improved" or greater., Conclusion: The results of this study support the safety and efficacy of diluted CaHA for treating cellulite dimpling in adult women., Level of Evidence Ii: 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 ., Clinical Trials Registration: This study is registered with clinicaltrials.gov (ID: NCT05885035) and can be found at this link: https://clinicaltrials.gov/study/NCT05885035 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose-response, safety, efficacy, and the ability to combine exosome treatment as a "skin primer"-for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA., Methods: Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a "homing inflammatory environment" for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide-generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment., Results: Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen., Conclusions: Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome "priming of the skin" yielded enhanced skin quality faster than exosomes or CaHA alone., (© 2023 The Author. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Short-track speed skating (STSS) is an extreme sport in pursuit of extreme speed and explosive force. In such a sport, once athletes fall down, they are susceptible to serious cervical spine injury (CSI) under the inertia of high-velocity movement. Nanohydroxyapatite/polyamide 66 (NHP66) bioactive cage is a high-tech product of nanotechnology in the medical field in recent years. With a structure similar to that of human cortical bone, NHP66 bioactive cage has extremely high toughness and strength, which tailors to the needs of STSS., Objective: This study mainly analyzed the therapeutic effect of NHP66 on patients with CSI in STSS, aiming to provide new opportunities for the treatment of this patient population., Methods: A total of 51 patients with CSI treated in our hospital were enrolled, including 19 cases of short-track speed skaters (observation group) and 32 cases of car accidents, falls from heights, or collision injuries (control group). The relevant surgical indicators (operation time, intraoperative blood loss, etc.), the incidence of adverse reactions, the Cobb angle of cervical lordosis before and after surgery, and the fusion segment height of the cage were observed and compared between the two groups. Postoperative pain was evaluated by the visual analog scale (VAS), improvement of spinal cord injury was assessed by the American Spinal Cord Injury Association (ASIA) Impairment Scale, and bone fusion, bone subsidence, and other motor functions were assessed by the Japanese Orthopaedic Association (JOA) score rating system., Results: The operation time, intraoperative blood loss, and incidence of adverse reactions in the observation group were significantly lower than those in the control group. The Cobb angle of cervical lordosis and the fusion segment height of cage increased significantly higher in both groups after surgery. In addition, the VAS scores of the observation group 2 h and 3 d after operation were significantly lower than those of the control group. In terms of improvement of spinal cord injury, ASIA and JOA scores in the observation group were significantly higher than those before treatment and in the control group. There was no significant difference in bone fusion activity between the two groups., Conclusions: In this study, it is found through experiments that NHP66 has higher safety and application value than autogenous iliac bone, confirming that NHP66 can achieve significant results as a cage for anterior cervical decompression and iliac bone graft fusion and internal fixation in short-track speed skaters after CSI., Competing Interests: The authors report no conflicts of interest in this work., (Copyright © 2022 Xinming Yang et al.)

Introduction: Jawline augmentation with calcium hydroxylapatite has not yet been evaluated in a prospective study with a split-face design. This study aims to perform the first randomized controlled, split-face study on the efficacy and safety of calcium hydroxylapatite for jawline augmentation using the needle and cannula technique., Objective: To perform the first randomized controlled, split-face study on the efficacy and safety of calcium hydroxylapatite for jawline augmentation using the needle and cannula technique., Materials and Methods: This is a single-site, randomized, evaluator-blind trial enrolling a total of 10 healthy subjects with at least Grade 1 (mild) on a 4-point Jawline Scale. One side of the face was randomized to receive 1 to 2 syringes of calcium hydroxylapatite with lidocaine (total of 3 mL) for correction of wrinkles and folds along the jawline using both the cannula and needle method, and a balancing treatment will be performed 1 month later. Blinded investigator and subject evaluations will be performed immediately after treatment and at the 30-, 60-, and 90-day visits., Results: Ten subjects were enrolled and completed the trial. There was a improvement in the degree of wrinkling and skin sagging in the 4-point Jawline Scale, with an average of a 1.3-point improvement in the scale on the day of treatment and at the Day 30 visit, which remained improved greater than baseline after 3 months as graded by blinded investigators. The Clinician Global Aesthetic Improvement Score for the treated side versus control, as assessed by blinded investigators, demonstrated a improvement with a 2.3-point improvement on the 5-point scale, and by the final visit on Day 90, most patients had a much improved appearance from baseline., Conclusion: This study demonstrates that calcium hydroxylapatite is effective and safe for restoration and augmentation of the jawline using the unique needle and cannula technique., (Copyright © 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The objective was to evaluate the long-term voice outcomes in pa-tients with unilateral vocal fold paralysis treated with injection laryngoplasty using either cal-cium hydroxylapatite (CaHA) or hyaluronic acid (HA)., Methods: A single-centre retrospective study was performed. There were 75 patients with dysphonia due to unilateral vocal fold paralysis: injected with CaHA or injected with HA. We analysed Voice Handicap Index-30 (VHI), videostroboscopic images, auditory-perceptual (GRBAS), and acoustic measures (MDVP) in 6, 12, and 24 months after augmentation., Results: The mean change in VHI 24 months after augmentation was 29.14 in the CaHA group, and 22.88 in the HA group. There was an improvement of glottal gap 6, 12, and 24 months after augmentation in both groups. The GRBAS parameters were similar in both groups throughout the whole period. The MDVP pa-rameters decreased 6 and 12 months after augmentation and were similar in both groups. There were 4 patients augmented with CaHA (12.5%) who needed reintervention within 2 years of surgery and another 4 (9.3%) augmented with HA., Conclusion: This study demonstrates that there are no long-term differences in voice outcomes or number of reaugmentations for injection laryn-goplasty with CaHA compared to HA., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate physicochemical properties, dentin bonding, cytotoxicity, and in vivo pulp response of experimental self-adhesive composites tailored to direct pulp capping., Materials and Methods: Experimental composites were prepared with beta-tricalcium phosphate and hydroxyapatite nanoparticles adsorbed with simvastatin and glutathione added at 0% (control resin), 1 wt% (Res 1%), and 10 wt% (Res 10%). A commercial light-curable calcium hydroxide (Ca(OH) 2 ) (Ultra-Blend Plus) was used as control material. The physicochemical properties investigated were flexural strength and modulus, calcium release, and degree of conversion. Dentin bonding was assessed by the push-out test. Proliferation and cell counting assays were performed to evaluate in vitro cytotoxicity using fluorescence microscopy. In vivo pulp capping was performed on molars of Wistar rats, which were euthanized after 14 days and evaluated by histological analysis., Results: No statistical difference was observed in flexural strength and cell viability ( p > 0.05). Res 10% presented higher modulus than control resin and Ca(OH) 2 . Also, Res 10% attained statistically higher degree of conversion when compared to other experimental composites. Ca(OH) 2 showed higher calcium release after 28 and 45 days of storage, with no statistical difference at 45 days to Res 10%. All experimental composites achieved significantly higher bond strength when compared to Ca(OH) 2 . While no significant difference was observed in the cell proliferation rates, resins at lower concentrations showed higher cell viability. In vivo evaluation of pulp response demonstrated no pulp damage with experimental composites., Conclusions: The experimental composite investigated in this study achieved adequate physicochemical properties with minor in vivo pulpal inflammation and proved to be a valuable alternative for direct pulp capping., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Julianne Coelho Silva et al.)

Objective: Injection laryngoplasty (IL) is considered safe in both the operating room and clinical setting. However, safety data is limited to single-institution studies with reduced sample sizes. The objective of this study is to examine a national database for adverse events related to IL in an effort to further confirm the safety of this procedure and better characterize potential complications., Materials and Methods: Retrospective analysis of the Manufacturer and User Facility Device Experience (MAUDE) database for reported adverse events of IL procedures utilizing calcium hydroxyapatite (CAHA), hyaluronic acid (HA) and carboxymethylcellulose (CMC) implants from 2009 to 2020., Results and Analysis: We identified 47 reported adverse events. The average patient age was 54 years old. 59.3% of patients were female. Adverse events more frequently involved the use of CAHA compared to HA or CMC (n = 27, 57.4%, n = 13, 27.7% and n = 7, 14.9%, respectively). The most common adverse events were laryngeal edema (n = 18, 39.1%), improper placement of injected material (n = 12, 26.1%), persistent dysphonia (n = 13, 28.3%), and post-injection dysphagia or odynophagia (n = 11, 23.9%). Major events, defined as requiring emergency room treatment, hospitalization, or surgical intervention accounted for 29 (60.4%) of cases. Four cases of edema required intubation, and one patient necessitated a surgical airway., Conclusion: Complications arising from IL range from minor events to airway obstruction and may happen with a variety of injectable materials including CAHA, HA and CMC. Few cases of airway obstruction requiring immediate intervention were identified, confirming the safety of IL in both the operative and office setting., (Copyright © 2021. Published by Elsevier Inc.)

The treatment of osteochondral (OC) defects remains challenging because of the lack of economical and feasible therapeutic strategies for OC repair and reconstruction. In this study, we report an integrated bilayer hydrogel with robust interface binding force (40 kPa) by facilitating the diffusion of calcium ions to the secondary crosslink of the bilayer hydrogel, in which gellan gum and sodium alginate acted as the chondral layer, gellan gum and hydroxyapatite acted as subchondral layer. This integrated construct has high cytocompatibility, and can seed with mesenchymal stem cells (MSCs) related to different functional protein expression for cartilage and bone formation, respectively. Furthermore, in the rabbit critical-sized osteochondral defect model (4.0 mm in diameter and 8.0 mm in depth), the calcium enriched hydrogel act as a calcium reservoir, promote neovascularization at week 4, and repair the critical defect at week 8, demonstrating the feasible preparation of an acellular hydrogel for OC repair., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Non-unions continue to present a challenge to trauma surgeons, as current treatment options are limited, duration of treatment is long, and the outcome often unsatisfactory. Additionally, standard treatment with autologous bone grafts is associated with comorbidity at the donor site. Therefore, alternatives to autologous bone grafts and further therapeutic strategies to improve on the outcome and reduce cost for care providers are desirable. In this study in Sprague-Dawley rats we employed a recently established sequential defect model, which provides a platform to test new potential therapeutic strategies on non-unions while gaining mechanistic insight into their actions. The effects of a combinatorial treatment of a bone graft substitute (HACaS+G) implantation and systemic PTH administration was assessed by µ-CT, histological analysis, and bio-mechanical testing and compared to monotreatment and controls. Although neither PTH alone nor the combination of a bone graft substitute and PTH led to the formation of a stable union, our data demonstrate a clear osteoinductive and osteoconductive effect of the bone graft substitute. Additionally, PTH administration was shown to induce vascularization, both as a single adjuvant treatment and in combination with the bone graft substitute. Thus, systemic PTH administration is a potential synergistic co-treatment to bone graft substitutes.

The nerve conduits have been developed for nerve defect repair. However, no artificial conduits have obtained comparable results to autografts to bridge the large gaps. A possible reason for this poor performance may be a lack of sustainable neurotrophic support for axonal regrowth. Previous studies suggested nanocomposite conduits can be used as a carrier for valproic acid (VPA), a common drug that can produce effects similar to the neurotrophic factors. Here, we developed the novel bioabsorbable conduits based on hydroxyapatite/poly d-l-lactic acid (PDLLA)/poly{(lactic acid)-co-[(glycolic acid)-alt-(l-lysine)]} with sustained release of VPA. Firstly, the sustained release of VPA in this conduit was examined by high-performance liquid chromatography. Then Schwann cells were treated with the conduit extracts. The cell metabolic activity and proliferation were assayed by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide and bromodeoxyuridine staining. A 10-mm segment of rat sciatic nerve was resected and then repaired, respectively, using the VPA conduit (Group A), the PDLLA conduit (Group B), or the autografts (Group C). Nerve conduction velocities (NCVs), compound muscle action potentials (CMAPs), and histological staining were assayed following the surgery. The cell metabolic activity and proliferation were significantly increased (p < .05) by the extracts from VPA-conduit extract compared to others. NCVs and CMAPs were significantly higher in Groups A and C than Group B (p < .05). The nerve density of Groups A and C was higher than Group B. There was no significant difference between Groups A and C. Taken together, this study suggested the sustained-release VPA conduit promoted peripheral nerve regeneration that was comparable to the autografts. It holds potential for future use in nerve regeneration., (© 2021 International Federation for Cell Biology.)

Background: Repairing bone defects generated by craniectomy is a major therapeutic challenge in terms of bone consolidation as well as functional and cognitive recovery. Furthermore, these surgical procedures are often grafted with complications such as infections, breaches, displacements and rejections leading to failure and thus explantation of the prosthesis., Objective: To evaluate cumulative explantation and infection rates following the implantation of a tailored cranioplasty CUSTOMBONE prosthesis made of porous hydroxyapatite. One hundred and ten consecutive patients requiring cranial reconstruction for a bone defect were prospectively included in a multicenter study constituted of 21 centres between December 2012 and July 2014. Follow-up lasted 2 years., Results: Mean age of patients included in the study was 42±15 years old (y.o), composed mainly by men (57.27%). Explantations of the CUSTOMBONE prosthesis were performed in 13/110 (11.8%) patients, significantly due to infections: 9/13 (69.2%) (p<0.0001), with 2 (15.4%) implant fracture, 1 (7.7%) skin defect and 1 (7.7%) following the mobilization of the implant. Cumulative explantation rates were successively 4.6% (SD 2.0), 7.4% (SD 2.5), 9.4% (SD 2.8) and 11.8% (SD 2.9%) at 2, 6, 12 and 24 months. Infections were identified in 16/110 (14.5%): 8/16 (50%) superficial and 8/16 (50%) deep. None of the following elements, whether demographic characteristics, indications, size, location of the implant, redo surgery, co-morbidities or medical history, were statistically identified as risk factors for prosthesis explantation or infection., Conclusion: Our study provides relevant clinical evidence on the performance and safety of CUSTOMBONE prosthesis in cranial procedures. Complications that are difficulty incompressible mainly occur during the first 6 months, but can appear at a later stage (>1 year). Thus assiduous, regular and long-term surveillances are necessary., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: During vocal fold vibration, the medial surface of both folds forms a convergent shape during opening and a divergent shape during closing. A greater maximum divergence angle is associated with greater closing forces which will increase the closing speed of the glottis. An increased closing speed results in a greater acoustic intensity and greater vocal efficiency. Indentation testing showed that as the strain increases, the inferior aspect of the folds becomes stiffer than the superior aspect, resulting in the vertical stiffness gradient (VSG). We hypothesize that a reduction of the vertical stiffness gradient will reduce the maximum divergence angle., Methods: Four excised canine larynges were tested. Stress-strain curves of the superior and inferior aspects of the fold in the mid membranous plane of the baseline larynges were taken using the indentation method. Calcium hydroxylapatite (CaHA) crystals were then injected into the superior aspect of the fold. The stress-strain tests were repeated. Particle imaging velocimetry (PIV) of the intraglottal velocity fields was performed in three larynges at different subglottal pressures in the mid coronal plane for the baseline and CaHA-injected larynges., Results: CaHA injection reduced the inferior-superior stiffness gradient in all larynges. The maximal divergence angle was markedly reduced. In some cases, there was not a divergent angle., Discussion: Marked reduction of the vertical stiffness gradient significantly reduces the maximum divergence angle. Clinical implications will be discussed., Level of Evidence: NA Laryngoscope, 131:E1934-E1940, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Calcium hydroxylapatite (CaHA) is indicated for correcting moderate-to-severe facial wrinkles and folds. Hyperdilute CaHA is increasingly being used for stimulating neocollagenesis to improve skin quality and firmness., Objective: This study assessed long-term effects of hyperdilute CaHA for improving chest wrinkle appearance., Methods and Materials: Adult female subjects (N=20) were treated with a 1:2 dilution of CaHA and evaluated at week 6, week 12, day 180, and day 360 using validated Merz D&eacute;colletage Scales. A Subject Satisfaction Questionnaire was used to assess overall satisfaction on a scale from 0 (Completely Dissatisfied) to 6 (Completely Satisfied)., Results: Subjects achieved significant improvements in baseline Merz D&eacute;colletage Scale&ndash;Dynamic scores at week 6, after a single treatment (P=0.02), at week 12 (two treatments) (P=0.01), day 180 (P=0.01), and day 360 (P&lt;0.01). Subjects also demonstrated significant improvement in baseline Merz D&eacute;colletage Scale&ndash;At Rest scores at week 6 (P&lt;0.01), remaining significant at week 12 (P&lt;0.01), day 180 (P&lt;0.01), and day 360 (P&lt;0.01). Subject Satisfaction scores increased from 3.25 at day 180 to 3.59 at day 360 using a 7-point scale., Conclusion: Hyperdilute CaHA significantly improves the dynamic and resting appearance of wrinkles of the d&eacute;collet&eacute;. These durable improvements persist for at least 1 year. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5680.

Objective: This is a single-surgeon series to prospectively evaluate the clinical and radiologic results of sacroiliac joint (SIJ) stabilization using hydroxyapatite (HA)-coated, fully threaded screws in patients with SIJ dysfunction., Methods: A total number of 40 patients underwent percutaneous SIJ stabilization using HA-coated screws between 2013 and 2015 at the University Hospital of LLandough with an age range of 33-84 years. Patients were followed up closely, and outcome scores were collected preoperative and 12 months after surgery. Preoperative and postoperative outcomes were evaluated using patient-reported outcome measures (PROMs), Short Form-36, Oswestry Disability Index, EuroQol-5D-5L, and Majeed Pelvic Scores., Results: Thirty-three patients (8 male and 32 female) out of the 40 patients completed follow-up. There was an overall improvement in all PROMs; however, only mental component of SF-36, Oswestry Disability Index, Majeed Pelvic Scores, and EuroQol-5D-5L were statistically significant. Twenty-one patients (63%) had lysis around the screw, and a subgroup analysis showed that improvement in PROMs was significantly less in patients with lysis around the screw. Four patients with lysis around the screw were offered revision due to ongoing pain. Revision was successful in only 1 patient., Conclusions: Percutaneous SIJ fixation procedure has been shown to have good clinical outcomes, but the use of HA-coated fully threaded screws in this procedure is not recommended on the basis of patient-reported outcome measures and radiologic findings in this prospective study., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The aim of this trial was to determine whether a toothpaste with microcrystalline hydroxyapatite is not inferior to a fluoride toothpaste in prevention of caries in children. This double-blinded randomized control trial compared two toothpastes regarding the occurrence of caries lesions using International Caries Detection and Assessment System (ICDAS) ≥ code 1 on the primary dentition within 336 days. The test group used a fluoride-free hydroxyapatite toothpaste three times daily while control group used a toothpaste with fluoride. 207 children were included in the intention-to-treat analysis; 177 of them finished the study per protocol. An increase in caries ICDAS ≥ code 1 per tooth was observed in 72.7% of the hydroxyapatite-group (n = 88), compared with 74.2% of the fluoride-group (n = 89). The exact one-sided upper 95% confidence limit for the difference in proportion of participants with ICDAS increase ≥ 1 (-1.4%) was 9.8%, which is below the non-inferiority margin of 20% demonstrating non-inferiority of hydroxyapatite compared to the fluoride control toothpaste. This RCT showed for the first time, that in children, the impact of the daily use of a toothpaste with microcrystalline hydroxyapatite on enamel caries progression in the primary dentition is not inferior to a fluoride control toothpaste (Clinical Trials NCT03553966).

Aim: To compare the clinical and radiological results of using synthetic bone graft versus autograft obtained from the spinous process in posterior lumbar interbody fusion., Material and Methods: This retrospective study included 102 patients with degenerative lumbar spondylolisthesis who underwent one-segment posterior lumbar interbody fusion (PLIF) followed by one-segment posterior transpedicular instrumentation. PLIF surgery was performed using a local solid bone graft obtained from the spinous process in group A and using a synthetic solid calcium hydroxyapatite block in group B. The Oswestry Disability Index (ODI), visual analogue scale (VAS) scores, degree of bone formation, intervertebral disc heights at the operation segment, wound infection, and instrumentation complications were compared between the 6-month and 5-year follow-ups., Results: In both groups, ODI and VAS scores significantly improved at the 6-month and 5-year follow-up. Bone formation at both 6 months and 5 years were higher in group A than that in group B, but without a significant difference when compared. Moreover, the difference in maintaining the intervertebral disc heights was not significant between the two groups. Surgical wound infection more commonly occurred in group B, but without significant difference between the two groups, and rod fractures were observed in two patients in group B; however, no metal breakage was observed in group A., Conclusion: Successful fusion of the intervertebral space and intervertebral height restoration can be achieved and maintained with an autograft from the patient's spinous processes.

Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate.

Background: Diluted/hyperdiluted calcium hydroxylapatite (CaHA) represents an emerging biostimulatory treatment. However, limited data concerning the effects of this agent on the face have been provided so far., Objective: To investigate the efficacy and safety of hyperdiluted CaHA 1:2 treatment for mid and lower face rejuvenation., Patients and Methods: A retrospective study of 40 patients seeking skin rejuvenation for mid and lower face, treated with hyperdiluted CaHA 1:2 technique at baseline (T0), was performed. Patients were classified according to validated scales of aging in the mid to lower face at T0 and efficacy was established with scales calculated again at 4-month post-treatment (T1). In addition, efficacy was assessed by blinded evaluation of T0/T1 clinical pictures, non-invasive skin imaging and patient satisfaction. Safety was assessed through pain scale and minor/major adverse events., Results: Hyperdiluted CaHA 1:2 successfully decreased aging severity scores of the mid and lower face. Variations of collagen morphology and increased vessel density at T1 were observed with noninvasive skin imaging. Most patients were very satisfied. Mean pain score was low and only minor adverse events were reported., Conclusion: Hyperdiluted CaHA 1:2 technique seems to be effective and safe for mid and lower face skin rejuvenation.

Objective: The aim of the study was to identify the effectiveness of the combination of tissue stabilized guided subcision, microfocused ultrasound, and minimally invasive calcium hydroxylapatite injections in various sequences for treating skin surface irregularities of the buttocks and thighs., Material and Methods: 61 females (body mass index: 22.6 &plusmn; 2.4 kg/m&sup2;, age: 37.2 &plusmn; 6.8 years) were enrolled in this randomized interventional prospective study. Treatment arms included a variable combination and sequence of three treatment modalities: (1) Tissue-stabilized guided subcision, (2) microfocused ultrasound, and (3) calcium hydroxylapatite injections. Six months after the final intervention skin laxity and skin dimpling severity scores were assessed by the study participants, the treating physicians and by eleven blinded independent board-certified experts., Results: No adverse events were observed during the study that required intervention outside the standard of care treatment protocol. The combination of three treatment modalities was shown to provide greater improvement in skin laxity 1.88 (95% CI, 0.66&ndash;5.37) and skin dimpling 1.31 (95% CI, 0.61&ndash;2.81) scores as compared to any combination of two modalities. The combination of concomitant microfocused ultrasound and calcium hydroxylapatite injections followed three months later by tissue stabilized guided subcision yielded the greatest improvement in skin laxity 2.23 (95% CI, 0.51&ndash;9.82) and skin dimpling 1.79 (95% CI, 0.67&ndash;4.78) at 9-month follow-up., Conclusion: This study provides evidence for the effectiveness of combination therapies for the improvement of skin surface irregularities on the buttocks and thighs. J Drugs Dermatol. 2020;19(11): 1030-1038. doi:10.36849/JDD.2020.5117.

Intensive selection in modern lines of fast-growing chickens has caused several skeletal disorders. Therefore, current research is focused on methods to improve the bones of birds. A new potential solution is in ovo technology using nanoparticles with a high specificity for the bone tissue. Thus, the objective of the present study was to evaluate the effect of in ovo application of hydroxyapatite nanoparticles (HA-NP) in different concentrations (50, 100 and 500 μg/ml colloids) on chicken embryo development, with a particular focus on the oxidative status and bone characteristics of the embryo. The results showed that in ovo treatment with HA-NP did not negatively affect hatchability and body weight. However, bone weight was reduced in 500 μg/ml group. The concentrations of calcium, phosphorus and crude ash were not affected. The modulatory effect of HA-NP was observed on the basis of antioxidative markers - superoxide dismutase, total antioxidant status, malondialdehyde in serum and selected tissues. Glutathione concentration in serum suggested higher metabolic stress. Among bone turnover markers, the concentration of osteocalcin was found to be significantly affected by HA-NP injection. Thus, the in ovo application of HA-NP could modify the molecular responses at the stage of embryogenesis but these changes were not reflected in embryo growth and even slowed down bone development. Nevertheless, the question for the follow-up research is whether in ovo administration of HA-NP would affect the antioxidative status and bone turnover resulting in improved bone conditions and body gain in post hatch chickens.