Enhancing osteoporosis treatment using a targeted, sustained-release drug delivery system based on macrocyclic amphiphile.

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.

Performance and Safety of Amino-Acid- and Hydroxyapatite Enriched-Hyaluronic Acid Intradermal Gel in Facial Skin Defects.

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.

Improved brachial skin hydration and appearance with hyperdiluted calcium hydroxylapatite.

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.

A Prospective, Multicenter, Evaluator-Blinded, Randomized Study of Diluted Calcium Hydroxylapatite to Treat Decollete Wrinkles.

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 décolleté 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 décolleté 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<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.  doi:10.36849/JDD.8261.

Hand Rejuvenation with Customizable Hybrid Fillers: Premixed Calcium Hydroxyapatite and Hyaluronic Acid.

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 .

The gold protocol: A combined treatment approach for neck rejuvenation with calcium hydroxyapatite, botulinum toxin, and hyaluronic acid in the same session.

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.

A Structured Approach for Treating Calcium Hydroxylapatite Focal Accumulations.

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.

A systematic review of Radiesse® (calcium hydroxylapatite): evidence and recommendations for the body.

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.

Dilutional rheology of Radiesse: Implications for regeneration and vascular safety.

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.

Safety and Efficacy of Diluted Calcium Hydroxylapatite for the Treatment of Cellulite Dimpling on the Buttocks: Results from an Open-Label, Investigator-Initiated, Single-Center, Prospective Clinical Study.

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/m2; 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 .

Combining topical dermal infused exosomes with injected calcium hydroxylapatite for enhanced tissue biostimulation.

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.

Efficacy of NHP66 Bioactive Cage on Patients with Cervical Spine Injury in Short-Track Speed Skating.

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.

Comparison of 24-month voice outcomes after injection laryngoplasty with calcium hydroxylapatite or hyaluronic acid in patients with unilateral vocal fold paralysis.

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.

A Randomized, Evaluator-Blind, Split-Face Study Evaluating the Safety and Efficacy of Calcium Hydroxylapatite for Jawline Augmentation.

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.

In Vitro and In Vivo Efficacy of New Composite for Direct Pulp Capping.

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.

Systemic Administration of PTH Supports Vascularization in Segmental Bone Defects Filled with Ceramic-Based Bone Graft Substitute.

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.

Gellan gum/alginate-based Ca-enriched acellular bilayer hydrogel with robust interface bonding for effective osteochondral repair.

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.

Adverse events following injection laryngoplasty: An analysis of the MAUDE database.

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.

Prospective Clinical Trial Evaluating the Long-Term Safety and Efficacy of Calcium Hydroxylapatite for Chest Rejuvenation.

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 Décolletage 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 Décolletage Scale–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<0.01). Subjects also demonstrated significant improvement in baseline Merz Décolletage Scale–At Rest scores at week 6 (P<0.01), remaining significant at week 12 (P<0.01), day 180 (P<0.01), and day 360 (P<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 décolleté. These durable improvements persist for at least 1 year. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5680.