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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.)

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: 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.

This case study presents an abnormal complication after routine injection augmentation using calcium hydroxylapatite (CaHA) vocal fold filler in-office on a 73-year-old female. The patient presented initially with severe dysphonia, hypophonia, and a past surgical history of total thyroidectomy, bilateral neck dissection, and a right lateral neck dissection for history of metastatic papillary thyroid carcinoma. She also had a past medical history of hypothyroidism. Post-injection of CaHA, the patient developed severe laryngeal edema, limited vocal cord mobility, obliteration of the pyriform, and a significantly reduced airway aperture requiring intensive care monitoring. Although uncommon, injectable fillers can result in complications which can be severe. Careful technique, the volume of injectate, and hypersensitivity should be considered in reducing complications following injection augmentation. There are multiple injection techniques to consider. The most direct approach is with direct laryngoscopy to allow for visualization of glottic incompetence. A smaller slotted laryngoscope can be considered for vocal fold injection as an alternative and without endotracheal intubation. Although these techniques allow for injection, real-time assessment of vocal fold closure is done in an awake patient. Therefore, laryngeal injection can be considered via percutaneous, per-oral, and trans-nasal approaches.

Introduction: Prosthetic dentistry has shifted toward prevention of caries occurrence surrounding restorative margin through the anti-demineralization process. This study examines the ability of nanohydroxyapatite (NHA) gel and Clinpro (CP) on enhancing resistance to demineralization of enamel and cementum at margin of restoration., Materials and Methods: Thirty extracted mandibular third molars were segregated at 1 mm above and below cementoenamel junction (CEJ) to separate CEJ portions and substituted with zirconia disks by bonding to crown and root portions with resin adhesive. The enamel and cementum area of 4 × 4 mm 2 neighboring zirconia was applied with either NHA or CP, while one group was left no treatment (NT) before demineralized with carbopal. Vickers hardness (VHN) of enamel and cementum was evaluated before material application ( B M ), after material application ( A M ), and after demineralization ( A D ). Analysis of variance (ANOVA) and post hoc multiple comparisons were used to justify for the significant difference ( α  = 0.05). Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were determined for surface evaluations., Results: The mean ± SD of VHN for B M , A M , and A D for enamel and cementum was 393.24 ± 26.27, 392.89 ± 17.22, 155.00 ± 5.68 and 69.89 ± 4.59, 66.28 ± 3.61, 18.13 ± 0.54 for NT groups, respectively, 390.10 ± 17.69, 406.77 ± 12.86, 181.55 ± 7.99 and 56.01 ± 9.26, 62.71 ± 6.15, 19.09 ± 1.16 for NHA groups, respectively, and 387.90 ± 18.07, 405.91 ± 9.83, 188.95 ± 7.43 and 54.68 ± 7.30, 61.81 ± 4.30, 19.22 ± 1.25 for CP groups, respectively. ANOVA indicated a significant increase in anti-demineralization of enamel and cementum upon application of NHA or CP ( p < 0.05). Multiple comparisons indicated the capability in inducing surface strengthening to resist demineralization for enamel and cementum of NHA which was comparable to CP ( p > 0.05) as evidenced by SEM and XRD data indicating NHA and CP deposition and crystallinity accumulation., Conclusion: NHA and CP were capable of enhancing anti-demineralization for enamel and cementum. The capability in resisting the demineralization process of NHA was comparable with CP. NHA was highly recommended for anti-demineralization for enamel and cementum surrounding restorative margin., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Niwut Juntavee et al.)

Introduction: Dentin hypersensitivity is a painful clinical condition. The frequency of its occurrence varies from 8 to 57%, depending on tested group and different methods of investigations. Recommended desensitizing agents have different mechanism of action and effectiveness. We are still looking for solutions that will improve their effectiveness and simultaneously allow for wider use of e.g. as a base material, counteracting postoperative hypersensitivity, reducing marginal microleakage. The aim of the study was to assess the effect of a selected desensitizing agent occluding dentin tubules with calcium hydroxyapatite on marginal microleakage formation of a class V composite restorations subjected to thermocycles., Materials and Methods: In study it was used 40 molars and premolars, which were alternately assigned into two groups. In both groups standardized cavities were prepared. In the study group (study group - SG) before application of bonding agent Teethmate Desensitizer (f. Kuraray, Noritake Dental Inc., Okayama, Japan) was used. In the control group (control group - CG) OptiBond All-in-one (f. Kerr, Bioggio, Switzerland) bonding agent was used and cavities were filled using composite material Gradia Direct (f. GC Europe N.V., Leuven, Belgium). After storage in saline, teeth were subjected to 600 thermocycles, passive dye penetration test was done, teeth were cut in the area of filling, according to its long axis. Under light microscope magnification value of microleakage was measured and marginal microleakage rate (M) was counted. The results of the tests were statistically analyzed using the package STATISTICA 12.0 (StatSoft, USA)., Results: The average value of M for the SG group was 0.46 (min 0.05, max 0.76, SD 0.226) and for CG was 0.22 (min 0, max 0.74, SD 0.235). The differences between M values were statistically significant (p = 0.0094)., Conclusion: A reduction in the number of retention sites for the bonding system, facilitates the formation of microleakage in the experimental conditions and reduces the degree of adhesion of the composite material to the hard tissues of the tooth.

Calcific tendinitis is a well-documented and extensively studied disease in the literature. Intramuscular and intraosseous migration are rare complications, which may present diagnostic challenges. This pictorial essay illustrates the imaging findings of these complications. Considering that neoplastic processes and infectious diseases are included in the differential diagnosis, recognizing the imaging findings of these complications is of critical importance.

Background: Volume restoration using filler in the dorsum of the hand is a simple and effective procedure to improve wrinkles and hide veins and tendons. Currently, calcium-hydroxyapatite (CaHA) filler is the only FDA-accepted material to use in the hand dorsum. However, it is not easy to inject due to swelling and redness. In addition, hand anatomy through sonography is wrongly described in Plastic and Reconstructive Surgery® Journal. Through incorrect marking in sonographic hand anatomy, physicians will conduct erroneous procedures and surgeries., Objectives: CaHA filler and hyaluronic acid (HA) filler were both injected into the hand to compare intra-individually the effect of each filler. Through this study, the author introduced detailed and refined sonographic anatomy. Overall, the author identified the correct injection method and depth., Methods: In this prospective, intra-individual, comparative study, patients were injected 1 cc of CaHA filler to the left hand and 3 cc (36 mg) of microphasic hyaluronic acid to the right. Outcomes were assessed by Merz hand grading scale, skin bio-parameters, dermascopic finding, and Global Aesthetic Improvement Scale (GAIS) with follow-up at 3, 6, 9, and 12 months., Results: The average GAIS score improved in both hands and generally maintained over the course of the study. There was significantly more bruising and swelling in the CaHA-injected hands compared with the HA-injected hands. The skin roughness and appearance improved in both sets of hands on dermascope. The average Trans-Epidermal-Water-Loss decreased and the average Stratum Corneum Hydration increased in HA-injected hands. The biopsy study showed that the HA particles lasted for 9 months., Conclusions: The author reestablished sonographic anatomy. Veins and tendons became less apparent after injections., (© 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Background: Several hydroxyapatite (HA)-coated femoral stems from a single manufacturer were identified to have aseptically loosened at mid-term follow-up despite prior radiographic appearance of osseointegration. Possible causes and associated risk factors for stem loosening were explored through radiographic review and implant retrieval analysis., Methods: Forty-six retrieved hip stems (Corail, DePuy-Synthes) were identified and grouped by bearing type: metal-on-metal (MoM), metal-on-polyethylene, and ceramic-on-ceramic. Stem lucency was graded on post-operative radiographs up to the time of revision. Stems were examined for stripping of the HA coating, taper corrosion, and bearing wear in metal-on-metal cases. Patient demographics, implant design features, and perioperative data were collected from electronic databases and patient charts., Results: Aseptic loosening occurred in 37% of cases examined. MoM bearings were associated with 7.25 times greater risk of loosening compared to other bearing types. Stem radiolucency was more prevalent for MoM cases and, although not statistically significant, demonstrated progressive lucency. Taper corrosion appeared more severe for MoM cases and correlated with proximal stem radiolucency. Removal of the HA coating from the stems was associated with both taper corrosion and MoM bearing wear. Length of implantation was a confounding factor for the MoM cases., Conclusion: This study has demonstrated a high risk of mid-term loosening of previously osseointegrated HA-coated femoral stems when paired with a MoM bearing. The mechanism of loosening appears progressive in nature and related to the MoM bearing, possibly interacting with the HA coating. If such loosening is recognized early, rapid revision may allow for retention of the femoral stem.

Simple bone cysts (SBCs) are benign lesions of unknown etiology. Because of its high relapse rate, they occasionally need a long period of treatment and restriction of activities in children and adolescent. Although various treatment modalities with variable differing outcomes have been described in the literature, no consensus has been reached regarding the standard treatment. The purpose of this study was to evaluate the outcome of a minimally invasive technique that uses a ceramic hydroxyapatite cannulated pin (HA pin) for the treatment of SBCs.Between 1998 and 2015, we have treated 75 patients with SBCs either with continuous decompression by inserting HA pins after curettage and multiple drilling (group 1, n = 39 patients) or with calcium phosphate cement (CPC) filling after curettage (group 2, n = 36 patients). These patients were retrospectively analyzed for recurrence-free survival (RFS) and factors implicated in SBC recurrence.Seventy-five patients (50 man and 25 females) with a mean age of 17.5 ± 11.6 years and a histopathologically confirmed diagnosis of SBCs were included. The mean follow-up period was 33 ± 25.3 months. RFS were 88% at 1 year and 81% at 5 years. Residual or progressing cysts were observed in 12 patients after the surgery and 10 of them underwent additional surgery. Recurrence rate was significantly higher in patients under the age of 10 years (P = .01), in long bone cysts (P = .01), and in active phase cysts (P = .003) (log-rank test). Multivariate analysis results revealed that age less than 10 years was an independent risk factor of recurrence (P = .04). No significant difference in recurrence rate was observed between groups 1 and 2. However, the mean operating time was significantly shorter in group 1. (62.4 ± 25.6 vs 110.5 ± 48.4 minutes in group 2).Continuous decompression using HA pin is a less invasive surgical technique for the treatment of SBCs compared with CPC filling and has a high healing rate. The relapse rate was still high when the cysts were caused in children aged less than 10 years, located in the long bone, or remained adjacent to the epiphysis., Level of Evidence: Level 3, Retrospective comparative study.

The recent approval in 2015 of Radiesse for injection into the hand by the FDA has spurred an increase in interest among patients and clinicians in nonsurgical hand rejuvenation using fillers. Application of the same techniques used to treat the face to the dorsum of the hands does not account for the unique nature of the skin and underlying anatomy, and can lead to suboptimal outcomes and an increased risk of adverse events such as the formation of nodules. Here, the authors discuss dilution strategies and injection techniques for hand rejuvenation using Radiesse for optimal patient safety and aesthetic outcomes.

Objective: This study aimed to investigate the damage mechanism of nanosized hydroxyapatite (nano-HAp) on mouse aortic smooth muscle cells (MOVASs) and the injury-inhibiting effects of diethyl citrate (Et 2 Cit) and sodium citrate (Na 3 Cit) to develop new drugs that can simultaneously induce anticoagulation and inhibit vascular calcification., Methods: The change in cell viability was evaluated using a cell proliferation assay kit, and the amount of lactate dehydrogenase (LDH) released was measured using an LDH kit. Intracellular reactive oxygen species (ROS) and mitochondrial damage were detected by DCFH-DA staining and JC-1 staining. Cell apoptosis and necrosis were detected by Annexin V staining. Intracellular calcium concentration and lysosomal integrity were measured using Fluo-4/AM and acridine orange, respectively., Results: Nano-HAp decreased cell viability and damaged the cell membrane, resulting in the release of a large amount of LDH. Nano-HAp entered the cells and damaged the mitochondria, and then induced cell apoptosis by producing a large amount of ROS. In addition, nano-HAp increased the intracellular Ca 2+ concentration, leading to lysosomal rupture and cell necrosis. On addition of the anticoagulant Et 2 Cit or Na 3 Cit, cell viability and mitochondrial membrane potential increased, whereas the amount of LDH released, ROS, and apoptosis rate decreased. Et 2 Cit and Na 3 Cit could also chelate with Ca + to inhibit the intracellular Ca 2+ elevations induced by nano-HAp, prevent lysosomal rupture, and reduce cell necrosis. High concentrations of Et 2 Cit and Na 3 Cit exhibited strong inhibitory effects. The inhibitory capacity of Na 3 Cit was stronger than that of Et 2 Cit at similar concentrations., Conclusion: Both Et 2 Cit and Na 3 Cit significantly reduced the cytotoxicity of nano-HAp on MOVASs and inhibited the apoptosis and necrosis induced by nano-HAp crystals. The chelating function of citrate resulted in both anticoagulation and binding to HAp. Et 2 Cit and Na 3 Cit may play a role as anticoagulants in reducing injury to the vascular wall caused by nano-HAp., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The extent of regeneration following biomaterial implantation is dependent on the microenvironment surrounding the implant. Since implant composition can have a profound effect on inflammation, it is essential to understand this process as a non-resolving inflammatory response can lead to fibrous encapsulation and insufficient integration. Incorporation of particulates into implants confers structural and functional benefits, thus optimizing particulate characteristics to enhance immune mediated efficacy is important. We investigated the relationship between the nature of hydroxyapatite (HA) particles and the innate immune response, focusing on how particle size (0.1 µm, 5 µm, 20 µm, 100 µm) and morphology (needle-shaped/spherical; smooth/rough surface) modulates inflammatory responses. We observed a shape and size-dependent activation of the NLRP3 inflammasome and IL-1β secretion; while needle-shaped and smaller HA particles significantly enhanced cytokine secretion, larger particles did not. Moreover, HA particle characteristics profoundly influenced patterns of innate immune cell recruitment and cytokine production following injection. While small, needle-shaped particles induced a strong inflammatory response, this was not observed with smooth, spherical particles of comparable size or with larger particles. These findings indicate that hydroxyapatite particle characteristics dictate immune cell recruitment and the ensuing inflammatory response, providing an opportunity to tailor HA particle characteristics to regulate immune responses induced after biomaterial implantation.

Unlabelled: Foreign body giant cells (FBGCs) and osteoclasts are multinucleated giant cells (MNGCs), both of which are formed by the fusion of macrophage-derived mononuclear cells. Osteoclasts are distinct from FBGCs due to their bone resorption ability; however, not only morphological, but also functional similarities may exist between these cells. The characterization and diversity of FBGCs that appear in an in vivo foreign body reaction currently remain incomplete. In the present study, we investigated an in vivo foreign body reaction using an extraskeletal implantation model of hydroxyapatite (HA) with different microstructures. The implantation of HA granules in rat subcutaneous tissue induced a foreign body reaction that was accompanied by various MNGCs. HA granules composed of rod-shaped particles predominantly induced cathepsin K (CTSK)-positive FBGCs, whereas HA granules composed of globular-shaped particles predominantly induced CTSK-negative FBGCs. Plasma, which was used as the binder of ceramic granules, stimulated the induction of CTSK-positive FBGCs more strongly than purified fibrin. Furthermore, the implantation of HA composed of rod-shaped particles with plasma induced tartrate-resistant acid phosphatase (TRAP)-positive MNGCs in contrast to HA composed of globular-shaped particles with purified fibrin, which predominantly induced CTSK-negative and TRAP-negative typical FBGCs. These results suggest that CTSK-positive, TRAP-positive, and CTSK- and TRAP-negative MNGCs are induced in this subcutaneous implantation model in a manner that is dependent on the microstructure of HA and presence or absence of plasma., Statement of Significance: We attempted to elucidate the mechanisms responsible for the foreign body reaction induced by the implantation of hydroxyapatite granules with different microstructures in rat subcutaneous tissue with or without plasma components as the binder of ceramic granules. By analyzing the expression of two reliable osteoclast markers, we detected tartrate-resistant acid phosphatase-positive multinucleated giant cells, cathepsin K-positive multinucleated giant cells, and tartrate-resistant acid phosphatase- and cathepsin K-negative multinucleated giant cells. The induction of tartrate-resistant acid phosphatase-positive multinucleated giant cells was plasma component-dependent while the induction of cathepsin K-positive multinucleated giant cells was influenced by the microstructure of hydroxyapatite. This is the first study to show the conditions dividing the three kinds of multinucleated giant cells in the foreign body reaction., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Filler injection for face augmentation is a common cosmetic procedure in the last decades, in our case report we describe long-term outcomes of a devastating complication of ophthalmic artery emboli following Calcium Hydroxylapatite filler injection to the nose bridge., Case Presentation: A healthy 24-year-old women received a Calcium Hydroxylapatite filler injection to her nose bridge for the correction of nose asymmetry 8 years post rhinoplasty. She developed sudden right eye ocular pain and visual disturbances. Visual acuity was 20/20 in both eyes and visual field in the right eye showed inferior arch with fixation sparing and supero-temporal central scotoma. Examination revealed marked periorbital edema and hematoma, ptosis, ocular movements limitation, an infero-temporal branch retinal artery occlusion and multiple choroidal emboli. Eighteen months post initial presentation ptosis and eye movements returned normal and choroidal emboli absorbed almost completely. However, visual acuity declined to 20/60, visual field showed severe progressive deterioration with a central and supero-nasal field remnant and the optic disc became pallor., Conclusion: Cosmetic injection of calcium hydroxylapatite to the nose bridge can result in arterial emboli to the ophthalmic system with optic nerve, retinal and choroidal involvement causing long term severe visual acuity and visual field impairment.

Biomedical implants have been widely used in bone repair applications. However, nanosized degradation products from these implants could elicit an inflammatory reaction, which may lead to implant failure. It is well known that the size, chemistry, and charge of these nanoparticles can modulate this response, but little is known regarding the role that the particle's morphology plays in inducing inflammation. The present study aims to investigate the effect of hydroxyapatite nanoparticle (HANPs) morphology on inflammation, in-vitro and in-vivo. Four distinct HANP morphologies were fabricated and characterized: long rods, dots, sheets, and fibers. Primary human polymorphonuclear cells (PMNCs), mononuclear cells (MNCs), and human dermal fibroblasts (hDFs) were exposed to HANPs and alterations in cell viability, morphology, apoptotic activity, and reactive oxygen species (ROS) production were evaluated, in vitro. PMNCs and hDFs experienced a 2-fold decrease in viability following exposure to fibers, while MNC viability decreased 5-fold after treatment with the dots. Additionally, the fibers stimulated an elevated ROS response in both PMNCs and MNCs, and the largest apoptotic behavior for all cell types. Furthermore, exposure to fibers and dots resulted in greater capsule thickness when implanted subcutaneously in mice. Collectively, these results suggest that nanoparticle morphology can significantly impact the inflammatory response., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Despite its increasing usage of facial applications, there is a paucity of objective data regarding calcium hydroxylapatite (CaHA)., Objectives: To systematically evaluate the complications from CaHA injection for facial soft tissue augmentation., Methods: Published studies on CaHA injection for facial soft tissue enhancement were identified through searches of the PubMed, EMBASE, and Cochrane Controlled Trial databases. Only randomized, controlled trials comparing CaHA injection to either placebo or an active comparator for facial cosmetic use were included. The outcome measures were the count (n) and frequency (%) of each complication, including edema (swelling), erythema (redness), ecchymosis (bruising), pain, pruritus (itching), hematomas, nodules, and extrusions., Results: Four studies on nasolabial fold (NLF) injection of CaHA consisting of two subgroups were included: (i) a CaHA-lidocaine vs CaHA subgroup and (ii) a CaHA vs hyaluronic acid (HA) subgroup. The addition of lidocaine to CaHA therapy displayed no significant effect on edema (RR (95% CI): 1.07 (0.94-1.21), P = .311), erythema (RR (95% CI): 0.91 (0.66-1.24), P = .544), ecchymosis (RR (95% CI): 1.04 (0.71-1.52), P = .843), pain (RR (95% CI): 0.88 (0.58-1.33), P = .553), or pruritus (RR (95% CI): 0.82 (0.45-1.50), P = .515). There was no significant difference between CaHA vs HA for hematomas (RR (95% CI): 0.24 (0.01-4.31), P = .332) or nodules (RR (95% CI): 0.18 (0.01-6.62), P = .353). There was no significant publication bias detected in either subgroup (Begg's test P > 0.05)., Conclusions: These findings support the addition of lidocaine to NLF injection of CaHA and suggest an equivalence between CaHA and HA with respect to hematoma and nodule formation. LEVEL OF EVIDENCE 2: Risk., (© 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

The adverse biological effect of nanoparticles is an unavoidable scientific problem because of their small size and high surface activity. In this review, we focus on nano-hydroxyapatite and TiO₂ nanoparticles (NPs) to clarify the potential systemic toxicological effect and cytotoxic response of wear nanoparticles because they are attractive materials for bone implants and are widely investigated to promote the repair and reconstruction of bone. The wear nanoparticles would be prone to binding with proteins to form protein-particle complexes, to interacting with visible components in the blood including erythrocytes, leukocytes, and platelets, and to being phagocytosed by macrophages or fibroblasts to deposit in the local tissue, leading to the formation of fibrous local pseudocapsules. These particles would also be translocated to and disseminated into the main organs such as the lung, liver and spleen via blood circulation. The inflammatory response, oxidative stress, and signaling pathway are elaborated to analyze the potential toxicological mechanism. Inhibition of the oxidative stress response and signaling transduction may be a new therapeutic strategy for wear debris-mediated osteolysis. Developing biomimetic materials with better biocompatibility is our goal for orthopedic implants.

Recent evidence suggests that Ca supplements increase the risk of cardiovascular events, but the mechanism(s) by which this occurs is uncertain. In a study primarily assessing the effects of various Ca supplements on blood Ca levels, we also investigated the effects of Ca supplements on blood pressure and their acute effects on blood coagulation. We randomised 100 post-menopausal women to 1 g/d of Ca or a placebo containing no Ca. Blood pressure was measured at baseline and every 2 h up to 8 h after their first dose and after 3 months of supplementation. Blood coagulation was measured by thromboelastography (TEG) in a subgroup of participants (n 40) up to 8 h only. Blood pressure declined over 8 h in both the groups, consistent with its normal diurnal rhythm. The reduction in systolic blood pressure was smaller in the Ca group compared with the control group by >5 mmHg between 2 and 6 h (P≤0·02), and the reduction in diastolic blood pressure was smaller at 2 h (between-groups difference 4·5 mmHg, P=0·004). Blood coagulability, assessed by TEG, increased from baseline over 8 h in the calcium citrate and control groups. At 4 h, the increase in the coagulation index was greater in the calcium citrate group compared with the control group (P=0·03), which appeared to be due to a greater reduction in the time to clot initiation. These data suggest that Ca supplements may acutely influence blood pressure and blood coagulation. Further investigation of this possibility is required.

The proliferation and activation of leukocytes upon contact with a biomaterial play a crucial role in the degree of inflammatory response, which may then determine the clinical failure or success of an implanted biomaterial. The aim of this study was to evaluate whether nano- and microstructured biomimetic hydroxyapatite substrates can influence the growth and activation of macrophage-like cells. Hydroxyapatite substrates with different crystal morphologies consisting of an entangled network of plate-like and needle-like crystals were evaluated. Macrophage proliferation was evaluated on the material surface (direct contact) and also in extracts i.e. media modified by the material (indirect contact). Additionally, the effect of supplementing the extracts with calcium ions and/or proteins was investigated. Macrophage activation on the substrates was evaluated by quantifying the release of reactive oxygen species and by morphological observations. The results showed that differences in the substrate's microstructure play a major role in the activation of macrophages as there was a higher release of reactive oxygen species after culturing the macrophages on plate-like crystals substrates compared to the almost non-existent release on needle-like substrates. However, the difference in macrophage proliferation was ascribed to different ionic exchanges and protein adsorption/retention from the substrates rather than to the texture of materials.

Background: We reported a case of sudden monocular vision loss after calcium hydroxyapatite (CaHA) injection into the nasal tip and dorsum with detailed retina images., Case Presentation: A healthy, 35-year-old woman received CaHA filler injection for nose augmentation. Ten minutes after the procedure, she developed nausea, vomiting, headache, ptosis, and left periorbital pain. After 30 minutes, she complained of progressively blurring vision in the left eye. The best-corrected visual acuity (BCVA) in her left eye was 30 cm ahead of hand motion. Left exotropia was noted in primary gaze. Limitations in adduction, supraduction, and infraduction of the left eye were also observed. Slit lamp examination of the left eye revealed a pink conjunctiva, a clear cornea, a mild anterior chamber reaction, a sluggish papillary light reflex, and a semi-dilated pupil. A positive relative afferent pupillary defect was observed in the left eye. Fundus examination revealed optic disc edema and some linear whitish opacity over the superior and temporal sites in the left eye, suggesting multiple CaHA emboli in the choroid vessels., Conclusions: Although the majority of adverse reactions are mild and transient, surgeons should be alert about extremely rare serious adverse events such as visual loss.

Purpose: To compare the inflammatory reaction caused by the injection of a sugarcane biopolymer (SCB) into the vocal fold of rabbits with that caused by calcium hydroxyapatite (CaH)., Methods: CaH (Radiesse(r)) and SCB gel were injected respectively into the right and left vocal cords of thirty rabbits. The rabbits were distributed into two equal groups and sacrificed at three and twelve weeks after injection. We then evaluated the intensity of the inflammatory reaction, plus levels of neovascularization, fibrogenesis and inflammatory changes in the vocal mucosa., Results: The vocal cords injected with CaH had a stronger inflammatory reaction by giant cells in both study periods. The SCB group had a more intense inflammatory involvement of polymorphonuclear cells three weeks after injection. SCB caused a higher level of neovascularization compared with CaH three weeks after the procedure., Conclusion: Whereas calcium hydroxyapatite triggers a more intense and lasting inflammatory reaction mediated by giant cells, sugarcane biopolymer causes a greater response from polymorphonuclear leukocytes, as well as higher levels of vneoascularization three weeks after injection.

Octacalcium phosphate (OCP) and hydroxyapatite (HAp) coatings were formed on Mg-3 mass% Al-1 mass% Zn (AZ31) magnesium alloy by a single-step chemical solution deposition method. Chemically polished AZ31 (Cpol-AZ31) and HAp- and OCP-coated AZ31 (HAp- and OCP-AZ31) were immersed in a medium for 52 weeks or implanted in transgenic mice for 16 weeks to examine the long-term corrosion behaviour and in situ inflammation behaviour. In the medium, Mg-ion release was restricted for the initial several days and the corrosion rate thereafter was suppressed by approximately one-half with the HAp and OCP coatings. HAp-AZ31 showed a ∼20% lower corrosion rate than OCP-AZ31. Tissues of the transgenic mouse emit fluorescence in proportion to the degree of inflammation in situ. The luminescence intensity level was too low to be a problem regardless of the coatings. A thinner fibrous tissue layer was formed around OCP- and HAp-AZ31 than around Cpol-AZ31, indicating that the HAp and OCP coatings suppressed corrosion and foreign-body reaction in vivo. Visible pits were formed in filiform and round shapes in vitro and in vivo, respectively. Corrosion was observed underneath the coatings, and almost uniform corrosion took place in vitro, while local corrosion was predominant in vivo. These differences in corrosion morphology are attributed to the adhesion of tissues and the lower diffusivity on the surface in vivo than that in vitro. Dissolution behaviour of OCP crystals in vivo was different from that in vitro. It was demonstrated that the HAp and OCP coatings developed have great potential for a biocompatible and corrosion protection coating., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Several clinical studies have reported that the use of hydroxyapatite- (HA) coated pins enhance external fixation. Although these studies have demonstrated higher extraction torques and lower rates of pin loosening with HA coating, there is little evidence to suggest that these biomechanical advantages translate to a lower rate of pin replacement prior to healing. The research question posed was "Is there sufficient evidence to prove that hydroxyapatite coating lowers the rate of pin replacement for external fixation?", Methods: An electronic search of Medline (Ovid, 1946 - December Week 4 2011), Embase (Ovid, 1980-2011 Week 52), and the Cochrane Central Register of Controlled Trials (Issue 4 of 4, October 2011) was conducted to identify all randomized and quasi-randomized controlled trials which compared HA-coated pins with non-coated pins for external fixation, with particular emphasis on the premature replacement of pins as a consequence of loosening., Results: The combined search strategies retrieved 72 citations. Four randomized controlled trials (101 patients, 327 HA-coated vs. 354 uncoated pins) were included in this review. None of the studies demonstrated a clear benefit between pin types with respect to premature replacement of pins prior to healing., Conclusion: This review did not find sufficient evidence to validate the preferential use of HA-coated pins over standard pins as a means of avoiding premature replacement of pins used for external fixation. The use of uncoated pins is justifiable, especially within the context of limited financial resources.

Background: To describe the first case of partial vision recovery in a 32-year-old woman with iatrogenic retinal artery occlusion (RAO) following glabella calcium hydroxylapatite (CaHA) injection, and to explore appropriate diagnostic and therapeutic measures according to a literature review., Case Presentation: A 32-year-old woman had left eye RAO and a bilateral visual field defect after CaHA injection into the glabella region. Topical and systemic intraocular pressure lowering agents, isovolemic hemodilution, globe massage, and anticoagulation with acetylsalicylic acid were prescribed. Carbogen inhalation and oral corticosteroids were also given. In addition to the above therapies, hyperbaric oxygen therapy (HBOT) was implemented as adjuvant treatment. The final best corrected visual acuity (BCVA) of the left eye improved from hand motion at 15 cm to 0.1. Improved retinal circulation and decreased retinal vessel leakage were found in the follow-up fluorescein angiography. However, there were still multiple emboli in the conjunctival and retinal arteries., Conclusion: This is the first case report on partial recovery of BCVA after iatrogenic RAO following cosmetic CaHA injection. Because no reliable treatments have been reported for such complications, HBOT may be considered as an alternative adjuvant therapy.

Background: Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF))., Methods/design: CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group., Discussion: CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment recommendations., Trial Registration Number: ClinicalTrials.gov: NCT01828905.

To reduce the incidence of implant-associated infection, we previously developed a novel coating technology using hydroxyapatite (HA) containing silver (Ag). This study examined in vivo acute and subacute toxicity associated with the Ag-HA coating in rat tibiae. Ten-week-old rats received implantation of HA-, 2% Ag-HA-, or 50% Ag-HA-coated titanium rods. Concentrations of silver in serum, brain, liver, kidneys, and spleen were measured in the acute phase (2-4 days after treatment) and subacute phase (4-12 weeks after treatment). Biochemical and histological examinations of those organs were also performed. Mean serum silver concentration peaked in the acute phase and then gradually decreased. Mean silver concentrations in all examined organs from the 2% Ag-HA coating groups showed no significant differences compared with the HA coating group. No significant differences in mean levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, creatinine, or blood urea nitrogen were seen between the three groups and controls. Histological examinations of all organs revealed no abnormal pathologic findings. No acute or subacute toxicity was seen in vivo for 2% Ag-HA coating or HA coating. Ag-HA coatings on implants may represent biologically safe antibacterial biomaterials and may be of value for reducing surgical-site infections related to implantation.

Background: Injectable fillers such as poly-L-lactic acid (PLLA) and calcium hydroxylapatite (CaHA) have shown promising results in the treatment of combination antiretroviral therapy (cART)-induced facial lipoatrophy (FLA). However, the effects of these substances on magnetic resonance imaging (MRI) have not yet been described., Objective: The authors analyze the association between the effects of treatment with semipermanent fillers on MRI and changes in quality of life (QOL)., Methods: Eighty-two human immunodeficiency virus (HIV)-positive patients with cART-induced FLA (grades 2-4) were enrolled in this prospective study. A mean volume of 58.2 mL (range, 12-105 mL) of PLLA (n = 41 patients) and 9.1 mL (range, 3-23 mL) of CaHA (n = 41) was injected in multiple sessions. The MRI examinations were performed prior to treatment and again 12 months after. The self-reported severity of FLA as well as QOL was measured using questionnaires based on Short Form 36, Medical Outcomes Study HIV Health Survey, and Center for Epidemiologic Studies Depression Scale formats., Results: Significant increases in total subcutaneous thickness (TST) of the injected regions could be identified on MRI in nearly all patients 1 year posttreatment. Patients reported that mental health and social and role functioning improved; depressive symptoms decreased after treatment. In addition, the increase in TST was positively associated with improvement of QOL., Conclusions: This study confirms that treatment with both PLLA and CaHA not only increases TST but also is associated with improved QOL for HIV-infected patients. Furthermore, the study also demonstrates that MRI can show filler-induced neocollagenesis and quantify FLA treatment effects.

In the present case of postoperative lumbar spinal stenosis after non-instrumented intertransverse fusion with granules of hydroxyapatite (HA), bone union was not completed and the patient felt the recurrence of his symptoms within two years. We performed re-decompression with fusion, and in hematoxylin and eosin staining of HA granulation harvested during revision surgery, fibrous tissue with hyaline degeneration surrounded the cavity where the HA had existed. Multinuclear giant cells and lymphocytes infiltrated some parts of the marginal layer of the cavity, and no obvious bony bridge had regenerated from autologous bone. No tartrate-resistant acid phosphate (TRAP) -positive osteoclasts could be seen in the new bone, suggesting that the activity of osteoclasts in the new bone decreased during the seven years after the primary surgery., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3483360258050263.

Foreign body giant cells (FBGCs) are formed by fusion of mononucleated macrophages during the foreign body response to a nanoparticulate hydroxyapatite (HA) implanted in defects of mini-pig femura. The molecular mechanisms underlying the formation of FBGCs are still largely obscure. Here we propose connexin 43 (cx43) and CD44 as candidate molecules involved in the fusion process. Immunohistochemistry and ultrastructural immunogold labeling indicated that cx43 is present within the ruffled border of FBGCs and is the main component of gap junctions formed between fusing macrophages. CD44 was strongly expressed during clustering and fusion of mononucleated macrophages. FBGCs adhering apically at the implanted HA showed CD44 reactivity only along the basolateral aspects of the plasma membranes, while podosome formation was observed within the sealing zone and ruffled border. Taken together, these findings demonstrate that cx43 and CD44 are part of the fusion machinery responsible for the formation of FBGCs. Furthermore, the results of microfilament and cx43 labeling suggest a functional role for podosomes and hemi-channels in biomaterial degradation., (Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The proinflammatory and catabolic cytokine IL-1β has been implicated in the pathogenesis of osteoarthritis (OA) by mediating synovial inflammation and cartilage degeneration. Although synovial macrophages are suggested to be the source of IL-1β, the mechanism remains unclear. Ectopic deposition of hydroxyapatite (HA) crystals in joints is closely associated with OA and other arthropathies, but the precise role of HA in arthritis pathogenesis has not been clearly demonstrated. Here we show that HA crystals of a particular size and shape can stimulate robust secretion of proinflammatory cytokines IL-1β and IL-18 from murine macrophages in a NLRP3 inflammasome-dependent manner. HA-induced inflammasome activation is dependent on potassium efflux, generation of reactive oxygen species (ROS), and lysosomal damage, but independent of cell death. Mice lacking the inflammasome components are protected against HA-induced neutrophilic inflammation in the air-pouch model of synovitis, and they show decreased joint pathology accompanying spontaneous HA deposition in the ank-deficient mouse model of arthritis. Moreover, calcium crystal positive synovial fluids from some OA patients exhibited inflammasome-stimulatory activity in vitro. These results demonstrate that the NLRP3 inflammasome mediates the pathological effect of HA crystals in vitro and in vivo and suggest a critical role for the inflammasome in the pathogenesis of OA.

The purpose of this study was to evaluate the tissue response to a 70% polyhydroxybutyrate and 30% hydroxyapatite composite in the form of a bone implant, placed intracortically in the distal metaphyseal of the right femur, and subcutaneous implants in cats. Samples of the composite were implanted subcutaneously in the dorsolumbar region and the distal metaphyseal region of the right femur of the animals. The study used 12 neutered adult mixed breed cats, weighing an average of 3.5kg. The cats were randomly divided into three groups: GI, GII and GIII, according to the length of the assessment period. The assessments of their subcutaneous and bone tissues were performed at 15, 30 and 45 days and at 30, 60 and 90 days, respectively. The subcutaneous and bone reactions to the composites were characterized by granulomatous inflammation with a predominance of macrophages and giant cells. The results showed that the composites triggered a chronic local inflammatory response, despite their clinical acceptance., (Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

This paper reports an investigation on human osteoblast-like cells (SaOs-2) seeded onto pure hydroxyapatite (HA) and silicon-substituted HA (SiHA) tablets under static and dynamic culture conditions. The biological characterizations were conducted in classical static conditions in multi-wells plates, and in a perfusion bioreactor that permits continuous circulation of culture medium at 2 mL/h. The morphology, proliferation and differentiation of osteoblastic cells were examined for the two types of samples in the both culture conditions after 1, 3 and 8 days. Under dynamic conditions, cells cultured on SiHA surfaces showed a faster adhesion process and the formation of longer and thinner focal adhesions than in static conditions. The number of cells grown onto both ceramic surfaces was higher in dynamic conditions when compared with static conditions. Moreover, a higher activity of alkaline phosphatase was found for cells seeded under dynamic conditions. Our findings suggest that the application of perfusion culture system on cells cultured on dense substrates is valuable for predicting in vivo behaviour of cells on biomaterials., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Due to good biocompatibility and mechanical properties, magnesium (Mg) and its alloys are considered promising degradable materials for orthopedic applications. In this work, a Mg metal matrix composite (MMC) was fabricated using Mg-2.9Zn-0.7Zr alloy as the matrix and 1 wt% nano-hydroxyapatite (n-HA) particles as reinforcements. In vitro corrosion behavior and cytocompatibility of a Mg-Zn-Zr/n-HA composite and a Mg-Zn-Zr alloy were investigated. In contrast with the Mg-Zn-Zr alloy, the MMC has better properties. The average corrosion rate of MMC is 0.75 mm/yr after immersion in simulated body fluid (SBF) for 20 days, and the surface of MMC is covered with white Ca-P precipitates. The electrochemical test results show that the corrosion potential (E(corr)) of MMC increases to -1.615 V and its polarization resistance (R(p)) is 2.56 KOmega with the addition of n-HA particles. The co-cultivation of MMC with osteoblasts results in the adhesion and proliferation of cells on the surface of the composite. The maximum cell density is calculated to be (1.85+/-0.15) x 10(4)/l after 5 days of co-culture with osteoblasts. The average cell numbers for two groups after culturing for 3 and 5 days (P<0.05) are significantly different. All the results demonstrate that the Mg-Zn-Zr/n-HA composite can be potentially used as biodegradable bone fixation material.

Background: Calcium hydroxylapatite (CaHA, Radiesse) is approved by the Food and Drug Administration for treatment of moderate to severe wrinkles and folds, including nasolabial folds (NLF). A pivotal NLF split-face study previously compared the performance of Radiesse to human-based collagen at six months and safety of Radiesse through one year., Objective: The authors assess the long-term safety and effectiveness of Radiesse for the treatment of NLF. Postapproval long-term results now extend to more than three years and are presented here., Methods: This study reports an extension phase of a previously reported one-year premarket study of 117 patients comparing Radiesse to collagen. During the initial study, patients were treated to optimal correction and then followed for 12 months; they were offered retreatment with Radiesse between six and 12 months in both folds to balance asymmetry. Of the 117 original split-face study subjects with moderate to severe NLF, 102 were enrolled in this extended follow-up. During this extension study, treating physicians used the Global Aesthetic Improvement Scale (GAIS) and clinical examination to evaluate subjects at intervals up to 39 months after the last injection of Radiesse., Results: Forty percent of the folds evaluated at least 30 months after the last Radiesse treatment were graded as "improved" or better on the GAIS. Expectedly, the reported improvement was substantially less at this later time point than had been seen at earlier points in the premarket study, indicating some moderate, sustained improvement in some patients. There were no long-term or delayed-onset adverse events in these 102 patients followed for three years, including no reports of nodules, granulomata, or infections, such as have been reported with certain other dermal fillers., Conclusions: These results demonstrate the long-term safety and effectiveness of Radiesse. Three years after Radiesse injection, no delayed-onset or long-term adverse events were reported. In addition, many patients showed some long-term cosmetic improvement. The durability and safety of Radiesse compare favorably with other injectable fillers.

Long-term studies have indicated that alloplastic bone grafts composed of nonresorbable hydroxyapatite (NHA) are clinically stable and safe. However, our previous report suggested that NHA grafts may be an etiological factor for recurrent periodontitis in the absence of supportive periodontal treatment (SPT). We removed infected NHA from the root surface by flap surgery in two cases of recurrent periodontitis. After removal of the infected NHA, the inflammation subsided in these cases and they were clinically stable for several years.

Vertebroplasty with hydroxyapatite blocks through a modified percutaneous approach was used to treat 30 patients with vertebral body fractures in 32 vertebral bodies between February 2003 and March 2007. The mean follow-up period was 16.6 months. The pain associated with this procedure, effects on adjacent vertebral bodies, and other complications were evaluated. The rate of recollapse after vertebroplasty was examined in 26 patients with 26 vertebral bodies treated and followed up for more than 3 months. Mean time of operation was 57 minutes and mean number of blocks used per vertebral body was 104. The mean visual analogue scale score was 7.0 preoperatively and 1.6 postoperatively. The mean decline in postoperative vertebral body height was 13%. New vertebral body fractures occurred postoperatively in 3 vertebral bodies in 2 patients. Leakage of blocks outside the vertebral body occurred in 2 patients during the operation, and after the operation in one patient, and the hydroxyapatite plug broke postoperatively in one patient. Hydroxyapatite blocks yielded good pain relief comparable to bone cement, with no serious complications such as a pulmonary embolism or leakage into the spinal canal, and are effective for percutaneous vertebroplasty.

Summary An evaluation was made of the local action of alendronate sodium (A), hydroxyapatite (HA) and the association of both substances (A + HA), in different molar concentrations, on the femur bone repair of ovariectomized rats. Ninety-eight animals were divided into seven groups: control (C), starch (S), alendronate 1 mol (A1), alendronate 2 mols (A2), hydroxyapatite 1 mol (HA1), hydroxyapatite 2 mols (HA2) and the association of alendronate + hydroxyapatite (A + HA). Rats weighing about 250 g were ovariectomized and 2.5-mm diameter bone defects were made on the left femur 30 days later. Each experimental group had defects filled with appropriate material, except for group C (control). The animals were killed 7 and 21 days after surgery. Histological, histomorphometric and statistical analyses of bone neoformation in the bone defect site were performed. From the histological standpoint, the major differences occurred after 21 days. All specimens in groups C, S, HA1 and HA2 presented linear closure of the bone defect, and most animals in groups A1, A2 and A + HA showed no bone neoformation in the central area of the defect. No statistically significant difference was found among the experimental groups after 7 days; after 21 days, group HA2 presented the highest amount of neoformed bone. There was no significant difference among groups A1, A2 and A + HA in the two study periods. It was concluded that alendronate, either isolated or in association with hydroxyapatite, had an adverse effect on bone repair in this experimental model. Moreover, the hydroxyapatite used here proved to be biocompatible and osteoconductive, with group HA2 showing the best results.

Particulate wear debris can activate defence cells and osteoclasts at the bone-implant interface possibly leading to bone resorption and implant failure. Cellular responses and inflammatory effects have been reported for particulate hydroxyapatite (HA). However, the immunological effects of particulate beta-tricalciumphosphate (beta-TCP) have not been studied and the question of whether beta-TCP is more biocompatible in this regard as is HA remains to be determined. Therefore the present work investigates effects of endotoxin-free HA and beta-TCP particles of the same size (d(50)=1 microm) and dose (SAR 10:1) on human peripheral blood mononuclear cells in vitro. The production of proinflammatory cytokines (TNF-alpha, IL-1beta, IL-8) and cytokines connected to osteoclast and dendritic cell differentiation (OPG, RANKL, M-CSF, GM-CSF) was determined by ELISA. After 6 and 18 h of incubation HA and beta-TCP caused a quite similar induction of TNF-alpha, IL-1beta and IL-8. Effects of particles on the production of M-CSF and OPG were not detectable. However, in sharp contrast to HA, beta-TCP caused less induction of GM-CSF and not any of RANKL, both known for promoting dendritic cells and osteoclastogenesis respectively. Therefore these in vitro data suggest that wear debris of beta-TCP poses lesser risk of the detrimental effects of osteoclast induction known from HA.

The popularity of cosmetic procedures for rejuvenating the face has undergone enormous growth over the past few years, such that at least one in four cosmetic procedures involves the use of soft-tissue augmentation. Of note is the trend away from surgical interventions and toward noninvasive cosmetic procedures, which now account for the majority of all cosmetic procedures performed in the United States. Adult patients of all ages are selecting soft-tissue augmentation, either as a precursor to or a substitute for surgery; there is a trend toward the use of injectable devices in younger patients (aged 35 - 50 years). Patients in different age groups have diverse treatment needs ranging from the correction of fine lines and wrinkles in younger patients to volume restoration in older patients. Thus, the treatment needs will dictate the treatment approach, particularly with injectable filler treatments. The aesthetic physician needs to help the patient understand and select the most appropriate rejuvenating treatment based on a variety of factors, specifically, patient age, motivating factors, timing, cosmetic area to be addressed, and desired outcome. This article suggests a series of steps to help determine the most appropriate approach for volume restoration with injectable devices for satisfying patient treatment expectations.

Soft-tissue augmentation of the face is an increasingly popular cosmetic procedure. In recent years, the number of available filling agents has also increased dramatically, improving the range of options available to physicians and patients. Understanding the different characteristics, capabilities, risks, and limitations of the available dermal and subdermal fillers can help physicians improve patient outcomes and reduce the risk of complications. The most popular fillers are those made from cross-linked hyaluronic acid (HA). A major and unique advantage of HA fillers is that they can be quickly and easily reversed by the injection of hyaluronidase into areas in which elimination of the filler is desired, either because there is excess HA in the area or to accelerate the resolution of an adverse reaction to treatment or to the product. In general, a lower incidence of complications (especially late-occurring or long-lasting effects) has been reported with HA fillers compared with the semi-permanent and permanent fillers. The implantation of nonreversible fillers requires more and different expertise on the part of the physician than does injection of HA fillers, and may produce effects and complications that are more difficult or impossible to manage even by the use of corrective surgery. Most practitioners use HA fillers as the foundation of their filler practices because they have found that HA fillers produce excellent aesthetic outcomes with high patient satisfaction, and a low incidence and severity of complications. Only limited subsets of physicians and patients have been able to justify the higher complexity and risks associated with the use of nonreversible fillers.

The nanostructured surface of a material can improve its interaction with cells and its acceptance as an implant. We compared two novel biomaterials with different nanostructures: Bioverit II with a coating of nanoporous silica and chitosan-hydroxyapatite composite materials. Pure Bioverit II served as a control. Platelets of these materials were implanted for 28, 85 and 300 days in the subcutaneous tissue in the neck of 38 rabbits. After excising the specimens they were fixed, embedded in epoxy resin and analyzed histologically. All coated Bioverit II implants showed a thin capsule of connective tissue. After 300 days, these capsules tended to be thicker than in pure Bioverit II. No signs of inflammation were observed and the materials appeared unaltered by visual inspection. In case of chitosan-hydroxyapatite composites, massive capsules consisting of dense connective tissue were found, and the material showed signs of biodegradation in form of fissures and cavities. In conclusion, the nanoporous coating showed no obvious positive effect with regard to capsule formation; the chitosan-hydroxyapatite implants provoked a stronger interaction between cells and material. However, most Bioverit II implants showed no alterations optically, whereas chitosan-hydroxyapatite was partly degraded in all cases.

Biodegradable polymer/bioceramic composite scaffolds can overcome the limitations of conventional ceramic bone substitutes such as brittleness and difficulty in shaping. However, conventional methods for fabricating polymer/bioceramic composite scaffolds often use organic solvents (e.g., the solvent casting and particulate leaching (SC/PL) method), which might be harmful to cells or tissues. In this study, Poly (D,L-lactide)/nano-hydroxyapatite (PDLLA/NHA) composites were prepared by in-situ polymerization, and highly porous scaffolds were fabricated using a novel method, supercritical CO2/salt-leaching method (SC CO2/SL). The materials and scaffolds were investigated by scanning electronic microscopy (SEM), transmission electronic microscopy (TEM) and gel permeation chromatography (GPC). GPC showed that the molecular weight of composites decreased with increase of NHA content. However, the water absorption and compressive strength increased dramatically. The SEM micrographs showed that the scaffolds with pore size about 250 microm were obtained by controlling parameters of SC CO2/SL. The biocompatibility of PDLLA/NHA porous scaffolds were evaluated in vitro and in vivo. The evaluation on the cytotoxicity were carried out by cell relative growth rate (RGR) method and cell direct contact method. The cytotoxicity of these scaffolds was in grade I according to ISO 10993-1. There was no toxicosis and death cases observed in acute systemic toxicity test. And histological observation of the tissue response (1 and 9 weeks after the implantation) showed that there are still some slight inflammation responses.

Background and Purpose: Most cement leaks during vertebroplasty are asymptomatic, but pulmonary cement embolism has been reported to cause cardiovascular disturbances and even death. Adding hydroxyapatite (HA) to polymethylmethacrylate (PMMA) cement to reduce the quantity of barium may aggravate cardiovascular deterioration in the event of cement embolism by activating coagulation. Thus, we investigated the cardiovascular changes after pulmonary cement embolism of PMMA with and without HA., Materials and Methods: In 13 sheep, cement (2.0 mL) was injected into the pulmonary trunk. Two different cements were used: 1) standard PMMA and 2) PMMA with 10% HA (PMMA & HA). Arterial, central venous and pulmonary arterial pressures, heart rate, and cardiac output were monitored continuously until 60 minutes after the injection. Blood gases and coagulation parameters (antithrombin, D-dimer) were measured before and after injection., Results: Mean pulmonary arterial pressure had increased by approximately 9% (PMMA) and 14% (PMMA & HA) 1 minute after injection and stayed elevated. There were no significant differences between the groups. No evidence of thromboembolism was detected., Conclusion: Cement embolism did not result in clinically significant pulmonary arterial hypertension. Adding HA to PMMA cement did not cause more severe cardiovascular changes.