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The aim of this study was to develop an osteo-inductive resorbable layer allowing the controlled elution of antibiotics to be used as a bone/implant bioactive interface particularly in the case of prosthetic joint infections, or as a preventative procedure with respect to primary joint replacement at a potentially infected site. An evaluation was performed of the vancomycin release kinetics, antimicrobial efficiency and cytocompatibility of collagen/hydroxyapatite layers containing vancomycin prepared employing different hydroxyapatite concentrations. Collagen layers with various levels of porosity and structure were prepared using three different methods: by means of the lyophilisation and electrospinning of dispersions with 0, 5 and 15wt% of hydroxyapatite and 10wt% of vancomycin, and by means of the electrospinning of dispersions with 0, 5 and 15wt% of hydroxyapatite followed by impregnation with 10wt% of vancomycin. The maximum concentration of the released active form of vancomycin characterised by means of HPLC was achieved via the vancomycin impregnation of the electrospun layers, whereas the lowest concentration was determined for those layers electrospun directly from a collagen solution containing vancomycin. Agar diffusion testing revealed that the electrospun impregnated layers exhibited the highest level of activity. It was determined that modification using hydroxyapatite exerts no strong effect on vancomycin evolution. All the tested samples exhibited sufficient cytocompatibility with no indication of cytotoxic effects using human osteoblastic cells in direct contact with the layers or in 24-hour infusions thereof. The results herein suggest that nano-structured collagen-hydroxyapatite layers impregnated with vancomycin following cross-linking provide suitable candidates for use as local drug delivery carriers., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Bone morphogenetic protein-2 (BMP-2) appears to be one of the most potent growth factors thus far studied. However, recent publications on the clinical application of BMP-2 revealed that its correct control is the paramount issue in clinical practice. For improving BMP-2 delivery, the cyclic administration might be an alternative. Accordingly, the authors cyclically injected BMP-2 in a cyclic injection model of large cranial defects to maintain the proper dosage during the bone healing process. A 10-mm diameter calvarial bone defect was produced using a round drill in 8-week-old Sprague-Dawley rats. Silk-hydroxyapatite scaffolds soaked in the appropriate concentration of BMP-2 were implanted into the defect. The animals were split into 4 single-injection groups and 3 multiple-injection groups; the latter groups received weekly subcutaneous injections of BMP-2 solution (1, 5, and 10 μg/mL) for 4 weeks, whereas the former groups received a single injection of BMP-2 at these concentrations. Each rat underwent computed tomography at 8 weeks. In terms of total volumes of the new bone, the 5 μg/mL multiple-injection BMP-2 group had significantly greater increases in bone volume than the single-injection groups. In terms of bone thickness, the multiple-injection groups had better outcomes than the single-injection groups. Thus, the cyclic injection protocol restored the original thickness without overgrowth. Cyclic injection of BMP-2 permits more accurate dosage control than single injection and improves thickness and dense bone regeneration. Therefore, it may represent a promising approach for future clinical trials. Further investigation using a greater number of animals is required.

Combination of tissue-engineered bone scaffolds with cell-adhesive, osteoconductive, or osteoinductive biomolecules is a critical strategy to improve their properties that significantly influence cellular behaviors, such as adhesion, proliferation, and differentiation, which is beneficial for critical-sized bone defects repairing. However, the traditional surface modification techniques, such as physical adsorption, coating, and plasma treatment, et al, have great limitations for immobilization of bioactive molecules due to undesirable controlled delivery performance or overly complex multistep procedures. In this study, we functionalized the chitosan/hydroxyapatite (CS/HA) biomimetic composite scaffold for controlled delivery of BMP2-derived peptide (P24) by the chemical grafting modification technique: firstly, P24 was conjugated with a thiolated chitosan, chitosan-4-thiobutylamidine (CS-TBA); secondly, the resultant CS-P24 was then combined with HA to prepare CS-P24/HA scaffolds. The effect of CS-P24/HA scaffolds on bone regeneration was evaluated, along with the underlying biological mechanisms responsible in vitro and in vivo . In vitro , the controlled and sustained release of bioactive P24 could last up to 90 days, furthermore, the release profiles of CS-5%P24/HA and CS-10%P24/HA were linear and could be fitted according to zero-order kinetic model (R 2 =0.9929; R 2 =0.9757); P24 on the scaffold significantly promoted cell adhesion, proliferation, osteodifferentiation, and mineralization with synergistic effects. Bone marrow stromal cells (BMSCs) revealed spindle-shaped surface morphology, indicating the CS-P24/HA scaffolds supported cell adhesion and possessed a high proliferation rate that varied according to the P24 concentration levels. Furthermore, mRNA levels for OCN, Runx2, and collagen I were significantly up-regulated on CS-P24/HA scaffolds compared with cells grown on CS/HA scaffolds in vitro ( p < 0.05). Similarly, the BMSCs exhibited a higher ALP expression and calcium deposition level on CS-P24/HA scaffolds compared with CS/HA scaffolds ( p < 0.05). In vivo , osteoinductive studies revealed a significantly higher ectopic osteogenesis level of CS-10%P24/HA scaffolds in rat dorsal muscle pockets compared with that of CS/HA scaffolds. Finally, CS-P24/HA scaffolds showed superior performance in the reconstruction of rat calvarial bone defects. This novel CS-P24/HA scaffold is deemed a strong potential candidate for the repair of bone defects in human bone tissue engineering., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objectives: The aim of this study was to evaluate the efficacy of the endoscopic injection of calcium hydroxyapatite (CaHA) into the bladder neck (BN) region of patients with urinary incontinence and bladder exstrophy-epispadias complex (BEEC)., Patients and Methods: We designed a retrospective cohort study in which we retrospectively studied medical charts of female and male patients of BEEC who had undergone CaHA or Deflux injection for continence improvement between 2009 and 2014. Sixteen incontinent patients with a mean ± SD age of 8.09 ± 3.5 years received an endoscopic submucosal injection of 5.4 ml of pure CaHA powder with autologous plasma (group A). Patients in group B (N = 21), control group, with a mean ± SD age of 7.51 ± 2.8 years received Deflux injection (5.1 ml). The mean follow-up after injection was 38 ± 5.2 and 33 ± 4.1 months in groups A and B, respectively., Results: No post-injection complication was detected in none of the patients during the follow-up. Eleven patients (68.75%) in group A became socially dry following 1-2 injections, the degree of incontinence was improved in 4 patients (25%), and there was no change in one patient (6.25%). However, Deflux injection resulted in complete dryness in 14 (66.66%), improvement in the degree of incontinence in 5 (23.81%) and no change in 2 patients (9.52%), leading to no significant difference in continence achievement between CaHA and Deflux groups (p = 0.9). The statistical analysis was not significantly different in terms of bladder capacity (p = 0.7) or Q max (p = 0.8)., Conclusion: The preliminary results of this study revealed that CaHA may be applied as an affordable bulking agent in treatment of urinary incontinence in BEEC.

Strontium ranelate and fluoride salts are therapeutic options to reduce fracture risk in osteoporosis. Incorporation of these elements in the physiological hydroxyapatite matrix of bone is accompanied by changes in bone remodeling, composition, and structure. However, a direct comparison of the effectiveness of strontium and fluoride treatment in human cortical bone with a focus on the resulting mechanical properties remains to be established. Study groups are composed of undecalcified specimens from healthy controls, treatment-naïve osteoporosis cases, and strontium ranelate or fluoride-treated osteoporosis cases. Concentrations of both elements were determined using instrumental neutron activation analysis (INAA). Backscattered electron imaging was carried out to investigate the calcium content and the cortical microstructure. In comparison to osteoporotic patients, fluoride and strontium-treated patients have a lower cortical porosity indicating an improvement in bone microstructure. Mechanical properties were assessed via reference point indentation as a measure of bone's resistance to deformation. The strontium-incorporation led to significantly lower total indentation distance values compared to osteoporotic cases; controls have the highest resistance to indentation. In conclusion, osteoporosis treatment with strontium and fluoride showed positive effects on the microstructure and the mechanical characteristics of bone in comparison to treatment-naïve osteoporotic bone. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 433-442, 2017., (© 2016 Wiley Periodicals, Inc.)

Hydrogels provide three-dimensional (3D) frames with tissue-like elasticity and high water content for tissue scaffolds. Previously, we reported the design and synthesis protocol of a biodegradable poly(carboxybetaine) poly(CB) hydrogel with a zwitterionic carboxybetaine methacrylate (CBMA) monomer and a disulfide-containing crosslinker via free radical polymerization. We also demonstrated that cells could be successfully encapsulated in the hydrogels without compromising cytoviability. In this study, we evaluated the cytoviability of three commonly used zwitterionic monomers (CBMA, 2-methacryloyloxyethyl phosphorylcholine (MPC) and sulfobetaine methacrylate (SBMA)) and the suitability of being utilized as precursor materials for in situ gel forming implants. These three zwitterionic monomers exhibited lower cell toxicity than other methacrylated monomers. Mixing these monomers with dimethacrylate crosslinkers initiated the gelation process in situ, which was further tested in vivo by injecting the precursor solutions subcutaneously into murine models. Poly(CB) implants retained their original shape up to 3 weeks, while poly(MPC) and poly(SB) hydrogels for shorter periods of time due to lower mechanical strengths. These hydrogels showed minimal inflammation at the injection site. We subsequently showed that the CBMA precursor solution mixed with Arg-Gly-Asp (RGD) and hydroxyapatite (HAp) nanoparticles could be applied in bone tissue engineering. Both in vitro and in vivo studies demonstrated that HAp containing poly(CB) hydrogels greatly enhanced the mineralization process of bone tissue formation. The non-cytotoxic and biodegradable poly(CB) hydrogel conjugated with cell affinity moieties is an excellent material for 3D tissue scaffolds.

Background: Calcium hydroxylapatite (CaHA; Radiesse (R)) provides safe and effective correction of moderate-to-deep lines, volume replacement, lift and contour, and induction of neocollagenesis and neoelastogenesis for improved skin quality. CaHA hyperdilution takes advantage of its skin-tightening properties without a volumizing effect., Objective: To evaluate the collagen- and elastin-stimulating effects of diluted CaHA in subjects with skin laxity in the neck and décolletage., Methods: Twenty subjects with skin laxity in the neck and décolletage received multiple, linear, subdermal injections of CaHA diluted with preserved saline at baseline and 4 months: 1:2 dilution (normal skin), 1:4 dilution (thin skin), and 1:6 dilution (atrophic skin). Subjects also received deep subdermal injection of CaHA (~0.1 ml) of the same dilution in the peri-auricular area for skin biopsy. Biopsy tissue was obtained at baseline, 4 months, and 7 months for immunohistochemical evaluation of neocollagenesis. Changes to skin mechanical properties were measured by ultrasound scanning and cutometry. Subject and investigator satisfaction was evaluated using the Global Aesthetic Improvement Scale., Results: Immunohistochemical analysis of biopsy tissue demonstrated signi cant increases in collagen I expression at 4 months (P less than 0.05) and 7 months (P less than 0.00001) compared with baseline. Increases in collagen III levels were also significant at 4 months (P less than 0.00001); they declined by 7 months but remained above baseline. Staining for elastin and angiogenesis signi cantly increased at 4 months (P less than 0.05 and P less than 0.01, respectively) and 7 months (P less than 0.00001 for both) compared with baseline. Immunohistochemical data correlated with improvements in skin elasticity and pliability evaluated by cutometry, and with ultrasound-assessed increases in dermal thickness. Subject and investigator satisfaction was high, and the procedure was well tolerated., Conclusions: Injection of diluted CaHA is very effective for skin tightening of the neck and décolletage. J Drugs Dermatol. 2017;16(1):68-74..

Reconstruction of complex skull defects requires collaboration between neurosurgeons and plastic surgeons to choose the most appropriate procedure, especially in growing children. The authors describe herein the reconstruction of an extensive traumatic bone and soft tissue defect of the cranial vault in an 11-year-old boy. The size of the defect, quality of the tissues, and patient's initial condition required a 2-stage approach. Ten months after an initial emergency procedure in which lacerated bone and soft tissue were excised, reconstruction was performed. The bone defect, situated on the left frontoparietal region, was 85 cm 2 and was filled by a custom-made porous hydroxyapatite implant. The quality of the overlying soft tissue did not allow the use of classic local and locoregional coverage techniques. A free latissimus dorsi muscle flap branched on the contralateral superficial temporal pedicle was used and left for secondary healing to take advantage of scar retraction and to minimize alopecia. Stable well-vascularized implant coverage as well as an esthetically pleasing skull shape was achieved. Results in this case suggest that concomitant reconstruction of large calvarial defects by cranioplasty with a custom-made hydroxyapatite implant covered by a free latissimus dorsi muscle flap is a safe and efficient procedure in children, provided that there is no underlying infection of the operative site.

Objective: There is growing interest in the use of cuttlefish bone (CB) as a bone graft material. Silicon (Si) plays an important role in bone formation and calcification. This study aimed to prepare Si-substituted CB-derived hydroxyapatite (Si-CB-HAp) using a natural CB to improve the bioactivity for bone formation., Materials and Methods: We prepared Si-HAp from CB (Si-CB-HAp) using a hydrothermal and solvothermal method. The microstructure and chemical composition were characterized by scanning electron microscope (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectrometer (EDS). The bioactivity of the Si-CB-HAp was evaluated using human mesenchymal stem cells. Furthermore, the in vivo bone regeneration efficiency was evaluated using a rabbit calvarial defect model., Results: Our results show that the Si content was 0.77 wt% in Si-CB-HAp, and its original microstructure was conserved. The presence of Si was shown to enhance cell proliferation and early cellular attachment of human mesenchymal stem cells. Additionally, results of alkaline phosphatase activity and real-time PCR for osteoblast marker genes show that Si substitution into CB-HAp enhanced osteoblast differentiation. In addition, in vivo bone defect healing experiments show that the formation of bone with Si-CB-HAp is higher than that with CB-HAp., Conclusion: These results indicate that Si-CB-HAp may potentially be used as a bone graft material to enhance bone healing., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cranioplasty is considered a simple reconstructive procedure, usually performed in a single stage. In some clinical conditions, such as in children with multifocal flap osteolysis, it could represent a surgical challenge. In these patients, the partially resorbed autologous flap should be removed and replaced with a precustomed prosthesis which should perfectly match the expected bone defect. We describe the technique used for a navigated cranioplasty in a 3-year-old child with multifocal autologous flap osteolysis. We decided to perform a cranioplasty using a custom-made hydroxyapatite porous ceramic flap. The prosthesis was produced with an epoxy resin 3D skull model of the patient, which included a removable flap corresponding to the planned cranioplasty. Preoperatively, a CT scan of the 3D skull model was performed without the removable flap. The CT scan images of the 3D skull model were merged with the preoperative 3D CT scan of the patient and navigated during the cranioplasty to define with precision the cranioplasty margins. After removal of the autologous resorbed flap, the hydroxyapatite prosthesis matched perfectly with the skull defect. The anatomical result was excellent. Thus, the implementation of cranioplasty with image merge navigation of a 3D skull model may improve cranioplasty accuracy, allowing precise anatomic reconstruction in complex skull defect cases., (© 2017 S. Karger AG, Basel.)

Hydroxyapatite (HAp) is a complicated ceramic material that varies between the way it appears in biological systems and how it is synthesized as various calcium phosphates. HAp varies in chemical composition of substituting atoms, crystallinity, grain size and electrical polarization. HAp can form solid to macro-, micro- and nanoporous structures. Also, particulate HAp can have highly porous structure. HAp can be used as coatings for metal implants in thicknesses from hundreds of microns down to hundreds of nanometers. Cotton wool-like HAp fibers can be electrospun compounded with polymers (or without) for tissue engineering (TE) scaffolds. This review describes the features of HAp that may be utilized further in developing novel applications. As a nanomaterial HAp has been applied for drug delivery. The adsorption of proteins and other compounds can be adjusted by modifying HAp composition, electrical polarization and wettability. Of special interest are the bisphosphonates that bind to HAp and thereby can be used to treat bone loss and also couple other drugs to the mineral. A new area for HAp constructs may appear in treating metallosis. HAp coating may function as a scavenger for the ions release from metal implants and thereby inhibit the adverse effects of the ion burden for the body. So far HAp is considered as safe biomaterial but nano HAp may insidiously possess adverse effects especially when ingested by cells and eliciting excess intracellular calcium. Thereby critical approach also for HAp biomaterials is of utmost importance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Spontaneous infectious spondylodiscitis is a rare, but serious disease with the risk of progressive neurological impairment. The surgical approach to spontaneous infectious spondylodiscitis is in most cases an anterior debridement and fusion, often in staged surgeries. Here we report a case of single-stage posterior debridement and posterior instrumented fusion in combination with an injectable calcium sulfate/hydroxyapatite composite eluting gentamicin., Case Presentation: A 59-year-old Caucasian man presented with a 6-week history of lumbar pain without sensory or motor disorders of his lower extremities. A magnetic resonance imaging scan of his lumbar spine in T2-weighted sequences showed a high signal of the intervertebral disc L4/L5 and in T1-weighted sequences an epidural abscess at the posterior wall of L4. Additional computed tomography imaging revealed osteolytic destruction of the base plate of L4 and the upper plate of L5. Antibiotic therapy was started with intravenous ciprofloxacin and clindamycin. We performed a posterior debridement via a minimally invasive approach, a posterior percutaneous stabilization using transpedicular screw-rod instrumentation and filled the intervertebral space with an injectable calcium sulfate/hydroxyapatite composite which elutes a high concentration of gentamicin. The patient's lower back pain improved quickly after surgery and no recurrence of infection has been noticed during the 1-year follow-up. Computed tomography at 11 months shows complete bony fusion of L4 and L5., Conclusions: An injectable calcium sulfate/hydroxyapatite composite releasing a high level of gentamicin can support the surgical treatment of spondylodiscitis in combination with posterior debridement and transpedicular screw-rod instrumentation.

Introduction and Hypothesis: Peri-urethral calcium hydroxylapatite injection is an established treatment for patients with stress urinary incontinence. Information is limited regarding calcium hydroxylapatite treatment and quality of life (QOL) outcomes. We hypothesize that patients might improve QOL after peri-urethral calcium hydroxylapatite injection, which was reflected in validated questionnaires., Methods: The peri-urethral calcium hydroxylapatite injection billing code was used to identify patients who underwent injection from 2011-2013. Female patients who completed the American Urological Association Symptom Score (AUASS), the AUASS QOL and Michigan Incontinence Symptom Index (M-ISI), and the bother score (M-ISI bother), or pad count at baseline and follow-up were included. Change in questionnaire scores and pads were assessed using the paired t test., Results: Sixty patients underwent 1 (30), 2 (63) or 3 (7 %) peri-urethral calcium hydroxylapatite injections performed by a single surgeon. Thirty-seven patients provided questionnaires and 38 provided pad counts, all with a mean age of 75 years. The overall AUASS, AUASS QOL, and overall M-ISI scores improved in 67.6, 54.8, and 61.3 % respectively (4.5 ± 7.9, 1.3 ± 1.7 and 5.5 ± 8.6 respectively). The M-ISI bother score improved in 44.8 % with a mean improvement of 0.5 ± 2.9, but did not reach significance. There was a 1.7 ± 3.7 decrease in the mean number of pads used daily after the procedure (p = 0.006) and 19 % experienced transient urinary retention., Conclusions: Peri-urethral calcium hydroxylapatite injections can improve urinary QOL scores in patients with initial and recurrent stress urinary incontinence. This short-term retrospective analysis suggests that larger long-term studies focusing on QOL outcomes are needed to evaluate the effect of peri-urethral calcium hydroxylapatite has on incontinence-specific QOL.

Background: One of the most important complications of fixed orthodontic treatment is the formation of white spots which are initial carious lesions. Addition of antimicrobial agents into orthodontic adhesives might be a wise solution for prevention of white spot formation. The aim of this study was to evaluate the antibacterial properties of a conventional orthodontic adhesive containing three different concentrations of silver/hydroxyapatite nanoparticles., Methods: One hundred and sixty-two Transbond XT composite discs containing 0, 1, 5, and 10 % silver/hydroxyapatite nanoparticles were prepared and sterilized. Antibacterial properties of these composite groups against Streptococcus mutans, Lactobacillus acidophilus, and Streptococcus sanguinis were investigated using three different antimicrobial tests. Disk agar diffusion test was performed to assess the diffusion of antibacterial agent on brain heart infusion agar plate by measuring bacterial growth inhibition zones. Biofilm inhibition test showed the antibacterial capacity of composite discs against resistant bacterial biofilms. Antimicrobial activity of eluted components from composite discs was investigated by comparing the viable counts of bacteria after 3, 15, and 30 days., Results: Composite discs containing 5 and 10 % silver/hydroxyapatite nanoparticles were capable of producing growth inhibition zones for all bacterial types. Results of biofilm inhibition test showed that all of the study groups reduced viable bacterial count in comparison to the control group. Antimicrobial activity of eluted components from composite discs was immensely diverse based on the bacterial type and the concentration of nanoparticles., Conclusions: Transbond XT composite discs containing 5 and 10 % silver/hydroxyapatite nanoparticles produce bacterial growth inhibition zones and show antibacterial properties against biofilms.

Background: Systemic administration of bisphosphonates has shown promising results in the treatment of osteonecrosis of the femoral head (ONFH). However, few studies have evaluated the efficacy of local zoledronate (ZOL) administration in the treatment of ONFH. The purpose of this study was to investigate whether local administration of bisphosphonate-soaked hydroxyapatite (HA) could improve bone healing in an experimental rabbit model of ONFH., Methods: This experimental study was conducted between October 2014 and June 2015. Forty-five rabbits underwent simulated ONFH surgery. Immediately following surgery, they were divided into three groups: model (untreated, n = 15), HA (treated with HA alone, n = 15), and HA + ZOL (treated with HA soaked in a low-dose ZOL solution, n = 15). Histological, immunohistochemical, and quantitative analyses were performed to evaluate bone formation and resorption 2, 4, and 8 weeks after surgery., Results: Gross bone matrix and hematopoietic tissue formation were observed in the HA + ZOL group 4 weeks after surgery. The immunohistochemical staining intensities for 5-bromodeoxyuridine, runt-related transcription factor 2, osteocalcin, osteopontin, and osteoprotegerin were significantly higher in the HA + ZOL group than that in the model (P < 0.001, P< 0.001, P< 0.001, P< 0.001, and P = 0.018, respectively) and HA groups (P = 0.003, P = 0.049, P< 0.001, P = 0.020, and P = 0.019, respectively), whereas receptor activator of the nuclear factor-κB ligand staining intensity was significantly lower in the HA + ZOL group than that in the model and HA groups (P = 0.029 and P = 0.015, respectively) 4 weeks after surgery. No significant differences in bone formation or bone resorption marker expression were found between the three groups 2 or 8 weeks after surgery (P > 0.05)., Conclusions: Local administration of HA soaked in a low-dose ZOL solution increased new bone formation while inhibiting bone resorption in an animal model of ONFH, which might provide new evidence for joint-preserving surgery in the treatment of ONFH.

A 29-year-old otherwise healthy woman presented with a lifetime history of hoarseness because it had begun to interfere with her career. Examination of both the woman and her 60-year-old father revealed bilateral sulcus vergeture, without inflammation or lesions attributable to phonotrauma. The woman responded well to injection augmentation; the father declined treatment. Combined with existing descriptions of other family groupings, all with sulcus vergeture without signs of inflammation, clinical progression, and little or no apparent behavioral component, this report further suggests that sulcus vergeture (Ford type 2) and sulcus vocalis (Ford type 3) are entirely different entities, despite architectural similarity., (Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

The present work evaluates the synergistic anticancer efficacy of bioactive Hydroxyapatite (HA) nanoparticles (HA NPs) loaded with Bendamustine HCl. Hydroxyapatite is a material with an excellent biological compatibility, a well-known fact which was also supported by the results of the Hemolytic studies and a high IC50 value observed in the MTT assay. HA NPs were prepared by the chemical precipitation method and loaded with the drug via physical adsorption. In-vitro release study was performed, which confirmed the sustained release of the drug from the drug loaded HA NPs. MTT assay, Cell Uptake and FACS studies on JURKAT E6.1 cell line and in-vivo pharmacokinetic studies in Wistar rats revealed that the drug loaded HA NPs could be easily internalized by the cells and release drug in a sustained manner. The drug loaded HA NPs showed cytotoxicity similar to the drug solution at 1/10th of the drug content, which indicates a possible synergism between the activity of the anticancer drug and calcium ions derived from the carrier. An increase in intracellular Ca(2+) ions is reported to induce apoptosis in cells. Tumor regression study in Balb/c mice Ehrlich's ascites model presented a similar synergistic efficacy. The drug solution was able to decrease the tumor volume by half, while the drug loaded HA NPs reduced the tumor size by 6 times., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Volumizing the face has become commonplace on the facial aesthetic scene, with a rapid explosion of popularity in the field of nonsurgical rejuvenation. Three-dimensional enhancement of the midface with fillers provides the surgeon with a minimal downtime opportunity to treat early aging or reverse nonsurgical volume loss. With new products come advancements in techniques and the understanding of reversal of the effects of aging. While providing minimal downtime and risk, complications can occur and the physician must be able to recognize and treat these issues. It is crucial for the injector to understand and process these factors to ensure patient satisfaction and safety., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

To obtain ideal nano-hydroxyapatite(n-HA) filler for poly(lactide-co-glycolide) (PLGA), a new surface-grafting with the assist of citric acid for nano-hydroxyapatite (n-HA) was designed, and the effect of n-HA surface-grafted with or without citric acid on in vitro degradation behavior and cells viability was studied by the experiments of soaking in simulated body fluid (SBF) and incubating with human osteoblast-like cells (MG-63). The change of pH value, tensile strength reduction, the surface deposits, cells attachment and proliferation of samples during the soaking and incubation were investigated by means of pH meter, electromechanical universal tester, scanning electron microscope (SEM) coupled with energy-dispersive spectro-scopy (EDS), fluorescence microscope and MTT method. The results showed that the introduction of citric acid not only delayed the strength reduction during the degradation by inhibiting the detachment of n-HA from PLGA, but also endowed it better cell attachment and proliferation, suggesting that the n-HA surface-grafted with the assist of citric acid was an important bioactive ceramic fillers for PLGA used as bone materials., (Copyright © 2016 Elsevier B.V. All rights reserved.)

"Nonsurgical rhinoplasty" refers to the use of injectable temporary fillers used to augment select areas of the nose to achieve improved appearance or function in select patients. Nonpermanent fillers can be used safely and must be properly chosen based on their properties and the desired effect. In addition to proper patient and product selection, a thorough understanding of nasal anatomy, analysis of the deformity, and recommended injection techniques are absolutely necessary to obtain good outcomes and avoid complications. The proper plane for injection is the deep fatty layer, just superficial to the perichondrium and periosteum. Erring on the side of undercorrection, small incremental boluses, and constant reassessment are the best way to avoid overfilling or producing irregularities and asymmetries. The most devastating and feared complications are vascular compromise, tissue necrosis, and even blindness, making the nose a challenging area to treat with fillers. The surgeon wishing to use fillers in the nose should be familiar with proper technique, recognition of developing problems, and have a practical plan in place for immediate reversal and treatment., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Hydroxyapatite (HA) nanocrystals are important inorganic constituents of biological hard tissues in vertebrates and have been proposed as a bone substitute or a coating material for prostheses in biomedicine. Hydroxyapatite is also amenable for its capacity to bind to a great variety of biomolecules and therapeutic agents. As drug carriers, apatite nanoparticles also have the advantage of pH dependent solubility and low toxicity. Thus HA nanoparticles are negligibly soluble at physiological pH but their dissolution is accelerated at lower pH such as that typically found in the vicinity of tumors. In the present study we have investigated the adsorption on and the release from biomimetic HA nanoparticles of two platinum derivatives of cis-1,4-diaminocyclohexane ([PtX2(cis-1,4-DACH)], X2 = Cl2 (1) and 1,1-cyclobutanedicarboxylate (CBDCA, 2)). The first of the two compounds proved to be active against colon cancer cells also resistant to oxaliplatin. The release has been investigated as a function of pH to mimic the different physiological environments of healthy tissues and tumors, and the in vitro cytotoxicity of the releasates from the HA matrices has been assessed against various human cancer cell lines. The results fully confirmed the potential of 1-loaded HA nanoparticles as bone-specific drug delivery devices.

Introduction: NovaMin is a synthetic mineral compound composed of calcium, sodium, phosphorus, and silica. It releases crystalline hydroxyl-carbonate apatite (HCA), which structurally resembles the minerals naturally found in the teeth. Nano-hydroxyapatite (NHA) is a biocompatible compound with high affinity for tooth enamel. NHA particles morphologically resemble dental enamel apatite crystals. Considering the efficacy of remineralizing agents and the importance of conservative preventive measures, this study aimed to compare the remin-eralizing effects of NovaMin and NHA on caries-like lesions in primary teeth., Materials and Methods: This in vitro experimental study was conducted on 30 sound human primary anterior teeth with no cracks or fractures. The surface microhardness (SMH) of each tooth was measured at baseline using a Vickers microhard-ness tester. The teeth were then subjected to remineralization/ demineralization cycles, and artificial caries lesions were created in them. The SMH of each tooth was measured again and the teeth were then randomly treated with toothpastes containing NovaMin or 10% NHA powder for 2 minutes daily for a period of 5 days. The SMH of each was again measured afterward. Data were statistically analyzed using independent t-tests and Mann-Whitney U tests., Results: The mean SMH was found to be higher in the teeth treated with NovaMin toothpaste (422.67 kgf/mm(2)) than in the teeth treated with NHA (384.2 kgf/mm(2)); However, this difference was not statistically significant., Conclusion: Both NHA and NovaMin were effective for reminer-alization of caries-like lesions of primary teeth and no significant difference was detected in their efficacy.

Nasal injectables and surface treatments alter the appearance of the nose both primarily and following nasal surgery. Fillers such as hyaluronic acids, calcium hydroxyapatite, and fat have a variety of advantages and disadvantages in eliminating small asymmetries postrhinoplasty. All nasal injectables have rare but severe ocular and cerebral ischemic complications. The injection of steroids following nasal reconstruction has a role in preventing supratip swelling and can improve the appearance of grafts to the nose. Resurfacing techniques reduce the appearance of autotransplanted grafts to the nose; there is little controversy about their benefit but surgeon preference for timing is varied., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To assess voice outcomes in patients undergoing vocal fold injection (VFI) augmentation laryngoplasty in a clinic-based setting., Methods: A prospective study of patients with unilateral vocal cord palsy undergoing Radiesse(®) vocal cord augmentation. We used the ten-item voice handicap index (VHI-10) as a postal survey before and after the intervention., Results: A total of 43 patients were referred to our ENT clinic from June 2011 to October 2014 with unilateral vocal cord palsy. The majority were referred from the oncology department with mediastinal tumours. Fifteen patients died of malignant disease. Twenty-one patients responded to our survey. VHI-10 scores were analysed using one-way analysis of variance (anova), and the results suggest a sustained improvement before and after the intervention (pre-injection versus 3 months post-injection P < 0.01; pre-injection versus 6 months post-injection P < 0.033)., Conclusion: This is the largest case series of patients who had a local anaesthetic vocal cord injection with calcium hydroxylapaptite using the trans-thyrohyoid approach. Early data would suggest that the results are similar to injections performed under general anaesthesia when performed by an experienced laryngologist. VFI in a clinic-based (awake) setting has the distinct advantage of providing instant feedback of vocal fold closure and voice outcome during the procedure, avoiding general anaesthesia with its inherent risks and cost and also the limitations of difficult exposure., (© 2015 John Wiley & Sons Ltd.)

Calcium hydroxylapatite microspheres in a carrier gel (CaHA; Radiesse®: Merz North America, Inc., Raleigh, NC) is approved by the United States Food and Drug Administration for subdermal implantation for the correction of moderate-to-severe facial wrinkles and folds, such as nasolabial folds (NLFs). Lidocaine is often mixed with injectable dermal fillers to reduce injection pain. A new formulation of CaHA has been developed with the convenience of integral 0.3% lidocaine, CaHA (+)., This multicenter, split-face, double-blind study randomized subjects to receive treatment with CaHA (+) in one NLF and CaHA without lidocaine in the contralateral NLF. The pain level for each NLF was evaluated immediately following the injection using a 10-cm visual analog scale (VAS), and every 15 minutes for 60 minutes plus follow-up visits. Additional endpoints included aesthetic outcomes and subject preference. All subjects (N=102) received treatment., CaHA (+) treatment resulted in a statistically and clinically significant reduction in pain ratings immediately after injection compared with CaHA. The mean difference in VAS scores for pain was -4.41 (P&lt;0.0001). In 90% of subjects, the VAS scores were ≥2.0 cm lower for the CaHA (+)-treated NLF. A significant reduction in pain ratings throughout the first hour after injection was observed with CaHA (+) compared with CaHA (P&lt;0.0001). Both treatment groups achieved significant aesthetic improvement; however, the pain differential resulted in a subject-reported preference for CaHA (+). CaHA (+) with integral lidocaine significantly reduces pain and is as effective as CaHA., , J Drugs Dermatol. 2016;15(8):1005-1010.

Introduction: Since one of the most important disadvantages of soft drinks includes their adverse effect on mineral content of enamel because of their low pH, this study examined the microhardness of enamel before and after exposure to a soft drink containing different concentrations of nano-hydroxyapatite (nano-HA) as an additive., Materials and Methods: Sixty caries free human premolars were mounted in epoxy resin. After polishing, the baseline micro-hardness was recorded three times for each specimen using a Vickers indenter at 50 gm load. Subsequently, the samples were divided into six groups, which were treated for 5 minutes at 9°C by a cola-based drink contacting 0, 0.5, 1, 5, and 10 wt.% of nano-HA while the control group was immersed in artificial saliva. Ultimately, the final microhardness was assessed three times again for each specimen., Results: Paired t-test showed that in groups containing 0 and 0.5 wt.% of nano-HA, the microhardness was significantly reduced after treatment protocol (p = 0.00 and 0.01 respectively). Whereas in the other groups the microhardness was not significantly changed after treatment (p > 0.05)., Conclusion: Pure cola-based drink has a pronounced adverse effect on enamel microhardness, while admixing it with nano-HA could act as a protective factor., Clinical Significance: Although soft beverages are hazardous to tooth structure, some additives could compensate their adverse effect.

Hand rejuvenation is an increasingly requested procedure in dermatology. Dorsal hand augmentation with soft tissue filler is one aspect of hand rejuvenation. Calcium hydroxyapatite is FDA approved for this purpose, while at the present time other filler products are utilized but are considered off-label for dorsal hand augmentation. This article reviews the relevant anatomy, the general and filler-specific techniques commonly employed, and potential complications that may arise. , , J Drugs Dermatol. 2016;15(7):809-815.

Recently, the application of nanostructured materials in the field of tissue engineering has garnered attention to mediate treatment and regeneration of bone defects. In this study, poly(l-lactic acid) (PLLA)/gelatin (PG) fibrous scaffolds are fabricated and β-cyclodextrin (βCD) grafted nano-hydroxyapatite (HAp) is coated onto the fibrous scaffold surface via an interaction between βCD and adamantane. Simvastatin (SIM), which is known to promote osteoblast viability and differentiation, is loaded into the remaining βCD. The specimen morphologies are characterized by scanning electron microscopy. The release profile of SIM from the drug loaded scaffold is also evaluated. In vitro proliferation and osteogenic differentiation of human adipose derived stem cells on SIM/HAp coated PG composite scaffolds is characterized by alkaline phosphatase (ALP) activity, mineralization (Alizarin Red S staining), and real time Polymerase chain reaction (PCR). The scaffolds are then implanted into rabbit calvarial defects and analyzed by microcomputed tomography for bone formation after four and eight weeks. These results demonstrate that SIM loaded PLLA/gelatin/HAp-(βCD) scaffolds promote significantly higher ALP activity, mineralization, osteogenic gene expression, and bone regeneration than control scaffolds. This suggests the potential application of this material toward bone tissue engineering., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recently, electrospun nanofibrous scaffolds are vastly taken into consideration in the bone tissue engineering due to mimicking the natural structure of native tissue. In our study, surface features of nanofibers were modified through simultaneous electrospining of the synthetic and natural polymers using poly l-lactide (PLLA) and gelatin to fabricate the hybrid scaffold (PLLA/gelatin). Then, hydroxyapatite nanoparticles (nHA) were loaded in electrospun PLLA nanofibers (PLLA,nHA/gelatin) and also dexamethasone (DEX) was incorporated in these fibers (PLLA,nHA,DEX/gelatin) in the second experiment. Fabricated nanofibrous composite scaffolds were characterized via SEM, FTIR spectroscopy, contact angle, tensile strength measurements, DEX release profile and MTT assay. After seeding adipose derived mesenchymal stem cells, osteoinductivity and osteoconductivity of fabricated scaffolds were analyzed using common osteogenic markers such as alkaline phosphatase activity, calcium depositions and gene expression. These results confirmed that all properties of nanofibers were improved by modifications. Moreover, osteogenic differentiation of stem cells increased in PLLA,nHA/gelatin group in comparison with PLLA/gelatin. The sustained release of DEX was obtained from PLLA,nHA,DEX/gelatin which subsequently led to more osteogenic differentiation. Taken together, PLLA,nHA,DEX/gelatin showed significant potential to support the stem cell proliferation and ostogenic differentiation, and can be a good candidates for tissue engineering and regenerative medicine applications., (Copyright © 2016 Elsevier B.V. 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.)

In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm(3)) as compared to rhBMP-2 alone (10.9 ± 2.1 mm(3)) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone.

Aims: The purpose of this paper was to fabricate PLLA/PCL nanofibrous scaffolds containing HAP to mimic the native bone extracellular matrix for potential applications as bone tissue engineering scaffolds materials and ultimately to help the repairing of bone defects., Materials and Methods: PLLA (MW 200kDa), PCL (MW 80kDa), HAP, dichloromethane, N,N-dimethylformamide; α-MEM, FBS, trypsin-EDTA, penicillin G, streptomycin, β-sodium glycerophosphate, l-ascorbic acid, dexamethasone; CCK-8, Alkaline Phosphatase Assay Kit, Mouse Osteocalcin ELISA Kit, MC3T3-E1 cells. PLLA, PCL and HAP were dissolved in the solution of DCM and DMF to fabricate nanofibrous scaffolds through electrospinning. The morphology of the scaffolds was investigated with SEM, while the diameter of the fibers, pore size and water uptake of the scaffolds were tested, respectively. TGA was carried out to verify the percentage of HAP in the composite scaffolds fabricated with different HAP concentrations. Cell count kit-8 assay, alkaline phosphatase (ALP) assay, and osteocalcin assay were applied to observe the MC3T3-E1 cells proliferation, differentiation on the composite scaffolds., Key Findings: MC3T3-E1 cells were found to grow actively on the composite scaffolds based on the results of CCK-8 assay. The level of MC3T3-E1 differentiation was evaluated through the ALP activity and osteocalcin concentration, which showed higher value with HAP containing (PLLA/PCL/HAP) than that ones without (PLLA/PCL)., Significance: The results demonstrated that the biocomposite PLLA/PCL/HAP nanofibrous scaffold should be a promising candidate for proliferation, differentiation and mineralization of osteoblasts, and potentially can be used for bone tissue regeneration., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The aims of the study were to describe ultrasound findings in women with stress urinary incontinence (SUI) after transurethral injection of Coaptite, to describe symptoms 3 months after injection, and to determine whether there was an association between degree of improvement and sonographic findings., Methods: This is a prospective cohort study of women with SUI undergoing transurethral Coaptite injection. Subjects completed the Urinary Distress Inventory and Incontinence Severity Index preinjection and 3 months postinjection. Translabial ultrasound was performed immediately after and 3 months postinjection. Two- and three-dimensional images were captured to measure the dimensions and location of Coaptite in relation to the bladder neck as well as degree of coaptation. Change in volume of injection over time was calculated using these measurements., Results: Twenty subjects were enrolled in the study. At 3 months, 45% of subjects had 90% or greater improvement, 45% had 50% to 75% improvement, and 10% had less than 30% improvement. Mean distance of Coaptite from the bladder neck at 3 months was not statistically different from the distance immediately after injection. There was a 40.9% to 45.8% mean reduction in volume at 3 months as well as a 39.5% reduction in coaptation. Degree of improvement was associated with mean change in volume over time: those with the least improvement had the greatest reduction in volume. Volume of initial injection, percent coaptation, and number of vials used to perform the injection were not associated with patient symptoms., Conclusions: In this series, 90% of patients who underwent Coaptite injection for SUI reported 50% or greater improvement. The volume of Coaptite decreased by 40% over time, and the degree of shrinkage correlated with clinical outcomes.

Purpose: The aim of this study was to compare the effect of ligature-induced periimplantitis on dental implants with and without hydroxyapatite (HA) coat., Methods: Thirty-two dental implants (3.3 mm wide, 13 mm long) with 4 surface treatments (8 implant/group) (M: machined, SA: sandblasted acid etched, S: sputter HA coat and P: plasma-sprayed HA coat) were inserted into canine mandibles. After 12 weeks, oral hygiene procedures were stopped and silk ligatures were placed around the implant abutments to allow plaque accumulation for the following 16 weeks. Implants with the surrounding tissues were retrieved and prepared for histological examination. Bone-to-implant contact (BIC) and implant surfaces were examined using scanning electron microscopy and energy dispersive x-ray spectroscopy., Results: Histological observation revealed marginal bone loss and large inflammatory cell infiltrates in the periimplant soft tissue. Sputter HA implants showed the largest BIC (98.1%) and machined implant showed the smallest values (70.4%). After 28 weeks, thin sputter HA coat was almost completely dissolved, whereas plasma-sprayed HA coat showed complete thickness preservation., Conclusion: Thin sputter HA-coated implants showed more bone implant contact and less marginal bone loss than thick HA-coated implants under periimplantitis condition.

Objective: To compare the effect of bone regeneration with two different ratios of nano-hydroxyapatite(nHA)/collagen(Col) (nHAC) after tooth extraction in canine., Methods: Two kinds of nHAC grafts were prepared with different nHA/collagen ratio of 3∶7 and 5∶5. Eighteen male healthy adult dogs had been randomly divided into three groups. Immediately after extraction of the mandibular second premolars, each kind of nHAC was implanted into extraction sockets as follow: Group A, nHA/Col=3∶7(12 sites); Group B, nHA/Col=5∶5(12 sites); Group C, blank control group(12 sites). The bone repairing abilities of the two grafts such as vertical distance of alveolar, CT values, general observation, histological observation, trabecular volume fraction and porosity were separately analyzed at 1st, 3rd and 6th month, respectively (each group had 4 sites in different time periods)., Results: nHAC were absorbed gradually after they were implanted into alveolar bone defect and were replaced by new bone. The vertical distance of alveolar bone in Group A([15.76±0.28] mm) was significant higher than that in Group B([14.88±0.36] mm), and CT values of Group A([879±31] HU) were higher than those in Group B([718±29] HU) (P<0.05). The trabecular bone volume percentage of Group A([22.2±0.4]%) was higher than that in Group B([20.3±0.4]%), and the bone porosity of Group A([23.6±0.9]%) was lower than that in Group B([27.6±0.6]%) (P<0.05). In addition, the vertical distance, CT values and the trabecular bone volume percentage of Group C was lower than those in Group A and B, but the bone porosity of Group C was higher., Conclusions: The nHAC with nHA/collagen ratio of 3∶7 could better promote bone regeneration than nHAC with the nHA/collagen ratio of 5∶5 did.

Various particles such as Alum or silica are known to act as an adjuvant if co-administered with vaccine antigens. Several reports have demonstrated that the adjuvanticity is strongly affected by the physicochemical properties of particles such as the size, shape and surface charge, although the required properties and its relationship to the adjuvanticity are still controversial. Hydroxyapatite particle (HAp) composed of calcium phosphate has been shown to work as adjuvant in mice. However, the properties of HAp required for the adjuvanticity have not been fully characterized yet. In this study, we examined the role of size or shape of HAps in the antibody responses after immunization with antigen. HAps whose diameter ranging between 100 and 400 nm provided significantly higher antibody responses than smaller or larger ones. By comparison between sphere and rod shaped HAps, rod shaped HAps induced stronger inflammasome-dependent IL-1β production than the sphere shaped ones in vitro. However, sphere- and rod-shaped HAp elicited comparable antibody response in WT mice. Vice versa, Nlrp3(-/-), Asc(-/-) or Caspase1(-/-) mice provided comparable level of antibody responses to HAp adjuvanted vaccination. Collectively, our results demonstrated that the size rather than shape is a more critical property, and IL-1β production via NLRP3 inflammasome is dispensable for the adjuvanticity of HAps in mice., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims . This study evaluated the effects of L-PRF presence and implant surface texture on bone healing around immediately placed implants. Methods . The first mandibular molars of 8 beagle dogs were bilaterally extracted, and implants (Blossom™, Intra-Lock International, Boca Raton, FL) were placed in the mesial or distal extraction sockets in an interpolated fashion per animal. Two implant surfaces were distributed per sockets: (1) dual acid-etched (DAE, micrometer scale textured) and (2) micrometer/nanometer scale textured (Ossean™ surface). L-PRF (Intraspin system, Intra-Lock International) was placed in a split-mouth design to fill the macrogap between implant and socket walls on one side of the mandible. The contralateral side received implants without L-PRF. A mixed-model ANOVA (at α = 0.05) evaluated the effect of implant surface, presence of L-PRF, and socket position (mesial or distal), individually or in combination on bone area fraction occupancy (BAFO). Results . BAFO values were significantly higher for the Ossean relative to the DAE surface on the larger mesial socket. The presence of L-PRF resulted in higher BAFO. The Ossean surface and L-PRF presence resulted in significantly higher BAFO. Conclusion. L-PRF and the micro-/nanometer scale textured surface resulted in increased bone formation around immediately placed implants., Competing Interests: The authors report no conflict of interests for the present study.

Lutetium-177 has been widely discussed as a radioisotope of choice for targeted radionuclide therapy. The simultaneous emission of imageable gamma photons [208 keV (11%) and 113 keV (6.4%)] along with particulate β(-) emission [β(max) = 497 keV] makes it a theranostically desirable radioisotope. In the present article, the possibility of using two 177Lu-based agents viz. 177Lu-EDTMP and 177Lu-DOTATATE for theranostic applications in metastatic bone pain palliation (MBPP) and peptide receptor radionuclide therapy (PRRT), have been explored. In the case of 177Lu-EDTMP, the whole-body images obtained are compared with those recorded using 99mTc-MDP in the same patient. On the other hand, pre-therapy images acquired with 177Lu-DOTA-TATE are compared with similar images obtained with standard agents, such as 99mTc-HYNIC-TOC (SPECT) and 68Ga-DOTA-TOC (PET) in the same patient. The advantage of the long physical half-life (T1/2) of 177Lu has been utilized in mapping the pharmacokinetics of two additional agents, 177Lu-labeled hydroxyapatite (HA) in radiation synovectomy of knee joints and 177Lu-HA for therapy of hepatocellular carcinoma. Results of these multiple studies conclusively document the potential of 177Lu as a theranostic radioisotope.

Recently, graphene-based nanomaterials, in the form of two dimensional substrates or three dimensional foams, have attracted considerable attention as bioactive scaffolds to promote the differentiation of various stem cells towards specific lineages. On the other hand, the potential advantages of using graphene-based hybrid composites directly as factors inducing cellular differentiation as well as tissue regeneration are unclear. This study examined whether nanocomposites of reduced graphene oxide (rGO) and hydroxyapatite (HAp) (rGO/HAp NCs) could enhance the osteogenesis of MC3T3-E1 preosteoblasts and promote new bone formation. When combined with HAp, rGO synergistically promoted the spontaneous osteodifferentiation of MC3T3-E1 cells without hindering their proliferation. This enhanced osteogenesis was corroborated from determination of alkaline phosphatase activity as early stage markers of osteodifferentiation and mineralization of calcium and phosphate as late stage markers. Immunoblot analysis showed that rGO/HAp NCs increase the expression levels of osteopontin and osteocalcin significantly. Furthermore, rGO/HAp grafts were found to significantly enhance new bone formation in full-thickness calvarial defects without inflammatory responses. These results suggest that rGO/HAp NCs can be exploited to craft a range of strategies for the development of novel dental and orthopedic bone grafts to accelerate bone regeneration because these graphene-based composite materials have potentials to stimulate osteogenesis.

Background: Measurement scales that quickly and rigorously evaluate the effectiveness of filler treatment in hands are important tools in clinical practice. The Merz Hand Grading Scale (MHGS) is used to grade the appearance of the dorsal hand. The MHGS has been validated for photographic and live assessment of the hands., Objective: To evaluate the sensitivity of the 5-point MHGS to detect clinically meaningful and aesthetically pleasing changes in hand appearance after treatment with a calcium hydroxylapatite (CaHA)-based dermal filler., Methods: The controlled 4-week study randomized 30 subjects (60 hands) 2:1 to a Treatment group (treatment at enrollment) or a Control group (treatment at end of study). Effectiveness was evaluated with live MHGS ratings and photographic assessments with the Global Aesthetic Improvement Scale (GAIS)., Results: At Week 4, all Treatment group subjects (20/20) achieved a ≥1-point improvement on the MHGS compared with 0/10 (0%) of the Control group (p < .0001). Subjects and treating physicians rated 92.5% (37/40) and 100% (40/40), respectively, of hands as at least "improved," using the GAIS., Conclusion: The MHGS is an appropriate and validated tool that clinicians can use to counsel patients and evaluate clinically meaningful and aesthetically pleasing changes after hand treatment with CaHA.

Background: Forty-six patients (38 females and 8 males) with infected knee arthroplasties were included in this study. In 31 patients (group A) an antibiotic-impregnated articulating spacer was used, whereas in 15 patients (group B) a combination of spacer and antibiotic carrier was used., Methods: All patients were reviewed weekly with laboratory examinations (white blood cell count [WBC], erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) prior to re-implantation. At a mean follow-up of 36 mo (range, 8-60 mo) no patient was lost to follow-up or had died., Results: White blood cell count and ESR showed no differences at any time interval. C-reactive protein values had a statistically significant difference between the two groups after the second week (third week p = 0.042) and group B had significantly lower CRP values at every checkpoint thereafter. The re-infection rate was 16.12% in group A and 6.6% in group B (p = 0.192).

There are several different classes of synthetic dermal fillers and volume enhancers including semipermanent and permanent products available in the United States. Based on clinical and scientific evidence, this article reviews the chemical and polymeric properties, clinical data, patient selection, indications for use, injection technique, and adverse event profiles of permanent synthetic injectables currently used in clinical practice in the United States: medical-grade liquid injectable silicone and polymethyl methacrylate. Understanding the unique characteristics of these two products reinforces the advantages and disadvantages of each, including under what circumstances they should be used and why they perform the way they do., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Multiple fillers are available: various hyaluronic acid products, calcium hydroxylapatite, and a few others that are biocompatible with good duration and a variety of mechanical properties allowing intradermal, subdermal, and supraperiosteal injection. Facial features can be reshaped with great control using these fillers. Aging changes, including facial volume loss, can be well-corrected. These treatments have become a mainstay of rejuvenation in the early facial aging patient. Injection technique is critical to obtaining excellent results. Threading, fanning, cross-hatching, bleb, and pillar techniques must be mastered. Technical execution can only measure up to, but not exceed, the quality of the aesthetic analysis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Radiesse is a well-tolerated facial injectable with unique filling and lifting capabilities. Although initially approved for facial volumizing in HIV-related lipodystrophy patients, it quickly gained wide acceptance for aesthetic facial rejuvenation. In the USA, the Food and Drug Administration has approved several new indications for its use. This synopsis presents the experience and injection techniques currently favored by the primary author after many years of use in thousands of patients., Methods: The anecdotal practice of an experienced injector is presented along with the current Food and Drug Administration-approved standards of Radiesse injection., Results: Radiesse has many on- and off-label applications that can be thoughtfully incorporated into clinical practice. Its unique chemical composition allows for immediate lifting and filling with long-term collagen stimulation. The product can be reconstituted to increase its versatility and minimize adverse events. Injections can be performed in the supraperiosteal space and the subcutaneous layer and are best administered in small, calculated doses to prevent nodules or vascular occlusion. Various techniques for Radiesse injection in specific areas are discussed in detail., Conclusions: Radiesse is a versatile injectable implant and a valuable tool for short- and long-term cosmetic and reconstructive treatments. In addition to various off-label uses, this injectable is often used in conjunction with botox, other injectables, collagen stimulators and tightening devices. A customized reconstitution of product increases its versatility for natural appearing and long lasting results that are both economical and effective for full facial rejuvenation.

Objectives/hypothesis: Chronic cough (CC) is a pervasive and expensive health problem in the United States. Almost as diverse as its etiologies are the available therapeutic options. When vocal fold paresis and CC coincide, injection augmentation may provide an alternative to standard medical and behavioral treatments for CC. Our objective was to assess the effect of injection augmentation in a selected group of patients with CC who had failed multiple medical and behavioral treatments., Study Design: The study design is a retrospective case review., Methods: Our study group included six subjects (1 male and 5 females; aged 24-84 y) who presented for laryngologic evaluation with a chief complaint of CC unresponsive to conventional medical and behavioral management. The cough severity index (CSI), reflux symptom index (RSI), dyspnea severity index (DSI), and voice handicap index-10 (VHI-10), as well as subjective evaluation were assessed before and after the injection augmentation of the vocal folds was undertaken., Results: Five of six patients reported subjective improvement in cough. CSI scores improved in all six (average change 7.3, range 2-13). RSI and DSI scores also improved significantly after injection, whereas VHI-10 scores did not significantly change. One patient reported transient hoarseness after injection that completely resolved. One patient received injection augmentation three times, as the material resorbed and symptoms returned., Conclusions: Injection augmentation effected relief from CC in a select group of patients with CC refractory to previous medical and/or behavioral treatments. This intervention is a novel option for such patients and offers an alternative approach to medical treatment., (Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

To assess the use and safety of calcium hydroxylapatite for volume restoration of the face and hands in clinical practice, subjects from four Italian aesthetic clinics who had received calcium hydroxylapatite augmentation treatment between January 2012 and December 2013 were recruited. Records were retrospectively reviewed for demographic characteristics, number of treatments, area treated, injection depth and volume, method of administration, and adverse events. A total of 1,783 treatments were administered to 800 subjects (female: 93.5%; mean age: 49.6 years). Overall, 620 (77.5%) subjects were treated over two sessions for a particular indication, and 243 (30.3%) treated over three sessions. The most frequently treated areas were the zygomatic area (men: 30.2%; women: 30.6% of all treatments), malar area (24.5% and 24.3%), and marionette lines (18.9% and 11.6%). A cannula was used for most treatments (86.7%). Injection volume ranged from 0.4 mL to 1.5 mL. Injection-site swelling and bruising occurred with 18.2% and 11.3% of treatments, respectively. Most cases resolved within one week and two weeks, respectively. No serious/unexpected adverse events occurred. In clinical practice, calcium hydroxylapatite is a versatile, well-tolerated treatment for filling folds and volume restoration of the face and hands.

Background: Three-dimensional (3D) changes in the midface following malar calcium hydroxyapatite (CaHa) injection have not been systematically analyzed., Objectives: The authors analyzed 3D volume changes in midface and naso-labial fold (NLF) volume, as well as lateral movement in the NLF/naso-labial crease (NLC) junction following malar injection of CaHa in a cadaver model., Methods: A single surgeon injected CaHa in the supraperiosteal plane. Sequential images were obtained with the VECTRA 3D system pre- and post-1.5- and 3-cc CaHa injections. All measurements were performed by a single examiner. Injection location was verified anatomically., Results: Injections were performed in 16 fresh cadaver hemi-faces. Maximal increases in projection were centered on the malar injection site, with associated decreases in projection and volume in the infero-medial locations. Relative mean increases in volume of 3.16 cc and 4.94 cc were observed following the 1.5-cc and 3-cc injections, respectively. There was a relative decrease in the volume of the NLF of -0.3 cc and -0.4 cc following the 1.5- and 3-cc injections, respectively. Injection of CaHa was associated with lateral movements of the NLF-NLC junction at the level of the nasal sill, philtral columns, and oral commissure, measuring 2.7, 2.5, and 1.9 mm and 2.8, 2.9, and 2.4 mm following the 1.5- and 3-cc injections, respectively. Anatomical dissection verified the location in the supraperiosteal space and within the middle malar fat pad., Conclusions: Following malar CaHa injection, 3D photographic analysis showed a measureable lifting effect with recruitment of ptotic tissue and lateral movement of the NLF-NLC junction in a cadaver model., (© 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Objectives: Hydroxyapatite (HA) is commonly used as bone substitute in clinical practices. However, only few studies have compared the relationship between the mixture ratio of bone graft in the actual clinical field and fusion rate according to bone graft volume. The study aimed to analyze the fusion rate according to the mixture ratio and the amount of bone graft in minimally invasive transforaminal lumbar interbody fusion (MI-TLIF)., Methods: A total number of 88 subjects who completed a 2-year follow-up after MI-TLIF participated in this study. Subjects were divided into three groups: Group 1 with local autograft, Group II with a mixture of HA and autobone of over 50%, and Group III with a mixture of HA and autobone of less than 50%. Subjects were also grouped into two groups: Group A with a graft volume of less than 12 ml and Group B with more than 12 ml. The correlation of mixture ratio and the graft volume with fusion rate was analyzed. For clinical analysis, visual analogue scale for pain and Oswestry Disability Index were used. Bone integration was evaluated based on the classification methods described in the Burkus study., Results: Fusion rates are increased according to the ratio of autograft in all groups: 90.9% in Group I, 87.8% in Group II, and 85.7% in Group III. However, there were no significant differences between groups (p = 0.22). The fusion rates significantly increased as the amount of bone graft increased to over 12 ml, showing 81.5% in Group A and 92.0% in Group B (p = 0.03)., Conclusions: A high rate of fusion was achieved in MI-TLIF in graft volume of more than 12 ml. We therefore recommend at least 12 ml of bone graft volume for successful fusion.

The osteogenic capacity of biomimetic calcium deficient hydroxyapatite microspheres with and without collagen obtained by emulsification of a calcium phosphate cement paste has been evaluated in an in vivo model, and compared with an injectable calcium phosphate cement with the same composition. The materials were implanted into a 5 mm defect in the femur condyle of rabbits, and bone formation was assessed after 1 and 3 months. The histological analysis revealed that the cements presented cellular activity only in the margins of the material, whereas each one of the individual microspheres was covered with osteogenic cells. Consequently, bone ingrowth was enhanced by the microspheres, with a tenfold increase compared to the cement, which was associated to the higher accessibility for the cells provided by the macroporous network between the microspheres, and the larger surface area available for osteoconduction. No significant differences were found in terms of bone formation associated with the presence of collagen in the materials, although a more extensive erosion of the collagen-containing microspheres was observed.