Polyethylene-glycol-coated gold nanoparticles improve cardiac function after myocardial infarction in mice.

Gold nanoparticles (AuNPs) are widely used for drug delivery because of their unique biological properties, such as their safety and ability to prolong drug action. Some studies have demonstrated that AuNPs accumulate in the heart, especially during pathological processes. Therefore, it is very important to understand the effect of AuNPs on the heart. Myocardial infarction (MI) is a major cause of morbidity and mortality; however, the effect of AuNPs on MI remains unclear. In the present study, we carried out a comprehensive evaluation of AuNPs on acute MI. The results showed that AuNPs accumulated in infarcted hearts, decreased infarction size, improved systolic function, and inhibited cardiac fibrosis and TNF-α accumulation. Our work indicated that AuNPs have cardioprotective effects and can be used in drug delivery systems for the treatment of cardiac diseases.

Preventive effects of simvastatin nanoliposome on isoproterenol-induced cardiac remodeling in mice.

In this study, simvastatin (SMV) and SMV nanoliposome (SMV-Lipo) were given to male BALB/c mice by either intragastric (i.g.) or intraperitoneal (i.p.) administration, and their effects on isoproterenol (ISO)-induced cardiac remodeling were compared. The results indicate that by i.p. administration, the SMV-Lipo at an equal SMV dose exhibited more significant inhibitory effects than the crude SMV on cardiac hypertrophy, fibrosis and inflammation. Comparing the SMV-Lipo on different administration regimens, i.p. group showed more significant inhibitory effects on cardiac remodeling than i.g. group. In addition, pharmacokinetic studies revealed that SMV-Lipo administrated by either i.p. or i.g. more significantly improved the plasma SMV concentration than the crude SMV. Therefore, the SMV-Lipo significantly enhanced the inhibitory effects of SMV on cardiac remodeling resulted from the enhanced absorption of SMV by nanoliposome formulation, and i.p. was better than i.g. administration.

A pH-neutral bioactive glass coated 3D-printed porous Ti6Al4V scaffold with enhanced osseointegration.

Osseointegration is vital for the success of non-degradable implants like those made of titanium alloys. In order to promote osseointegration, implants are made porous, providing space for bone ingrowth. Despite extensive optimization of the pore geometry and porosity, bone ingrowth into implants is still marginal; further modification to promote bone ingrowth as well as osseointegration becomes paramount. In this study, a pH neutral bioactive glass with the composition of 10.8% P2O5-54.2% SiO2-35% CaO (mol%; hereinafter referred to as PSC) was successfully coated on 3D-printed porous Ti6Al4V scaffolds using an in situ sol-gel method. This PSC coating is strongly bonded to the substrate and quickly induces the formation of hydroxyapatite on the scaffold surface upon contact with body fluid. In vitro, the PSC-coated Ti6Al4V scaffolds showed superior biocompatibility, cell proliferation promotion, cell adhesion, osteogenic differentiation and mineralization compared to their bare counterparts, implying better osseointegration. In vivo experiments confirmed this expectation; after being implanted, the coated scaffolds had more bone ingrowth and osseointegration, and consequently, higher push-out strength was achieved, proving the validity of the proposed concept in this study. In conclusion, PSC coating on 3D-printed porous Ti6Al4V scaffolds can improve osteogenesis, bone ingrowth, and osseointegration. Together with the versatility of this in situ sol-gel coating method, titanium alloy implants with better biological performances may be developed for immediate clinical applications.

The development of binary Mg-Ca alloys for use as biodegradable materials within bone.

Binary Mg-Ca alloys with various Ca contents were fabricated under different working conditions. X-ray diffraction (XRD) analysis and optical microscopy observations showed that Mg-xCa (x=1-3 wt%) alloys were composed of two phases, alpha (Mg) and Mg2Ca. The results of tensile tests and in vitro corrosion tests indicated that the mechanical properties could be adjusted by controlling the Ca content and processing treatment. The yield strength (YS), ultimate tensile strength (UTS) and elongation decreased with increasing Ca content. The UTS and elongation of as-cast Mg-1Ca alloy (71.38+/-3.01 MPa and 1.87+/-0.14%) were largely improved after hot rolling (166.7+/-3.01 MPa and 3+/-0.78%) and hot extrusion (239.63+/-7.21 MPa and 10.63+/-0.64%). The in vitro corrosion test in simulated body fluid (SBF) indicated that the microstructure and working history of Mg-xCa alloys strongly affected their corrosion behaviors. An increasing content of Mg2Ca phase led to a higher corrosion rate whereas hot rolling and hot extrusion could reduce it. The cytotoxicity evaluation using L-929 cells revealed that Mg-1Ca alloy did not induce toxicity to cells, and the viability of cells for Mg-1Ca alloy extraction medium was better than that of control. Moreover, Mg-1Ca alloy pins, with commercial pure Ti pins as control, were implanted into the left and right rabbit femoral shafts, respectively, and observed for 1, 2 and 3 months. High activity of osteoblast and osteocytes were observed around the Mg-1Ca alloy pins as shown by hematoxylin and eosin stained tissue sections. Radiographic examination revealed that the Mg-1Ca alloy pins gradually degraded in vivo within 90 days and the newly formed bone was clearly seen at month 3. Both the in vitro and in vivo corrosion suggested that a mixture of Mg(OH)2 and hydroxyapatite formed on the surface of Mg-1Ca alloy with the extension of immersion/implantation time. In addition, no significant difference (p>0.05) of serum magnesium was detected at different degradation stages. All these results revealed that Mg-1Ca alloy had the acceptable biocompatibility as a new kind of biodegradable implant material. Based on the above results, a solid alloy/liquid solution interface model was also proposed to interpret the biocorrosion process and the associated hydroxyapatite mineralization.

PEG-coated gold nanoparticles attenuate ß-adrenergic receptor-mediated cardiac hypertrophy.

Gold nanoparticles (AuNPs) are widely used as a drug delivery vehicle, which can accumulate in the heart through blood circulation. Therefore, it is very important to understand the effect of AuNPs on the heart, especially under pathological conditions. In this study, we found that PEG-coated AuNPs attenuate ß-adrenergic receptor (ß-AR)-mediated acute cardiac hypertrophy and inflammation. However, both isoproterenol, a non-selective ß-AR agonist, and AuNPs did not induce cardiac function change or cardiac fibrosis. AuNPs exerted an anti-cardiac hypertrophy effect by decreasing ß1-AR expression and its downstream ERK1/2 hypertrophic pathway. Our results indicated that AuNPs might be safe and have the potential to be used as multi-functional materials (drug carrier systems and anti-cardiac hypertrophy agents).

Reversible cardiac hypertrophy induced by PEG-coated gold nanoparticles in mice.

Gold nanoparticles (GNPs) are attracting more and more attention for their great potential value in biomedical application. Currently, no study has been reported on the chronic cardiac toxicity of GNPs after repeated administration. Here we carried out a comprehensive evaluation of the chronic cardiac toxicity of GNPs to the heart. Polyethylene glycol (PEG) -coated GNPs at three different sizes (10, 30 and 50 nm) or PBS was administrated to mice via tail vein for 14 consecutive days. Then the mice were euthanized at 2 weeks, 4 weeks or 12 weeks after the first injection. The accumulation of GNPs in the mouse heart and their effects on cardiac function, structure, fibrosis and inflammation were analysized. GNPs with smaller size showed higher accumulation and faster elimination. None of the three sizes of GNPs affected cardiac systolic function. The LVIDd (left ventricular end-diastolicinner-dimension), LVMass (left ventricular mass) and HW/BW (heart weight/body weight) were significantly increased in the mice receiving 10 nm PEG-GNPs for 2 weeks, but not for 4 weeks or 12 weeks. These results indicated that the accumulation of small size GNPs can induce reversible cardiac hypertrophy. Our results provide the basis for the further biomedical applications of GNPs in cardiac diseases.

Orthodontic treatment of a patient with cleidocranial dysplasia: A case report.

Cleidocranial dysplasia (CCD) is a rare autosomal dominant condition that affects ossification. The dental abnormalities associated with CCD present an obstacle to orthodontic treatment planning. Early diagnosis is crucial to provide the patient with different treatment modalities that will suit the particular patient. In the present case, combined surgical and orthodontic treatment were performed to guide multiple impacted teeth. A single nucleotide missense variation was identified in exon 3 of runt-related transcription factor 2 (RUNX2) in this patient. The current results suggest a correlation between dental alterations and mutations in the runt domain of RUNX2 in CCD patients. Further clinical and genetic studies may required to confirm the association between phenotypes and genotypes in CCD and to identify other factors that may influence the clinical features of this disease. Patients with cleidocranial dysplasia require a team approach which demands good communication and cooperation from the patient. Timing of the intervention is critical, and numerous surgeries may be required. The patient in the present case report was treated by a team of practitioners, which involved several dental specialties to achieve an optimal result.

No overt structural or functional changes associated with PEG-coated gold nanoparticles accumulation with acute exposure in the mouse heart.

In this study, we investigated the cardiac biodistribution of polyethylene glycol (PEG)-coated AuNPs and their effects on cardiac function, structure and inflammation in both normal and cardiac remodeling mice. The model of cardiac remodeling was induced by subcutaneously injection of isoproterenol (ISO), a non-selective beta-adrenergic agonist, for 7 days. After AuNPs were injected intravenously in mice for 7 consecutive days, Au content in different organs was determined quantitatively by inductively coupled plasma mass spectrometry (ICP-MS), cardiac function and structure were measured by echocardiography, cardiac fibrosis was examined with picrosirius red staining, the morphology of cardiomyocytes was observed with hematoxylin and eosin (H & E) staining. The accumulation of AuNPs in hearts did not affect cardiac function or induce cardiac hypertrophy, cardiac fibrosis and cardiac inflammation under normal physiological condition. Cardiac AuNPs content was 6-fold higher in the cardiac remodeling mouse than normal mice. However, the increased accumulation of AuNPs in the heart did not aggravate ISO-induced cardiac hypertrophy, cardiac fibrosis or cardiac inflammation. These observations suggest that PEG-coated AuNPs possess excellent biocompatibility under both physiological and pathological conditions. Thus, AuNPs may be safe for cardiac patients and hold great promise for further development for various biomedical applications.

Intraoperative monitoring for safety of total hip arthroplasty using third-generation cementing technique.

BACKGROUND: Controversies on the safety of the cement application between cemented and uncemented total hip arthroplasty (THA) have been existing for decades. The purpose of this study was to observe the changes in mean arterial pressure (MAP), heart rate (HR) and oxygen pressure (PaO(2)) during cemented THA, and to evaluate the intraoperative safety of using the third-generation cementing technique and investigate whether the intraoperative risk is higher in acute femoral neck fracture patients than non-traumatic patients. METHODS: Forty-two patients who underwent cemented THA between November 2005 and September 2007 were prospectively included in this study. The third-generation cementing technique as vacuum mixing and pulsatile lavage was used strictly. The MAP and HR were monitored and documented during each operation. Blood gas analysis was performed at exposure, cup implantation, stem implantation and wound closure. MAP, HR and PaO(2) were compared between pre- and post-cement application. Comparisons of MAP, HR and PaO(2) between patients with acute femoral neck fracture and non-traumatic patients were performed as well. RESULTS: No intraoperative cardiopulmonary complication occurred in these cases. No obvious changes were observed in MAP, HR and PaO(2) after cement application. There was no significant difference in MAP, HR and PaO(2) between acute femoral fracture patients (18 patients) and non-traumatic patients (24 patients). CONCLUSIONS: The results of this study suggested that the invasive blood pressure monitoring and blood gas analysis are essential for patients undergoing cemented THA, especially for patients with femoral neck fracture. The third-generation cementing technique is safe to use in THA.