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Polylactic acid (PLA) is one of the most promising biodegradable and recyclable thermoplastic biopolymer derived from renewable feedstock. Nanocellulose reinforced PLA biocomposites have received increasing attention in academic and industrial communities. In the present study, cellulose nanofibrils (CNFs) was liberated by combined enzymatic pretreatment and high-pressure homogenization, and then subsequently incorporated into the PLA matrix to synthesize PLA/CNF biocomposite films via solution casting and melt compression. The prepared PLA/CNF biocomposite films were characterized in terms of transparency (UV-Vis spectroscopy), chemical structure (attenuated total reflectance-Fourier transform infrared, ATR-FTIR; X-ray powder diffraction, XRD), thermal (thermogravimetric analyzer, TGA; differential scanning calorimetry, DSC), and tensile properties. With 1.0–5.0 wt % additions of CNF to the PLA matrix, noticeable improvements in thermal and physical properties were observed for the resulting PLA/CNF biocomposites. The 2.5 wt % addition of CNF increased the tensile strength by 8.8%. The Tonset (initial degradation temperature) and Tmax (maximum degradation temperature) after adding 5.0 wt % CNF was increased by 20 °C, and 10 °C, respectively in the nitrogen atmosphere. These improvements were attributed to the good dispersibility and improved interfacial interaction of CNF in the PLA matrix.

Plasma-treatment of oral implant biomaterials prior to clinical insertion is envisaged as a potential surface modification method for enhanced implant healing. To investigate a putative effect of plasma-functionalized implant biomaterials on oral tissue cells, this investigation examined the response of alveolar bone osteoblasts and gingival fibroblasts to clinically established zirconia- and titanium-based implant surfaces for bone and soft tissue integration. The biomaterials were either functionalized with oxygen-plasma in a plasma-cleaner or left untreated as controls, and were characterized in terms of topography and wettability. For the biological evaluation, the cell adhesion, morphogenesis, metabolic activity and proliferation were examined, since these parameters are closely interconnected during cell-biomaterial interaction. The results revealed that plasma-functionalization increased implant surface wettability. The magnitude of this effect thereby depended on surface topography parameters and initial wettability of the biomaterials. Concerning the cell response, plasma-functionalization of smooth surfaces affected initial fibroblast morphogenesis, whereas osteoblast morphology on rough surfaces was mainly influenced by topography. The plasma- and topography-induced differential cell morphologies were however not strong enough to trigger a change in proliferation behaviour. Hence, the results indicate that oxygen plasma-functionalization represents a possible cytocompatible implant surface modification method which can be applied for tailoring implant surface wettability.

Boron nitride nanotubes (BNNTs) are tubular nanoparticles with a structure analogous to that of carbon nanotubes, but with B and N atoms that completely replace the C atoms. Many favorable results indicate BNNTs as safe nanomaterials; however, important concerns have recently been raised about ultra-pure, long (˜10 µm) BNNTs tested on several cell types. Here, we propose additional experiments with the same BNNTs, but shortened (˜1.5 µm) with a homogenization/sonication treatment that allows for their dispersion in gum Arabic aqueous solutions. Obtained BNNTs are tested on human endothelial and neuron-like cells with several independent biocompatibility assays. Moreover, for the first time, their strong sum-frequency generation signal is exploited to assess the cellular uptake. Our data demonstrate no toxic effects up to concentrations of 20 µg/ml, once more confirming biosafety of BNNTs, and again highlighting that nanoparticle aspect ratio plays a key role in the biocompatibility evaluation. Original submitted 3 December 2013; Revised submitted 28 January 2014; Published online 6 February 2014

Background: Two types of surface coating for cardiopulmonary bypass (CPB) are used: bioactive (heparin, nitric oxide) and biopassive (albumin, polyethyleneoxide (PEO), phosphorylcholine). When haemocompatible coatings are combined with the separation of pleuro-pericardial aspiration, attenuation of both the coagulation and complement cascades, as well as better platelet preservation, has been demonstrated. This study wants to investigate if the combination of a bioactive with a biopassive coating (unfractionated heparin embedded in a phosphorylcholine matrix) combines the beneficial effects of both approaches. Materials and methods: Thirty patients undergoing elective CABG were prospectively randomized into two groups of 15 patients. The sole exclusion criterion was an ejection fraction of less than 40%. In the control group (PC), the whole CPB circuit was coated with phosphorylcholine (PC). In the study group (XPC), unfractionated heparin was embedded in the PC matrix of the oxygenator and arterial line filter. Results: No differences were found for haemolytic index, thrombin-anti-thrombin complex (TAT), IL-6, IL-10 and blood loss. PF4 plasma concentration increased from 27.6±22.0 IU/mL to 165.7±43.9 IU/mL (p<0.001) at 15 minutes of CPB in the PC and from 16.0±9.7 IU/mL to 150.9 ± 61.3 IU/mL (p<0.001) in the XPC group. Terminal complement complex (TCC) increased over time in both groups until the end of CPB (Figure 2A). Within each group, TCC generation was statistically significantly higher after the release of the aortic cross-clamp (p<0.001) and at the end of CPB (p<0.001). Total TCC generation was statistically significantly higher in the XPC group compared to the PC group (p=0.026). The difference was statistically significant after the release of the aortic cross-clamp (p=0.005) and at the end of CPB (p=0.001). Conclusions: Based on our results, there is no additional benefit in combining phosphorylcholine with unfractionated heparin in elective patients undergoing coronary artery bypass grafting (CABG). Massive haemodilution leads to enhanced complement activation.

The objective of this study was to fabricate and characterize chitosan combined with different amounts of simvastatin-loaded nanoparticles and to investigate their potential for guided bone regeneration in vitro and in vivo. Different SIM-CSN formulations were combined into a chitosan scaffold (SIM-CSNs-S), and the morphology, simvastatin release profile, and effect on cell proliferation and differentiation were investigated. For in vivo experiments, ectopic osteogenesis and the critical-size cranial defect model in SD rats were chosen to evaluate bone regeneration potential. All three SIM-CSNs-S formulations had a porous structure and exhibited sustained simvastatin release. CSNs-S showed excellent degradation and biocompatibility characteristics. The 4 mg SIM-CSNs-S formulation stimulated higher BMSC ALP activity levels, demonstrated significantly earlier collagen enhancement, and led to faster bone regeneration than the other formulations. SIM-CSNs-S should have a significant effect on bone regeneration. Highlights Simvastatin-loaded nanoparticles of chitosan. The preparing process of Chitosan scaffolds combined with simvastatin loaded is simple, low-cost and environmental friendly. A sustained release of simvastatin.

Background Different superparamagnetic iron oxide nanoparticles have been tested for their potential use in cancer treatment, as they enter into cells with high effectiveness, do not induce cytotoxicity, and are retained for relatively long periods of time inside the cells. We have analyzed the interaction, internalization and biocompatibility of dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles with an average diameter of 15 nm and negative surface charge in MCF-7 breast cancer cells. Results Cells were incubated with dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles for different time intervals, ranging from 0.5 to 72 h. These nanoparticles showed efficient internalization and relatively slow clearance. Time-dependent uptake studies demonstrated the maximum accumulation of dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles after 24 h of incubation, and afterwards they were slowly removed from cells. Superparamagnetic iron oxide nanoparticles were internalized by energy dependent endocytosis and localized in endosomes. Transmission electron microscopy studies showed macropinocytosis uptake and clathrin-mediated internalization depending on the nanoparticles aggregate size. MCF-7 cells accumulated these nanoparticles without any significant effect on cell morphology, cytoskeleton organization, cell cycle distribution, reactive oxygen species generation and cell viability, showing a similar behavior to untreated control cells. Conclusions All these findings indicate that dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles have excellent properties in terms of efficiency and biocompatibility for application to target breast cancer cells.

A randomized open-heart surgery study comprising 30 patients was undertaken to compare the biocompatibility of Phisio-(phosphorylcholine) and PMEA-(poly-2-methoxyethyl acrylate) coated cardiopulmonary bypass (CPB) circuits and to assess the initial complement pathway activation during open-heart surgery. Blood samples were obtained at five time points, from the start of surgery to 24 hours postoperatively. The following analyses were performed: haemoglobin, lactate dehydrogenase, leukocyte and platelet counts, myeloperoxidase and neutrophil-activating peptide-2, thrombin-anti-thrombin complexes, syndecan-1 and the complement activation products C1rs-C1-inhibitor complexes, C4bc, C3bc, C3bBbP and the terminal complement complex (TCC). No significant inter-group difference was found in any parameters, except for the concentration of TCC which was moderately lower in the PMEA group at termination of CPB. Complement activation during open-heart surgery was mainly mediated through the alternative pathway. In conclusion, PMEA- and Phisio-coated circuits displayed similar biocompatibility with respect to inflammatory and haemostatic responses during and after open-heart surgery.

Background The use of gold nanoparticles (AuNPs) for diagnostic applications and for drug and gene-delivery is currently under intensive investigation. For such applications, biocompatibility and the absence of cytotoxicity of AuNPs is essential. Although generally considered as highly biocompatible, previous in vitro studies have shown that cytotoxicity of AuNPs in certain human epithelial cells was observed. In particular, the degree of purification of AuNPs (presence of sodium citrate residues on the particles) was shown to affect the proliferation and induce cytotoxicity in these cells. To expand these studies, we have examined if the effects are related to nanoparticle size (10, 11 nm, 25 nm), to the presence of sodium citrate on the particles' surface or they are due to a varying degree of internalization of the AuNPs. Since two cell types are present in the major barriers to the outside in the human body, we have also included endothelial cells from the vasculature and blood brain barrier. Results Transmission electron microscopy demonstrates that the internalized gold nanoparticles are located within vesicles. Increased cytotoxicity was observed after exposure to AuNPs and was found to be concentration-dependent. In addition, cell viability and the proliferation of both endothelial cells decreased after exposure to gold nanoparticles, especially at high concentrations. Moreover, in contrast to the size of the particles (10 nm, 11 nm, 25 nm), the presence of sodium citrate on the nanoparticle surface appeared to enhance these effects. The effects on microvascular endothelial cells from blood vessels were slightly enhanced compared to the effects on brain-derived endothelial cells. A quantification of AuNPs within cells by ICP-AES showed that epithelial cells internalized a higher quantity of AuNPs compared to endothelial cells and that the quantity of uptake is not correlated with the amount of sodium citrate on the nanoparticles’ surface. Conclusions In conclusion the higher amount of citrate on the particle surface resulted in a higher impairment of cell viability, but did not enhance or reduce the uptake behavior in endothelial or epithelial cells. In addition, epithelial and endothelial cells exhibited different uptake behaviors for citrate-stabilized gold nanoparticles, which might be related to different interactions occurring at the nanoparticle-cell-surface interface. The different uptake in epithelial cells might explain the higher reduction of proliferation of these cells after exposure to AuNPs treatment although more detailed investigations are necessary to determine subcellular events. Nevertheless an extrinsic effect of sodium-citrate stabilized particles could not be excluded. Thus, the amount of sodium citrate should be reduced to a level on which the stability of the particles and the safety for biomedical applications are guaranteed.

Osteonecrosis of the femoral head (ONFH) is a major cause of morbidity, and total hip arthroplasty is both traumatic and expensive. Here, we created a gelatine scaffold embedded in uniquely shaped, 3D-printed porous titanium parts, which could attract and promote the proliferation of osteoblasts as well as bone regeneration, as the extracellular matrix (ECM) does in vivo. Interestingly, after hybridisation with platelets, the scaffold exhibited a low yet considerable rate of stable, safe and long-term growth factor release. Additionally, a novel ONFH model was constructed and verified. Scaffolds implanted in this model were found to accelerate bone repair. In conclusion, our scaffold successfully simulates the ECM and considerably accelerates bone regeneration, in which platelets play an indispensable role. We believe that platelets should be emphasised as carriers that may be employed to transport drugs, cytokines and other small molecules to target locations in vivo. In addition, this novel scaffold is a useful material for treating ONFH.An overview of the novel scaffold mimicking the extracellular environment in bone repair. a and b: A gelatine scaffold was cross-linked and freeze-dried within 3D-printed porous titanium. c: Platelets were coated onto the gelatine microscaffold after freeze-drying platelet-rich plasma. d: The microscaffold supported the migration of cells into the titanium pores and their subsequent growth, while the platelets slowly released cell factors, exerting bioactivity.

The surface properties of biomaterials play a vital role in cell morphology and behaviors such as cell adhesion, migration, proliferation and differentiation. Three different crystal phases of titania film (rutile, anatase and amorphous titania) with similar roughness were successfully synthesized by DC reactive magnetron sputtering. The surface roughness of each film was about 8–10 nm. Primary rat osteoblasts were used to observe changes in morphology and to evaluate cell behavior at the film surface. The number of the osteoblasts on anatase film was significantly higher than rutile and amorphous films after 36 and 72 h incubation. More importantly, synthesis of alkaline phosphatase was significantly greater by osteoblasts cultured on anatase film than on rutile and amorphous films after 7 and 14 days. In addition, the cells grown on the anatase phase film had the largest spreading area; the actin filaments in cells with regular directions were well defined and fully spreaded. The results indicate that the anatase phase of titania with nanoscale topography yield the best biological effects for cell adhesion, spreading, proliferation and differentiation. There are strong therapeutic prospects for this biomaterial film for osteoblast proliferation, with possible applications for orthopedic and dental implant.