Polyelectrolyte-coated mesoporous bioactive glasses via layer-by-layer deposition for sustained co-delivery of therapeutic ions and drugs

In the field of bone regeneration, considerable attention has been addressed towards the use of mesoporous bioactive glasses (MBGs), as multifunctional therapeutic platforms for advanced medical devices. In fact, their extremely high exposed surface area and pore volume allow to load and the release of several drugs, while their framework can be enriched with specific therapeutic ions allowing to boost the tissue regeneration. However, due to the open and easily accessible mesopore structure of MBG, the release of the incorporated therapeutic molecules shows an initial burst effect leading to unsuitable release kinetics. Hence, a still open challenge in the design of drug delivery systems based on MBGs is the control of their release behavior. In this work, Layer-by-layer (LbL) deposition of polyelectrolyte multi-layers was exploited as a powerful and versatile technique for coating the surface of Cu-substituted MBG nanoparticles with innovative multifunctional drug delivery systems for co-releasing of therapeutic copper ions (exerting pro-angiogenic and anti-bacterial effects) and an anti-inflammatory drug (ibuprofen). Two different routes were investigated: in the first strategy, chitosan and alginate were assembled by forming the multi-layered surface, and, successively, ibuprofen was loaded by incipient wetness impregnation, while in the second approach, alginate was replaced by ibuprofen, introduced as polyelectrolyte layer. Zeta-potential, TGA and FT-IR spectroscopy were measured after the addition of each polyelectrolyte layer, confirming the occurrence of the stepwise deposition. In addition, the in vitro bioactivity and the ability to modulate the release of the cargo were evaluated. The polyelectrolyte coated-MBGs were proved to retain the peculiar ability to induce hydroxyapatite formation after 7 days of soaking in Simulated Body Fluid. Both copper ions and ibuprofen were co-released over time, showing a sustained release profile up to 14 days and 24 h, respectively, with a significantly lower burst release compared to the bare MBG particles

LIFECYCLE MANAGEMENT, MONITORING AND ASSESSMENT FOR SAFE LARGE-SCALE INFRASTRUCTURES: CHALLENGES AND NEEDS

Many European infrastructures dating back to ’50 and ’60 of the last century like bridges and viaducts are approaching the end of their design lifetime. In most European countries costs related to maintenance of infrastructures reach a quite high percentage of the construction budget and additional costs in terms of traffic delay are due to downtime related to the inspection and maintenance interventions. In the last 30 years, the rate of deterioration of these infrastructures has increased due to increased traffic loads, climate change related events and man-made hazards. A sustainable approach to infrastructures management over their lifecycle plays a key role in reducing the impact of mobility on safety (over 50 000 fatalities in EU per year) and the impact of greenhouse gases emission related to fossil fuels. The events related to the recent collapse of the Morandi bridge in Italy tragically highlighted the sheer need to improve resilience of aging transport infrastructures, in order to increase the safety for people and goods and to reduce losses of functionality and the related consequences. In this focus Structural Health Monitoring (SHM) is one of the key strategies with a great potential to provide a new approach to performance assessment and maintenance over the life cycle for an efficient, safe, resilient and sustainable management of the infrastructures. In this paper research efforts, needs and challenges in terms of performance monitoring, assessment and standardization are described and discussed.The networking support of COST Action TU1402 on ‘Quantifying the Value of Structural Health Monitoring’ and of COST Action TU1406 on ‘Quality specifications for roadway bridges, standardization at a European level (BridgeSpec)

Erratum to: Analysis of in vitro ADCC and clinical response to trastuzumab: possible relevance of Fc\u3b3RIIIA/Fc\u3b3RIIA gene polymorphisms and HER-2 expression levels on breast cancer cell lines

BACKGROUND: Trastuzumab is a humanized monoclonal antibody (mAb) currently used for the treatment of breast cancer (BC) patients with HER-2 overexpressing tumor subtype. Previous data reported the involvement of FcγRIIIA/IIA gene polymorphisms and/or antibody-dependent cellular cytotoxicity (ADCC) in the therapeutic efficacy of trastuzumab, although results on these issues are still controversial. This study was aimed to evaluate in vitro the functional relationships among FcγRIIIA/IIA polymorphisms, ADCC intensity and HER-2 expression on tumor target cells and to correlate them with response to trastuzumab. PATIENTS AND METHODS: Twenty-five patients with HER-2 overexpressing BC, receiving trastuzumab in a neoadjuvant (NEO) or metastatic (MTS) setting, were genotyped for the FcγRIIIA 158V>F and FcγRIIA 131H>R polymorphisms by a newly developed pyrosequencing assay and by multiplex Tetra-primer-ARMS PCR, respectively. Trastuzumab-mediated ADCC of patients’ peripheral blood mononuclear cells (PBMCs) was evaluated prior to therapy and measured by (51)Chromium release using as targets three human BC cell lines showing different levels of reactivity with trastuzumab. RESULTS: We found that the FcγRIIIA 158F and/or the FcγRIIA 131R variants, commonly reported as unfavorable in BC, may actually behave as ADCC favorable genotypes, in both the NEO (P ranging from 0.009 to 0.039 and from 0.007 to 0.047, respectively) and MTS (P ranging from 0.009 to 0.032 and P = 0.034, respectively) patients. The ADCC intensity was affected by different levels of trastuzumab reactivity with BC target cells. In this context, the MCF-7 cell line, showing the lowest reactivity with trastuzumab, resulted the most suitable cell line for evaluating ADCC and response to trastuzumab. Indeed, we found a statistically significant correlation between an increased frequency of patients showing ADCC of MCF-7 and complete response to trastuzumab in the NEO setting (P = 0.006). CONCLUSIONS: Although this study was performed in a limited number of patients, it would indicate a correlation of FcγR gene polymorphisms to the ADCC extent in combination with the HER-2 expression levels on tumor target cells in BC patients. However, to confirm our findings further experimental evidences obtained from a larger cohort of BC patients are mandatory. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0680-0) contains supplementary material, which is available to authorized users

Thermal stability and flame retardancy of polyester fabrics sol-gel treated in the presence of boehmite nanoparticles

Polyester fabrics have been treated with hybrid organic-inorganic sols containing aluminium hydroxide, namely a synthetic boehmite. The treated fabrics have been thoroughly investigated by infrared spectroscopy, scanning electron microscopy coupled to elemental analysis and thermogravimetry. Furthermore, the flammability of the coated fabrics has been assessed and compared with that achieved by applying the two components separately. More specifically, flammability tests have shown that the sol-gel treatment in the presence of boehmite nanoparticles is able to suppress the dripping phenomenon, which represents the main issue to fulfil for polyester fabric

Bio-inspired micro-drills for future planetary exploration

In a domain such as space technology, where robustness, mass, volume and power efficiency are key, biological organisms may provide inspiration for new systems with high performance. By using micro-technology processes, designers of space systems may take advantage of the millions of years over which miniaturised mechanisms in plants and animals have been optimised for survival. Space exploration often requires systems equipped with drills, and miniaturised drillers could enable a number of new space operations. Two natural digging systems have been studied as potential miniature space digging systems; the ovipositors of the female locust and of sirex noctilio, a species of woodwasp. Being insectoid systems, the mechanics of their design work on an inherently small scale, though they are also thought to be scalable. Results of preliminary studies, performed during collaboration between the Advanced Concepts Team of ESA, the University of Bath, the University of Surrey, D'appolonia and EADS-Astrium, are presented and discussed. Engineering solutions are proposed and analysed to assess the potential of new bio-inspired miniaturised digging systems for space applications. Copyright © 2006 by ASME

Dielectric relaxation phenomena of UV-cured epoxy systems treated with layer-by-layer nanosilica assemblies

This work focuses on dielectric relaxation phenomena of hybrid organic-inorganic epoxy systems obtained through the application of a Layer-by-Layer (LbL) silica assembly on a UV-cured epoxy system, based on the copolymerization of a cycloaliphatic diepoxy monomer (namely 3,4-epoxycyclohexylmethyl-3',4'-epoxy-cyclohexane carboxylate-CE) with a flexibilizing comonomer (1,6-hexanediol diglycidyl ether-HDGE). More specifically, UV-cured HDGE/CE films (containing 30 wt.% CE) were LbL treated by 10 and 20 silica bilayers (positively charged/negatively charged) on both sides. The dielectric properties of the LbL treated films were investigated and compared to those of the untreated counterparts, using broadband dielectric spectroscopy over a wide range of frequencies (10 -1 Hz-1 MHz) and over a temperature span ranging from 173 to 373 K. The frequency dependence of the dielectric losses for the analysed films allowed to highlight three relaxation peaks, associated with molecular motions of the polymer chains (γ, β and α), which turned out to evolve as a function of temperature. Furthermore, the thermal properties obtained using thermogravimetric analysis and differential scanning calorimetry have been assessed. The results were correlated with the structural morphology of the copolymer film with the nanosilica bilayers

Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries - A randomized trial

Context Percutaneous coronary revascularization of small vessels is associated with a high restenosis rate. Sirolimus-eluting stents reduce restenosis in simple and previously untreated lesions of large coronary arteries, but their outcomes in small vessels have not been adequately investigated. Objective To determine whether sirolimus-eluting stents are associated with a reduced 8-month rate of angiographic restenosis in comparison with an uncoated stent. Design, Setting, and Patients This was a randomized, multicenter, single-blind, prospective trial performed with 257 patients undergoing percutaneous coronary revascularization for ischemic heart disease, and who had a previously untreated atherosclerotic lesion located in a small segment with a diameter of 2.75 mm or less, in 20 Italian centers between August 2002 and December 2003. Intervention Patients were randomly assigned to receive a sirolimus-eluting stent (129 patients) or an uncoated stent having an identical architecture and radiographic appearance (128 patients). Main Outcome Measures The primary end point was the 8-month binary in-segment restenosis rate; secondary end points included procedural success and the 8-month rate of major adverse cardiac and cerebrovascular events. Results The mean (SD) reference diameter of the treated segment was 2.2 (0.28) mm; the lesion length, 11.84(6.15) mm. After 8 months, the binary in-segment restenosis rate was 53.1% (60/113) in the patients receiving an uncoated stent and 9.8% (12/123) in those receiving a sirolimus-eluting stent (relative risk [RR], 0.18; 95% confidence interval [CI], 0.10-0.32; P<.001). Fewer patients randomized to sirolimus-eluting stents experienced major adverse cardiac events (12/129 [9.3%] vs 40/128 [31.3%]; RR, 0.30; 95% CI, 0.15-0.55; P<.001) mainly because of a reduction in target lesion revascularization (9/129 [7%] vs 27/128 [21.1%]; RR, 0.33; 95% CI, 0.14-0.70; P=.002) and myocardial infarction (2/129 [1.6%] vs 10/129 [7.8%]; RR, 0.20; 95% CI, 0.01-0.93; P=.04). Conclusion The use of sirolimus-eluting stents to treat atherosclerotic lesions in small coronary arteries reduces restenosis and may also reduce major adverse cardiac events