Tissue engineering scaffolds have emerged as a powerful tool within regenerative medicine. These materials are being designed to create environments that promote regeneration through a combination ...of: (i) scaffold architecture, (ii) the use of scaffolds as vehicles for transplanting progenitor cells, and/or (iii) localized delivery of inductive factors or genes encoding for these inductive factors. This review describes the techniques associated with each of these components. Additionally, the immune response is increasingly recognized as a factor influencing regeneration. The immune reaction to an implant begins with an acute response to the injury and innate recognition of foreign materials, with the subsequent chronic immune response involving specific recognition of antigens (e.g., transplanted cells) by the adaptive immune response, which can eventually lead to rejection of the implant. Thus, we also describe the impact of each component on the immune response, and strategies (e.g., material design, anti-inflammatory cytokine delivery, and immune cell recruitment/transplantation) to modulate, yet not eliminate, the local immune response in order to promote regeneration, which represents another important tool for regenerative medicine.
Micropollutants (MP) are only partly removed from municipal wastewater by nutrient removal plants and are seen increasingly as a threat to aquatic ecosystems and to the safety of drinking water ...resources. The addition of powder activated carbon (PAC) is a promising technology to complement municipal nutrient removal plants in order to achieve a significant reduction of MPs and ecotoxicity in receiving waters. This paper presents the salient outcomes of pilot- and full-scale applications of PAC addition in different flow schemes for micropollutant removal in municipal wastewater treatment plants (WWTPs). The sorption efficiency of PAC is reduced with increasing dissolved organic carbon (DOC). Adequate treatment of secondary effluent with 5-10 g DOC m(-3) requires 10-20 g PAC m(-3) of effluent. Counter-current use of PAC by recycling waste PAC from post-treatment in a contact tank with an additional clarifier to the biology tank improved the overall MP removal by 10 to 50% compared with effluent PAC application alone. A dosage of 15 g PAC m(-3) to a full-scale flocculation sand filtration system and recycling the backwash water to the biology tank showed similar MP elimination. Due to an adequate mixing regime and the addition of adapted flocculants, a good retention of the fine fraction of the PAC in the deep-bed filter were observed (1-3 g TSS m(-3); TSS: total suspended solids). With double use of PAC, only half of the PAC was required to reach MP removal efficiencies similar to the direct single dosage of PAC to the biology tank. Overall, the application of PAC in WWTPs seems to be an adequate and feasible technology for efficient MP elimination (>80%) from wastewater comparable with post ozonation.
The aim of this study was to compare the pharmacokinetics (PK) of selexipag and its active metabolite ACT-333679 following single oral administration of one tablet of 200 µg selexipag (Treatment A) ...for adult use vs. 4 tablets of 50 µg (Treatment B) for pediatric use, in healthy adult male subjects.
Abstract Gene delivery from tissue engineering scaffolds provides the opportunity to control the microenvironment by inducing expression of regenerative factors. Hydroxyapatite (HAp) nanoparticles ...can bind lentivirus, and we investigated the incorporation of HAp into poly(lactide-co-glycolide) (PLG) scaffolds in order to retain lentivirus added to the scaffold. PLG/HAp scaffolds loaded with lentivirus enhanced transgene expression over 10-fold in vitro relative to scaffolds without HAp. Following in vivo implantation, PLG/HAp scaffolds promoted transgene expression for more than 100 days, with the level and duration enhanced relative to control scaffolds with lentivirus/HAp complexes added to PLG scaffolds. The extent of HAp incorporated into the scaffold influenced transgene expression, in part through its impact on porous architecture. Expression in vivo was localized to PLG/HAp scaffolds, with macrophages the primary cell type transduced at day 3, yet transduction of neutrophils and dendritic cells was also observed. At day 21 in PLG/HAp scaffolds, non-immune cells were transduced to a greater extent than immune cells, a trend that was opposite results from PLG scaffolds. Thus, in addition to retaining the virus, PLG/HAp influenced cell infiltration and preferentially transduced non-immune cells.
Methods This was an open-label, randomized, two-treatment, two-period, crossover study including 20 healthy male subjects. In the presence of multiple-dose gemfibrozil, a 2-fold increase in selexipag ...exposure was observed (geometric mean ratios Treatment B/Treatment A and 90% confidence intervals CIs for maximum plasma concentration (Cmax) and area under the plasma...
Methods This was an open-label, randomized, two-treatment, two-period, crossover study including 20 healthy male subjects. Concomitant administration of selexipag and multiple-dose rifampicin led to ...no relevant change in exposure to selexipag (geometric mean ratios Treatment B/Treatment A and 90% confidence intervals CIs for maximum plasma concentration (Cmax) and area under...
The disposal of sewage sludge and the agricultural use of stabilised sludge are decreasing due to more stringent regulations in Europe. An increasing fraction of sewage sludge must therefore be ...dewatered, dried, incinerated and the ashes disposed of in landfills. These processes are cost-intensive and also lead to the loss of the valuable phosphate resources incorporated in the sludge ash. The implementation of processes that could reduce excess sludge production and recycle phosphate is therefore recommended. Partial ozonation of the return sludge of an activated sludge system significantly reduces excess sludge production, improves the settling properties of the sludge and reduces bulking and scumming. The solubilised COD will also improve denitrification if the treated sludge is recycled to the anoxic zone. However, ozonation partly kills nitrifiers and could therefore lead to a decrease of the effective solid retention time of the nitrifier, thus reducing the safety of the nitrification. This paper discusses the effect of ozonation on sludge reduction, the operating stability of nitrification, the improvement of denitrification and also presents an energy and cost evaluation.
The disposal of sewage sludge and the agricultural use of stabilised sludge are decreasing due to more stringent regulations in Europe. An increasing fraction of sewage sludge must therefore be ...dewatered, dried, incinerated and the ashes disposed of in landfills. These processes are cost-intensive and also lead to the loss of valuable phosphate resources incorporated in the sludge ash. The implementation of processes that could reduce excess sludge production and recycle phosphate is therefore recommended. Disintegration of biological sludge by mechanical, thermal and physical methods could significantly reduce excess sludge production, improve the settling properties of the sludge and reduce bulking and scumming. The solubilised COD could also improve denitrification if the treated sludge is recycled to the anoxic zone. However, disintegration partly inhibits and kills nitrifiers and could therefore shorten their effective solid retention time, thus reducing the safety of the nitrification. This paper discusses the potential of disintegration on sludge reduction, the operating stability of nitrification, the improvement of denitrification and also presents an energy and cost evaluation.
To protect the ecosystem and drinking water resources in Switzerland and in the countries of the downstream catchments, a new Swiss water protection act entered into force in 2016 aiming to reduce ...the discharge of micropollutants from wastewater treatment plants (WWTPs). As a consequence, selected WWTPs must be upgraded by an advanced treatment for micropollutant abatement with suitable and economic options such as (powdered) activated carbon treatment or ozonation. WWTP Neugut (105′000 people equivalent) was the first WWTP in Switzerland to implement a long-term full-scale ozonation. Differing specific ozone doses in the range of 0.35–0.97 g O3/g DOC were applied to determine the adequate ozone dose to fulfill the requirements of the Swiss water protection act. Based on this assessment, a specific ozone dose of 0.55 g O3/g DOC is recommended at this plant to ensure an average abatement of the twelve selected indicator substances by ≥80% over the whole treatment. A monitoring of 550 substances confirmed that this dose was very efficient to abate a broad range of micropollutants by >79% on average. After ozonation, an additional biological post-treatment is required to eliminate possible negative ecotoxicological effects generated during ozonation caused by biodegradable ozonation transformation products (OTPs) and oxidation by-products (OBPs). Three biological treatments (sand filtration, moving bed, fixed bed) and granular activated carbon (GAC, fresh and pre-loaded) filtration were evaluated as post-treatments after ozonation. In parallel, a fresh GAC filter directly connected to the effluent of the secondary clarifier was assessed. Among the three purely biological post-treatments, the sand filtration performed best in terms of removal of dissolved organic carbon (DOC), assimilable organic carbon (AOC) and total suspended solids (TSS). The fresh activated carbon filtration ensured a significant additional micropollutants abatement after ozonation due to sorption. The relative abatement of the indicator substances ranged between 20 and 89% after 27′000 bed volumes (BV) and was still substantial at 50′000 BV. In an identical GAC filter running in parallel and being fed with the effluent of the secondary clarifier, the elimination was less efficient. Seven primary OTPs (chlorothiazide and six N-oxides) formed during ozonation could be quantified thanks to available reference standards. Their concentration decreased with increasing specific ozone doses with the concomitant formation of other OTPs. The seven OTPs were found to be stable compounds and were not abated in the biological post-treatments. They were sorbed in the fresh GAC filter, but less efficiently than the corresponding parent compounds. Two OBPs, bromate (BrO3−) and N-nitrosodimethylamine (NDMA), were formed during ozonation but did not exceeded 5 μg/L for bromate and 30 ng/L for NDMA at the recommended specific ozone dose of 0.55 g O3/g DOC. NDMA was well abated in all post-treatments (minimum 41% during fixed bed filtration, maximum 83% during fresh GAC filtration), while bromate was very stable as expected.
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•The abatement of around 200 micropollutants during biological treatment and ozonation.•Micropollutants removal during GAC filtration before and after ozonation was compared.•The fate of 19 ozonation products was investigated in various post-treatments.•Bromate and NDMA levels in the receiving surface water were below critical values.
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