Antimicrobial ‘inks’ for 3D printing: block copolymer-silver nanoparticle composites synthesised using supercritical CO2

Silver nanoparticles (AgNP) are widely exploited for their effective antimicrobial activity against a range of pathogens. Their high efficacy in this regard has seen the global demand for AgNP in consumer products steadily increase in recent years, necessitating research into novel low environmental impact synthesis approaches. Here we present a new synthetic methodology to produce polymer-AgNP composite microparticles using supercritical carbon dioxide (scCO2) and avoiding use of any petrochemically derived solvents. Poly(methyl methacrylate)-poly(4-vinylpyridine) (PMMA-b-P4VP) block copolymers were synthesised via RAFT-mediated dispersion polymerisation in scCO2, with in situ thermal degradation of various amounts of a CO2-soluble silver complex. Selective interaction of the silver with the pyridinyl moieties of the block copolymer allowed the formation of AgNP, dispersed within the block copolymer microparticles, leading to homogeneous composites. The by-products of the reaction were also removed by extracting with a flow of CO2 to yield a clean dry product in a single process. The composites were found to be non-cytotoxic and proved to have good antimicrobial activity against two bacterial strains. Though no significant activity was seen for at least the first 24 hours, inhibition of bacterial growth afterwards proved to be extremely persistent, with inhibition observed even after 15 days. Finally, the microparticulate nature of the synthesised composites was exploited and tested for compatibility in the Laser Sintering (LS) 3D printing process. Composite microparticles were fused to produce solid objects, without aggregation of the AgNP. With further optimisation, these composites could prove to be an incredibly versatile ‘ink’ that may be used within additive manufacturing and 3D printing to rapidly produce bespoke medical devices with inherent antimicrobial activity

2‐Methyltetrahydrofuran (2‐MeTHF) as a versatile green solvent for the synthesis of amphiphilic copolymers via ROP, FRP, and RAFT tandem polymerizations

2‐methyltetrahydrofuran (2‐MeTHF) is a readily available, inexpensive, neoteric, bio‐based solvent. It has been adopted across a wide range of chemical processes including the batch manufacture of fine chemicals, enzymatic polycondensations and ring opening polymerizations. To reduce the environmental burden related to the synthesis of pharmaceutical‐grade polymers based on lactide and caprolactone, we envisaged the use of 2‐MeTHF. For the first time, we combined a series of metal‐free and enzymatic ROPs with free radical and controlled RAFT polymerizations (carried out separately and in tandem) in 2‐MeTHF, in order to easily tune the chemistry and the architecture of the final polymers. After a simple purification, the amphiphilic polymers were formulated into nanoparticles and tested for their cytocompatibility in three model cell lines, to assess their application as potential polymeric excipients for nanomedicines

A ‘greener’ one-pot synthesis of monoterpene-functionalised lactide oligomers

© 2020 Elsevier Ltd In this work we aimed to achieve a totally sustainable Ring Opening Polymerisation (ROP) process, by harmonising the use of naturally occurring or derivable initiators and the green solvent 2-Methyltetrahydrofuran (2-MeTHF). First, a library of novel monoterpene-alcohols and existing terpenoids was used to provide renewably sourced initiators for a metal-free ROP synthetic step. A number of these initiators are derived from waste materials, further improving their sustainability. Secondly, we selected lactide (LA) as a monomer, because not only is it derived from biomass, but its resultant polymers are biocompatible and biodegradable. Interestingly, these new polymers self-assembled in water producing well defined, biocompatible nanoparticles (NPs) via direct nanoprecipitation without the use of additional stabilisers. We have highlighted a novel and promising (ROP) approach to produce biodegradable, amphiphilic ester-based macromolecules, based on lactide and terpenes (as initiators) in a green solvent, 2-MeTHF thus reducing solvent toxicity in an efficient, simple and sustainable new synthesis. The monoterpenes may provide a highly functionalisable and bio-renewable toolbox for a new generation of ROP initiators

A Behavioral Change Perspective of Maroon Soil Fertility Management in Traditional Shifting Cultivation in Suriname

In Suriname, the Maroons have practiced shifting cultivation for generations, but now the increasing influence of modern society is causing a trend of decreasing fallow periods with potentially adverse effects for the vulnerable tropical soils. Adoption of appropriate soil fertility management (SFM) practices is currently slow. Combining methods from cultural ecology and environmental psychology, this study identifies two groups with divergent behavioral intentions which we term semi-permanent cultivators and shifting cultivators. Semi-permanent cultivators intend to practice more permanent agriculture and experiment individually with plot-level SFM. Shifting cultivators rely on traditional knowledge that is not adequate for their reduced fallow periods, but perceive constraints that prevent them practicing more permanent agriculture. Semi-permanent cultivators act as a strong reference group setting a subjective norm, yet feel no need to exchange knowledge with shifting cultivators who are in danger of feeling marginalized. Drawing on a political ecology perspective, we conclude that cultural ecological knowledge declined due to negative perceptions of external actors setting a strong subjective norm. Semi-permanent cultivators who wish to enter the market economy are most likely to adopt SFM. We conclude that any future SFM intervention must be based on an in-depth understanding of each group’s behavior, in order to avoid exacerbating processes of marginalization

A coleção fotográfica de Marcel Gautherot

Considering contemporary Anthropologys debate around photography, there is a\ud keen interest in the understanding of one of the most important open to public consultation\ud photographic collections on 20th Century Brazil, that of Frenchman Marcel Gautherot (1910-\ud 1996). The collection comprises around 25,000 photographs, purchased in 1999 by Instituto\ud Moreira Salles and kept in its fund in the city of Rio de Janeiro. The text comments on the\ud photographers work, linked to documentary projects under the patronage of institutions such as\ud the Musée de l´Homme in Paris, at the end of the 1930s, and both the National Historic and\ud Artistic Patrimony Service and the Brazilian Folklore Defence Campaign, in Brazil, between the\ud years of 1940 -1960. Such commitments and interests define important thematic groupings in\ud the production and organisation of his personal photographic archive. A discussion about criteria and technical procedures adopted by the photographer is attempted, detailing series\ud and visual narratives about Brazilian cultures density. With the photographs purchase by the\ud IMS, the oeuvres aesthetic quality, now as an institutional collection, is highlighted. The collections\ud manners of preservation and conservation, reproduction and circulation are redefined

N-Hydroxyethyl acrylamide as a functional eROP initiator for the preparation of nanoparticles under “greener” reaction conditions

N-Hydroxyethyl acrylamide was used as a functional initiator for the enzymatic ring-opening polymerisation of ε-caprolactone and δ-valerolactone. N-Hydroxyethyl acrylamide was found not to undergo self-reaction in the presence of Lipase B from Candida antarctica under the reaction conditions employed. By contrast, this is a major problem for 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate which both show significant transesterification issues leading to unwanted branching and cross-linking. Surprisingly, N-hydroxyethyl acrylamide did not react fully during enzymatic ring-opening polymerisation. Computational docking studies helped us understand that the initiated polymer chains have a higher affinity for the enzyme active site than the initiator alone, leading to polymer propagation proceeding at a faster rate than polymer initiation leading to incomplete initiator consumption. Hydroxyl end group fidelity was confirmed by organocatalytic chain extension with lactide. N-Hydroxyethyl acrylamide initiated polycaprolactones were free-radical copolymerised with PEGMA to produce a small set of amphiphilic copolymers. The amphiphilic polymers were shown to self-assemble into nanoparticles, and to display low cytotoxicity in 2D in vitro experiments. To increase the green credentials of the synthetic strategies, all reactions were carried out in 2-methyl tetrahydrofuran, a solvent derived from renewable resources and an alternative for the more traditionally used fossil-based solvents tetrahydrofuran, dichloromethane, and toluene

Poly (diglycerol adipate) variants as enhanced nanocarrier replacements in drug delivery applications

Sustainably derived poly(glycerol adipate) (PGA) has been deemed to deliver all the desirable features expected in a polymeric scaffold for drug-delivery, including biodegradability, biocompatibility, self-assembly into nanoparticles (NPs) and a functionalisable pendant group. Despite showing these advantages over commercial alkyl polyesters, PGA suffers from a series of key drawbacks caused by poor amphiphilic balance. This leads to weak drug-polymer interactions and subsequent low drug-loading in NPs, as well as low NPs stability. To overcome this, in the present work, we applied a more significant variation of the polyester backbone while maintaining mild and sustainable polymerisation conditions. We have investigated the effect of the variation of both hydrophilic and hydrophobic segments upon physical properties and drug interactions as well as self-assembly and NPs stability. For the first time we have replaced glycerol with the more hydrophilic diglycerol, as well as adjusting the final amphiphilic balance of the polyester repetitive units by incorporating the more hydrophobic 1,6-n-hexanediol (Hex). The properties of the novel poly(diglycerol adipate) (PDGA) variants have been compared against known polyglycerol-based polyesters. Interestingly, while the bare PDGA showed improved water solubility and diminished self-assembling ability, the Hex variation demonstrated enhanced features as a nanocarrier. In this regard, PDGAHex NPs were tested for their stability in different environments and for their ability to encode enhanced drug loading. Moreover, the novel materials have shown good biocompatibility in both in vitro and in vivo (whole organism) experiments

Glycerol-based sustainably sourced resin for volumetric printing

Volumetric Additive Manufacturing (VAM) represents a revolutionary advancement in the field of Additive Manufacturing, as it allows for the creation of objects in a single, cohesive process, rather than in a layer-by-layer approach. This innovative technique offers unparalleled design freedom and significantly reduces printing times. A current limitation of VAM is the availability of suitable resins with the required photoreactive chemistry and from sustainable sources. To support the application of this technology, we have developed a sustainable resin based on polyglycerol, a bioderived (e.g., vegetable origin), colourless, and easily functionisable oligomer produced from glycerol. To transform polyglycerol-6 into an acrylate photo-printable resin we adopted a simple, one-step, and scalable synthesis route. Polyglycerol-6-acrylate fulfils all the necessary criteria for volumetric printing (transparency, photo-reactivity, viscosity) and was successfully used to print a variety of models with intricate geometries and good resolution. The waste resin was found to be reusable with minimal performance issues, improving resin utilisation and minimising waste material. Furthermore, by incorporating dopants such as poly(glycerol) adipate acrylate (PGA-A) and 10,12-pentacosadyinoic acid (PCDA), we demonstrated the ability to print objects with a diverse range of functionalities, including temperature sensing probes and a polyester excipient, highlighting the potential applications of these new resins

A self-crosslinking monomer, ?-pinene methacrylate: understanding and exploiting hydrogen abstraction

Crosslinking is a valuable route to creating new polymeric materials and normally involves introduction of a cross linker or some form of secondary processing. Here we report the discovery and analysis of a self-crosslinking sustainable terpene derived monomer, ?-pinene methacrylate (?PMA). This monomer undergoes crosslinking during free radical homopolymerisation and with comonomers e.g. methyl methacrylate (MMA). ?PMA does not appear to contain any obvious functionality that would induce crosslinking such as vinyl bonds, but we postulate that it may undergo a fortuitous abstraction of a hydrogen atom from the pendant group. A combined computational (DFT) and experimental approach has been applied to investigate this. Further, we used DFT analysis to predict the behaviour of a related monomer, beta-pinene methacrylate (?PMA). To the best of our knowledge this is the first-time that self-crosslinking has been observed in free radical polymerisation of methacrylates via chain transfer through hydrogen abstraction from a pendant group. We have exploited this crosslinking to generate new, renewable poly high internal phase emulsions (polyHIPEs) that could rival those derived from fossil-based styrene- polyHIPEs and we have done this in a process which does not require any additional cross-linking agent

Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

Rationale Asthma phenotyping requires novel biomarker discovery. Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs). Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA