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Presented in this work is the use of a molecular descriptor, termed the α parameter, to aid in the design of a series of novel, terpene-based, and sustainable polymers that were resistant to biofilm formation by the model bacterial pathogen

Graphical abstract, Environmental structure describes physical structure that can determine heterogenous spatial distribution of biotic and abiotic (nutrients, stressors etc.) components of a microorganism’s microenvironment. This study investigated the impact of micrometre-scale structure on microbial stress sensing, using yeast cells exposed to copper in microfluidic devices comprising either complex soil-like architectures or simplified environmental structures. In the soil micromodels, the responses of individual cells to inflowing medium supplemented with high copper (using cells expressing a copper-responsive pCUP1-reporter fusion) could be described neither by spatial metrics developed to quantify proximity to environmental structures and surrounding space, nor by computational modelling of fluid flow in the systems. In contrast, the proximities of cells to structures did correlate with their responses to elevated copper in microfluidic chambers that contained simplified environmental structure. Here, cells within more open spaces showed the stronger responses to the copper-supplemented inflow. These insights highlight not only the importance of structure for microbial responses to their chemical environment, but also how predictive modelling of these interactions can depend on complexity of the system, even when deploying controlled laboratory conditions and microfluidics.

Tissue engineered bone scaffolds are potential alternatives to bone allografts and autografts. Porous scaffolds based on triply periodic minimal surfaces (TPMS) are good candidates for tissue growth because they offer high surface-to-volume ratio, have tailorable stiffness, and can be easily fabricated by additive manufacturing. However, the range of TPMS scaffold types is extensive, and it is not yet clear which type provides the fastest cell or tissue growth while being sufficiently stiff to act as a bone graft. Nor is there currently an established methodology for TPMS bone scaffold design which can be quickly adopted by medical designers or biologists designing implants. In this study, we examine six TPMS scaffold types for use as tissue growth scaffolds and propose a general methodology to optimise their geometry. At the macro-scale, the optimisation routine ensures a scaffold stiffness within suitable limits for bone, while at the micro-scale it maximises the cell growth rate. The optimisation procedure also ensures the scaffold pores are of sufficient diameter to allow oxygen and nutrient delivery via capillaries. Of the examined TPMS structures, the Lidinoid and Split P cell types provide the greatest cell growth rates and are therefore the best candidates for bone scaffolds.

Pristine graphene and graphene-based heterostructures can exhibit exceptionally high electron mobility if their surface contains few electron-scattering impurities. Mobility directly influences electrical conductivity and its dependence on the carrier density. But linking these key transport parameters remains a challenging task for both theorists and experimentalists. Here, we report numerical and analytical models of carrier transport in graphene, which reveal a universal connection between graphene’s carrier mobility and the variation of its electrical conductivity with carrier density. Our model of graphene conductivity is based on a convolution of carrier density and its uncertainty, which is verified by numerical solution of the Boltzmann transport equation including the effects of charged impurity scattering and optical phonons on the carrier mobility. This model reproduces, explains, and unifies experimental mobility and conductivity data from a wide range of samples and provides a way to predict a priori all key transport parameters of graphene devices. Our results open a route for controlling the transport properties of graphene by doping and for engineering the properties of 2D materials and heterostructures. Graphene exhibits both extremely high electrical conductivity and electron mobility but an incomplete understanding of the underlying mechanisms so far limits potential applications in electrical devices. Here, the authors theoretically and experimentally investigate the role of charged impurities and optical phonons on the conductivity properties of graphene and establish a universal connection between the mobility and conductivity.

Chronic infection as a result of bacterial biofilm formation on implanted medical devices is a major global healthcare problem requiring new biocompatible, biofilm-resistant materials. Here we demonstrate how bespoke devices can be manufactured through ink-jet-based 3D printing using bacterial biofilm inhibiting formulations without the need for eluting antibiotics or coatings. Candidate monomers were formulated and their processability and reliability demonstrated. Formulations for in vivo evaluation of the 3D printed structures were selected on the basis of their in vitro bacterial biofilm inhibitory properties and lack of mammalian cell cytotoxicity. In vivo in a mouse implant infection model, Pseudomonas aeruginosa biofilm formation on poly-TCDMDA was reduced by ∼99% when compared with medical grade silicone. Whole mouse bioluminescence imaging and tissue immunohistochemistry revealed the ability of the printed device to modulate host immune responses as well as preventing biofilm formation on the device and infection of the surrounding tissues. Since 3D printing can be used to manufacture devices for both prototyping and clinical use, the versatility of ink-jet based 3D-printing to create personalised functional medical devices is demonstrated by the biofilm resistance of both a finger joint prosthetic and a prostatic stent printed in poly-TCDMDA towards P. aeruginosa and Staphylococcus aureus.

One of the most striking characteristics of 3D printing is its capability to produce multi-material objects with complex geometry. In pharmaceutics this translates to the possibility of dosage forms with multi-drug loading, tailored dosing and release. We have developed a novel dual material hot-melt inkjet 3D printing system which allows for precisely controlled multi-material solvent free inkjet printing. This reduces the need for time-consuming exchanges of printable inks and expensive post processing steps. With this printer, we show the potential for design of printed dosage forms for tailored drug release, including single and multi-material complex 3D patterns with defined localised drug loading where a drug-free ink is used as a release-retarding barrier. For this, we used Compritol HD5 ATO (matrix material) and Fenofibrate (model drug) to prepare both drug-free and drug-loaded inks with drug concentrations varying between 5% and 30% (w/w). The printed constructs demonstrated the required physical properties and displayed immediate, extended, delayed and pulsatile drug release depending on drug localisation inside of the printed formulations. For the first time, this paper demonstrates that a commonly used pharmaceutical lipid, Compritol HD5 ATO, can be printed via hot-melt inkjet printing as single ink material, or in combination with a drug, without the need for additional solvents. Concurrently, this paper demonstrates the capabilities of dual material hot-melt inkjet 3D printing system to produce multi-material personalised solid dosage forms.

The physical environments in which microorganisms naturally reside rarely have homogeneous structure, and changes in their porous architecture may have effects on microbial activities that are not typically captured in conventional laboratory studies. In this study, to investigate the influence of environmental structure on microbial responses to stress, we constructed structured environments with different pore properties (determined by X-ray computed tomography). First, using glass beads in different arrangements and inoculated with the soil yeast Saitozyma podzolica, increases in the average equivalent spherical diameters (ESD) of a structure’s porous architecture led to decreased survival of the yeast under a toxic metal challenge with lead nitrate. This relationship was reproduced when yeasts were introduced into additively manufactured lattice structures, comprising regular arrays with ESDs comparable to those of the bead structures. The pore ESD dependency of metal resistance was not attributable to differences in cell density in microenvironments delimited by different pore sizes, supporting the inference that pore size specifically was the important parameter in determining survival of stress. These findings highlight the importance of the physical architecture of an organism’s immediate environment for its response to environmental perturbation, while offering new tools for investigating these interactions in the laboratory. IMPORTANCE Interactions between cells and their structured environments are poorly understood but have significant implications for organismal success in both natural and nonnatural settings. This work used a multidisciplinary approach to develop laboratory models with which the influence of a key parameter of environmental structure—pore size—on cell activities can be dissected. Using these new methods in tandem with additive manufacturing, we demonstrated that resistance of yeast soil isolates to stress (from a common metal pollutant) is inversely related to pore size of their environment. This has important ramifications for understanding how microorganisms respond to stress in different environments. The findings also establish new pathways for resolving the effects of physical environment on microbial activity, enabling important understanding that is not readily attainable with traditional bulk sampling and analysis approaches.

We report the first successful combination of three distinct high-throughput techniques to deliver the accelerated design, synthesis, and property screening of a library of novel, bio-instructive, polymeric, comb-graft surfactants. These three-dimensional, surface-active materials were successfully used to control the surface properties of particles by forming a unimolecular deep layer on the surface of the particles via microfluidic processing. This strategy deliberately utilizes the surfactant to both create the stable particles and deliver a desired cell-instructive behavior. Therefore, these specifically designed, highly functional surfactants are critical to promoting a desired cell response. This library contained surfactants constructed from 20 molecularly distinct (meth)acrylic monomers, which had been pre-identified by HT screening to exhibit specific, varied, and desirable bacterial biofilm inhibitory responses. The surfactant's self-assembly properties in water were assessed by developing a novel, fully automated, HT method to determine the critical aggregation concentration. These values were used as the input data to a computational-based evaluation of the key molecular descriptors that dictated aggregation behavior. Thus, this combination of HT techniques facilitated the rapid design, generation, and evaluation of further novel, highly functional, cell-instructive surfaces by application of designed surfactants possessing complex molecular architectures.

Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. Phase separation has been exploited to fabricate intricate microstructures in many fields including cell biology, tissue engineering, optics, and electronics. The aim of this study was to use phase separation to tailor the spatial location of drugs and thereby generate release profiles of drug payload over periods ranging from 1 week to months by exploiting different mechanisms: polymer degradation, polymer diluent dissolution, and control of microstructure. To achieve this, we used drop-on-demand inkjet three-dimensional (3D) printing. We predicted the microstructure resulting from phase separation using high-throughput screening combined with a model based on the Flory-Huggins interaction parameter and were able to show that drug release from 3D-printed objects can be predicted from observations based on single drops of mixtures. We demonstrated for the first time that inkjet 3D printing yields controllable phase separation using picoliter droplets of blended photoreactive oligomers/monomers. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be "dialled up" without manipulation of device geometry. We exemplify this approach by fabricating a biodegradable, long-term, multiactive drug delivery subdermal implant ("polyimplant") for combination therapy and personalized treatment of coronary heart disease. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be easily exploited, which brings a hitherto unseen level of understanding to emergent material properties of 3D printing.

Nowadays there is a worldwide growing interest in the Inkjet Printing technology owing to its potentially high levels of geometrical complexity, personalization and resolution. There is also social concern about usage, disposal and accumulation of plastic materials. In this work, it is shown that sugar-based biodegradable polyurethane polymers exhibit outstanding properties as polymer-matrix for gold nanoparticles composites. These materials could reach exceptional stabilization levels, and demonstrated potential as novel robust inks for Inkjet based Printing. Furthermore, a physical comparison among different polymers is discussed based on stability and printability experiments to search for the best ink candidate. The University of Seville logo was printed by employing those inks, and the presence of gold was confirmed by ToF-SIMS. This approach has the potential to open new routes and applications for fabrication of enhanced biomedical nanometallic-sensors using stabilized AuNP. Spanish Ministerio de Economía y Competitividad MINECO, (Grants Nos. CTQ2016- 78703-P and MAT2016-78703-P) Junta de Andalucía (Consolidation Grant for Research Group FQM135 and 2017/FQM-386, P-2018/809) University of Seville (V y VI Plan Propio PP2016-5937)

Inkjet printing of metal nanoparticles allows for design flexibility, rapid processing and enables the 3D printing of functional electronic devices through co-deposition of multiple materials. However, the performance of printed devices, especially their electrical conductivity, is lower than those made by traditional manufacturing methods and is not fully understood. Here, we reveal that anisotropic electrical conductivity of printed metal nanoparticles is caused by organic residuals from their inks. We employ a combination of electrical resistivity tests, morphological analysis and 3D nanoscale chemical analysis of printed devices using silver nanoparticles to show that the polymer stabiliser polyvinylpyrrolidone tends to concentrate between vertically stacked nanoparticle layers as well as at dielectric/conductive interfaces. Understanding the behaviour of organic residues in printed nanoparticles reveals potential new strategies to improve nanomaterial ink formulations for functional printed electronics. Inkjet printed metal nanoparticles are known to have lower electrical conductivity than those produced by traditional approaches. Here, anisotropic electrical conductivity is attributed to organic residuals from the metal nanoparticle ink, reducing conductivity.

In this paper, we present the development of a family of novel, UV-curable, highly flexible, 3D printable silicone-based materials, the mechanical properties of which can be tuned simply by varying the ratio of the polymerisable reagents within the formulation. This tuneability is achieved by exploiting the balance between in-cure phase separation and differential reactivity within the formulation to successfully produce composite structures via both casting and valve-based jetting processes. The structure and properties of both cast and 3D printed materials were examined in a range of compositions of silicone to acrylate between 30:70 and 70:30. The phase segregated structure, evidenced from distinct glass transitions, and the thermal stability of these materials were both shown to be insensitive to the composition ratio, whereas the elastic properties were strongly dependent on the composition. The stiffness could be made to vary from ~50 kPa to ~180 kPa by increasing the silicone content. This study will guide the formation of a new generation of Additive Manufacturing (AM) silicone elastomeric functional structures for various applications ranging from flexible electronics to regenerative medicine, which will benefit from local changes in mechanical properties within the same material family.

International audience; Inkjet 3D printing is an additive manufacturing method that allows the user to produce a small batch of customized devices for comparative study versus commercial products. Here, we describe the use of a commercial 2D ink development system (Dimatix material printing) to manufacture small batches of 3D medical or other devices using a recently characterized fungal anti-attachment material. Such printed devices may resist problems that beset commercial medical products due to colonization by the fungal pathogen Candida albicans. By sequentially introducing the cross-section bitmaps of the product's CAD model and elevating the print head height using the auto-clicking script, we were able to create complex self-support geometries with the 2D ink development system. The use of this protocol allows researchers to produce a small batch of specimens for characterization from only a few grams of raw material. Additionally, we describe the testing of manufactured specimens for fungal anti-attachment. In comparison with most commercial AM systems, which require at least a few hundred grams of ink for printing trials, our protocol is well suited for smaller-scale production in material studies.

An extrusion-based 3D printer has been used for the manufacturing of sustained drug release poly(e-caprolactone) (PCL) implants. Such implants can address issues of reduced patient compliance due to the necessary frequent administration of conventional drug delivery systems, such as tablets, capsules and solutions. The selected model drug for this study was lidocaine. Polycaprolactone core-shell implants, as well as polymeric implants with no barrier shell were printed with different drug loading, without the addition of solvents or further excipients. Scanning Electron Microscopy (SEM) analysis revealed the structural integrity of the printed formulations, while Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD) and Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) were used to detect potential chemical interactions or modifications. Raman spectroscopy was also used to study material distribution in the prints. The drug release rate of the differently printed formulations was evaluated using a USP4 flow-through cell apparatus. All printed implants demonstrated sustained lidocaine release and the effectiveness of the PCL barrier in this regard. The Korsmeyer-Peppas model was suggested as the best fit to drug release profiles for all the produced implants. This work demonstrates that hot-melt extrusion-based 3D printing is a robust and promising technology for the production of personalisable drug-eluting implants.

In the pharmaceutical industry, the ability to improve the understanding of the effect of surface roughness on interparticulate interactions is critical. Dry powder inhalers often possess poor efficiency, as the powder formulations are inherently adhesive and cohesive due to their size. The complex interplay of factors that affect interparticulate interactions, means it has been difficult to isolate the effect of surface morphology. Using two photon polymerisation, this study shows the fabrication of bespoke sub-micron geometric structures, with a consistent surface chemistry. These are used to investigate the effect of surface morphologies on particle adhesion by utilising AFM force-volume mapping, to model spheres and carrier particles. This demonstrates the significant effect varying surface morphology can have on particle-surface adhesion. This approach allows for the first time an in-depth examination of the local variation effect of surface features on particle adhesion and may facilitate the design and optimisation of powder processes.

© 2020 The Author(s) Spatial structure over scales ranging from nanometres to centimetres (and beyond) varies markedly in diverse habitats and the industry-relevant settings that support microbial activity. Developing an understanding of the interplay between a structured environment and the associated microbial processes and ecology is fundamental, but challenging. Several novel approaches have recently been developed and implemented to help address key questions for the field: from the use of imaging tools such as X-ray Computed Tomography to explore microbial growth in soils, to the fabrication of scratched materials to examine microbial-surface interactions, to the design of microfluidic devices to track microbial biofilm formation and the metabolic processes therein. This review discusses new approaches and challenges for incorporating structured elements into the study of microbial processes across different scales. We highlight how such methods can be pivotal for furthering our understanding of microbial interactions with their environments.

Analytical effective refractive index (n eff ) calculations for unit cells of ring/spoke structures, fabricated by two-photon polymerization, are undertaken. Geometrical parameters (spoke width, spoke length and number of spokes) are varied. Resulting n eff values are mapped to a hyperbolic-secant profile resulting in a gradient index optic.

We demonstrate the formulation of advanced functional 3D printing inks that prevent the formation of bacterial biofilms in vivo. Starting from polymer libraries, we show that a biofilm resistant object can be 3D printed with the potential for shape and cell instructive function to be selected independently. When tested in vivo, the candidate materials not only resisted bacterial attachment but drove the recruitment of host defences in order to clear infection. To exemplify our approach, we manufacture a finger prosthetic and demonstrate that it resists biofilm formation – a cell instructive function that can prevent the development of infection during surgical implantation. More widely, cell instructive behaviours can be ‘dialled up’ from available libraries and may include in the future such diverse functions as the modulation of immune response and the direction of stem cell fate.

As our understanding of disease grows, it is becoming established that treatment needs to be personalized and targeted to the needs of the individual. In this paper we show that multi-material inkjet-based 3D printing, when backed with generative design algorithms, can bring a step change in the personalization of medical devices. We take cell-instructive materials known for their resistance to bacterial biofilm formation and reformulate for multi-material inkjet-based 3D printing. Specimens with customizable mechanical moduli are obtained without loss of their cell-instructive properties. The manufacturing is coupled to a design algorithm that takes a user-specified deformation and computes the distribution of the materials needed to meet the target under given load constraints. Optimisation led to a voxel map file defining where different materials should be placed. Manufactured products were assessed against the mechanical and cell-instructive specifications and ultimately showed how multifunctional personalization emerges from generative design driven 3D printing.

Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. In this study, we show that ink jet 3D printing of polymer blends gives rise to controllable phase separation that can be used to tailor the release of drugs. We predicted phase separation using high throughput screening combined with a model based on the Flory-Huggins interaction parameter, and were able to show that drug release from 3D printed structures can be predicted from observations based on single drops of mixtures. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be ‘dialed up’ without any manipulation of geometry. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be exploited, bringing a hitherto unseen level of understanding to emergent material properties of 3D printing.

Anti-attachment materials that are sprayable and 3D-printable passively prevent colonization by harmful fungi., Fungi have major, negative socioeconomic impacts, but control with bioactive agents is increasingly restricted, while resistance is growing. Here, we describe an alternative fungal control strategy via materials operating passively (i.e., no killing effect). We screened hundreds of (meth)acrylate polymers in high throughput, identifying several that reduce attachment of the human pathogen Candida albicans, the crop pathogen Botrytis cinerea, and other fungi. Specific polymer functional groups were associated with weak attachment. Low fungal colonization materials were not toxic, supporting their passive, anti-attachment utility. We developed a candidate monomer formulation for inkjet-based 3D printing. Printed voice prosthesis components showed up to 100% reduction in C. albicans biofilm versus commercial materials. Furthermore, spray-coated leaf surfaces resisted fungal infection, with no plant toxicity. This is the first high-throughput study of polymer chemistries resisting fungal attachment. These materials are ready for incorporation in products to counteract fungal deterioration of goods, food security, and health.

Maintenance of the epithelium relies on stem cells residing within specialized microenvironments, known as epithelial crypts. Two-photon polymerization (2PP) is a valuable tool for fabricating 3D micro/nanostructures for stem cell niche engineering applications. Herein, biomimetic gelatin methacrylate-based constructs, replicating the precise geometry of the limbal epithelial crypt structures (limbal stem cell "microniches") as an exemplar epithelial niche, are fabricated using 2PP. Human limbal epithelial stem cells (hLESCs) are seeded within the microniches in xeno-free conditions to investigate their ability to repopulate the crypts and the expression of various differentiation markers. Cell proliferation and a zonation in cell phenotype along the z-axis are observed without the use of exogenous signaling molecules. Significant differences in cell phenotype between cells located at the base of the microniche and those situated towards the rim are observed, demonstrating that stem cell fate is strongly influenced by its location within a niche and the geometrical details of where it resides. This study provides insight into the influence of the niche's spatial geometry on hLESCs and demonstrates a flexible approach for the fabrication of biomimetic crypt-like structures in epithelial tissues. This has significant implications for regenerative medicine applications and can ultimately lead to implantable synthetic "niche-based" treatments.

Environmental perturbation, anthropogenic or otherwise, can have a profound effect on soil microbiota and essential biogeochemical processes. The general resistance and adaptation of yeasts and other fungi to stressors has been well studied in vitro however, the influence of key physical variables, such as how soil structure regulates fungal response to perturbation, is poorly understood. In this study, we developed an approach to manufacture soil macroaggregates that are characteristically similar to their natural counterpart (determined by X-ray CT) and with defined microbial composition. This new tool allowed us to examine the influence of soil aggregation on fungal stress response by manufacturing aggregates with yeast cells either within, or on, the aggregate surface. Environmental stressors including heavy metals, anoxia, and heat stress were applied to these aggregates to capture an array of environmental stressors and assay differences in survival between exo-and-endo aggregate cells. Results generated with this new tool indicate that the location of yeast cells in soil macroaggregates can impact on their survival, in a stressor- and time-dependent manner.

The advent of additive manufacturing (AM) or 3D printing as a tool for producing multifunctional and multimaterial objects has inspired great interest from the scientific community in various engineering and biomedical fields. This chapter will explore the recent developments in biomaterials and their composites for use in 3D and 4D printing. The expanding library of bioinks, ranging from synthetic polymers to ceramics to living cells, is discussed and their deposition via a number of AM processes, including stereolithography (SLA), extrusion printing, inkjet printing, and selective laser sintering, described. Furthermore, 4D printing is introduced as an emerging technology where time is integrated within the printing process, allowing objects to change their shape or function in response to external stimuli. Finally, the novel applications of the complex bioconstructs produced are examined with emphasis on the advantages or disadvantages of this emerging technology.

© 2020 The Royal Society of Chemistry. Using a novel molecular design approach, we have prepared a thermo-responsive supramolecular polyurethane as a matrix material for use in drug eluting implants. The dynamic supramolecular polyurethane (SPU) is able to self-assemble through hydrogen bonding and π-π stacking interactions, resulting in an addressable polymer network with a relatively low processing temperature. The mechanical properties of the SPU demonstrated the material was self-supporting, stiff, yet flexible thus making it suitable for hot-melt extrusion processing, inclusive of related 3D printing approaches. Cell-based toxicity assays revealed the SPU to be non-toxic and therefore a viable candidate as a biocompatible polymer for implant applications. To this end, the SPU was formulated with paracetamol (16% w/w) and 4 wt% or 8 wt% poly(ethylene glycol) (PEG) as an excipient and hot melt extruded at 100 °C to afford a 3D printed prototype implant to explore the extended drug release required for an implant and the potential manipulation of the release profile. Furthermore, rheological, infra-red spectroscopy, powder X-ray diffraction and scanning electron microscopy studies revealed the chemical and physical properties and compatibility of the formulation components. Successful release of paracetamol was achieved from in vitro dissolution studies and it was predicted that the drug would be released over a period of up to 8.5 months with hydrophilic PEG being able to influence the release rate. This extended release time is consistent with applications of this novel dynamic polymer as a drug eluting implant matrix.

Drop-on-demand jetting of metals offers a fully digital manufacturing approach to surpass the limitations of the current generation powder-based additive manufacturing technologies. However, research on this topic has been restricted mainly to near-net shaping of relatively low melting temperature metals. Here it is proposed a novel approach to jet molten metals at high-temperatures (>1000 °C) to enable the direct digital additive fabrication of micro- to macro-scale objects. The technique used in our research – “MetalJet” - is discussed by studying the ejection and the deposition of two example metals, tin and silver. The applicability of this new technology to additive manufacturing is evaluated through the study of the interface formed between the droplets and the substrate, the inter-droplets bonding, the microstructure and the geometrical fidelity of the printed objects. The research shows that the integrity of the samples (in terms of density as well as metallurgy) varies dramatically in the two investigated materials due to the different conditions that are required to melt the interface of the stacked droplets. Nevertheless the research shows that by a careful choice of the jetting strategy and sintering treatments 3D structures of various complexity can be formed. This research paves the way towards the next generation metal additive manufacturing where various printing resolutions and multi-material capabilities could be used to obtain functional components for applications in printed electronics, medicine and the automotive sectors.

An extrusion-based 3D printer was used to fabricate paracetamol tablets with different geometries (mesh, ring and solid) from a single paste-based formulation formed from standard pharmaceutical ingredients. The tablets demonstrate that tunable drug release profiles can be achieved from this single formulation even with high drug loading (> 80% w/w). The tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed well-defined release profiles (from immediate to sustained release) controlled by their different geometries. The dissolution results showed dependency of drug release on the surface area/volume (SA/V) ratio and the SA of the different tablets. The tablets with larger SA/V ratios and SA had faster drug release. The 3D printed tablets were also evaluated for physical and mechanical properties including tablet dimension, drug content, weight variation and breaking force and were within acceptable range as defined by the international standards stated in the US Pharmacopoeia. X-ray powder diffraction, differential scanning calorimetry and attenuated total reflectance Fourier transform infrared spectroscopy were used to identify the physical form of the active and to assess possible drug-excipient interactions. These data again showed that the tablets meet USP requirement. These results clearly demonstrate the potential of 3D printing to create unique pharmaceutical manufacturing, and potentially clinical, opportunities. The ability to use a single unmodified formulation to achieve defined release profiles could allow, for example, relatively straightforward personalization of medicines for individuals with different metabolism rates for certain drugs and hence could offer significant development and clinical opportunities.

The label additive manufacturing, also known as three-dimensional printing, serves as an umbrella term for a number of technologies designed to deposit product geometries directly from build materials and digital design information. However, as a relatively recent addition to the spectrum of manufacturing processes, the relationship between process type, system characteristics and cost performance is still broadly unclear for several technology types. To address this gap, the current research develops comprehensive and robust additive manufacturing cost models for two less-studied polymeric additive manufacturing technology variants, material jetting and mask projection stereolithography. Despite sharing the fundamental principle of photopolymerization, the operating processes of both systems are markedly different. This is reflected in the constructed cost models, which incorporate process maps to capture ancillary process elements, ensure efficient capacity utilisation through optimised build volume packing and approximate the expected cost impact of build failure. On this basis, this article estimates a set of specific cost indices reflecting the overall total cost performance of the investigated systems in an example application from the medical devices domain. Specific cost results range from £2.01 to £1.19/cm3 deposited on the Objet Connex 260 system and from £1.59 to £1.00/cm3 of material deposited on the Perfactory system. These results are discussed in the context of similar cost indices extracted from the empirical engineering literature. This article shows that next to increases in build speed, improvements in overall process automation and process stability are needed to enhance the commercial proposition of the investigated technology variants.

The adoption of additive manufacturing technology is gaining interest for processing precious metals. In this study, the capability of inkjet printing was explored to fabricate macroscopic parts from commercial silver nanoparticle ink (AgNPs). A bespoke JETx® three dimensional (3D) inkjet printing machine was used to print and subsequently sinter up to 1000 layers of AgNPs using an infrared source. Examination of the sample using X-ray computed tomography and scanning electron microscopy revealed the existence of both micro- and nano-scale pores within the structure. Pinning effect, residual surface temperature, insufficient droplet overlap and surface defects were the key factors contributing to the voids. Elemental mapping confirmed the structure to be composed of 87% of silver along with carbon and oxygen. The 750 dpi sample showed a 25% reduction in nanopores and 77% lower micro-pores compared to the 600 dpi sample. In terms of hardness, the 750 dpi sample was 29% harder than the 600 dpi sample, showcasing samples with higher print resolution can contribute towards less voids and improved mechanical properties. Thus by demonstrating the possibility to fabricate dense parts from AgNPs using inkjet technology, this study opens a novel route for processing nano-scale particulates and precious metals in 3D. Keywords: Additive manufacturing, 3D–printing, Silver nanoparticles, Inkjet printing, Precious metals

A predictive model is developed to assist in the design and manufacture of structures by inkjet based 3D printing (IJ3DP)/additive manufacturing. IJ3DP often exploits photopolymerisation to rapidly convert a photoreactive liquid ink into a solid product. Unfortunately, deviations from the intended design and product performance are often observed and a lack of understanding of the underlying processes and their interactions prevents users from resolving these issues. We develop and validate a predictive model that incorporates the critical processing parameters, including UV source pathway, UV intensity, printing strategy, and interlayer attenuation, such that we are able to predict the degree of ink conversion throughout the product. We show how this model can then be used to guide users by demonstrating the coupling of this description with a cost model and illustrating how printing strategy affects descriptors of both the quality and cost of production.

Bacterial Biofilm Resistant Composite Devices Medical implants would benefit from bespoke 3D printing, however microbial infection remains a challenge. By combining functional materials, voxelated manufacturing and algorithmic design, Morgan R. Alexander, Ricky D. Wildman, and co‐workers demonstrate in article number 2100249 a multi‐material inkjet 3D printed device that inhibits the development of bacterial biofilm, while achieving highly customizable geometry and local stiffness, opening further opportunities for biomedical 3D printing. [Image: see text]

The variety of UV-curable monomers for 3D printing is limited by a requirement for rapid curing after each sweep depositing a layer. This study proposes to trigger supramolecular self-assembly during the process by a gemini imidazolium-based low-molecular-weight gelator, allowing printing of certain monomers. The as-printed hydrogel structures were supported by a gelator network immobilising monomer:water solutions. A thixotropic hydrogel was formed with a recovery time of

The interest in Additive Manufacturing (AM) technology, also known as 3D printing, is unbroken. In many industries, however, stakeholders are struggling to understand AM's potential for manufacturing value creation. Most available literature on the cost of AM stresses the importance of ancillary processes and treats the relationship between process efficiency and capacity utilization. The most recently added - and overdue - aspect included in the extant AM costing literature considers the expected impact of so-called ill-structured costs, mainly relating to process failure and product rejection. Available research has investigated this aspect across a variety of technology types and process elements. This paper develops a new AM cost model that is generally specified so it can represent the probability and expected cost effect of failure events for all existing AM technologies. To demonstrate the implementation of this model, this paper applies it to the manufacture of pharmaceutical products (tablets) using the AM technology variant material jetting. The paper thus provides a robust indication of achievable unit cost levels, the cost effect of process failure, and also broaches the usefulness of cost models in guiding further process improvements.