Nanoroughness, Surface Chemistry and Drug Delivery Control by Atmospheric Plasma Jet on Implantable Devices

Implantable devices need specific tailored surface morphologies and chemistries to interact with the living systems or to actively induce a biological response also by the release of drugs or proteins. These customised requirements foster technologies that can be implemented in additive manufacturing systems. Here we present a novel approach based on spraying processes that allows to control separately topographic features in the submicron range ( 3d 60 nm - 2 \ub5m), ammine or carboxylic chemistry and fluorophore release even on temperature sensitive biodegradable polymers such as polycaprolactone (PCL). We developed a two-steps process with a first deposition of 220 nm silica and poly(lactic-co-glycolide) (PLGA) fluorescent nanoparticles by aerosol followed by the deposition of a fixing layer by atmospheric pressure plasma jet (APPJ). The nanoparticles can be used to create the nano-roughness and to include active molecule release, while the capping layer ensures stability and the chemical functionalities. The process is enabled by a novel APPJ which allows deposition rates of 10 - 20 nm\ub7s-1 at temperatures lower than 50 \ub0C using argon as process gas. This approach was assessed on titanium alloys for dental implants and on PCL films. The surfaces were characterized by FT-IR, AFM and SEM. Titanium alloys were tested with pre-osteoblasts murine cells line, while PCL film with fibroblasts. Cell behaviour was evaluated by viability and adhesion assays, protein adsorption, cell proliferation, focal adhesion formation and SEM. The release of a fluorophore molecule was assessed in the cell growing media, simulating a drug release. Osteoblast adhesion on the plasma treated materials increased by 20% with respect to commercial titanium alloys implants. Fibroblast adhesion increased by a 100% compared to smooth PCL substrate. The release of the fluorophore by the dissolution of the PLGA nanoparticles was verified and the integrity of the encapsulated drug model confirmed

Replicative Use of an External Model in Simulation Variance Reduction

The use of control variates is a well-known variance reduction technique for discrete event simulation experiments. Currently, internal control variates are used almost exclusively by practitioners and researchers when using control variates. The primary objective of this study is to explore the variance reduction achieved by the replicative use of an external, analytical model to generate control variates. Performance for the analytical control variates is compared to the performance of typical internal and external control variates for both an open and a closed queueing network. Performance measures used are confidence interval width reduction, realized coverage, and estimated Mean Square Error. Results of this study indicate analytical control variates achieve comparable confidence interval width reduction with internal and external control variates. However, the analytical control variates exhibit greater levels of estimated bias. Possible causes and remedies for the observed bias are discussed and areas for future research and use of analytical control variates conclude the study

How Not To Drown in Data:A Guide for Biomaterial Engineers

High-throughput assays that produce hundreds of measurements per sample are powerful tools for quantifying cell–material interactions. With advances in automation and miniaturization in material fabrication, hundreds of biomaterial samples can be rapidly produced, which can then be characterized using these assays. However, the resulting deluge of data can be overwhelming. To the rescue are computational methods that are well suited to these problems. Machine learning techniques provide a vast array of tools to make predictions about cell–material interactions and to find patterns in cellular responses. Computational simulations allow researchers to pose and test hypotheses and perform experiments in silico. This review describes approaches from these two domains that can be brought to bear on the problem of analyzing biomaterial screening data

Functional shift with maintained regenerative potential following portal vein ligation

Selective portal vein ligation (PVL) allows the two-stage surgical resection of primarily unresectable liver tumours by generating the atrophy and hypertrophy of portally ligated (LL) and non-ligated lobes (NLL), respectively. To evaluate critically important underlying functional alterations, present study characterised in vitro and vivo liver function in male Wistar rats (n = 106; 210-250 g) before, and 24/48/72/168/336 h after PVL. Lobe weights and volumes by magnetic resonance imaging confirmed the atrophy-hypertrophy complex. Proper expression and localization of key liver transporters (Ntcp, Bsep) and tight junction protein ZO-1 in isolated hepatocytes demonstrated constantly present viable and well-polarised cells in both lobes. In vitro taurocholate and bilirubin transport, as well as in vivo immunohistochemical Ntcp and Mrp2 expressions were bilaterally temporarily diminished, whereas LL and NLL structural acinar changes were divergent. In vivo bile and bilirubin-glucuronide excretion mirrored macroscopic changes, whereas serum bilirubin levels remained unaffected. In vivo functional imaging (indocyanine-green clearance test; (99mTc)-mebrofenin hepatobiliary scintigraphy; confocal laser endomicroscopy) indicated transitionally reduced global liver uptake and -excretion. While LL functional involution was permanent, NLL uptake and excretory functions recovered excessively. Following PVL, functioning cells remain even in LL. Despite extensive bilateral morpho-functional changes, NLL functional increment restores temporary declined transport functions, emphasising liver functional assessment

Relating the impacts of regenerative farming practices to soil health and carbon sequestration on Gotland, Sweden

Land degradation, greenhouse gas emissions and biodiversity loss through agriculture are some of the greatest challenges we are facing today. Fertile and productive soils are the basis of life on this planet and need to be protected and restored to support a growing population and lower negative impacts of climate change. Regenerative agriculture (RA) claims to improve environmental, social, and economic facets of food production. Its emphasis lies on carbon sequestration for climate change mitigation, biodiversity, and food security through the regeneration of degraded land. The concept of regenerative agriculture has gained attention both in mainstream media and in academic literature in recent years. However, there is no uniform definition of the term so far, and further there is a lack of comprehensive scientific studies on “real-life” farms that are changing their management from conventional to regenerative practices. This thesis investigates the contemporary and historical context of the emerging term regenerative agriculture and identifies the main themes, movements, and debates associated with it by a broad literature research. Further, we compare regenerative farms with conventional farms on Gotland, Sweden in order to draw first conclusions about the impact of certain farming practices on soil physical, chemical, and biological parameters. The soil health on 24 different plots is assessed by a variety of indicators, i.a. total, organic, active, and microbial biomass carbon, C:N ratio, wet aggregate stability, root depth and abundance, earthworm number, nutrient leaching, and soil texture. These parameters are related to four main management practices: application of organic matter, soil disturbance through tillage, crop diversity, and share of legumes through a principal component analysis and multiple linear regressions. We found that the amount of carbon added to the soil had a significant impact on several soil health indicators, mainly organic and active carbon, bulk density, number of earthworms, root abundance, water infiltration, and vegetation density. Reduced tillage was connected to higher wet aggregate stability, and vegetation density. These findings need to be confirmed in the coming years; however, they show that higher organic inputs and less soil disturbance generally had a positive impact on soil health on the investigated farms. Soil sampling will be continued on the same plots in the future to thoroughly investigate the impacts over a longer time period, as the thesis is part of the project Time Zero! Land surveys during farm conversion from abandoned land to regenerative agriculture performed at the Department of Soil and Environment at the Swedish University of Agriculture, Uppsala

Discrete Film Cooling in a Rocket with Curved Walls

This study quantified the effects of discrete wall-based film cooling in a rocket with curved walls. Simulations and experiments showed decreasing with wall radius of curvature, holding jet diameter constant, improves net heat flux reduction (NHFR) and adiabatic effectiveness (η) for 90˚ compound injected cylindrical jets, though η is reduced at the highest curvature. NHFR and η improved further with a high favorable stream-wise pressure gradient (K=2.1x10-5) at all tested blowing ratios, but were affected little by a high density ratio (DR=1.76) using carbon dioxide as the coolant. Experiments were run at a Reynolds number of 31K and a free-stream turbulence intensity of 26% with varying wall and jet radii. Simulations showed the Rannie transpiration model may be used to predict the cooling performance of a wall with full coverage film cooling using a correction formula based on the hole coverage area. Three improvements were made to the method of simultaneous acquisition of adiabatic wall temperature and heat flux coefficient: solving for the needed variables via a multi- point non-linear least squares curve fit instead of a two-point direct solution; correctly applying the free-stream fluid temperature boundary condition to account for drifting temperature instead of assuming it to be constant; and showing a repeatable way to reduce uncertainty in the test start time