Oxygen Concentration Gradient Research Articles

Oxygen gas transfer through oak barrels: a macroscopic approach

The oak barrel maturation step is nowadays strongly rooted in the production of quality wines. Two main physico‑chemical phenomena contribute to the modification and improvement of wine: the solubilisation of volatile and non-volatile wood compounds concomitant with the dissolution of oxygen from the air into the wine. Indeed, wood is a porous material and gas transfer (especially oxygen transfer, expressed as oxygen transfer rate or OTR) through oak barrels, is an intrinsic parameter which ensures wine oxygen supply during maturation. Due to its oenological impact, it has been actively studied over recent decades using several approaches based on the same principle: the monitoring of oxygen in a model wine solution in the barrel. This project aimed at assaying barrel OTR by using a new tool based on the theoretical knowledge of gas transfer through porous materials. An oxygen concentration gradient was created on each side of a barrel kept in an airtight stainless-steel tank. The concentration of the oxygen in the atmosphere around the barrel was monitored in order to quantify oxygen transfer, thus the avoiding common drawbacks of interactions between dissolved oxygen ingress kinetics and the consumption of oxygen in the liquid phase by wood components. This study reports for the first time, the diffusion coefficient of entire oak barrels (Q. sessilis) to be between 10-10 and 10-9 m²/s, and it contributes to increasing knowledge on the complex phenomena driving oxygen ingress during the maturation of wine in barrels kept in cellar conditions. The results highlight the important role of wood moisture content in oxygen transfer, and provides a simple and reliable parameter to monitor it: the weight of the barrel. Following methodology developed by the authors, the OTR of a new oak barrel was found to be 11.4 mg/L per year. Taking into account the oxygen released through the wood pores, a new barrel will contribute 14.4 mg/L per year of oxygen to the wine, of which 46 % in the first three months of aging.

Au/Pt‐Egg‐in‐Nest Nanomotor for Glucose‐Powered Catalytic Motion and Enhanced Molecular Transport to Living Cells

AbstractNanostructures converting chemical energy to mechanical work by using benign metabolic fuels, have huge implications in biomedical science. Here, we introduce Au/Pt‐based Janus nanostructures, resembling to “egg‐in‐nest” morphology (Au/Pt‐ENs), showing enhanced motion as a result of dual enzyme‐relay‐like catalytic cascade in physiological biomedia, and in turn showing molecular‐laden transport to living cells. We developed dynamic‐casting approach using silica yolk‐shell nanoreactors: first, to install a large Au‐seed fixing the silica‐yolk aside while providing the anisotropically confined concave hollow nanospace to grow curved Pt‐dendritic networks. Owing to the intimately interfaced Au and Pt catalytic sites integrated in a unique anisotropic nest‐like morphology, Au/Pt‐ENs exhibited high diffusion rates and displacements as the result of glucose‐converted oxygen concentration gradient. High diffusiophoresis in cell culture media increased the nanomotor‐membrane interaction events, in turn facilitated the cell internalization. In addition, the porous network of Au/Pt‐ENs facilitated the drug‐molecule cargo loading and delivery to the living cells.

Au/Pt-Egg-in-Nest Nanomotor for Glucose-Powered Catalytic Motion and Enhanced Molecular Transport to Living Cells.

Nanostructures converting chemical energy to mechanical work by using benign metabolic fuels, have huge implications in biomedical science. Here, we introduce Au/Pt-based Janus nanostructures, resembling to "egg-in-nest" morphology (Au/Pt-ENs), showing enhanced motion as a result of dual enzyme-relay-like catalytic cascade in physiological biomedia, and in turn showing molecular-laden transport to living cells. We developed dynamic-casting approach using silica yolk-shell nanoreactors: first, to install a large Au-seed fixing the silica-yolk aside while providing the anisotropically confined concave hollow nanospace to grow curved Pt-dendritic networks. Owing to the intimately interfaced Au and Pt catalytic sites integrated in a unique anisotropic nest-like morphology, Au/Pt-ENs exhibited high diffusion rates and displacements as the result of glucose-converted oxygen concentration gradient. High diffusiophoresis in cell culture media increased the nanomotor-membrane interaction events, in turn facilitated the cell internalization. In addition, the porous network of Au/Pt-ENs facilitated the drug-molecule cargo loading and delivery to the living cells.

Interface induced diffusion

Interface induced diffusion had been identified in a thin film system damaged by electron bombardment. This new phenomenon was observed in Al2O3 (some nm thick)/Si substrate system, which was subjected to low energy (5 keV) electron bombardment producing defects in the Al2O3 layer. The defects produced partially relaxed. The rate of relaxation is, however, was different in the vicinity of the interface and in the "bulk" parts of the Al2O3 layer. This difference creates an oxygen concentration gradient and consequently oxygen diffusion, resulting in an altered layer which grows from the Al2O3/Si substrate interface. The relative rate of the diffusion and relaxation is strongly temperature dependent, resulting in various altered layer compositions, SiO2 (at room temperature), Al2O3 + AlOx + Si (at 500 °C), Al2O3 + Si (at 700 °C), as the temperature during irradiation varies. Utilizing this finding it is possible to produce area selective interface patterning.

Experimentally calibrated electro-thermal modeling of temperature dynamics in memristors

As nanoscale electronic devices are being packed into dense three-dimensional arrays, the effects of the thermal environment of the system during device operation become critical, but are not clearly understood. Predicting the temperature evolution using a robust model will provide critical design guidelines for complex memory and computing systems. Here, we used in-operando thermal and x-ray mapping with sub-micrometer spatial and sub-microsecond temporal resolutions on functioning tantalum oxide memristive switches and observed hot spots corresponding to oxygen concentration gradients, indicating the presence of localized conductive filaments. We constructed a hybrid electro-thermal model comprising 3D heat transfer and 0D resistive switching models to predict electrical characteristics and the temperature rise and calibrated it against the measurements. We also demonstrated thermal crosstalk in an array of memristors to illustrate localized heating. Such a model will guide system design by considering thermal performance, which is critical to most future electronic chips.

Oxygen Vacancy-Dependent Synaptic Dynamic Behavior of TiO x -Based Transparent Memristor

Transparent synaptic devices remain great prospects for a future comprehensive simulation of artificial synapses with the combination of photoelectric coupling characteristics in the neuromorphic system. In this article, one type of memristors based on a stack structure of ITO/TiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">y</sub> /TiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> /TiN with high transmittance ( T > 81%) is fabricated, in which an oxygen-deficient TiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">y</sub> layer between TiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> and ITO top electrode is introduced to adjust the gradual current characteristics during the SET/RESET process. Furthermore, the devices with different thickness ratios (1:4, 1:2, 1:1, 2:1) of oxygen-deficient TiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">y</sub> active layers are designed to realize the adjustability of the multilevel resistance state and the analog resistive switching (RS) behavior and improve electrical performances and synaptic simulation characteristics. Meantime, the device based on optimum thickness ratio (1:2) offers excellent uniformity for 1000 cycles and better nonlinearity (0.69) at a low programming power consumption, which reveals further simulation of essential synaptic functions, including paired-pulse facilitation (PPF), and spike-timing-dependent plasticity (STDP) as well as learning-relearning characteristics. In addition, oxygen concentration gradient could be regulated by controlling the thickness ratio to drive oxygen vacancy redistribution at the interfacial layer, which are also demonstrated by high-resolution transmission electron microscopy (HRTEM) and improve electronic properties and analog modulation characteristics.

A new model for the emergence of blood capillary networks

We propose a new model for the emergence of blood capillary networks. We assimilate the tissue and extra cellular matrix as a porous medium, using Darcy's law for describing both blood and intersticial fluid flows. Oxygen obeys a convection-diffusionreaction equation describing advection by the blood, diffusion and consumption by the tissue. Discrete agents named capillary elements and modelling groups of endothelial cells are created or deleted according to different rules involving the oxygen concentration gradient, the blood velocity, the sheer stress or the capillary element density. Once created, a capillary element locally enhances the hydraulic conductivity matrix, contributing to a local increase of the blood velocity and oxygen flow. No connectivity between the capillary elements is imposed. The coupling between blood, oxygen flow and capillary elements provides a positive feedback mechanism which triggers the emergence of a network of channels of high hydraulic conductivity which we identify as new blood capillaries. We provide two different, biologically relevant geometrical settings and numerically analyze the influence of each of the capillary creation mechanism in detail. All mechanisms seem to concur towards a harmonious network but the most important ones are those involving oxygen gradient and sheer stress. A detailed discussion of this model with respect to the literature and its potential future developments concludes the paper.

Substrate oxygen sponge effect: A parameter for epitaxial manganite thin film growth

The emergent phenomena in complex oxide thin films are strongly tied to the oxygen content, which is often engineered by the oxygen partial pressure during growth. However, such oxygen control by the growth pressure is challenging to synthesize for some oxide films, which requires a subtle control of the oxygen content. A parameter of controlling the oxygen content independent of the growth pressure is desired. Here, we propose a method of controlling the oxygen content of films by engineering the substrate before the growth. The oxide substrate serves as an oxygen sponge, which provides a tunable oxygen environment ranging from oxygen-rich to oxygen-poor for the film growth, depending on the pre-substrate annealing (PSA) conditions. Using manganite as a model system, we demonstrate that this simple PSA method leads to remarkable changes in the structure and physical properties of the as-grown films. This substrate oxygen sponge effect, driven by the large oxygen concentration gradient at high temperatures, can be applied to explore not only emergent interfacial phenomena but also the growth of a variety of functional oxide thin films and nanocomposites.

Evaluating multi‐step oxidative stabilization behavior of coal tar pitch‐based fiber

AbstractOxidative stabilization is an important step for isotropic pitch‐based carbon fiber preparation; coal tar pitch‐based fiber is treated by multi‐step oxidative stabilization under various conditions to investigate the oxidative stabilization mechanism. The chemical structure changes of isotropic pitch‐based fiber during the oxidative stabilization and carbonization stage are systematically characterized by In‐situ diffuse reflectance infrared Fourier transform, elemental analysis, mass spectroscopy, X‐ray photoelectron spectroscopy, nuclear magnetic resonance, scanning electron microscope with an energy dispersive X‐ray spectrometer. These results show that the oxygen distribution gradient in oxidative stabilized fiber radial direction become homogeneously with the increasing of oxidation temperature and time under multi‐step oxidative stabilization. The resultant carbon fiber shows tensile strength of 942 ± 42 MPa and Young's modulus of 42.8 ± 3.1 GPa due to appropriate oxygen content, homogeneous oxygen distribution, more cross‐link bond (C‐O‐C) content, higher aromaticity and lower weight loss introduced in multi‐step oxidative stabilized pitch fiber. The multi‐step oxidative stabilization provides synergy effect between reaction rate and the oxygen diffusion rate as well as eliminates the oxygen concentration gradient, it provides an time‐saving and energy‐effective method for the oxidative stabilization of isotropic pitch‐based carbon material (pitch fiber, pitch microsphere, etc.) and improve the resultant carbon material performance.

Simultaneous biodegradability enhancement and high-efficient nitrogen removal in an innovative single stage anaerobic/anoxic/aerobic hybrid airlift bioreactor (HALBR) for composting leachate treatment: Process modeling and optimization

A novel hybrid airlift bioreactor (HALBR) for simultaneous carbon and nitrogen removal from composting leachate was studied. In contrast to conventional airlift bioreactors, an anaerobic chamber was mounted at the bottom part to improve biodegradability of composting leachate and optimize overall COD removal. Desired aerobic and anoxic conditions provided by airlift configuration and oxygen concentration gradients within the biofilm increased the capability of system for TN removal through SND. Three independent variables, hydraulic retention time (HRT) (18–30 h), air flow rate (AFR) (1–2 Lair/min), and aerobic volume ratio (AVR) (0.22–0.26) were evaluated as operating parameters. The optimum conditions were an HRT of 28.3–30 h and AFR of 1.7–2 Lair/min, giving 3600 mg/L (90%) of COD and 598.4 mg/L (80%) of TN removal, respectively with an effluent turbidity less than 70 NTU. The outcomes demonstrated that this innovative single HALBR is a feasible and reliable technology for treatment of composting leachate.

Development of simultaneous nitrification-denitrification and anammox and in-situ analysis of microbial structure in a novel plug-flow membrane-aerated sludge blanket

This study proposed a novel one-stage plug-flow microaerobic sludge blanket (PMSB) with membrane aerated for treating low carbon to nitrogen (C/N) ratio municipal sewage. The performance of simultaneous nitrification, denitrification, and anammox in the reactor was investigated. The results illustrated that the removal efficiencies of ammonium and total nitrogen (TN) were 93.2% and 87.1% with a C/N ratio of 4. High throughput sequencing revealed that aerobic bacteria, anaerobic bacteria and facultative anaerobe could co-exist at the same time in the sludge blanket. Meanwhile, a notable correlation between the oxygen concentration and the distance of the membrane module was analyzed. It was shown that the microbial community of functional bacteria developed in different aeration sites due to the oxygen concentration gradient. Microbial community structure was analyzed depending on the sludge stratification in the sludge blanket.

Ultralow operation voltages of a transparent memristor based on bilayer ITO

Traditional memristors based on metal/insulator/metal sandwich structures generally require the operation voltages of several volts to switch the device between different resistance states. In this work, we report the ultralow set and reset voltages of 14 mV and 0.3 V in a simple bilayer device, respectively, which is composed of the widely used indium tin oxide (ITO) solely. Such low operation voltages might be ascribed to the synergistic effect of the loose porous structure in the upper ITO layer deposited by electron beam evaporation, the amorphous interface between two ITO layers, and the formation of an oxygen concentration gradient triggered by an initiation process. Based on the superior resistive switching properties of this kind bilayer device, synaptic functions and image memorization are achieved by applying ultralow electrical stimulus. The prototype device not only paves the way for simplifying the device structure and the fabrication process but also offers possibilities to develop transparent multifunctional devices with low power consumption.

A Relatively Small Gradient of Extracellular pH Directs Migration of MDA-MB-231 Cells In Vitro.

Hematogenous tumor metastasis begins with the invasion and spread of primary tumor cells in the local tissue leading to intravasation. We hypothesized that tumor cells might actively migrate toward intratumor vessels with the extracellular metabolic gradient acting as a guiding cue. Here, we determined in vitro whether the extracellular gradient of pH can act as a cue for directional migration in MDA-MB-231 cells. Cell migration was determined by the wound-healing assay under gradients of extracellular pH (~0.2 units/mm) and oxygen concentration (~6% O2/mm) that were produced by a microfluidic device, gap cover glass (GCG). Without GCG, the migration of cells was spatially homogeneous; the same number of cells migrated to the rectangular wound space from the left and right boundaries. In contrast, when GCG generated pH/O2 gradients across the wound space, the number of cells migrating to the wound space from the boundary with higher pH/O2 values was considerably decreased, indicating a preferential movement of cells toward the region of higher pH/O2 in the gradient. The addition of hepes in the extracellular medium abolished both the extracellular pH gradient and the directional cell migration under GCG. We conclude that relatively small gradients of pH in the extracellular medium compared to those found in Na+/H+ exchanger-driven cell migration were sufficient to guide MDA-MB-231 cells. The directional cell migration as guided by the metabolic gradient could effectively elevate the probability of intravasation and, ultimately, hematogenous metastasis.

Study on Drug Resistance to Tumor Cell in Oxygen Gradient and Co-culture Microfluidic Chip

Abstract The tumor microenvironment is a complex system that plays a vital role in proliferation, invasion and metastasis. In this work, an oxygen concentration gradient microfluidic chip was designed to construct an in vitro model of tumor hypoxic microenvironment. The microfluidic chip was composed of two parts, one was a serpentine-shape channel for hypoxia reagent mix to generate oxygen gradient, the other part contained three parallel channels for the co-culture of cancer cells (Heap1-6 cells) and hepatic stellate cells (JS-1 cells). Using the microfluidic chip, oxygen gradient was created under the culture condition to simulate hypoxic tumor microenvironment in vivo. In the hypoxic gradient environment, the drug resistance of Hepa1-6 cells to paclitaxel and tirapazamine (TPZ) was studied and the potential molecular mechanism was supposed. The results showed that the concentration of oxygen gradient ranged from 2.3% to 16.7%. Under this hypoxic condition, the viability of co-cultured Hepa1-6 cells decreased significantly under TPZ intervention, while the Hepa1-6 cells expressed resistance to paclitaxel. The results of immunofluorescence assay showed that hypoxia and co-culture condition could promote the expression of TIMP-1 and TGF-β, which induced the activation of JS-1 cell and further enhanced the drug resistance of Hepa1-6 cell to paclitaxel.

Maximizing the Value of Cancer Drug Screening in Multicellular Tumor Spheroid Cultures: A Case Study in Five Head and Neck Squamous Cell Carcinoma Cell Lines.

With approval rates <5% and the probability of success in oncology clinical trials of 3.4%, more physiologically relevant in vitro three-dimensional models are being deployed during lead generation to select better drug candidates for solid tumors. Multicellular tumor spheroids (MCTSs) resemble avascular tumor nodules, micrometastases, or the intervascular regions of large solid tumors with respect to morphology, cell-cell and cell-extracellular matrix contacts, and volume growth kinetics. MCTSs develop gradients of nutrient and oxygen concentration resulting in diverse microenvironments with differential proliferation and drug distribution zones. We produced head and neck squamous cell carcinoma (HNSCC) MCTSs in 384-well U-bottom ultra-low-attachment microtiter plates and used metabolic viability and imaging methods to measure morphologies, growth phenotypes and the effects of 19 anticancer drugs. We showed that cell viability measurements underestimated the impact of drug exposure in HNSCC MCTS cultures, but that incorporating morphology and dead-cell staining analyses increased the number of drugs judged to have substantially impacted MCTS cultures. A cumulative multiparameter drug impact score enabled us to stratify MCTS drug responses into high-, intermediate-, and low-impact tiers, and maximized the value of these more physiologically relevant tumor cultures. It is conceivable that the viable cells present in MCTS cultures after drug exposure arise from drug-resistant populations that could represent a source of drug failure and recurrence. Long-term monitoring of treated MCTS cultures could provide a strategy to determine whether these drug-resistant populations represent circumstances where tumor growth is delayed and may ultimately give rise to regrowth.

Divergent northern and southern populations and demographic history of the pearl oyster in the western Pacific revealed with genomic SNPs.

In the open ocean without terrain boundaries, marine invertebrates with pelagic larvae can migrate long distances using ocean currents, suggesting reduced genetic diversification. Contrary to this assumption, however, genetic differentiation is often observed in marine invertebrates. In the present study, we sought to explain how population structure is established in the western Pacific Ocean, where the strong Kuroshio Current maintains high levels of gene flow from south to north, presumably promoting genetic homogeneity. We determined the population structure of the pearl oyster, Pinctada fucata, in the Indo‐Pacific Ocean using genome‐wide genotyping data from multiple sampling localities. Cluster analysis showed that the western Pacific population is distinct from that of the Indian Ocean, and that it is divided into northern (Japanese mainland) and southern (Nansei Islands, China, and Cambodia) populations. Genetic differentiation of P. fucata can be explained by geographic barriers in the Indian Ocean and a local lagoon, and by environmental gradients of sea surface temperature (SST) and oxygen concentration in the western Pacific. A genome scan showed evidence of adaptive evolution in genomic loci, possibly associated with changes in environmental factors, including SST and oxygen concentration. Furthermore, Bayesian simulation demonstrated that the past population expansion and division are congruent with ocean warming after the last glacial period. It is highly likely that the environmental gradient forms a genetic barrier that diversifies P. fucata populations in the western Pacific. This hypothesis helps to explain genetic differentiation and possible speciation of marine invertebrates.

Intracellular Mechanisms of Oxygen Sensing.

The review describes molecular mechanisms for sensing oxygen levels in various compartments of animal cell. Several pathways for intracellular oxygen sensing are discussed together with details of functioning of the near-membrane and cytoplasmic pools of molecular components in hypoxic cells. The data on the role of mitochondria in cell sensitivity to a decreased oxygen content are presented. Details of mutual influence of the operational and chronic intracellular mechanisms for detecting the negative gradients of molecular oxygen concentration and their relationship with cell metabolism response to the oxidative stress are discussed.

Gold Nanowires/Fibrin Nanostructure as Microfluidics Platforms for Enhancing Stem Cell Differentiation: Bio-AFM Study.

Organ-on-a-chip technology has gained great interest in recent years given its ability to control the spatio-temporal microenvironments of cells and tissues precisely. While physical parameters of the respective niche such as microchannel network sizes, geometric features, flow rates, and shear forces, as well as oxygen tension and concentration gradients, have been optimized for stem cell cultures, little has been done to improve cell-matrix interactions in microphysiological systems. Specifically, detailed research on the effect of matrix elasticity and extracellular matrix (ECM) nanotopography on stem cell differentiation are still in its infancy, an aspect that is known to alter a stem cell’s fate. Although a wide range of hydrogels such as gelatin, collagen, fibrin, and others are available for stem cell chip cultivations, only a limited number of elasticities are generally employed. Matrix elasticity and the corresponding nanotopography are key factors that guide stem cell differentiation. Given this, we investigated the addition of gold nanowires into hydrogels to create a tunable biointerface that could be readily integrated into any organ-on-a-chip and cell chip system. In the presented work, we investigated the matrix elasticity (Young’s modulus, stiffness, adhesive force, and roughness) and nanotopography of gold nanowire loaded onto fibrin hydrogels using the bio-AFM (atomic force microscopy) method. Additionally, we investigated the capacity of human amniotic mesenchymal stem cells (hAMSCs) to differentiate into osteo- and chondrogenic lineages. Our results demonstrated that nanogold structured-hydrogels promoted differentiation of hAMSCs as shown by a significant increase in Collagen I and II production. Additionally, there was enhanced calcium mineralization activity and proteoglycans formation after a cultivation period of two weeks within microfluidic devices.

Correction to 'Microbes and macro-invertebrates show parallel β-diversity but contrasting α-diversity patterns in a marine natural experiment'.

Documenting ecological patterns across spatially, temporally and taxonomically diverse ecological communities is necessary for a general understanding of the processes shaping biodiversity. A major gap in our understanding remains the comparison of diversity patterns across a broad spectrum of evolutionarily and functionally diverse organisms, particularly in the marine realm. Here, we aim to narrow this gap by comparing the diversity patterns of free-living microbes and macro-invertebrates across a natural experiment provided by the marine lakes of Palau: geographically discrete and environmentally heterogeneous bodies of seawater with comparable geological and climatic history, and a similar regional species pool. We find contrasting patterns of α-diversity but remarkably similar patterns of β-diversity between microbial and macro-invertebrate communities among lakes. Pairwise dissimilarities in community composition among lakes are positively correlated between microbes and macro-invertebrates, and influenced to a similar degree by marked gradients in oxygen concentration and salinity. Our findings indicate that a shared spatio-temporal and environmental context may result in parallel patterns of β-diversity in microbes and macro-invertebrates, in spite of key trait differences between these organisms. This raises the possibility that parallel processes also influence transitions among regional biota across the tree of life, at least in the marine realm.

Effect of Atomized Delivery of Nutrients on the Growth Characteristics and Microstructure Morphology of Bacterial Cellulose.

This work demonstrates a general strategy for introducing remarkable changes in matrix organization and, consequently, functional properties of bacterial cellulose (BC). BC-producing cells were induced, using a well-defined atomized droplet nutrient delivery (ADND) system, to form pellicles with a regular layered morphology that persists throughout the mat depth. In contrast, the morphology of mats formed by conventional static medium nutrient delivery (SMND) is irregular with no distinguishable pattern. ADND also resulted in larger meso-scale average pore sizes but did not alter the fibril diameter (∼70 nm) and crystallinity index (92-95%). The specific modulus and specific tensile strength of ADND mats are higher than those of SMND mats. This is due to the regularity of dense layers that are present in ADND mats that are able to sustain tensile loads, when applied parallel to these layers. The density of BC films prepared by ADND is 1.63-fold lower than that of the SMND BC film. Consequently, the water contents (g/g) of ADND- and SMND-prepared BC mats are 263 ± 8.85 and 99.6 ± 2.04, respectively. A model that rationalizes differences in mat morphology resulting from these nutrient delivery methods based on nutrient and oxygen concentration gradients is proposed. This work raises questions as to the extent that ADND can be used to fine-tune the matrix morphology and how the resulting lower density mats will alter the diffusion of actives from the films to wound sites and increase the ability of cells to infiltrate the matrix during tissue engineering.