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Showing papers in "Bioengineering in 2017"


Journal ArticleDOI
TL;DR: In this paper, challenges and opportunities regarding polyhydroxyalkanoate production are presented and discussed, covering key steps of their overall production process by applying pure and mixed culture biotechnology, from raw bioprocess development to downstream processing.
Abstract: Sustainable biofuels, biomaterials, and fine chemicals production is a critical matter that research teams around the globe are focusing on nowadays. Polyhydroxyalkanoates represent one of the biomaterials of the future due to their physicochemical properties, biodegradability, and biocompatibility. Designing efficient and economic bioprocesses, combined with the respective social and environmental benefits, has brought together scientists from different backgrounds highlighting the multidisciplinary character of such a venture. In the current review, challenges and opportunities regarding polyhydroxyalkanoate production are presented and discussed, covering key steps of their overall production process by applying pure and mixed culture biotechnology, from raw bioprocess development to downstream processing.

448 citations


Journal ArticleDOI
TL;DR: The aim of this review is to give an overview about the current techniques employed in 3D printing medicines, highlighting their advantages, disadvantages, along with the polymer and drug requirements for a successful printing.
Abstract: The interindividual variability is an increasingly global problem when treating patients from different backgrounds with diverse customs, metabolism, and necessities. Dose adjustment is frequently based on empirical methods, and therefore, the chance of undesirable side effects to occur is high. Three-dimensional (3D) Printed medicines are revolutionsing the pharmaceutical market as potential tools to achieve personalised treatments adapted to the specific requirements of each patient, taking into account their age, weight, comorbidities, pharmacogenetic, and pharmacokinetic characteristics. Additive manufacturing or 3D printing consists of a wide range of techniques classified in many categories but only three of them are mostly used in the 3D printing of medicines: printing-based inkjet systems, nozzle-based deposition systems, and laser-based writing systems. There are several drawbacks when using each technique and also the type of polymers readily available do not always possess the optimal properties for every drug. The aim of this review is to give an overview about the current techniques employed in 3D printing medicines, highlighting their advantages, disadvantages, along with the polymer and drug requirements for a successful printing. The major application of these techniques will be also discussed.

174 citations


Journal ArticleDOI
TL;DR: A survey of biocompatibility and bioactive molecule release studies, leveraging polysaccharide’s naturally derived properties, is highlighted in the text, while challenges and future directions for wound dressing development using emerging fabrication techniques such as 3D bioprinting are outlined in the conclusion.
Abstract: Wound dressings are critical for wound care because they provide a physical barrier between the injury site and outside environment, preventing further damage or infection. Wound dressings also manage and even encourage the wound healing process for proper recovery. Polysaccharide biopolymers are slowly becoming popular as modern wound dressings materials because they are naturally derived, highly abundant, inexpensive, absorbent, non-toxic and non-immunogenic. Polysaccharide biopolymers have also been processed into biomimetic platforms that offer a bioactive component in wound dressings that aid the healing process. This review primarily focuses on the fabrication and biocompatibility assessment of polysaccharide materials. Specifically, fabrication platforms such as electrospun fibers and hydrogels, their fabrication considerations and popular polysaccharides such as chitosan, alginate, and hyaluronic acid among emerging options such as arabinoxylan are discussed. A survey of biocompatibility and bioactive molecule release studies, leveraging polysaccharide’s naturally derived properties, is highlighted in the text, while challenges and future directions for wound dressing development using emerging fabrication techniques such as 3D bioprinting are outlined in the conclusion. This paper aims to encourage further investigation and open up new, disruptive avenues for polysaccharides in wound dressing material development.

152 citations


Journal ArticleDOI
TL;DR: The recent advances and the potential of 3D cell-printing technology in engineering organs-on-chips are discussed, and the future perspectives of this technology are provided to establish the highly reliable and useful drug-screening platforms.
Abstract: Organ-on-a-chip engineering aims to create artificial living organs that mimic the complex and physiological responses of real organs, in order to test drugs by precisely manipulating the cells and their microenvironments. To achieve this, the artificial organs should to be microfabricated with an extracellular matrix (ECM) and various types of cells, and should recapitulate morphogenesis, cell differentiation, and functions according to the native organ. A promising strategy is 3D printing, which precisely controls the spatial distribution and layer-by-layer assembly of cells, ECMs, and other biomaterials. Owing to this unique advantage, integration of 3D printing into organ-on-a-chip engineering can facilitate the creation of micro-organs with heterogeneity, a desired 3D cellular arrangement, tissue-specific functions, or even cyclic movement within a microfluidic device. Moreover, fully 3D-printed organs-on-chips more easily incorporate other mechanical and electrical components with the chips, and can be commercialized via automated massive production. Herein, we discuss the recent advances and the potential of 3D cell-printing technology in engineering organs-on-chips, and provides the future perspectives of this technology to establish the highly reliable and useful drug-screening platforms.

132 citations


Journal ArticleDOI
TL;DR: Methods of fabrication for microfluidic assays and inducing factors for vascularization are reviewed and applications using engineered vasculature such as in vitro vascular disease models, vasculatures in organ-on-chips and drug screening platforms are discussed.
Abstract: Vascularization, the formation of new blood vessels, is an essential biological process. As the vasculature is involved in various fundamental physiological phenomena and closely related to several human diseases, it is imperative that substantial research is conducted on characterizing the vasculature and its related diseases. A significant evolution has been made to describe the vascularization process so that in vitro recapitulation of vascularization is possible. The current microfluidic systems allow elaborative research on the effects of various cues for vascularization, and furthermore, in vitro technologies have a great potential for being applied to the vascular disease models for studying pathological events and developing drug screening platforms. Here, we review methods of fabrication for microfluidic assays and inducing factors for vascularization. We also discuss applications using engineered vasculature such as in vitro vascular disease models, vasculature in organ-on-chips and drug screening platforms.

120 citations


Journal ArticleDOI
TL;DR: An overview of the main 3D-printing technologies currently employed in the case of poly (lactic acid) (PLA) and polyhydroxyalkanoates (PHA), two of the most important classes of thermoplastic aliphatic polyesters.
Abstract: 3D printing represents a valuable alternative to traditional processing methods, clearly demonstrated by the promising results obtained in the manufacture of various products, such as scaffolds for regenerative medicine, artificial tissues and organs, electronics, components for the automotive industry, art objects and so on. This revolutionary technique showed unique capabilities for fabricating complex structures, with precisely controlled physical characteristics, facile tunable mechanical properties, biological functionality and easily customizable architecture. In this paper, we provide an overview of the main 3D-printing technologies currently employed in the case of poly (lactic acid) (PLA) and polyhydroxyalkanoates (PHA), two of the most important classes of thermoplastic aliphatic polyesters. Moreover, a short presentation of the main 3D-printing methods is briefly discussed. Both PLA and PHA, in the form of filaments or powder, proved to be suitable for the fabrication of artificial tissue or scaffolds for bone regeneration. The processability of PLA and PHB blends and composites fabricated through different 3D-printing techniques, their final characteristics and targeted applications in bioengineering are thoroughly reviewed.

120 citations


Journal ArticleDOI
TL;DR: Estimation errors were found to be significantly high for the existing HHV correlations, and thus, they are not suitable for predicting the HHV of the torrefied biomass, and new and more accurate correlations were developed.
Abstract: Many correlations are available in the literature to predict the higher heating value (HHV) of raw biomass using the proximate and ultimate analyses. Studies on biomass torrefaction are growing tremendously, which suggest that the fuel characteristics, such as HHV, proximate analysis and ultimate analysis, have changed significantly after torrefaction. Such changes may cause high estimation errors if the existing HHV correlations were to be used in predicting the HHV of torrefied biomass. No study has been carried out so far to verify this. Therefore, this study seeks answers to the question: “Can the existing correlations be used to determine the HHV of the torrefied biomass”? To answer this, the existing HHV predicting correlations were tested using torrefied biomass data points. Estimation errors were found to be significantly high for the existing HHV correlations, and thus, they are not suitable for predicting the HHV of the torrefied biomass. New correlations were then developed using data points of torrefied biomass. The ranges of reported data for HHV, volatile matter (VM), fixed carbon (FC), ash (ASH), carbon (C), hydrogen (H) and oxygen (O) contents were 14.90 MJ/kg–33.30 MJ/kg, 13.30%–88.57%, 11.25%–82.74%, 0.08%–47.62%, 35.08%–86.28%, 0.53%–7.46% and 4.31%–44.70%, respectively. Correlations with the minimum mean absolute errors and having all components of proximate and ultimate analyses were selected for future use. The selected new correlations have a good accuracy of prediction when they are validated using another set of data (26 samples). Thus, these new and more accurate correlations can be useful in modeling different thermochemical processes, including combustion, pyrolysis and gasification processes of torrefied biomass.

102 citations


Journal ArticleDOI
TL;DR: This review summarizes the recent advances in cyanobacterial PHA production and reports the working experience with different strains and cultivating conditions in a 200 L pilot plant built at the coal power plant in Dürnrohr, Austria in 2013.
Abstract: Cyanobacteria, as photoautotrophic organisms, provide the opportunity to convert CO2 to biomass with light as the sole energy source. Like many other prokaryotes, especially under nutrient deprivation, most cyanobacteria are able to produce polyhydroxyalkanoates (PHAs) as intracellular energy and carbon storage compounds. In contrast to heterotrophic PHA producers, photoautotrophic cyanobacteria do not consume sugars and, therefore, do not depend on agricultural crops, which makes them a green alternative production system. This review summarizes the recent advances in cyanobacterial PHA production. Furthermore, this study reports the working experience with different strains and cultivating conditions in a 200 L pilot plant. The tubular photobioreactor was built at the coal power plant in Durnrohr, Austria in 2013 for direct utilization of flue gases. The main challenges were the selection of robust production strains, process optimization, and automation, as well as the CO2 availability.

102 citations


Journal ArticleDOI
TL;DR: An insight into the theoretical aspects of microwave irradiation practices is provided and the potential of the microwave technology to accomplish superior outcomes over the conventional methods in biodiesel production is presented.
Abstract: The conversion of biomass into chemicals and biofuels is an active research area as trends move to replace fossil fuels with renewable resources due to society’s increased concern towards sustainability. In this context, microwave processing has emerged as a tool in organic synthesis and plays an important role in developing a more sustainable world. Integration of processing methods with microwave irradiation has resulted in a great reduction in the time required for many processes, while the reaction efficiencies have been increased markedly. Microwave processing produces a higher yield with a cleaner profile in comparison to other methods. The microwave processing is reported to be a better heating method than the conventional methods due to its unique thermal and non-thermal effects. This paper provides an insight into the theoretical aspects of microwave irradiation practices and highlights the importance of microwave processing. The potential of the microwave technology to accomplish superior outcomes over the conventional methods in biodiesel production is presented. A green process for biodiesel production using a non-catalytic method is still new and very costly because of the supercritical condition requirement. Hence, non-catalytic biodiesel conversion under ambient pressure using microwave technology must be developed, as the energy utilization for microwave-based biodiesel synthesis is reported to be lower and cost-effective.

100 citations


Journal ArticleDOI
TL;DR: It was shown that a product-producing strain has significantly higher inducer uptake rates when being compared to a non-producer strain, and glycerol has beneficial effects on viability of cells and on productivity of the recombinant protein compared to glucose.
Abstract: The Gram-negative bacterium E. coli is the host of choice for a multitude of used recombinant proteins. Generally, cultivation is easy, media are cheap, and a high product titer can be obtained. However, harsh induction procedures using isopropyl β-d-1 thiogalactopyranoside as inducer are often referred to cause stress reactions, leading to a phenomenon known as "metabolic" or "product burden". These high expressions of recombinant proteins mainly result in decreased growth rates and cell lysis at elevated induction times. Therefore, approaches tend to use "soft" or "tunable" induction with lactose and reduce the stress level of the production host. The usage of glucose as energy source in combination with lactose as induction reagent causes catabolite repression effects on lactose uptake kinetics and as a consequence reduced product titer. Glycerol-as an alternative carbon source-is already known to have positive impact on product formation when coupled with glucose and lactose in auto-induction systems, and has been referred to show no signs of repression when cultivated with lactose concomitantly. In recent research activities, the impact of different products on the lactose uptake using glucose as carbon source was highlighted, and a mechanistic model for glucose-lactose induction systems showed correlations between specific substrate uptake rate for glucose or glycerol (qs,C) and the maximum specific lactose uptake rate (qs,lac,max). In this study, we investigated the mechanistic of glycerol uptake when using the inducer lactose. We were able to show that a product-producing strain has significantly higher inducer uptake rates when being compared to a non-producer strain. Additionally, it was shown that glycerol has beneficial effects on viability of cells and on productivity of the recombinant protein compared to glucose.

81 citations


Journal ArticleDOI
TL;DR: The present review summarizes published data regarding the production of nanomaterials with special features via sustainable methodologies based on the utilization of natural bioresources and is expected that these outstanding findings will encourage researchers and attract newcomers to continue and extend the exploration of possibilities offered by nature.
Abstract: Several methodologies have been devised for the design of nanomaterials. The "Holy Grail" for materials scientists is the cost-effective, eco-friendly synthesis of nanomaterials with controlled sizes, shapes and compositions, as these features confer to the as-produced nanocrystals unique properties making them appropriate candidates for valuable bio-applications. The present review summarizes published data regarding the production of nanomaterials with special features via sustainable methodologies based on the utilization of natural bioresources. The richness of the latter, the diversity of the routes adopted and the tuned experimental parameters have led to the fabrication of nanomaterials belonging to different chemical families with appropriate compositions and displaying interesting sizes and shapes. It is expected that these outstanding findings will encourage researchers and attract newcomers to continue and extend the exploration of possibilities offered by nature and the design of innovative and safer methodologies towards the synthesis of unique nanomaterials, possessing desired features and exhibiting valuable properties that can be exploited in a profusion of fields.

Journal ArticleDOI
TL;DR: Among the various wild-type halophilic archaeal strains screened, Halogeometricum borinquense strain E3 showed better growth and PHA accumulation as compared to Haloferaxvolcanii strain BBK2, Haloarcula japonica strain BS2, and Halococcus salifodinae strain BK6.
Abstract: Sugarcane bagasse (SCB), one of the major lignocellulosic agro-industrial waste products, was used as a substrate for biosynthesis of polyhydroxyalkanoates (PHA) by halophilic archaea. Among the various wild-type halophilic archaeal strains screened, Halogeometricum borinquense strain E3 showed better growth and PHA accumulation as compared to Haloferaxvolcanii strain BBK2, Haloarcula japonica strain BS2, and Halococcus salifodinae strain BK6. Growth kinetics and bioprocess parameters revealed the maximum PHA accumulated by strain E3 to be 50.4 ± 0.1 and 45.7 ± 0.19 (%) with specific productivity (qp) of 3.0 and 2.7 (mg/g/h) using NaCl synthetic medium supplemented with 25% and 50% SCB hydrolysate, respectively. PHAs synthesized by strain E3 were recovered in chloroform using a Soxhlet apparatus. Characterization of the polymer using crotonic acid assay, X-ray diffraction (XRD), differential scanning calorimeter (DSC), Fourier transform infrared (FT-IR), and proton nuclear magnetic resonance (¹H-NMR) spectroscopy analysis revealed the polymer obtained from SCB hydrolysate to be a co-polymer of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] comprising of 13.29 mol % 3HV units.

Journal ArticleDOI
TL;DR: The aim of the present work was to study the encapsulation of Origanum onites L. essential oil (oregano EO) in β-cyclodextrin (β-CD) inclusion complexes (ICs), using the co-precipitation method, and to determine the inclusion efficacy and the study of the encapsulated oregana EO release profile.
Abstract: The aim of the present work was to study the encapsulation of Origanum onites L. essential oil (oregano EO) in β-cyclodextrin (β-CD) inclusion complexes (ICs), using the co-precipitation method. The formed β-CD–oregano EO ICs were characterized by diverse methods, such as Dynamic Light Scattering (DLS), FT-IR spectroscopy, Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Nuclear Magnetic Resonance (NMR) spectroscopy and Scanning Electron Microscopy (SEM). UV-Vis spectroscopy was used for the determination of the inclusion efficacy and the study of the encapsulated oregano EO release profile. The interactions between host (β-CD) and guest (oregano EO) in the formed ICs were proven by the FT-IR, DSC, TG and NMR analyses. The ICs, which derived from different batches, presented nanoscale size (531.8 ± 7.7 nm and 450.3 ± 11.5 nm, respectively), good size dispersion (0.308 ± 0.062 and 0.484 ± 0.029, respectively) and satisfactory stability in suspension (ζ-potential = −21.5 ± 1.2 mV and −30.7 ± 1.8 mV). Inclusion efficiency reached up to 26%, whereas the oregano EO release from the ICs followed a continuous delivery profile for up to 11 days, based on in vitro experiments. The formed ICs can find diverse applications, such as in the preparation of films for active packaging of food products, in personal care products for the improvement of their properties (e.g., antioxidant, antimicrobial, etc.), as well as in insect repellent products.

Journal ArticleDOI
Martin Koller1
TL;DR: The article shows how the issue’s individual research articles are interrelated to each other, reflecting the entire PHA process chain including strain selection, metabolic and genetic considerations, feedstock evaluation, fermentation regimes, process engineering, and polymer processing towards high-value marketable products.
Abstract: This editorial paper provides a synopsis of the contributions to the Bioengineering special issue “Advances in Polyhydroxyalkanoate (PHA) Production”. It illustrates the embedding of the issue’s individual research articles in the current global research and development landscape related to polyhydroxyalkanoates (PHA). The article shows how these articles are interrelated to each other, reflecting the entire PHA process chain including strain selection, metabolic and genetic considerations, feedstock evaluation, fermentation regimes, process engineering, and polymer processing towards high-value marketable products.

Journal ArticleDOI
TL;DR: Lignite was identified as a promising alternative sorbent which can be used for detoxification of lignocellulose hydrolyzates and used lignite can be simply utilized as a fuel to, at least partially, cover heat and energetic demands of fermentation, which should improve the economic feasibility of the process.
Abstract: Polyhydroxyalkanoates (PHAs) are bacterial polyesters which are considered biodegradable alternatives to petrochemical plastics PHAs have a wide range of potential applications, however, the production cost of this bioplastic is several times higher A major percentage of the final cost is represented by the price of the carbon source used in the fermentation Burkholderia cepacia and Burkholderia sacchari are generally considered promising candidates for PHA production from lignocellulosic hydrolyzates The wood waste biomass has been subjected to hydrolysis The resulting hydrolyzate contained a sufficient amount of fermentable sugars Growth experiments indicated a strong inhibition by the wood hydrolyzate Over-liming and activated carbon as an adsorbent of inhibitors were employed for detoxification All methods of detoxification had a positive influence on the growth of biomass and PHB production Furthermore, lignite was identified as a promising alternative sorbent which can be used for detoxification of lignocellulose hydrolyzates Detoxification using lignite instead of activated carbon had lower inhibitor removal efficiency, but greater positive impact on growth of the bacterial culture and overall PHA productivity Moreover, lignite is a significantly less expensive adsorbent in comparison with activated charcoal and; moreover, used lignite can be simply utilized as a fuel to, at least partially, cover heat and energetic demands of fermentation, which should improve the economic feasibility of the process

Journal ArticleDOI
TL;DR: Time-frequency distributions were often used to estimate the spectrotemporal signal features and appeared more suited for estimating IF of actual SCG signals, and STFT had lower error than CWT methods for most test signals and PCT had the most consistently accurate IF estimations.
Abstract: Accurate estimation of seismocardiographic (SCG) signal features can help successful signal characterization and classification in health and disease. This may lead to new methods for diagnosing and monitoring heart function. Time-frequency distributions (TFD) were often used to estimate the spectrotemporal signal features. In this study, the performance of different TFDs (e.g., short-time Fourier transform (STFT), polynomial chirplet transform (PCT), and continuous wavelet transform (CWT) with different mother functions) was assessed using simulated signals, and then utilized to analyze actual SCGs. The instantaneous frequency (IF) was determined from TFD and the error in estimating IF was calculated for simulated signals. Results suggested that the lowest IF error depended on the TFD and the test signal. STFT had lower error than CWT methods for most test signals. For a simulated SCG, Morlet CWT more accurately estimated IF than other CWTs, but Morlet did not provide noticeable advantages over STFT or PCT. PCT had the most consistently accurate IF estimations and appeared more suited for estimating IF of actual SCG signals. PCT analysis showed that actual SCGs from eight healthy subjects had multiple spectral peaks at 9.20 ± 0.48, 25.84 ± 0.77, 50.71 ± 1.83 Hz (mean ± SEM). These may prove useful features for SCG characterization and classification.

Journal ArticleDOI
TL;DR: This work developed OpenDrop, an integrated electromicrofluidic platform that allows users to develop and program their own bio-applications, and addresses the main challenges that users may encounter: accessibility, bio-protocol design and interaction with microfluidics.
Abstract: Biochips, or digital labs-on-chip, are developed with the purpose of being used by laboratory technicians or biologists in laboratories or clinics In this article, we expand this vision with the goal of enabling everyone, regardless of their expertise, to use biochips for their own personal purposes We developed OpenDrop, an integrated electromicrofluidic platform that allows users to develop and program their own bio-applications We address the main challenges that users may encounter: accessibility, bio-protocol design and interaction with microfluidics OpenDrop consists of a do-it-yourself biochip, an automated software tool with visual interface and a detailed technique for at-home operations of microfluidics We report on two years of use of OpenDrop, released as an open-source platform Our platform attracted a highly diverse user base with participants originating from maker communities, academia and industry Our findings show that 47% of attempts to replicate OpenDrop were successful, the main challenge remaining the assembly of the device In terms of usability, the users managed to operate their platforms at home and are working on designing their own bio-applications Our work provides a step towards a future in which everyone will be able to create microfluidic devices for their personal applications, thereby democratizing parts of health care

Journal ArticleDOI
TL;DR: 3D printing-based pre-vascularization technologies correlated with implementing blood perfusion throughout the engineered tissue equivalent may offer a unique approach that results in the physiological mimicry of human cardiovascular tissues to aid in drug development and therapeutic approaches.
Abstract: Numerous microfabrication approaches have been developed to recapitulate morphologically and functionally organized tissue microarchitectures in vitro; however, the technical and operational limitations remain to be overcome. 3D printing technology facilitates the building of a construct containing biomaterials and cells in desired organizations and shapes that have physiologically relevant geometry, complexity, and micro-environmental cues. The selection of biomaterials for 3D printing is considered one of the most critical factors to achieve tissue function. It has been reported that some printable biomaterials, having extracellular matrix-like intrinsic microenvironment factors, were capable of regulating stem cell fate and phenotype. In particular, this technology can control the spatial positions of cells, and provide topological, chemical, and complex cues, allowing neovascularization and maturation in the engineered cardiovascular tissues. This review will delineate the state-of-the-art 3D bioprinting techniques in the field of cardiovascular tissue engineering and their applications in translational medicine. In addition, this review will describe 3D printing-based pre-vascularization technologies correlated with implementing blood perfusion throughout the engineered tissue equivalent. The described engineering method may offer a unique approach that results in the physiological mimicry of human cardiovascular tissues to aid in drug development and therapeutic approaches.

Journal ArticleDOI
TL;DR: This review focuses on the use of the subtle changes of pH between healthy and diseased areas along the body to trigger the release of the cargo in pH-responsive nanocarriers based on supramolecular structures acting as pore capping agents.
Abstract: The application of nanotechnology to medicine constitutes a major field of research nowadays. In particular, the use of mesoporous silica and carbon nanoparticles has attracted the attention of numerous researchers due to their unique properties, especially when applied to cancer treatment. Many strategies based on stimuli-responsive nanocarriers have been developed to control the drug release and avoid premature release. Here, we focus on the use of the subtle changes of pH between healthy and diseased areas along the body to trigger the release of the cargo. In this review, different approximations of pH-responsive systems are considered: those based on the use of the host-guest interactions between the nanocarriers and the drugs, those based on the hydrolysis of acid-labile bonds and those based on supramolecular structures acting as pore capping agents.

Journal ArticleDOI
TL;DR: In this review, recent progress regarding microfluidic devices and their applications in cell cultures is discussed and future challenges regarding the simulation of OCs are discussed to explain the advantages and limitations of these systems.
Abstract: A multichannel three-dimensional chip of a microfluidic cell culture which enables the simulation of organs is called an “organ on a chip” (OC). With the integration of many other technologies, OCs have been mimicking organs, substituting animal models, and diminishing the time and cost of experiments which is better than the preceding conventional in vitro models, which make them imperative tools for finding functional properties, pathological states, and developmental studies of organs. In this review, recent progress regarding microfluidic devices and their applications in cell cultures is discussed to explain the advantages and limitations of these systems. Microfluidics is not a solution but only an approach to create a controlled environment, however, other supporting technologies are needed, depending upon what is intended to be achieved. Microfluidic platforms can be integrated with additional technologies to enhance the organ on chip simulations. Besides, new directions and areas are mentioned for interested researchers in this field, and future challenges regarding the simulation of OCs are also discussed, which will make microfluidics more accurate and beneficial for biological applications.

Journal ArticleDOI
TL;DR: At the moment, biofuel production from seaweed has been determined not to be economically feasible, but achieving economic production may be possible by lowering production costs and increasing the area under cultivation.
Abstract: A techno-economic evaluation of bioenergy production from macroalgae was carried out in this study. Six different scenarios were examined for the production of different energy products and by-products. Seaweed was produced either via the longline method or the grid method. Final products of these scenarios were either ethanol from fermentation, or electricity from anaerobic digestion (AD). By-products were digestate for AD, and animal feed, or electricity and digestate, for the fermentation pathway. Bioenergy breakeven selling prices were investigated according to the cost components and the feedstock supply chain, while suggestions for potential optimization of costs were provided. The lowest production level of dry seaweed to meet 0.93 ($/L) for ethanol fuel and 0.07 $/kW-h for electricity was found to be 0.68 and 3.7 million tonnes (dry basis), respectively. At the moment, biofuel production from seaweed has been determined not to be economically feasible, but achieving economic production may be possible by lowering production costs and increasing the area under cultivation.

Journal ArticleDOI
TL;DR: This review highlights the recent advancements of engineered tumor microenvironment systems that enable the unprecedented mechanistic examination of cancer progression and metastasis and discusses the progress and future perspective of these microengineered biomimetic approaches for anticancer drug prescreening applications.
Abstract: Tumors develop in intricate microenvironments required for their sustained growth, invasion, and metastasis. The tumor microenvironment plays a critical role in the malignant or drug resistant nature of tumors, becoming a promising therapeutic target. Microengineered physiological systems capable of mimicking tumor environments are one emerging platform that allows for quantitative and reproducible characterization of tumor responses with pathophysiological relevance. This review highlights the recent advancements of engineered tumor microenvironment systems that enable the unprecedented mechanistic examination of cancer progression and metastasis. We discuss the progress and future perspective of these microengineered biomimetic approaches for anticancer drug prescreening applications.

Journal ArticleDOI
TL;DR: Tests with different types of sludge from a WWTP were investigated regarding their volatile fatty acids (VFA) production-potential and a potential analysis showed that the theoretically possible production of biopolymers in Germany amounts to more than 19% of the 2016 worldwide biopolymer production.
Abstract: This work describes the production of polyhydroxyalkanoates (PHA) as a side stream process on a municipal waste water treatment plant (WWTP) and a subsequent analysis of the production potential in Germany and the European Union (EU). Therefore, tests with different types of sludge from a WWTP were investigated regarding their volatile fatty acids (VFA) production-potential. Afterwards, primary sludge was used as substrate to test a series of operating conditions (temperature, pH, retention time (RT) and withdrawal (WD)) in order to find suitable settings for a high and stable VFA production. In a second step, various tests regarding a high PHA production and stable PHA composition to determine the influence of substrate concentration, temperature, pH and cycle time of an installed feast/famine-regime were conducted. Experiments with a semi-continuous reactor operation showed that a short RT of 4 days and a small WD of 25% at pH = 6 and around 30 °C is preferable for a high VFA production rate (PR) of 1913 mgVFA/(L×d) and a stable VFA composition. A high PHA production up to 28.4% of cell dry weight (CDW) was reached at lower substrate concentration, 20 °C, neutral pH-value and a 24 h cycle time. A final step a potential analysis, based on the results and detailed data from German waste water treatment plants, showed that the theoretically possible production of biopolymers in Germany amounts to more than 19% of the 2016 worldwide biopolymer production. In addition, a profound estimation regarding the EU showed that in theory about 120% of the worldwide biopolymer production (in 2016) could be produced on European waste water treatment plants.

Journal ArticleDOI
TL;DR: A picture of composite systems and coatings based on mesoporous glasses is provided and the challenges for the future are highlighted, including the great potential of inorganic–organic hybrid sol-gel biomaterials.
Abstract: Bioactive glasses are able to bond to bone and stimulate the growth of new tissue while dissolving over time, which makes them ideal materials for regenerative medicine. The advent of mesoporous glasses, which are typically synthesized via sol-gel routes, allowed researchers to develop a broad and versatile class of novel biomaterials that combine superior bone regenerative potential (compared to traditional melt-derived glasses) with the ability of incorporating drugs and various biomolecules for targeted therapy in situ. Mesoporous glass particles can be directly embedded as a bioactive phase within a non-porous (e.g., microspheres), porous (3D scaffolds) or injectable matrix, or be processed to manufacture a surface coating on inorganic or organic (macro)porous substrates, thereby obtaining hierarchical structures with multiscale porosity. This review provides a picture of composite systems and coatings based on mesoporous glasses and highlights the challenges for the future, including the great potential of inorganic-organic hybrid sol-gel biomaterials.

Journal ArticleDOI
TL;DR: 3D printing and bioprinting have huge potential in revolutionizing the field of tissue engineering and regenerative medicine.
Abstract: Additive manufacturing, commonly referred to as 3D printing, is a technology that builds three-dimensional structures and components layer by layer. Bioprinting is the use of 3D printing technology to fabricate tissue constructs for regenerative medicine from cell-laden bio-inks. 3D printing and bioprinting have huge potential in revolutionizing the field of tissue engineering and regenerative medicine. This paper reviews the application of 3D printing and bioprinting in the field of pediatrics.

Journal ArticleDOI
TL;DR: This paper reports on synergistic effects of inorganic cerium oxide (IV) nanoparticles conjugated with the antioxidative enzymes superoxide dismutase and catalase on scavenging oxygen and nitrogen radicals.
Abstract: Interactions of nanoparticles with biological matter-both somatically and in nature-draw scientists' attention. Nanoparticulate systems are believed to be our saviors, acting as versatile drug delivery vehicles. However, they can also cause life-threatening bodily damage. One of the most important properties of nanocrystalline cerium dioxide is its antioxidant activity, which decreases the abundance of reactive oxygen species during inflammation. In this paper, we report on synergistic effects of inorganic cerium oxide (IV) nanoparticles conjugated with the antioxidative enzymes superoxide dismutase and catalase on scavenging oxygen and nitrogen radicals.

Journal ArticleDOI
TL;DR: Thermoanalysis revealed improved material properties of the second polyester in terms of reduced melting temperature Tm and decreased degree of crystallinity Xc and decreased rate of specific growth rate µmax, indicating its enhanced suitability for polymer processing.
Abstract: Based on direct sucrose conversion, the bacterium Burkholderia sacchari is an excellent producer of the microbial homopolyester poly(3-hydroxybutyrate) (PHB). Restrictions of the strain’s wild type in metabolizing structurally related 3-hydroxyvalerate (3HV) precursors towards 3HV-containing polyhydroxyalkanoate (PHA) copolyester calls for alternatives. We demonstrate the highly productive biosynthesis of PHA copolyesters consisting of 3-hydroxybuytrate (3HB) and 4-hydroxybutyrate (4HB) monomers. Controlled bioreactor cultivations were carried out using saccharose from the Brazilian sugarcane industry as the main carbon source, with and without co-feeding with the 4HB-related precursor γ-butyrolactone (GBL). Without GBL co-feeding, the homopolyester PHB was produced at a volumetric productivity of 1.29 g/(L•h), a mass fraction of 0.52 g PHB per g biomass, and a final PHB concentration of 36.5 g/L; the maximum specific growth rate µmax amounted to 0.15 1/h. Adding GBL, we obtained 3HB and 4HB monomers in the polyester at a volumetric productivity of 1.87 g/(L•h), a mass fraction of 0.72 g PHA per g biomass, a final PHA concentration of 53.7 g/L, and a µmax of 0.18 1/h. Thermoanalysis revealed improved material properties of the second polyester in terms of reduced melting temperature Tm (161 °C vs. 178 °C) and decreased degree of crystallinity Xc (24% vs. 71%), indicating its enhanced suitability for polymer processing.

Journal ArticleDOI
TL;DR: The study confirms the potential of inkjet printing for the rapid production of tablets through the deposition of a photocurable bioink designed for hydrophilic APIs.
Abstract: Novel strategies are required to manufacture customized oral solid dosage forms for personalized medicine applications. 3D Pharming, the direct printing of pharmaceutical tablets, is an attractive strategy, since it allows for the rapid production of solid dosage forms containing custom drug dosages. This study reports on the design and characterization of a biocompatible photocurable pharmaceutical polymer for inkjet 3D printing that is suitable for hydrophilic active pharmaceutical ingredients (API). Specifically, hyaluronic acid was functionalized with norbornene moieties that, in the presence of poly(ethylene) glycol dithiol, Eosin Y as a photoinitiator, and a visible light source, undergoes a rapid step-growth polymerization reaction through thiol-ene chemistry. The engineered bioink was loaded with Ropinirole HCL, dispensed through a piezoelectric nozzle onto a blank preform tablet, and polymerized. Drug release analysis of the tablet resulted in 60% release within 15 min of tablet dissolution. The study confirms the potential of inkjet printing for the rapid production of tablets through the deposition of a photocurable bioink designed for hydrophilic APIs.

Journal ArticleDOI
TL;DR: In this study, an in silico method to predict the formation of population heterogeneity by combining computational fluid dynamics (CFD) with a cell cycle model of Pseudomonas putida KT2440 was developed and underline the potential of CFD linked to structured cell cycle models for predicting large-scale heterogeneity insilico and ab initio.
Abstract: Successful scale-up of bioprocesses requires that laboratory-scale performance is equally achieved during large-scale production to meet economic constraints. In industry, heuristic approaches are often applied, making use of physical scale-up criteria that do not consider cellular needs or properties. As a consequence, large-scale productivities, conversion yields, or product purities are often deteriorated, which may prevent economic success. The occurrence of population heterogeneity in large-scale production may be the reason for underperformance. In this study, an in silico method to predict the formation of population heterogeneity by combining computational fluid dynamics (CFD) with a cell cycle model of Pseudomonas putida KT2440 was developed. The glucose gradient and flow field of a 54,000 L stirred tank reactor were generated with the Euler approach, and bacterial movement was simulated as Lagrange particles. The latter were statistically evaluated using a cell cycle model. Accordingly, 72% of all cells were found to switch between standard and multifork replication, and 10% were likely to undergo massive, transcriptional adaptations to respond to extracellular starving conditions. At the same time, 56% of all cells replicated very fast, with µ ≥ 0.3 h-1 performing multifork replication. The population showed very strong heterogeneity, as indicated by the observation that 52.9% showed higher than average adenosine triphosphate (ATP) maintenance demands (12.2%, up to 1.5 fold). These results underline the potential of CFD linked to structured cell cycle models for predicting large-scale heterogeneity in silico and ab initio.

Journal ArticleDOI
TL;DR: The corroboration of the molecular structure of polyhydroxyalkanoates obtained by the conversion of waste polyethylene via non-oxygenated PE wax (N-PEW) as an additional carbon source for a bacterial species is demonstrated.
Abstract: There is an increasing demand for bio-based polymers that are developed from recycled materials. The production of biodegradable polymers can include bio-technological (utilizing microorganisms or enzymes) or chemical synthesis procedures. This report demonstrates the corroboration of the molecular structure of polyhydroxyalkanoates (PHAs) obtained by the conversion of waste polyethylene (PE) via non-oxygenated PE wax (N-PEW) as an additional carbon source for a bacterial species. The N-PEW, obtained from a PE pyrolysis reaction, has been found to be a beneficial carbon source for PHA production with Cupriavidus necator H16. The production of the N-PEW is an alternative to oxidized polyethylene wax (O-PEW) (that has been used as a carbon source previously) as it is less time consuming to manufacture and offers fewer industrial applications. A range of molecular structural analytical techniques were performed on the PHAs obtained; which included nuclear magnetic resonance (NMR) and electrospray ionisation tandem mass spectrometry (ESI-MS/MS). Our study showed that the PHA formed from N-PEW contained 3-hydroxybutyrate (HB) with 11 mol% of 3-hydroxyvalerate (HV) units.