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Bioengineering
Volume 5
Issue 2
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Bioengineering, Volume 5, Issue 2 (June 2018) – 23 articles

Cover Story (view full-size image): There is an evident need to screen for the toxicity and efficacy of drugs and cosmetics applied to the skin. Multi-organ chips are an attractive alternative to animal testing. Among them, the two-organ chip is designed to hold 96-well cell culture inserts for testing small-sized skin equivalents. Here, full-thickness skin equivalents were generated inside these 96-well culture inserts and were successfully integrated into a two-organ chip. This system was employed to implement permeation in a computational fluid dynamics simulation. The results support its use in long-term permeation studies. View Paper here.
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15 pages, 997 KiB  
Review
Dynamic Cultivation of Mesenchymal Stem Cell Aggregates
by Dominik Egger, Carla Tripisciano, Viktoria Weber, Massimo Dominici and Cornelia Kasper
Bioengineering 2018, 5(2), 48; https://doi.org/10.3390/bioengineering5020048 - 19 Jun 2018
Cited by 62 | Viewed by 11253
Abstract
Mesenchymal stem cells (MSCs) are considered as primary candidates for cell-based therapies due to their multiple effects in regenerative medicine. Pre-conditioning of MSCs under physiological conditions—such as hypoxia, three-dimensional environments, and dynamic cultivation—prior to transplantation proved to optimize their therapeutic efficiency. When cultivated [...] Read more.
Mesenchymal stem cells (MSCs) are considered as primary candidates for cell-based therapies due to their multiple effects in regenerative medicine. Pre-conditioning of MSCs under physiological conditions—such as hypoxia, three-dimensional environments, and dynamic cultivation—prior to transplantation proved to optimize their therapeutic efficiency. When cultivated as three-dimensional aggregates or spheroids, MSCs display increased angiogenic, anti-inflammatory, and immunomodulatory effects as well as improved stemness and survival rates after transplantation, and cultivation under dynamic conditions can increase their viability, proliferation, and paracrine effects, alike. Only few studies reported to date, however, have utilized dynamic conditions for three-dimensional aggregate cultivation of MSCs. Still, the integration of dynamic bioreactor systems, such as spinner flasks or stirred tank reactors might pave the way for a robust, scalable bulk expansion of MSC aggregates or MSC-derived extracellular vesicles. This review summarizes recent insights into the therapeutic potential of MSC aggregate cultivation and focuses on dynamic generation and cultivation techniques of MSC aggregates. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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20 pages, 410 KiB  
Article
Deep Artificial Neural Networks for the Diagnostic of Caries Using Socioeconomic and Nutritional Features as Determinants: Data from NHANES 2013–2014
by Laura A. Zanella-Calzada, Carlos E. Galván-Tejada, Nubia M. Chávez-Lamas, Jesús Rivas-Gutierrez, Rafael Magallanes-Quintanar, Jose M. Celaya-Padilla, Jorge I. Galván-Tejada and Hamurabi Gamboa-Rosales
Bioengineering 2018, 5(2), 47; https://doi.org/10.3390/bioengineering5020047 - 18 Jun 2018
Cited by 43 | Viewed by 7094
Abstract
Oral health represents an essential component in the quality of life of people, being a determinant factor in general health since it may affect the risk of suffering other conditions, such as chronic diseases. Oral diseases have become one of the main public [...] Read more.
Oral health represents an essential component in the quality of life of people, being a determinant factor in general health since it may affect the risk of suffering other conditions, such as chronic diseases. Oral diseases have become one of the main public health problems, where dental caries is the condition that most affects oral health worldwide, occurring in about 90% of the global population. This condition has been considered a challenge because of its high prevalence, besides being a chronic but preventable disease which can be caused depending on the consumption of certain nutritional elements interacting simultaneously with different factors, such as socioeconomic factors. Based on this problem, an analysis of a set of 189 dietary and demographic determinants is performed in this work, in order to find the relationship between these factors and the oral situation of a set of subjects. The oral situation refers to the presence and absence/restorations of caries. The methodology is performed constructing a dense artificial neural network (ANN), as a computer-aided diagnosis tool, looking for a generalized model that allows for classifying subjects. As validation, the classification model was evaluated through a statistical analysis based on a cross validation, calculating the accuracy, loss function, receiving operating characteristic (ROC) curve and area under the curve (AUC) parameters. The results obtained were statistically significant, obtaining an accuracy ≃ 0.69 and AUC values of 0.69 and 0.75. Based on these results, it is possible to conclude that the classification model developed through the deep ANN is able to classify subjects with absence of caries from subjects with presence or restorations with high accuracy, according to their demographic and dietary factors. Full article
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27 pages, 18325 KiB  
Review
Honey-Based Templates in Wound Healing and Tissue Engineering
by Benjamin A. Minden-Birkenmaier and Gary L. Bowlin
Bioengineering 2018, 5(2), 46; https://doi.org/10.3390/bioengineering5020046 - 14 Jun 2018
Cited by 126 | Viewed by 17073
Abstract
Over the past few decades, there has been a resurgence in the clinical use of honey as a topical wound treatment. A plethora of in vitro and in vivo evidence supports this resurgence, demonstrating that honey debrides wounds, kills bacteria, penetrates biofilm, lowers [...] Read more.
Over the past few decades, there has been a resurgence in the clinical use of honey as a topical wound treatment. A plethora of in vitro and in vivo evidence supports this resurgence, demonstrating that honey debrides wounds, kills bacteria, penetrates biofilm, lowers wound pH, reduces chronic inflammation, and promotes fibroblast infiltration, among other beneficial qualities. Given these results, it is clear that honey has a potential role in the field of tissue engineering and regeneration. Researchers have incorporated honey into tissue engineering templates, including electrospun meshes, cryogels, and hydrogels, with varying degrees of success. This review details the current state of the field, including challenges which have yet to be overcome, and makes recommendations for the direction of future research in order to develop effective tissue regeneration therapies. Full article
(This article belongs to the Special Issue Advanced Tissue Engineering Scaffolds)
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9 pages, 1992 KiB  
Article
3D Cell Migration Studies for Chemotaxis on Microfluidic-Based Chips: A Comparison between Cardiac and Dermal Fibroblasts
by Sandra Pérez-Rodríguez, Esther Tomás-González and José Manuel García-Aznar
Bioengineering 2018, 5(2), 45; https://doi.org/10.3390/bioengineering5020045 - 12 Jun 2018
Cited by 12 | Viewed by 6561
Abstract
Fibroblast migration to damaged zones in different tissues is crucial to regenerate and recuperate their functional activity. However, fibroblast migration patterns have hardly been studied in disease terms. Here, we study this fundamental process in dermal and cardiac fibroblasts by means of microfluidic-based [...] Read more.
Fibroblast migration to damaged zones in different tissues is crucial to regenerate and recuperate their functional activity. However, fibroblast migration patterns have hardly been studied in disease terms. Here, we study this fundamental process in dermal and cardiac fibroblasts by means of microfluidic-based experiments, which simulate a three-dimensional matrix in which fibroblasts are found in physiological conditions. Cardiac fibroblasts show a higher mean and effective speed, as well as greater contractile force, in comparison to dermal fibroblasts. In addition, we generate chemical gradients to study fibroblast response to platelet derived growth factor (PDGF) and transforming growth factor beta (TGF-β) gradients. Dermal fibroblasts were attracted to PDGF, whereas cardiac fibroblasts are not. Notwithstanding, cardiac fibroblasts increased their mean and effective velocity in the presence of TGF-β. Therefore, given that we observe that the application of these growth factors does not modify fibroblasts’ morphology, these alterations in the migration patterns may be due to an intracellular regulation. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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12 pages, 1393 KiB  
Review
Photobiomodulation Therapy (PBMT) in Peripheral Nerve Regeneration: A Systematic Review
by Marcelie Priscila de Oliveira Rosso, Daniela Vieira Buchaim, Natália Kawano, Gabriela Furlanette, Karina Torres Pomini and Rogério Leone Buchaim
Bioengineering 2018, 5(2), 44; https://doi.org/10.3390/bioengineering5020044 - 9 Jun 2018
Cited by 90 | Viewed by 13026
Abstract
Photobiomodulation therapy (PBMT) has been investigated because of its intimate relationship with tissue recovery processes, such as on peripheral nerve damage. Based on the wide range of benefits that the PBMT has shown and its clinical relevance, the aim of this research was [...] Read more.
Photobiomodulation therapy (PBMT) has been investigated because of its intimate relationship with tissue recovery processes, such as on peripheral nerve damage. Based on the wide range of benefits that the PBMT has shown and its clinical relevance, the aim of this research was to carry out a systematic review of the last 10 years, ascertaining the influence of the PBMT in the regeneration of injured peripheral nerves. The search was performed in the PubMed/MEDLINE database with the combination of the keywords: low-level laser therapy AND nerve regeneration. Initially, 54 articles were obtained, 26 articles of which were chosen for the study according to the inclusion criteria. In the qualitative aspect, it was observed that PBMT was able to accelerate the process of nerve regeneration, presenting an increase in the number of myelinated fibers and a better lamellar organization of myelin sheath, besides improvement of electrophysiological function, immunoreactivity, high functionality rate, decrease of inflammation, pain, and the facilitation of neural regeneration, release of growth factors, increase of vascular network and collagen. It was concluded that PBMT has beneficial effects on the recovery of nerve lesions, especially when related to a faster regeneration and functional improvement, despite the variety of parameters. Full article
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19 pages, 6195 KiB  
Article
Bioengineering of a Full-Thickness Skin Equivalent in a 96-Well Insert Format for Substance Permeation Studies and Organ-On-A-Chip Applications
by Katharina Schimek, Hao-Hsiang Hsu, Moritz Boehme, Jacob Jan Kornet, Uwe Marx, Roland Lauster, Ralf Pörtner and Gerd Lindner
Bioengineering 2018, 5(2), 43; https://doi.org/10.3390/bioengineering5020043 - 7 Jun 2018
Cited by 38 | Viewed by 11407
Abstract
The human skin is involved in protecting the inner body from constant exposure to outer environmental stimuli. There is an evident need to screen for toxicity and the efficacy of drugs and cosmetics applied to the skin. To date, animal studies are still [...] Read more.
The human skin is involved in protecting the inner body from constant exposure to outer environmental stimuli. There is an evident need to screen for toxicity and the efficacy of drugs and cosmetics applied to the skin. To date, animal studies are still the standard method for substance testing, although they are currently controversially discussed Therefore, the multi-organ chip is an attractive alternative to replace animal testing. The two-organ chip is designed to hold 96-well cell culture inserts (CCIs). Small-sized skin equivalents are needed for this. In this study, full-thickness skin equivalents (ftSEs) were generated successfully inside 96-well CCIs. These skin equivalents developed with in vivo-like histological architecture, with normal differentiation marker expressions and proliferation rates. The 96-well CCI-based ftSEs were successfully integrated into the two-organ chip. The permeation of fluorescein sodium salt through the ftSEs was monitored during the culture. The results show a decreasing value for the permeation over time, which seems a promising method to track the development of the ftSEs. Additionally, the permeation was implemented in a computational fluid dynamics simulation, as a tool to predict results in long-term experiments. The advantage of these ftSEs is the reduced need for cells and substances, which makes them more suitable for high throughput assays. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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9 pages, 704 KiB  
Article
Large Scale Production and Downstream Processing of Labyrinthopeptins from the Actinobacterium Actinomadura namibiensis
by Zeljka Rupcic, Stephan Hüttel, Steffen Bernecker, Sae Kanaki and Marc Stadler
Bioengineering 2018, 5(2), 42; https://doi.org/10.3390/bioengineering5020042 - 5 Jun 2018
Cited by 7 | Viewed by 6371
Abstract
A method was established for the production of 1.2-fold and 4.2-fold increased amounts of the antiviral and central nervous system-active lantipeptides, labyrinthopeptins A1 and A2, respectively, isolated from the actinobacterium Actinomadura namibiensis, to enable production in gram scale. We then performed in [...] Read more.
A method was established for the production of 1.2-fold and 4.2-fold increased amounts of the antiviral and central nervous system-active lantipeptides, labyrinthopeptins A1 and A2, respectively, isolated from the actinobacterium Actinomadura namibiensis, to enable production in gram scale. We then performed in vivo characterization of this promising compound class. The labyrinthopeptins A1 and A2 have similar chemical structures and physical properties but differ drastically in their bioactivities. Therefore, large quantities of highly pure material are required for pharmacological studies. An effective methodology was established for the first time for their production in bioreactors, their separation involving gel permeation chromatography on LH20 material, followed by reversed phase-high performance liquid chromatography. With an optimized methodology, 580 mg of labyrinthopeptin A1 and 510 mg of labyrinthopeptin A2 were quantitatively isolated with recovery rates of 72.5% and 42.3% from 7.5 L of culture broth, respectively. However, the fermentation that had already resulted in maximum yields of over 100 mg/L of both target molecules after 300 h in a 10-L scale bioreactor, still requires further optimisation. Full article
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14 pages, 3906 KiB  
Review
Comminution of Dry Lignocellulosic Biomass, a Review: Part I. From Fundamental Mechanisms to Milling Behaviour
by Claire Mayer-Laigle, Nicolas Blanc, Rova Karine Rajaonarivony and Xavier Rouau
Bioengineering 2018, 5(2), 41; https://doi.org/10.3390/bioengineering5020041 - 2 Jun 2018
Cited by 56 | Viewed by 8070
Abstract
The comminution of lignocellulosic biomass is a key operation for many applications as bio-based materials, bio-energy or green chemistry. The grinder used can have a significant impact on the properties of the ground powders, of those of the end-products and on the energy [...] Read more.
The comminution of lignocellulosic biomass is a key operation for many applications as bio-based materials, bio-energy or green chemistry. The grinder used can have a significant impact on the properties of the ground powders, of those of the end-products and on the energy consumption. Since several years, the milling of lignocellulosic biomass has been the subject of numerous studies most often focused on specific materials and/or applications but there is still a lack of generic knowledge about the relation between the histological structure of the raw materials, the milling technologies and the physical and chemical properties of the powders. This review aims to point out the main process parameters and plant raw material properties that influence the milling operation and their consequences on the properties of ground powders and on the energy consumption during the comminution. Full article
(This article belongs to the Special Issue Advances in Biomass Preprocessing and Pretreatments and Valorization to Energy)
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20 pages, 2946 KiB  
Article
A Microfluidic System for the Investigation of Tumor Cell Extravasation
by Claudia Kühlbach, Sabrina Da Luz, Frank Baganz, Volker C. Hass and Margareta M. Mueller
Bioengineering 2018, 5(2), 40; https://doi.org/10.3390/bioengineering5020040 - 23 May 2018
Cited by 27 | Viewed by 8391
Abstract
Metastatic dissemination of cancer cells is a very complex process. It includes the intravasation of cells into the metastatic pathways, their passive distribution within the blood or lymph flow, and their extravasation into the surrounding tissue. Crucial steps during extravasation are the adhesion [...] Read more.
Metastatic dissemination of cancer cells is a very complex process. It includes the intravasation of cells into the metastatic pathways, their passive distribution within the blood or lymph flow, and their extravasation into the surrounding tissue. Crucial steps during extravasation are the adhesion of the tumor cells to the endothelium and their transendothelial migration. However, the molecular mechanisms that are underlying this process are still not fully understood. Novel three dimensional (3D) models for research on the metastatic cascade include the use of microfluidic devices. Different from two dimensional (2D) models, these devices take cell–cell, structural, and mechanical interactions into account. Here we introduce a new microfluidic device in order to study tumor extravasation. The device consists of three different parts, containing two microfluidic channels and a porous membrane sandwiched in between them. A smaller channel together with the membrane represents the vessel equivalent and is seeded separately with primary endothelial cells (EC) that are isolated from the lung artery. The second channel acts as reservoir to collect the migrated tumor cells. In contrast to many other systems, this device does not need an additional coating to allow EC growth, as the primary EC that is used produces their own basement membrane. VE-Cadherin, an endothelial adherence junction protein, was expressed in regular localization, which indicates a tight barrier function and cell–cell connections of the endothelium. The EC in the device showed in vivo-like behavior under flow conditions. The GFP-transfected tumor cells that were introduced were of epithelial or mesenchymal origin and could be observed by live cell imaging, which indicates tightly adherent tumor cells to the endothelial lining under different flow conditions. These results suggest that the new device can be used for research on molecular requirements, conditions, and mechanism of extravasation and its inhibition. Full article
(This article belongs to the Special Issue Advances in Micro-Bioreactor Design for Organ Cell Studies)
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11 pages, 995 KiB  
Article
Effect of Methylcellulose Molecular Weight on the Properties of Self-Assembling MC-g-PNtBAm Nanogels
by Marion Jamard and Heather Sheardown
Bioengineering 2018, 5(2), 39; https://doi.org/10.3390/bioengineering5020039 - 23 May 2018
Cited by 6 | Viewed by 5282
Abstract
The efficiency of drug delivery to the eye using topical drop therapy is limited by the ocular clearance mechanisms. Nanocarriers, able to encapsulate bioactive compounds and slow down their release, may allow for prolonged on-eye residence times when combined with topical application for [...] Read more.
The efficiency of drug delivery to the eye using topical drop therapy is limited by the ocular clearance mechanisms. Nanocarriers, able to encapsulate bioactive compounds and slow down their release, may allow for prolonged on-eye residence times when combined with topical application for treatment of ocular conditions. Previously, self-assemblies of methylcellulose (MC) hydrophobized with N-tert-butylacrylamide side chains (MC-g-PNtBAm) were developed. The purpose of the current study was to investigate the impact of the methylcellulose backbone length on the properties of the nanogels. We synthesized MC-g-PNtBAm nanogels using four different molecular weights of MC with two degrees of hydrophobic modification and investigated the physical and chemical properties of the resulting polymeric nanogels. While no significant change could be observed at a high degree of hydrophobization, properties were affected at a lower one. Increasing the molecular weight of MC improved the swelling capacity of the nanogels, increasing their size in water. An effect on the drug release was also noted. Nanogels prepared using MC with a molecular weight of 30 kDa did not retain as much dexamethasone and released it faster compared to those prepared using 230 kDa MC. Thus, besides the degree of hydrophobization, the length of MC chains provides another means of tuning the properties of MC-g-PNtBAm nanogels. Full article
(This article belongs to the Special Issue Bioengineering Nano and Micro-Gels for Biomedical Applications)
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12 pages, 10884 KiB  
Article
Guiding Device for the Patellar Cut in Total Knee Arthroplasty: Design and Validation
by Erica L. Rex, Cinzia Gaudelli, Emmanuel M. Illical, John Person, Karen C. T. Arlt, Barry Wylant and Carolyn Anglin
Bioengineering 2018, 5(2), 38; https://doi.org/10.3390/bioengineering5020038 - 10 May 2018
Cited by 4 | Viewed by 5511
Abstract
An incorrect cut of the patella (kneecap) during total knee arthroplasty, affects the thickness in different quadrants of the patella, leading to pain and poor function. Because of the disadvantages of existing devices, many surgeons choose to perform the cut freehand. Given this [...] Read more.
An incorrect cut of the patella (kneecap) during total knee arthroplasty, affects the thickness in different quadrants of the patella, leading to pain and poor function. Because of the disadvantages of existing devices, many surgeons choose to perform the cut freehand. Given this mistrust of existing devices, a quick, but accurate, method is needed that guides the cut, without constraining the surgeon. A novel device is described that allows the surgeon to mark a line at the desired cutting plane parallel to the front (anterior) surface using a cautery tool, remove the device, and then align the saw guide, reamer, or freehand saw with the marked line to cut the patella. The device was tested on 36 artificial patellae, custom-molded from two shapes considered easier and harder to resect accurately, and eight paired cadaveric specimens, each in comparison to the conventional saw guide technique. The mediolateral angle, superoinferior angle, difference from intended thickness, and time were comparable or better for the new device. Addressing the remaining outliers should be possible through additional design changes. Use of this guidance device has the potential to improve patellar resection accuracy, as well as provide training to residents and a double-check and feedback tool for expert surgeons. Full article
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14 pages, 2455 KiB  
Article
Anti-RSV Peptide-Loaded Liposomes for the Inhibition of Respiratory Syncytial Virus
by Sameer Joshi, Atul A. Chaudhari, Vida Dennis, Daniel J. Kirby, Yvonne Perrie and Shree Ram Singh
Bioengineering 2018, 5(2), 37; https://doi.org/10.3390/bioengineering5020037 - 9 May 2018
Cited by 17 | Viewed by 6477
Abstract
Although respiratory syncytial virus (RSV) is one of the leading causes of acute respiratory tract infection in infants and adults, effective treatment options remain limited. To circumvent this issue, there is a novel approach, namely, the development of multifunctional liposomes for the delivery [...] Read more.
Although respiratory syncytial virus (RSV) is one of the leading causes of acute respiratory tract infection in infants and adults, effective treatment options remain limited. To circumvent this issue, there is a novel approach, namely, the development of multifunctional liposomes for the delivery of anti RSV-peptides. While most of the peptides that are used for loading with the particulate delivery systems are the penetrating peptides, an alternative approach is the development of liposome-peptide systems, which are loaded with an RSV fusion peptide (RF-482), which has been designed to inhibit the RSV fusion and block infection. The results of this work have revealed that the liposomes themselves can serve as potential RSV inhibitors, whilst the anti-RSV-peptide with liposomes can significantly increase the RSV inhibition when compared with the anti-RSV peptide alone. Full article
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13 pages, 2882 KiB  
Article
A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device
by Jonas Christoffersson, Florian Meier, Henning Kempf, Kristin Schwanke, Michelle Coffee, Mario Beilmann, Robert Zweigerdt and Carl-Fredrik Mandenius
Bioengineering 2018, 5(2), 36; https://doi.org/10.3390/bioengineering5020036 - 4 May 2018
Cited by 29 | Viewed by 9304
Abstract
Three-dimensional (3D) models with cells arranged in clusters or spheroids have emerged as valuable tools to improve physiological relevance in drug screening. One of the challenges with cells cultured in 3D, especially for high-throughput applications, is to quickly and non-invasively assess the cellular [...] Read more.
Three-dimensional (3D) models with cells arranged in clusters or spheroids have emerged as valuable tools to improve physiological relevance in drug screening. One of the challenges with cells cultured in 3D, especially for high-throughput applications, is to quickly and non-invasively assess the cellular state in vitro. In this article, we show that the number of cells growing out from human induced pluripotent stem cell (hiPSC)-derived cardiac spheroids can be quantified to serve as an indicator of a drug’s effect on spheroids captured in a microfluidic device. Combining this spheroid-on-a-chip with confocal high content imaging reveals easily accessible, quantitative outgrowth data. We found that effects on outgrowing cell numbers correlate to the concentrations of relevant pharmacological compounds and could thus serve as a practical readout to monitor drug effects. Here, we demonstrate the potential of this semi-high-throughput “cardiac cell outgrowth assay” with six compounds at three concentrations applied to spheroids for 48 h. The image-based readout complements end-point assays or may be used as a non-invasive assay for quality control during long-term culture. Full article
(This article belongs to the Special Issue Advances in Micro-Bioreactor Design for Organ Cell Studies)
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12 pages, 3160 KiB  
Article
Cardiac Arrhythmia Classification by Multi-Layer Perceptron and Convolution Neural Networks
by Shalin Savalia and Vahid Emamian
Bioengineering 2018, 5(2), 35; https://doi.org/10.3390/bioengineering5020035 - 4 May 2018
Cited by 130 | Viewed by 13868
Abstract
The electrocardiogram (ECG) plays an imperative role in the medical field, as it records heart signal over time and is used to discover numerous cardiovascular diseases. If a documented ECG signal has a certain irregularity in its predefined features, this is called arrhythmia, [...] Read more.
The electrocardiogram (ECG) plays an imperative role in the medical field, as it records heart signal over time and is used to discover numerous cardiovascular diseases. If a documented ECG signal has a certain irregularity in its predefined features, this is called arrhythmia, the types of which include tachycardia, bradycardia, supraventricular arrhythmias, and ventricular, etc. This has encouraged us to do research that consists of distinguishing between several arrhythmias by using deep neural network algorithms such as multi-layer perceptron (MLP) and convolution neural network (CNN). The TensorFlow library that was established by Google for deep learning and machine learning is used in python to acquire the algorithms proposed here. The ECG databases accessible at PhysioBank.com and kaggle.com were used for training, testing, and validation of the MLP and CNN algorithms. The proposed algorithm consists of four hidden layers with weights, biases in MLP, and four-layer convolution neural networks which map ECG samples to the different classes of arrhythmia. The accuracy of the algorithm surpasses the performance of the current algorithms that have been developed by other cardiologists in both sensitivity and precision. Full article
(This article belongs to the Special Issue Advanced Biomaterials for Cardiovascular Tissue Engineering Applications)
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11 pages, 1064 KiB  
Article
Kinetic Modeling of Corn Fermentation with S. cerevisiae Using a Variable Temperature Strategy
by Augusto C. M. Souza, Mohammad Mousaviraad, Kenneth O. M. Mapoka and Kurt A. Rosentrater
Bioengineering 2018, 5(2), 34; https://doi.org/10.3390/bioengineering5020034 - 24 Apr 2018
Cited by 8 | Viewed by 7158
Abstract
While fermentation is usually done at a fixed temperature, in this study, the effect of having a controlled variable temperature was analyzed. A nonlinear system was used to model batch ethanol fermentation, using corn as substrate and the yeast Saccharomyces cerevisiae, at [...] Read more.
While fermentation is usually done at a fixed temperature, in this study, the effect of having a controlled variable temperature was analyzed. A nonlinear system was used to model batch ethanol fermentation, using corn as substrate and the yeast Saccharomyces cerevisiae, at five different fixed and controlled variable temperatures. The lower temperatures presented higher ethanol yields but took a longer time to reach equilibrium. Higher temperatures had higher initial growth rates, but the decay of yeast cells was faster compared to the lower temperatures. However, in a controlled variable temperature model, the temperature decreased with time with the initial value of 40 ∘ C. When analyzing a time window of 60 h, the ethanol production increased 20% compared to the batch with the highest temperature; however, the yield was still 12% lower compared to the 20 ∘ C batch. When the 24 h’ simulation was analyzed, the controlled model had a higher ethanol concentration compared to both fixed temperature batches. Full article
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15 pages, 13549 KiB  
Article
Efficient Computational Design of a Scaffold for Cartilage Cell Regeneration
by Tannaz Tajsoleiman, Mohammad Jafar Abdekhodaie, Krist V. Gernaey and Ulrich Krühne
Bioengineering 2018, 5(2), 33; https://doi.org/10.3390/bioengineering5020033 - 24 Apr 2018
Cited by 9 | Viewed by 6129
Abstract
Due to the sensitivity of mammalian cell cultures, understanding the influence of operating conditions during a tissue generation procedure is crucial. In this regard, a detailed study of scaffold based cell culture under a perfusion flow is presented with the aid of mathematical [...] Read more.
Due to the sensitivity of mammalian cell cultures, understanding the influence of operating conditions during a tissue generation procedure is crucial. In this regard, a detailed study of scaffold based cell culture under a perfusion flow is presented with the aid of mathematical modelling and computational fluid dynamics (CFD). With respect to the complexity of the case study, this work focuses solely on the effect of nutrient and metabolite concentrations, and the possible influence of fluid-induced shear stress on a targeted cell (cartilage) culture. The simulation set up gives the possibility of predicting the cell culture behavior under various operating conditions and scaffold designs. Thereby, the exploitation of the predictive simulation into a newly developed stochastic routine provides the opportunity of exploring improved scaffold geometry designs. This approach was applied on a common type of fibrous structure in order to increase the process efficiencies compared with the regular used formats. The suggested topology supplies a larger effective surface for cell attachment compared to the reference design while the level of shear stress is kept at the positive range of effect. Moreover, significant improvement of mass transfer is predicted for the suggested topology. Full article
(This article belongs to the Special Issue Advances in Micro-Bioreactor Design for Organ Cell Studies)
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10 pages, 225 KiB  
Review
Role of Bioreactor Technology in Tissue Engineering for Clinical Use and Therapeutic Target Design
by Clare Selden and Barry Fuller
Bioengineering 2018, 5(2), 32; https://doi.org/10.3390/bioengineering5020032 - 24 Apr 2018
Cited by 67 | Viewed by 12252
Abstract
Micro and small bioreactors are well described for use in bioprocess development in pre-production manufacture, using ultra-scale down and microfluidic methodology. However, the use of bioreactors to understand normal and pathophysiology by definition must be very different, and the constraints of the physiological [...] Read more.
Micro and small bioreactors are well described for use in bioprocess development in pre-production manufacture, using ultra-scale down and microfluidic methodology. However, the use of bioreactors to understand normal and pathophysiology by definition must be very different, and the constraints of the physiological environment influence such bioreactor design. This review considers the key elements necessary to enable bioreactors to address three main areas associated with biological systems. All entail recreation of the in vivo cell niche as faithfully as possible, so that they may be used to study molecular and cellular changes in normal physiology, with a view to creating tissue-engineered grafts for clinical use; understanding the pathophysiology of disease at the molecular level; defining possible therapeutic targets; and enabling appropriate pharmaceutical testing on a truly representative organoid, thus enabling better drug design, and simultaneously creating the potential to reduce the numbers of animals in research. The premise explored is that not only cellular signalling cues, but also mechano-transduction from mechanical cues, play an important role. Full article
(This article belongs to the Special Issue Advances in Micro-Bioreactor Design for Organ Cell Studies)
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14 pages, 4426 KiB  
Article
Musculoskeletal Model Development of the Elbow Joint with an Experimental Evaluation
by Munsur Rahman, Mohsen Sharifi Renani, Akin Cil and Antonis P. Stylianou
Bioengineering 2018, 5(2), 31; https://doi.org/10.3390/bioengineering5020031 - 20 Apr 2018
Cited by 10 | Viewed by 9876
Abstract
A dynamic musculoskeletal model of the elbow joint in which muscle, ligament, and articular surface contact forces are predicted concurrently would be an ideal tool for patient-specific preoperative planning, computer-aided surgery, and rehabilitation. Existing musculoskeletal elbow joint models have limited clinical applicability because [...] Read more.
A dynamic musculoskeletal model of the elbow joint in which muscle, ligament, and articular surface contact forces are predicted concurrently would be an ideal tool for patient-specific preoperative planning, computer-aided surgery, and rehabilitation. Existing musculoskeletal elbow joint models have limited clinical applicability because of idealizing the elbow as a mechanical hinge joint or ignoring important soft tissue (e.g., cartilage) contributions. The purpose of this study was to develop a subject-specific anatomically correct musculoskeletal elbow joint model and evaluate it based on experimental kinematics and muscle electromyography measurements. The model included three-dimensional bone geometries, a joint constrained by multiple ligament bundles, deformable contacts, and the natural oblique wrapping of ligaments. The musculoskeletal model predicted the bone kinematics reasonably accurately in three different velocity conditions. The model predicted timing and number of muscle excitations, and the normalized muscle forces were also in agreement with the experiment. The model was able to predict important in vivo parameters that are not possible to measure experimentally, such as muscle and ligament forces, and cartilage contact pressure. In addition, the developed musculoskeletal model was computationally efficient for body-level dynamic simulation. The maximum computation time was less than 30 min for our 35 s simulation. As a predictive clinical tool, the potential medical applications for this model and modeling approach are significant. Full article
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21 pages, 14679 KiB  
Article
Biocatalyst Screening with a Twist: Application of Oxygen Sensors Integrated in Microchannels for Screening Whole Cell Biocatalyst Variants
by Ana C. Fernandes, Julia M. Halder, Bettina M. Nestl, Bernhard Hauer, Krist V. Gernaey and Ulrich Krühne
Bioengineering 2018, 5(2), 30; https://doi.org/10.3390/bioengineering5020030 - 9 Apr 2018
Cited by 12 | Viewed by 7443
Abstract
Selective oxidative functionalization of molecules is a highly relevant and often demanding reaction in organic chemistry. The use of biocatalysts allows the stereo- and regioselective introduction of oxygen molecules in organic compounds at milder conditions and avoids the use of complex group-protection schemes [...] Read more.
Selective oxidative functionalization of molecules is a highly relevant and often demanding reaction in organic chemistry. The use of biocatalysts allows the stereo- and regioselective introduction of oxygen molecules in organic compounds at milder conditions and avoids the use of complex group-protection schemes and toxic compounds usually applied in conventional organic chemistry. The identification of enzymes with the adequate properties for the target reaction and/or substrate requires better and faster screening strategies. In this manuscript, a microchannel with integrated oxygen sensors was applied to the screening of wild-type and site-directed mutated variants of naphthalene dioxygenase (NDO) from Pseudomonas sp. NICB 9816-4. The oxygen sensors were used to measure the oxygen consumption rate of several variants during the conversion of styrene to 1-phenylethanediol. The oxygen consumption rate allowed the distinguishing of endogenous respiration of the cell host from the oxygen consumed in the reaction. Furthermore, it was possible to identify the higher activity and different reaction rate of two variants, relative to the wild-type NDO. The meander microchannel with integrated oxygen sensors can therefore be used as a simple and fast screening platform for the selection of dioxygenase mutants, in terms of their ability to convert styrene, and potentially in terms of substrate specificity. Full article
(This article belongs to the Special Issue Advances in Micro-Bioreactor Design for Organ Cell Studies)
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10 pages, 46693 KiB  
Article
A 3D Microfluidic Model to Recapitulate Cancer Cell Migration and Invasion
by Yi-Chin Toh, Anju Raja, Hanry Yu and Danny Van Noort
Bioengineering 2018, 5(2), 29; https://doi.org/10.3390/bioengineering5020029 - 8 Apr 2018
Cited by 49 | Viewed by 10810
Abstract
We have developed a microfluidic-based culture chip to simulate cancer cell migration and invasion across the basement membrane. In this microfluidic chip, a 3D microenvironment is engineered to culture metastatic breast cancer cells (MX1) in a 3D tumor model. A chemo-attractant was incorporated [...] Read more.
We have developed a microfluidic-based culture chip to simulate cancer cell migration and invasion across the basement membrane. In this microfluidic chip, a 3D microenvironment is engineered to culture metastatic breast cancer cells (MX1) in a 3D tumor model. A chemo-attractant was incorporated to stimulate motility across the membrane. We validated the usefulness of the chip by tracking the motilities of the cancer cells in the system, showing them to be migrating or invading (akin to metastasis). It is shown that our system can monitor cell migration in real time, as compare to Boyden chambers, for example. Thus, the chip will be of interest to the drug-screening community as it can potentially be used to monitor the behavior of cancer cell motility, and, therefore, metastasis, in the presence of anti-cancer drugs. Full article
(This article belongs to the Special Issue Advances in Micro-Bioreactor Design for Organ Cell Studies)
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18 pages, 328 KiB  
Review
Therapeutic Use of Stem Cells for Myocardial Infarction
by Mariah Madigan and Rony Atoui
Bioengineering 2018, 5(2), 28; https://doi.org/10.3390/bioengineering5020028 - 6 Apr 2018
Cited by 59 | Viewed by 10316
Abstract
Myocardial infarction is a leading cause of morbidity and mortality worldwide. Although medical and surgical treatments can significantly improve patient outcomes, no treatment currently available is able to generate new contractile tissue or reverse ischemic myocardium. Driven by the recent/novel understanding that regenerative [...] Read more.
Myocardial infarction is a leading cause of morbidity and mortality worldwide. Although medical and surgical treatments can significantly improve patient outcomes, no treatment currently available is able to generate new contractile tissue or reverse ischemic myocardium. Driven by the recent/novel understanding that regenerative processes do exist in the myocardium—tissue previously thought not to possess regenerative properties—the use of stem cells has emerged as a promising therapeutic approach with high expectations. The literature describes the use of cells from various sources, categorizing them as either embryonic, induced pluripotent, or adult/tissue stem cells (mesenchymal, hematopoietic, skeletal myoblasts, cardiac stem cells). Many publications show the successful use of these cells to regenerate damaged myocardium in both animal and human models; however, more studies are needed to directly compare cells of various origins in efforts to draw conclusions on the ideal source. Although numerous challenges exist in this developing area of research and clinical practice, prospects are encouraging. The following aims to provide a concise review outlining the different types of stem cells used in patients after myocardial infarction. Full article
8 pages, 2563 KiB  
Review
Non-Transfusional Hemocomponents: From Biology to the Clinic—A Literature Review
by Roberta Gasparro, Erda Qorri, Alessandra Valletta, Michele Masucci, Pasquale Sammartino, Alessandra Amato and Gaetano Marenzi
Bioengineering 2018, 5(2), 27; https://doi.org/10.3390/bioengineering5020027 - 31 Mar 2018
Cited by 24 | Viewed by 6012
Abstract
Non-transfusional hemocomponents for surgical use are autogenous products prepared through the centrifugation of a blood sample from a patient. Their potential beneficial outcomes include hard and soft tissue regeneration, local hemostasis, and the acceleration of wound healing. Therefore, they are suitable for application [...] Read more.
Non-transfusional hemocomponents for surgical use are autogenous products prepared through the centrifugation of a blood sample from a patient. Their potential beneficial outcomes include hard and soft tissue regeneration, local hemostasis, and the acceleration of wound healing. Therefore, they are suitable for application in different medical fields as therapeutic options and in surgical practices that require tissue regeneration. Full article
(This article belongs to the Special Issue Functional Biomaterials for Regenerative Engineering)
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14 pages, 2881 KiB  
Article
Towards Control of a Transhumeral Prosthesis with EEG Signals
by D.S.V. Bandara, Jumpei Arata and Kazuo Kiguchi
Bioengineering 2018, 5(2), 26; https://doi.org/10.3390/bioengineering5020026 - 22 Mar 2018
Cited by 28 | Viewed by 7927
Abstract
Robotic prostheses are expected to allow amputees greater freedom and mobility. However, available options to control transhumeral prostheses are reduced with increasing amputation level. In addition, for electromyography-based control of prostheses, the residual muscles alone cannot generate sufficiently different signals for accurate distal [...] Read more.
Robotic prostheses are expected to allow amputees greater freedom and mobility. However, available options to control transhumeral prostheses are reduced with increasing amputation level. In addition, for electromyography-based control of prostheses, the residual muscles alone cannot generate sufficiently different signals for accurate distal arm function. Thus, controlling a multi-degree of freedom (DoF) transhumeral prosthesis is challenging with currently available techniques. In this paper, an electroencephalogram (EEG)-based hierarchical two-stage approach is proposed to achieve multi-DoF control of a transhumeral prosthesis. In the proposed method, the motion intention for arm reaching or hand lifting is identified using classifiers trained with motion-related EEG features. For this purpose, neural network and k-nearest neighbor classifiers are used. Then, elbow motion and hand endpoint motion is estimated using a different set of neural-network-based classifiers, which are trained with motion information recorded using healthy subjects. The predictions from the classifiers are compared with residual limb motion to generate a final prediction of motion intention. This can then be used to realize multi-DoF control of a prosthesis. The experimental results show the feasibility of the proposed method for multi-DoF control of a transhumeral prosthesis. This proof of concept study was performed with healthy subjects. Full article
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