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Bioengineering, Volume 5, Issue 3 (September 2018)

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Cover Story (view full-size image) A low percentage of novel drug candidates succeed and reach the end of the drug discovery pipeline. [...] Read more.
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Open AccessReview Endometrial Stem Cells in Farm Animals: Potential Role in Uterine Physiology and Pathology
Bioengineering 2018, 5(3), 75; https://doi.org/10.3390/bioengineering5030075
Received: 31 July 2018 / Revised: 7 September 2018 / Accepted: 14 September 2018 / Published: 18 September 2018
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Abstract
The endometrium is an accessible source of mesenchymal stem cells. Most investigations of endometrial mesenchymal stem cells (eMSCs) have been conducted in humans. In animals, particularly in livestock, eMSC research is scarce. Such cells have been described in the bovine, ovine, caprine, porcine,
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The endometrium is an accessible source of mesenchymal stem cells. Most investigations of endometrial mesenchymal stem cells (eMSCs) have been conducted in humans. In animals, particularly in livestock, eMSC research is scarce. Such cells have been described in the bovine, ovine, caprine, porcine, and equine endometrium. Here we provide the state of the art of eMSCs in farm animals with a focus on the bovine species. In bovines, eMSCs have been identified during the phases of the estrous cycle, during which their functionality and the presence of eMSC-specific markers has been shown to change. Moreover, postpartum inflammation related to endometritis affects the presence and functionality of eMSCs, and prostaglandin E2 (PGE2) may be the mediator of such changes. We demonstrated that exposure to PGE2 in vitro modifies the transcriptomic profile of eMSCs, showing its potential role in the fate of stem cell activation, migration, and homing during pathological uterine inflammation in endometritis and in healthy puerperal endometrium. Farm animal research on eMSCs can be of great value in translational research for certain uterine pathologies and for immunomodulation of local responses to pathogens, hormones, and other substances. Further research is necessary in areas such as in vivo location of the niches and their immunomodulatory and anti-infective properties. Full article
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Open AccessArticle Adverse Hemodynamic Conditions Associated with Mechanical Heart Valve Leaflet Immobility
Bioengineering 2018, 5(3), 74; https://doi.org/10.3390/bioengineering5030074
Received: 24 July 2018 / Revised: 8 September 2018 / Accepted: 10 September 2018 / Published: 16 September 2018
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Abstract
Artificial heart valves may dysfunction, leading to thrombus and/or pannus formations. Computational fluid dynamics is a promising tool for improved understanding of heart valve hemodynamics that quantify detailed flow velocities and turbulent stresses to complement Doppler measurements. This combined information can assist in
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Artificial heart valves may dysfunction, leading to thrombus and/or pannus formations. Computational fluid dynamics is a promising tool for improved understanding of heart valve hemodynamics that quantify detailed flow velocities and turbulent stresses to complement Doppler measurements. This combined information can assist in choosing optimal prosthesis for individual patients, aiding in the development of improved valve designs, and illuminating subtle changes to help guide more timely early intervention of valve dysfunction. In this computational study, flow characteristics around a bileaflet mechanical heart valve were investigated. The study focused on the hemodynamic effects of leaflet immobility, specifically, where one leaflet does not fully open. Results showed that leaflet immobility increased the principal turbulent stresses (up to 400%), and increased forces and moments on both leaflets (up to 600% and 4000%, respectively). These unfavorable conditions elevate the risk of blood cell damage and platelet activation, which are known to cascade to more severe leaflet dysfunction. Leaflet immobility appeared to cause maximal velocity within the lateral orifices. This points to the possible importance of measuring maximal velocity at the lateral orifices by Doppler ultrasound (in addition to the central orifice, which is current practice) to determine accurate pressure gradients as markers of valve dysfunction. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Open AccessReview Neurocognitive and Psychosocial Outcomes in Pediatric Brain Tumor Survivors
Bioengineering 2018, 5(3), 73; https://doi.org/10.3390/bioengineering5030073
Received: 3 August 2018 / Revised: 6 September 2018 / Accepted: 8 September 2018 / Published: 11 September 2018
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Abstract
The late neurocognitive and psychosocial effects of treatment for pediatric brain tumor (PBT) represent important areas of clinical focus and ongoing research. Neurocognitive sequelae and associated problems with learning and socioemotional development negatively impact PBT survivors’ overall health-related quality of life, educational attainment
[...] Read more.
The late neurocognitive and psychosocial effects of treatment for pediatric brain tumor (PBT) represent important areas of clinical focus and ongoing research. Neurocognitive sequelae and associated problems with learning and socioemotional development negatively impact PBT survivors’ overall health-related quality of life, educational attainment and employment rates. Multiple factors including tumor features and associated complications, treatment methods, individual protective and vulnerability factors and accessibility of environmental supports contribute to the neurocognitive and psychosocial outcomes in PBT survivors. Declines in overall measured intelligence are common and may persist years after treatment. Core deficits in attention, processing speed and working memory are postulated to underlie problems with overall intellectual development, academic achievement and career attainment. Additionally, psychological problems after PBT can include depression, anxiety and psychosocial adjustment issues. Several intervention paradigms are briefly described, though to date research on innovative, specific and effective interventions for neurocognitive late effects is still in its early stages. This article reviews the existing research for understanding PBT late effects and highlights the need for innovative research to enhance neurocognitive and psychosocial outcomes in PBT survivors. Full article
(This article belongs to the Special Issue Update in Pediatric Neuro-Oncology)
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Open AccessArticle Synthesis and Characterization of Controlled Nitric Oxide Release from S-Nitroso-N-Acetyl-d-Penicillamine Covalently Linked to Polyvinyl Chloride (SNAP-PVC)
Bioengineering 2018, 5(3), 72; https://doi.org/10.3390/bioengineering5030072
Received: 10 August 2018 / Revised: 30 August 2018 / Accepted: 3 September 2018 / Published: 5 September 2018
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Abstract
Polyvinyl chloride (PVC) is one of the most widely used polymers in medicine but has very poor biocompatibility when in contact with tissue or blood. To increase biocompatibility, controlled release of nitric oxide (NO) can be utilized to mitigate and reduce the inflammatory
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Polyvinyl chloride (PVC) is one of the most widely used polymers in medicine but has very poor biocompatibility when in contact with tissue or blood. To increase biocompatibility, controlled release of nitric oxide (NO) can be utilized to mitigate and reduce the inflammatory response. A synthetic route is described where PVC is aminated to a specified degree and then further modified by covalently linking S-nitroso-N-acetyl-d-penicillamine (SNAP) groups to the free primary amine sites to create a nitric oxide releasing polymer (SNAP-PVC). Controllable release of NO from SNAP-PVC is described using photoinitiation from light emitting diodes (LEDs). Ion-mediated NO release is also demonstrated as another pathway to provide a passive mechanism for NO delivery. The large range of NO fluxes obtained from the SNAP-PVC films indicate many potential uses in mediating unwanted inflammatory response in blood- and tissue-contacting devices and as a tool for delivering precise amounts of NO in vitro. Full article
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Open AccessReview Understanding the Impact of Stent and Scaffold Material and Strut Design on Coronary Artery Thrombosis from the Basic and Clinical Points of View
Bioengineering 2018, 5(3), 71; https://doi.org/10.3390/bioengineering5030071
Received: 1 August 2018 / Revised: 23 August 2018 / Accepted: 30 August 2018 / Published: 4 September 2018
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Abstract
The technology of percutaneous coronary intervention (PCI) is constantly being refined in order to overcome the shortcomings of present day technologies. Even though current generation metallic drug-eluting stents (DES) perform very well in the short-term, concerns still exist about their long-term efficacy. Late
[...] Read more.
The technology of percutaneous coronary intervention (PCI) is constantly being refined in order to overcome the shortcomings of present day technologies. Even though current generation metallic drug-eluting stents (DES) perform very well in the short-term, concerns still exist about their long-term efficacy. Late clinical complications including late stent thrombosis (ST), restenosis, and neoatherosclerosis still exist and many of these events may be attributed to either the metallic platform and/or the drug and polymer left behind in the arterial wall. To overcome this limitation, the concept of totally bioresorbable vascular scaffolds (BRS) was invented with the idea that by eliminating long-term exposure of the vessel wall to the metal backbone, drug, and polymer, late outcomes would improve. The Absorb-bioabsorbable vascular scaffold (Absorb-BVS) represented the most advanced attempt to make such a device, with thicker struts, greater vessel surface area coverage and less radial force versus contemporary DES. Unfortunately, almost one year after its initial approval by the U.S. Food and Drug Administration, this scaffold was withdrawn from the market due to declining devise utilization driven by the concerns about scaffold thrombosis (ScT) seen in both early and late time points. Additionally, the specific causes of ScT have not yet been fully elucidated. In this review, we discuss the platform, vascular response, and clinical data of past and current metallic coronary stents with the Absorb-BVS and newer generation BRS, concentrating on their material/design and the mechanisms of thrombotic complications from the pre-clinical, pathologic, and clinical viewpoints. Full article
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Open AccessArticle Acoustic Reconstruction for Photothermal Imaging
Bioengineering 2018, 5(3), 70; https://doi.org/10.3390/bioengineering5030070
Received: 28 July 2018 / Revised: 18 August 2018 / Accepted: 22 August 2018 / Published: 29 August 2018
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Abstract
Pulsed illumination of a sample, e.g., of a biological tissue, causes a sudden temperature increase of light absorbing structures, such as blood vessels, which results in an outgoing acoustic wave, as well as heat diffusion, of the absorbed energy. Both of the signals,
[...] Read more.
Pulsed illumination of a sample, e.g., of a biological tissue, causes a sudden temperature increase of light absorbing structures, such as blood vessels, which results in an outgoing acoustic wave, as well as heat diffusion, of the absorbed energy. Both of the signals, pressure and temperature, can be measured at the sample surface and are used to reconstruct the initial temperature or pressure distribution, called photoacoustic or photothermal reconstruction respectively. We have demonstrated that both signals at the same surface pixel are connected by a temporal transformation. This allows for the calculation of a so-called acoustical virtual wave from the surface temperature evolution as measured by an infrared camera. The virtual wave is the solution of a wave equation and can be used to reconstruct the initial temperature distribution immediately after the excitation pulse. This virtual wave reconstruction method was used for the reconstruction of inclined steel rods in an epoxy sample, which were heated by a short pulse. The reconstructed experimental images show clearly the degradation of the spatial resolution with increasing depth, which is theoretically described by a depth-dependent thermographic point-spread-function. Full article
(This article belongs to the Special Issue Biomedical Photoacoustic and Photothermal Sensing and Imaging)
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Open AccessArticle A Three-Dimensional Collagen-Elastin Scaffold for Heart Valve Tissue Engineering
Bioengineering 2018, 5(3), 69; https://doi.org/10.3390/bioengineering5030069
Received: 17 July 2018 / Revised: 10 August 2018 / Accepted: 24 August 2018 / Published: 28 August 2018
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Abstract
Since most of the body’s extracellular matrix (ECM) is composed of collagen and elastin, we believe the choice of these materials is key for the future and promise of tissue engineering. Once it is known how elastin content of ECM guides cellular behavior
[...] Read more.
Since most of the body’s extracellular matrix (ECM) is composed of collagen and elastin, we believe the choice of these materials is key for the future and promise of tissue engineering. Once it is known how elastin content of ECM guides cellular behavior (in 2D or 3D), one will be able to harness the power of collagen-elastin microenvironments to design and engineer stimuli-responsive tissues. Moreover, the implementation of such matrices to promote endothelial-mesenchymal transition of primary endothelial cells constitutes a powerful tool to engineer 3D tissues. Here, we design a 3D collagen-elastin scaffold to mimic the native ECM of heart valves, by providing the strength of collagen layers, as well as elasticity. Valve interstitial cells (VICs) were encapsulated in the collagen-elastin hydrogels and valve endothelial cells (VECs) cultured onto the surface to create an in vitro 3D VEC-VIC co-culture. Over a seven-day period, VICs had stable expression levels of integrin β1 and F-actin and continuously proliferated, while cell morphology changed to more elongated. VECs maintained endothelial phenotype up to day five, as indicated by low expression of F-actin and integrin β1, while transformed VECs accounted for less than 7% of the total VECs in culture. On day seven, over 20% VECs were transformed to mesenchymal phenotype, indicated by increased actin filaments and higher expression of integrin β1. These findings demonstrate that our 3D collagen-elastin scaffolds provided a novel tool to study cell-cell or cell-matrix interactions in vitro, promoting advances in the current knowledge of valvular endothelial cell mesenchymal transition. Full article
(This article belongs to the Special Issue Applying Polymeric Biomaterials in 3D Tissue Constructs)
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Open AccessArticle Core-Shell Nanofibrous Scaffold Based on Polycaprolactone-Silk Fibroin Emulsion Electrospinning for Tissue Engineering Applications
Bioengineering 2018, 5(3), 68; https://doi.org/10.3390/bioengineering5030068
Received: 29 June 2018 / Revised: 9 August 2018 / Accepted: 16 August 2018 / Published: 21 August 2018
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Abstract
The vast domain of regenerative medicine comprises complex interactions between specific cells’ extracellular matrix (ECM) towards intracellular matrix formation, its secretion, and modulation of tissue as a whole. In this domain, engineering scaffold utilizing biomaterials along with cells towards formation of living tissues
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The vast domain of regenerative medicine comprises complex interactions between specific cells’ extracellular matrix (ECM) towards intracellular matrix formation, its secretion, and modulation of tissue as a whole. In this domain, engineering scaffold utilizing biomaterials along with cells towards formation of living tissues is of immense importance especially for bridging the existing gap of late; nanostructures are offering promising capability of mechano-biological response needed for tissue regeneration. Materials are selected for scaffold fabrication by considering both the mechanical integrity and bioactivity cues they offer. Herein, polycaprolactone (PCL) (biodegradable polyester) and ‘nature’s wonder’ biopolymer silk fibroin (SF) are explored in judicious combinations of emulsion electrospinning rather than conventional electrospinning of polymer blends. The water in oil (W/O) emulsions’ stability is found to be dependent upon the concentration of SF (aqueous phase) dispersed in the PCL solution (organic continuous phase). The spinnability of the emulsions is more dependent upon the viscosity of the solution, dominated by the molecular weight of PCL and its concentration than the conductivity. The nanofibers exhibited distinct core-shell structure with better cytocompatibility and cellular growth with the incorporation of the silk fibroin biopolymer. Full article
(This article belongs to the Special Issue Advanced Tissue Engineering Scaffolds)
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Open AccessArticle Label-Free Imaging of Melanoma with Confocal Photothermal Microscopy: Differentiation between Malignant and Benign Tissue
Bioengineering 2018, 5(3), 67; https://doi.org/10.3390/bioengineering5030067
Received: 16 June 2018 / Revised: 10 August 2018 / Accepted: 12 August 2018 / Published: 15 August 2018
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Abstract
Label-free confocal photothermal (CPT) microscopy was utilized for the first time to investigate malignancy in mouse skin cells. Laser diodes (LDs) with 405 nm or 488 nm wavelengths were used as pumps, and a 638 nm LD was used as a probe for
[...] Read more.
Label-free confocal photothermal (CPT) microscopy was utilized for the first time to investigate malignancy in mouse skin cells. Laser diodes (LDs) with 405 nm or 488 nm wavelengths were used as pumps, and a 638 nm LD was used as a probe for the CPT microscope. A Grey Level Cooccurrence Matrix (GLCM) for texture analysis was applied to the CPT images. Nine GLCM parameters were calculated with definite definitions for the intracellular super-resolved CPT images, and the parameters Entropy, Contrast, and Variance were found to be most suited among the nine parameters to discriminate clearly between healthy cells and malignant cells when a 405 nm pump was used. Prominence, Variance, and Shade were most suited when a pump wavelength of 488 nm was used. Full article
(This article belongs to the Special Issue Biomedical Photoacoustic and Photothermal Sensing and Imaging)
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Open AccessArticle A Precisely Flow-Controlled Microfluidic System for Enhanced Pre-Osteoblastic Cell Response for Bone Tissue Engineering
Bioengineering 2018, 5(3), 66; https://doi.org/10.3390/bioengineering5030066
Received: 3 July 2018 / Revised: 3 August 2018 / Accepted: 9 August 2018 / Published: 12 August 2018
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Abstract
Bone tissue engineering provides advanced solutions to overcome the limitations of currently used therapies for bone reconstruction. Dynamic culturing of cell-biomaterial constructs positively affects the cell proliferation and differentiation. In this study, we present a precisely flow-controlled microfluidic system employed for the investigation
[...] Read more.
Bone tissue engineering provides advanced solutions to overcome the limitations of currently used therapies for bone reconstruction. Dynamic culturing of cell-biomaterial constructs positively affects the cell proliferation and differentiation. In this study, we present a precisely flow-controlled microfluidic system employed for the investigation of bone-forming cell responses cultured on fibrous collagen matrices by applying two flow rates, 30 and 50 μL/min. We characterized the collagen substrates morphologically by means of scanning electron microscopy, investigated their viscoelastic properties, and evaluated the orientation, proliferation and osteogenic differentiation capacity of pre-osteoblastic cells cultured on them. The cells are oriented along the direction of the flow at both rates, in contrast to a random orientation observed under static culture conditions. The proliferation of cells after 7 days in culture was increased at both flow rates, with the flow rate of 50 μL/min indicating a significant increase compared to the static culture. The alkaline phosphatase activity after 7 days increased at both flow rates, with the rate of 30 μL/min indicating a significant enhancement compared to static conditions. Our results demonstrate that precisely flow-controlled microfluidic cell culture provides tunable control of the cell microenvironment that directs cellular activities involved in bone regeneration. Full article
(This article belongs to the Special Issue Advanced Tissue Engineering Scaffolds)
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Open AccessEditorial Advanced Dynamic Cell and Tissue Culture
Bioengineering 2018, 5(3), 65; https://doi.org/10.3390/bioengineering5030065
Received: 3 August 2018 / Accepted: 9 August 2018 / Published: 11 August 2018
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(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
Open AccessEditorial Advances in Micro-Bioreactor Design for Organ Cell Studies
Bioengineering 2018, 5(3), 64; https://doi.org/10.3390/bioengineering5030064
Received: 6 August 2018 / Accepted: 9 August 2018 / Published: 10 August 2018
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(This article belongs to the Special Issue Advances in Micro-Bioreactor Design for Organ Cell Studies)
Open AccessArticle Impedance Pumping and Resonance in a Multi-Vessel System
Bioengineering 2018, 5(3), 63; https://doi.org/10.3390/bioengineering5030063
Received: 10 June 2018 / Revised: 3 August 2018 / Accepted: 7 August 2018 / Published: 9 August 2018
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Abstract
Impedance pumping is a mechanism that generates flow in a compliant vessel by repeatedly actuating the vessel asymmetrically, without employing any internal valves, blades, or other mechanisms. The net flow is obtained by establishing a constructive wave pattern. Elaborate studies of impedance pumping
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Impedance pumping is a mechanism that generates flow in a compliant vessel by repeatedly actuating the vessel asymmetrically, without employing any internal valves, blades, or other mechanisms. The net flow is obtained by establishing a constructive wave pattern. Elaborate studies of impedance pumping in a single vessel have shown that the flow rate strongly depends on the actuation frequency, as well as on other parameters, such as actuator location and amplitude, and that it operates best in the resonance mode. The present study extends these principles to a network of multiple compliant vessels, representing a cardiovascular system. The flow is modeled numerically by the one-dimensional approximation of the Navier-Stokes equations. Two configurations were examined, systems consisting of three and five compliant vessels. First, the natural frequencies of these configurations were identified. Then, the dependence of the net flow rate (NFR) on the actuating frequency was explored, showing that impedance pumping operates best in the resonance mode in the case of a network of vessels as well. The impact of other parameters were studied as well, such as the location of one or two actuators, actuation amplitude, actuator width, the duty cycle, and the phase lag between the actuators. The results show that impedance pumps can generate significant NFR and the obtained NFR can be manipulated by properly setting up one or more of the governing parameters. These findings indicate that impedance pumping principles may be applied to flow control of the cardiovascular system. Full article
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Open AccessArticle Evaluation of a Computer-Aided Diagnosis System in the Classification of Lesions in Breast Strain Elastography Imaging
Bioengineering 2018, 5(3), 62; https://doi.org/10.3390/bioengineering5030062
Received: 12 June 2018 / Revised: 27 July 2018 / Accepted: 6 August 2018 / Published: 9 August 2018
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Abstract
Purpose: Evaluation of the performance of a computer-aided diagnosis (CAD) system based on the quantified color distribution in strain elastography imaging to evaluate the malignancy of breast tumors. Methods: The database consisted of 31 malignant and 52 benign lesions. A radiologist who was
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Purpose: Evaluation of the performance of a computer-aided diagnosis (CAD) system based on the quantified color distribution in strain elastography imaging to evaluate the malignancy of breast tumors. Methods: The database consisted of 31 malignant and 52 benign lesions. A radiologist who was blinded to the diagnosis performed the visual analysis of the lesions. After six months with no eye contact on the breast images, the same radiologist and other two radiologists manually drew the contour of the lesions in B-mode ultrasound, which was masked in the elastography image. In order to measure the amount of hard tissue in a lesion, we developed a CAD system able to identify the amount of hard tissue, represented by red color, and quantify its predominance in a lesion, allowing classification as soft, intermediate, or hard. The data obtained with the CAD system were compared with the visual analysis. We calculated the sensitivity, specificity, and area under the curve (AUC) for the classification using the CAD system from the manual delineation of the contour by each radiologist. Results: The performance of the CAD system for the most experienced radiologist achieved sensitivity of 70.97%, specificity of 88.46%, and AUC of 0.853. The system presented better performance compared with his visual diagnosis, whose sensitivity, specificity, and AUC were 61.29%, 88.46%, and 0.829, respectively. The system obtained sensitivity, specificity, and AUC of 67.70%, 84.60%, and 0.783, respectively, for images segmented by Radiologist 2, and 51.60%, 92.30%, and 0.771, respectively, for those segmented by the Resident. The intra-class correlation coefficient was 0.748. The inter-observer agreement of the CAD system with the different contours was good in all comparisons. Conclusions: The proposed CAD system can improve the radiologist performance for classifying breast masses, with excellent inter-observer agreement. It could be a promising tool for clinical use. Full article
(This article belongs to the Special Issue Biosignal Processing)
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Open AccessArticle Host Response and Neo-Tissue Development during Resorption of a Fast Degrading Supramolecular Electrospun Arterial Scaffold
Bioengineering 2018, 5(3), 61; https://doi.org/10.3390/bioengineering5030061
Received: 29 May 2018 / Revised: 23 July 2018 / Accepted: 3 August 2018 / Published: 6 August 2018
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Abstract
In situ vascular tissue engineering aims to regenerate vessels “at the target site” using synthetic scaffolds that are capable of inducing endogenous regeneration. Critical to the success of this approach is a fine balance between functional neo-tissue formation and scaffold degradation. Circulating immune
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In situ vascular tissue engineering aims to regenerate vessels “at the target site” using synthetic scaffolds that are capable of inducing endogenous regeneration. Critical to the success of this approach is a fine balance between functional neo-tissue formation and scaffold degradation. Circulating immune cells are important regulators of this process as they drive the host response to the scaffold and they play a central role in scaffold resorption. Despite the progress made with synthetic scaffolds, little is known about the host response and neo-tissue development during and after scaffold resorption. In this study, we designed a fast-degrading biodegradable supramolecular scaffold for arterial applications and evaluated this development in vivo. Bisurea-modified polycaprolactone (PCL2000-U4U) was electrospun in tubular scaffolds and shielded by non-degradable expanded polytetrafluoroethylene in order to restrict transmural and transanastomotic cell ingrowth. In addition, this shield prevented graft failure, permitting the study of neo-tissue and host response development after degradation. Scaffolds were implanted in 60 healthy male Lewis rats as an interposition graft into the abdominal aorta and explanted at different time points up to 56 days after implantation to monitor sequential cell infiltration, differentiation, and tissue formation in the scaffold. Endogenous tissue formation started with an acute immune response, followed by a dominant presence of pro-inflammatory macrophages during the first 28 days. Next, a shift towards tissue-producing cells was observed, with a striking increase in α-Smooth Muscle Actin-positive cells and extracellular matrix by day 56. At that time, the scaffold was resorbed and immune markers were low. These results suggest that neo-tissue formation was still in progress, while the host response became quiescent, favoring a regenerative tissue outcome. Future studies should confirm long-term tissue homeostasis, but require the strengthening of the supramolecular scaffold if a non-shielded model will be used. Full article
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Open AccessArticle Merging Heterocyclic Chemistry and Biocatalysis in One-Pot Processes through Compartmentalization of the Reaction Steps
Bioengineering 2018, 5(3), 60; https://doi.org/10.3390/bioengineering5030060
Received: 11 July 2018 / Revised: 27 July 2018 / Accepted: 30 July 2018 / Published: 1 August 2018
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Abstract
A proof of concept for a one-pot process merging a heterocycle formation by a classical chemical approach at basic conditions with a biocatalytic reduction, running at neutral pH conditions, is reported. A crucial component for this process is the compartmentalization of the single
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A proof of concept for a one-pot process merging a heterocycle formation by a classical chemical approach at basic conditions with a biocatalytic reduction, running at neutral pH conditions, is reported. A crucial component for this process is the compartmentalization of the single reactions by the use of polydimethylsiloxane thimbles. This process was applied successfully towards an asymmetric synthesis of (S)-2,2,3-trimethyl-1-thia-4-azaspiro[4.4]nonane, leading to excellent enantioselectivities of 99% enantiomeric excess (ee). Full article
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Open AccessArticle Three-Dimensional (3D) Printed Microneedles for Microencapsulated Cell Extrusion
Bioengineering 2018, 5(3), 59; https://doi.org/10.3390/bioengineering5030059
Received: 26 June 2018 / Revised: 22 July 2018 / Accepted: 26 July 2018 / Published: 31 July 2018
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Abstract
Cell-hydrogel based therapies offer great promise for wound healing. The specific aim of this study was to assess the viability of human hepatocellular carcinoma (HepG2) cells immobilized in atomized alginate capsules (3.5% (w/v) alginate, d = 225 µm ±
[...] Read more.
Cell-hydrogel based therapies offer great promise for wound healing. The specific aim of this study was to assess the viability of human hepatocellular carcinoma (HepG2) cells immobilized in atomized alginate capsules (3.5% (w/v) alginate, d = 225 µm ± 24.5 µm) post-extrusion through a three-dimensional (3D) printed methacrylate-based custom hollow microneedle assembly (circular array of 13 conical frusta) fabricated using stereolithography. With a jetting reliability of 80%, the solvent-sterilized device with a root mean square roughness of 158 nm at the extrusion nozzle tip (d = 325 μm) was operated at a flowrate of 12 mL/min. There was no significant difference between the viability of the sheared and control samples for extrusion times of 2 h (p = 0.14, α = 0.05) and 24 h (p = 0.5, α = 0.05) post-atomization. Factoring the increase in extrusion yield from 21.2% to 56.4% attributed to hydrogel bioerosion quantifiable by a loss in resilience from 5470 (J/m3) to 3250 (J/m3), there was no significant difference in percentage relative payload (p = 0.2628, α = 0.05) when extrusion occurred 24 h (12.2 ± 4.9%) when compared to 2 h (9.9 ± 2.8%) post-atomization. Results from this paper highlight the feasibility of encapsulated cell extrusion, specifically protection from shear, through a hollow microneedle assembly reported for the first time in literature. Full article
(This article belongs to the Special Issue Advances in Wound Healing Systems)
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Open AccessReview Assessment of Skeletal Tumor Load in Metastasized Castration-Resistant Prostate Cancer Patients: A Review of Available Methods and an Overview on Future Perspectives
Bioengineering 2018, 5(3), 58; https://doi.org/10.3390/bioengineering5030058
Received: 1 July 2018 / Revised: 23 July 2018 / Accepted: 26 July 2018 / Published: 28 July 2018
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Abstract
Metastasized castration-resistant prostate cancer (mCRPC), is the most advanced form of prostate neoplasia, where massive spread to the skeletal tissue is frequent. Patients with this condition are benefiting from an increasing number of treatment options. However, assessing tumor response in patients with multiple
[...] Read more.
Metastasized castration-resistant prostate cancer (mCRPC), is the most advanced form of prostate neoplasia, where massive spread to the skeletal tissue is frequent. Patients with this condition are benefiting from an increasing number of treatment options. However, assessing tumor response in patients with multiple localizations might be challenging. For this reason, many computational approaches have been developed in the last decades to quantify the skeletal tumor burden and treatment response. In this review, we analyzed the progressive development and diffusion of such approaches. A computerized literature search of the PubMed/Medline was conducted, including articles between January 2008 and March 2018. The search was expanded by manually reviewing the reference list of the chosen articles. Thirty-five studies were identified. The number of eligible studies greatly increased over time. Studies could be categorized in the following categories: automated analysis of 2D scans, SUV-based thresholding, hybrid CT- and SUV-based thresholding, and MRI-based thresholding. All methods are discussed in detail. Automated analysis of bone tumor burden in mCRPC is a growing field of research; when choosing the appropriate method of analysis, it is important to consider the possible advantages as well as the limitations thoroughly. Full article
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Open AccessReview Trinity of Three-Dimensional (3D) Scaffold, Vibration, and 3D Printing on Cell Culture Application: A Systematic Review and Indicating Future Direction
Bioengineering 2018, 5(3), 57; https://doi.org/10.3390/bioengineering5030057
Received: 31 May 2018 / Revised: 14 July 2018 / Accepted: 16 July 2018 / Published: 23 July 2018
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Abstract
Cell culture and cell scaffold engineering have previously developed in two directions. First can be ‘static into dynamic’, with proven effects that dynamic cultures have benefits over static ones. Researches in this direction have used several mechanical means, like external vibrators or shakers,
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Cell culture and cell scaffold engineering have previously developed in two directions. First can be ‘static into dynamic’, with proven effects that dynamic cultures have benefits over static ones. Researches in this direction have used several mechanical means, like external vibrators or shakers, to approximate the dynamic environments in real tissue, though such approaches could only partly address the issue. Second, can be ‘2D into 3D’, that is, artificially created three-dimensional (3D) passive (also called ‘static’) scaffolds have been utilized for 3D cell culture, helping external culturing conditions mimic real tissue 3D environments in a better way as compared with traditional two-dimensional (2D) culturing. In terms of the fabrication of 3D scaffolds, 3D printing (3DP) has witnessed its high popularity in recent years with ascending applicability, and this tendency might continue to grow along with the rapid development in scaffold engineering. In this review, we first introduce cell culturing, then focus 3D cell culture scaffold, vibration stimulation for dynamic culture, and 3DP technologies fabricating 3D scaffold. Potential interconnection of these realms will be analyzed, as well as the limitations of current 3D scaffold and vibration mechanisms. In the recommendation part, further discussion on future scaffold engineering regarding 3D vibratory scaffold will be addressed, indicating 3DP as a positive bridging technology for future scaffold with integrated and localized vibratory functions. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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Open AccessReview Conceptual Design of Micro-Bioreactors and Organ-on-Chips for Studies of Cell Cultures
Bioengineering 2018, 5(3), 56; https://doi.org/10.3390/bioengineering5030056
Received: 9 June 2018 / Revised: 13 July 2018 / Accepted: 14 July 2018 / Published: 19 July 2018
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Abstract
Engineering design of microbioreactors (MBRs) and organ-on-chip (OoC) devices can take advantage of established design science theory, in which systematic evaluation of functional concepts and user requirements are analyzed. This is commonly referred to as a conceptual design. This review article compares how
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Engineering design of microbioreactors (MBRs) and organ-on-chip (OoC) devices can take advantage of established design science theory, in which systematic evaluation of functional concepts and user requirements are analyzed. This is commonly referred to as a conceptual design. This review article compares how common conceptual design principles are applicable to MBR and OoC devices. The complexity of this design, which is exemplified by MBRs for scaled-down cell cultures in bioprocess development and drug testing in OoCs for heart and eye, is discussed and compared with previous design solutions of MBRs and OoCs, from the perspective of how similarities in understanding design from functionality and user purpose perspectives can more efficiently be exploited. The review can serve as a guideline and help the future design of MBR and OoC devices for cell culture studies. Full article
(This article belongs to the Special Issue Advances in Micro-Bioreactor Design for Organ Cell Studies)
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Open AccessArticle Gelatin-Methacryloyl (GelMA) Hydrogels with Defined Degree of Functionalization as a Versatile Toolkit for 3D Cell Culture and Extrusion Bioprinting
Bioengineering 2018, 5(3), 55; https://doi.org/10.3390/bioengineering5030055
Received: 30 May 2018 / Revised: 9 July 2018 / Accepted: 11 July 2018 / Published: 18 July 2018
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Abstract
Gelatin-methacryloyl (GelMA) is a semi-synthetic hydrogel which consists of gelatin derivatized with methacrylamide and methacrylate groups. These hydrogels provide cells with an optimal biological environment (e.g., RGD motifs for adhesion) and can be quickly photo-crosslinked, which provides shape fidelity and stability at physiological
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Gelatin-methacryloyl (GelMA) is a semi-synthetic hydrogel which consists of gelatin derivatized with methacrylamide and methacrylate groups. These hydrogels provide cells with an optimal biological environment (e.g., RGD motifs for adhesion) and can be quickly photo-crosslinked, which provides shape fidelity and stability at physiological temperature. In the present work, we demonstrated how GelMA hydrogels can be synthesized with a specific degree of functionalization (DoF) and adjusted to the intended application as a three-dimensional (3D) cell culture platform. The focus of this work lays on producing hydrogel scaffolds which provide a cell promoting microenvironment for human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) and are conductive to their adhesion, spreading, and proliferation. The control of mechanical GelMA properties by variation of concentration, DoF, and ultraviolet (UV) polymerization conditions is described. Moreover, hAD-MSC cell viability and morphology in GelMA of different stiffness was evaluated and compared. Polymerized hydrogels with and without cells could be digested in order to release encapsulated cells without loss of viability. We also demonstrated how hydrogel viscosity can be increased by the use of biocompatible additives, in order to enable the extrusion bioprinting of these materials. Taken together, we demonstrated how GelMA hydrogels can be used as a versatile tool for 3D cell cultivation. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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Open AccessArticle Fabrication and In Vitro Characterization of Bioactive Glass/Nano Hydroxyapatite Reinforced Electrospun Poly(ε-Caprolactone) Composite Membranes for Guided Tissue Regeneration
Bioengineering 2018, 5(3), 54; https://doi.org/10.3390/bioengineering5030054
Received: 4 June 2018 / Revised: 5 July 2018 / Accepted: 8 July 2018 / Published: 15 July 2018
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Abstract
Background: Current resorbable and non-resorbable membranes act as a physical barrier to avoid connective and epithelial tissue downgrowth into the defect, favoring the regeneration of periodontal tissues. These conventional membranes possess many structural and bio-functional limitations. We hypothesized that the next-generation of guided
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Background: Current resorbable and non-resorbable membranes act as a physical barrier to avoid connective and epithelial tissue downgrowth into the defect, favoring the regeneration of periodontal tissues. These conventional membranes possess many structural and bio-functional limitations. We hypothesized that the next-generation of guided tissue regeneration (GTR) membranes for periodontal tissue engineering will be a biologically active, spatially designed nanofibrous biomaterial that closely mimics the native extra-cellular matrix (ECM). Methods: GTR membranes made of poly(ε-Caprolactone) with a molecular weight of 80,000 reinforced with different weight concentrations of nano-Hydroxyapatite/Bioactive glass (2%, 5%, 10%, 15%) is fabricated by the method of electrospinning. After fabrication, in vitro properties are evaluated. Results: The electrospun nanofibrous membranes possessed excellent mechanical properties initially and after one month of degradation in phosphate buffer solution (PBS). Moreover, none of the fabricated membranes were found to be cytotoxic at lower concentrations and higher concentrations. Comparing the overall properties, PCL (poly(e-caprolactone)) + BG (Bioactive glass) 2% exhibited superior cell attachment and percentage of viable cells, increased fiber and pore diameter which satisfies the ideal properties needed for GTR membranes. Conclusion: Composite nanofibrous membranes prepared by electrospinning are suitable for use as a GTR membrane and are a useful prototype for further development of a final membrane for clinical use. Full article
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Open AccessArticle Radio-Fluorogenic Gel Dosimetry with Coumarin
Bioengineering 2018, 5(3), 53; https://doi.org/10.3390/bioengineering5030053
Received: 8 May 2018 / Revised: 19 June 2018 / Accepted: 5 July 2018 / Published: 10 July 2018
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Abstract
Gel dosimeters are attractive detectors for radiation therapy, with properties similar to biological tissue and the potential to visualize volumetric dose distributions. Radio-fluorogenesis is the yield of fluorescent chemical products in response to energy deposition from ionizing radiation. This report shares the development
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Gel dosimeters are attractive detectors for radiation therapy, with properties similar to biological tissue and the potential to visualize volumetric dose distributions. Radio-fluorogenesis is the yield of fluorescent chemical products in response to energy deposition from ionizing radiation. This report shares the development of a novel radio-fluorogenic gel (RFG) dosimeter, gelatin infused with coumarin-3-carboxlyic acid (C3CA), for the quantification of imparted energy. Aqueous solutions exposed to ionizing radiation result in the production of hydroxyl free radicals through water radiolysis. Interactions between hydroxyl free radicals and coumarin-3-carboxylic acid produce a fluorescent product. 7-hydroxy-coumarin-3-carboxylic acid has a blue (445 nm) emission following ultra-violet (UV) to near UV (365–405 nm) excitation. Effects of C3CA concentration and pH buffers were investigated. The response of the RFG was explored with respect to strength, type, and exposure rate of high-energy radiation. Results show a linear dose response relationship independent of energy and type, with a dose-rate dependency. This report demonstrates increased photo-yield with high pH and the utility of gelatin-RFG for phantom studies of radiation dosimetry. Full article
(This article belongs to the Special Issue Bioengineering Nano and Micro-Gels for Biomedical Applications)
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Open AccessArticle Generation of Gellan Gum-Based Adipose-Like Microtissues
Bioengineering 2018, 5(3), 52; https://doi.org/10.3390/bioengineering5030052
Received: 30 April 2018 / Revised: 12 June 2018 / Accepted: 21 June 2018 / Published: 27 June 2018
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Abstract
Adipose tissue is involved in many physiological processes. Therefore, the need for adipose tissue-like analogues either for soft tissue reconstruction or as in vitro testing platforms is undeniable. In this work, we explored the natural features of gellan gum (GG) to recreate injectable
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Adipose tissue is involved in many physiological processes. Therefore, the need for adipose tissue-like analogues either for soft tissue reconstruction or as in vitro testing platforms is undeniable. In this work, we explored the natural features of gellan gum (GG) to recreate injectable stable adipose-like microtissues. GG hydrogel particles with different percentages of polymer (0.5%, 0.75%, 1.25%) were developed and the effect of obtained mechanical properties over the ability of hASCs to differentiate towards the adipogenic lineage was evaluated based on the expression of the early (PPARγ) and late (FABP4) adipogenic markers, and on lipids formation and accumulation. Constructs were cultured in adipogenic induction medium up to 21 days or for six days in induction plus nine days in maintenance media. Overall, no significant differences were observed in terms of hASCs adipogenic differentiation within the range of Young’s moduli between 2.7 and 12.9 kPa. The long-term (up to six weeks) stability of the developed constructs supported its application in soft tissue reconstruction. Moreover, their ability to function as adipose-like microtissue models for drug screening was demonstrated by confirming its sensitivity to TNFα and ROCK inhibitor, respectively involved in the repression and induction of the adipogenic differentiation. Full article
(This article belongs to the Special Issue Bioengineering Nano and Micro-Gels for Biomedical Applications)
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Open AccessReview Smart Wound Dressings for Diabetic Chronic Wounds
Bioengineering 2018, 5(3), 51; https://doi.org/10.3390/bioengineering5030051
Received: 26 May 2018 / Revised: 13 June 2018 / Accepted: 19 June 2018 / Published: 26 June 2018
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Abstract
Given their severity and non-healing nature, diabetic chronic wounds are a significant concern to the 30.3 million Americans diagnosed with diabetes mellitus (2015). Peripheral arterial diseases, neuropathy, and infection contribute to the development of these wounds, which lead to an increased incidence of
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Given their severity and non-healing nature, diabetic chronic wounds are a significant concern to the 30.3 million Americans diagnosed with diabetes mellitus (2015). Peripheral arterial diseases, neuropathy, and infection contribute to the development of these wounds, which lead to an increased incidence of lower extremity amputations. Early recognition, debridement, offloading, and controlling infection are imperative for timely treatment. However, wound characterization and treatment are highly subjective and based largely on the experience of the treating clinician. Many wound dressings have been designed to address particular clinical presentations, but a prescriptive method is lacking for identifying the particular state of chronic, non-healing wounds. The authors suggest that recent developments in wound dressings and biosensing may allow for the quantitative, real-time representation of the wound environment, including exudate levels, pathogen concentrations, and tissue regeneration. Development of such sensing capability could enable more strategic, personalized care at the onset of ulceration and limit the infection leading to amputation. This review presents an overview of the pathophysiology of diabetic chronic wounds, a brief summary of biomaterial wound dressing treatment options, and biosensor development for biomarker sensing in the wound environment. Full article
(This article belongs to the Special Issue Advances in Wound Healing Systems)
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Open AccessReview Comminution of Dry Lignocellulosic Biomass: Part II. Technologies, Improvement of Milling Performances, and Security Issues
Bioengineering 2018, 5(3), 50; https://doi.org/10.3390/bioengineering5030050
Received: 11 April 2018 / Revised: 11 June 2018 / Accepted: 20 June 2018 / Published: 22 June 2018
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Abstract
Lignocellulosic feedstocks present a growing interest in many industrial processes as they are an ecological alternative to petroleum-based products. Generally, the size of plant raw materials needs to be reduced by milling step(s), to increase density, facilitate transport and storage, and to increase
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Lignocellulosic feedstocks present a growing interest in many industrial processes as they are an ecological alternative to petroleum-based products. Generally, the size of plant raw materials needs to be reduced by milling step(s), to increase density, facilitate transport and storage, and to increase reactivity. However, this unit operation can prove to be important in term of investments, functioning costs, and energy consumption if the process is not fully adapted to the histological structure of the plant material, possibly challenging the profitability of the whole chain of the biomass conversion. In this paper, the different technologies that can be used for the milling of lignocellulosic biomass were reviewed and different avenues are suggested to improve the milling performances thanks to thermal pretreatments. Based on examples on wheat straw milling, the main points to take into consideration in the choice of a milling technologies have been highlighted in regards to the specifications of ground powder. A specific focus on the hazards associated to the milling and the manipulation of fine biomass particles is also realized at the end of the paper from the perspective of industrial applications. Full article
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Open AccessReview Towards Multi-Organoid Systems for Drug Screening Applications
Bioengineering 2018, 5(3), 49; https://doi.org/10.3390/bioengineering5030049
Received: 14 May 2018 / Revised: 15 June 2018 / Accepted: 19 June 2018 / Published: 21 June 2018
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Abstract
A low percentage of novel drug candidates succeed and reach the end of the drug discovery pipeline, mainly due to poor initial screening and assessment of the effects of the drug and its metabolites over various tissues in the human body. For that,
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A low percentage of novel drug candidates succeed and reach the end of the drug discovery pipeline, mainly due to poor initial screening and assessment of the effects of the drug and its metabolites over various tissues in the human body. For that, emerging technologies involving the production of organoids from human pluripotent stem cells (hPSCs) and the use of organ-on-a-chip devices are showing great promise for developing a more reliable, rapid and cost-effective drug discovery process when compared with the current use of animal models. In particular, the possibility of virtually obtaining any type of cell within the human body, in combination with the ability to create patient-specific tissues using human induced pluripotent stem cells (hiPSCs), broadens the horizons in the fields of drug discovery and personalized medicine. In this review, we address the current progress and challenges related to the process of obtaining organoids from different cell lineages emerging from hPSCs, as well as how to create devices that will allow a precise examination of the in vitro effects generated by potential drugs in different organ systems. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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