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Bioengineering, Volume 5, Issue 4 (December 2018)

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Open AccessReview Geometric Effect for Biological Reactors and Biological Fluids
Bioengineering 2018, 5(4), 110; https://doi.org/10.3390/bioengineering5040110
Received: 20 November 2018 / Revised: 7 December 2018 / Accepted: 10 December 2018 / Published: 13 December 2018
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Abstract
As expressed “God made the bulk; the surface was invented by the devil” by W. Pauli, the surface has remarkable properties because broken symmetry in surface alters the material properties. In biological systems, the smallest functional and structural unit, which has a functional
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As expressed “God made the bulk; the surface was invented by the devil” by W. Pauli, the surface has remarkable properties because broken symmetry in surface alters the material properties. In biological systems, the smallest functional and structural unit, which has a functional bulk space enclosed by a thin interface, is a cell. Cells contain inner cytosolic soup in which genetic information stored in DNA can be expressed through transcription (TX) and translation (TL). The exploration of cell-sized confinement has been recently investigated by using micron-scale droplets and microfluidic devices. In the first part of this review article, we describe recent developments of cell-free bioreactors where bacterial TX-TL machinery and DNA are encapsulated in these cell-sized compartments. Since synthetic biology and microfluidics meet toward the bottom-up assembly of cell-free bioreactors, the interplay between cellular geometry and TX-TL advances better control of biological structure and dynamics in vitro system. Furthermore, biological systems that show self-organization in confined space are not limited to a single cell, but are also involved in the collective behavior of motile cells, named active matter. In the second part, we describe recent studies where collectively ordered patterns of active matter, from bacterial suspensions to active cytoskeleton, are self-organized. Since geometry and topology are vital concepts to understand the ordered phase of active matter, a microfluidic device with designed compartments allows one to explore geometric principles behind self-organization across the molecular scale to cellular scale. Finally, we discuss the future perspectives of a microfluidic approach to explore the further understanding of biological systems from geometric and topological aspects. Full article
(This article belongs to the Special Issue Frontiers of Microfluidics in Biology)
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Open AccessEditorial Introduction to the Special Issue on Pediatric Neuro-Oncology
Bioengineering 2018, 5(4), 109; https://doi.org/10.3390/bioengineering5040109
Received: 25 November 2018 / Accepted: 6 December 2018 / Published: 11 December 2018
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Abstract
Pediatric Neuro-Oncology is a highly specialized field encompassing molecular biology, clinical acumen, evidence based medicine, cancer genetics and neuropsychological care for the diagnosis and treatment of children with central nervous system (CNS) tumors. [...] Full article
(This article belongs to the Special Issue Update in Pediatric Neuro-Oncology)
Open AccessArticle The Effect of Carbon Monoxide on the Exergy Behavior of the Lungs
Bioengineering 2018, 5(4), 108; https://doi.org/10.3390/bioengineering5040108
Received: 9 October 2018 / Revised: 16 November 2018 / Accepted: 30 November 2018 / Published: 7 December 2018
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Abstract
The present work evaluates the impact of carbon monoxide (CO) inhalation on the human lung’s exergy behavior by considering different levels of intoxication and amounts of hemoglobin. Its impact is significant because CO is one of the most common air pollutants in cities
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The present work evaluates the impact of carbon monoxide (CO) inhalation on the human lung’s exergy behavior by considering different levels of intoxication and amounts of hemoglobin. Its impact is significant because CO is one of the most common air pollutants in cities and an increase in destroyed exergy may be correlated with lifespan reduction or the malfunctioning of certain human organs. An evaluation of the severity of intoxication as a function of city altitude may intensify the hazard associated with carbon monoxide. A computational model of human lungs obtained from the literature was used to calculate the concentrations of oxygen (O2), carbon monoxide (CO), and carbon dioxide (CO2) in the respiratory system. With the purpose of better evaluating the different levels of CO intoxication and hemoglobin concentration (which is a function of acclimatization time and some pathologies, such as anemia), a model calculating exergy efficiency for the lungs was proposed. From this model, it was possible to conclude that a higher level of intoxication is associated with lower exergy efficiency values. When associated with carbon monoxide intoxication, higher hemoglobin levels also result in lower efficiency. Eventually, a comparison between previous studies and the current study was carried out, regarding the method employed to calculate the exergy destroyed in the lungs, considering not only gas transport, but also hemoglobin concentration and its reaction with the gases from a second law perspective. Full article
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Open AccessArticle Detection of Osteoporosis from Percussion Responses Using an Electronic Stethoscope and Machine Learning
Bioengineering 2018, 5(4), 107; https://doi.org/10.3390/bioengineering5040107
Received: 8 November 2018 / Revised: 26 November 2018 / Accepted: 3 December 2018 / Published: 5 December 2018
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Abstract
Osteoporosis is an asymptomatic bone condition that affects a large proportion of the elderly population around the world, resulting in increased bone fragility and increased risk of fracture. Previous studies had shown that the vibroacoustic response of bone can indicate the quality of
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Osteoporosis is an asymptomatic bone condition that affects a large proportion of the elderly population around the world, resulting in increased bone fragility and increased risk of fracture. Previous studies had shown that the vibroacoustic response of bone can indicate the quality of the bone condition. Therefore, the aim of the authors’ project is to develop a new method to exploit this phenomenon to improve detection of osteoporosis in individuals. In this paper a method is described that uses a reflex hammer to exert testing stimuli on a patient’s tibia and an electronic stethoscope to acquire the impulse responses. The signals are processed as mel frequency cepstrum coefficients and passed through an artificial neural network to determine the likelihood of osteoporosis from the tibia’s impulse responses. Following some discussions of the mechanism and procedure, this paper details the signal acquisition using the stethoscope and the subsequent signal processing and the statistical machine learning algorithm. Pilot testing with 12 patients achieved over 80% sensitivity with a false positive rate below 30% and accuracies in the region of 70%. An extended dataset of 110 patients achieved an error rate of 30% with some room for improvement in the algorithm. By using common clinical apparatus and strategic machine learning, this method might be suitable as a large population screening test for the early diagnosis of osteoporosis, thus avoiding secondary complications. Full article
(This article belongs to the Special Issue Biosignal Processing)
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Open AccessArticle Growth Behavior of Human Adipose Tissue-Derived Stromal/Stem Cells at Small Scale: Numerical and Experimental Investigations
Bioengineering 2018, 5(4), 106; https://doi.org/10.3390/bioengineering5040106
Received: 6 November 2018 / Revised: 23 November 2018 / Accepted: 30 November 2018 / Published: 4 December 2018
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Abstract
Human adipose tissue-derived stromal/stem cells (hASCs) are a valuable source of cells for clinical applications, especially in the field of regenerative medicine. Therefore, it comes as no surprise that the interest in hASCs has greatly increased over the last decade. However, in order
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Human adipose tissue-derived stromal/stem cells (hASCs) are a valuable source of cells for clinical applications, especially in the field of regenerative medicine. Therefore, it comes as no surprise that the interest in hASCs has greatly increased over the last decade. However, in order to use hASCs in clinically relevant numbers, in vitro expansion is required. Single-use stirred bioreactors in combination with microcarriers (MCs) have shown themselves to be suitable systems for this task. However, hASCs tend to be less robust, and thus, more shear sensitive than conventional production cell lines for therapeutic antibodies and vaccines (e.g., Chinese Hamster Ovary cells CHO, Baby Hamster Kidney cells BHK), for which these bioreactors were originally designed. Hence, the goal of this study was to investigate the influence of different shear stress levels on the growth of humane telomerase reversed transcriptase immortalized hASCs (hTERT-ASC) and aggregate formation in stirred single-use systems at the mL scale: the 125 mL (=SP100) and the 500 mL (=SP300) disposable Corning® spinner flask. Computational fluid dynamics (CFD) simulations based on an Euler–Euler and Euler–Lagrange approach were performed to predict the hydrodynamic stresses (0.06–0.87 Pa), the residence times (0.4–7.3 s), and the circulation times (1.6–16.6 s) of the MCs in different shear zones for different impeller speeds and the suspension criteria (Ns1u, Ns1). The numerical findings were linked to experimental data from cultivations studies to develop, for the first time, an unstructured, segregated mathematical growth model for hTERT-ASCs. While the 125 mL spinner flask with 100 mL working volume (SP100) provided up to 1.68 × 105 hTERT-ASC/cm2 (=0.63 × 106 living hTERT-ASCs/mL, EF 56) within eight days, the peak living cell density of the 500 mL spinner flask with 300 mL working volume (SP300) was 2.46 × 105 hTERT-ASC/cm2 (=0.88 × 106 hTERT-ASCs/mL, EF 81) and was achieved on day eight. Optimal cultivation conditions were found for Ns1u < N < Ns1, which corresponded to specific power inputs of 0.3–1.1 W/m3. The established growth model delivered reliable predictions for cell growth on the MCs with an accuracy of 76–96% for both investigated spinner flask types. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture, Volume 2)
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Open AccessArticle Predicting the Biodegradation of Magnesium Alloy Implants: Modeling, Parameter Identification, and Validation
Bioengineering 2018, 5(4), 105; https://doi.org/10.3390/bioengineering5040105
Received: 30 September 2018 / Revised: 19 November 2018 / Accepted: 20 November 2018 / Published: 29 November 2018
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Abstract
Magnesium (Mg) and its alloys can degrade gradually up to complete dissolution in the physiological environment. This property makes these biomaterials appealing for different biomedical applications, such as bone implants. In order to qualify Mg and its alloys for bone implant applications, there
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Magnesium (Mg) and its alloys can degrade gradually up to complete dissolution in the physiological environment. This property makes these biomaterials appealing for different biomedical applications, such as bone implants. In order to qualify Mg and its alloys for bone implant applications, there is a need to precisely model their degradation (corrosion) behavior in the physiological environment. Therefore, the primary objective develop a model that can be used to predict the corrosion behavior of Mg-based alloys in vitro, while capturing the effect of pitting corrosion. To this end, a customized FORTRAN user material subroutine (or VUMAT) that is compatible with the finite element (FE) solver Abaqus/Explicit (Dassault Systèmes, Waltham, MA, USA) was developed. Using the developed subroutine, a continuum damage mechanism (CDM) FE model was developed to phenomenologically estimate the corrosion rate of a biocompatible Mg–Zn–Ca alloy. In addition, the mass loss immersion test was conducted to measure mass loss over time by submerging Mg–Zn–Ca coupons in a glass reactor filled with simulated body fluid (SBF) solution at pH 7.4 and 37 °C. Then, response surface methodology (RSM) was applied to calibrate the corrosion FE model parameters (i.e., Gamma (γ), Psi (ψ), Beta (β), and kinetic parameter (Ku)). The optimum values for γ, ψ, β and Ku were found to be 2.74898, 2.60477, 5.1, and 0.1005, respectively. Finally, given the good fit between FE predictions and experimental data, it was concluded that the numerical framework precisely captures the effect of corrosion on the mass loss over time. Full article
(This article belongs to the Special Issue Engineering Bone-Implant Materials)
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Open AccessReview The Emerging Role of Amino Acid PET in Neuro-Oncology
Bioengineering 2018, 5(4), 104; https://doi.org/10.3390/bioengineering5040104
Received: 15 September 2018 / Revised: 19 November 2018 / Accepted: 21 November 2018 / Published: 28 November 2018
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Abstract
Imaging plays a critical role in the management of the highly complex and widely diverse central nervous system (CNS) malignancies in providing an accurate diagnosis, treatment planning, response assessment, prognosis, and surveillance. Contrast-enhanced magnetic resonance imaging (MRI) is the primary modality for CNS
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Imaging plays a critical role in the management of the highly complex and widely diverse central nervous system (CNS) malignancies in providing an accurate diagnosis, treatment planning, response assessment, prognosis, and surveillance. Contrast-enhanced magnetic resonance imaging (MRI) is the primary modality for CNS disease management due to its high contrast resolution, reasonable spatial resolution, and relatively low cost and risk. However, defining tumor response to radiation treatment and chemotherapy by contrast-enhanced MRI is often difficult due to various factors that can influence contrast agent distribution and perfusion, such as edema, necrosis, vascular alterations, and inflammation, leading to pseudoprogression and pseudoresponse assessments. Amino acid positron emission tomography (PET) is emerging as the method of resolving such equivocal lesion interpretations. Amino acid radiotracers can more specifically differentiate true tumor boundaries from equivocal lesions based on their specific and active uptake by the highly metabolic cellular component of CNS tumors. These therapy-induced metabolic changes detected by amino acid PET facilitate early treatment response assessments. Integrating amino acid PET in the management of CNS malignancies to complement MRI will significantly improve early therapy response assessment, treatment planning, and clinical trial design. Full article
(This article belongs to the Special Issue Update in Pediatric Neuro-Oncology)
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Open AccessArticle Tracking Lysosome Migration within Chinese Hamster Ovary (CHO) Cells Following Exposure to Nanosecond Pulsed Electric Fields
Bioengineering 2018, 5(4), 103; https://doi.org/10.3390/bioengineering5040103
Received: 21 September 2018 / Revised: 2 November 2018 / Accepted: 18 November 2018 / Published: 23 November 2018
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Abstract
Above a threshold electric field strength, 600 ns-duration pulsed electric field (nsPEF) exposure substantially porates and permeabilizes cellular plasma membranes in aqueous solution to many small ions. Repetitive exposures increase permeabilization to calcium ions (Ca2+) in a dosage-dependent manner. Such exposure
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Above a threshold electric field strength, 600 ns-duration pulsed electric field (nsPEF) exposure substantially porates and permeabilizes cellular plasma membranes in aqueous solution to many small ions. Repetitive exposures increase permeabilization to calcium ions (Ca2+) in a dosage-dependent manner. Such exposure conditions can create relatively long-lived pores that reseal after passive lateral diffusion of lipids should have closed the pores. One explanation for eventual pore resealing is active membrane repair, and an ubiquitous repair mechanism in mammalian cells is lysosome exocytosis. A previous study shows that intracellular lysosome movement halts upon a 16.2 kV/cm, 600-ns PEF exposure of a single train of 20 pulses at 5 Hz. In that study, lysosome stagnation qualitatively correlates with the presence of Ca2+ in the extracellular solution and with microtubule collapse. The present study tests the hypothesis that limitation of nsPEF-induced Ca2+ influx and colloid osmotic cell swelling permits unabated lysosome translocation in exposed cells. The results indicate that the efforts used herein to preclude Ca2+ influx and colloid osmotic swelling following nsPEF exposure did not prevent attenuation of lysosome translocation. Intracellular lysosome movement is inhibited by nsPEF exposure(s) in the presence of PEG 300-containing solution or by 20 pulses of nsPEF in the presence of extracellular calcium. The only cases with no significant decreases in lysosome movement are the sham and exposure to a single nsPEF in Ca2+-free solution. Full article
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Open AccessReview Laboratory Automation in Clinical Microbiology
Bioengineering 2018, 5(4), 102; https://doi.org/10.3390/bioengineering5040102
Received: 17 October 2018 / Revised: 16 November 2018 / Accepted: 19 November 2018 / Published: 22 November 2018
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Abstract
Laboratory automation is currently the main organizational challenge for microbiologists. Automating classic workflows is a strenuous process for the laboratory personnel and a huge and long-lasting financial investment. The investments are rewarded through increases in quality and shortened time to report. However, the
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Laboratory automation is currently the main organizational challenge for microbiologists. Automating classic workflows is a strenuous process for the laboratory personnel and a huge and long-lasting financial investment. The investments are rewarded through increases in quality and shortened time to report. However, the benefits for an individual laboratory can only be estimated after the implementation and depending on the classic workflows currently performed. The two main components of automation are hardware and workflow. This review focusses on the workflow aspects of automation and describes some of the main developments during recent years. Additionally, it tries to define some terms which are related to automation and specifies some developments which would further improve automated systems. Full article
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Open AccessArticle Accelerated Bioprocess Development of Endopolygalacturonase-Production with Saccharomyces cerevisiae Using Multivariate Prediction in a 48 Mini-Bioreactor Automated Platform
Bioengineering 2018, 5(4), 101; https://doi.org/10.3390/bioengineering5040101
Received: 16 October 2018 / Revised: 9 November 2018 / Accepted: 14 November 2018 / Published: 21 November 2018
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Abstract
Mini-bioreactor systems enabling automatized operation of numerous parallel cultivations are a promising alternative to accelerate and optimize bioprocess development allowing for sophisticated cultivation experiments in high throughput. These include fed-batch and continuous cultivations with multiple options of process control and sample analysis which
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Mini-bioreactor systems enabling automatized operation of numerous parallel cultivations are a promising alternative to accelerate and optimize bioprocess development allowing for sophisticated cultivation experiments in high throughput. These include fed-batch and continuous cultivations with multiple options of process control and sample analysis which deliver valuable screening tools for industrial production. However, the model-based methods needed to operate these robotic facilities efficiently considering the complexity of biological processes are missing. We present an automated experiment facility that integrates online data handling, visualization and treatment using multivariate analysis approaches to design and operate dynamical experimental campaigns in up to 48 mini-bioreactors (8–12 mL) in parallel. In this study, the characterization of Saccharomyces cerevisiae AH22 secreting recombinant endopolygalacturonase is performed, running and comparing 16 experimental conditions in triplicate. Data-driven multivariate methods were developed to allow for fast, automated decision making as well as online predictive data analysis regarding endopolygalacturonase production. Using dynamic process information, a cultivation with abnormal behavior could be detected by principal component analysis as well as two clusters of similarly behaving cultivations, later classified according to the feeding rate. By decision tree analysis, cultivation conditions leading to an optimal recombinant product formation could be identified automatically. The developed method is easily adaptable to different strains and cultivation strategies, and suitable for automatized process development reducing the experimental times and costs. Full article
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Open AccessArticle Decellularized Human Umbilical Artery Used as Nerve Conduit
Bioengineering 2018, 5(4), 100; https://doi.org/10.3390/bioengineering5040100
Received: 28 September 2018 / Revised: 8 November 2018 / Accepted: 16 November 2018 / Published: 21 November 2018
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Abstract
Treatment of injuries to peripheral nerves after a segmental defect is one of the most challenging surgical problems. Despite advancements in microsurgical techniques, complete recovery of nerve function after repair has not been achieved. The purpose of this study was to evaluate the
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Treatment of injuries to peripheral nerves after a segmental defect is one of the most challenging surgical problems. Despite advancements in microsurgical techniques, complete recovery of nerve function after repair has not been achieved. The purpose of this study was to evaluate the use of the decellularized human umbilical artery (hUA) as nerve guidance conduit. A segmental peripheral nerve injury was created in 24 Sprague–Dawley rats. The animals were organized into two experimental groups with different forms of repair: decellularized hUA (n = 12), and autologous nerve graft (n = 12). Sciatic faction index and gastrocnemius muscle values were calculated for functional recovery evaluation. Nerve morphometry was used to analyze nerve regeneration. Results showed that decellularized hUAs after implantation were rich in nerve fibers and characterized by improved Sciatic Functional index (SFI) values. Decellularized hUA may support elongation and bridging of the 10 mm nerve gap. Full article
(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)
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Open AccessArticle Thermoplastic PCL-b-PEG-b-PCL and HDI Polyurethanes for Extrusion-Based 3D-Printing of Tough Hydrogels
Bioengineering 2018, 5(4), 99; https://doi.org/10.3390/bioengineering5040099
Received: 18 September 2018 / Revised: 26 October 2018 / Accepted: 3 November 2018 / Published: 14 November 2018
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Abstract
Novel tough hydrogel materials are required for 3D-printing applications. Here, a series of thermoplastic polyurethanes (TPUs) based on poly(ɛ-caprolactone)-b-poly(ethylene glycol)-b-poly(ɛ-caprolactone) (PCL-b-PEG-b-PCL) triblock copolymers and hexamethylene diisocyanate (HDI) were developed with PEG contents varying between 30
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Novel tough hydrogel materials are required for 3D-printing applications. Here, a series of thermoplastic polyurethanes (TPUs) based on poly(ɛ-caprolactone)-b-poly(ethylene glycol)-b-poly(ɛ-caprolactone) (PCL-b-PEG-b-PCL) triblock copolymers and hexamethylene diisocyanate (HDI) were developed with PEG contents varying between 30 and 70 mol%. These showed excellent mechanical properties not only when dry, but also when hydrated: TPUs prepared from PCL-b-PEG-b-PCL with PEG of Mn 6 kg/mol (PCL7-PEG6-PCL7) took up 122 wt.% upon hydration and had an E-modulus of 52 ± 10 MPa, a tensile strength of 17 ± 2 MPa, and a strain at break of 1553 ± 155% in the hydrated state. They had a fracture energy of 17976 ± 3011 N/mm2 and a high tearing energy of 72 kJ/m2. TPUs prepared using PEG with Mn of 10 kg/mol (PCL5-PEG10-PCL5) took up 534% water and were more flexible. When wet, they had an E-modulus of 7 ± 2 MPa, a tensile strength of 4 ± 1 MPa, and a strain at break of 147 ± 41%. These hydrogels had a fracture energy of 513 ± 267 N/mm2 and a tearing energy of 16 kJ/m2. The latter TPU was first extruded into filaments and then processed into designed porous hydrogel structures by 3D-printing. These hydrogels can be used in 3D printing of tissue engineering scaffolds with high fracture toughness. Full article
(This article belongs to the Special Issue Applying Polymeric Biomaterials in 3D Tissue Constructs)
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Open AccessArticle Breast Cancer Estimate Modeling via PDE Thermal Analysis Algorithms
Bioengineering 2018, 5(4), 98; https://doi.org/10.3390/bioengineering5040098
Received: 11 August 2018 / Revised: 14 October 2018 / Accepted: 23 October 2018 / Published: 5 November 2018
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Abstract
The significance of this study lies in the importance of (1) nondestructive testing in defect studies and (2) securing the reliability of breast cancer prediction through thermal analysis in nondestructive testing. Most nondestructive tests have negative effects on the human body. Moreover, the
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The significance of this study lies in the importance of (1) nondestructive testing in defect studies and (2) securing the reliability of breast cancer prediction through thermal analysis in nondestructive testing. Most nondestructive tests have negative effects on the human body. Moreover, the precision and accuracy of such tests are poor. This study analyzes these drawbacks and increases the reliability of such methods. A theoretical model was constructed, by which simulated inner breast tissue was observed in a nondestructive way through thermal analysis, and the presence and extent of simulated breast cancer were estimated based on the thermal observations. Herein, we studied the medical diagnosis of breast cancer by creating a theoretical environment that simulated breast cancer in a real-world setting; the model used two-dimensional modeling and partial differential equation (PDE) thermal analysis. Our theoretical analysis, based on partial differential equations, allowed us to demonstrate that non-wounding defect detection is possible and, in many ways, preferable. The main contribution of this paper lies in studying long-term estimates. In addition, the model in this study can be extended to predict breast cancer through pure heat and can also be used for various other cancer and tumor analyses in the human body. Full article
(This article belongs to the Special Issue Biosignal Processing)
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Open AccessReview Radiotherapy Advances in Pediatric Neuro-Oncology
Bioengineering 2018, 5(4), 97; https://doi.org/10.3390/bioengineering5040097
Received: 6 October 2018 / Revised: 26 October 2018 / Accepted: 1 November 2018 / Published: 4 November 2018
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Abstract
Radiation therapy (RT) represents an integral component in the treatment of many pediatric brain tumors. Multiple advances have emerged within pediatric radiation oncology that aim to optimize the therapeutic ratio—improving disease control while limiting RT-related toxicity. These include innovations in treatment planning with
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Radiation therapy (RT) represents an integral component in the treatment of many pediatric brain tumors. Multiple advances have emerged within pediatric radiation oncology that aim to optimize the therapeutic ratio—improving disease control while limiting RT-related toxicity. These include innovations in treatment planning with magnetic resonance imaging (MRI) simulation, as well as increasingly sophisticated radiation delivery techniques. Advanced RT techniques, including photon-based RT such as intensity-modulated RT (IMRT) and volumetric-modulated arc therapy (VMAT), as well as particle beam therapy and stereotactic RT, have afforded an array of options to dramatically reduce radiation exposure of uninvolved normal tissues while treating target volumes. Along with advances in image guidance of radiation treatments, novel RT approaches are being implemented in ongoing and future prospective clinical trials. As the era of molecular risk stratification unfolds, personalization of radiation dose, target, and technique holds the promise to meaningfully improve outcomes for pediatric neuro-oncology patients. Full article
(This article belongs to the Special Issue Update in Pediatric Neuro-Oncology)
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Open AccessCommunication Polo-Like Kinase 4 (PLK4) Is Overexpressed in Central Nervous System Neuroblastoma (CNS-NB)
Bioengineering 2018, 5(4), 96; https://doi.org/10.3390/bioengineering5040096
Received: 28 August 2018 / Revised: 19 October 2018 / Accepted: 1 November 2018 / Published: 4 November 2018
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Abstract
Neuroblastoma (NB) is the most common extracranial solid tumor in pediatrics, with rare occurrences of primary and metastatic tumors in the central nervous system (CNS). We previously reported the overexpression of the polo-like kinase 4 (PLK4) in embryonal brain tumors. PLK4 has also
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Neuroblastoma (NB) is the most common extracranial solid tumor in pediatrics, with rare occurrences of primary and metastatic tumors in the central nervous system (CNS). We previously reported the overexpression of the polo-like kinase 4 (PLK4) in embryonal brain tumors. PLK4 has also been found to be overexpressed in a variety of peripheral adult tumors and recently in peripheral NB. Here, we investigated PLK4 expression in NBs of the CNS (CNS-NB) and validated our findings by performing a multi-platform transcriptomic meta-analysis using publicly available data. We evaluated the PLK4 expression by quantitative real-time PCR (qRT-PCR) on the CNS-NB samples and compared the relative expression levels among other embryonal and non-embryonal brain tumors. The relative PLK4 expression levels of the NB samples were found to be significantly higher than the non-embryonal brain tumors (p-value < 0.0001 in both our samples and in public databases). Here, we expand upon our previous work that detected PLK4 overexpression in pediatric embryonal tumors to include CNS-NB. As we previously reported, inhibiting PLK4 in embryonal tumors led to decreased tumor cell proliferation, survival, invasion and migration in vitro and tumor growth in vivo, and therefore PLK4 may be a potential new therapeutic approach to CNS-NB. Full article
(This article belongs to the Special Issue Update in Pediatric Neuro-Oncology)
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Open AccessArticle Evaluation of HLA-G Expression in Multipotent Mesenchymal Stromal Cells Derived from Vitrified Wharton’s Jelly Tissue
Bioengineering 2018, 5(4), 95; https://doi.org/10.3390/bioengineering5040095
Received: 18 October 2018 / Revised: 27 October 2018 / Accepted: 31 October 2018 / Published: 1 November 2018
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Abstract
Background: Mesenchymal Stromal Cells (MSCs) from Wharton’s Jelly (WJ) tissue express HLA-G, a molecule which exerts several immunological properties. This study aimed at the evaluation of HLA-G expression in MSCs derived from vitrified WJ tissue. Methods: WJ tissue samples were isolated from human
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Background: Mesenchymal Stromal Cells (MSCs) from Wharton’s Jelly (WJ) tissue express HLA-G, a molecule which exerts several immunological properties. This study aimed at the evaluation of HLA-G expression in MSCs derived from vitrified WJ tissue. Methods: WJ tissue samples were isolated from human umbilical cords, vitrified with the use of VS55 solution and stored for 1 year at −196 °C. After 1 year of storage, the WJ tissue was thawed and MSCs were isolated. Then, MSCs were expanded until reaching passage 8, followed by estimation of cell number, cell doubling time (CDT), population doubling (PD) and cell viability. In addition, multilineage differentiation, Colony-Forming Units (CFUs) assay and immunophenotypic analyses were performed. HLA-G expression in MSCs derived from vitrified samples was evaluated by immunohistochemistry, RT-PCR/PCR, mixed lymphocyte reaction (MLR) and immunofluorescence. MSCs derived from non-vitrified WJ tissue were used in order to validate the results obtained from the above methods. Results: MSCs were successfully obtained from vitrified WJ tissues retaining their morphological and multilineage differentiation properties. Furthermore, MSCs from vitrified WJ tissues successfully expressed HLA-G. Conclusion: The above results indicated the successful expression of HLA-G by MSCs from vitrified WJ tissues, thus making them ideal candidates for immunomodulation. Full article
(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)
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Open AccessArticle Viscous Fingering of Miscible Liquids in Porous and Swellable Media for Rapid Diagnostic Tests
Bioengineering 2018, 5(4), 94; https://doi.org/10.3390/bioengineering5040094
Received: 15 September 2018 / Revised: 22 October 2018 / Accepted: 23 October 2018 / Published: 29 October 2018
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Abstract
In lateral flow and colorimetric test strip diagnostics, the effects of capillary action and diffusion on speed and sensitivity have been well studied. However, another form of fluid motion can be generated due to stresses and instabilities generated in pores when two miscible
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In lateral flow and colorimetric test strip diagnostics, the effects of capillary action and diffusion on speed and sensitivity have been well studied. However, another form of fluid motion can be generated due to stresses and instabilities generated in pores when two miscible liquids with different densities and viscosities come into contact. This study explored how a swellable test pad can be deployed for measuring urea in saliva by partially prefilling the pad with a miscible solution of greater viscosity and density. The resultant Korteweg stresses and viscous fingering patterns were analyzed using solutions with added food color through video analysis and image processing. Image analysis was simplified using the saturation channel after converting RGB image sequences to HSB. The kinetics of liquid mixing agreed with capillary displacement results for miscible liquids undergoing movement from Korteweg stresses. After capillary filling, there was significant movement of liquid due to these fluidic effects, which led to mixing of the saliva sample with an enzyme test solution. Owing to the simplicity and speed of this test method, urea can be analyzed with an electronic nose over a useful range for detecting salivary urea concentration for rapid and early detection of dehydration. Full article
(This article belongs to the Special Issue Frontiers of Microfluidics in Biology)
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Open AccessReview A Review on Bioconversion of Agro-Industrial Wastes to Industrially Important Enzymes
Bioengineering 2018, 5(4), 93; https://doi.org/10.3390/bioengineering5040093
Received: 5 October 2018 / Revised: 24 October 2018 / Accepted: 26 October 2018 / Published: 28 October 2018
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Abstract
Agro-industrial waste is highly nutritious in nature and facilitates microbial growth. Most agricultural wastes are lignocellulosic in nature; a large fraction of it is composed of carbohydrates. Agricultural residues can thus be used for the production of various value-added products, such as industrially
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Agro-industrial waste is highly nutritious in nature and facilitates microbial growth. Most agricultural wastes are lignocellulosic in nature; a large fraction of it is composed of carbohydrates. Agricultural residues can thus be used for the production of various value-added products, such as industrially important enzymes. Agro-industrial wastes, such as sugar cane bagasse, corn cob and rice bran, have been widely investigated via different fermentation strategies for the production of enzymes. Solid-state fermentation holds much potential compared with submerged fermentation methods for the utilization of agro-based wastes for enzyme production. This is because the physical–chemical nature of many lignocellulosic substrates naturally lends itself to solid phase culture, and thereby represents a means to reap the acknowledged potential of this fermentation method. Recent studies have shown that pretreatment technologies can greatly enhance enzyme yields by several fold. This article gives an overview of how agricultural waste can be productively harnessed as a raw material for fermentation. Furthermore, a detailed analysis of studies conducted in the production of different commercially important enzymes using lignocellulosic food waste has been provided. Full article
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Open AccessArticle Analysis of the Intrinsic Self-Organising Properties of Mesenchymal Stromal Cells in Three-Dimensional Co-Culture Models with Endothelial Cells
Bioengineering 2018, 5(4), 92; https://doi.org/10.3390/bioengineering5040092
Received: 21 September 2018 / Revised: 23 October 2018 / Accepted: 24 October 2018 / Published: 26 October 2018
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Abstract
Mesenchymal stem/stromal cells (MSCs) are typically characterised by their ability to differentiate into skeletal (osteogenic, chondrogenic and adipogenic) lineages. MSCs also appear to have additional non-stem cell functions in coordinating tissue morphogenesis and organising vascular networks through interactions with endothelial cells (ECs). However,
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Mesenchymal stem/stromal cells (MSCs) are typically characterised by their ability to differentiate into skeletal (osteogenic, chondrogenic and adipogenic) lineages. MSCs also appear to have additional non-stem cell functions in coordinating tissue morphogenesis and organising vascular networks through interactions with endothelial cells (ECs). However, suitable experimental models to examine these apparently unique MSC properties are lacking. Following previous work, we have developed our 3D in vitro co-culture models to enable us to track cellular self-organisation events in heterotypic cell spheroids combining ECs, MSCs and their differentiated progeny. In these systems, MSCs, but not related fibroblastic cell types, promote the assembly of ECs into interconnected networks through intrinsic mechanisms, dependent on the relative abundance of MSC and EC numbers. Perturbation of endogenous platelet-derived growth factor (PDGF) signalling significantly increased EC network length, width and branching. When MSCs were pre-differentiated towards an osteogenic or chondrogenic lineage and co-cultured as mixed 3D spheroids, they segregated into polarised osseous and chondral regions. In the presence of ECs, the pre-differentiated MSCs redistributed to form a central mixed cell core with an outer osseous layer. Our findings demonstrate the intrinsic self-organising properties of MSCs, which may broaden their use in regenerative medicine and advance current approaches. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cells in Tissue Regeneration)
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Open AccessReview Augmentation of Dermal Wound Healing by Adipose Tissue-Derived Stromal Cells (ASC)
Bioengineering 2018, 5(4), 91; https://doi.org/10.3390/bioengineering5040091
Received: 20 September 2018 / Revised: 21 October 2018 / Accepted: 24 October 2018 / Published: 26 October 2018
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Abstract
The skin is the largest organ of the human body and is the first line of defense against physical and biological damage. Thus, the skin is equipped to self-repair and regenerates after trauma. Skin regeneration after damage comprises a tightly spatial-temporally regulated process
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The skin is the largest organ of the human body and is the first line of defense against physical and biological damage. Thus, the skin is equipped to self-repair and regenerates after trauma. Skin regeneration after damage comprises a tightly spatial-temporally regulated process of wound healing that involves virtually all cell types in the skin. Wound healing features five partially overlapping stages: homeostasis, inflammation, proliferation, re-epithelization, and finally resolution or fibrosis. Dysreguled wound healing may resolve in dermal scarring. Adipose tissue is long known for its suppressive influence on dermal scarring. Cultured adipose tissue-derived stromal cells (ASCs) secrete a plethora of regenerative growth factors and immune mediators that influence processes during wound healing e.g., angiogenesis, modulation of inflammation and extracellular matrix remodeling. In clinical practice, ASCs are usually administered as part of fractionated adipose tissue i.e., as part of enzymatically isolated SVF (cellular SVF), mechanically isolated SVF (tissue SVF), or as lipograft. Enzymatic isolation of SVF obtained adipose tissue results in suspension of adipocyte-free cells (cSVF) that lack intact intercellular adhesions or connections to extracellular matrix (ECM). Mechanical isolation of SVF from adipose tissue destructs the parenchyma (adipocytes), which results in a tissue SVF (tSVF) with intact connections between cells, as well as matrix. To date, due to a lack of well-designed prospective randomized clinical trials, neither cSVF, tSVF, whole adipose tissue, or cultured ASCs can be indicated as the preferred preparation procedure prior to therapeutic administration. In this review, we present and discuss current literature regarding the different administration options to apply ASCs (i.e., cultured ASCs, cSVF, tSVF, and lipografting) to augment dermal wound healing, as well as the available indications for clinical efficacy. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cells in Tissue Regeneration)
Open AccessArticle Stacked PZT Discs Generate Necessary Power for Bone Healing through Electrical Stimulation in a Composite Spinal Fusion Implant
Bioengineering 2018, 5(4), 90; https://doi.org/10.3390/bioengineering5040090
Received: 26 August 2018 / Revised: 8 October 2018 / Accepted: 13 October 2018 / Published: 23 October 2018
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Abstract
Electrical stimulation devices can be used as adjunct therapy to lumbar spinal fusion to promote bone healing, but their adoption has been hindered by the large battery packs necessary to provide power. Piezoelectric composite materials within a spinal interbody cage to produce power
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Electrical stimulation devices can be used as adjunct therapy to lumbar spinal fusion to promote bone healing, but their adoption has been hindered by the large battery packs necessary to provide power. Piezoelectric composite materials within a spinal interbody cage to produce power in response to physiological lumbar loads have recently been investigated. A piezoelectric macro-fiber composite spinal interbody generated sufficient power to stimulate bone growth in a pilot ovine study, despite fabrication challenges. The objective of the present study was to electromechanically evaluate three new piezoelectric disc composites, 15-disc insert, seven-disc insert, and seven-disc Compliant Layer Adaptive Composite Stack (CLACS) insert, within a spinal interbody, and validate their use for electrical stimulation and promoting bone growth. All implants were electromechanically assessed under cyclic loads of 1000 N at 2 Hz, representing physiological lumbar loading. All three configurations produced at least as much power as the piezoelectric macro-fiber composites, validating the use of piezoelectric discs for this application. Future work is needed to characterize the electromechanical performance of commercially manufactured piezoelectric stacks under physiological lumbar loads, and mechanically assess the composite implants according to FDA guidelines for lumbar interbody fusion devices. Full article
(This article belongs to the Special Issue Implantable Medical Devices)
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Open AccessReview The Goldilocks Approach: A Review of Employing Design of Experiments in Prokaryotic Recombinant Protein Production
Bioengineering 2018, 5(4), 89; https://doi.org/10.3390/bioengineering5040089
Received: 20 September 2018 / Revised: 9 October 2018 / Accepted: 12 October 2018 / Published: 19 October 2018
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Abstract
The production of high yields of soluble recombinant protein is one of the main objectives of protein biotechnology. Several factors, such as expression system, vector, host, media composition and induction conditions can influence recombinant protein yield. Identifying the most important factors for optimum
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The production of high yields of soluble recombinant protein is one of the main objectives of protein biotechnology. Several factors, such as expression system, vector, host, media composition and induction conditions can influence recombinant protein yield. Identifying the most important factors for optimum protein expression may involve significant investment of time and considerable cost. To address this problem, statistical models such as Design of Experiments (DoE) have been used to optimise recombinant protein production. This review examines the application of DoE in the production of recombinant proteins in prokaryotic expression systems with specific emphasis on media composition and culture conditions. The review examines the most commonly used DoE screening and optimisation designs. It provides examples of DoE applied to optimisation of media and culture conditions. Full article
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Open AccessReview Cutting Edge Therapeutic Insights Derived from Molecular Biology of Pediatric High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG)
Bioengineering 2018, 5(4), 88; https://doi.org/10.3390/bioengineering5040088
Received: 8 August 2018 / Revised: 12 October 2018 / Accepted: 15 October 2018 / Published: 18 October 2018
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Abstract
Pediatric high-grade glioma (pHGG) and brainstem gliomas are some of the most challenging cancers to treat in children, with no effective therapies and 5-year survival at ~2% for diffuse intrinsic pontine glioma (DIPG) patients. The standard of care for pHGG as a whole
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Pediatric high-grade glioma (pHGG) and brainstem gliomas are some of the most challenging cancers to treat in children, with no effective therapies and 5-year survival at ~2% for diffuse intrinsic pontine glioma (DIPG) patients. The standard of care for pHGG as a whole remains surgery and radiation combined with chemotherapy, while radiation alone is standard treatment for DIPG. Unfortunately, these therapies lack specificity for malignant glioma cells and have few to no reliable biomarkers of efficacy. Recent discoveries have revealed that epigenetic disruption by highly conserved mutations in DNA-packaging histone proteins in pHGG, especially DIPG, contribute to the aggressive nature of these cancers. In this review we pose unanswered questions and address unexplored mechanisms in pre-clinical models and clinical trial data from pHGG patients. Particular focus will be paid towards therapeutics targeting chromatin modifiers and other epigenetic vulnerabilities that can be exploited for pHGG therapy. Further delineation of rational therapeutic combinations has strong potential to drive development of safe and efficacious treatments for pHGG patients. Full article
(This article belongs to the Special Issue Update in Pediatric Neuro-Oncology)
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Open AccessArticle Microfabricated and 3-D Printed Soft Bioelectronic Constructs from PAn-PAAMPSA-Containing Hydrogels
Bioengineering 2018, 5(4), 87; https://doi.org/10.3390/bioengineering5040087
Received: 16 September 2018 / Revised: 12 October 2018 / Accepted: 13 October 2018 / Published: 17 October 2018
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Abstract
The formation of hybrid bioactive and inherently conductive constructs of composites formed from polyaniline-polyacrylamidomethylpropane sulfonic acid (PAn-PAAMPSA) nanomaterials (0.00–10.0 wt%) within poly(2-hydroxy ethyl methacrylate-co-N-{Tris(hydroxymethyl)methyl} acrylamide)-co-polyethyleneglycol methacrylate) p(HEMA-co-HMMA-co-PEGMA) hydrogels was made possible using microlithographic fabrication and
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The formation of hybrid bioactive and inherently conductive constructs of composites formed from polyaniline-polyacrylamidomethylpropane sulfonic acid (PAn-PAAMPSA) nanomaterials (0.00–10.0 wt%) within poly(2-hydroxy ethyl methacrylate-co-N-{Tris(hydroxymethyl)methyl} acrylamide)-co-polyethyleneglycol methacrylate) p(HEMA-co-HMMA-co-PEGMA) hydrogels was made possible using microlithographic fabrication and 3-D printing. Hybrid constructs formed by combining a non-conductive base (0.00 wt% PAn-PAAMPSA) and electroconductive (ECH) (varying wt% PAn-PAAMPSA) hydrogels using these two production techniques were directly compared. Hydrogels were electrically characterized using two-point probe resistivity and electrochemical impedance spectroscopy. Results show that incorporation of >0.10 wt% PAn-PAAMPSA within the base hydrogel matrices was enough to achieve percolation and high conductivity with a membrane resistance (RM) of 2140 Ω and 87.9 Ω for base (0.00 wt%) and ECH (10.0 wt%), respectively. UV-vis spectroscopy of electroconductive hydrogels indicated a bandgap of 2.8 eV that was measurable at concentrations of >0.10 wt% PAn-PAAMPSA. Both base and electroconductive hydrogels supported the attachment and growth of NIH/3T3 fibroblast cells. When the base hydrogel was rendered bioactive by the inclusion of collagen (>200 µg/mL), it also supported the attachment, but not the differentiation, of PC-12 neural progenitor cells. Full article
(This article belongs to the Special Issue Functional Biomaterials for Regenerative Engineering)
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Open AccessArticle A Standardized Collagen-Based Scaffold Improves Human Hepatocyte Shipment and Allows Metabolic Studies over 10 Days
Bioengineering 2018, 5(4), 86; https://doi.org/10.3390/bioengineering5040086
Received: 24 August 2018 / Revised: 12 October 2018 / Accepted: 14 October 2018 / Published: 16 October 2018
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Abstract
Due to pronounced species differences, hepatotoxicity of new drugs often cannot be detected in animal studies. Alternatively, human hepatocytes could be used, but there are some limitations. The cells are not always available on demand or in sufficient amounts, so far there has
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Due to pronounced species differences, hepatotoxicity of new drugs often cannot be detected in animal studies. Alternatively, human hepatocytes could be used, but there are some limitations. The cells are not always available on demand or in sufficient amounts, so far there has been only limited success to allow the transport of freshly isolated hepatocytes without massive loss of function or their cultivation for a long time. Since it is well accepted that the cultivation of hepatocytes in 3D is related to an improved function, we here tested the Optimaix-3D Scaffold from Matricel for the transport and cultivation of hepatocytes. After characterization of the scaffold, we shipped cells on the scaffold and/or cultivated them over 10 days. With the evaluation of hepatocyte functions such as urea production, albumin synthesis, and CYP activity, we showed that the metabolic activity of the cells on the scaffold remained nearly constant over the culture time whereas a significant decrease in metabolic activity occurred in 2D cultures. In addition, we demonstrated that significantly fewer cells were lost during transport. In summary, the collagen-based scaffold allows the transport and cultivation of hepatocytes without loss of function over 10 days. Full article
(This article belongs to the Special Issue Applying Polymeric Biomaterials in 3D Tissue Constructs)
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Open AccessReview Palliative Care for Children with Central Nervous System Malignancies
Bioengineering 2018, 5(4), 85; https://doi.org/10.3390/bioengineering5040085
Received: 15 August 2018 / Revised: 1 October 2018 / Accepted: 3 October 2018 / Published: 13 October 2018
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Abstract
Children with central nervous system (CNS) malignancies often suffer from high symptom burden and risk of death. Pediatric palliative care is a medical specialty, provided by an interdisciplinary team, which focuses on enhancing quality of life and minimizing suffering for children with life-threatening
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Children with central nervous system (CNS) malignancies often suffer from high symptom burden and risk of death. Pediatric palliative care is a medical specialty, provided by an interdisciplinary team, which focuses on enhancing quality of life and minimizing suffering for children with life-threatening or life-limiting disease, and their families. Primary palliative care skills, which include basic symptom management, facilitation of goals-of-care discussions, and transition to hospice, can and should be developed by all providers of neuro-oncology care. This chapter will review the fundamentals of providing primary pediatric palliative care. Full article
(This article belongs to the Special Issue Update in Pediatric Neuro-Oncology)
Open AccessArticle Medial Collateral Ligament Deficiency of the Elbow Joint: A Computational Approach
Bioengineering 2018, 5(4), 84; https://doi.org/10.3390/bioengineering5040084
Received: 4 August 2018 / Revised: 2 October 2018 / Accepted: 8 October 2018 / Published: 10 October 2018
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Abstract
Computational elbow joint models, capable of simulating medial collateral ligament deficiency, can be extremely valuable tools for surgical planning and refinement of therapeutic strategies. The objective of this study was to investigate the effects of varying levels of medial collateral ligament deficiency on
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Computational elbow joint models, capable of simulating medial collateral ligament deficiency, can be extremely valuable tools for surgical planning and refinement of therapeutic strategies. The objective of this study was to investigate the effects of varying levels of medial collateral ligament deficiency on elbow joint stability using subject-specific computational models. Two elbow joint models were placed at the pronated forearm position and passively flexed by applying a vertical downward motion on humeral head. The models included three-dimensional bone geometries, multiple ligament bundles wrapped around the joint, and the discretized cartilage representation. Four different ligament conditions were simulated: All intact ligaments, isolated medial collateral ligament (MCL) anterior bundle deficiency, isolated MCL posterior bundle deficiency, and complete MCL deficiency. Minimal kinematic differences were observed for isolated anterior and posterior bundle deficient elbows. However, sectioning the entire MCL resulted in significant kinematic differences and induced substantial elbow instability. Joint contact areas were nearly similar for the intact and isolated posterior bundle deficiency. Minor differences were observed for the isolated anterior bundle deficiency, and major differences were observed for the entire MCL deficiency. Complete elbow dislocations were not observed for any ligament deficiency level. As expected, during isolated anterior bundle deficiency, the remaining posterior bundle experiences higher load and vice versa. Overall, the results indicate that either MCL anterior or posterior bundle can provide anterior elbow stability, but the anterior bundle has a somewhat bigger influence on joint kinematics and contact characteristics than posterior one. A study with a larger sample size could help to strengthen the conclusion and statistical significant. Full article
(This article belongs to the Special Issue Engineering Bone-Implant Materials)
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Open AccessArticle GSK461364A, a Polo-Like Kinase-1 Inhibitor Encapsulated in Polymeric Nanoparticles for the Treatment of Glioblastoma Multiforme (GBM)
Bioengineering 2018, 5(4), 83; https://doi.org/10.3390/bioengineering5040083
Received: 17 August 2018 / Revised: 4 October 2018 / Accepted: 6 October 2018 / Published: 9 October 2018
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Abstract
Glioblastoma Multiforme (GBM) is a common primary brain cancer with a poor prognosis and a median survival of less than 14 months. Current modes of treatment are associated with deleterious side effects that reduce the life span of the patients. Nanomedicine enables site-specific
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Glioblastoma Multiforme (GBM) is a common primary brain cancer with a poor prognosis and a median survival of less than 14 months. Current modes of treatment are associated with deleterious side effects that reduce the life span of the patients. Nanomedicine enables site-specific delivery of active pharmaceutical ingredients and facilitates entrapment inside the tumor. Polo-like kinase 1 (PLK-1) inhibitors have shown promising results in tumor cells. GSK461364A (GSK) is one such targeted inhibitor with reported toxicity issues in phase 1 clinical trials. We have demonstrated in our study that the action of GSK is time dependent across all concentrations. There is a distinct 15−20% decrease in cell viability via apoptosis in U87-MG cells dosed with GSK at low concentrations (within the nanomolar and lower micromolar range) compared to higher concentrations of the drug. Additionally, we have confirmed that PLGA-PEG nanoparticles (NPs) containing GSK have shown significant reduction in cell viability of tumor cells compared to their free equivalents. Thus, this polymeric nanoconstruct encapsulating GSK can be effective even at low concentrations and could improve the effectiveness of the drug while reducing side effects at the lower effective dose. This is the first study to report a PLK-1 inhibitor (GSK) encapsulated in a nanocarrier for cancer applications. Full article
(This article belongs to the Special Issue Nanoparticles in Therapeutic Applications)
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Open AccessArticle Milieu for Endothelial Differentiation of Human Adipose-Derived Stem Cells
Bioengineering 2018, 5(4), 82; https://doi.org/10.3390/bioengineering5040082
Received: 30 August 2018 / Revised: 25 September 2018 / Accepted: 26 September 2018 / Published: 3 October 2018
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Abstract
Human adipose-derived stem cells (hASCs) have been shown to differentiate down many lineages including endothelial lineage. We hypothesized that hASCs would more efficiently differentiate toward the endothelial lineage when formed as three-dimensional (3D) spheroids and with the addition of vascular endothelial growth factor
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Human adipose-derived stem cells (hASCs) have been shown to differentiate down many lineages including endothelial lineage. We hypothesized that hASCs would more efficiently differentiate toward the endothelial lineage when formed as three-dimensional (3D) spheroids and with the addition of vascular endothelial growth factor (VEGF). Three conditions were tested: uncoated tissue culture polystyrene (TCPS) surfaces that induced a 2D monolayer formation; elastin-like polypeptide (ELP)-collagen composite hydrogel scaffolds that induced encapsulated 3D spheroid culture; and ELP-polyethyleneimine-coated TCPS surfaces that induced 3D spheroid formation in scaffold-free condition. Cells were exposed to endothelial differentiation medium containing no additional VEGF or 20 and 50 ng/mL of VEGF for 7 days and assayed for viability and endothelial differentiation markers. While endothelial differentiation media supported endothelial differentiation of hASCs, our 3D spheroid cultures augmented this differentiation and produced more von Willebrand factor than 2D cultures. Likewise, 3D cultures were able to uptake LDL, whereas the 2D cultures were not. Higher concentrations of VEGF further enhanced differentiation. Establishing angiogenesis is a key factor in regenerative medicine. Future studies aim to elucidate how to produce physiological changes such as neoangiogenesis and sprouting of vessels which may enhance the survival of regenerated tissues. Full article
(This article belongs to the Special Issue Applying Polymeric Biomaterials in 3D Tissue Constructs)
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Open AccessReview Preclinical Models of Pediatric Brain Tumors—Forging Ahead
Bioengineering 2018, 5(4), 81; https://doi.org/10.3390/bioengineering5040081
Received: 21 August 2018 / Revised: 22 September 2018 / Accepted: 27 September 2018 / Published: 2 October 2018
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Abstract
Approximately five out of 100,000 children from 0 to 19 years old are diagnosed with a brain tumor. These children are treated with medication designed for adults that are highly toxic to a developing brain. Those that survive are at high risk for
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Approximately five out of 100,000 children from 0 to 19 years old are diagnosed with a brain tumor. These children are treated with medication designed for adults that are highly toxic to a developing brain. Those that survive are at high risk for a lifetime of limited physical, psychological, and cognitive abilities. Despite much effort, not one drug exists that was designed specifically for pediatric patients. Stagnant government funding and the lack of economic incentives for the pharmaceutical industry greatly limits preclinical research and the development of clinically applicable pediatric brain tumor models. As more data are collected, the recognition of disease sub-groups based on molecular heterogeneity increases the need for designing specific models suitable for predictive drug screening. To overcome these challenges, preclinical approaches will need continual enhancement. In this review, we examine the advantages and shortcomings of in vitro and in vivo preclinical pediatric brain tumor models and explore potential solutions based on past, present, and future strategies for improving their clinical relevancy. Full article
(This article belongs to the Special Issue Update in Pediatric Neuro-Oncology)
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