Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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16 pages, 17630 KiB  
Article
In Situ Visualization for 3D Ultrasound-Guided Interventions with Augmented Reality Headset
by Nadia Cattari, Sara Condino, Fabrizio Cutolo, Mauro Ferrari and Vincenzo Ferrari
Bioengineering 2021, 8(10), 131; https://doi.org/10.3390/bioengineering8100131 - 25 Sep 2021
Cited by 19 | Viewed by 4778
Abstract
Augmented Reality (AR) headsets have become the most ergonomic and efficient visualization devices to support complex manual tasks performed under direct vision. Their ability to provide hands-free interaction with the augmented scene makes them perfect for manual procedures such as surgery. This study [...] Read more.
Augmented Reality (AR) headsets have become the most ergonomic and efficient visualization devices to support complex manual tasks performed under direct vision. Their ability to provide hands-free interaction with the augmented scene makes them perfect for manual procedures such as surgery. This study demonstrates the reliability of an AR head-mounted display (HMD), conceived for surgical guidance, in navigating in-depth high-precision manual tasks guided by a 3D ultrasound imaging system. The integration between the AR visualization system and the ultrasound imaging system provides the surgeon with real-time intra-operative information on unexposed soft tissues that are spatially registered with the surrounding anatomic structures. The efficacy of the AR guiding system was quantitatively assessed with an in vitro study simulating a biopsy intervention aimed at determining the level of accuracy achievable. In the experiments, 10 subjects were asked to perform the biopsy on four spherical lesions of decreasing sizes (10, 7, 5, and 3 mm). The experimental results showed that 80% of the subjects were able to successfully perform the biopsy on the 5 mm lesion, with a 2.5 mm system accuracy. The results confirmed that the proposed integrated system can be used for navigation during in-depth high-precision manual tasks. Full article
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15 pages, 4832 KiB  
Article
Amphiphilic and Perfluorinated Poly(3-Hydroxyalkanoate) Nanocapsules for 19F Magnetic Resonance Imaging
by Marion Le Gal, Estelle Renard, Christelle Simon-Colin, Benoit Larrat and Valérie Langlois
Bioengineering 2021, 8(9), 121; https://doi.org/10.3390/bioengineering8090121 - 9 Sep 2021
Cited by 3 | Viewed by 3840
Abstract
Nanoparticles have recently emerged as valuable tools in biomedical imaging techniques. Here PEGylated and fluorinated nanocapsules based on poly(3-hydroxyalkanoate) containing a liquid core of perfluorooctyl bromide PFOB were formulated by an emulsion-evaporation process as potential 19F MRI imaging agents. Unsaturated poly(hydroxyalkanoate), PHAU, [...] Read more.
Nanoparticles have recently emerged as valuable tools in biomedical imaging techniques. Here PEGylated and fluorinated nanocapsules based on poly(3-hydroxyalkanoate) containing a liquid core of perfluorooctyl bromide PFOB were formulated by an emulsion-evaporation process as potential 19F MRI imaging agents. Unsaturated poly(hydroxyalkanoate), PHAU, was produced by marine bacteria using coprah oil and undecenoic acid as substrates. PHA-g-(F; PEG) was prepared by two successive controlled thiol-ene reactions from PHAU with firstly three fluorinated thiols having from 3 up to 17 fluorine atoms and secondly with PEG-SH. The resulting PHA-g-(F; PEG)-based PFOB nanocapsules, with a diameter close to 250–300 nm, are shown to be visible in 19F MRI with an acquisition time of 15 min. The results showed that PFOB-nanocapsules based on PHA-g-(F; PEG) have the potential to be used as novel contrast agents for 19F MRI. Full article
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21 pages, 2821 KiB  
Review
Pichia pastoris (Komagataella phaffii) as a Cost-Effective Tool for Vaccine Production for Low- and Middle-Income Countries (LMICs)
by Salomé de Sá Magalhães and Eli Keshavarz-Moore
Bioengineering 2021, 8(9), 119; https://doi.org/10.3390/bioengineering8090119 - 31 Aug 2021
Cited by 34 | Viewed by 9313
Abstract
Vaccination is of paramount importance to global health. With the advent of the more recent pandemics, the urgency to expand the range has become even more evident. However, the potential limited availability and affordability of vaccines to resource low- and middle-income countries has [...] Read more.
Vaccination is of paramount importance to global health. With the advent of the more recent pandemics, the urgency to expand the range has become even more evident. However, the potential limited availability and affordability of vaccines to resource low- and middle-income countries has created a need for solutions that will ensure cost-effective vaccine production methods for these countries. Pichia pastoris (P. pastoris) (also known as Komagataella phaffii) is one of the most promising candidates for expression of heterologous proteins in vaccines development. It combines the speed and ease of highly efficient prokaryotic platforms with some key capabilities of mammalian systems, potentially reducing manufacturing costs. This review will examine the latest developments in P. pastoris from cell engineering and design to industrial production systems with focus on vaccine development and with reference to specific key case studies. Full article
(This article belongs to the Special Issue From Yeast to Biotechnology)
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29 pages, 7773 KiB  
Review
Stem Cell Niche Microenvironment: Review
by Mohamed Abdul-Al, George Kumi Kyeremeh, Morvarid Saeinasab, Saeed Heidari Keshel and Farshid Sefat
Bioengineering 2021, 8(8), 108; https://doi.org/10.3390/bioengineering8080108 - 28 Jul 2021
Cited by 24 | Viewed by 5809
Abstract
The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving clarity and visibility. Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live [...] Read more.
The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving clarity and visibility. Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live at the bottom of the limbal crypts, in a physically enclosed microenvironment with a number of neighboring niche cells. Scientists also simplified features of these diverse microenvironments for more analysis in situ by designing and recreating features of different SCNs. Recent methods for regenerating the corneal epithelium after serious trauma, including burns and allergic assaults, focus mainly on regenerating the LESCs. Mesenchymal stem cells, which can transform into self-renewing and skeletal tissues, hold immense interest for tissue engineering and innovative medicinal exploration. This review summarizes all types of LESCs, identity and location of the human epithelial stem cells (HESCs), reconstruction of LSCN and artificial stem cells for self-renewal. Full article
(This article belongs to the Special Issue Design and Fabrication of Artificial Stem Cell Microenvironments)
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29 pages, 9902 KiB  
Review
Bioremediation of Agricultural Soils Polluted with Pesticides: A Review
by Carla Maria Raffa and Fulvia Chiampo
Bioengineering 2021, 8(7), 92; https://doi.org/10.3390/bioengineering8070092 - 2 Jul 2021
Cited by 142 | Viewed by 23144
Abstract
Pesticides are chemical compounds used to eliminate pests; among them, herbicides are compounds particularly toxic to weeds, and this property is exploited to protect the crops from unwanted plants. Pesticides are used to protect and maximize the yield and quality of crops. The [...] Read more.
Pesticides are chemical compounds used to eliminate pests; among them, herbicides are compounds particularly toxic to weeds, and this property is exploited to protect the crops from unwanted plants. Pesticides are used to protect and maximize the yield and quality of crops. The excessive use of these chemicals and their persistence in the environment have generated serious problems, namely pollution of soil, water, and, to a lower extent, air, causing harmful effects to the ecosystem and along the food chain. About soil pollution, the residual concentration of pesticides is often over the limits allowed by the regulations. Where this occurs, the challenge is to reduce the amount of these chemicals and obtain agricultural soils suitable for growing ecofriendly crops. The microbial metabolism of indigenous microorganisms can be exploited for degradation since bioremediation is an ecofriendly, cost-effective, rather efficient method compared to the physical and chemical ones. Several biodegradation techniques are available, based on bacterial, fungal, or enzymatic degradation. The removal efficiencies of these processes depend on the type of pollutant and the chemical and physical conditions of the soil. The regulation on the use of pesticides is strictly connected to their environmental impacts. Nowadays, every country can adopt regulations to restrict the consumption of pesticides, prohibit the most harmful ones, and define the admissible concentrations in the soil. However, this variability implies that each country has a different perception of the toxicology of these compounds, inducing different market values of the grown crops. This review aims to give a picture of the bioremediation of soils polluted with commercial pesticides, considering the features that characterize the main and most used ones, namely their classification and their toxicity, together with some elements of legislation into force around the world. Full article
(This article belongs to the Special Issue Bioengineering in Remediation of Polluted Environments)
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18 pages, 3075 KiB  
Article
3D Printing of Thermoresponsive Hydrogel Laden with an Antimicrobial Agent towards Wound Healing Applications
by Martyna Nizioł, Justyna Paleczny, Adam Junka, Amin Shavandi, Anna Dawiec-Liśniewska and Daria Podstawczyk
Bioengineering 2021, 8(6), 79; https://doi.org/10.3390/bioengineering8060079 - 8 Jun 2021
Cited by 59 | Viewed by 9848
Abstract
Thermoresponsive hydrogel-based wound dressings with an incorporated antimicrobial agent can be fabricated employing 3D printing technology. A novel printable ink containing poly(N-isopropylacrylamide) (PNIPAAm) precursors, sodium alginate (ALG), methylcellulose (MC) that is laden with a mixture of octenidine dihydrochloride and 2-phenoxyethanol (Octenisept®, [...] Read more.
Thermoresponsive hydrogel-based wound dressings with an incorporated antimicrobial agent can be fabricated employing 3D printing technology. A novel printable ink containing poly(N-isopropylacrylamide) (PNIPAAm) precursors, sodium alginate (ALG), methylcellulose (MC) that is laden with a mixture of octenidine dihydrochloride and 2-phenoxyethanol (Octenisept®, OCT) possess accurate printability and shape fidelity. This study also provides the protocol of ink’s use for the 3D printing of hydrogel scaffolds. The hydrogel’s physicochemical properties and drug release profiles from the hydrogel specimens to the external solution have been determined at two temperatures (20 and 37 °C). The release test showed a sustained OCT delivery into ultrapure water and the PBS solution. The temperature-responsive hydrogel exhibited antimicrobial activity against Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa and demonstrated non-cytotoxicity towards fibroblasts. The thermoresponsive behavior along with biocompatibility, antimicrobial activity, and controlled drug release make this hydrogel a promising class of materials for wound dressing applications. Full article
(This article belongs to the Special Issue 3D Printing of Functional Biomaterials and Nanocomposites)
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15 pages, 868 KiB  
Review
Collagen in Wound Healing
by Shomita S. Mathew-Steiner, Sashwati Roy and Chandan K. Sen
Bioengineering 2021, 8(5), 63; https://doi.org/10.3390/bioengineering8050063 - 11 May 2021
Cited by 641 | Viewed by 39104
Abstract
Normal wound healing progresses through inflammatory, proliferative and remodeling phases in response to tissue injury. Collagen, a key component of the extracellular matrix, plays critical roles in the regulation of the phases of wound healing either in its native, fibrillar conformation or as [...] Read more.
Normal wound healing progresses through inflammatory, proliferative and remodeling phases in response to tissue injury. Collagen, a key component of the extracellular matrix, plays critical roles in the regulation of the phases of wound healing either in its native, fibrillar conformation or as soluble components in the wound milieu. Impairments in any of these phases stall the wound in a chronic, non-healing state that typically requires some form of intervention to guide the process back to completion. Key factors in the hostile environment of a chronic wound are persistent inflammation, increased destruction of ECM components caused by elevated metalloproteinases and other enzymes and improper activation of soluble mediators of the wound healing process. Collagen, being central in the regulation of several of these processes, has been utilized as an adjunct wound therapy to promote healing. In this work the significance of collagen in different biological processes relevant to wound healing are reviewed and a summary of the current literature on the use of collagen-based products in wound care is provided. Full article
(This article belongs to the Special Issue Biomedical Applications of Collagen)
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28 pages, 1774 KiB  
Review
COVID-19 Diagnostic Strategies Part II: Protein-Based Technologies
by Tina Shaffaf and Ebrahim Ghafar-Zadeh
Bioengineering 2021, 8(5), 54; https://doi.org/10.3390/bioengineering8050054 - 28 Apr 2021
Cited by 18 | Viewed by 10262
Abstract
After the initiation of the current outbreak, humans’ lives have been profoundly impacted by COVID-19. During the first months, no rapid and reliable detecting tool was readily available to sufficiently respond to the requirement of massive testing. In this situation, when the development [...] Read more.
After the initiation of the current outbreak, humans’ lives have been profoundly impacted by COVID-19. During the first months, no rapid and reliable detecting tool was readily available to sufficiently respond to the requirement of massive testing. In this situation, when the development of an effective vaccine requires at least a few months, it is crucial to be prepared by developing and commercializing affordable, accurate, rapid and adaptable biosensors not only to fight Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) but also to be armed to avoid the pandemic in the earliest stages in the future. The COVID-19 diagnostic tools are categorized into two main groups of Nucleic Acid (NA)-based and protein-based tests. To date, nucleic acid-based detection has been announced as the gold-standard strategy for coronavirus detection; however, protein-based tests are promising alternatives for rapid and large-scale screening of susceptible groups. In this review, we discuss the current protein-based biosensing tools, the research advances and the potential protein-detecting strategies for COVID-19 detection. This narrative review aims to highlight the importance of the diagnostic tests, encourage the academic research groups and the companies to eliminate the shortcomings of the current techniques and step forward to mass-producing reliable point-of-care (POC) and point-of-need (PON) adaptable diagnostic tools for large-scale screening in the future outbreaks. Full article
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29 pages, 2446 KiB  
Review
COVID-19 Diagnostic Strategies. Part I: Nucleic Acid-Based Technologies
by Tina Shaffaf and Ebrahim Ghafar-Zadeh
Bioengineering 2021, 8(4), 49; https://doi.org/10.3390/bioengineering8040049 - 17 Apr 2021
Cited by 24 | Viewed by 9835
Abstract
The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused respiratory infection, resulting in more than two million deaths globally and hospitalizing thousands of people by March 2021. A considerable percentage of the SARS-CoV-2 positive patients are asymptomatic or pre-symptomatic carriers, facilitating [...] Read more.
The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused respiratory infection, resulting in more than two million deaths globally and hospitalizing thousands of people by March 2021. A considerable percentage of the SARS-CoV-2 positive patients are asymptomatic or pre-symptomatic carriers, facilitating the viral spread in the community by their social activities. Hence, it is critical to have access to commercialized diagnostic tests to detect the infection in the earliest stages, monitor the disease, and follow up the patients. Various technologies have been proposed to develop more promising assays and move toward the mass production of fast, reliable, cost-effective, and portable PoC diagnostic tests for COVID-19 detection. Not only COVID-19 but also many other pathogens will be able to spread and attach to human bodies in the future. These technologies enable the fast identification of high-risk individuals during future hazards to support the public in such outbreaks. This paper provides a comprehensive review of current technologies, the progress in the development of molecular diagnostic tests, and the potential strategies to facilitate innovative developments in unprecedented pandemics. Full article
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26 pages, 872 KiB  
Review
Protein-Based 3D Biofabrication of Biomaterials
by Mahta Mirzaei, Oseweuba Valentine Okoro, Lei Nie, Denise Freitas Siqueira Petri and Amin Shavandi
Bioengineering 2021, 8(4), 48; https://doi.org/10.3390/bioengineering8040048 - 16 Apr 2021
Cited by 44 | Viewed by 7736
Abstract
Protein/peptide-based hydrogel biomaterial inks with the ability to incorporate various cells and mimic the extracellular matrix’s function are promising candidates for 3D printing and biomaterials engineering. This is because proteins contain multiple functional groups as reactive sites for enzymatic, chemical modification or physical [...] Read more.
Protein/peptide-based hydrogel biomaterial inks with the ability to incorporate various cells and mimic the extracellular matrix’s function are promising candidates for 3D printing and biomaterials engineering. This is because proteins contain multiple functional groups as reactive sites for enzymatic, chemical modification or physical gelation or cross-linking, which is essential for the filament formation and printing processes in general. The primary mechanism in the protein gelation process is the unfolding of its native structure and its aggregation into a gel network. This network is then stabilized through both noncovalent and covalent cross-link. Diverse proteins and polypeptides can be obtained from humans, animals, or plants or can be synthetically engineered. In this review, we describe the major proteins that have been used for 3D printing, highlight their physicochemical properties in relation to 3D printing and their various tissue engineering application are discussed. Full article
(This article belongs to the Special Issue 3D Printing of Functional Biomaterials and Nanocomposites)
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16 pages, 1404 KiB  
Review
Collagen-Based Electrospun Materials for Tissue Engineering: A Systematic Review
by Britani N. Blackstone, Summer C. Gallentine and Heather M. Powell
Bioengineering 2021, 8(3), 39; https://doi.org/10.3390/bioengineering8030039 - 18 Mar 2021
Cited by 66 | Viewed by 8674
Abstract
Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match [...] Read more.
Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures. Full article
(This article belongs to the Special Issue Biomedical Applications of Collagen)
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12 pages, 372 KiB  
Article
Deep Neural Networks and Transfer Learning on a Multivariate Physiological Signal Dataset
by Andrea Bizzego, Giulio Gabrieli and Gianluca Esposito
Bioengineering 2021, 8(3), 35; https://doi.org/10.3390/bioengineering8030035 - 6 Mar 2021
Cited by 30 | Viewed by 6148
Abstract
While Deep Neural Networks (DNNs) and Transfer Learning (TL) have greatly contributed to several medical and clinical disciplines, the application to multivariate physiological datasets is still limited. Current examples mainly focus on one physiological signal and can only utilise applications that are customised [...] Read more.
While Deep Neural Networks (DNNs) and Transfer Learning (TL) have greatly contributed to several medical and clinical disciplines, the application to multivariate physiological datasets is still limited. Current examples mainly focus on one physiological signal and can only utilise applications that are customised for that specific measure, thus it limits the possibility of transferring the trained DNN to other domains. In this study, we composed a dataset (n=813) of six different types of physiological signals (Electrocardiogram, Electrodermal activity, Electromyogram, Photoplethysmogram, Respiration and Acceleration). Signals were collected from 232 subjects using four different acquisition devices. We used a DNN to classify the type of physiological signal and to demonstrate how the TL approach allows the exploitation of the efficiency of DNNs in other domains. After the DNN was trained to optimally classify the type of signal, the features that were automatically extracted by the DNN were used to classify the type of device used for the acquisition using a Support Vector Machine. The dataset, the code and the trained parameters of the DNN are made publicly available to encourage the adoption of DNN and TL in applications with multivariate physiological signals. Full article
(This article belongs to the Special Issue Advances in Multivariate Physiological Signal Analysis)
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31 pages, 7647 KiB  
Review
Advantages of Additive Manufacturing for Biomedical Applications of Polyhydroxyalkanoates
by Alberto Giubilini, Federica Bondioli, Massimo Messori, Gustav Nyström and Gilberto Siqueira
Bioengineering 2021, 8(2), 29; https://doi.org/10.3390/bioengineering8020029 - 23 Feb 2021
Cited by 38 | Viewed by 8389
Abstract
In recent years, biopolymers have been attracting the attention of researchers and specialists from different fields, including biotechnology, material science, engineering, and medicine. The reason is the possibility of combining sustainability with scientific and technological progress. This is an extremely broad research topic, [...] Read more.
In recent years, biopolymers have been attracting the attention of researchers and specialists from different fields, including biotechnology, material science, engineering, and medicine. The reason is the possibility of combining sustainability with scientific and technological progress. This is an extremely broad research topic, and a distinction has to be made among different classes and types of biopolymers. Polyhydroxyalkanoate (PHA) is a particular family of polyesters, synthetized by microorganisms under unbalanced growth conditions, making them both bio-based and biodegradable polymers with a thermoplastic behavior. Recently, PHAs were used more intensively in biomedical applications because of their tunable mechanical properties, cytocompatibility, adhesion for cells, and controllable biodegradability. Similarly, the 3D-printing technologies show increasing potential in this particular field of application, due to their advantages in tailor-made design, rapid prototyping, and manufacturing of complex structures. In this review, first, the synthesis and the production of PHAs are described, and different production techniques of medical implants are compared. Then, an overview is given on the most recent and relevant medical applications of PHA for drug delivery, vessel stenting, and tissue engineering. A special focus is reserved for the innovations brought by the introduction of additive manufacturing in this field, as compared to the traditional techniques. All of these advances are expected to have important scientific and commercial applications in the near future. Full article
(This article belongs to the Section Nanobiotechnology and Biofabrication)
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19 pages, 1669 KiB  
Review
High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases
by Hasan Aldewachi, Radhwan N. Al-Zidan, Matthew T. Conner and Mootaz M. Salman
Bioengineering 2021, 8(2), 30; https://doi.org/10.3390/bioengineering8020030 - 23 Feb 2021
Cited by 143 | Viewed by 23232
Abstract
Neurodegenerative diseases (NDDs) are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells in the central nervous system (CNS). Identification of viable therapeutic targets and new treatments for CNS disorders and in particular, for NDDs is a major [...] Read more.
Neurodegenerative diseases (NDDs) are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells in the central nervous system (CNS). Identification of viable therapeutic targets and new treatments for CNS disorders and in particular, for NDDs is a major challenge in the field of drug discovery. These difficulties can be attributed to the diversity of cells involved, extreme complexity of the neural circuits, the limited capacity for tissue regeneration, and our incomplete understanding of the underlying pathological processes. Drug discovery is a complex and multidisciplinary process. The screening attrition rate in current drug discovery protocols mean that only one viable drug may arise from millions of screened compounds resulting in the need to improve discovery technologies and protocols to address the multiple causes of attrition. This has identified the need to screen larger libraries where the use of efficient high-throughput screening (HTS) becomes key in the discovery process. HTS can investigate hundreds of thousands of compounds per day. However, if fewer compounds could be screened without compromising the probability of success, the cost and time would be largely reduced. To that end, recent advances in computer-aided design, in silico libraries, and molecular docking software combined with the upscaling of cell-based platforms have evolved to improve screening efficiency with higher predictability and clinical applicability. We review, here, the increasing role of HTS in contemporary drug discovery processes, in particular for NDDs, and evaluate the criteria underlying its successful application. We also discuss the requirement of HTS for novel NDD therapies and examine the major current challenges in validating new drug targets and developing new treatments for NDDs. Full article
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19 pages, 938 KiB  
Review
Natural Biomaterials and Their Use as Bioinks for Printing Tissues
by Claire Benwood, Josie Chrenek, Rebecca L. Kirsch, Nadia Z. Masri, Hannah Richards, Kyra Teetzen and Stephanie M. Willerth
Bioengineering 2021, 8(2), 27; https://doi.org/10.3390/bioengineering8020027 - 20 Feb 2021
Cited by 173 | Viewed by 15119
Abstract
The most prevalent form of bioprinting—extrusion bioprinting—can generate structures from a diverse range of materials and viscosities. It can create personalized tissues that aid in drug testing and cancer research when used in combination with natural bioinks. This paper reviews natural bioinks and [...] Read more.
The most prevalent form of bioprinting—extrusion bioprinting—can generate structures from a diverse range of materials and viscosities. It can create personalized tissues that aid in drug testing and cancer research when used in combination with natural bioinks. This paper reviews natural bioinks and their properties and functions in hard and soft tissue engineering applications. It discusses agarose, alginate, cellulose, chitosan, collagen, decellularized extracellular matrix, dextran, fibrin, gelatin, gellan gum, hyaluronic acid, Matrigel, and silk. Multi-component bioinks are considered as a way to address the shortfalls of individual biomaterials. The mechanical, rheological, and cross-linking properties along with the cytocompatibility, cell viability, and printability of the bioinks are detailed as well. Future avenues for research into natural bioinks are then presented. Full article
(This article belongs to the Special Issue 3D Bioprinting for Tissue Engineering and Regenerative Medicine)
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9 pages, 2752 KiB  
Article
An Open-Source COVID-19 CT Dataset with Automatic Lung Tissue Classification for Radiomics
by Paolo Zaffino, Aldo Marzullo, Sara Moccia, Francesco Calimeri, Elena De Momi, Bernardo Bertucci, Pier Paolo Arcuri and Maria Francesca Spadea
Bioengineering 2021, 8(2), 26; https://doi.org/10.3390/bioengineering8020026 - 16 Feb 2021
Cited by 28 | Viewed by 7755
Abstract
The coronavirus disease 19 (COVID-19) pandemic is having a dramatic impact on society and healthcare systems. In this complex scenario, lung computerized tomography (CT) may play an important prognostic role. However, datasets released so far present limitations that hamper the development of tools [...] Read more.
The coronavirus disease 19 (COVID-19) pandemic is having a dramatic impact on society and healthcare systems. In this complex scenario, lung computerized tomography (CT) may play an important prognostic role. However, datasets released so far present limitations that hamper the development of tools for quantitative analysis. In this paper, we present an open-source lung CT dataset comprising information on 50 COVID-19-positive patients. The CT volumes are provided along with (i) an automatic threshold-based annotation obtained with a Gaussian mixture model (GMM) and (ii) a scoring provided by an expert radiologist. This score was found to significantly correlate with the presence of ground glass opacities and the consolidation found with GMM. The dataset is freely available in an ITK-based file format under the CC BY-NC 4.0 license. The code for GMM fitting is publicly available, as well. We believe that our dataset will provide a unique opportunity for researchers working in the field of medical image analysis, and hope that its release will lay the foundations for the successfully implementation of algorithms to support clinicians in facing the COVID-19 pandemic. Full article
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20 pages, 2998 KiB  
Article
CRISPR/Cas9-Based Lateral Flow and Fluorescence Diagnostics
by Mark J. Osborn, Akshay Bhardwaj, Samuel P. Bingea, Friederike Knipping, Colby J. Feser, Christopher J. Lees, Daniel P. Collins, Clifford J. Steer, Bruce R. Blazar and Jakub Tolar
Bioengineering 2021, 8(2), 23; https://doi.org/10.3390/bioengineering8020023 - 12 Feb 2021
Cited by 30 | Viewed by 13746
Abstract
Clustered regularly interspaced short palindromic repeat (CRISPR/Cas) proteins can be designed to bind specified DNA and RNA sequences and hold great promise for the accurate detection of nucleic acids for diagnostics. We integrated commercially available reagents into a CRISPR/Cas9-based lateral flow assay that [...] Read more.
Clustered regularly interspaced short palindromic repeat (CRISPR/Cas) proteins can be designed to bind specified DNA and RNA sequences and hold great promise for the accurate detection of nucleic acids for diagnostics. We integrated commercially available reagents into a CRISPR/Cas9-based lateral flow assay that can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences with single-base specificity. This approach requires minimal equipment and represents a simplified platform for field-based deployment. We also developed a rapid, multiplex fluorescence CRISPR/Cas9 nuclease cleavage assay capable of detecting and differentiating SARS-CoV-2, influenza A and B, and respiratory syncytial virus in a single reaction. Our findings provide proof-of-principle for CRISPR/Cas9 point-of-care diagnosis as well as a scalable fluorescent platform for identifying respiratory viral pathogens with overlapping symptomology. Full article
(This article belongs to the Special Issue CRISPR-Cas: Discovery, Function and Application)
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16 pages, 4571 KiB  
Article
Characterization of Gelatin Hydrogels Cross-Linked with Microbial Transglutaminase as Engineered Skeletal Muscle Substrates
by Divya Gupta, Jeffrey W. Santoso and Megan L. McCain
Bioengineering 2021, 8(1), 6; https://doi.org/10.3390/bioengineering8010006 - 6 Jan 2021
Cited by 38 | Viewed by 8521
Abstract
Engineered in vitro models of skeletal muscle are essential for efficiently screening drug safety and efficacy. However, conventional culture substrates poorly replicate physical features of native muscle and do not support long-term culture, which limits tissue maturity. Micromolded gelatin hydrogels cross-linked with microbial [...] Read more.
Engineered in vitro models of skeletal muscle are essential for efficiently screening drug safety and efficacy. However, conventional culture substrates poorly replicate physical features of native muscle and do not support long-term culture, which limits tissue maturity. Micromolded gelatin hydrogels cross-linked with microbial transglutaminase (gelatin-MTG hydrogels) have previously been shown to induce C21C2 myotube alignment and improve culture longevity. However, several properties of gelatin-MTG hydrogels have not been systematically characterized, such as changes in elastic modulus during incubation in culture-like conditions and their ability to support sarcomere maturation. In this study, various gelatin-MTG hydrogels were fabricated and incubated in ambient or culture-like conditions. Elastic modulus, mass, and transmittance were measured over a one- or two-week period. Compared to hydrogels in phosphate buffered saline (PBS) or ambient air, hydrogels in Dulbecco’s Modified Eagle Medium (DMEM) and 5% CO2 demonstrated the most stable elastic modulus. A subset of gelatin-MTG hydrogels was micromolded and seeded with C2C12 or primary chick myoblasts, which aligned and fused into multinucleated myotubes with relatively mature sarcomeres. These data are important for fabricating gelatin-MTG hydrogels with predictable and stable mechanical properties and highlight their advantages as culture substrates for engineering relatively mature and stable muscle tissues. Full article
(This article belongs to the Special Issue Advances in Skeletal Muscle Tissue Engineering)
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24 pages, 3948 KiB  
Review
Collagen Mimetic Peptides
by Yujia Xu and Michele Kirchner
Bioengineering 2021, 8(1), 5; https://doi.org/10.3390/bioengineering8010005 - 5 Jan 2021
Cited by 52 | Viewed by 13102
Abstract
Since their first synthesis in the late 1960s, collagen mimetic peptides (CMPs) have been used as a molecular tool to study collagen, and as an approach to develop novel collagen mimetic biomaterials. Collagen, a major extracellular matrix (ECM) protein, plays vital roles in [...] Read more.
Since their first synthesis in the late 1960s, collagen mimetic peptides (CMPs) have been used as a molecular tool to study collagen, and as an approach to develop novel collagen mimetic biomaterials. Collagen, a major extracellular matrix (ECM) protein, plays vital roles in many physiological and pathogenic processes. Applications of CMPs have advanced our understanding of the structure and molecular properties of a collagen triple helix—the building block of collagen—and the interactions of collagen with important molecular ligands. The accumulating knowledge is also paving the way for developing novel CMPs for biomedical applications. Indeed, for the past 50 years, CMP research has been a fast-growing, far-reaching interdisciplinary field. The major development and achievement of CMPs were documented in a few detailed reviews around 2010. Here, we provided a brief overview of what we have learned about CMPs—their potential and their limitations. We focused on more recent developments in producing heterotrimeric CMPs, and CMPs that can form collagen-like higher order molecular assemblies. We also expanded the traditional view of CMPs to include larger designed peptides produced using recombinant systems. Studies using recombinant peptides have provided new insights on collagens and promoted progress in the development of collagen mimetic fibrillar self-assemblies. Full article
(This article belongs to the Special Issue Biomedical Applications of Collagen)
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23 pages, 13871 KiB  
Review
Collagen Structure-Function Mapping Informs Applications for Regenerative Medicine
by James D. San Antonio, Olena Jacenko, Andrzej Fertala and Joseph P.R.O. Orgel
Bioengineering 2021, 8(1), 3; https://doi.org/10.3390/bioengineering8010003 - 29 Dec 2020
Cited by 75 | Viewed by 11584
Abstract
Type I collagen, the predominant protein of vertebrates, assembles into fibrils that orchestrate the form and function of bone, tendon, skin, and other tissues. Collagen plays roles in hemostasis, wound healing, angiogenesis, and biomineralization, and its dysfunction contributes to fibrosis, atherosclerosis, cancer metastasis, [...] Read more.
Type I collagen, the predominant protein of vertebrates, assembles into fibrils that orchestrate the form and function of bone, tendon, skin, and other tissues. Collagen plays roles in hemostasis, wound healing, angiogenesis, and biomineralization, and its dysfunction contributes to fibrosis, atherosclerosis, cancer metastasis, and brittle bone disease. To elucidate the type I collagen structure-function relationship, we constructed a type I collagen fibril interactome, including its functional sites and disease-associated mutations. When projected onto an X-ray diffraction model of the native collagen microfibril, data revealed a matrix interaction domain that assumes structural roles including collagen assembly, crosslinking, proteoglycan (PG) binding, and mineralization, and the cell interaction domain supporting dynamic aspects of collagen biology such as hemostasis, tissue remodeling, and cell adhesion. Our type III collagen interactome corroborates this model. We propose that in quiescent tissues, the fibril projects a structural face; however, tissue injury releases blood into the collagenous stroma, triggering exposure of the fibrils’ cell and ligand binding sites crucial for tissue remodeling and regeneration. Applications of our research include discovery of anti-fibrotic antibodies and elucidating their interactions with collagen, and using insights from our angiogenesis studies and collagen structure-function model to inform the design of super-angiogenic collagens and collagen mimetics. Full article
(This article belongs to the Special Issue Biomedical Applications of Collagen)
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35 pages, 2462 KiB  
Review
Electrospun Fiber Scaffolds for Engineering Glial Cell Behavior to Promote Neural Regeneration
by Devan L. Puhl, Jessica L. Funnell, Derek W. Nelson, Manoj K. Gottipati and Ryan J. Gilbert
Bioengineering 2021, 8(1), 4; https://doi.org/10.3390/bioengineering8010004 - 29 Dec 2020
Cited by 39 | Viewed by 8193
Abstract
Electrospinning is a fabrication technique used to produce nano- or micro- diameter fibers to generate biocompatible, biodegradable scaffolds for tissue engineering applications. Electrospun fiber scaffolds are advantageous for neural regeneration because they mimic the structure of the nervous system extracellular matrix and provide [...] Read more.
Electrospinning is a fabrication technique used to produce nano- or micro- diameter fibers to generate biocompatible, biodegradable scaffolds for tissue engineering applications. Electrospun fiber scaffolds are advantageous for neural regeneration because they mimic the structure of the nervous system extracellular matrix and provide contact guidance for regenerating axons. Glia are non-neuronal regulatory cells that maintain homeostasis in the healthy nervous system and regulate regeneration in the injured nervous system. Electrospun fiber scaffolds offer a wide range of characteristics, such as fiber alignment, diameter, surface nanotopography, and surface chemistry that can be engineered to achieve a desired glial cell response to injury. Further, electrospun fibers can be loaded with drugs, nucleic acids, or proteins to provide the local, sustained release of such therapeutics to alter glial cell phenotype to better support regeneration. This review provides the first comprehensive overview of how electrospun fiber alignment, diameter, surface nanotopography, surface functionalization, and therapeutic delivery affect Schwann cells in the peripheral nervous system and astrocytes, oligodendrocytes, and microglia in the central nervous system both in vitro and in vivo. The information presented can be used to design and optimize electrospun fiber scaffolds to target glial cell response to mitigate nervous system injury and improve regeneration. Full article
(This article belongs to the Special Issue Electrospinning for Tissue Engineering)
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14 pages, 1061 KiB  
Review
Spinal Deformities and Advancement in Corrective Orthoses
by Athar Ali, Vigilio Fontanari, Marco Fontana and Werner Schmölz
Bioengineering 2021, 8(1), 2; https://doi.org/10.3390/bioengineering8010002 - 25 Dec 2020
Cited by 24 | Viewed by 16706
Abstract
Spinal deformity is an abnormality in the spinal curves and can seriously affect the activities of daily life. The conventional way to treat spinal deformities, such as scoliosis, kyphosis, and spondylolisthesis, is to use spinal orthoses (braces). Braces have been used for centuries [...] Read more.
Spinal deformity is an abnormality in the spinal curves and can seriously affect the activities of daily life. The conventional way to treat spinal deformities, such as scoliosis, kyphosis, and spondylolisthesis, is to use spinal orthoses (braces). Braces have been used for centuries to apply corrective forces to the spine to treat spinal deformities or to stabilize the spine during postoperative rehabilitation. Braces have not modernized with advancements in technology, and very few braces are equipped with smart sensory design and active actuation. There is a need to enable the orthotists, ergonomics practitioners, and developers to incorporate new technologies into the passive field of bracing. This article presents a review of the conventional passive braces and highlights the advancements in spinal orthoses in terms of improved sensory designs, active actuation mechanisms, and new construction methods (CAD/CAM, three-dimensional (3D) printing). This review includes 26 spinal orthoses, comprised of passive rigid/soft braces, active dynamics braces, and torso training devices for the rehabilitation of the spine. Full article
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