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Bioengineering, Volume 6, Issue 1 (March 2019)

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Cover Story (view full-size image) Cover story: A new era of manufacturing is emerging through the use of 3D printing which is [...] Read more.
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Open AccessArticle Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli
Bioengineering 2019, 6(1), 27; https://doi.org/10.3390/bioengineering6010027
Received: 29 January 2019 / Revised: 14 March 2019 / Accepted: 19 March 2019 / Published: 21 March 2019
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Abstract
Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation. The addition of glycans to proteins remains [...] Read more.
Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation. The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones. Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b. Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed. Full article
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Open AccessReview Nanostructured Materials for Food Applications: Spectroscopy, Microscopy and Physical Properties
Bioengineering 2019, 6(1), 26; https://doi.org/10.3390/bioengineering6010026
Received: 7 March 2019 / Revised: 12 March 2019 / Accepted: 14 March 2019 / Published: 19 March 2019
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Abstract
Nanotechnology deals with matter of atomic or molecular scale. Other factors that define the character of a nanoparticle are its physical and chemical properties, such as surface area, surface charge, hydrophobicity of the surface, thermal stability of the nanoparticle and its antimicrobial activity. [...] Read more.
Nanotechnology deals with matter of atomic or molecular scale. Other factors that define the character of a nanoparticle are its physical and chemical properties, such as surface area, surface charge, hydrophobicity of the surface, thermal stability of the nanoparticle and its antimicrobial activity. A nanoparticle is usually characterized by using microscopic and spectroscopic techniques. Microscopic techniques are used to characterise the size, shape and location of the nanoparticle by producing an image of the individual nanoparticle. Several techniques, such as scanning electron microscopy (SEM), transmission electron microscopy/high resolution transmission electron microscopy (TEM/HRTEM), atomic force microscopy (AFM) and scanning tunnelling microscopy (STM) have been developed to observe and characterise the surface and structural properties of nanostructured material. Spectroscopic techniques are used to study the interaction of a nanoparticle with electromagnetic radiations as the function of wavelength, such as Raman spectroscopy, UV–Visible spectroscopy, attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), dynamic light scattering spectroscopy (DLS), Zeta potential spectroscopy, X-ray photoelectron spectroscopy (XPS) and X-ray photon correlation spectroscopy. Nanostructured materials have a wide application in the food industry as nanofood, nano-encapsulated probiotics, edible nano-coatings and in active and smart packaging. Full article
(This article belongs to the Special Issue Noble Metal Functionalized Nanoparticles for Biomedical Applications)
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Open AccessPerspective Data Integration and Interoperability for Patient-Centered Remote Monitoring of Cardiovascular Implantable Electronic Devices
Bioengineering 2019, 6(1), 25; https://doi.org/10.3390/bioengineering6010025
Received: 1 February 2019 / Revised: 1 March 2019 / Accepted: 7 March 2019 / Published: 17 March 2019
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Abstract
The prevalence of cardiovascular implantable electronic devices with remote monitoring capabilities continues to grow, resulting in increased volume and complexity of biomedical data. These data can provide diagnostic information for timely intervention and maintenance of implanted devices, improving quality of care. Current remote [...] Read more.
The prevalence of cardiovascular implantable electronic devices with remote monitoring capabilities continues to grow, resulting in increased volume and complexity of biomedical data. These data can provide diagnostic information for timely intervention and maintenance of implanted devices, improving quality of care. Current remote monitoring procedures do not utilize device diagnostics to their potential, due to the lack of interoperability and data integration among proprietary systems and electronic medical record platforms. However, the development of a technical framework that standardizes the data and improves interoperability shows promise for improving remote monitoring. Along with encouraging the implementation of this framework, we challenge the current paradigm and propose leveraging the framework to provide patients with their remote monitoring data. Patient-centered remote monitoring may empower patients and improve collaboration and care with health care providers. In this paper, we describe the implementation of technology to deliver remote monitoring data to patients in two recent studies. Our body of work explains the potential for developing a patent-facing information display that affords the meaningful use of implantable device data and enhances interactions with providers. This paradigm shift in remote monitoring—empowering the patient with data—is critical to using the vast amount of complex and clinically relevant biomedical data captured and transmitted by implantable devices to full potential. Full article
(This article belongs to the Special Issue Implantable Medical Devices)
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Open AccessArticle Nut and Bolt Microfluidics with Helical Minichannel for Counting CD4+ T-Cells
Bioengineering 2019, 6(1), 24; https://doi.org/10.3390/bioengineering6010024
Received: 26 February 2019 / Revised: 7 March 2019 / Accepted: 12 March 2019 / Published: 15 March 2019
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Abstract
In this study, we developed the prototype of an optical imaging-based point-of-care (POC) device for monitoring human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) progression that can detect CD4+ T-lymphocytes in human blood. The proposed portable cell-counting system, Helios CD4 Analyzer (Helios), can acquire [...] Read more.
In this study, we developed the prototype of an optical imaging-based point-of-care (POC) device for monitoring human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) progression that can detect CD4+ T-lymphocytes in human blood. The proposed portable cell-counting system, Helios CD4 Analyzer (Helios), can acquire sample images and analyze the cells automatically using a simple fluorescence imaging module and sample cartridge with a three-dimensional (3D) helical minichannel. The helical minichannel formed on the cylindrical surface enables the sample cartridge to hold a cell suspension present in a fixed sample volume for absolute counting of the cells. With a given total channel length, the helical minichannel-based sample cartridge is smaller than the conventional sample cartridge with a planar microchannel. The implemented nut and bolt mechanism allows the scanning of a relatively large volume of the sample along the helical minichannel by just rotating the cylindrical chamber coupled with a single DC motor rather than using a two-axis motorized translation stage, which considerably simplifies the associated electromechanical parts. It has distinct advantages over the existing devices because of its small size and simple scanning mechanism. We optimized various imaging parameters to enhance the fluorescence detection efficiency of the prototype. Performance evaluations using human blood samples demonstrated good agreement for low CD4 count between the Helios and the PIMATM, one of the most widely used POC CD4+ analyzers. Full article
(This article belongs to the Special Issue Frontiers of Microfluidics in Biology)
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Open AccessCommunication Lanthanide-Loaded Nanoparticles as Potential Fluorescent and Mass Probes for High-Content Protein Analysis
Bioengineering 2019, 6(1), 23; https://doi.org/10.3390/bioengineering6010023
Received: 11 February 2019 / Revised: 4 March 2019 / Accepted: 7 March 2019 / Published: 15 March 2019
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Abstract
Multiparametric and high-content protein analysis of single cells or tissues cannot be accomplished with the currently available flow cytometry or imaging techniques utilizing fluorophore-labelled antibodies, because the number of spectrally resolvable fluorochromes is limited. In contrast, mass cytometry can resolve more signals by [...] Read more.
Multiparametric and high-content protein analysis of single cells or tissues cannot be accomplished with the currently available flow cytometry or imaging techniques utilizing fluorophore-labelled antibodies, because the number of spectrally resolvable fluorochromes is limited. In contrast, mass cytometry can resolve more signals by exploiting lanthanide-tagged antibodies; however, only about 100 metal reporters can be attached to an antibody molecule. This makes the sensitivity of lanthanide-tagged antibodies substantially lower than fluorescent reporters. A new probe that can carry more lanthanide molecules per antibody is a desirable way to enhance the sensitivity needed for the detection of protein with low cellular abundance. Herein, we report on the development of new probes utilizing mesoporous silica nanoparticles (MSNPs) with hydroxyl, amine, or phosphonate functional groups. The phosphonated MSNPs proved to be best at loading lanthanides for up to 1.4 × 106 molecules per particle, and could be loaded with various lanthanide elements (Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb, and Lu) at relatively similar molar extents. The modified MSNPs can also load a fluorescent dye, allowing bimodal mass and fluorescence-based detection. We achieved specificity of antibody-conjugated nanoparticles (at 1.4 × 103 antibodies per nanoparticle) for targeting proteins on the cell surface. The new materials can potentially be used as mass cytometry probes and provide a method for simultaneous monitoring of a large host of factors comprising the tumor microenvironment (e.g., extracellular matrix, cancer cells, and immune cells). These novel probes may also benefit personalized medicine by allowing for high-throughput analysis of multiple proteins in the same specimen. Full article
(This article belongs to the collection Nanoparticles in Therapeutic Applications)
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Open AccessReview Regenerative Medicine: A Review of the Evolution of Autologous Chondrocyte Implantation (ACI) Therapy
Bioengineering 2019, 6(1), 22; https://doi.org/10.3390/bioengineering6010022
Received: 26 February 2019 / Revised: 6 March 2019 / Accepted: 9 March 2019 / Published: 13 March 2019
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Abstract
Articular cartilage is composed of chondrons within a territorial matrix surrounded by a highly organized extracellular matrix comprising collagen II fibrils, proteoglycans, glycosaminoglycans, and non-collagenous proteins. Damaged articular cartilage has a limited potential for healing and untreated defects often progress to osteoarthritis. High [...] Read more.
Articular cartilage is composed of chondrons within a territorial matrix surrounded by a highly organized extracellular matrix comprising collagen II fibrils, proteoglycans, glycosaminoglycans, and non-collagenous proteins. Damaged articular cartilage has a limited potential for healing and untreated defects often progress to osteoarthritis. High hopes have been pinned on regenerative medicine strategies to meet the challenge of preventing progress to late osteoarthritis. One such strategy, autologous chondrocyte implantation (ACI), was first reported in 1994 as a treatment for deep focal articular cartilage defects. ACI has since evolved to become a worldwide well-established surgical technique. For ACI, chondrocytes are harvested from the lesser weight bearing edge of the joint by arthroscopy, their numbers expanded in monolayer culture for at least four weeks, and then re-implanted in the damaged region under a natural or synthetic membrane via an open joint procedure. We consider the evolution of ACI to become an established cell therapy, its current limitations, and on-going strategies to improve its efficacy. The most promising developments involving cells and natural or synthetic biomaterials will be highlighted. Full article
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Open AccessArticle Administration of Adipose Derived Mesenchymal Stem Cells and Platelet Lysate in Erectile Dysfunction: A Single Center Pilot Study
Bioengineering 2019, 6(1), 21; https://doi.org/10.3390/bioengineering6010021
Received: 16 January 2019 / Revised: 26 February 2019 / Accepted: 28 February 2019 / Published: 5 March 2019
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Abstract
Erectile dysfunction (ED) affects more than 30 million men; endothelial dysfunction plays a significant role in EDs pathogenesis. The aim of this study was to administer mesenchymal stem cells (MSC) derived from adipose tissue and platelet lysate (PL) into patients with erectile dysfunction. [...] Read more.
Erectile dysfunction (ED) affects more than 30 million men; endothelial dysfunction plays a significant role in EDs pathogenesis. The aim of this study was to administer mesenchymal stem cells (MSC) derived from adipose tissue and platelet lysate (PL) into patients with erectile dysfunction. This pilot study enrolled eight patients with diagnosed ED. Patients enrolled were suffering from organic ED due to diabetes melitus, hypertension, hypercholesterolaemia, and Peyronie disease. The patients were distributed in 2 groups. Patients in group A received adipose derived mesenchymal stem cells (ADMSC) resuspended in PL while patients in group B received only PL. ADMSCs were isolated from patients’ adipose tissue and expanded. In addition, blood sampling was obtained from the patients in order to isolate platelet lysate. After the application of the above treatments, patients were evaluated with an International Index of Erectile Function (IIEF-5) questionnaire, penile triplex, and reported morning erections. After MSCs and PL administration, patients presented improved erectile function after 1 and 3 months of follow-up. A statistically significant difference was observed in the IIEF-5 score before and after administration of both treatments after the first month (p < 0.05) and the third month (p < 0.05). No statistically significant difference was observed in the IIEF-5 score between group A and B patients. All patients were characterized by improved penile triplex and increased morning erections. No severe adverse reactions were observed in any patient except a minor pain at the site of injection, which was in the limits of tolerability. The results of this study indicated the satisfactory use of MSCs and PL in ED. MSCs in combination with PL or PL alone seems to be very promising, especially without having the negative effects of the current therapeutic treatment. Full article
(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)
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Open AccessOpinion Introducing the Language of “Relativity” for New Scaffold Categorization
Bioengineering 2019, 6(1), 20; https://doi.org/10.3390/bioengineering6010020
Received: 10 January 2019 / Revised: 12 February 2019 / Accepted: 22 February 2019 / Published: 26 February 2019
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Abstract
Research related with scaffold engineering tends to be cross-domain and miscellaneous. Several realms may need to be focused simultaneously, including biomedicine for cell culture and 3D scaffold, physics for dynamics, manufacturing for technologies like 3D printing, chemistry for material composition, as well as [...] Read more.
Research related with scaffold engineering tends to be cross-domain and miscellaneous. Several realms may need to be focused simultaneously, including biomedicine for cell culture and 3D scaffold, physics for dynamics, manufacturing for technologies like 3D printing, chemistry for material composition, as well as architecture for scaffold’s geometric control. As a result, researchers with different backgrounds sometimes could have different understanding towards the product described as ‘Scaffold’. After reviewing the literature, numerous studies termed their developed scaffold as ‘novel’, compared with scaffolds previously designed by others using comparing criterion like ‘research time’, ‘manufacturing method’, ‘geometry’, and so on. While it may have been convenient a decade ago to, for example, categorize scaffold with ‘Dualistic Thinking’ logic into ‘simple-complicated’ or ‘traditional-novel’, this method for categorizing ‘novelty’ and distinguishing scaffold is insufficiently persuasive and precise when it comes to modern or future scaffold. From this departure of philosophical language, namely the language of ‘relativity’, it is important to distinguish between different scaffolds. Other than attempting to avoid ambiguity in perceiving scaffold, this language also provides clarity regarding the ‘evolution stage’ where the focused scaffolds currently stand, where they have been developed, and where in future they could possibly evolve. Full article
(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)
Open AccessArticle A Study of the Biomechanical Behavior of the Implantation Method of Inverted Shoulder Prosthesis (BIO–RSA) under Different Abduction Movements
Bioengineering 2019, 6(1), 19; https://doi.org/10.3390/bioengineering6010019
Received: 19 December 2018 / Revised: 2 February 2019 / Accepted: 6 February 2019 / Published: 19 February 2019
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Abstract
The shoulder is the most mobile joint of the human body, but it is very fragile; several pathologies, and especially muscular degenerations in the elderly, can affect its stability. These are more commonly called rotator cuff fractures. In the case of this type [...] Read more.
The shoulder is the most mobile joint of the human body, but it is very fragile; several pathologies, and especially muscular degenerations in the elderly, can affect its stability. These are more commonly called rotator cuff fractures. In the case of this type of pathology, the mobility of the shoulder decreases and pain appears. In order to restore mobility and reduce pain, implantation of an inverted shoulder prosthesis is recommended. Unfortunately, over time a notch phenomenon has been observed. In the lower position of the arm, part of the implant comes into contact with the scapula and therefore causes deterioration of the bone. Among the solutions adopted is the lateralized method with bone grafting. However, a main disadvantage of this method concerns the reconstruction of the graft in the case of prosthesis revision. In this context, the aim of the present work was to reconstruct the shoulder joint in 3D in order to obtain a bio-faithful geometry, and then study the behavior of different types of biomaterials that can replace bone grafting. To this end, three arm abduction motions were examined for three individuals. From the results obtained, it appears that grafts in ultra-high molecular weight polyethylene (UHMWPE) exhibit a behavior closer to that of bones. Full article
(This article belongs to the Special Issue Engineering Bone-Implant Materials)
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Open AccessReview Cardiac Assist Devices: Early Concepts, Current Technologies, and Future Innovations
Bioengineering 2019, 6(1), 18; https://doi.org/10.3390/bioengineering6010018
Received: 21 December 2018 / Revised: 21 January 2019 / Accepted: 2 February 2019 / Published: 15 February 2019
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Abstract
Congestive heart failure (CHF) is a debilitating condition that afflicts tens of millions of people worldwide and is responsible for more deaths each year than all cancers combined. Because donor hearts for transplantation are in short supply, a safe and durable means of [...] Read more.
Congestive heart failure (CHF) is a debilitating condition that afflicts tens of millions of people worldwide and is responsible for more deaths each year than all cancers combined. Because donor hearts for transplantation are in short supply, a safe and durable means of mechanical circulatory support could extend the lives and reduce the suffering of millions. But while the profusion of blood pumps available to clinicians in 2019 tend to work extremely well in the short term (hours to weeks/months), every long-term cardiac assist device on the market today is limited by the same two problems: infections caused by percutaneous drivelines and thrombotic events associated with the use of blood-contacting surfaces. A fundamental change in device design is needed to address both these problems and ultimately make a device that can support the heart indefinitely. Toward that end, several groups are currently developing devices without blood-contacting surfaces and/or extracorporeal power sources with the aim of providing a safe, tether-free means to support the failing heart over extended periods of time. Full article
(This article belongs to the Special Issue Implantable Medical Devices)
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Open AccessReview Application of Metal Nanoparticle–Hydrogel Composites in Tissue Regeneration
Bioengineering 2019, 6(1), 17; https://doi.org/10.3390/bioengineering6010017
Received: 17 January 2019 / Revised: 31 January 2019 / Accepted: 5 February 2019 / Published: 11 February 2019
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Abstract
Challenges in organ transplantation such as high organ demand and biocompatibility issues have led scientists in the field of tissue engineering and regenerative medicine to work on the use of scaffolds as an alternative to transplantation. Among different types of scaffolds, polymeric hydrogel [...] Read more.
Challenges in organ transplantation such as high organ demand and biocompatibility issues have led scientists in the field of tissue engineering and regenerative medicine to work on the use of scaffolds as an alternative to transplantation. Among different types of scaffolds, polymeric hydrogel scaffolds have received considerable attention because of their biocompatibility and structural similarity to native tissues. However, hydrogel scaffolds have several limitations, such as weak mechanical property and a lack of bioactive property. On the other hand, noble metal particles, particularly gold (Au) and silver (Ag) nanoparticles (NPs), can be incorporated into the hydrogel matrix to form NP–hydrogel composite scaffolds with enhanced physical and biological properties. This review aims to highlight the potential of these hybrid materials in tissue engineering applications. Additionally, the main approaches that have been used for the synthesis of NP–hydrogel composites and the possible limitations and challenges associated with the application of these materials are discussed. Full article
(This article belongs to the Special Issue Noble Metal Functionalized Nanoparticles for Biomedical Applications)
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Open AccessArticle 3D Printing for Bio-Synthetic Biliary Stents
Bioengineering 2019, 6(1), 16; https://doi.org/10.3390/bioengineering6010016
Received: 8 January 2019 / Revised: 5 February 2019 / Accepted: 6 February 2019 / Published: 9 February 2019
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Abstract
Three-dimensional (3D) printing is an additive manufacturing method that holds great potential in a variety of future patient-specific medical technologies. This project validated a novel crosslinked polyvinyl alcohol (XL-PVA) 3D printed stent infused with collagen, human placental mesenchymal stem cells (PMSCs), and cholangiocytes. [...] Read more.
Three-dimensional (3D) printing is an additive manufacturing method that holds great potential in a variety of future patient-specific medical technologies. This project validated a novel crosslinked polyvinyl alcohol (XL-PVA) 3D printed stent infused with collagen, human placental mesenchymal stem cells (PMSCs), and cholangiocytes. The biofabrication method in the present study examined 3D printing and collagen injection molding for rapid prototyping of customized living biliary stents with clinical applications in the setting of malignant and benign bile duct obstructions. XL-PVA stents showed hydrophilic swelling and addition of radiocontrast to the stent matrix improved radiographic opacity. Collagen loaded with PMSCs contracted tightly around hydrophilic stents and dense choloangiocyte coatings were verified through histology and fluorescence microscopy. It is anticipated that design elements used in these stents may enable appropriate stent placement, provide protection of the stent-stem cell matrix against bile constituents, and potentially limit biofilm development. Overall, this approach may allow physicians to create personalized bio-integrating stents for use in biliary procedures and lays a foundation for new patient-specific stent fabrication techniques. Full article
(This article belongs to the Special Issue Bioengineering Liver Transplantation)
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Open AccessArticle Human Neonatal Thymus Mesenchymal Stem/Stromal Cells and Chronic Right Ventricle Pressure Overload
Bioengineering 2019, 6(1), 15; https://doi.org/10.3390/bioengineering6010015
Received: 31 January 2019 / Revised: 5 February 2019 / Accepted: 6 February 2019 / Published: 9 February 2019
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Abstract
Right ventricle (RV) failure secondary to pressure overload is associated with a loss of myocardial capillary density and an increase in oxidative stress. We have previously found that human neonatal thymus mesenchymal stem cells (ntMSCs) promote neovascularization, but the ability of ntMSCs to [...] Read more.
Right ventricle (RV) failure secondary to pressure overload is associated with a loss of myocardial capillary density and an increase in oxidative stress. We have previously found that human neonatal thymus mesenchymal stem cells (ntMSCs) promote neovascularization, but the ability of ntMSCs to express the antioxidant extracellular superoxide dismutase (SOD3) is unknown. We hypothesized that ntMSCs express and secrete SOD3 as well as improve survival in the setting of chronic pressure overload. To evaluate this hypothesis, we compared SOD3 expression in ntMSCs to donor-matched bone-derived MSCs and evaluated the effect of ntMSCs in a rat RV pressure overload model induced by pulmonary artery banding (PAB). The primary outcome was survival, and secondary measures were an echocardiographic assessment of RV size and function as well as histological studies of the RV. We found that ntMSCs expressed SOD3 to a greater degree as compared to bone-derived MSCs. In the PAB model, all ntMSC-treated animals survived to the study endpoint whereas control animals had significantly decreased survival. Treatment animals had significantly less RV fibrosis and increased RV capillary density as compared to controls. We conclude that human ntMSCs demonstrate a therapeutic effect in a model of chronic RV pressure overload, which may in part be due to their antioxidative, antifibrotic, and proangiogenic effects. Given their readily available source, human ntMSCs may be a candidate cell therapy for individuals with congenital heart disease and a pressure-overloaded RV. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cells in Tissue Regeneration)
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Open AccessReview Ear Reconstruction Simulation: From Handcrafting to 3D Printing
Bioengineering 2019, 6(1), 14; https://doi.org/10.3390/bioengineering6010014
Received: 7 December 2018 / Revised: 29 January 2019 / Accepted: 1 February 2019 / Published: 5 February 2019
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Abstract
Microtia is a congenital malformation affecting one in 5000 individuals and is characterized by physical deformity or absence of the outer ear. Nowadays, surgical reconstruction with autologous tissue is the most common clinical practice. The procedure requires a high level of manual and [...] Read more.
Microtia is a congenital malformation affecting one in 5000 individuals and is characterized by physical deformity or absence of the outer ear. Nowadays, surgical reconstruction with autologous tissue is the most common clinical practice. The procedure requires a high level of manual and artistic techniques of a surgeon in carving and sculpting of harvested costal cartilage of the patient to recreate an auricular framework to insert within a skin pocket obtained at the malformed ear region. The aesthetic outcomes of the surgery are highly dependent on the experience of the surgeon performing the surgery. For this reason, surgeons need simulators to acquire adequate technical skills out of the surgery room without compromising the aesthetic appearance of the patient. The current paper aims to describe and analyze the different materials and methods adopted during the history of autologous ear reconstruction (AER) simulation to train surgeons by practice on geometrically and mechanically accurate physical replicas. Recent advances in 3D modelling software and manufacturing technologies to increase the effectiveness of AER simulators are particularly described to provide more recent outcomes. Full article
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Open AccessReview Extracellular Vesicles from the Protozoa Acanthamoeba castellanii: Their Role in Pathogenesis, Environmental Adaptation and Potential Applications
Bioengineering 2019, 6(1), 13; https://doi.org/10.3390/bioengineering6010013
Received: 7 December 2018 / Revised: 22 January 2019 / Accepted: 26 January 2019 / Published: 1 February 2019
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Abstract
Extracellular vesicles (EVs) are membranous compartments of distinct cellular origin and biogenesis, displaying different sizes and include exosomes, microvesicles, and apoptotic bodies. The EVs have been described in almost every living organism, from simple unicellular to higher evolutionary scale multicellular organisms, such as [...] Read more.
Extracellular vesicles (EVs) are membranous compartments of distinct cellular origin and biogenesis, displaying different sizes and include exosomes, microvesicles, and apoptotic bodies. The EVs have been described in almost every living organism, from simple unicellular to higher evolutionary scale multicellular organisms, such as mammals. Several functions have been attributed to these structures, including roles in energy acquisition, cell-to-cell communication, gene expression modulation and pathogenesis. In this review, we described several aspects of the recently characterized EVs of the protozoa Acanthamoeba castellanii, a free-living amoeba (FLA) of emerging epidemiological importance, and compare their features to other parasites’ EVs. These A. castellanii EVs are comprised of small microvesicles and exosomes and carry a wide range of molecules involved in many biological processes like cell signaling, carbohydrate metabolism and proteolytic activity, such as kinases, glucanases, and proteases, respectively. Several biomedical applications of these EVs have been proposed lately, including their use in vaccination, biofuel production, and the pharmaceutical industry, such as platforms for drug delivery. Full article
(This article belongs to the Special Issue Extracellular Vesicles: From Biology to Biomedical Applications)
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Open AccessArticle Biomass Grinding Process Optimization Using Response Surface Methodology and a Hybrid Genetic Algorithm
Bioengineering 2019, 6(1), 12; https://doi.org/10.3390/bioengineering6010012
Received: 23 December 2018 / Revised: 19 January 2019 / Accepted: 21 January 2019 / Published: 25 January 2019
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Abstract
Biomass could be a key source of renewable energy. Agricultural waste products, such as corn stover, provide a convenient means to replace fossil fuels, such as coal, and a large amount of feedstock is currently available for energy consumption in the U.S. This [...] Read more.
Biomass could be a key source of renewable energy. Agricultural waste products, such as corn stover, provide a convenient means to replace fossil fuels, such as coal, and a large amount of feedstock is currently available for energy consumption in the U.S. This study has two main objectives: (1) to understand the impact of corn stover moisture content and grinder speed on grind physical properties; and (2) develop response surface models and optimize these models using a hybrid genetic algorithm. The response surface models developed were used to draw surface plots to understand the interaction effects of the corn stover grind moisture content and grinder speed on the grind physical properties and specific energy consumption. The surface plots indicated that a higher corn stover grind moisture content and grinder speed had a positive effect on the bulk and tapped density. The final grind moisture content was highly influenced by the initial moisture content of the corn stover grind. Optimization of the response surface models using the hybrid genetic algorithm indicated that moisture content in the range of 17 to 19% (w.b.) and a grinder speed of 47 to 49 Hz maximized the bulk and tapped density and minimized the geomantic mean particle length. The specific energy consumption was minimized when the grinder speed was about 20 Hz and the corn stover grind moisture content was about 10% (w.b.). Full article
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Open AccessArticle Looking for A Place for Dose-Dense TMZ Regimens in GBM Patients: An Experience with MGMT Exploratory Evaluation
Bioengineering 2019, 6(1), 11; https://doi.org/10.3390/bioengineering6010011
Received: 18 December 2018 / Revised: 19 January 2019 / Accepted: 21 January 2019 / Published: 22 January 2019
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Abstract
Prolonged exposure to temozolomide (TMZ) could improve clinical outcomes in recurrent glioblastoma multiforme (GBM) patients. We previously developed a dose-dense regimen of TMZ in a phase II study (180 mg/m2 from days 1 to 5 every two weeks). A retrospective analysis of [...] Read more.
Prolonged exposure to temozolomide (TMZ) could improve clinical outcomes in recurrent glioblastoma multiforme (GBM) patients. We previously developed a dose-dense regimen of TMZ in a phase II study (180 mg/m2 from days 1 to 5 every two weeks). A retrospective analysis of patients with macroscopic residual GBM treated with “post-induction” dose-dense TMZ was conducted, adding an explorative subgroup analyses among patients with different O6-methylguanine DNA methyltransferase (MGMT) expressions (negative vs positive, < vs ≥ of 50 % of cells stained, < vs ≥ 70% of cells stained). Thirty-six patients were evaluated; after a median follow-up of 36 weeks, median Progression Free Survival (PFS) and median Overall Survival (OS) were 19 and 34 weeks, respectively. MGMT expression (70% cut-off) and sex were confirmed as independent predictors for disease control rate (DCR) at multivariate analysis. At univariate analysis ECOG-PS, Sex (female), extensive tumor resection was shown to be related to a longer PFS, while MGMT expression (cut-off 70%) to a shorter PFS. Multivariate analysis with Cox hazard regression confirmed only ECOG-PS as an independent predictor for PFS. ECOG-PS showed to be significant related to a longer OS. Our analysis showed that dose-dense TMZ regimens are still an option for patients with recurrent GBM, but should be used for re-challenge treatments. MGMT immunohistochemistry high expression might be used as a “surrogate” negative predictor for DCR for dd-TMZ treatments. Full article
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Open AccessReview Noble Metal Nanoparticles Applications: Recent Trends in Food Control
Bioengineering 2019, 6(1), 10; https://doi.org/10.3390/bioengineering6010010
Received: 14 December 2018 / Revised: 15 January 2019 / Accepted: 19 January 2019 / Published: 21 January 2019
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Abstract
Scientific research in the nanomaterials field is constantly evolving, making it possible to develop new materials and above all to find new applications. Therefore, nanoparticles (NPs) are suitable for different applications: nanomedicine, drug delivery, sensors, optoelectronics and food control. This review explores the [...] Read more.
Scientific research in the nanomaterials field is constantly evolving, making it possible to develop new materials and above all to find new applications. Therefore, nanoparticles (NPs) are suitable for different applications: nanomedicine, drug delivery, sensors, optoelectronics and food control. This review explores the recent trend in food control of using noble metallic nanoparticles as determination tools. Two major uses of NPs in food control have been found: the determination of contaminants and bioactive compounds. Applications were found for the determination of mycotoxins, pesticides, drug residues, allergens, probable carcinogenic compounds, bacteria, amino acids, gluten and antioxidants. The new developed methods are competitive for their use in food control, demonstrated by their validation and application to real samples. Full article
(This article belongs to the Special Issue Noble Metal Functionalized Nanoparticles for Biomedical Applications)
Open AccessReview Brain Organoids—A Bottom-Up Approach for Studying Human Neurodevelopment
Bioengineering 2019, 6(1), 9; https://doi.org/10.3390/bioengineering6010009
Received: 28 November 2018 / Revised: 8 January 2019 / Accepted: 11 January 2019 / Published: 18 January 2019
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Abstract
Brain organoids have recently emerged as a three-dimensional tissue culture platform to study the principles of neurodevelopment and morphogenesis. Importantly, brain organoids can be derived from human stem cells, and thus offer a model system for early human brain development and human specific [...] Read more.
Brain organoids have recently emerged as a three-dimensional tissue culture platform to study the principles of neurodevelopment and morphogenesis. Importantly, brain organoids can be derived from human stem cells, and thus offer a model system for early human brain development and human specific disorders. However, there are still major differences between the in vitro systems and in vivo development. This is in part due to the challenge of engineering a suitable culture platform that will support proper development. In this review, we discuss the similarities and differences of human brain organoid systems in comparison to embryonic development. We then describe how organoids are used to model neurodevelopmental diseases. Finally, we describe challenges in organoid systems and how to approach these challenges using complementary bioengineering techniques. Full article
(This article belongs to the Special Issue Organs-on-Chips)
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Open AccessArticle Characterization of Plasma-Derived Extracellular Vesicles Isolated by Different Methods: A Comparison Study
Bioengineering 2019, 6(1), 8; https://doi.org/10.3390/bioengineering6010008
Received: 30 November 2018 / Revised: 8 January 2019 / Accepted: 11 January 2019 / Published: 17 January 2019
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Abstract
Extracellular vesicles (EV) are small membrane structures released by cells that act as potent mediators of intercellular communication. The study of EV biology is important, not only to strengthen our knowledge of their physiological roles, but also to better understand their involvement in [...] Read more.
Extracellular vesicles (EV) are small membrane structures released by cells that act as potent mediators of intercellular communication. The study of EV biology is important, not only to strengthen our knowledge of their physiological roles, but also to better understand their involvement in several diseases. In the field of biomedicine they have been studied as a novel source of biomarkers and drug delivery vehicles. The most commonly used method for EV enrichment in crude pellet involves serial centrifugation and ultracentrifugation. Recently, different protocols and techniques have been developed to isolate EV that imply less time and greater purification. Here we carry out a comparative analysis of three methods to enrich EV from plasma of healthy controls: ultracentrifugation, ExoQuickTM precipitation solution (System Biosciences), and Total Exosome Isolation kit (Invitrogen). Our results show that commercial precipitation reagents are more efficient and enable higher EV enrichment factors compared with traditional ultracentrifugation, although subsequent imaging analysis is not possible with some of them. We hope that this work will contribute to the current research on isolation techniques to assist the progress of clinical applications with diagnostic or therapeutic objectives. Full article
(This article belongs to the Special Issue Extracellular Vesicles: From Biology to Biomedical Applications)
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Open AccessReview Extracellular Vesicle Quantification and Characterization: Common Methods and Emerging Approaches
Bioengineering 2019, 6(1), 7; https://doi.org/10.3390/bioengineering6010007
Received: 23 December 2018 / Revised: 14 January 2019 / Accepted: 15 January 2019 / Published: 16 January 2019
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Abstract
Extracellular vesicles (EVs) are a family of small membrane vesicles that carry information about cells by which they are secreted. Growing interest in the role of EVs in intercellular communication, but also in using their diagnostic, prognostic and therapeutic potential in (bio) medical [...] Read more.
Extracellular vesicles (EVs) are a family of small membrane vesicles that carry information about cells by which they are secreted. Growing interest in the role of EVs in intercellular communication, but also in using their diagnostic, prognostic and therapeutic potential in (bio) medical applications, demands for accurate assessment of their biochemical and physical properties. In this review, we provide an overview of available technologies for EV analysis by describing their working principles, assessing their utility in EV research and summarising their potential and limitations. To emphasise the innovations in EV analysis, we also highlight the unique possibilities of emerging technologies with high potential for further development. Full article
(This article belongs to the Special Issue Extracellular Vesicles: From Biology to Biomedical Applications)
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Open AccessEditorial Acknowledgement to Reviewers of Bioengineering in 2018
Bioengineering 2019, 6(1), 6; https://doi.org/10.3390/bioengineering6010006
Published: 14 January 2019
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Abstract
Rigorous peer-review is the corner-stone of high-quality academic publishing [...] Full article
Open AccessReview Mobile Microfluidics
Bioengineering 2019, 6(1), 5; https://doi.org/10.3390/bioengineering6010005
Received: 18 November 2018 / Revised: 22 December 2018 / Accepted: 24 December 2018 / Published: 3 January 2019
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Abstract
Microfluidics platforms can program small amounts of fluids to execute a bio-protocol, and thus, can automate the work of a technician and also integrate a large part of laboratory equipment. Although most microfluidic systems have considerably reduced the size of a laboratory, they [...] Read more.
Microfluidics platforms can program small amounts of fluids to execute a bio-protocol, and thus, can automate the work of a technician and also integrate a large part of laboratory equipment. Although most microfluidic systems have considerably reduced the size of a laboratory, they are still benchtop units, of a size comparable to a desktop computer. In this paper, we argue that achieving true mobility in microfluidics would revolutionize the domain by making laboratory services accessible during traveling or even in daily situations, such as sport and outdoor activities. We review the existing efforts to achieve mobility in microfluidics, and we discuss the conditions mobile biochips need to satisfy. In particular, we show how we adapted an existing biochip for mobile use, and we present the results when using it during a train ride. Based on these results and our systematic discussion, we identify the challenges that need to be overcome at technical, usability and social levels. In analogy to the history of computing, we make some predictions on the future of mobile biochips. In our vision, mobile biochips will disrupt how people interact with a wide range of healthcare processes, including medical testing and synthesis of on-demand medicine. Full article
(This article belongs to the Special Issue Frontiers of Microfluidics in Biology)
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Open AccessReview Stem Cell Extracellular Vesicles in Skin Repair
Bioengineering 2019, 6(1), 4; https://doi.org/10.3390/bioengineering6010004
Received: 30 November 2018 / Revised: 19 December 2018 / Accepted: 25 December 2018 / Published: 30 December 2018
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Abstract
Stem cell extracellular vesicles (EVs) have been widely studied because of their excellent therapeutic potential. EVs from different types of stem cell can improve vascularization as well as aid in the treatment of cancer and neurodegenerative diseases. The skin is a complex organ [...] Read more.
Stem cell extracellular vesicles (EVs) have been widely studied because of their excellent therapeutic potential. EVs from different types of stem cell can improve vascularization as well as aid in the treatment of cancer and neurodegenerative diseases. The skin is a complex organ that is susceptible to various types of injury. Strategies designed to restore epithelial tissues’ integrity with stem cell EVs have shown promising results. Different populations of stem cell EVs are able to control inflammation, accelerate skin cell migration and proliferation, control wound scarring, improve angiogenesis, and even ameliorate signs of skin aging. However, large-scale production of such stem cell EVs for human therapy is still a challenge. This review focuses on recent studies that explore the potential of stem cell EVs in skin wound healing and skin rejuvenation, as well as challenges of their use in therapy. Full article
(This article belongs to the Special Issue Extracellular Vesicles: From Biology to Biomedical Applications)
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Open AccessCommunication Optimization of Decellularization Procedure in Rat Esophagus for Possible Development of a Tissue Engineered Construct
Bioengineering 2019, 6(1), 3; https://doi.org/10.3390/bioengineering6010003
Received: 5 December 2018 / Revised: 19 December 2018 / Accepted: 20 December 2018 / Published: 24 December 2018
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Abstract
Background: Current esophageal treatment is associated with significant morbidity. The gold standard therapeutic strategies are stomach interposition or autografts derived from the jejunum and colon. However, severe adverse reactions, such as esophageal leakage, stenosis and infection, accompany the above treatments, which, most times, [...] Read more.
Background: Current esophageal treatment is associated with significant morbidity. The gold standard therapeutic strategies are stomach interposition or autografts derived from the jejunum and colon. However, severe adverse reactions, such as esophageal leakage, stenosis and infection, accompany the above treatments, which, most times, are life threating. The aim of this study was the optimization of a decellularization protocol in order to develop a proper esophageal tissue engineered construct. Methods: Rat esophagi were obtained from animals and were decellularized. The decellularization process involved the use of 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) and sodium dodecyl sulfate (SDS) buffers for 6 h each, followed by incubation in a serum medium. The whole process involved two decellularization cycles. Then, a histological analysis was performed. In addition, the amounts of collagen, sulphated glycosaminoglycans and DNA content were quantified. Results: The histological analysis revealed that only the first decellularization cycle was enough to produce a cellular and nuclei free esophageal scaffold with a proper extracellular matrix orientation. These results were further confirmed by biochemical quantification. Conclusions: Based on the above results, the current decellularization protocol can be applied successfully in order to produce an esophageal tissue engineered construct. Full article
(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)
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Open AccessArticle Feature Extraction of Shoulder Joint’s Voluntary Flexion-Extension Movement Based on Electroencephalography Signals for Power Assistance
Bioengineering 2019, 6(1), 2; https://doi.org/10.3390/bioengineering6010002
Received: 16 November 2018 / Revised: 19 December 2018 / Accepted: 20 December 2018 / Published: 24 December 2018
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Abstract
Brain-Machine Interface (BMI) has been considered as an effective way to help and support both the disabled rehabilitation and healthy individuals’ daily lives to use their brain activity information instead of their bodies. In order to reduce costs and control exoskeleton robots better, [...] Read more.
Brain-Machine Interface (BMI) has been considered as an effective way to help and support both the disabled rehabilitation and healthy individuals’ daily lives to use their brain activity information instead of their bodies. In order to reduce costs and control exoskeleton robots better, we aim to estimate the necessary torque information for a subject from his/her electroencephalography (EEG) signals when using an exoskeleton robot to perform the power assistance of the upper limb without using external torque sensors nor electromyography (EMG) sensors. In this paper, we focus on extracting the motion-relevant EEG signals’ features of the shoulder joint, which is the most complex joint in the human’s body, to construct a power assistance system using wearable upper limb exoskeleton robots with BMI technology. We extract the characteristic EEG signals when the shoulder joint is doing flexion and extension movement freely which are the main motions of the shoulder joint needed to be assisted. Independent component analysis (ICA) is used to extract the source information of neural components, and then the average method is used to extract the characteristic signals that are fundamental to achieve the control. The proposed approach has been experimentally verified. The results show that EEG signals begin to increase at 300–400 ms before the motion and then decrease at the beginning of the generation of EMG signals, and the peaks appear at about one second after the motion. At the same time, we also confirmed the relationship between the change of EMG signals and the EEG signals on the time dimension, and these results also provide a theoretical basis for the delay parameter in the linear model which will be used to estimate the necessary torque information in future. Our results suggest that the estimation of torque information based on EEG signals is feasible, and demonstrate the potential of using EEG signals via the control of brain-machine interface to support human activities continuously. Full article
(This article belongs to the Special Issue Biosignal Processing)
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Open AccessArticle A Three-Compartment Pharmacokinetic Model to Predict the Interstitial Concentration of Talaporfin Sodium in the Myocardium for Photodynamic Therapy: A Method Combining Measured Fluorescence and Analysis of the Compartmental Origin of the Fluorescence
Bioengineering 2019, 6(1), 1; https://doi.org/10.3390/bioengineering6010001
Received: 14 November 2018 / Revised: 10 December 2018 / Accepted: 19 December 2018 / Published: 21 December 2018
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Abstract
To evaluate the effectiveness of photodynamic therapy occurring in the interstitial space of the myocardium, we estimated the interstitial concentration of talaporfin sodium in the canine myocardium by constructing a three-compartment pharmacokinetic model based on measured changes in talaporfin sodium plasma concentration and [...] Read more.
To evaluate the effectiveness of photodynamic therapy occurring in the interstitial space of the myocardium, we estimated the interstitial concentration of talaporfin sodium in the canine myocardium by constructing a three-compartment pharmacokinetic model based on measured changes in talaporfin sodium plasma concentration and myocardial fluorescence. Differential rate equations of talaporfin sodium concentration in the plasma, interstitial space, and cell compartment were developed with individual compartment volume, concentration, and rate constants. Using measured volume ratios based on histological examinations, we defined that the myocardial fluorescence consisted of the linear addition of fluorescence generated from these three compartments. The rate constants were obtained by fitting to minimize the sum of the squared errors between the measured talaporfin sodium concentrations and the calculated concentrations divided by the number of data points using the conjugate gradient method in MATLAB. We confirmed that this fitting operation may be appropriate, because a coefficient of determination between the measured talaporfin sodium changes and the calculated concentrations using our equations was 0.99. Consequently, to estimate the interstitial concentration in the canine myocardium, we propose a three-compartment pharmacokinetic model construction methodology using measured changes in talaporfin sodium plasma concentration and changes in myocardial fluorescence. Full article
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