Bioengineering

27 pages, 7176 KiB

Open AccessEditor’s ChoiceArticle

Helmet Radio Frequency Phased Array Applicators Enhance Thermal Magnetic Resonance of Brain Tumors

by Faezeh Rahimi, Bilguun Nurzed, Thomas W. Eigentler, Mostafa Berangi, Eva Oberacker, Andre Kuehne, Pirus Ghadjar, Jason M. Millward, Rolf Schuhmann and Thoralf Niendorf

Bioengineering 2024, 11(7), 733; https://doi.org/10.3390/bioengineering11070733 - 19 Jul 2024

Viewed by 928

Abstract

Thermal Magnetic Resonance (ThermalMR) integrates Magnetic Resonance Imaging (MRI) diagnostics and targeted radio-frequency (RF) heating in a single theranostic device. The requirements for MRI (magnetic field) and targeted RF heating (electric field) govern the design of ThermalMR applicators. We hypothesize that helmet RF [...] Read more.

Thermal Magnetic Resonance (ThermalMR) integrates Magnetic Resonance Imaging (MRI) diagnostics and targeted radio-frequency (RF) heating in a single theranostic device. The requirements for MRI (magnetic field) and targeted RF heating (electric field) govern the design of ThermalMR applicators. We hypothesize that helmet RF applicators (HPA) improve the efficacy of ThermalMR of brain tumors versus an annular phased RF array (APA). An HPA was designed using eight broadband self-grounded bow-tie (SGBT) antennae plus two SGBTs placed on top of the head. An APA of 10 equally spaced SGBTs was used as a reference. Electromagnetic field (EMF) simulations were performed for a test object (phantom) and a human head model. For a clinical scenario, the head model was modified with a tumor volume obtained from a patient with glioblastoma multiforme. To assess performance, we introduced multi-target evaluation (MTE) to ensure whole-brain slice accessibility. We implemented time multiplexed vector field shaping to optimize RF excitation. Our EMF and temperature simulations demonstrate that the HPA improves performance criteria critical to MRI and enhances targeted RF and temperature focusing versus the APA. Our findings are a foundation for the experimental implementation and application of a HPA en route to ThermalMR of brain tumors. Full article

(This article belongs to the Special Issue Advances in Thermal Therapy)

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13 pages, 4398 KiB

Open AccessEditor’s ChoiceArticle

Fabrication and Evaluation of PCL/PLGA/β-TCP Spiral-Structured Scaffolds for Bone Tissue Engineering

by Weiwei Wang, Xiaqing Zhou, Haoyu Wang, Gan Zhou and Xiaojun Yu

Bioengineering 2024, 11(7), 732; https://doi.org/10.3390/bioengineering11070732 - 19 Jul 2024

Viewed by 809

Abstract

Natural bone is a complex material that has been carefully designed. To prepare a successful bone substitute, two challenging conditions need to be met: biocompatible and bioactive materials for cell proliferation and differentiation, and appropriate mechanical stability after implantation. Therefore, a hybrid Poly [...] Read more.

Natural bone is a complex material that has been carefully designed. To prepare a successful bone substitute, two challenging conditions need to be met: biocompatible and bioactive materials for cell proliferation and differentiation, and appropriate mechanical stability after implantation. Therefore, a hybrid Poly ε-caprolactone/Poly(lactic-co-glycolide)/β-tricalcium phosphate (PCL/PLGA/β-TCP) scaffold has been introduced as a suitable composition that satisfies the above two conditions. The blended PCL and PLGA can improve the scaffold’s mechanical properties and biocompatibility compared to single PCL or PLGA scaffolds. In addition, the incorporated β-TCP increases the mechanical strength and osteogenic potential of PCL/PLGA scaffolds, while the polymer improves the mechanical stability of ceramic scaffolds. The PCL/PLGA/β-TCP scaffold is designed using spiral structures to provide a much better transport system through the gaps between spiral walls than conventional cylindrical scaffolds. Human fetal osteoblasts (hFOBs) were cultured on spiral PCL/PLGA/β-TCP (PPBS), cylindrical PCL/PLGA/β-TCP (PPBC), and cylindrical PCL scaffolds for a total of 28 days. The cell proliferation, viability, and osteogenic differentiation capabilities were analyzed. Compared with PCL and PPBC scaffolds, the PPBS scaffold exhibits great biocompatibility and potential to stimulate cell proliferation and differentiation and, therefore, can serve as a bone substitute for bone tissue regeneration. Full article

(This article belongs to the Special Issue Biomaterial Scaffolds for Tissue Engineering)

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22 pages, 4120 KiB

Open AccessEditor’s ChoiceArticle

Three-Dimensionally Printed Agarose Micromold Supports Scaffold-Free Mouse Ex Vivo Follicle Growth, Ovulation, and Luteinization

by Emily J. Zaniker, Prianka H. Hashim, Samuel Gauthier, James A. Ankrum, Hannes Campo and Francesca E. Duncan

Bioengineering 2024, 11(7), 719; https://doi.org/10.3390/bioengineering11070719 - 15 Jul 2024

Viewed by 3472

Abstract

Ex vivo follicle growth is an essential tool, enabling interrogation of folliculogenesis, ovulation, and luteinization. Though significant advancements have been made, existing follicle culture strategies can be technically challenging and laborious. In this study, we advanced the field through development of a custom [...] Read more.

Ex vivo follicle growth is an essential tool, enabling interrogation of folliculogenesis, ovulation, and luteinization. Though significant advancements have been made, existing follicle culture strategies can be technically challenging and laborious. In this study, we advanced the field through development of a custom agarose micromold, which enables scaffold-free follicle culture. We established an accessible and economical manufacturing method using 3D printing and silicone molding that generates biocompatible hydrogel molds without the risk of cytotoxicity from leachates. Each mold supports simultaneous culture of multiple multilayer secondary follicles in a single focal plane, allowing for constant timelapse monitoring and automated analysis. Mouse follicles cultured using this novel system exhibit significantly improved growth and ovulation outcomes with comparable survival, oocyte maturation, and hormone production profiles as established three-dimensional encapsulated in vitro follicle growth (eIVFG) systems. Additionally, follicles recapitulated aspects of in vivo ovulation physiology with respect to their architecture and spatial polarization, which has not been observed in eIVFG systems. This system offers simplicity, scalability, integration with morphokinetic analyses of follicle growth and ovulation, and compatibility with existing microphysiological platforms. This culture strategy has implications for fundamental follicle biology, fertility preservation strategies, reproductive toxicology, and contraceptive drug discovery. Full article

(This article belongs to the Special Issue Bioengineering Technologies to Advance Reproductive Health)

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10 pages, 225 KiB

Open AccessEditor’s ChoiceCommentary

Bridging the Gap: Integrating 3D Bioprinting and Microfluidics for Advanced Multi-Organ Models in Biomedical Research

by Marco De Spirito, Valentina Palmieri, Giordano Perini and Massimiliano Papi

Bioengineering 2024, 11(7), 664; https://doi.org/10.3390/bioengineering11070664 - 28 Jun 2024

Viewed by 775

Abstract

Recent advancements in 3D bioprinting and microfluidic lab-on-chip systems offer promising solutions to the limitations of traditional animal models in biomedical research. Three-dimensional bioprinting enables the creation of complex, patient-specific tissue models that mimic human physiology more accurately than animal models. These 3D [...] Read more.

Recent advancements in 3D bioprinting and microfluidic lab-on-chip systems offer promising solutions to the limitations of traditional animal models in biomedical research. Three-dimensional bioprinting enables the creation of complex, patient-specific tissue models that mimic human physiology more accurately than animal models. These 3D bioprinted tissues, when integrated with microfluidic systems, can replicate the dynamic environment of the human body, allowing for the development of multi-organ models. This integration facilitates more precise drug screening and personalized therapy development by simulating interactions between different organ systems. Such innovations not only improve predictive accuracy but also address ethical concerns associated with animal testing, aligning with the three Rs principle. Future directions include enhancing bioprinting resolution, developing advanced bioinks, and incorporating AI for optimized system design. These technologies hold the potential to revolutionize drug development, regenerative medicine, and disease modeling, leading to more effective, personalized, and humane treatments. Full article

(This article belongs to the Section Biomedical Engineering and Biomaterials)

20 pages, 3488 KiB

Open AccessEditor’s ChoiceReview

Digital Twins for Healthcare Using Wearables

by Zachary Johnson and Manob Jyoti Saikia

Bioengineering 2024, 11(6), 606; https://doi.org/10.3390/bioengineering11060606 - 13 Jun 2024

Viewed by 1924

Abstract

Digital twins are a relatively new form of digital modeling that has been gaining popularity in recent years. This is in large part due to their ability to update in real time to their physical counterparts and connect across multiple devices. As a [...] Read more.

Digital twins are a relatively new form of digital modeling that has been gaining popularity in recent years. This is in large part due to their ability to update in real time to their physical counterparts and connect across multiple devices. As a result, much interest has been directed towards using digital twins in the healthcare industry. Recent advancements in smart wearable technologies have allowed for the utilization of human digital twins in healthcare. Human digital twins can be generated using biometric data from the patient gathered from wearables. These data can then be used to enhance patient care through a variety of means, such as simulated clinical trials, disease prediction, and monitoring treatment progression remotely. This revolutionary method of patient care is still in its infancy, and as such, there is limited research on using wearables to generate human digital twins for healthcare applications. This paper reviews the literature pertaining to human digital twins, including methods, applications, and challenges. The paper also presents a conceptual method for creating human body digital twins using wearable sensors. Full article

(This article belongs to the Special Issue Wearable Sensors and Measurement Systems for Human Physiology Monitoring)

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13 pages, 2959 KiB

Open AccessEditor’s ChoiceReview

Alexander Friedenstein, Mesenchymal Stem Cells, Shifting Paradigms and Euphemisms

by Donald G. Phinney

Bioengineering 2024, 11(6), 534; https://doi.org/10.3390/bioengineering11060534 - 23 May 2024

Viewed by 971

Abstract

Six decades ago, Friedenstein and coworkers published a series of seminal papers identifying a cell population in bone marrow with osteogenic potential, now referred to as mesenchymal stem cells (MSCs). This work was also instrumental in establishing the identity of hematopoietic stem cell [...] Read more.

Six decades ago, Friedenstein and coworkers published a series of seminal papers identifying a cell population in bone marrow with osteogenic potential, now referred to as mesenchymal stem cells (MSCs). This work was also instrumental in establishing the identity of hematopoietic stem cell and the identification of skeletal stem/progenitor cell (SSPC) populations in various skeletal compartments. In recognition of the centenary year of Friedenstein’s birth, I review key aspects of his work and discuss the evolving concept of the MSC and its various euphemisms indorsed by changing paradigms in the field. I also discuss the recent emphasis on MSC stromal quality attributes and how emerging data demonstrating a mechanistic link between stromal and stem/progenitor functions bring renewed relevance to Friedenstein’s contributions and much needed unity to the field. Full article

(This article belongs to the Special Issue A Tribute to Professor Alexander Friedenstein and His Outstanding Achievements in the Area of Stromal Stem Cells)

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16 pages, 1572 KiB

Open AccessEditor’s ChoiceReview

Where Does Auto-Segmentation for Brain Metastases Radiosurgery Stand Today?

by Matthew Kim, Jen-Yeu Wang, Weiguo Lu, Hao Jiang, Strahinja Stojadinovic, Zabi Wardak, Tu Dan, Robert Timmerman, Lei Wang, Cynthia Chuang, Gregory Szalkowski, Lianli Liu, Erqi Pollom, Elham Rahimy, Scott Soltys, Mingli Chen and Xuejun Gu

Bioengineering 2024, 11(5), 454; https://doi.org/10.3390/bioengineering11050454 - 3 May 2024

Viewed by 1401

Abstract

Detection and segmentation of brain metastases (BMs) play a pivotal role in diagnosis, treatment planning, and follow-up evaluations for effective BM management. Given the rising prevalence of BM cases and its predominantly multiple onsets, automated segmentation is becoming necessary in stereotactic radiosurgery. It [...] Read more.

Detection and segmentation of brain metastases (BMs) play a pivotal role in diagnosis, treatment planning, and follow-up evaluations for effective BM management. Given the rising prevalence of BM cases and its predominantly multiple onsets, automated segmentation is becoming necessary in stereotactic radiosurgery. It not only alleviates the clinician’s manual workload and improves clinical workflow efficiency but also ensures treatment safety, ultimately improving patient care. Recent strides in machine learning, particularly in deep learning (DL), have revolutionized medical image segmentation, achieving state-of-the-art results. This review aims to analyze auto-segmentation strategies, characterize the utilized data, and assess the performance of cutting-edge BM segmentation methodologies. Additionally, we delve into the challenges confronting BM segmentation and share insights gleaned from our algorithmic and clinical implementation experiences. Full article

(This article belongs to the Special Issue Artificial Intelligence in Biomedical Diagnosis and Prognosis)

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14 pages, 2236 KiB

Open AccessEditor’s ChoiceArticle

Polyhydroxyalkanoate Copolymer Production by Recombinant Ralstonia eutropha Strain 1F2 from Fructose or Carbon Dioxide as Sole Carbon Source

by Chih-Ting Wang, Ramamoorthi M Sivashankari, Yuki Miyahara and Takeharu Tsuge

Bioengineering 2024, 11(5), 455; https://doi.org/10.3390/bioengineering11050455 - 2 May 2024

Cited by 1 | Viewed by 1480

Abstract

Ralstonia eutropha strain H16 is a chemoautotrophic bacterium that oxidizes hydrogen and accumulates poly[(R)-3-hydroxybutyrate] [P(3HB)], a prominent polyhydroxyalkanoate (PHA), within its cell. R. eutropha utilizes fructose or CO₂ as its sole carbon source for this process. A PHA-negative mutant of [...] Read more.

Ralstonia eutropha strain H16 is a chemoautotrophic bacterium that oxidizes hydrogen and accumulates poly[(R)-3-hydroxybutyrate] [P(3HB)], a prominent polyhydroxyalkanoate (PHA), within its cell. R. eutropha utilizes fructose or CO₂ as its sole carbon source for this process. A PHA-negative mutant of strain H16, known as R. eutropha strain PHB⁻4, cannot produce PHA. Strain 1F2, derived from strain PHB⁻4, is a leucine analog-resistant mutant. Remarkably, the recombinant 1F2 strain exhibits the capacity to synthesize 3HB-based PHA copolymers containing 3-hydroxyvalerate (3HV) and 3-hydroxy-4-methyvalerate (3H4MV) comonomer units from fructose or CO_2. This ability is conferred by the expression of a broad substrate-specific PHA synthase and tolerance to feedback inhibition of branched amino acids. However, the total amount of comonomer units incorporated into PHA was up to around 5 mol%. In this study, strain 1F2 underwent genetic engineering to augment the comonomer supply incorporated into PHA. This enhancement involved several modifications, including the additional expression of the broad substrate-specific 3-ketothiolase gene (bktB), the heterologous expression of the 2-ketoacid decarboxylase gene (kivd), and the phenylacetaldehyde dehydrogenase gene (padA). Furthermore, the genome of strain 1F2 was altered through the deletion of the 3-hydroxyacyl-CoA dehydrogenase gene (hbdH). The introduction of bktB-kivd-padA resulted in increased 3HV incorporation, reaching 13.9 mol% from fructose and 6.4 mol% from CO₂. Additionally, the hbdH deletion resulted in the production of PHA copolymers containing (S)-3-hydroxy-2-methylpropionate (3H2MP). Interestingly, hbdH deletion increased the weight-average molecular weight of the PHA to over 3.0 × 10⁶ on fructose. Thus, it demonstrates the positive effects of hbdH deletion on the copolymer composition and molecular weight of PHA. Full article

(This article belongs to the Special Issue Advances in Polyhydroxyalkanoate (PHA) Production, 4th Edition)

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17 pages, 3345 KiB

Open AccessEditor’s ChoiceArticle

Predictive Refined Computational Modeling of ACL Tear Injury Patterns

by Mirit Sharabi, Raz Agron, Amir Dolev, Rami Haj-Ali and Mustafa Yassin

Bioengineering 2024, 11(5), 413; https://doi.org/10.3390/bioengineering11050413 - 23 Apr 2024

Viewed by 1320

Abstract

Anterior cruciate ligament (ACL) ruptures are prevalent knee injuries, with approximately 200,000 ruptures annually, and treatment costs exceed USD two billion in the United States alone. Typically, the initial detection of ACL tears and anterior tibial laxity (ATL) involves manual assessments like the [...] Read more.

Anterior cruciate ligament (ACL) ruptures are prevalent knee injuries, with approximately 200,000 ruptures annually, and treatment costs exceed USD two billion in the United States alone. Typically, the initial detection of ACL tears and anterior tibial laxity (ATL) involves manual assessments like the Lachman test, which examines anterior knee laxity. Partial ACL tears can go unnoticed if they minimally affect knee laxity; however, they will progress to a complete ACL tear requiring surgical treatment. In this study, a computational finite element model (FEM) of the knee joint was generated to investigate the effect of partial ACL tears under the Lachman test (GNRB^® testing system) boundary conditions. The ACL was modeled as a hyperelastic composite structure with a refined representation of collagen bundles. Five different tear types (I–V), classified by location and size, were modeled to predict the relationship between tear size, location, and anterior tibial translation (ATT). The results demonstrated different levels of ATT that could not be manually detected. Type I tears demonstrated an almost linear increase in ATT, with the growth in tear size ranging from 3.7 mm to 4.2 mm, from 25% to 85%, respectively. Type II partial tears showed a less linear incline in ATT (3.85, 4.1, and 4.75 mm for 25%, 55%, and 85% partial tears, respectively). Types III, IV, and V maintained a nonlinear trend, with ATTs of 3.85 mm, 4.2 mm, and 4.95 mm for Type III, 3.85 mm, 4.25 mm, and 5.1 mm for Type IV, and 3.6 mm, 4.25 mm, and 5.3 mm for Type V, for 25%, 55%, and 85% partial tears, respectively. Therefore, for small tears (25%), knee stability was most affected when the tears were located around the center of the ligament. For moderate tears (55%), the effect on knee stability was the greatest for tears at the proximal half of the ACL. However, severe tears (85%) demonstrated considerable growth in knee instability from the distal to the proximal ends of the tissue, with a substantial increase in knee instability around the insertion sites. The proposed model can enhance the characterization of partial ACL tears, leading to more accurate preliminary diagnoses. It can aid in developing new techniques for repairing partially torn ACLs, potentially preventing more severe injuries. Full article

(This article belongs to the Special Issue Computational Biomechanics, Volume II)

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11 pages, 1891 KiB

Open AccessEditor’s ChoiceArticle

Application of the Single Source—Detector Separation Algorithm in Wearable Neuroimaging Devices: A Step toward Miniaturized Biosensor for Hypoxia Detection

by Thien Nguyen, Soongho Park, Jinho Park, Asma Sodager, Tony George and Amir Gandjbakhche

Bioengineering 2024, 11(4), 385; https://doi.org/10.3390/bioengineering11040385 - 16 Apr 2024

Viewed by 1409

Abstract

Most currently available wearable devices to noninvasively detect hypoxia use the spatially resolved spectroscopy (SRS) method to calculate cerebral tissue oxygen saturation (StO₂). This study applies the single source—detector separation (SSDS) algorithm to calculate StO₂. Near-infrared spectroscopy (NIRS) data [...] Read more.

Most currently available wearable devices to noninvasively detect hypoxia use the spatially resolved spectroscopy (SRS) method to calculate cerebral tissue oxygen saturation (StO₂). This study applies the single source—detector separation (SSDS) algorithm to calculate StO₂. Near-infrared spectroscopy (NIRS) data were collected from 26 healthy adult volunteers during a breath-holding task using a wearable NIRS device, which included two source—detector separations (SDSs). These data were used to derive oxyhemoglobin (HbO) change and StO₂. In the group analysis, both HbO change and StO₂ exhibited significant change during a breath-holding task. Specifically, they initially decreased to minimums at around 10 s and then steadily increased to maximums, which were significantly greater than baseline levels, at 25–30 s (p-HbO < 0.001 and p-StO₂ < 0.05). However, at an individual level, the SRS method failed to detect changes in cerebral StO₂ in response to a short breath-holding task. Furthermore, the SSDS algorithm is more robust than the SRS method in quantifying change in cerebral StO₂ in response to a breath-holding task. In conclusion, these findings have demonstrated the potential use of the SSDS algorithm in developing a miniaturized wearable biosensor to monitor cerebral StO₂ and detect cerebral hypoxia. Full article

(This article belongs to the Special Issue Neuroimaging Techniques for Wearable Devices in Bioengineering)

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23 pages, 9165 KiB

Open AccessEditor’s ChoiceArticle

Motion Analysis of the Wrist and Finger Joints in Sport Climbing

by Gabriella Fischer, Micha Schneeberger, Stefan Andreas Petter, Anne-Gita Scheibler, Peter Wolf, Maurizio Calcagni, Andreas Schweizer and Lisa Reissner

Bioengineering 2024, 11(4), 370; https://doi.org/10.3390/bioengineering11040370 - 12 Apr 2024

Cited by 1 | Viewed by 1102

Abstract

Climbing is a fast-growing sport, with one of the most common injuries being a rupture of the finger flexor tendon pulley. The strain on pulleys increases as finger joints flex. However, to our knowledge, no study has conducted a kinematic analysis of climbers’ [...] Read more.

Climbing is a fast-growing sport, with one of the most common injuries being a rupture of the finger flexor tendon pulley. The strain on pulleys increases as finger joints flex. However, to our knowledge, no study has conducted a kinematic analysis of climbers’ fingers. Thus, this study aimed to examine finger kinematics during typical climbing tasks. Eleven elite climbers performed a sequence of four climbing moves, which were recorded by an optical motion capture system. Participants used crimp, half-crimp, and open-hand grips for three trials each, with the fourth condition involving campusing using any grip except crimp. Mean proximal interphalangeal joint (PIP) flexion during the holding phase was 87° (SD 12°), 70° (14°) and 39° (27°) for the crimp, half-crimp and open-hand grip, respectively. Hence, inter-individual PIP flexion ranges overlap between different gripping conditions. Two different movement patterns emerged in the open-hand grip, possibly influenced by the use of the little finger, leading to varying degrees of flexion in the middle and ring fingers. Avoiding little finger usage in the open-hand grip may reduce load during pulley rupture rehabilitation. The implications of PIP joint angle variability on individual pulley injury risk or prevention warrant further investigation. Motion capture proved effective for understanding finger kinematics during climbing and could guide future studies on pulley injury risk factors. Full article

(This article belongs to the Special Issue Biomechanics and Sports Medicine in Sport Climbing, Featuring Selected Contributions Presented at the 6th IRCRA Congress 2023)

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31 pages, 6645 KiB

Open AccessEditor’s ChoiceReview

Recent Advances in Wearable Healthcare Devices: From Material to Application

by Xiao Luo, Handong Tan and Weijia Wen

Bioengineering 2024, 11(4), 358; https://doi.org/10.3390/bioengineering11040358 - 6 Apr 2024

Cited by 1 | Viewed by 4949

Abstract

In recent years, the proliferation of wearable healthcare devices has marked a revolutionary shift in the personal health monitoring and management paradigm. These devices, ranging from fitness trackers to advanced biosensors, have not only made healthcare more accessible, but have also transformed the [...] Read more.

In recent years, the proliferation of wearable healthcare devices has marked a revolutionary shift in the personal health monitoring and management paradigm. These devices, ranging from fitness trackers to advanced biosensors, have not only made healthcare more accessible, but have also transformed the way individuals engage with their health data. By continuously monitoring health signs, from physical-based to biochemical-based such as heart rate and blood glucose levels, wearable technology offers insights into human health, enabling a proactive rather than a reactive approach to healthcare. This shift towards personalized health monitoring empowers individuals with the knowledge and tools to make informed decisions about their lifestyle and medical care, potentially leading to the earlier detection of health issues and more tailored treatment plans. This review presents the fabrication methods of flexible wearable healthcare devices and their applications in medical care. The potential challenges and future prospectives are also discussed. Full article

(This article belongs to the Special Issue Bioanalysis Systems: Materials, Methods, Designs and Applications)

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16 pages, 2619 KiB

Open AccessEditor’s ChoiceArticle

Deciphering Metabolic Pathways in High-Seeding-Density Fed-Batch Processes for Monoclonal Antibody Production: A Computational Modeling Perspective

by Carolin Bokelmann, Alireza Ehsani, Jochen Schaub and Fabian Stiefel

Bioengineering 2024, 11(4), 331; https://doi.org/10.3390/bioengineering11040331 - 28 Mar 2024

Viewed by 1377

Abstract

Due to their high specificity, monoclonal antibodies (mAbs) have garnered significant attention in recent decades, with advancements in production processes, such as high-seeding-density (HSD) strategies, contributing to improved titers. This study provides a thorough investigation of high seeding processes for mAb production in [...] Read more.

Due to their high specificity, monoclonal antibodies (mAbs) have garnered significant attention in recent decades, with advancements in production processes, such as high-seeding-density (HSD) strategies, contributing to improved titers. This study provides a thorough investigation of high seeding processes for mAb production in Chinese hamster ovary (CHO) cells, focused on identifying significant metabolites and their interactions. We observed high glycolytic fluxes, the depletion of asparagine, and a shift from lactate production to consumption. Using a metabolic network and flux analysis, we compared the standard fed-batch (STD FB) with HSD cultivations, exploring supplementary lactate and cysteine, and a bolus medium enriched with amino acids. We reconstructed a metabolic network and kinetic models based on the observations and explored the effects of different feeding strategies on CHO cell metabolism. Our findings revealed that the addition of a bolus medium (BM) containing asparagine improved final titers. However, increasing the asparagine concentration in the feed further prevented the lactate shift, indicating a need to find a balance between increased asparagine to counteract limitations and lower asparagine to preserve the shift in lactate metabolism. Full article

(This article belongs to the Special Issue Metabolic Modeling and Engineering)

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23 pages, 1871 KiB

Open AccessEditor’s ChoiceReview

Natural Killer Cell Mechanosensing in Solid Tumors

by Suzanne Lightsey and Blanka Sharma

Bioengineering 2024, 11(4), 328; https://doi.org/10.3390/bioengineering11040328 - 28 Mar 2024

Viewed by 1767

Abstract

Natural killer (NK) cells, which are an exciting alternative cell source for cancer immunotherapies, must sense and respond to their physical environment to traffic to and eliminate cancer cells. Herein, we review the mechanisms by which NK cells receive mechanical signals and explore [...] Read more.

Natural killer (NK) cells, which are an exciting alternative cell source for cancer immunotherapies, must sense and respond to their physical environment to traffic to and eliminate cancer cells. Herein, we review the mechanisms by which NK cells receive mechanical signals and explore recent key findings regarding the impact of the physical characteristics of solid tumors on NK cell functions. Data suggest that different mechanical stresses present in solid tumors facilitate NK cell functions, especially infiltration and degranulation. Moreover, we review recent engineering advances that can be used to systemically study the role of mechanical forces on NK cell activity. Understanding the mechanisms by which NK cells interpret their environment presents potential targets to enhance NK cell immunotherapies for the treatment of solid tumors. Full article

(This article belongs to the Section Regenerative Engineering)

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23 pages, 15127 KiB

Open AccessEditor’s ChoiceArticle

Leveraging Multi-Annotator Label Uncertainties as Privileged Information for Acute Respiratory Distress Syndrome Detection in Chest X-ray Images

by Zijun Gao, Emily Wittrup and Kayvan Najarian

Bioengineering 2024, 11(2), 133; https://doi.org/10.3390/bioengineering11020133 - 29 Jan 2024

Cited by 1 | Viewed by 1701

Abstract

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening lung injury for which early diagnosis and evidence-based treatment can improve patient outcomes. Chest X-rays (CXRs) play a crucial role in the identification of ARDS; however, their interpretation can be difficult due to non-specific radiological [...] Read more.

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening lung injury for which early diagnosis and evidence-based treatment can improve patient outcomes. Chest X-rays (CXRs) play a crucial role in the identification of ARDS; however, their interpretation can be difficult due to non-specific radiological features, uncertainty in disease staging, and inter-rater variability among clinical experts, thus leading to prominent label noise issues. To address these challenges, this study proposes a novel approach that leverages label uncertainty from multiple annotators to enhance ARDS detection in CXR images. Label uncertainty information is encoded and supplied to the model as privileged information, a form of information exclusively available during the training stage and not during inference. By incorporating the Transfer and Marginalized (TRAM) network and effective knowledge transfer mechanisms, the detection model achieved a mean testing AUROC of 0.850, an AUPRC of 0.868, and an F1 score of 0.797. After removing equivocal testing cases, the model attained an AUROC of 0.973, an AUPRC of 0.971, and an F1 score of 0.921. As a new approach to addressing label noise in medical image analysis, the proposed model has shown superiority compared to the original TRAM, Confusion Estimation, and mean-aggregated label training. The overall findings highlight the effectiveness of the proposed methods in addressing label noise in CXRs for ARDS detection, with potential for use in other medical imaging domains that encounter similar challenges. Full article

(This article belongs to the Special Issue Artificial Intelligence in Biomedical Imaging)

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17 pages, 15365 KiB

Open AccessEditor’s ChoiceArticle

Intramyocardial Injection of Hypoxia-Conditioned Extracellular Vesicles Modulates Response to Oxidative Stress in the Chronically Ischemic Myocardium

by Dwight D. Harris, Sharif A. Sabe, Mark Broadwin, Cynthia Xu, Christopher Stone, Meghamsh Kanuparthy, Akshay Malhotra, M. Ruhul Abid and Frank W. Sellke

Bioengineering 2024, 11(2), 125; https://doi.org/10.3390/bioengineering11020125 - 28 Jan 2024

Cited by 2 | Viewed by 1371

Abstract

Introduction: Patients with advanced coronary artery disease (CAD) who are not eligible for stenting or surgical bypass procedures have limited treatment options. Extracellular vesicles (EVs) have emerged as a potential therapeutic target for the treatment of advanced CAD. These EVs can be conditioned [...] Read more.

Introduction: Patients with advanced coronary artery disease (CAD) who are not eligible for stenting or surgical bypass procedures have limited treatment options. Extracellular vesicles (EVs) have emerged as a potential therapeutic target for the treatment of advanced CAD. These EVs can be conditioned to modify their contents. In our previous research, we demonstrated increased perfusion, decreased inflammation, and reduced apoptosis with intramyocardial injection of hypoxia-conditioned EVs (HEVs). The goal of this study is to further understand the function of HEVs by examining their impact on oxidative stress using our clinically relevant and extensively validated swine model of chronic myocardial ischemia. Methods: Fourteen Yorkshire swine underwent a left thoracotomy for the placement of an ameroid constrictor on the left circumflex coronary artery to model chronic myocardial ischemia. After two weeks of recovery, the swine underwent a redo thoracotomy with injection of either HEVs (n = 7) or a saline control (CON, n = 7) into the ischemic myocardium. Five weeks after injection, the swine were subjected to terminal harvest. Protein expression was measured using immunoblotting. OxyBlot analysis and 3-nitrotyrosine staining were used to quantify total oxidative stress. Results: There was a significant increase in myocardial expression of the antioxidants SOD 2, GPX-1, HSF-1, UCP-2, catalase, and HO-1 (all p ≤ 0.05) in the HEV group when compared to control animals. The HEVs also exhibited a significant increase in pro-oxidant NADPH oxidase (NOX) 1, NOX 3, p47phox, and p67phox (all p ≤ 0.05). However, no change was observed in the expression of NFkB, KEAP 1, and PRDX1 (all p > 0.05) between the HEV and CON groups. There were no significant differences in total oxidative stress as determined by OxyBlot and 3-nitrotyrosine staining (p = 0.64, p = 0.32) between the groups. Conclusions: Administration of HEVs in ischemic myocardium induces a significant increase in pro- and antioxidant proteins without a net change in total oxidative stress. These findings suggest that HEV-induced changes in redox signaling pathways may play a role in increased perfusion, decreased inflammation, and reduced apoptosis in ischemic myocardium. Further studies are required to determine if HEVs alter the net oxidative stress in ischemic myocardium at an earlier time point of HEV administration. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Tissue-Engineering)

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0 pages, 11527 KiB

Open AccessEditor’s ChoiceArticle

Perfusable Tissue Bioprinted into a 3D-Printed Tailored Bioreactor System

by Marius Gensler, Christoph Malkmus, Philipp Ockermann, Marc Möllmann, Lukas Hahn, Sahar Salehi, Robert Luxenhofer, Aldo R. Boccaccini and Jan Hansmann

Bioengineering 2024, 11(1), 68; https://doi.org/10.3390/bioengineering11010068 - 9 Jan 2024

Cited by 1 | Viewed by 2539

Abstract

Bioprinting provides a powerful tool for regenerative medicine, as it allows tissue construction with a patient’s specific geometry. However, tissue culture and maturation, commonly supported by dynamic bioreactors, are needed. We designed a workflow that creates an implant-specific bioreactor system, which is easily [...] Read more.

Bioprinting provides a powerful tool for regenerative medicine, as it allows tissue construction with a patient’s specific geometry. However, tissue culture and maturation, commonly supported by dynamic bioreactors, are needed. We designed a workflow that creates an implant-specific bioreactor system, which is easily producible and customizable and supports cell cultivation and tissue maturation. First, a bioreactor was designed and different tissue geometries were simulated regarding shear stress and nutrient distribution to match cell culture requirements. These tissues were then directly bioprinted into the 3D-printed bioreactor. To prove the ability of cell maintenance, C2C12 cells in two bioinks were printed into the system and successfully cultured for two weeks. Next, human mesenchymal stem cells (hMSCs) were successfully differentiated toward an adipocyte lineage. As the last step of the presented strategy, we developed a prototype of an automated mobile docking station for the bioreactor. Overall, we present an open-source bioreactor system that is adaptable to a wound-specific geometry and allows cell culture and differentiation. This interdisciplinary roadmap is intended to close the gap between the lab and clinic and to integrate novel 3D-printing technologies for regenerative medicine. Full article

(This article belongs to the Special Issue Tissue Engineering and Regenerative Medicine in Bioengineering)

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16 pages, 3896 KiB

Open AccessEditor’s ChoiceArticle

Mechanical Behaviour of Plantar Adipose Tissue: From Experimental Tests to Constitutive Analysis

by Sofia Pettenuzzo, Elisa Belluzzi, Assunta Pozzuoli, Veronica Macchi, Andrea Porzionato, Rafael Boscolo-Berto, Pietro Ruggieri, Alice Berardo, Emanuele Luigi Carniel and Chiara Giulia Fontanella

Bioengineering 2024, 11(1), 42; https://doi.org/10.3390/bioengineering11010042 - 31 Dec 2023

Cited by 1 | Viewed by 1475

Abstract

Plantar adipose tissue is a connective tissue whose structural configuration changes according to the foot region (rare or forefoot) and is related to its mechanical role, providing a damping system able to adsorb foot impact and bear the body weight. Considering this, the [...] Read more.

Plantar adipose tissue is a connective tissue whose structural configuration changes according to the foot region (rare or forefoot) and is related to its mechanical role, providing a damping system able to adsorb foot impact and bear the body weight. Considering this, the present work aims at fully describing the plantar adipose tissue’s behaviour and developing a proper constitutive formulation. Unconfined compression tests and indentation tests have been performed on samples harvested from human donors and cadavers. Experimental results provided the initial/final elastic modulus for each specimen and assessed the non-linear and time-dependent behaviour of the tissue. The different foot regions were investigated, and the main differences were observed when comparing the elastic moduli, especially the final elastic ones. It resulted in a higher level for the medial region (89 ± 77 MPa) compared to the others (from 51 ± 29 MPa for the heel pad to 11 ± 7 for the metatarsal). Finally, results have been used to define a visco-hyperelastic constitutive model, whose hyperelastic component, which describes tissue non-linear behaviour, was described using an Ogden formulation. The identified and validated tissue constitutive parameters could serve, in the early future, for the computational model of the healthy foot. Full article

(This article belongs to the Section Biomechanics and Sports Medicine)

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24 pages, 15417 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Morlet Wavelet Analysis for Artifact Detection in Low-Frequency Commercial Near-Infrared Spectroscopy Systems

by Tobias Bergmann, Logan Froese, Alwyn Gomez, Amanjyot Singh Sainbhi, Nuray Vakitbilir, Abrar Islam, Kevin Stein, Izzy Marquez, Fiorella Amenta, Kevin Park, Younis Ibrahim and Frederick A. Zeiler

Bioengineering 2024, 11(1), 33; https://doi.org/10.3390/bioengineering11010033 - 27 Dec 2023

Cited by 1 | Viewed by 1596

Abstract

Regional cerebral oxygen saturation (rSO₂), a method of cerebral tissue oxygenation measurement, is recorded using non-invasive near-infrared Spectroscopy (NIRS) devices. A major limitation is that recorded signals often contain artifacts. Manually removing these artifacts is both resource and time consuming. The [...] Read more.

Regional cerebral oxygen saturation (rSO₂), a method of cerebral tissue oxygenation measurement, is recorded using non-invasive near-infrared Spectroscopy (NIRS) devices. A major limitation is that recorded signals often contain artifacts. Manually removing these artifacts is both resource and time consuming. The objective was to evaluate the applicability of using wavelet analysis as an automated method for simple signal loss artifact clearance of rSO₂ signals obtained from commercially available devices. A retrospective observational study using existing populations (healthy control (HC), elective spinal surgery patients (SP), and traumatic brain injury patients (TBI)) was conducted. Arterial blood pressure (ABP) and rSO₂ data were collected in all patients. Wavelet analysis was determined to be successful in removing simple signal loss artifacts using wavelet coefficients and coherence to detect signal loss artifacts in rSO₂ signals. The removal success rates in HC, SP, and TBI populations were 100%, 99.8%, and 99.7%, respectively (though it had limited precision in determining the exact point in time). Thus, wavelet analysis may prove to be useful in a layered approach NIRS signal artifact tool utilizing higher-frequency data; however, future work is needed. Full article

(This article belongs to the Special Issue Wearable Sensors and Measurement Systems for Human Physiology Monitoring)

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14 pages, 9078 KiB

Open AccessEditor’s ChoiceArticle

Validation of Automatically Quantified Swim Stroke Mechanics Using an Inertial Measurement Unit in Paralympic Athletes

by Matthew Slopecki, Mathieu Charbonneau, Jean-Michel Lavallière, Julie N. Côté and Julien Clément

Bioengineering 2024, 11(1), 15; https://doi.org/10.3390/bioengineering11010015 - 23 Dec 2023

Viewed by 1641

Abstract

Biomechanics and training load monitoring are important for performance evaluation and injury prevention in elite swimming. Monitoring of performance and swim stroke parameters is possible with inertial measurement units (IMU) but has not been validated in para-swimmers. The purpose of this study was [...] Read more.

Biomechanics and training load monitoring are important for performance evaluation and injury prevention in elite swimming. Monitoring of performance and swim stroke parameters is possible with inertial measurement units (IMU) but has not been validated in para-swimmers. The purpose of this study was to validate a single IMU-based system to accurately estimate pool-swam lap time, stroke count (SC), stroke duration, instantaneous stroke rate (ISR), and distance per stroke (DPS). Eight Paralympic athletes completed 4 × 50 m swims with an IMU worn on the sacrum. Strokes cycles were identified using a zero-crossing algorithm on the medio-lateral (freestyle and backstroke) or forward-backward (butterfly and breaststroke) instantaneous velocity data. Video-derived metrics were estimated using Dartfish and Kinovea. Agreement analyses, including Bland–Altman and Intraclass Correlation Coefficient (ICC), were performed on all outcome variables. SC Bland–Altman bias was 0.13 strokes, and ICC was 0.97. ISR Bland–Altman biases were within 1.5 strokes/min, and ICCs ranged from 0.26 to 0.96. DPS Bland–Altman biases were within 0.20 m, and ICCs ranged from 0.39 to 0.93. A single-IMU system can provide highly valid performance and swim stroke monitoring data for elite para-swimmers for the majority of strokes, with the exception of backstroke. Future work should improve bilateral stroke detection algorithms in this population. Full article

(This article belongs to the Special Issue Advances in Wearable Technologies for ”In-Field” Assessment of Biomechanical Risk)

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12 pages, 3813 KiB

Open AccessEditor’s ChoiceArticle

Exploring the Role of Desmoplastic Physical Stroma in Pancreatic Cancer Progression Using a Three-Dimensional Collagen Matrix Model

by Xiaoyu Song, Yuma Nihashi, Masamichi Yamamoto, Daiki Setoyama, Yuya Kunisaki and Yasuyuki S. Kida

Bioengineering 2023, 10(12), 1437; https://doi.org/10.3390/bioengineering10121437 - 18 Dec 2023

Cited by 1 | Viewed by 1648

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a refractory tumor with a poor prognosis, and its complex microenvironment is characterized by a fibrous interstitial matrix surrounding PDAC cells. Type I collagen is a major component of this interstitial matrix. Abundant type I collagen promotes its [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is a refractory tumor with a poor prognosis, and its complex microenvironment is characterized by a fibrous interstitial matrix surrounding PDAC cells. Type I collagen is a major component of this interstitial matrix. Abundant type I collagen promotes its deposition and cross-linking to form a rigid and dense physical barrier, which limits drug penetration and immune cell infiltration and provides drug resistance and metabolic adaptations. In this study, to identify the physical effect of the stroma, type I collagen was used as a 3D matrix to culture Capan-1 cells and generate a 3D PDAC model. Using transcriptome analysis, a link between type I collagen-induced physical effects and the promotion of Capan-1 cell proliferation and migration was determined. Moreover, metabolomic analysis revealed that the physical effect caused a shift in metabolism toward a glycolytic phenotype. In particular, the high expression of proline in the metabolites suggests the ability to maintain Capan-1 cell proliferation under hypoxic and nutrient-depleted conditions. In conclusion, we identified type I collagen-induced physical effects in promoting Capan-1 cells, which cause PDAC progression, providing support for the role of dense stroma in the PDAC microenvironment and identifying a fundamental method for modeling the complex PDAC microenvironment. Full article

(This article belongs to the Special Issue The New Frontiers of Artificial Organs Engineering)

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24 pages, 13599 KiB

Open AccessEditor’s ChoiceArticle

A Critical Assessment of Generative Models for Synthetic Data Augmentation on Limited Pneumonia X-ray Data

by Daniel Schaudt, Christian Späte, Reinhold von Schwerin, Manfred Reichert, Marianne von Schwerin, Meinrad Beer and Christopher Kloth

Bioengineering 2023, 10(12), 1421; https://doi.org/10.3390/bioengineering10121421 - 14 Dec 2023

Viewed by 2156

Abstract

In medical imaging, deep learning models serve as invaluable tools for expediting diagnoses and aiding specialized medical professionals in making clinical decisions. However, effectively training deep learning models typically necessitates substantial quantities of high-quality data, a resource often lacking in numerous medical imaging [...] Read more.

In medical imaging, deep learning models serve as invaluable tools for expediting diagnoses and aiding specialized medical professionals in making clinical decisions. However, effectively training deep learning models typically necessitates substantial quantities of high-quality data, a resource often lacking in numerous medical imaging scenarios. One way to overcome this deficiency is to artificially generate such images. Therefore, in this comparative study we train five generative models to artificially increase the amount of available data in such a scenario. This synthetic data approach is evaluated on a a downstream classification task, predicting four causes for pneumonia as well as healthy cases on 1082 chest X-ray images. Quantitative and medical assessments show that a Generative Adversarial Network (GAN)-based approach significantly outperforms more recent diffusion-based approaches on this limited dataset with better image quality and pathological plausibility. We show that better image quality surprisingly does not translate to improved classification performance by evaluating five different classification models and varying the amount of additional training data. Class-specific metrics like precision, recall, and F1-score show a substantial improvement by using synthetic images, emphasizing the data rebalancing effect of less frequent classes. However, overall performance does not improve for most models and configurations, except for a DreamBooth approach which shows a +0.52 improvement in overall accuracy. The large variance of performance impact in this study suggests a careful consideration of utilizing generative models for limited data scenarios, especially with an unexpected negative correlation between image quality and downstream classification improvement. Full article

(This article belongs to the Special Issue Artificial Intelligence (AI) for Medical Image Processing)

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18 pages, 8714 KiB

Open AccessEditor’s ChoiceArticle

Training Postural Balance Control with Pelvic Force Field at the Boundary of Stability

by Isirame Omofuma, Victor Santamaria, Xupeng Ai and Sunil Agrawal

Bioengineering 2023, 10(12), 1398; https://doi.org/10.3390/bioengineering10121398 - 6 Dec 2023

Viewed by 1568

Abstract

This study characterizes the effects of a postural training program on balance and muscle control strategies in a virtual reality (VR) environment. The Robotic Upright Stand Trainer (RobUST), which applies perturbative forces on the trunk and assistive forces on the pelvis, was used [...] Read more.

This study characterizes the effects of a postural training program on balance and muscle control strategies in a virtual reality (VR) environment. The Robotic Upright Stand Trainer (RobUST), which applies perturbative forces on the trunk and assistive forces on the pelvis, was used to deliver perturbation-based balance training (PBT) in a sample of 10 healthy participants. The VR task consisted of catching, aiming, and throwing a ball at a target. All participants received trunk perturbations during the VR task with forces tailored to the participant’s maximum tolerance. A subgroup of these participants additionally received assistive forces at the pelvis during training. Postural kinematics were calculated before and after RobUST training, including (i) maximum perturbation force tolerated, (ii) center of pressure (COP) and pelvic excursions, (iii) postural muscle activations (EMG), and (iv) postural control strategies (the ankle and hip strategies). We observed an improvement in the maximum perturbation force and postural stability area in both groups and decreases in muscle activity. The behavior of the two groups differed for perturbations in the posterior direction where the unassisted group moved towards greater use of the hip strategy. In addition, the assisted group changed towards a lower margin of stability and higher pelvic excursion. We show that training with force assistance leads to a reactive balance strategy that permits pelvic excursion but that is efficient at restoring balance from displaced positions while training without assistance leads to reactive balance strategies that restrain pelvic excursion. Patient populations can benefit from a platform that encourages greater use of their range of motion. Full article

(This article belongs to the Special Issue Sports Biomechanics and Wearable Technology)

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27 pages, 4562 KiB

Open AccessEditor’s ChoiceArticle

Reproducibility and Robustness of a Liver Microphysiological System PhysioMimix LC12 under Varying Culture Conditions and Cell Type Combinations

by Alicia Y. Lim, Yuki Kato, Courtney Sakolish, Alan Valdiviezo, Gang Han, Piyush Bajaj, Jason Stanko, Stephen S. Ferguson, Remi Villenave, Philip Hewitt, Rhiannon N. Hardwick and Ivan Rusyn

Bioengineering 2023, 10(10), 1195; https://doi.org/10.3390/bioengineering10101195 - 14 Oct 2023

Cited by 2 | Viewed by 2404

Abstract

The liver is one of the key organs for exogenous and endogenous metabolism and is often a target for drug- and chemical-driven toxicity. A wide range of experimental approaches has been established to model and characterize the mechanisms of drug- and chemical-induced hepatotoxicity. [...] Read more.

The liver is one of the key organs for exogenous and endogenous metabolism and is often a target for drug- and chemical-driven toxicity. A wide range of experimental approaches has been established to model and characterize the mechanisms of drug- and chemical-induced hepatotoxicity. A number of microfluidics-enabled in vitro models of the liver have been developed, but the unclear translatability of these platforms has hindered their adoption by the pharmaceutical industry; to achieve wide use for drug and chemical safety evaluation, demonstration of reproducibility and robustness under various contexts of use is required. One of these commercially available platforms is the PhysioMimix LC12, a microfluidic device where cells are seeded into a 3D scaffold that is continuously perfused with recirculating cell culture media to mimic liver sinusoids. Previous studies demonstrated this model’s functionality and potential applicability to preclinical drug development. However, to gain confidence in PhysioMimix LC12’s robustness and reproducibility, supplementary characterization steps are needed, including the assessment of various human hepatocyte sources, contribution of non-parenchymal cells (NPCs), and comparison to other models. In this study, we performed replicate studies averaging 14 days with either primary human hepatocytes (PHHs) or induced pluripotent stem cell (iPSC)-derived hepatocytes, with and without NPCs. Albumin and urea secretion, lactate dehydrogenase, CYP3A4 activity, and metabolism were evaluated to assess basal function and metabolic capacity. Model performance was characterized by different cell combinations under intra- and inter-experimental replication and compared to multi-well plates and other liver platforms. PhysioMimix LC12 demonstrated the highest metabolic function with PHHs, with or without THP-1 or Kupffer cells, for up to 10–14 days. iPSC-derived hepatocytes and PHHs co-cultured with additional NPCs demonstrated sub-optimal performance. Power analyses based on replicate experiments and different contexts of use will inform future study designs due to the limited throughput and high cell demand. Overall, this study describes a workflow for independent testing of a complex microphysiological system for specific contexts of use, which may increase end-user adoption in drug development. Full article

(This article belongs to the Special Issue Advanced 3D Cell Culture Technologies and Formats)

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17 pages, 4764 KiB

Open AccessEditor’s ChoiceReview

Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients

by Max Baron, Philip Drohat, Brooke Crawford, Francis J. Hornicek, Thomas M. Best and Dimitrios Kouroupis

Bioengineering 2023, 10(10), 1187; https://doi.org/10.3390/bioengineering10101187 - 13 Oct 2023

Cited by 4 | Viewed by 2202

Abstract

Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone [...] Read more.

Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone regeneration arise. To determine the appropriate amount of bone to be removed, preoperative imaging techniques such as bone and CT scans are employed. To prevent local recurrence, the current standard of care suggests maintaining bony and soft tissue margins from 3 to 7 cm beyond the tumor. The amount of bone removed in an OS patient leaves too large of a deficit for bone to form on its own and requires reconstruction with metal implants or allografts. Both methods require the bone to heal, either to the implant or across the allograft junction, often in the setting of marrow-killing chemotherapy. Therefore, the issue of bone regeneration within the surgically resected margins remains an important challenge for the patient, family, and treating providers. Mesenchymal stem/stromal cells (MSCs) are potential agents for enhancing bone regeneration post tumor resection. MSCs, used with scaffolds and growth factors, show promise in fostering bone regeneration in OS cases. We spotlight two MSC types—bone marrow-derived (BM-MSCs) and adipose tissue-derived (ASCs)—highlighting their bone regrowth facilitation and immunomodulatory effects on immune cells like macrophages and T cells, enhancing therapeutic outcomes. The objective of this review is two-fold: review work demonstrating any ability of MSCs to target the deranged immune system in the OS microenvironment, and synthesize the available literature on the use of MSCs as a therapeutic option for stimulating bone regrowth in OS patients post bone resection. When it comes to repairing bone defects, both MB-MSCs and ASCs hold great potential for stimulating bone regeneration. Research has showcased their effectiveness in reconstructing bone defects while maintaining a non-tumorigenic role following wide resection of bone tumors, underscoring their capability to enhance bone healing and regeneration following tumor excisions. Full article

(This article belongs to the Special Issue A Tribute to Professor Alexander Friedenstein and His Outstanding Achievements in the Area of Stromal Stem Cells)

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19 pages, 9239 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of a Granular Bone Substitute for Bone Regeneration Using an Optimized In Vivo Alveolar Cleft Model

by Alban Destrez, Emilien Colin, Sylvie Testelin, Bernard Devauchelle, Stéphanie Dakpé and Marie Naudot

Bioengineering 2023, 10(9), 1035; https://doi.org/10.3390/bioengineering10091035 - 2 Sep 2023

Cited by 1 | Viewed by 1167

Abstract

Alveolar cleft is a common congenital deformity that requires surgical intervention, notably using autologous bone grafts in young children. Bone substitutes, in combination with mesenchymal stem cells (MSCs), have shown promise in the repair of these defects. This study aimed to evaluate the [...] Read more.

Alveolar cleft is a common congenital deformity that requires surgical intervention, notably using autologous bone grafts in young children. Bone substitutes, in combination with mesenchymal stem cells (MSCs), have shown promise in the repair of these defects. This study aimed to evaluate the regenerative capabilities of a granular bone substitute using an optimized alveolar cleft model. Thirty-six rats underwent a surgical procedure for the creation of a defect filled with a fragment of silicone. After 5 weeks, the silicone was removed and the biomaterial, with or without Wharton’s jelly MSCs, was put into the defect, except for the control group. The rats underwent μCT scans immediately and after 4 and 8 weeks. Analyses showed a statistically significant improvement in bone regeneration in the two treatment groups compared with control at weeks 4 and 8, both for bone volume (94.64% ± 10.71% and 91.33% ± 13.30%, vs. 76.09% ± 7.99%) and mineral density (96.13% ± 24.19% and 93.01% ± 27.04%, vs. 51.64% ± 16.51%), but without having fully healed. This study validates our optimized alveolar cleft model in rats, but further work is needed to allow for the use of this granular bone substitute in the treatment of bone defects. Full article

(This article belongs to the Special Issue Novel Approaches for the Treatment of Maxillofacial Defects: From Bone to Skin Regeneration)

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18 pages, 2992 KiB

Open AccessEditor’s ChoiceArticle

Enhanced Expansion of Human Pluripotent Stem Cells and Somatic Cell Reprogramming Using Defined and Xeno-Free Culture Conditions

by Suraj Timilsina, Kaitlyn Faith McCandliss, Evan Trivedi and Luis G. Villa-Diaz

Bioengineering 2023, 10(9), 999; https://doi.org/10.3390/bioengineering10090999 - 24 Aug 2023

Cited by 1 | Viewed by 1488

Abstract

Human embryonic stem cells and induced pluripotent stem cells (hPSC) have an unprecedented opportunity to revolutionize the fields of developmental biology as well as tissue engineering and regenerative medicine. However, their applications have been significantly limited by the lack of chemically defined and [...] Read more.

Human embryonic stem cells and induced pluripotent stem cells (hPSC) have an unprecedented opportunity to revolutionize the fields of developmental biology as well as tissue engineering and regenerative medicine. However, their applications have been significantly limited by the lack of chemically defined and xeno-free culture conditions. The demand for the high-quality and scaled-up production of cells for use in both research and clinical studies underscores the need to develop tools that will simplify the in vitro culture process while reducing the variables. Here, we describe a systematic study to identify the optimal conditions for the initial cell attachment of hPSC to tissue culture dishes grafted with polymers of N-(3-Sulfopropyl)-N-Methacryloxyethyl-N, N-Dimethylammoniun Betaine (PMEDSAH) in combination with chemically defined and xeno-free culture media. After testing multiple supplements and chemicals, we identified that pre-conditioning of PMEDSAH grafted plates with 10% human serum (HS) supported the initial cell attachment, which allowed for the long-term culture and maintenance of hPSC compared to cells cultured on Matrigel-coated plates. Using this culture condition, a 2.1-fold increase in the expansion of hPSC was observed without chromosomal abnormalities. Furthermore, this culture condition supported a higher reprogramming efficiency (0.37% vs. 0.22%; p < 0.0068) of somatic cells into induced pluripotent stem cells compared to the non-defined culture conditions. This defined and xeno-free hPSC culture condition may be used in obtaining the large populations of hPSC and patient-derived iPSC required for many applications in regenerative and translational medicine. Full article

(This article belongs to the Special Issue Stem Cell Bioprocessing and Tissue Reconstruction)

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22 pages, 4893 KiB

Open AccessEditor’s ChoiceArticle

Optimizing Bioink Composition for Human Chondrocyte Expression of Lubricin

by Kari Martyniak, Sean Kennedy, Makan Karimzadeh, Maria A. Cruz, Oju Jeon, Eben Alsberg and Thomas J. Kean

Bioengineering 2023, 10(9), 997; https://doi.org/10.3390/bioengineering10090997 - 23 Aug 2023

Cited by 2 | Viewed by 1843

Abstract

The surface zone of articular cartilage is the first area impacted by cartilage defects, commonly resulting in osteoarthritis. Chondrocytes in the surface zone of articular cartilage synthesize and secrete lubricin, a proteoglycan that functions as a lubricant protecting the deeper layers from shear [...] Read more.

The surface zone of articular cartilage is the first area impacted by cartilage defects, commonly resulting in osteoarthritis. Chondrocytes in the surface zone of articular cartilage synthesize and secrete lubricin, a proteoglycan that functions as a lubricant protecting the deeper layers from shear stress. Notably, 3D bioprinting is a tissue engineering technique that uses cells encapsulated in biomaterials to fabricate 3D constructs. Gelatin methacrylate (GelMA) is a frequently used biomaterial for 3D bioprinting cartilage. Oxidized methacrylated alginate (OMA) is a chemically modified alginate designed for its tunable degradation rate and mechanical properties. To determine an optimal combination of GelMA and OMA for lubricin expression, we used our novel high-throughput human articular chondrocyte reporter system. Primary human chondrocytes were transduced with PRG4 (lubricin) promoter-driven Gaussia luciferase, allowing for temporal assessment of lubricin expression. A lubricin expression-driven Design of Experiment screen and subsequent validation identified 14% GelMA/2% OMA for further study. Therefore, DoE optimized 14% GelMA/2% OMA, 14% GelMA control, and 16% GelMA (total solid content control) were 3D bioprinted. The combination of lubricin protein expression and shape retention over the 22 days in culture, successfully determined the 14% GelMA/2%OMA to be the optimal formulation for lubricin secretion. This strategy allows for rapid analysis of the role(s) of biomaterial composition, stiffness or other cell manipulations on lubricin expression by chondrocytes, which may improve therapeutic strategies for cartilage regeneration. Full article

(This article belongs to the Special Issue Tissue Engineering Scaffolds in Regenerative Medicine)

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12 pages, 1363 KiB

Open AccessEditor’s ChoiceArticle

Assessing the Genotoxicity of Cellulose Nanomaterials in a Co-Culture of Human Lung Epithelial Cells and Monocyte-Derived Macrophages

by Célia Ventura, Fátima Pinto, Ana Filipa Lourenço, Jorge F. S. Pedrosa, Susete N. Fernandes, Rafaela R. da Rosa, Maria Helena Godinho, Paulo J. T. Ferreira, Henriqueta Louro and Maria João Silva

Bioengineering 2023, 10(8), 986; https://doi.org/10.3390/bioengineering10080986 - 21 Aug 2023

Cited by 1 | Viewed by 1841

Abstract

Cellulose micro/nanomaterials (CMNMs) are innovative materials with a wide spectrum of industrial and biomedical applications. Although cellulose has been recognized as a safe material, the unique properties of its nanosized forms have raised concerns about their safety for human health. Genotoxicity is an [...] Read more.

Cellulose micro/nanomaterials (CMNMs) are innovative materials with a wide spectrum of industrial and biomedical applications. Although cellulose has been recognized as a safe material, the unique properties of its nanosized forms have raised concerns about their safety for human health. Genotoxicity is an endpoint that must be assessed to ensure that no carcinogenic risks are associated with exposure to nanomaterials. In this study, we evaluated the genotoxicity of two types of cellulose micro/nanofibrils (CMF and CNF) and one sample of cellulose nanocrystals (CNC), obtained from industrial bleached Eucalyptus globulus kraft pulp. For that, we exposed co-cultures of human alveolar epithelial A549 cells and THP-1 monocyte-derived macrophages to a concentration range of each CMNM and used the micronucleus (MN) and comet assays. Our results showed that only the lowest concentrations of the CMF sample were able to induce DNA strand breaks (FPG-comet assay). However, none of the three CMNMs produced significant chromosomal alterations (MN assay). These findings, together with results from previous in vitro studies using monocultures of A549 cells, indicate that the tested CNF and CNC are not genotoxic under the conditions tested, while the CMF display a low genotoxic potential. Full article

(This article belongs to the Special Issue Biopolymers and Nano-Objects Applications in Bioengineering)

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9 pages, 517 KiB

Open AccessEditor’s ChoiceCommunication

Retrospective Analysis of Responders and Impaired Patients with Knee Osteoarthritis Treated with Two Consecutive Injections of Very Pure Platelet-Rich Plasma (PRP)

by Alain Silvestre, Pierre-Francois Lintingre, Lionel Pesquer, Philippe Meyer, Marie-Hélène Moreau-Durieux and Benjamin Dallaudiére

Bioengineering 2023, 10(8), 922; https://doi.org/10.3390/bioengineering10080922 - 3 Aug 2023

Cited by 2 | Viewed by 1862

Abstract

Objectives: To assess the effectiveness of two consecutive intraarticular injections of PRP to treat knee osteoarthritis (KOA), discriminating between responders and impaired patients. Methods: This retrospective study included 73 consecutive patients who were referred for two intra-articular PRP injections (one week apart) for [...] Read more.

Objectives: To assess the effectiveness of two consecutive intraarticular injections of PRP to treat knee osteoarthritis (KOA), discriminating between responders and impaired patients. Methods: This retrospective study included 73 consecutive patients who were referred for two intra-articular PRP injections (one week apart) for treating symptomatic moderate/severe KOA. Biological characterization of the PRP, including platelets, leukocytes and erythrocytes, was evaluated. Patient’s subjective symptoms were recorded before the treatment and 1 year after the second injection using pain VAS and WOMAC scores. Responders were defined by an improvement of 10 points on WOMAC. Results: At a 1-year follow up, we found 36 (49.3%) patients who fulfilled the criteria of responders, and 21 (28.8%) patients were impaired. A statistically and clinically significant global improvement of −29.2 ± 14.3 (p < 0.001) points in WOMAC score was observed 1 year after treatment in the responder group, with a higher response rate in patients with KL 2 (57.7%) compared to KL IV (28.6%). The percentage of patients with KL IV was higher in the impaired group (48.0%) compared to the responders (16.6%). As expected, the evaluation of the functionality of the knee in the impaired group indicates that it significantly worsened after one year from treatment (p = 0.027). However, the average pain score remained stable with no significant differences after 1 year (p = 0.843). No clinical complications or severe adverse events after the PRP injections were reported. Conclusion: The present study suggests that two intra-articular injections of 10 mL of very pure PRP provide pain and functional improvement in symptomatic KOA. Full article

(This article belongs to the Special Issue Advances in Autologous PRP Therapy)

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17 pages, 3240 KiB

Open AccessEditor’s ChoiceArticle

Ex Vivo Model to Evaluate the Antibacterial and Anti-Inflammatory Effects of Gelatin–Tricalcium Phosphate Composite Incorporated with Emodin and Lumbrokinase for Bone Regeneration

by Wen-Ling Wang, Yuan-Man Hsu, Meng-Liang Lin, Shih-Shun Chen, Yi-Hui Lai, Chiung-Hua Huang and Chun-Hsu Yao

Bioengineering 2023, 10(8), 906; https://doi.org/10.3390/bioengineering10080906 - 31 Jul 2023

Cited by 2 | Viewed by 1756

Abstract

Tricalcium phosphate (TCP) has gained attention due to its interconnected porous structures which promote fibrovascular invasion and bony replacement. Moreover, when gelatin is added and crosslinked with genipin (GGT), TCP exhibits robust biocompatibility and stability, making it an excellent bone substitute. In this [...] Read more.

Tricalcium phosphate (TCP) has gained attention due to its interconnected porous structures which promote fibrovascular invasion and bony replacement. Moreover, when gelatin is added and crosslinked with genipin (GGT), TCP exhibits robust biocompatibility and stability, making it an excellent bone substitute. In this study, we incorporated emodin and lumbrokinase (LK) into GGT to develop an antibacterial biomaterial. Emodin, derived from various plants, possesses antibacterial and anti-inflammatory properties. LK comprises proteolytic enzymes extracted from the earthworm Lumbricus rubellus and exhibits fibrinolytic activity, enabling it to dissolve biofilms. Additionally, LK stimulates osteoblast activity while inhibiting osteoclast differentiation. GGT was combined with emodin and lumbrokinase to produce the GGTELK composite. The biomedical effects of GGTELK were assessed through in vitro assays and an ex vivo bone defect model. The GGTELK composite demonstrated antibacterial properties, inhibiting the growth of S. aureus and reducing biofilm formation. Moreover, it exhibited anti-inflammatory effects by reducing the secretion of IL-6 in both in vivo cell experiments and the ex vivo model. Therefore, the GGTELK composite, with its stability, efficient degradation, biocompatibility, and anti-inflammatory function, is expected to serve as an ideal bone substitute. Full article

(This article belongs to the Special Issue Biomaterials for Cartilage and Bone Tissue Engineering)

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20 pages, 7670 KiB

Open AccessEditor’s ChoiceArticle

A Novel Non-Contact Detection and Identification Method for the Post-Disaster Compression State of Injured Individuals Using UWB Bio-Radar

by Ding Shi, Fulai Liang, Jiahao Qiao, Yaru Wang, Yidan Zhu, Hao Lv, Xiao Yu, Teng Jiao, Fuyuan Liao, Keding Yan, Jianqi Wang and Yang Zhang

Bioengineering 2023, 10(8), 905; https://doi.org/10.3390/bioengineering10080905 - 30 Jul 2023

Cited by 2 | Viewed by 1675

Abstract

Building collapse leads to mechanical injury, which is the main cause of injury and death, with crush syndrome as its most common complication. During the post-disaster search and rescue phase, if rescue personnel hastily remove heavy objects covering the bodies of injured individuals [...] Read more.

Building collapse leads to mechanical injury, which is the main cause of injury and death, with crush syndrome as its most common complication. During the post-disaster search and rescue phase, if rescue personnel hastily remove heavy objects covering the bodies of injured individuals and fail to provide targeted medical care, ischemia-reperfusion injury may be triggered, leading to rhabdomyolysis. This may result in disseminated intravascular coagulation or acute respiratory distress syndrome, further leading to multiple organ failure, which ultimately leads to shock and death. Using bio-radar to detect vital signs and identify compression states can effectively reduce casualties during the search for missing persons behind obstacles. A time-domain ultra-wideband (UWB) bio-radar was applied for the non-contact detection of human vital sign signals behind obstacles. An echo denoising algorithm based on PSO-VMD and permutation entropy was proposed to suppress environmental noise, along with a wounded compression state recognition network based on radar-life signals. Based on training and testing using over 3000 data sets from 10 subjects in different compression states, the proposed multiscale convolutional network achieved a 92.63% identification accuracy. This outperformed SVM and 1D-CNN models by 5.30% and 6.12%, respectively, improving the casualty rescue success and post-disaster precision. Full article

(This article belongs to the Special Issue Contactless Technologies for Human Vital Signs Monitoring)

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17 pages, 1545 KiB

Open AccessEditor’s ChoiceReview

Recent Advancements in Deep Learning Using Whole Slide Imaging for Cancer Prognosis

by Minhyeok Lee

Bioengineering 2023, 10(8), 897; https://doi.org/10.3390/bioengineering10080897 - 28 Jul 2023

Cited by 6 | Viewed by 2638

Abstract

This review furnishes an exhaustive analysis of the latest advancements in deep learning techniques applied to whole slide images (WSIs) in the context of cancer prognosis, focusing specifically on publications from 2019 through 2023. The swiftly maturing field of deep learning, in combination [...] Read more.

This review furnishes an exhaustive analysis of the latest advancements in deep learning techniques applied to whole slide images (WSIs) in the context of cancer prognosis, focusing specifically on publications from 2019 through 2023. The swiftly maturing field of deep learning, in combination with the burgeoning availability of WSIs, manifests significant potential in revolutionizing the predictive modeling of cancer prognosis. In light of the swift evolution and profound complexity of the field, it is essential to systematically review contemporary methodologies and critically appraise their ramifications. This review elucidates the prevailing landscape of this intersection, cataloging major developments, evaluating their strengths and weaknesses, and providing discerning insights into prospective directions. In this paper, a comprehensive overview of the field aims to be presented, which can serve as a critical resource for researchers and clinicians, ultimately enhancing the quality of cancer care outcomes. This review’s findings accentuate the need for ongoing scrutiny of recent studies in this rapidly progressing field to discern patterns, understand breakthroughs, and navigate future research trajectories. Full article

(This article belongs to the Special Issue Machine-Learning-Driven Medical Image Analysis)

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15 pages, 3450 KiB

Open AccessEditor’s ChoiceArticle

In Vivo Assessment of High-Strength and Corrosion-Controlled Magnesium-Based Bone Implants

by Hamdy Ibrahim, Caroline Billings, Moataz Abdalla, Ahmed Korra and David Edger Anderson

Bioengineering 2023, 10(7), 877; https://doi.org/10.3390/bioengineering10070877 - 24 Jul 2023

Cited by 4 | Viewed by 1509

Abstract

The biodegradable nature of magnesium in aqueous mediums makes it an attractive material for various biomedical applications when it is not recommended that the material stay permanently in the body. Some of the main challenges that hinder the use of magnesium for bone [...] Read more.

The biodegradable nature of magnesium in aqueous mediums makes it an attractive material for various biomedical applications when it is not recommended that the material stay permanently in the body. Some of the main challenges that hinder the use of magnesium for bone fracture repair are its limited mechanical strength and fast corrosion rates. To this end, we developed a novel Mg-Zn-Ca-Mn-based alloy and post-fabrication methods that can deliver high-strength and corrosion-controlled implant materials to address these challenges. This study is focused on assessing the in vitro corrosion and in vivo biocompatibility of the developed magnesium-based alloy and post-fabrication processes. The developed heat treatment process resulted in an increase in the microhardness from 71.9 ± 5.4 HV for the as-cast Mg alloy to as high as 98.1 ± 6.5 HV for the heat-treated Mg alloy, and the ceramic coating resulted in a significant reduction in the corrosion rate from 10.37 mm/yr for the uncoated alloy to 0.03 mm/yr after coating. The in vivo assessments showed positive levels of biocompatibility in terms of degradation rates and integration of the implants in a rabbit model. In the rabbit studies, the implants became integrated into the bone defect and showed minimal evidence of an immune response. The results of this study show that it is possible to produce biocompatible Mg-based implants with stronger and more corrosion-controlled properties based on the developed Mg-Zn-Ca-Mn-based alloy and post-fabrication methods. Full article

(This article belongs to the Special Issue Engineering Biodegradable-Implant Materials, 2nd Edition)

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16 pages, 1621 KiB

Open AccessEditor’s ChoiceArticle

Correlations between Ratings and Technical Measurements in Hand-Intensive Work

by Gunilla Dahlgren, Per Liv, Fredrik Öhberg, Lisbeth Slunga Järvholm, Mikael Forsman and Börje Rehn

Bioengineering 2023, 10(7), 867; https://doi.org/10.3390/bioengineering10070867 - 21 Jul 2023

Viewed by 1788

Abstract

An accurate rating of hand activity and force is essential in risk assessment and for the effective prevention of work-related musculoskeletal disorders. However, it is unclear whether the subjective ratings of workers and observers correlate to corresponding objective technical measures of exposure. Fifty-nine [...] Read more.

An accurate rating of hand activity and force is essential in risk assessment and for the effective prevention of work-related musculoskeletal disorders. However, it is unclear whether the subjective ratings of workers and observers correlate to corresponding objective technical measures of exposure. Fifty-nine workers were video recorded while performing a hand-intensive work task at their workplace. Self-ratings of hand activity level (HAL) and force (Borg CR10) using the Hand Activity Threshold Limit Value^® were assessed. Four ergonomist observers, in two pairs, also rated the hand activity and force level for each worker from video recordings. Wrist angular velocity was measured using inertial movement units. Muscle activity in the forearm muscles flexor carpi radialis (FCR) and extensor carpi radialis (ECR) was measured with electromyography root mean square values (RMS) and normalized to maximal voluntary electrical activation (MVE). Kendall’s tau-b correlations were statistically significant between self-rated hand activity and wrist angular velocity at the 10th, 50th, and 90th percentiles (0.26, 0.31, and 0.23) and for the ratings of observers (0.32, 0.41, and 0.34). Significant correlations for force measures were found only for observer-ratings in five of eight measures (FCR 50th percentile 0.29, time > 10%MVE 0.43, time > 30%MVE 0.44, time < 5% −0.47) and ECR (time > 30%MVE 0.26). The higher magnitude of correlation for observer-ratings suggests that they may be preferred to the self-ratings of workers. When possible, objective technical measures of wrist angular velocity and muscle activity should be preferred to subjective ratings when assessing risks of work-related musculoskeletal disorders. Full article

(This article belongs to the Special Issue Human Movement and Ergonomics)

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19 pages, 9511 KiB

Open AccessEditor’s ChoiceArticle

Biofunctionalized Decellularized Tissue-Engineered Heart Valve with Mesoporous Silica Nanoparticles for Controlled Release of VEGF and RunX2-siRNA against Calcification

by Wenpeng Yu, Xiaowei Zhu, Jichun Liu and Jianliang Zhou

Bioengineering 2023, 10(7), 859; https://doi.org/10.3390/bioengineering10070859 - 20 Jul 2023

Cited by 3 | Viewed by 1747

Abstract

The goal of tissue-engineered heart valves (TEHV) is to replace normal heart valves and overcome the shortcomings of heart valve replacement commonly used in clinical practice. However, calcification of TEHV is the major bottleneck to break for both clinical workers and researchers. Endothelialization [...] Read more.

The goal of tissue-engineered heart valves (TEHV) is to replace normal heart valves and overcome the shortcomings of heart valve replacement commonly used in clinical practice. However, calcification of TEHV is the major bottleneck to break for both clinical workers and researchers. Endothelialization of TEHV plays a crucial role in delaying valve calcification by reducing platelet adhesion and covering the calcified spots. In the present study, we loaded RunX2-siRNA and VEGF into mesoporous silica nanoparticles and investigated the properties of anti-calcification and endothelialization in vitro. Then, the mesoporous silica nanoparticle was immobilized on the decellularized porcine aortic valve (DPAV) by layer self-assembly and investigated the anti-calcification and endothelialization. Our results demonstrated that the mesoporous silica nanoparticles delivery vehicle demonstrated good biocompatibility, and a stable release of RunX2-siRNA and VEGF. The hybrid decellularized valve exhibited a low hemolysis rate and promoted endothelial cell proliferation and adhesion while silencing RunX2 gene expression in valve interstitial cells, and the hybrid decellularized valve showed good mechanical properties. Finally, the in vivo experiment showed that the mesoporous silica nanoparticles delivery vehicle could enhance the endothelialization of the hybrid valve. In summary, we constructed a delivery system based on mesoporous silica to biofunctionalized TEHV scaffold for endothelialization and anti-calcification. Full article

(This article belongs to the Special Issue Recent Progress in Cardiovascular Tissue Engineering and Regenerative Medicine)

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19 pages, 6368 KiB

Open AccessEditor’s ChoiceArticle

Hydrogel-Impregnated Self-Oxygenating Electrospun Scaffolds for Bone Tissue Engineering

by Robin Augustine, Vasilios K. Nikolopoulos and Gulden Camci-Unal

Bioengineering 2023, 10(7), 854; https://doi.org/10.3390/bioengineering10070854 - 19 Jul 2023

Cited by 1 | Viewed by 2092

Abstract

Bone defects resulting from trauma, disease, or aging present significant challenges in the clinic. Although biomaterial scaffolds for bone-tissue engineering have shown promising results, challenges remain, including the need for adequate mechanical strength and suitable bioactive agents within scaffolds to promote bone formation. [...] Read more.

Bone defects resulting from trauma, disease, or aging present significant challenges in the clinic. Although biomaterial scaffolds for bone-tissue engineering have shown promising results, challenges remain, including the need for adequate mechanical strength and suitable bioactive agents within scaffolds to promote bone formation. Oxygen is a critical factor for successful bone formation, and low oxygen tension inhibits it. In this study, we developed gelatin methacryloyl (GelMA) hydrogel-impregnated electrospun polycaprolactone (PCL) scaffolds that can release oxygen over 3 weeks. We investigated the potential of composite scaffolds for cell survival in bone-tissue engineering. Our results showed that the addition of an increased amount of CaO₂ nanoparticles to the PCL scaffolds significantly increased oxygen generation, which was modulated by GelMA impregnation. Moreover, the resulting scaffolds showed improved cytocompatibility, pre-osteoblast adhesion, and proliferation under hypoxic conditions. This finding is particularly relevant since hypoxia is a prevalent feature in various bone diseases. In addition to providing oxygen, CaO₂ nanoparticles also act as reinforcing agents improving the mechanical property of the scaffolds, while the incorporation of GelMA enhances cell adhesion and proliferation properties. Overall, our newly developed self-oxygenating composite biomaterials are promising scaffolds for bone-tissue engineering applications. Full article

(This article belongs to the Section Regenerative Engineering)

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16 pages, 1005 KiB

Open AccessEditor’s ChoiceReview

Microbial PolyHydroxyAlkanoate (PHA) Biopolymers—Intrinsically Natural

by Anindya Mukherjee and Martin Koller

Bioengineering 2023, 10(7), 855; https://doi.org/10.3390/bioengineering10070855 - 19 Jul 2023

Cited by 15 | Viewed by 5265

Abstract

Global pollution from fossil plastics is one of the top environmental threats of our time. At their end-of-life phase, fossil plastics, through recycling, incineration, and disposal result in microplastic formation, elevated atmospheric CO₂ levels, and the pollution of terrestrial and aquatic environments. [...] Read more.

Global pollution from fossil plastics is one of the top environmental threats of our time. At their end-of-life phase, fossil plastics, through recycling, incineration, and disposal result in microplastic formation, elevated atmospheric CO₂ levels, and the pollution of terrestrial and aquatic environments. Current regional, national, and global regulations are centered around banning plastic production and use and/or increasing recycling while ignoring efforts to rapidly replace fossil plastics through the use of alternatives, including those that occur in nature. In particular, this review demonstrates how microbial polyhydroxyalkanoates (PHAs), a class of intrinsically natural polymers, can successfully remedy the fossil and persistent plastic dilemma. PHAs are bio-based, biosynthesized, biocompatible, and biodegradable, and thus, domestically and industrially compostable. Therefore, they are an ideal replacement for the fossil plastics pollution dilemma, providing us with the benefits of fossil plastics and meeting all the requirements of a truly circular economy. PHA biopolyesters are natural and green materials in all stages of their life cycle. This review elaborates how the production, consumption, and end-of-life profile of PHAs are embedded in the current and topical, 12 Principles of Green Chemistry, which constitute the basis for sustainable product manufacturing. The time is right for a paradigm shift in plastic manufacturing, use, and disposal. Humankind needs alternatives to fossil plastics, which, as recalcitrant xenobiotics, contribute to the increasing deterioration of our planet. Natural PHA biopolyesters represent that paradigm shift. Full article

(This article belongs to the Special Issue Advances in Polyhydroxyalkanoate (PHA) Production, 4th Edition)

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26 pages, 8055 KiB

Open AccessEditor’s ChoiceArticle

Muscular and Kinematic Responses to Unexpected Translational Balance Perturbation: A Pilot Study in Healthy Young Adults

by Cheuk Ying Tong, Ringo Tang-Long Zhu, Yan To Ling, Eduardo Mendonça Scheeren, Freddy Man Hin Lam, Hong Fu and Christina Zong-Hao Ma

Bioengineering 2023, 10(7), 831; https://doi.org/10.3390/bioengineering10070831 - 13 Jul 2023

Cited by 3 | Viewed by 1764

Abstract

Falls and fall-related injuries are significant public health problems in older adults. While balance-controlling strategies have been extensively researched, there is still a lack of understanding regarding how fast the lower-limb muscles contract and coordinate in response to a sudden loss of standing [...] Read more.

Falls and fall-related injuries are significant public health problems in older adults. While balance-controlling strategies have been extensively researched, there is still a lack of understanding regarding how fast the lower-limb muscles contract and coordinate in response to a sudden loss of standing balance. Therefore, this pilot study aims to investigate the speed and timing patterns of multiple joint/muscles’ activities among the different challenges in standing balance. Twelve healthy young subjects were recruited, and they received unexpected translational balance perturbations with randomized intensities and directions. Electromyographical (EMG) and mechanomyographical (MMG) signals of eight dominant-leg’s muscles, dominant-leg’s three-dimensional (3D) hip/knee/ankle joint angles, and 3D postural sways were concurrently collected. Two-way ANOVAs were used to examine the difference in timing and speed of the collected signals among muscles/joint motions and among perturbation intensities. This study has found that (1) agonist muscles resisting the induced postural sway tended to activate more rapidly than the antagonist muscles, and ankle muscles contributed the most with the fastest rate of response; (2) voluntary corrective lower-limb joint motions and postural sways could occur as early as the perturbation-induced passive ones; (3) muscles reacted more rapidly under a larger perturbation intensity, while the joint motions or postural sways did not. These findings expand the current knowledge on standing-balance-controlling mechanisms and may potentially provide more insights for developing future fall-prevention strategies in daily life. Full article

(This article belongs to the Special Issue Biomechanics-Based Motion Analysis, Volume II)

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16 pages, 1974 KiB

Open AccessEditor’s ChoiceReview

Cancer Drug Delivery Systems Using Bacterial Toxin Translocation Mechanisms

by Linxiang Yin and Hatim Thaker

Bioengineering 2023, 10(7), 813; https://doi.org/10.3390/bioengineering10070813 - 7 Jul 2023

Cited by 2 | Viewed by 2292

Abstract

Recent advances in targeted cancer therapy hold great promise for both research and clinical applications and push the boundaries in finding new treatments for various currently incurable cancers. However, these therapies require specific cell-targeting mechanisms for the efficient delivery of drug cargo across [...] Read more.

Recent advances in targeted cancer therapy hold great promise for both research and clinical applications and push the boundaries in finding new treatments for various currently incurable cancers. However, these therapies require specific cell-targeting mechanisms for the efficient delivery of drug cargo across the cell membrane to reach intracellular targets and avoid diffusion to unwanted tissues. Traditional drug delivery systems suffer from a limited ability to travel across the barriers posed by cell membranes and, therefore, there is a need for high doses, which are associated with adverse reactions and safety concerns. Bacterial toxins have evolved naturally to specifically target cell subtypes via their receptor binding module, penetrating the cell membrane efficiently through the membrane translocation process and then successfully delivering the toxic cargo into the host cytosol. They have, thus, been harnessed for the delivery of various drugs. In this review, we focus on bacterial toxin translocation mechanisms and recent progress in the targeted delivery systems of cancer therapy drugs that have been inspired by the receptor binding and membrane translocation processes of the anthrax toxin protective antigen, diphtheria toxin, and Pseudomonas exotoxin A. We also discuss the challenges and limitations of these studies that should be addressed before bacterial toxin-based drug delivery systems can become a viable new generation of drug delivery approaches in clinical translation. Full article

(This article belongs to the Special Issue Advances in Bacterial Toxin-Based Platforms)

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15 pages, 2580 KiB

Open AccessEditor’s ChoiceArticle

Model-Based Characterization of E. coli Strains with Impaired Glucose Uptake

by Niels Krausch, Lucas Kaspersetz, Rogelio Diego Gaytán-Castro, Marie-Therese Schermeyer, Alvaro R. Lara, Guillermo Gosset, Mariano Nicolas Cruz Bournazou and Peter Neubauer

Bioengineering 2023, 10(7), 808; https://doi.org/10.3390/bioengineering10070808 - 5 Jul 2023

Cited by 2 | Viewed by 2711

Abstract

The bacterium Escherichia coli is a widely used organism in biotechnology. For high space-time yields, glucose-limited fed-batch technology is the industry standard; this is because an overflow metabolism of acetate occurs at high glucose concentrations. As an interesting alternative, various strains with limited [...] Read more.

The bacterium Escherichia coli is a widely used organism in biotechnology. For high space-time yields, glucose-limited fed-batch technology is the industry standard; this is because an overflow metabolism of acetate occurs at high glucose concentrations. As an interesting alternative, various strains with limited glucose uptake have been developed. However, these have not yet been characterized under process conditions. To demonstrate the efficiency of our previously developed high-throughput robotic platform, in the present work, we characterized three different exemplary E. coli knockout (KO) strains with limited glucose uptake capacities at three different scales (microtiter plates, 10 mL bioreactor system and 100 mL bioreactor system) under excess glucose conditions with different initial glucose concentrations. The extensive measurements of growth behavior, substrate consumption, respiration, and overflow metabolism were then used to determine the appropriate growth parameters using a mechanistic mathematical model, which allowed for a comprehensive comparative analysis of the strains. The analysis was performed coherently with these different reactor configurations and the results could be successfully transferred from one platform to another. Single and double KO mutants showed reduced specific rates for substrate uptake q_Smax and acetate production q_Apmax; meanwhile, higher glucose concentrations had adverse effects on the biomass yield coefficient Y_XSem. Additional parameters compared to previous studies for the oxygen uptake rate and carbon dioxide production rate indicated differences in the specific oxygen uptake rate q_Omax. This study is an example of how automated robotic equipment, together with mathematical model-based approaches, can be successfully used to characterize strains and obtain comprehensive information more quickly, with a trade-off between throughput and analytical capacity. Full article

(This article belongs to the Special Issue Design, Optimization and Scale-Up of Industrial Bioprocess)

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15 pages, 6536 KiB

Open AccessEditor’s ChoiceArticle

Co-Electrospun Poly(ε-Caprolactone)/Zein Articular Cartilage Scaffolds

by Andre M. Souza Plath, Stephanie Huber, Serena R. Alfarano, Daniel F. Abbott, Minghan Hu, Victor Mougel, Lucio Isa and Stephen J. Ferguson

Bioengineering 2023, 10(7), 771; https://doi.org/10.3390/bioengineering10070771 - 27 Jun 2023

Cited by 1 | Viewed by 2041

Abstract

Osteoarthritis scaffold-based grafts fail because of poor integration with the surrounding soft tissue and inadequate tribological properties. To circumvent this, we propose electrospun poly(ε-caprolactone)/zein-based scaffolds owing to their biomimetic capabilities. The scaffold surfaces were characterized using Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, static [...] Read more.

Osteoarthritis scaffold-based grafts fail because of poor integration with the surrounding soft tissue and inadequate tribological properties. To circumvent this, we propose electrospun poly(ε-caprolactone)/zein-based scaffolds owing to their biomimetic capabilities. The scaffold surfaces were characterized using Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, static water contact angles, and profilometry. Scaffold biocompatibility properties were assessed by measuring protein adsorption (Bicinchoninic Acid Assay), cell spreading (stained F-actin), and metabolic activity (PrestoBlue™ Cell Viability Reagent) of primary bovine chondrocytes. The data show that zein surface segregation in the membranes not only completely changed the hydrophobic behavior of the materials, but also increased the cell yield and metabolic activity on the scaffolds. The surface segregation is verified by the infrared peak at 1658 cm⁻¹, along with the presence and increase in N1 content in the survey XPS. This observation could explain the decrease in the water contact angles from 125° to approximately 60° in zein-comprised materials and the decrease in the protein adsorption of both bovine serum albumin and synovial fluid by half. Surface nano roughness in the PCL/zein samples additionally benefited the radial spreading of bovine chondrocytes. This study showed that co-electrospun PCL/zein scaffolds have promising surface and biocompatibility properties for use in articular-tissue-engineering applications. Full article

(This article belongs to the Special Issue Biopolymers and Nano-Objects Applications in Bioengineering)

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17 pages, 10148 KiB

Open AccessEditor’s ChoiceArticle

Progressive Rehabilitation Based on EMG Gesture Classification and an MPC-Driven Exoskeleton

by Daniel Bonilla, Manuela Bravo, Stephany P. Bonilla, Angela M. Iragorri, Diego Mendez, Ivan F. Mondragon, Catalina Alvarado-Rojas and Julian D. Colorado

Bioengineering 2023, 10(7), 770; https://doi.org/10.3390/bioengineering10070770 - 27 Jun 2023

Cited by 2 | Viewed by 2235

Abstract

Stroke is a leading cause of disability and death worldwide, with a prevalence of 200 millions of cases worldwide. Motor disability is presented in 80% of patients. In this context, physical rehabilitation plays a fundamental role for gradually recovery of mobility. In this [...] Read more.

Stroke is a leading cause of disability and death worldwide, with a prevalence of 200 millions of cases worldwide. Motor disability is presented in 80% of patients. In this context, physical rehabilitation plays a fundamental role for gradually recovery of mobility. In this work, we designed a robotic hand exoskeleton to support rehabilitation of patients after a stroke episode. The system acquires electromyographic (EMG) signals in the forearm, and automatically estimates the movement intention for five gestures. Subsequently, we developed a predictive adaptive control of the exoskeleton to compensate for three different levels of muscle fatigue during the rehabilitation therapy exercises. The proposed system could be used to assist the rehabilitation therapy of the patients by providing a repetitive, intense, and adaptive assistance. Full article

(This article belongs to the Section Biosignal Processing)

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16 pages, 7410 KiB

Open AccessEditor’s ChoiceArticle

The Power of ECG in Semi-Automated Seizure Detection in Addition to Two-Channel behind-the-Ear EEG

by Miguel Bhagubai, Kaat Vandecasteele, Lauren Swinnen, Jaiver Macea, Christos Chatzichristos, Maarten De Vos and Wim Van Paesschen

Bioengineering 2023, 10(4), 491; https://doi.org/10.3390/bioengineering10040491 - 20 Apr 2023

Cited by 3 | Viewed by 2397

Abstract

Long-term home monitoring of people living with epilepsy cannot be achieved using the standard full-scalp electroencephalography (EEG) coupled with video. Wearable seizure detection devices, such as behind-the-ear EEG (bte-EEG), offer an unobtrusive method for ambulatory follow-up of this population. Combining bte-EEG with electrocardiography [...] Read more.

Long-term home monitoring of people living with epilepsy cannot be achieved using the standard full-scalp electroencephalography (EEG) coupled with video. Wearable seizure detection devices, such as behind-the-ear EEG (bte-EEG), offer an unobtrusive method for ambulatory follow-up of this population. Combining bte-EEG with electrocardiography (ECG) can enhance automated seizure detection performance. However, such frameworks produce high false alarm rates, making visual review necessary. This study aimed to evaluate a semi-automated multimodal wearable seizure detection framework using bte-EEG and ECG. Using the SeizeIT1 dataset of 42 patients with focal epilepsy, an automated multimodal seizure detection algorithm was used to produce seizure alarms. Two reviewers evaluated the algorithm’s detections twice: (1) using only bte-EEG data and (2) using bte-EEG, ECG, and heart rate signals. The readers achieved a mean sensitivity of 59.1% in the bte-EEG visual experiment, with a false detection rate of 6.5 false detections per day. Adding ECG resulted in a higher mean sensitivity (62.2%) and a largely reduced false detection rate (mean of 2.4 false detections per day), as well as an increased inter-rater agreement. The multimodal framework allows for efficient review time, making it beneficial for both clinicians and patients. Full article

(This article belongs to the Special Issue Advances in Smart Sensing and Data Computing for Sleep Analysis, Sleep Disorders Detection and Epileptic Seizure Detection and Prediction)

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15 pages, 41119 KiB

Open AccessEditor’s ChoiceArticle

Establishment of Surgical Difficulty Grading System and Application of MRI-Based Artificial Intelligence to Stratify Difficulty in Laparoscopic Rectal Surgery

by Zhen Sun, Wenyun Hou, Weimin Liu, Jingjuan Liu, Kexuan Li, Bin Wu, Guole Lin, Huadan Xue, Junjun Pan and Yi Xiao

Bioengineering 2023, 10(4), 468; https://doi.org/10.3390/bioengineering10040468 - 12 Apr 2023

Cited by 3 | Viewed by 2034

Abstract

(1) Background: The difficulty of pelvic operation is greatly affected by anatomical constraints. Defining this difficulty and assessing it based on conventional methods has some limitations. Artificial intelligence (AI) has enabled rapid advances in surgery, but its role in assessing the difficulty of [...] Read more.

(1) Background: The difficulty of pelvic operation is greatly affected by anatomical constraints. Defining this difficulty and assessing it based on conventional methods has some limitations. Artificial intelligence (AI) has enabled rapid advances in surgery, but its role in assessing the difficulty of laparoscopic rectal surgery is unclear. This study aimed to establish a difficulty grading system to assess the difficulty of laparoscopic rectal surgery, as well as utilize this system to evaluate the reliability of pelvis-induced difficulties described by MRI-based AI. (2) Methods: Patients who underwent laparoscopic rectal surgery from March 2019 to October 2022 were included, and were divided into a non-difficult group and difficult group. This study was divided into two stages. In the first stage, a difficulty grading system was developed and proposed to assess the surgical difficulty caused by the pelvis. In the second stage, AI was used to build a model, and the ability of the model to stratify the difficulty of surgery was evaluated at this stage, based on the results of the first stage; (3) Results: Among the 108 enrolled patients, 53 patients (49.1%) were in the difficult group. Compared to the non-difficult group, there were longer operation times, more blood loss, higher rates of anastomotic leaks, and poorer specimen quality in the difficult group. In the second stage, after training and testing, the average accuracy of the four-fold cross validation models on the test set was 0.830, and the accuracy of the merged AI model was 0.800, the precision was 0.786, the specificity was 0.750, the recall was 0.846, the F1-score was 0.815, the area under the receiver operating curve was 0.78 and the average precision was 0.69; (4) Conclusions: This study successfully proposed a feasible grading system for surgery difficulty and developed a predictive model with reasonable accuracy using AI, which can assist surgeons in determining surgical difficulty and in choosing the optimal surgical approach for rectal cancer patients with a structurally difficult pelvis. Full article

(This article belongs to the Special Issue Deep Learning and Medical Innovation in Minimally Invasive Surgery)

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19 pages, 2715 KiB

Open AccessEditor’s ChoiceReview

Electrical Stimulation in Cartilage Tissue Engineering

by Raminta Vaiciuleviciute, Ilona Uzieliene, Paulius Bernotas, Vitalij Novickij, Aidas Alaburda and Eiva Bernotiene

Bioengineering 2023, 10(4), 454; https://doi.org/10.3390/bioengineering10040454 - 7 Apr 2023

Cited by 8 | Viewed by 2890

Abstract

Electrical stimulation (ES) has been frequently used in different biomedical applications both in vitro and in vivo. Numerous studies have demonstrated positive effects of ES on cellular functions, including metabolism, proliferation, and differentiation. The application of ES to cartilage tissue for increasing extracellular [...] Read more.

Electrical stimulation (ES) has been frequently used in different biomedical applications both in vitro and in vivo. Numerous studies have demonstrated positive effects of ES on cellular functions, including metabolism, proliferation, and differentiation. The application of ES to cartilage tissue for increasing extracellular matrix formation is of interest, as cartilage is not able to restore its lesions owing to its avascular nature and lack of cells. Various ES approaches have been used to stimulate chondrogenic differentiation in chondrocytes and stem cells; however, there is a huge gap in systematizing ES protocols used for chondrogenic differentiation of cells. This review focuses on the application of ES for chondrocyte and mesenchymal stem cell chondrogenesis for cartilage tissue regeneration. The effects of different types of ES on cellular functions and chondrogenic differentiation are reviewed, systematically providing ES protocols and their advantageous effects. Moreover, cartilage 3D modeling using cells in scaffolds/hydrogels under ES are observed, and recommendations on reporting about the use of ES in different studies are provided to ensure adequate consolidation of knowledge in the area of ES. This review brings novel insights into the further application of ES in in vitro studies, which are promising for further cartilage repair techniques. Full article

(This article belongs to the Special Issue Design and Fabrication of Artificial Stem Cell Microenvironments II)

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23 pages, 4305 KiB

Open AccessEditor’s ChoiceArticle

Human-Derived Cortical Neurospheroids Coupled to Passive, High-Density and 3D MEAs: A Valid Platform for Functional Tests

by Lorenzo Muzzi, Donatella Di Lisa, Matteo Falappa, Sara Pepe, Alessandro Maccione, Laura Pastorino, Sergio Martinoia and Monica Frega

Bioengineering 2023, 10(4), 449; https://doi.org/10.3390/bioengineering10040449 - 6 Apr 2023

Cited by 3 | Viewed by 3294

Abstract

With the advent of human-induced pluripotent stem cells (hiPSCs) and differentiation protocols, methods to create in-vitro human-derived neuronal networks have been proposed. Although monolayer cultures represent a valid model, adding three-dimensionality (3D) would make them more representative of an in-vivo environment. Thus, human-derived [...] Read more.

With the advent of human-induced pluripotent stem cells (hiPSCs) and differentiation protocols, methods to create in-vitro human-derived neuronal networks have been proposed. Although monolayer cultures represent a valid model, adding three-dimensionality (3D) would make them more representative of an in-vivo environment. Thus, human-derived 3D structures are becoming increasingly used for in-vitro disease modeling. Achieving control over the final cell composition and investigating the exhibited electrophysiological activity is still a challenge. Thence, methodologies to create 3D structures with controlled cellular density and composition and platforms capable of measuring and characterizing the functional aspects of these samples are needed. Here, we propose a method to rapidly generate neurospheroids of human origin with control over cell composition that can be used for functional investigations. We show a characterization of the electrophysiological activity exhibited by the neurospheroids by using micro-electrode arrays (MEAs) with different types (i.e., passive, C-MOS, and 3D) and number of electrodes. Neurospheroids grown in free culture and transferred on MEAs exhibited functional activity that can be chemically and electrically modulated. Our results indicate that this model holds great potential for an in-depth study of signal transmission to drug screening and disease modeling and offers a platform for in-vitro functional testing. Full article

(This article belongs to the Special Issue 3D Cell Culture in Disease Modeling and Tissue Regeneration)

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20 pages, 3466 KiB

Open AccessEditor’s ChoiceArticle

Fabrication of Hydrogel-Based Composite Fibers and Computer Simulation of the Filler Dynamics in the Composite Flow

by Thomas Gruhn, Camilo Ortiz Monsalve, Claudia Müller, Susanne Heid, Aldo R. Boccaccini and Sahar Salehi

Bioengineering 2023, 10(4), 448; https://doi.org/10.3390/bioengineering10040448 - 6 Apr 2023

Cited by 3 | Viewed by 2388

Abstract

Fibrous structures with anisotropic fillers as composites have found increasing interest in the field of biofabrication since they can mimic the extracellular matrix of anisotropic tissues such as skeletal muscle or nerve tissue. In the present work, the inclusion of anisotropic fillers in [...] Read more.

Fibrous structures with anisotropic fillers as composites have found increasing interest in the field of biofabrication since they can mimic the extracellular matrix of anisotropic tissues such as skeletal muscle or nerve tissue. In the present work, the inclusion of anisotropic fillers in hydrogel-based filaments with an interpenetrating polymeric network (IPN) was evaluated and the dynamics of such fillers in the composite flow were analyzed using computational simulations. In the experimental part, microfabricated rods (200 and 400 μm length, 50 μm width) were used as anisotropic fillers in extrusion of composite filaments using two techniques of wet spinning and 3D printing. Hydrogels such as oxidized alginate (ADA) and methacrylated gelatin (GelMA) were used as matrices. In the computational simulation, a combination of computational fluid dynamics and coarse-grained molecular dynamics was used to study the dynamics of rod-like fillers in the flow field of a syringe. It showed that, during the extrusion process, microrods are far from being well aligned. Instead, many of them tumble on their way through the needle leading to a random orientation in the fiber which was confirmed experimentally. Full article

(This article belongs to the Special Issue 3D-Bioprinting in Bioengineering)

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20 pages, 1639 KiB

Open AccessEditor’s ChoiceSystematic Review

Machine Learning for Brain MRI Data Harmonisation: A Systematic Review

by Grace Wen, Vickie Shim, Samantha Jane Holdsworth, Justin Fernandez, Miao Qiao, Nikola Kasabov and Alan Wang

Bioengineering 2023, 10(4), 397; https://doi.org/10.3390/bioengineering10040397 - 23 Mar 2023

Cited by 4 | Viewed by 3817

Abstract

Background: Magnetic Resonance Imaging (MRI) data collected from multiple centres can be heterogeneous due to factors such as the scanner used and the site location. To reduce this heterogeneity, the data needs to be harmonised. In recent years, machine learning (ML) has been [...] Read more.

Background: Magnetic Resonance Imaging (MRI) data collected from multiple centres can be heterogeneous due to factors such as the scanner used and the site location. To reduce this heterogeneity, the data needs to be harmonised. In recent years, machine learning (ML) has been used to solve different types of problems related to MRI data, showing great promise. Objective: This study explores how well various ML algorithms perform in harmonising MRI data, both implicitly and explicitly, by summarising the findings in relevant peer-reviewed articles. Furthermore, it provides guidelines for the use of current methods and identifies potential future research directions. Method: This review covers articles published through PubMed, Web of Science, and IEEE databases through June 2022. Data from studies were analysed based on the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Quality assessment questions were derived to assess the quality of the included publications. Results: a total of 41 articles published between 2015 and 2022 were identified and analysed. In the review, MRI data has been found to be harmonised either in an implicit (n = 21) or an explicit (n = 20) way. Three MRI modalities were identified: structural MRI (n = 28), diffusion MRI (n = 7) and functional MRI (n = 6). Conclusion: Various ML techniques have been employed to harmonise different types of MRI data. There is currently a lack of consistent evaluation methods and metrics used across studies, and it is recommended that the issue be addressed in future studies. Harmonisation of MRI data using ML shows promises in improving performance for ML downstream tasks, while caution should be exercised when using ML-harmonised data for direct interpretation. Full article

(This article belongs to the Special Issue Artificial Intelligence in Biomedical Imaging)

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48 pages, 4845 KiB

Open AccessEditor’s ChoiceReview

Connectivity Analysis in EEG Data: A Tutorial Review of the State of the Art and Emerging Trends

by Giovanni Chiarion, Laura Sparacino, Yuri Antonacci, Luca Faes and Luca Mesin

Bioengineering 2023, 10(3), 372; https://doi.org/10.3390/bioengineering10030372 - 17 Mar 2023

Cited by 33 | Viewed by 9768

Abstract

Understanding how different areas of the human brain communicate with each other is a crucial issue in neuroscience. The concepts of structural, functional and effective connectivity have been widely exploited to describe the human connectome, consisting of brain networks, their structural connections and [...] Read more.

Understanding how different areas of the human brain communicate with each other is a crucial issue in neuroscience. The concepts of structural, functional and effective connectivity have been widely exploited to describe the human connectome, consisting of brain networks, their structural connections and functional interactions. Despite high-spatial-resolution imaging techniques such as functional magnetic resonance imaging (fMRI) being widely used to map this complex network of multiple interactions, electroencephalographic (EEG) recordings claim high temporal resolution and are thus perfectly suitable to describe either spatially distributed and temporally dynamic patterns of neural activation and connectivity. In this work, we provide a technical account and a categorization of the most-used data-driven approaches to assess brain-functional connectivity, intended as the study of the statistical dependencies between the recorded EEG signals. Different pairwise and multivariate, as well as directed and non-directed connectivity metrics are discussed with a pros–cons approach, in the time, frequency, and information-theoretic domains. The establishment of conceptual and mathematical relationships between metrics from these three frameworks, and the discussion of novel methodological approaches, will allow the reader to go deep into the problem of inferring functional connectivity in complex networks. Furthermore, emerging trends for the description of extended forms of connectivity (e.g., high-order interactions) are also discussed, along with graph-theory tools exploring the topological properties of the network of connections provided by the proposed metrics. Applications to EEG data are reviewed. In addition, the importance of source localization, and the impacts of signal acquisition and pre-processing techniques (e.g., filtering, source localization, and artifact rejection) on the connectivity estimates are recognized and discussed. By going through this review, the reader could delve deeply into the entire process of EEG pre-processing and analysis for the study of brain functional connectivity and learning, thereby exploiting novel methodologies and approaches to the problem of inferring connectivity within complex networks. Full article

(This article belongs to the Special Issue Featured Papers in Computer Methods in Biomedicine)

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