Bioengineering

9 pages, 2282 KB

Open AccessEditor’s ChoiceArticle

Computational Fluid Dynamic Optimization of Micropatterned Surfaces: Towards Biofunctionalization of Artificial Organs

by Wenxuan He, Aminat M. Ibrahim, Abhishek Karmakar, Shivani Tuli, Jonathan T. Butcher and James F. Antaki

Bioengineering 2024, 11(11), 1092; https://doi.org/10.3390/bioengineering11111092 - 30 Oct 2024

Viewed by 1609

Abstract

Modifying surface topography to prevent surface-induced thrombosis in cardiovascular implants allows endothelialization, which is the natural thrombo-resistance of blood-contacting surfaces, and is deemed to be the only long-term solution for hemocompatible materials. We adapted a simulation framework to predict platelet deposition on a [...] Read more.

Modifying surface topography to prevent surface-induced thrombosis in cardiovascular implants allows endothelialization, which is the natural thrombo-resistance of blood-contacting surfaces, and is deemed to be the only long-term solution for hemocompatible materials. We adapted a simulation framework to predict platelet deposition on a modified surface and developed an optimization strategy to promote endothelial retention and limit platelet deposition. Under supraphysiological bulk shear stress, a maximum of 79% linear coverage was achieved. This study concludes that the addition of microtrenches promotes endothelial retention and can be improved through the optimal selection of geometric parameters. Full article

(This article belongs to the Special Issue Engineered Analysis of Tissue Mechanics and Blood Flow for Cardiovascular Host-Device Interaction)

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5 pages, 184 KB

Open AccessEditor’s ChoiceEditorial

Interdisciplinary Innovations and Applications of Bionics and Bioengineering in Kinesiology

by Wei-Hsun Tai, Wenjian Wu, Haibin Yu and Rui Zhang

Bioengineering 2024, 11(10), 1042; https://doi.org/10.3390/bioengineering11101042 - 18 Oct 2024

Viewed by 2367

Abstract

Kinesiology, as an interdisciplinary field, emphasizes the study of human physical activity, with a particular focus on biomechanics and sports science [...] Full article

(This article belongs to the Special Issue Biomechanics and Bionics in Sport and Exercise, Volume II)

15 pages, 2088 KB

Open AccessEditor’s ChoiceReview

The Psychological Nature of Female Gait Attractiveness

by Hiroko Tanabe and Kota Yamamoto

Bioengineering 2024, 11(10), 1037; https://doi.org/10.3390/bioengineering11101037 - 17 Oct 2024

Cited by 3 | Viewed by 4472

Abstract

Walking, a basic physical movement of the human body, is a resource for observers in forming interpersonal impressions. We have previously investigated the expression and perception of the attractiveness of female gaits. In this paper, drawing on our previous research, additional analysis, and [...] Read more.

Walking, a basic physical movement of the human body, is a resource for observers in forming interpersonal impressions. We have previously investigated the expression and perception of the attractiveness of female gaits. In this paper, drawing on our previous research, additional analysis, and reviewing previous studies, we seek to deepen our understanding of the function of gait attractiveness. First, we review previous research on gait as nonverbal information. Then, we show that fashion models’ gaits reflect sociocultural genderlessness, while nonmodels express reproductive-related biological attractiveness. Next, we discuss the functions of gait attractiveness based on statistical models that link gait parameters and attractiveness scores. Finally, we focus on observers’ perception of attractiveness, constructing a model of the visual information processing with respect to gait attractiveness. Overall, our results suggest that there are not only biological but also sociocultural criteria for gait attractiveness, and men and women place greater importance on the former and latter criteria, respectively, when assessing female gait attractiveness. This paper forms a major step forward in neuroaesthetics to understand the beauty of the human body and the generation of biological motions. Full article

(This article belongs to the Special Issue Bioengineering of the Motor System)

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22 pages, 2282 KB

Open AccessEditor’s ChoiceArticle

Emotion Recognition Using EEG Signals and Audiovisual Features with Contrastive Learning

by Ju-Hwan Lee, Jin-Young Kim and Hyoung-Gook Kim

Bioengineering 2024, 11(10), 997; https://doi.org/10.3390/bioengineering11100997 - 3 Oct 2024

Cited by 12 | Viewed by 5951

Abstract

Multimodal emotion recognition has emerged as a promising approach to capture the complex nature of human emotions by integrating information from various sources such as physiological signals, visual behavioral cues, and audio-visual content. However, current methods often struggle with effectively processing redundant or [...] Read more.

Multimodal emotion recognition has emerged as a promising approach to capture the complex nature of human emotions by integrating information from various sources such as physiological signals, visual behavioral cues, and audio-visual content. However, current methods often struggle with effectively processing redundant or conflicting information across modalities and may overlook implicit inter-modal correlations. To address these challenges, this paper presents a novel multimodal emotion recognition framework which integrates audio-visual features with viewers’ EEG data to enhance emotion classification accuracy. The proposed approach employs modality-specific encoders to extract spatiotemporal features, which are then aligned through contrastive learning to capture inter-modal relationships. Additionally, cross-modal attention mechanisms are incorporated for effective feature fusion across modalities. The framework, comprising pre-training, fine-tuning, and testing phases, is evaluated on multiple datasets of emotional responses. The experimental results demonstrate that the proposed multimodal approach, which combines audio-visual features with EEG data, is highly effective in recognizing emotions, highlighting its potential for advancing emotion recognition systems. Full article

(This article belongs to the Special Issue Recent Advances in Machine Learning and Explainable Artificial Intelligence in Biomedical Data Mining, and Disease Diagnosis Frameworks)

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33 pages, 3011 KB

Open AccessEditor’s ChoiceReview

Building an Ethical and Trustworthy Biomedical AI Ecosystem for the Translational and Clinical Integration of Foundation Models

by Baradwaj Simha Sankar, Destiny Gilliland, Jack Rincon, Henning Hermjakob, Yu Yan, Irsyad Adam, Gwyneth Lemaster, Dean Wang, Karol Watson, Alex Bui, Wei Wang and Peipei Ping

Bioengineering 2024, 11(10), 984; https://doi.org/10.3390/bioengineering11100984 - 29 Sep 2024

Cited by 12 | Viewed by 5495

Abstract

Foundation Models (FMs) are gaining increasing attention in the biomedical artificial intelligence (AI) ecosystem due to their ability to represent and contextualize multimodal biomedical data. These capabilities make FMs a valuable tool for a variety of tasks, including biomedical reasoning, hypothesis generation, and [...] Read more.

Foundation Models (FMs) are gaining increasing attention in the biomedical artificial intelligence (AI) ecosystem due to their ability to represent and contextualize multimodal biomedical data. These capabilities make FMs a valuable tool for a variety of tasks, including biomedical reasoning, hypothesis generation, and interpreting complex imaging data. In this review paper, we address the unique challenges associated with establishing an ethical and trustworthy biomedical AI ecosystem, with a particular focus on the development of FMs and their downstream applications. We explore strategies that can be implemented throughout the biomedical AI pipeline to effectively tackle these challenges, ensuring that these FMs are translated responsibly into clinical and translational settings. Additionally, we emphasize the importance of key stewardship and co-design principles that not only ensure robust regulation but also guarantee that the interests of all stakeholders—especially those involved in or affected by these clinical and translational applications—are adequately represented. We aim to empower the biomedical AI community to harness these models responsibly and effectively. As we navigate this exciting frontier, our collective commitment to ethical stewardship, co-design, and responsible translation will be instrumental in ensuring that the evolution of FMs truly enhances patient care and medical decision-making, ultimately leading to a more equitable and trustworthy biomedical AI ecosystem. Full article

(This article belongs to the Special Issue Machine Learning Technology in Biomedical Engineering—2nd Edition)

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15 pages, 1321 KB

Open AccessEditor’s ChoiceCommentary

The Use of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles in the Treatment of Osteoarthritis: Insights from Preclinical Studies

by Mitch Jones, Elena Jones and Dimitrios Kouroupis

Bioengineering 2024, 11(10), 961; https://doi.org/10.3390/bioengineering11100961 - 26 Sep 2024

Cited by 5 | Viewed by 3230

Abstract

Osteoarthritis (OA) is a prominent cause of disability, and has severe social and economic ramifications across the globe. The main driver of OA’s pervasiveness is the fact that no current medical interventions exist to reverse or even attenuate the degeneration of cartilage within [...] Read more.

Osteoarthritis (OA) is a prominent cause of disability, and has severe social and economic ramifications across the globe. The main driver of OA’s pervasiveness is the fact that no current medical interventions exist to reverse or even attenuate the degeneration of cartilage within the articular joint. Crucial for cell-to-cell communication, extracellular vesicles (EVs) contribute to OA progression through the delivery of bioactive molecules in the inflammatory microenvironment. By repurposing this acellular means of signal transmission, therapeutic drugs may be administered to degenerated cartilage tissue in the hopes of encouraging regeneration. Positive outcomes are apparent in in vivo studies on this subject; however, for this therapy to prove itself in the clinical world, efforts towards standardizing the characterization, application, biological contents, and dosage are essential. Full article

(This article belongs to the Section Regenerative Engineering)

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6 pages, 213 KB

Open AccessEditor’s ChoiceEditorial

Microalgae Biotechnology: Methods and Applications

by Xianmin Wang, Songlin Ma and Fantao Kong

Bioengineering 2024, 11(10), 965; https://doi.org/10.3390/bioengineering11100965 - 26 Sep 2024

Cited by 8 | Viewed by 4729

Abstract

Microalgae are regarded as sustainable and promising chassis for biotechnology due to their efficient photosynthesis and ability to convert CO₂ into valuable products [...] Full article

(This article belongs to the Section Biochemical Engineering)

23 pages, 6104 KB

Open AccessEditor’s ChoiceArticle

Mesenchymal Stem Cell-Conditioned Media-Loaded Microparticles Enhance Acute Patency in Silk-Based Vascular Grafts

by Katherine L. Lorentz, Ande X. Marini, Liza A. Bruk, Prerak Gupta, Biman B. Mandal, Morgan V. DiLeo, Justin S. Weinbaum, Steven R. Little and David A. Vorp

Bioengineering 2024, 11(9), 947; https://doi.org/10.3390/bioengineering11090947 - 21 Sep 2024

Cited by 1 | Viewed by 3258

Abstract

Coronary artery disease leads to over 360,000 deaths annually in the United States, and off-the-shelf bypass graft options are currently limited and/or have high failure rates. Tissue-engineered vascular grafts (TEVGs) present an attractive option, though the promising mesenchymal stem cell (MSC)-based implants face [...] Read more.

Coronary artery disease leads to over 360,000 deaths annually in the United States, and off-the-shelf bypass graft options are currently limited and/or have high failure rates. Tissue-engineered vascular grafts (TEVGs) present an attractive option, though the promising mesenchymal stem cell (MSC)-based implants face uncertain regulatory pathways. In this study, “artificial MSCs” (ArtMSCs) were fabricated by encapsulating MSC-conditioned media (CM) in poly(lactic-co-glycolic acid) microparticles. ArtMSCs and control microparticles (Blank-MPs) were incubated over 7 days to assess the release of total protein and the vascular endothelial growth factor (VEGF-A); releasates were also assessed for cytotoxicity and promotion of smooth muscle cell (SMC) proliferation. Each MP type was loaded in previously published “lyogel” silk scaffolds and implanted as interposition grafts in Lewis rats for 1 or 8 weeks. Explanted grafts were assessed for patency and cell content. ArtMSCs had a burst release of protein and VEGF-A. CM increased proliferation in SMCs, but not after encapsulation. TEVG explants after 1 week had significantly higher patency rates with ArtMSCs compared to Blank-MPs, but similar to unseeded lyogel grafts. ArtMSC explants had lower numbers of infiltrating macrophages compared to Blank-MP explants, suggesting a modulation of inflammatory response by the ArtMSCs. TEVG explants after 8 weeks showed no significant difference in patency among the three groups. The ArtMSC explants showed higher numbers of SMCs and endothelial cells within the neotissue layer of the graft compared to Blank-MP explants. In sum, while the ArtMSCs had positive effects acutely, efficacy was lost in the longer term; therefore, further optimization is needed. Full article

(This article belongs to the Section Regenerative Engineering)

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15 pages, 1570 KB

Open AccessEditor’s ChoiceArticle

Machine Learning-Driven Prediction of Brain Age for Alzheimer’s Risk: APOE4 Genotype and Gender Effects

by Carter Woods, Xin Xing, Subash Khanal and Ai-Ling Lin

Bioengineering 2024, 11(9), 943; https://doi.org/10.3390/bioengineering11090943 - 20 Sep 2024

Cited by 2 | Viewed by 4054

Abstract

Background: Alzheimer’s disease (AD) is a leading cause of dementia, and it is significantly influenced by the apolipoprotein E4 (APOE4) gene and gender. This study aimed to use machine learning (ML) algorithms to predict brain age and assess AD risk by considering the [...] Read more.

Background: Alzheimer’s disease (AD) is a leading cause of dementia, and it is significantly influenced by the apolipoprotein E4 (APOE4) gene and gender. This study aimed to use machine learning (ML) algorithms to predict brain age and assess AD risk by considering the effects of the APOE4 genotype and gender. Methods: We collected brain volumetric MRI data and medical records from 1100 cognitively unimpaired individuals and 602 patients with AD. We applied three ML regression models—XGBoost, random forest (RF), and linear regression (LR)—to predict brain age. Additionally, we introduced two novel metrics, brain age difference (BAD) and integrated difference (ID), to evaluate the models’ performances and analyze the influences of the APOE4 genotype and gender on brain aging. Results: Patients with AD displayed significantly older brain ages compared to their chronological ages, with BADs ranging from 6.5 to 10 years. The RF model outperformed both XGBoost and LR in terms of accuracy, delivering higher ID values and more precise predictions. Comparing the APOE4 carriers with noncarriers, the models showed enhanced ID values and consistent brain age predictions, improving the overall performance. Gender-specific analyses indicated slight enhancements, with the models performing equally well for both genders. Conclusions: This study demonstrates that robust ML models for brain age prediction can play a crucial role in the early detection of AD risk through MRI brain structural imaging. The significant impact of the APOE4 genotype on brain aging and AD risk is also emphasized. These findings highlight the potential of ML models in assessing AD risk and suggest that utilizing AI for AD identification could enable earlier preventative interventions. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Imaging: 2nd Edition)

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10 pages, 2484 KB

Open AccessEditor’s ChoiceArticle

Thermal Evaluation of Bone Drilling: Assessing Drill Bits and Sequential Drilling

by Sihana Rugova and Marcus Abboud

Bioengineering 2024, 11(9), 928; https://doi.org/10.3390/bioengineering11090928 - 16 Sep 2024

Cited by 6 | Viewed by 2430

Abstract

Sequential drilling is a common practice in dental implant surgery aimed at minimizing thermal damage to bone. This study evaluates the thermal effects of sequential drilling and assesses modifications to drilling protocols to manage heat generation. We utilized a custom drill press and [...] Read more.

Sequential drilling is a common practice in dental implant surgery aimed at minimizing thermal damage to bone. This study evaluates the thermal effects of sequential drilling and assesses modifications to drilling protocols to manage heat generation. We utilized a custom drill press and artificial bone models to test five drill bits under various protocols, including sequential drilling with different loads, spindle speeds, and peck drilling. Infrared thermography recorded temperature changes during the drilling process, with temperatures monitored at various depths around the osteotomy. The results reveal sequential drilling does not eliminate the thermal damage zone it creates (well over 70 °C). It creates harmful heat to surrounding bone that can spread up to 10 mm from the osteotomy. The first drill used in sequential drilling produces the highest temperatures (over 100 °C), and subsequent drill bits cannot remove the thermal trauma incurred; rather, they add to it. Modifying drill bit design and employing proper drilling techniques, such as reducing drilling RPM and load, can reduce thermal trauma by reducing friction. Inadequate management of heat can lead to prolonged recovery, increased patient discomfort, and potential long-term complications such as impaired bone-to-implant integration and chronic conditions like peri-implantitis. Ensuring healthy bone conditions is critical for successful implant outcomes. Full article

(This article belongs to the Special Issue Advanced Assessment of Medical Devices)

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5 pages, 154 KB

Open AccessEditor’s ChoiceEditorial

Advanced Engineering Technology in Orthopedic Research

by Rongshan Cheng, Huizhi Wang and Cheng-Kung Cheng

Bioengineering 2024, 11(9), 925; https://doi.org/10.3390/bioengineering11090925 - 15 Sep 2024

Cited by 2 | Viewed by 1870

Abstract

Musculoskeletal injuries are increasing in conjunction with the aging of populations and the rising frequency of exercise [...] Full article

(This article belongs to the Special Issue Advanced Engineering Technology in Orthopaedic Research)

18 pages, 1415 KB

Open AccessEditor’s ChoiceArticle

Optimizing Fall Risk Diagnosis in Older Adults Using a Bayesian Classifier and Simulated Annealing

by Enrique Hernandez-Laredo, Ángel Gabriel Estévez-Pedraza, Laura Mercedes Santiago-Fuentes and Lorena Parra-Rodríguez

Bioengineering 2024, 11(9), 908; https://doi.org/10.3390/bioengineering11090908 - 11 Sep 2024

Cited by 1 | Viewed by 2161

Abstract

The aim of this study was to improve the diagnostic ability of fall risk classifiers using a Bayesian approach and the Simulated Annealing (SA) algorithm. A total of 47 features from 181 records (40 Center of Pressure (CoP) indices and 7 patient descriptive [...] Read more.

The aim of this study was to improve the diagnostic ability of fall risk classifiers using a Bayesian approach and the Simulated Annealing (SA) algorithm. A total of 47 features from 181 records (40 Center of Pressure (CoP) indices and 7 patient descriptive variables) were analyzed. The wrapper method of feature selection using the SA algorithm was applied to optimize the cost function based on the difference of the mean minus the standard deviation of the Area Under the Curve (AUC) of the fall risk classifiers across multiple dimensions. A stratified 60–20–20% hold-out method was used for train, test, and validation sets, respectively. The results showed that although the highest performance was observed with 31 features (0.815 ± 0.110), lower variability and higher explainability were achieved with only 15 features (0.780 ± 0.055). These findings suggest that the SA algorithm is a valuable tool for feature selection for acceptable fall risk diagnosis. This method offers an alternative or complementary resource in situations where clinical tools are difficult to apply. Full article

(This article belongs to the Special Issue Musculoskeletal Disorders and Diseases: Biomechanical Modeling in Sport, Health, Rehabilitation and Ergonomics)

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18 pages, 7246 KB

Open AccessEditor’s ChoiceArticle

Comparative Study of Alternative Methods for Measuring Leg Length Discrepancy after Robot-Assisted Total Hip Arthroplasty

by Hamad Nazmy, Giovanni Solitro, Benjamin Domb and Farid Amirouche

Bioengineering 2024, 11(8), 853; https://doi.org/10.3390/bioengineering11080853 - 21 Aug 2024

Cited by 3 | Viewed by 4455

Abstract

Background: Our study addresses the lack of consensus on measuring leg length discrepancy (LLD) after total hip arthroplasty (THA). We will assess the inter-observer variability and correlation between the five most commonly used LLD methods and investigate the use of trigonometric principles in [...] Read more.

Background: Our study addresses the lack of consensus on measuring leg length discrepancy (LLD) after total hip arthroplasty (THA). We will assess the inter-observer variability and correlation between the five most commonly used LLD methods and investigate the use of trigonometric principles in overcoming the limitations of current techniques. Methods: LLD was measured on postoperative AP pelvic radiographs using five conventional methods. CT images created a 3D computer model of the pelvis and femur. The resulting models were projected onto a 2D, used to measure LLD by the five methods. The measurements were evaluated via Taguchi analysis, a statistical method identifying the process’s most influential factors. The approach was used to assess the new trigonometric method. Results: Conventional methods demonstrated poor correlation. Methods referenced to the centers of the femoral heads were insensitive to LLD originating outside the acetabular cup. Methods referencing either the inter-ischial line or the inter-obturator foramina to the lesser trochanter were sensitive to acetabular and femoral components. Trigonometry-based measurements showed a higher correlation. Conclusions: Our results underscore clinicians’ need to specify the methods used to assess LLD. Applying trigonometric principles was shown to be accurate and reliable, but it was contingent on proper radiographic alignment. Full article

(This article belongs to the Special Issue Fundamentals of Orthopaedic Biomechanics: Implants, AI, and Innovation in Surgery)

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20 pages, 4364 KB

Open AccessEditor’s ChoiceArticle

3D Quantitative-Amplified Magnetic Resonance Imaging (3D q-aMRI)

by Itamar Terem, Kyan Younes, Nan Wang, Paul Condron, Javid Abderezaei, Haribalan Kumar, Hillary Vossler, Eryn Kwon, Mehmet Kurt, Elizabeth Mormino, Samantha Holdsworth and Kawin Setsompop

Bioengineering 2024, 11(8), 851; https://doi.org/10.3390/bioengineering11080851 - 20 Aug 2024

Cited by 6 | Viewed by 4236

Abstract

Amplified MRI (aMRI) is a promising new technique that can visualize pulsatile brain tissue motion by amplifying sub-voxel motion in cine MRI data, but it lacks the ability to quantify the sub-voxel motion field in physical units. Here, we introduce a novel post-processing [...] Read more.

Amplified MRI (aMRI) is a promising new technique that can visualize pulsatile brain tissue motion by amplifying sub-voxel motion in cine MRI data, but it lacks the ability to quantify the sub-voxel motion field in physical units. Here, we introduce a novel post-processing algorithm called 3D quantitative amplified MRI (3D q-aMRI). This algorithm enables the visualization and quantification of pulsatile brain motion. 3D q-aMRI was validated and optimized on a 3D digital phantom and was applied in vivo on healthy volunteers for its ability to accurately measure brain parenchyma and CSF voxel displacement. Simulation results show that 3D q-aMRI can accurately quantify sub-voxel motions in the order of 0.01 of a voxel size. The algorithm hyperparameters were optimized and tested on in vivo data. The repeatability and reproducibility of 3D q-aMRI were shown on six healthy volunteers. The voxel displacement field extracted by 3D q-aMRI is highly correlated with the displacement measurements estimated by phase contrast (PC) MRI. In addition, the voxel displacement profile through the cerebral aqueduct resembled the CSF flow profile reported in previous literature. Differences in brain motion was observed in patients with dementia compared with age-matched healthy controls. In summary, 3D q-aMRI is a promising new technique that can both visualize and quantify pulsatile brain motion. Its ability to accurately quantify sub-voxel motion in physical units holds potential for the assessment of pulsatile brain motion as well as the indirect assessment of CSF homeostasis. While further research is warranted, 3D q-aMRI may provide important diagnostic information for neurological disorders such as Alzheimer’s disease. Full article

(This article belongs to the Special Issue Novel MRI Techniques and Biomedical Image Processing)

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14 pages, 3003 KB

Open AccessEditor’s ChoiceArticle

Stable and Thin-Polymer-Based Modification of Neurovascular Stents with 2-Methacryloyloxyethyl Phosphorylcholine Polymer for Antithrombogenicity

by Naoki Inuzuka, Yasuhiro Shobayashi, Satoshi Tateshima, Yuya Sato, Yoshio Ohba, Kazuhiko Ishihara and Yuji Teramura

Bioengineering 2024, 11(8), 833; https://doi.org/10.3390/bioengineering11080833 - 15 Aug 2024

Cited by 4 | Viewed by 4030

Abstract

The advent of intracranial stents has revolutionized the endovascular treatment of cerebral aneurysms. The utilization of stents has rendered numerous cerebral aneurysm amenable to endovascular treatment, thereby obviating the need for otherwise invasive open surgical options. Stent placement has become a mainstream approach [...] Read more.

The advent of intracranial stents has revolutionized the endovascular treatment of cerebral aneurysms. The utilization of stents has rendered numerous cerebral aneurysm amenable to endovascular treatment, thereby obviating the need for otherwise invasive open surgical options. Stent placement has become a mainstream approach because of its safety and efficacy. However, further improvements are required for clinically approved devices to avoid the frequent occurrence of thrombotic complications. Therefore, controlling the thrombotic complications associated with the use of devices is of significant importance. Our group has developed a unique stent coated with a 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer. In this study, the surface characteristics of the polymer coating were verified using X-ray photoelectron spectroscopy and atomic force microscopy. Subsequently, the antithrombotic properties of the coating were evaluated by measuring platelet count and thrombin–antithrombin complex levels of whole human blood after 3 h of incubation in a Chandler loop model. Scanning electron microscopy was utilized to examine thrombus formation on the stent surface. We observed that MPC polymer-coated stents significantly reduced thrombus formation as compared to bare stents and several clinically approved devices. Finally, the coated stents were further analyzed by implanting them in the internal thoracic arteries of pigs. Angiographic imaging and histopathological examinations that were performed one week after implantation revealed that the vascular lumen was well maintained and coated stents were integrated within the vascular endothelium without inducing adverse effects. Thus, we demonstrated the efficacy of MPC polymer coating as a viable strategy for avoiding the thrombotic risks associated with neurovascular stents. Full article

(This article belongs to the Special Issue Advanced Biomaterials, Coatings, and Techniques: Applications in Medicine)

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16 pages, 5882 KB

Open AccessEditor’s ChoiceArticle

Perlecan: An Islet Basement Membrane Protein with Protective Anti-Inflammatory Characteristics

by Daniel Brandhorst, Heide Brandhorst, Samuel Acreman and Paul R. V. Johnson

Bioengineering 2024, 11(8), 828; https://doi.org/10.3390/bioengineering11080828 - 13 Aug 2024

Cited by 1 | Viewed by 1849

Abstract

Throughout the isolation process, human islets are subjected to destruction of the islet basement membrane (BM) and reduced oxygen supply. Reconstruction of the BM represents an option to improve islet function and survival post-transplant and may particularly be relevant for islet encapsulation devices [...] Read more.

Throughout the isolation process, human islets are subjected to destruction of the islet basement membrane (BM) and reduced oxygen supply. Reconstruction of the BM represents an option to improve islet function and survival post-transplant and may particularly be relevant for islet encapsulation devices and scaffolds. In the present study, we assessed whether Perlecan, used alone or combined with the BM proteins (BMPs) Collagen-IV and Laminin-521, has the ability to protect isolated human islets from hypoxia-induced damage. Islets isolated from the pancreas of seven different organ donors were cultured for 4–5 days at 2% oxygen in plain CMRL (sham-treated controls) or in CMRL supplemented with BMPs used either alone or in combination. Postculture, islets were characterized regarding survival, in vitro function and production of chemokines and reactive oxygen species (ROS). Individually added BMPs significantly doubled islet survival and increased in vitro function. Combining BMPs did not provide a synergistic effect. Among the tested BMPs, Perlecan demonstrated the significantly strongest inhibitory effect on chemokine and ROS production when compared with sham-treatment (p < 0.001). Perlecan may be useful to improve islet survival prior to and after transplantation. Its anti-inflammatory potency should be considered to optimise encapsulation and scaffolds to protect isolated human islets post-transplant. Full article

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

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4 pages, 179 KB

Open AccessEditor’s ChoiceEditorial

Advancements in Biomedical and Bioengineering Technologies in Sports Monitoring and Healthcare

by Yaodong Gu and Justin Fernandez

Bioengineering 2024, 11(8), 816; https://doi.org/10.3390/bioengineering11080816 - 12 Aug 2024

Viewed by 2480

Abstract

The intersection of biomedical and bioengineering technologies with sports monitoring and healthcare has recently emerged as a key area of innovation and research [...] Full article

(This article belongs to the Special Issue Biomedical and Bioengineering Technology: Current Applications in Sports Monitoring and Health Care)

25 pages, 1522 KB

Open AccessEditor’s ChoiceReview

Toward Fully Automated Personalized Orthopedic Treatments: Innovations and Interdisciplinary Gaps

by Yunhua Luo

Bioengineering 2024, 11(8), 817; https://doi.org/10.3390/bioengineering11080817 - 12 Aug 2024

Cited by 10 | Viewed by 3657

Abstract

Personalized orthopedic devices are increasingly favored for their potential to enhance long-term treatment success. Despite significant advancements across various disciplines, the seamless integration and full automation of personalized orthopedic treatments remain elusive. This paper identifies key interdisciplinary gaps in integrating and automating advanced [...] Read more.

Personalized orthopedic devices are increasingly favored for their potential to enhance long-term treatment success. Despite significant advancements across various disciplines, the seamless integration and full automation of personalized orthopedic treatments remain elusive. This paper identifies key interdisciplinary gaps in integrating and automating advanced technologies for personalized orthopedic treatment. It begins by outlining the standard clinical practices in orthopedic treatments and the extent of personalization achievable. The paper then explores recent innovations in artificial intelligence, biomaterials, genomic and proteomic analyses, lab-on-a-chip, medical imaging, image-based biomechanical finite element modeling, biomimicry, 3D printing and bioprinting, and implantable sensors, emphasizing their contributions to personalized treatments. Tentative strategies or solutions are proposed to address the interdisciplinary gaps by utilizing innovative technologies. The key findings highlight the need for the non-invasive quantitative assessment of bone quality, patient-specific biocompatibility, and device designs that address individual biological and mechanical conditions. This comprehensive review underscores the transformative potential of these technologies and the importance of multidisciplinary collaboration to integrate and automate them into a cohesive, intelligent system for personalized orthopedic treatments. Full article

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

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16 pages, 3418 KB

Open AccessEditor’s ChoiceArticle

Biomechanical Study of Symmetric Bending and Lifting Behavior in Weightlifter with Lumbar L4-L5 Disc Herniation and Physiological Straightening Using Finite Element Simulation

by Caiting Zhang, Yang Song, Qiaolin Zhang, Ee-Chon Teo and Wei Liu

Bioengineering 2024, 11(8), 825; https://doi.org/10.3390/bioengineering11080825 - 12 Aug 2024

Cited by 2 | Viewed by 5217

Abstract

Background: Physiological curvature changes of the lumbar spine and disc herniation can cause abnormal biomechanical responses of the lumbar spine. Finite element (FE) studies on special weightlifter models are limited, yet understanding stress in damaged lumbar spines is crucial for preventing and rehabilitating [...] Read more.

Background: Physiological curvature changes of the lumbar spine and disc herniation can cause abnormal biomechanical responses of the lumbar spine. Finite element (FE) studies on special weightlifter models are limited, yet understanding stress in damaged lumbar spines is crucial for preventing and rehabilitating lumbar diseases. This study analyzes the biomechanical responses of a weightlifter with lumbar straightening and L4-L5 disc herniation during symmetric bending and lifting to optimize training and rehabilitation. Methods: Based on the weightlifter’s computed tomography (CT) data, an FE lumbar spine model (L1-L5) was established. The model included normal intervertebral discs (IVDs), vertebral endplates, ligaments, and a degenerated L4-L5 disc. The bending angle was set to 45°, and weights of 15 kg, 20 kg, and 25 kg were used. The flexion moment for lifting these weights was theoretically calculated. The model was tilted at 45° in Abaqus 2021 (Dassault Systèmes Simulia Corp., Johnston, RI, USA), with L5 constrained in all six degrees of freedom. A vertical load equivalent to the weightlifter’s body mass and the calculated flexion moments were applied to L1 to simulate the weightlifter’s bending and lifting behavior. Biomechanical responses within the lumbar spine were then analyzed. Results: The displacement and range of motion (ROM) of the lumbar spine were similar under all three loading conditions. The flexion degree increased with the load, while extension remained unchanged. Right-side movement and bending showed minimal change, with slightly more right rotation. Stress distribution trends were similar across loads, primarily concentrated in the vertebral body, increasing with load. Maximum stress occurred at the anterior inferior margin of L5, with significant stress at the posterior joints, ligaments, and spinous processes. The posterior L5 and margins of L1 and L5 experienced high stress. The degenerated L4-L5 IVD showed stress concentration on its edges, with significant stress also on L3-L4 IVD. Stress distribution in the lumbar spine was uneven. Conclusions: Our findings highlight the impact on spinal biomechanics and suggest reducing anisotropic loading and being cautious of loaded flexion positions affecting posterior joints, IVDs, and vertebrae. This study offers valuable insights for the rehabilitation and treatment of similar patients. Full article

(This article belongs to the Special Issue Advances in Trauma and Injury Biomechanics)

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17 pages, 5078 KB

Open AccessEditor’s ChoiceReview

Advancing Cordyceps militaris Industry: Gene Manipulation and Sustainable Biotechnological Strategies

by Yan Hu, Yijian Wu, Jiayi Song, Maomao Ma, Yunzhu Xiao and Bin Zeng

Bioengineering 2024, 11(8), 783; https://doi.org/10.3390/bioengineering11080783 - 2 Aug 2024

Cited by 4 | Viewed by 6613

Abstract

Cordyceps militaris is considered to be of great medicinal potential due to its remarkable pharmacological effects, safety, and edible characteristics. With the completion of the genome sequence and the advancement of efficient gene-editing technologies, coupled with the identification of gene functions in Cordyceps [...] Read more.

Cordyceps militaris is considered to be of great medicinal potential due to its remarkable pharmacological effects, safety, and edible characteristics. With the completion of the genome sequence and the advancement of efficient gene-editing technologies, coupled with the identification of gene functions in Cordyceps militaris, this fungus is poised to emerge as an outstanding strain for medicinal engineering applications. This review focuses on the development and application of genomic editing techniques, including Agrobacterium tumefaciens-mediated transformation (ATMT), PEG-mediated protoplast transformation (PMT), and CRISPR/Cas9. Through the application of these techniques, researchers can engineer the biosynthetic pathways of valuable secondary metabolites to boost yields; such metabolites include cordycepin, polysaccharides, and ergothioneine. Furthermore, by identifying and modifying genes that influence the growth, disease resistance, and tolerance to environmental stress in Cordyceps militaris, it is possible to stimulate growth, enhance desirable traits, and increase resilience to unfavorable conditions. Finally, the green sustainable industrial development of C. militaris using agricultural waste to produce high-value-added products and the future research directions of C. militaris were discussed. This review will provide future directions for the large-scale production of bioactive ingredients, molecular breeding, and sustainable development of C. militaris. Full article

(This article belongs to the Section Biochemical Engineering)

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29 pages, 1873 KB

Open AccessEditor’s ChoiceReview

Biohacking Nerve Repair: Novel Biomaterials, Local Drug Delivery, Electrical Stimulation, and Allografts to Aid Surgical Repair

by Jordan R. Crabtree, Chilando M. Mulenga, Khoa Tran, Konstantin Feinberg, J. Paul Santerre and Gregory H. Borschel

Bioengineering 2024, 11(8), 776; https://doi.org/10.3390/bioengineering11080776 - 31 Jul 2024

Cited by 10 | Viewed by 6196

Abstract

The regenerative capacity of the peripheral nervous system is limited, and peripheral nerve injuries often result in incomplete healing and poor outcomes even after repair. Transection injuries that induce a nerve gap necessitate microsurgical intervention; however, even the current gold standard of repair, [...] Read more.

The regenerative capacity of the peripheral nervous system is limited, and peripheral nerve injuries often result in incomplete healing and poor outcomes even after repair. Transection injuries that induce a nerve gap necessitate microsurgical intervention; however, even the current gold standard of repair, autologous nerve graft, frequently results in poor functional recovery. Several interventions have been developed to augment the surgical repair of peripheral nerves, and the application of functional biomaterials, local delivery of bioactive substances, electrical stimulation, and allografts are among the most promising approaches to enhance innate healing across a nerve gap. Biocompatible polymers with optimized degradation rates, topographic features, and other functions provided by their composition have been incorporated into novel nerve conduits (NCs). Many of these allow for the delivery of drugs, neurotrophic factors, and whole cells locally to nerve repair sites, mitigating adverse effects that limit their systemic use. The electrical stimulation of repaired nerves in the perioperative period has shown benefits to healing and recovery in human trials, and novel biomaterials to enhance these effects show promise in preclinical models. The use of acellular nerve allografts (ANAs) circumvents the morbidity of donor nerve harvest necessitated by the use of autografts, and improvements in tissue-processing techniques may allow for more readily available and cost-effective options. Each of these interventions aid in neural regeneration after repair when applied independently, and their differing forms, benefits, and methods of application present ample opportunity for synergistic effects when applied in combination. Full article

(This article belongs to the Special Issue Bioengineering Strategies for Nerve Repair)

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13 pages, 4398 KB

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

Cited by 11 | Viewed by 3688

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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27 pages, 7176 KB

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

Cited by 2 | Viewed by 2921

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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22 pages, 4120 KB

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

Cited by 5 | Viewed by 6112

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 KB

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

Cited by 22 | Viewed by 3601

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 KB

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

Cited by 25 | Viewed by 9812

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 KB

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

Cited by 4 | Viewed by 2966

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 KB

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

Cited by 4 | Viewed by 3541

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 KB

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 4 | Viewed by 4100

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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16 pages, 3345 KB

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

Cited by 1 | Viewed by 3522

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 KB

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

Cited by 2 | Viewed by 2550

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 KB

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 4 | Viewed by 3781

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 KB

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 36 | Viewed by 20629

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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23 pages, 1871 KB

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

Cited by 5 | Viewed by 4115

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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16 pages, 2619 KB

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 3672

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, 15127 KB

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 2 | Viewed by 3561

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 KB

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 5 | Viewed by 2402

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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16 pages, 11527 KB

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 9 | Viewed by 5900

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, 3847 KB

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 6 | Viewed by 2995

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 KB

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 4 | Viewed by 2961

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 KB

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

Cited by 7 | Viewed by 4276

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 KB

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 2 | Viewed by 3084

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 KB

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

Cited by 9 | Viewed by 4413

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 KB

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

Cited by 3 | Viewed by 3733

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 KB

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 14 | Viewed by 4320

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 KB

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 11 | Viewed by 4263

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 KB

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 5 | Viewed by 2024

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 KB

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 3 | Viewed by 3015

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 KB

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 4 | Viewed by 2849

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 KB

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 8 | Viewed by 3237

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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