Bioengineering

21 pages, 1795 KB

Open AccessEditor’s ChoiceReview

Nanoparticle-Based Delivery Systems for Synergistic Therapy in Lung Cancers

by Zicheng Deng, Ali Al Siraj, Isabella Lowry, Ellen Ruan, Rohan Patel, Wen Gao, Tanya V. Kalin and Vladimir V. Kalinichenko

Bioengineering 2025, 12(9), 968; https://doi.org/10.3390/bioengineering12090968 - 9 Sep 2025

Cited by 2 | Viewed by 2212

Abstract

Lung cancer remains the leading cause of cancer-related mortality worldwide, with conventional treatments often limited by systemic toxicity, different tumor sensitivity to the drugs, and the emergence of multidrug resistance. To address these challenges, nanoparticle-based delivery systems have emerged as an innovative strategy, [...] Read more.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with conventional treatments often limited by systemic toxicity, different tumor sensitivity to the drugs, and the emergence of multidrug resistance. To address these challenges, nanoparticle-based delivery systems have emerged as an innovative strategy, enabling the simultaneous transport of multiple agents, including chemotherapeutic drugs and expression vectors, to enhance treatment efficacy and overcome tumor resistance. This review explores various nanocarrier platforms, such as liposomes, solid lipid nanoparticles, polymeric micelles, and inorganic nanoparticles, specifically designed for lung cancer therapy. Synergistic effects and physicochemical properties of therapeutic agents must be carefully considered in the design of nanoparticle-based co-delivery systems for lung cancer therapy. We highlight the applications of these nanoparticle systems in drug–drug, gene–gene, and drug–gene co-delivery approaches. By addressing the limitations of traditional therapies, nanoparticle-based systems offer a promising avenue to improve outcomes in patients with lung cancers. Full article

(This article belongs to the Section Nanobiotechnology and Biofabrication)

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Graphical abstract

36 pages, 4960 KB

Open AccessEditor’s ChoiceSystematic Review

The Effects of Rehabilitation Programs Incorporating Breathing Interventions on Chronic Neck Pain Among Patients with Forward Head Posture: A Systematic Review and Meta-Analysis

by Seri Park, Kihyun Kim and Minbong Kang

Bioengineering 2025, 12(9), 947; https://doi.org/10.3390/bioengineering12090947 - 31 Aug 2025

Viewed by 5270

Abstract

The effectiveness of breathing interventions on postural alignment, pain reduction, and functional improvement in patients with forward head posture (FHP) and chronic neck pain remains uncertain. Previously conducted randomized controlled trials (RCTs) that involved breathing interventions were identified through searches of the PubMed, [...] Read more.

The effectiveness of breathing interventions on postural alignment, pain reduction, and functional improvement in patients with forward head posture (FHP) and chronic neck pain remains uncertain. Previously conducted randomized controlled trials (RCTs) that involved breathing interventions were identified through searches of the PubMed, Cochrane Library, Web of Science, and Scopus databases. Studies were included if they applied diaphragmatic breathing, breathing muscle training, or feedback breathing exercises for at least 2 weeks to chronic neck pain (duration ≥ 3 months) and/or forward head posture. The craniovertebral angle (CVA), the visual analog scale (VAS), and the neck disability index (NDI) were the primary outcome measures. The results showed that breathing interventions had a moderate effect size in terms of improving the CVA. Limited effects were observed for pain reduction, and improvements in neck disability approached statistical significance. However, despite these positive findings, the overall evidence was rated as ‘very low certainty’ in the GRADE assessment, primarily due to high heterogeneity among studies, limited sample sizes, and the potential for unit-of-analysis errors in diagnosis-based subgroup analyses. Consequently, their overall effectiveness in chronic neck pain was limited. Future research is needed to explore a multidisciplinary approach to neck pain using standardized protocols and larger samples. Full article

(This article belongs to the Special Issue Physical Therapy and Rehabilitation)

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52 pages, 44108 KB

Open AccessEditor’s ChoiceArticle

Experimental Validation of Time-Explicit Ultrasound Propagation Models with Sound Diffusivity or Viscous Attenuation in Biological Tissues Using COMSOL Multiphysics

by Nuno A. T. C. Fernandes, Shivam Sharma, Ana Arieira, Betina Hinckel, Filipe Silva, Ana Leal and Óscar Carvalho

Bioengineering 2025, 12(9), 946; https://doi.org/10.3390/bioengineering12090946 - 31 Aug 2025

Cited by 4 | Viewed by 2647

Abstract

Ultrasonic wave attenuation in biological tissues arises from complex interactions between mechanical, structural, and fluidic properties, making it essential to identify dominant mechanisms for accurate simulation and device design. This work introduces a novel integration of experimentally measured tissue parameters into time-explicit nonlinear [...] Read more.

Ultrasonic wave attenuation in biological tissues arises from complex interactions between mechanical, structural, and fluidic properties, making it essential to identify dominant mechanisms for accurate simulation and device design. This work introduces a novel integration of experimentally measured tissue parameters into time-explicit nonlinear acoustic wave simulations, in which the equations are directly solved in the time domain using an explicit solver. This approach captures the full transient waveform without relying on frequency-domain simplifications, offering a more realistic representation of ultrasound propagation in heterogeneous media. The study estimates both sound diffusivity and viscous damping parameters (dynamic and bulk viscosity) for a broad range of ex vivo tissues (skin, adipose tissue, skeletal muscle, trabecular/cortical bone, liver, myocardium, kidney, tendon, ligament, cartilage, and gray/white brain matter). Four regression models (power law, linear, exponential, logarithmic) were applied to characterize their frequency dependence between 0.5 and 5 MHz. Results show that attenuation is more strongly driven by bulk viscosity than dynamic viscosity, particularly in fluid-rich tissues such as liver and myocardium, where compressional damping dominates. The power-law model consistently provided the best fit for all attenuation metrics, revealing a scale-invariant frequency relationship. Tissues such as cartilage and brain showed weaker viscous responses, suggesting the need for alternative modeling approaches. These findings not only advance fundamental understanding of attenuation mechanisms but also provide validated parameters and modeling strategies to improve predictive accuracy in therapeutic ultrasound planning and the design of non-invasive, tissue-specific acoustic devices. Full article

(This article belongs to the Special Issue Recent Advances in the Application of Mathematical and Computational Models in Biomedical Science and Engineering (2nd Edition))

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14 pages, 752 KB

Open AccessEditor’s ChoiceArticle

High-Precision Multi-Axis Robotic Printing: Optimized Workflow for Complex Tissue Creation

by Erfan Shojaei Barjuei, Joonhwan Shin, Keekyoung Kim and Jihyun Lee

Bioengineering 2025, 12(9), 949; https://doi.org/10.3390/bioengineering12090949 - 31 Aug 2025

Viewed by 1310

Abstract

Three-dimensional bioprinting holds great promise for tissue engineering, but struggles with fabricating complex curved geometries such as vascular networks. Though precise, traditional Cartesian bioprinters are constrained by linear layer-by-layer deposition along fixed axes, resulting in limitations such as the stair-step effect. Multi-axis robotic [...] Read more.

Three-dimensional bioprinting holds great promise for tissue engineering, but struggles with fabricating complex curved geometries such as vascular networks. Though precise, traditional Cartesian bioprinters are constrained by linear layer-by-layer deposition along fixed axes, resulting in limitations such as the stair-step effect. Multi-axis robotic bioprinting addresses these challenges by allowing dynamic nozzle orientation and motion along curvilinear paths, enabling conformal printing on anatomically relevant surfaces. Although robotic arms offer lower mechanical precision than CNC stages, accuracy can be enhanced through methods such as vision-based toolpath correction. This study presents a modular multi-axis robotic embedded bioprinting platform that integrates a six-degrees-of-freedom robotic arm, a pneumatic extrusion system, and a viscoplastic support bath. A streamlined workflow combines CAD modeling, CAM slicing, robotic simulation, and automated execution for efficient fabrication. Two case studies validate the system’s ability to print freeform surfaces and vascular-inspired tubular constructs with high fidelity. The results highlight the platform’s versatility and potential for complex tissue fabrication and future in situ bioprinting applications. Full article

(This article belongs to the Special Issue Insights in Tissue Engineering: Novel Developments, Current Challenges, and Future Perspectives)

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16 pages, 1173 KB

Open AccessEditor’s ChoiceReview

by Ezra T. Yoseph, Rukayat Taiwo, Ali Kiapour, Gavin Touponse, Elie Massaad, Marinos Theologitis, Janet Y. Wu, Theresa Williamson and Corinna C. Zygourakis

Bioengineering 2025, 12(8), 858; https://doi.org/10.3390/bioengineering12080858 - 10 Aug 2025

Viewed by 5182

Abstract

Pregnancy induces substantial anatomical, hormonal, and biomechanical changes in the spine and pelvis to accommodate fetal growth and maintain postural adaptation. This narrative review synthesizes peer-reviewed evidence regarding pregnancy-related spinal biomechanics, with a particular focus on low back pain, spinopelvic alignment, sacroiliac joint [...] Read more.

Pregnancy induces substantial anatomical, hormonal, and biomechanical changes in the spine and pelvis to accommodate fetal growth and maintain postural adaptation. This narrative review synthesizes peer-reviewed evidence regarding pregnancy-related spinal biomechanics, with a particular focus on low back pain, spinopelvic alignment, sacroiliac joint dysfunction, and potential contributions to degenerative spinal conditions. A systematic search of PubMed, Embase, and Google Scholar was conducted using Boolean operators and relevant terms, yielding 1050 unique records, with 53 peer-reviewed articles ultimately cited. The review reveals that increased lumbar lordosis, ligamentous laxity, altered gait mechanics, and muscular deconditioning elevate mechanical load on the lumbar spine, predisposing up to 56% of pregnant individuals to low back pain. These changes are often associated with sacroiliac joint laxity, anterior pelvic tilt, and multiparity. Long-term risks may include degenerative disc disease and spondylolisthesis. Conservative interventions such as pelvic floor muscle training, prenatal exercise, and surface topography monitoring offer symptom relief and support early rehabilitation, although standardized protocols and longitudinal outcome data remain limited. Pregnancy-related spinal changes are multifactorial and clinically relevant; an interdisciplinary approach involving spinal biomechanics, physical therapy, and obstetric care is critical for optimizing maternal musculoskeletal health. Full article

(This article belongs to the Special Issue Spine Biomechanics)

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13 pages, 2210 KB

Open AccessEditor’s ChoiceArticle

The Use of Therapeutic Peptides in Combination with Full-Thickness Skin Columns to Improve Healing of Excisional Wounds

by Anders H. Carlsson, Ira M. Herman, Sean Christy, David Larson, Rodney K. Chan, Thomas N. Darling and Kristo Nuutila

Bioengineering 2025, 12(8), 856; https://doi.org/10.3390/bioengineering12080856 - 9 Aug 2025

Cited by 1 | Viewed by 1311

Abstract

Split-thickness skin grafting (STSG) is the standard of care for skin replacement therapy. While STSG is a well-established technique, it has several limitations at both the donor and recipient sites. Full-thickness skin column (FTSC) grafting is an alternative approach that involves the orthogonal [...] Read more.

Split-thickness skin grafting (STSG) is the standard of care for skin replacement therapy. While STSG is a well-established technique, it has several limitations at both the donor and recipient sites. Full-thickness skin column (FTSC) grafting is an alternative approach that involves the orthogonal harvesting of small skin columns containing the epidermis, dermis, and associated skin appendages. Peptides have been shown to promote wound repair through various reparative and regenerative mechanisms. In this study, we aimed to evaluate the extent to which FTSCs and the matrix-derived peptide TSN6, individually or in combination, influenced the rate and quality of healing, as assessed by metrics such as epithelialization, epithelial thickness, and the presence of adnexal structures. TSN6 peptide and its scrambled form was synthetized in a laboratory and mixed with a carboxymethylcellulose (CMC) hydrogel. Up to 16 standardized full-thickness excisional wounds (∅ 5 cm) were created on the dorsum of two anesthetized pigs. FTSC biopsies (∅ 1.5 mm) were harvested from donor sites located on the rump of the pig at a ratio of up to eight 1.5 mm-diameter skin columns/1 cm². Subsequently, the wounds were randomized to receive either (1) FTSC + TSN6, (2) FTSC + scrambled peptide, (3) FTSC alone, and (4) blank CMC hydrogel. Healing was monitored for 14 or 28 days. After euthanasia, the wounds were excised and processed for histology. Additionally, non-invasive imaging systems were utilized to assess wound healing. By day 14, wounds treated with FTSC or FTSC + TSN6 were significantly more re-epithelialized compared to those treated with blank CMC hydrogel. By day 28, all FTSC-transplanted wounds were fully re-epithelialized. Notably, wounds treated with FTSC + TSN6 exhibited improved healing quality, characterized by a thicker neo-epidermis and increased rete ridges at day 28 post-transplantation. All FTSC-transplanted wounds healed better than the untransplanted controls. The TSN6 peptide further improved healing quality when applied in combination with FTSCs, particularly by enhancing epidermal maturation. Full article

(This article belongs to the Special Issue Advanced Techniques and Applications in Burn Reconstruction: A Bioengineering Perspective)

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18 pages, 2593 KB

Open AccessEditor’s ChoiceArticle

Accuracy of Drill Sleeve Housing in 3D-Printed and Milled Implant Surgical Guides: A 3D Analysis Considering Machine Type, Layer Thickness, Sleeve Position, and Steam Sterilization

by Anna Seidel, Kai Zerrahn, Manfred Wichmann and Ragai Edward Matta

Bioengineering 2025, 12(8), 799; https://doi.org/10.3390/bioengineering12080799 - 25 Jul 2025

Cited by 1 | Viewed by 1167

Abstract

Successful dental implant therapy relies on accurate planning and placement, e.g., through static, computer-aided implant surgery using CAD/CAM-fabricated surgical guides. This study examined production methods’ influence on surgical guide sleeve housing geometry. A model with two edentulous spaces was digitized using intraoral scanning [...] Read more.

Successful dental implant therapy relies on accurate planning and placement, e.g., through static, computer-aided implant surgery using CAD/CAM-fabricated surgical guides. This study examined production methods’ influence on surgical guide sleeve housing geometry. A model with two edentulous spaces was digitized using intraoral scanning and CBCT, and two virtually positioned implants were planned. Ten guides per group were produced using milling (MCX5), DLP printing (ASIGA and SHERA), and SLA printing (FORM), printing with 50 µm and 100 µm layers each. Each guide (n = 70) was then digitized using an industrial scanner before and after sterilization. Superimposition of the actual guide data with the reference data allowed for evaluation of deviations at the drill sleeve housing along the x-, y-, z-, and dxyz-axes. Descriptive and statistical evaluation was performed (significance level: p ≤ 0.0125). Significant differences existed among the production methods: Milling and SLA showed higher deviations than the DLP group (p < 0.001). Milled guides post-sterilization showed the highest deviations (0.352 ± 0.08 mm), while one DLP printer at 50 μm layer thickness showed lowest deviations (0.091 ± 0.04 mm). The layer thickness was insignificant, whereas sterilization increased deviation (p < 0.001). DLP produced the most precise implant surgical guides. All 3D printers were suitable for fabricating clinically acceptable surgical guides. Full article

(This article belongs to the Special Issue Advances in Additive Manufacturing Technologies in the Clinical, Pharmaceutical and Biomedical Sectors)

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12 pages, 1338 KB

Open AccessEditor’s ChoiceReview

Most Custom Oral Appliances for Obstructive Sleep Apnea Do Not Meet the Definition of Custom

by Leonard A. Liptak, Erin Mosca, Edward Sall, Shouresh Charkhandeh, Sung Kim and John E. Remmers

Bioengineering 2025, 12(8), 798; https://doi.org/10.3390/bioengineering12080798 - 25 Jul 2025

Cited by 1 | Viewed by 3208

Abstract

Obstructive sleep apnea is a highly prevalent respiratory disease linked to increased morbidity and mortality, a reduced quality of life, and increased economic costs if not treated. Oral appliances are an emerging treatment option for obstructive sleep apnea. This review concluded that many [...] Read more.

Obstructive sleep apnea is a highly prevalent respiratory disease linked to increased morbidity and mortality, a reduced quality of life, and increased economic costs if not treated. Oral appliances are an emerging treatment option for obstructive sleep apnea. This review concluded that many oral appliances marketed as “custom” include modifications and prefabricated items, and therefore do not meet the definition of “custom” oral appliances. This misclassification could hinder the accurate characterization, evaluation, and appropriate prescription of oral appliances. To better inform the clinical utilization of custom oral appliances and to more closely align sleep medicine with the benefits of personalized medicine, we propose that the custom oral appliance classification be further refined into semi-custom and precision-custom categories. Full article

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

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11 pages, 584 KB

Open AccessEditor’s ChoiceSystematic Review

Artificial Intelligence for Non-Invasive Prediction of Molecular Signatures in Spinal Metastases: A Systematic Review

by Vivek Sanker, Sai Sanikommu, Alexander Thaller, Zhikai Li, Philip Heesen, Srinath Hariharan, Emil O. R. Nordin, Maria Jose Cavagnaro, John Ratliff and Atman Desai

Bioengineering 2025, 12(8), 791; https://doi.org/10.3390/bioengineering12080791 - 23 Jul 2025

Cited by 2 | Viewed by 870

Abstract

Background: Spinal metastases (SMs) are associated with poor prognosis and significant morbidity. We hypothesize that artificial intelligence (AI) models can enhance the identification and clinical utility of genetic and molecular signatures associated with SMs, improving diagnostic accuracy and enabling personalized treatment strategies. Methods: [...] Read more.

Background: Spinal metastases (SMs) are associated with poor prognosis and significant morbidity. We hypothesize that artificial intelligence (AI) models can enhance the identification and clinical utility of genetic and molecular signatures associated with SMs, improving diagnostic accuracy and enabling personalized treatment strategies. Methods: A systematic review of five databases was conducted to identify studies that used AI to predict genetic alterations and SMs outcomes. Accuracy, area under the receiver operating curve (AUC), and sensitivity were used for comparison. Data analysis was performed in R. Results: Eleven studies met the inclusion criteria, covering three different primary tumor origins, comprising a total of 2211 patients with an average of 201 ± 90 patients (range: 76–359 patients) per study. EGFR, Ki-67, and HER-2 were studied in ten (90.9%), two (18.1%), and one (9.1%) study, respectively. The weighted average AUC is 0.849 (95% CI: 0.835–0.863) and 0.791 (95% CI: 0.738–0.844) for internal and external validation of the established models, respectively. Conclusions: AI, through radiomics and machine learning, shows strong potential in predicting molecular markers in SMs. Our study demonstrates that AI can predict molecular markers in SMs with high accuracy. Full article

(This article belongs to the Section Biosignal Processing)

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19 pages, 259 KB

Open AccessEditor’s ChoiceArticle

Understanding the Impact of Assistive Technology on Users’ Lives in England: A Capability Approach

by Rebecca Joskow, Dilisha Patel, Anna Landre, Kate Mattick, Catherine Holloway, Jamie Danemayer and Victoria Austin

Bioengineering 2025, 12(7), 750; https://doi.org/10.3390/bioengineering12070750 - 9 Jul 2025

Cited by 3 | Viewed by 2338

Abstract

This study presents an analysis of England’s 2023 national assessment of assistive technology (AT) access and use, with a particular focus on the qualitative impact of AT as described by users. It aims to address limitations in conventional AT impact assessments, which often [...] Read more.

This study presents an analysis of England’s 2023 national assessment of assistive technology (AT) access and use, with a particular focus on the qualitative impact of AT as described by users. It aims to address limitations in conventional AT impact assessments, which often prioritize clinical outcomes or user satisfaction, by offering a deeper account of how impact is experienced in everyday life. Drawing on data from a nationally representative survey of 7000 disabled adults and children, as well as six focus group discussions and 28 semi-structured interviews with stakeholders across the WHO 5Ps framework (People, Providers, Personnel, Policy, and Products), the study applies Amartya Sen and Martha Nussbaum’s Capability Approach to explore these experiences. Using inductive thematic analysis, we identify three main domains of user-reported impact: Functions and Activities (e.g., mobility, communication, vision, leisure, daily routines, and cognitive support), Outcomes (e.g., autonomy, quality of life, safety, social participation, wellbeing, and work and learning), and Lived Experience (e.g., access barriers, essentiality, identity and emotional connection, peace of mind, and sense of control and confidence). These findings offer a more user-centered understanding of AT impact and can inform the development of future measurement tools, research design, and government-led interventions to improve AT provision. Full article

(This article belongs to the Special Issue Measuring Outcomes and Impact Related to Assistive Technology and Accessibility for Disability)

11 pages, 2829 KB

Open AccessEditor’s ChoiceArticle

Biomimetic Full-Thickness Artificial Skin Using Stromal Vascular Fraction Cells and Autologous Keratinocytes in a Single Scaffold for Wound Healing

by Jung Huh, Seong-Ho Jeong, Eun-Sang Dhong, Seung-Kyu Han and Kyung-Chul Moon

Bioengineering 2025, 12(7), 736; https://doi.org/10.3390/bioengineering12070736 - 5 Jul 2025

Viewed by 1243

Abstract

We developed biomimetic full-thickness artificial skin using stromal vascular fraction (SVF) cells and autologous keratinocytes for the dermal and epidermal layers of skin, respectively. Full-thickness artificial skin scaffolds were fabricated using 4% porcine collagen and/or elastin in a low-temperature three-dimensional printer. Two types [...] Read more.

We developed biomimetic full-thickness artificial skin using stromal vascular fraction (SVF) cells and autologous keratinocytes for the dermal and epidermal layers of skin, respectively. Full-thickness artificial skin scaffolds were fabricated using 4% porcine collagen and/or elastin in a low-temperature three-dimensional printer. Two types of scaffolds with collagen-to-elastin ratios of 100:0 and 100:4 were printed and compared. The scaffolds were analyzed for collagenase degradation, tensile strength, and structural features using scanning electron microscopy. By 24 h, the collagen-only scaffolds showed gradual degradation, and the collagen-elastin scaffolds retained the highest structural integrity but were not degraded. In the tensile strength tests, the collagen-only scaffolds exhibited a tensile strength of 2.2 N, while the collagen-elastin scaffolds showed a tensile strength of 4.2 N. Cell viability tests for keratinocytes displayed an initial viability of 89.32 ± 3.01% on day 1, which gradually increased to 97.22 ± 4.99% by day 7. Similarly, SVF cells exhibited a viability of 93.68 ± 1.82% on day 1, which slightly improved to 97.12 ± 1.64% on day 7. This study presents a novel strategy for full-thickness artificial skin development, combining SVF and keratinocytes with an optimized single collagen scaffold and a gradient pore-density structure. Full article

(This article belongs to the Special Issue Advances and Innovations in Wound Repair and Regeneration)

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12 pages, 1893 KB

Open AccessEditor’s ChoiceArticle

Solid-State Anaerobic Digestion of Organic Solid Poultry Waste for Biomethane Production

by Faryal Fatima and Raghava R. Kommalapati

Bioengineering 2025, 12(7), 712; https://doi.org/10.3390/bioengineering12070712 - 29 Jun 2025

Cited by 1 | Viewed by 1405

Abstract

This study examines biodegradability (BD) and optimum conditions for the solid-state anaerobic digestion (SS-AD) of organic solid poultry waste (organs, intestines, offal, and unprocessed meat) to maximize biomethane production. Three main parameters, substrate-to-inoculum (S/I) ratio, pH, and temperature, were evaluated for the SS-AD [...] Read more.

This study examines biodegradability (BD) and optimum conditions for the solid-state anaerobic digestion (SS-AD) of organic solid poultry waste (organs, intestines, offal, and unprocessed meat) to maximize biomethane production. Three main parameters, substrate-to-inoculum (S/I) ratio, pH, and temperature, were evaluated for the SS-AD of organic solid poultry waste. pH was evaluated at non-adjusted pH, initially adjusted pH, and controlled pH conditions at a constant S/I ratio of 0.5 and temperature of 35 ± 1 °C. The S/I ratios were examined at (0.3, 0.5, 1, and 2) at a controlled pH of ≈7.9 and temperature of 35 ± 1 °C. The temperature was assessed at mesophilic (35 ± 1 °C) and thermophilic (55 ± 1 °C) conditions with a constant S/I ratio of 0.5 and controlled pH of ≈7.9. The results demonstrate that the highest biomethane production and BD were achieved with a controlled pH of ≈7.9 (689 ± 10 mg/L, 97.5 ± 1.4%). The initially adjusted pH (688 ± 14 mg/L, 97.3 ± 1.9%) and an S/I ratio of 0.3 (685 ± 8 mg/L, 96.8 ± 1.2%) had approximately equivalent outcomes. The thermophilic conditions yielded 78% lower biomethane yield than mesophilic conditions. The challenge of lower biomethane yield under thermophilic conditions will be resolved in future studies by determining the rate-limiting step. These observations highlight that SS-AD is a promising technology for biomethane production from solid organic poultry waste. Full article

(This article belongs to the Special Issue Anaerobic Digestion Advances in Biomass and Waste Treatment)

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44 pages, 1445 KB

Open AccessEditor’s ChoiceReview

Artificial Intelligence in the Diagnostic Use of Transcranial Doppler and Sonography: A Scoping Review of Current Applications and Future Directions

by Giuseppe Miceli, Maria Grazia Basso, Elena Cocciola and Antonino Tuttolomondo

Bioengineering 2025, 12(7), 681; https://doi.org/10.3390/bioengineering12070681 - 21 Jun 2025

Cited by 2 | Viewed by 5836

Abstract

Artificial intelligence (AI) is revolutionizing the field of medical imaging, offering unprecedented capabilities in data analysis, image interpretation, and decision support. Transcranial Doppler (TCD) and Transcranial Color-Coded Doppler (TCCD) are widely used, non-invasive modalities for evaluating cerebral hemodynamics in acute and chronic conditions. [...] Read more.

Artificial intelligence (AI) is revolutionizing the field of medical imaging, offering unprecedented capabilities in data analysis, image interpretation, and decision support. Transcranial Doppler (TCD) and Transcranial Color-Coded Doppler (TCCD) are widely used, non-invasive modalities for evaluating cerebral hemodynamics in acute and chronic conditions. Yet, their reliance on operator expertise and subjective interpretation limits their full potential. AI, particularly machine learning and deep learning algorithms, has emerged as a transformative tool to address these challenges by automating image acquisition, optimizing signal quality, and enhancing diagnostic accuracy. Key applications reviewed include the automated identification of cerebrovascular abnormalities such as vasospasm and embolus detection in TCD, AI-guided workflow optimization, and real-time feedback in general ultrasound imaging. Despite promising advances, significant challenges remain, including data standardization, algorithm interpretability, and the integration of these tools into clinical practice. Developing robust, generalizable AI models and integrating multimodal imaging data promise to enhance diagnostic and prognostic capabilities in TCD and ultrasound. By bridging the gap between technological innovation and clinical utility, AI has the potential to reshape the landscape of neurovascular and diagnostic imaging, driving advancements in personalized medicine and improving patient outcomes. This review highlights the critical role of interdisciplinary collaboration in achieving these goals, exploring the current applications and future directions of AI in TCD and TCCD imaging. This review included 41 studies on the application of artificial intelligence (AI) in neurosonology in the diagnosis and monitoring of vascular and parenchymal brain pathologies. Machine learning, deep learning, and convolutional neural network algorithms have been effectively utilized in the analysis of TCD and TCCD data for several conditions. Conversely, the application of artificial intelligence techniques in transcranial sonography for the assessment of parenchymal brain disorders, such as dementia and space-occupying lesions, remains largely unexplored. Nonetheless, this area holds significant potential for future research and clinical innovation. Full article

(This article belongs to the Special Issue Advancements in Imaging Informatics: Radiology and Pathology from Diagnosis to Management)

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2 pages, 122 KB

Open AccessEditor’s ChoiceEditorial

Advances in Wearable Technologies for the In-Field Assessment of Biomechanical Risk

by Micaela Porta and Massimiliano Pau

Bioengineering 2025, 12(6), 632; https://doi.org/10.3390/bioengineering12060632 - 10 Jun 2025

Viewed by 592

Abstract

The exceptional improvements that have characterized the technology of wearable devices for biomedical applications in recent decades have made it possible for researchers and practitioners to provide advanced solutions for the assessment of biomechanical and physiological variables in the present day, exploiting miniaturized, [...] Read more.

The exceptional improvements that have characterized the technology of wearable devices for biomedical applications in recent decades have made it possible for researchers and practitioners to provide advanced solutions for the assessment of biomechanical and physiological variables in the present day, exploiting miniaturized, lightweight, and low-power-consumption devices at affordable costs [...] Full article

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

21 pages, 1280 KB

Open AccessEditor’s ChoiceReview

A Review of Bioelectrochemical Strategies for Enhanced Polyhydroxyalkanoate Production

by Alejandro Chamizo-Ampudia, Raúl. M. Alonso, Luisa Ariza-Carmona, África Sanchiz and María Isabel San-Martín

Bioengineering 2025, 12(6), 616; https://doi.org/10.3390/bioengineering12060616 - 5 Jun 2025

Cited by 3 | Viewed by 2813

Abstract

The growing demand for sustainable bioplastics has driven research toward more efficient and cost-effective methods of producing polyhydroxyalkanoates (PHAs). Among the emerging strategies, bioelectrochemical technologies have been identified as a promising approach to enhance PHA production by supplying electrons to microorganisms either directly [...] Read more.

The growing demand for sustainable bioplastics has driven research toward more efficient and cost-effective methods of producing polyhydroxyalkanoates (PHAs). Among the emerging strategies, bioelectrochemical technologies have been identified as a promising approach to enhance PHA production by supplying electrons to microorganisms either directly or indirectly. This review provides an overview of recent advancements in bioelectrochemical PHA synthesis, highlighting the advantages of this method, including increased production rates, the ability to utilize a wide range of substrates (including industrial and agricultural waste), and the potential for process integration with existing systems. Various bioelectrochemical systems (BES), electrode materials, and microbial strategies used for PHA biosynthesis are discussed, with a focus on the roles of electrode potentials and microbial electron transfer mechanisms in improving the polymer yield. The integration of BES into PHA production processes has been shown to reduce costs, enhance productivity, and support the use of renewable carbon sources. However, challenges remain, such as optimizing reactor design, scaling up processes, and improving the electron transfer efficiency. This review emphasizes the advancement of bioelectrochemical technologies combined with the use of agro-industrial waste as a carbon source, aiming to maximize the efficiency and sustainability of PHA production for large-scale industrial applications. Full article

(This article belongs to the Special Issue Development of Bioelectrochemical Systems for Environmental Engineering)

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12 pages, 1627 KB

Open AccessEditor’s ChoiceArticle

Wheat Bran Polymer Scaffolds: Supporting Triple-Negative Breast Cancer Cell Growth and Development

by Abulquasem Rayat Hossain, Md Sultan Mahmud, Kaydee Koistinen, George Davisson, Brooke Roeges, Hayle Boechler, Md Abdur Rahim Badsha, Md Rakib Hasan Khan, Michael Kjelland, Dorsa Fereydoonpour, Mohiuddin Quadir, Sanku Mallik and Khwaja Hossain

Bioengineering 2025, 12(6), 568; https://doi.org/10.3390/bioengineering12060568 - 26 May 2025

Cited by 1 | Viewed by 1156

Abstract

Arabinoxylans (AX) are functional biopolymers, the main non-starch polysaccharides in cereals and other plants. AX is composed of xylose and arabinose, and the ester-linkage of ferulic acid to arabinose confers its bioactive properties. The backbone of AX resembles that of glycosaminoglycans, a major [...] Read more.

Arabinoxylans (AX) are functional biopolymers, the main non-starch polysaccharides in cereals and other plants. AX is composed of xylose and arabinose, and the ester-linkage of ferulic acid to arabinose confers its bioactive properties. The backbone of AX resembles that of glycosaminoglycans, a major component of the human extracellular matrix. This study explores the potential of wheat bran AX-based scaffolds as a novel platform for the growth and development of triple-negative breast cancer (TNBC) cells, an aggressive form of breast cancer. Importantly, patients face the worst prognosis due to the stemness of the TNBC cells and the formation of hypoxic cell clumps. Wheat bran constitutes 15–25% of the byproducts after milling and adds limited economic value. We have extracted AX from wheat bran (WBAX) and developed soft scaffolds with Na-alginate. The scaffolds were seeded with the triple-negative breast cancer cell line MDA-MB-231. Over 21 days, cell growth and development, cell migration within the hydrogels, and the formation of hypoxic regions within cell clumps were observed. These findings suggest that WBAX-based scaffolds provide a conducive environment for TNBC cell proliferation and development, offering a promising avenue for further research into cancer cell biology and potential therapeutic applications. Full article

(This article belongs to the Special Issue From Residues to Bio-Based Products through Bioprocess Engineering)

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19 pages, 1118 KB

Open AccessEditor’s ChoiceReview

Long-Acting Extracellular Vesicle-Based Biologics in Osteoarthritis Immunotherapy

by Philip Drohat, Max Baron, Lee D. Kaplan, Thomas M. Best and Dimitrios Kouroupis

Bioengineering 2025, 12(5), 525; https://doi.org/10.3390/bioengineering12050525 - 15 May 2025

Cited by 3 | Viewed by 3315

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by low-grade inflammation, cartilage breakdown, and persistent pain. Despite its prevalence, current therapeutic strategies primarily focus on symptom management rather than modifying disease progression. Monoclonal antibodies and cytokine inhibitors targeting inflammatory pathways, including TNF-α [...] Read more.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by low-grade inflammation, cartilage breakdown, and persistent pain. Despite its prevalence, current therapeutic strategies primarily focus on symptom management rather than modifying disease progression. Monoclonal antibodies and cytokine inhibitors targeting inflammatory pathways, including TNF-α and IL-1, have shown promise but remain limited by inconsistent efficacy and safety concerns. Long-acting biologic therapies—ranging from extended-release formulations, such as monoclonal antibodies and cytokine inhibitors, to gene therapy approaches—have emerged as promising strategies to enhance treatment durability and improve patient outcomes. Extracellular vesicles (EVs) have gained particular attention as a novel delivery platform due to their inherent stability, biocompatibility, and ability to transport therapeutic cargo, including biologics and immunomodulatory agents, directly to joint tissues. This review explores the evolving role of EVs in OA treatment, highlighting their ability to extend drug half-life, improve targeting, and modulate inflammatory responses. Additionally, strategies for EV engineering, including endogenous and exogenous cargo loading, genetic modifications, and biomaterial-based delivery systems, are discussed. Full article

(This article belongs to the Special Issue Integrating Novel Therapeutics and Personalized Medicine into Osteoarthritis Treatment: Advancements in Cartilage Regeneration and Joint Preservation)

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21 pages, 4080 KB

Open AccessEditor’s ChoiceReview

Integrating Artificial Intelligence in Orthopedic Care: Advancements in Bone Care and Future Directions

by Rahul Kumar, Kyle Sporn, Joshua Ong, Ethan Waisberg, Phani Paladugu, Swapna Vaja, Tamer Hage, Tejas C. Sekhar, Amar S. Vadhera, Alex Ngo, Nasif Zaman, Alireza Tavakkoli and Mouayad Masalkhi

Bioengineering 2025, 12(5), 513; https://doi.org/10.3390/bioengineering12050513 - 13 May 2025

Cited by 5 | Viewed by 5467

Abstract

Artificial intelligence (AI) is revolutionizing the field of orthopedic bioengineering by increasing diagnostic accuracy and surgical precision and improving patient outcomes. This review highlights using AI for orthopedics in preoperative planning, intraoperative robotics, smart implants, and bone regeneration. AI-powered imaging, automated 3D anatomical [...] Read more.

Artificial intelligence (AI) is revolutionizing the field of orthopedic bioengineering by increasing diagnostic accuracy and surgical precision and improving patient outcomes. This review highlights using AI for orthopedics in preoperative planning, intraoperative robotics, smart implants, and bone regeneration. AI-powered imaging, automated 3D anatomical modeling, and robotic-assisted surgery have dramatically changed orthopedic practices. AI has improved surgical planning by enhancing complex image interpretation and providing augmented reality guidance to create highly accurate surgical strategies. Intraoperatively, robotic-assisted surgeries enhance accuracy and reduce human error while minimizing invasiveness. AI-powered smart implant sensors allow for in vivo monitoring, early complication detection, and individualized rehabilitation. It has also advanced bone regeneration devices and neuroprosthetics, highlighting its innovation capabilities. While AI advancements in orthopedics are exciting, challenges remain, like the need for standardized surgical system validation protocols, assessing ethical consequences of AI-derived decision-making, and using AI with bioprinting for tissue engineering. Future research should focus on proving the reliability and predictability of the performance of AI-pivoted systems and their adoption within clinical practice. This review synthesizes recent developments and highlights the increasing impact of AI in orthopedic bioengineering and its potential future effectiveness in bone care and beyond. Full article

(This article belongs to the Section Biosignal Processing)

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31 pages, 5264 KB

Open AccessEditor’s ChoiceArticle

StructureNet: Physics-Informed Hybridized Deep Learning Framework for Protein–Ligand Binding Affinity Prediction

by Arjun Kaneriya, Madhav Samudrala, Harrish Ganesh, James Moran, Somanath Dandibhotla and Sivanesan Dakshanamurthy

Bioengineering 2025, 12(5), 505; https://doi.org/10.3390/bioengineering12050505 - 10 May 2025

Viewed by 2705

Abstract

Accurately predicting protein–ligand binding affinity is an important step in the drug discovery process. Deep learning (DL) methods have improved binding affinity prediction by using diverse categories of molecular data. However, many models rely heavily on interaction and sequence data, which impedes proper [...] Read more.

Accurately predicting protein–ligand binding affinity is an important step in the drug discovery process. Deep learning (DL) methods have improved binding affinity prediction by using diverse categories of molecular data. However, many models rely heavily on interaction and sequence data, which impedes proper learning and limits performance in de novo applications. To address these limitations, we developed a novel graph neural network model, called StructureNet (structure-based graph neural network), to predict protein–ligand binding affinity. StructureNet improves existing DL methods by focusing entirely on structural descriptors to mitigate data memorization issues introduced by sequence and interaction data. StructureNet represents the protein and ligand structures as graphs, which are processed using a GNN-based ensemble deep learning model. StructureNet achieved a PCC of 0.68 and an AUC of 0.75 on the PDBBind v.2020 Refined Set, outperforming similar structure-based models. External validation on the DUDE-Z dataset showed that StructureNet can effectively distinguish between active and decoy ligands. Further testing on a small subset of well-known drugs indicates that StructureNet has high potential for rapid virtual screening applications. We also hybridized StructureNet with interaction- and sequence-based models to investigate their impact on testing accuracy and found minimal difference (0.01 PCC) between merged models and StructureNet as a standalone model. An ablation study found that geometric descriptors were the key drivers of model performance, with their removal leading to a PCC decrease of over 15.7%. Lastly, we tested StructureNet on ensembles of binding complex conformers generated using molecular dynamics (MD) simulations and found that incorporating multiple conformations of the same complex often improves model accuracy by capturing binding site flexibility. Overall, the results show that structural data alone are sufficient for binding affinity predictions and can address pattern recognition challenges introduced by sequence and interaction features. Additionally, structural representations of protein–ligand complexes can be considerably improved using geometric and topological descriptors. We made StructureNet GUI interface freely available online. Full article

(This article belongs to the Section Biosignal Processing)

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23 pages, 4534 KB

Open AccessEditor’s ChoiceReview

Branding a New Technological Outlook for Future Orthopaedics

by Nicole Tueni and Farid Amirouche

Bioengineering 2025, 12(5), 494; https://doi.org/10.3390/bioengineering12050494 - 7 May 2025

Cited by 4 | Viewed by 3139

Abstract

Orthopedics is undergoing a transformative shift driven by personalized medical technologies that enhance precision, efficiency, and patient outcomes. Virtual surgical planning, robotic assistance, and real-time 3D navigation have revolutionized procedures like total knee arthroplasty and hip replacement, offering unparalleled accuracy and reducing recovery [...] Read more.

Orthopedics is undergoing a transformative shift driven by personalized medical technologies that enhance precision, efficiency, and patient outcomes. Virtual surgical planning, robotic assistance, and real-time 3D navigation have revolutionized procedures like total knee arthroplasty and hip replacement, offering unparalleled accuracy and reducing recovery times. Integrating artificial intelligence, advanced imaging, and 3D-printed patient-specific implants further elevates surgical precision, minimizes intraoperative complications, and supports individualized care. In sports orthopedics, wearable sensors and motion analysis technologies are revolutionizing diagnostics, injury prevention, and rehabilitation, enabling real-time decision-making and improved patient safety. Health-tracking devices are advancing recovery and supporting preventative care, transforming athletic performance management. Concurrently, breakthroughs in biologics, biomaterials, and bioprinting are reshaping treatments for cartilage defects, ligament injuries, osteoporosis, and meniscal damage. These innovations are poised to establish new benchmarks for regenerative medicine in orthopedics. By combining cutting-edge technologies with interdisciplinary collaboration, the field is redefining surgical standards, optimizing patient care, and paving the way for a highly personalized and efficient future. Full article

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

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13 pages, 2387 KB

Open AccessEditor’s ChoiceArticle

WATCH-PR: Comparison of the Pulse Rate of a WATCH-Type Blood Pressure Monitor with the Pulse Rate of a Conventional Ambulatory Blood Pressure Monitor

by Mathini Vaseekaran, Marcus Wiemer, Sven Kaese, Dennis Görlich, Jochen Hinkelbein, Gerrit Jansen and Alexander Samol

Bioengineering 2025, 12(5), 492; https://doi.org/10.3390/bioengineering12050492 - 5 May 2025

Cited by 1 | Viewed by 2250

Abstract

Background: Monitoring pulse rate is fundamental to cardiovascular health management and early detection of rhythm disturbances. While oscillometric blood pressure measurement is well established and validated in clinical practice, its use for pulse rate monitoring, particularly via wrist-worn devices, remains largely unexplored. Objective: [...] Read more.

Background: Monitoring pulse rate is fundamental to cardiovascular health management and early detection of rhythm disturbances. While oscillometric blood pressure measurement is well established and validated in clinical practice, its use for pulse rate monitoring, particularly via wrist-worn devices, remains largely unexplored. Objective: This study investigates whether a smartwatch that performs oscillometric blood pressure measurements at the wrist can also deliver reliable pulse rate readings using the same method. Methods: This study compared pulse rates recorded by the Omron HeartGuide smartwatch and conventional ambulatory blood pressure monitors in 50 patients over 24 h. Measurements were taken consecutively, and data were analyzed using intraclass correlation coefficients (ICCs) and Bland–Altman plots. Results: The study showed a high ICC of 0.971, indicating excellent agreement between devices. The average pulse rate difference was 1.5 bpm, with the Omron HeartGuide reporting slightly lower rates, especially in patients with atrial fibrillation. Conclusions: This study demonstrates that oscillometric pulse-rate monitoring at the wrist can achieve a high degree of accuracy, comparable to conventional upper-arm devices. Given that oscillometric smartwatches like the Omron HeartGuide are already used for blood pressure monitoring, the findings suggest that they may also be suitable for pulse rate measurement, potentially enhancing their role in telemetric healthcare, but further research is needed, particularly in patients with arrhythmias. Full article

(This article belongs to the Special Issue Smart Applications and Technology for Cardiovascular Disease Management)

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19 pages, 5913 KB

Open AccessEditor’s ChoiceArticle

Putative Endoplasmic Reticulum Stress Inducers Enhance Triacylglycerol Accumulation in Chlorella sorokiniana

by Yoomi Roh, Sujeong Je, Naeun Sheen, Chang Hun Shin and Yasuyo Yamaoka

Bioengineering 2025, 12(5), 452; https://doi.org/10.3390/bioengineering12050452 - 25 Apr 2025

Cited by 2 | Viewed by 1549

Abstract

Chlorella, recognized for its high lipid and protein content, is increasingly studied for its potential in the food and bio industries. To enhance its production and understand the underlying mechanisms of lipid accumulation, this study investigated the role of endoplasmic reticulum (ER) [...] Read more.

Chlorella, recognized for its high lipid and protein content, is increasingly studied for its potential in the food and bio industries. To enhance its production and understand the underlying mechanisms of lipid accumulation, this study investigated the role of endoplasmic reticulum (ER) stress in modulating lipid metabolism in Chlorella sorokiniana UTEX 2714, using six putative ER stress inducers: 2-deoxy-D-glucose (2-DG), dithiothreitol (DTT), tunicamycin (TM), thapsigargin (TG), brefeldin A (BFA), and monensin (Mon). The results showed that 2-DG, DTT, TM, BFA, and Mon significantly inhibited cell growth in C. sorokiniana. Treatment with 2-DG, DTT, TM, BFA, or Mon resulted in substantial increases in the triacylglycerol (TAG) to total fatty acid (tFA) ratio, with fold changes of 14.8, 7.9, 6.2, 10.1, and 8.9, respectively. Among the tFAs, cells treated with these compounds exhibited higher levels of saturated fatty acids and lower levels of polyunsaturated fatty acids (PUFAs). In contrast, the fatty acid composition of TAGs showed the opposite trend, with relative enrichment in PUFAs. This study enhances our understanding of Chlorella lipid metabolism, providing valuable insights for optimizing lipid production, particularly TAGs enriched with PUFA content, for applications in functional foods, nutraceuticals, and sustainable bioresources. Full article

(This article belongs to the Special Issue Microalgae Biotechnology and Microbiology: Prospects and Applications)

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18 pages, 21454 KB

Open AccessEditor’s ChoiceArticle

Digital Workflow with Open-Source CAD-CAM Software Aimed to Design a Customized 3D Laser-Printed Titanium Mesh for Guided Bone Regeneration

by Claudio Cirrincione, Giulia Guarnieri and Annamaria Morelli

Bioengineering 2025, 12(5), 436; https://doi.org/10.3390/bioengineering12050436 - 22 Apr 2025

Cited by 1 | Viewed by 1561

Abstract

Guided bone regeneration (GBR) is a procedure used for the treatment of bone deficiencies. Computer-Aided Designed–Computer-Aided Manufacturing (CAD-CAM) allows us to design a titanium mesh (TM) for GBR directly on a 3D bone defect model (3DBM). The design and printing of TMs are [...] Read more.

Guided bone regeneration (GBR) is a procedure used for the treatment of bone deficiencies. Computer-Aided Designed–Computer-Aided Manufacturing (CAD-CAM) allows us to design a titanium mesh (TM) for GBR directly on a 3D bone defect model (3DBM). The design and printing of TMs are often delegated to specialized 3D printing centers, thus preventing the surgeon from controlling surgical parameters such as the thickness, pore width, texture, and stiffness. Therefore, we have here proposed a personalized digital workflow for designing a TM. The 3DBM was uploaded to an open-source CAD-CAM software. Following a GBR simulation, a TM was designed as a Standard Tesselation Language (STL) file and 3D laser-printed. The TM was applied to a graft of 50/50% autologous/xenogenic bone, fixed with a bone screw, and covered with a dermal membrane. No TM exposure was observed during the healing phase. The regenerated bone volume was 970 cc, and pseudoperiosteum was class 1. At the 6-month reentry, a 4.1 × 10 standard dental implant with a primary stability of 40 N/cm was placed and after 3 months a zirconia crown screw-on implant was placed. This proposed digital workflow enabled us to successfully tackle this clinical case. However, further clinical investigations will be necessary to confirm the long-term benefits of this procedure. Full article

(This article belongs to the Section Regenerative Engineering)

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20 pages, 6681 KB

Open AccessEditor’s ChoiceArticle

CRISPR-Cas9-Mediated ATF6B Gene Editing Enhances Membrane Protein Production in HEK293T Cells

by Ho Joong Choi, Ba Reum Kim, Ok-Hee Kim and Say-June Kim

Bioengineering 2025, 12(4), 409; https://doi.org/10.3390/bioengineering12040409 - 11 Apr 2025

Viewed by 1616

Abstract

This study aims to enhance membrane protein production in HEK293T cells through genetic modification. HEK293T cells are used for recombinant protein and viral vector production due to their human origin and post-translational modification capabilities. This study explores enhancing membrane protein production in these [...] Read more.

This study aims to enhance membrane protein production in HEK293T cells through genetic modification. HEK293T cells are used for recombinant protein and viral vector production due to their human origin and post-translational modification capabilities. This study explores enhancing membrane protein production in these cells by deleting the C-terminal of the ATF6B gene using CRISPR-Cas9 technology. The objective of this research is to investigate the effect of C-terminal deletion of the ATF6B gene on membrane protein production in HEK293T cells using CRISPR-Cas9 technology. To identify effective gene targets, sgRNAs were initially designed against multiple UPR-related genes, including ATF6A, IRE1A, IRE1B, PERK, and ATF6B. Among them, ATF6B was selected as the primary target for further investigation due to its superior editing efficiency. The efficiency of sgRNAs was evaluated using the T7E1 assay, and sequencing was performed to verify gene editing patterns. Membrane proteins were extracted from both ATF6B C-terminally deleted (ATF6B-ΔC) and wild-type (WT) cell lines for comparison. Flow cytometry was employed to assess membrane protein production by analyzing GFP expression in Membrane-GFP-expressing cells. HEK293T cells with C-terminally deleted ATF6B (ATF6B-ΔC) significantly increased membrane protein production by approximately 40 ± 17.6% compared to WT cells (p < 0.05). Sequencing revealed 11, 14, 1, and 10 bp deletions in the ATF6B-ΔC edited cells, which disrupted exon sequences, induced exon skipping, and introduced premature stop codons, suppressing normal protein expression. Flow cytometry confirmed a 23.9 ± 4.2% increase in GFP intensity in ATF6B-ΔC cells, corroborating the enhanced membrane protein production. These findings suggest that CRISPR-Cas9-mediated C-terminal deletion of the ATF6B gene can effectively enhance membrane protein production in HEK293T cells by activating the unfolded protein response pathway and improving the cell’s capacity to manage misfolded proteins. This strategy presents significant potential for the biotechnology and pharmaceutical industries, where efficient membrane protein production is essential for drug development and various applications. Full article

(This article belongs to the Section Cellular and Molecular Bioengineering)

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14 pages, 2718 KB

Open AccessEditor’s ChoiceArticle

An Explainable Fusion of ECG and SpO₂-Based Models for Real-Time Sleep Apnea Detection

by Tanmoy Paul, Omiya Hassan, Christina S. McCrae, Syed Kamrul Islam and Abu Saleh Mohammad Mosa

Bioengineering 2025, 12(4), 382; https://doi.org/10.3390/bioengineering12040382 - 3 Apr 2025

Cited by 2 | Viewed by 2613

Abstract

Obstructive sleep apnea (OSA) is a common disorder characterized by disrupted breathing during sleep, leading to serious health consequences such as daytime fatigue, hypertension, metabolic issues, and cardiovascular disease. Polysomnography (PSG) is the standard diagnostic method but is costly and uncomfortable for patients, [...] Read more.

Obstructive sleep apnea (OSA) is a common disorder characterized by disrupted breathing during sleep, leading to serious health consequences such as daytime fatigue, hypertension, metabolic issues, and cardiovascular disease. Polysomnography (PSG) is the standard diagnostic method but is costly and uncomfortable for patients, which has led to interest in artificial intelligence (AI) for automated OSA detection. To develop an explainable AI model that utilizes electrocardiogram (ECG) and blood oxygen saturation (SpO2) data for real-time apnea detection, providing visual explanations to enhance interpretability and support clinical decisions. It emphasizes giving visual explanations to show how specific segments of the signal contribute to the AI’s conclusions. Furthermore, it explores the combination of individual models to improve detection accuracy. The fusion of individual models demonstrates an enhanced performance in detection accuracy. Visual explanations for AI decisions highlight the importance of certain signal features, making the model’s operations transparent to healthcare providers. The proposed AI model addresses the crucial need for transparent and interpretable AI in healthcare. By providing real-time, explainable OSA detection, this approach represents a significant advancement in the field, potentially improving patient care and aiding in the early identification and management of OSA. Full article

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

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31 pages, 55958 KB

Open AccessEditor’s ChoiceArticle

Computational Modelling of Protected and Unprotected Head Impacts in Rugby

by Thea Hodges, Adam Jones, Lucía Pérez del Olmo, Ashwin Mishra, Brian Caulfield, Tahar Kechadi, David MacManus and Michael D. Gilchrist

Bioengineering 2025, 12(4), 361; https://doi.org/10.3390/bioengineering12040361 - 31 Mar 2025

Viewed by 1901

Abstract

This study involved the simulation of five real-world head impact events in rugby, to assess the level of protection provided by a novel foam headguard, the N-Pro. The University College Dublin Brain Trauma Model (UCDBTM) was used to estimate the peak resultant head [...] Read more.

This study involved the simulation of five real-world head impact events in rugby, to assess the level of protection provided by a novel foam headguard, the N-Pro. The University College Dublin Brain Trauma Model (UCDBTM) was used to estimate the peak resultant head accelerations and brain tissue responses in different head impact scenarios. The input kinematics were obtained from two sources: video analysis of impact events, and real-time data obtained through instrumented mouthguards. The impact events were simulated under both unprotected and protected conditions. All simulations were performed against a rigid, non-compliant surface model. The results obtained in this study demonstrate the significant potential of the N-Pro in reducing peak head accelerations and brain tissue stress/strain responses by up to c. 70% compared to unprotected head impacts. This study highlights the headguard’s promising potential to reduce the severity of impact-related injuries by effectively attenuating stresses and strains, as well as linear and rotational kinematics. Additionally, the study supports the recommendation in the literature that kinematic data collected from wearable sensors should be supplemented by video analysis to improve accident reconstructions. Full article

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

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18 pages, 2351 KB

Open AccessEditor’s ChoiceReview

Pulsed Field Ablation: A Review of Preclinical and Clinical Studies

by Andrew P. Sullivan, Martin Aguilar and Zachary Laksman

Bioengineering 2025, 12(4), 329; https://doi.org/10.3390/bioengineering12040329 - 22 Mar 2025

Cited by 3 | Viewed by 6887

Abstract

Pulsed field ablation (PFA) is an emerging technology that utilizes ultra-short high-voltage electric pulses to create nanopores in cell membranes, leading to cell death through irreversible electroporation (IRE). PFA is touted to be highly tissue-selective, which may mitigate the risk of collateral injury [...] Read more.

Pulsed field ablation (PFA) is an emerging technology that utilizes ultra-short high-voltage electric pulses to create nanopores in cell membranes, leading to cell death through irreversible electroporation (IRE). PFA is touted to be highly tissue-selective, which may mitigate the risk of collateral injury to vital adjacent structures. In the field of cardiac electrophysiology, initial studies have shown promising results for acute pulmonary vein isolation (PVI) and lesion durability, with overall freedom from recurrent atrial arrhythmia comparable to traditional thermal ablation modalities. While further large studies are required for long-term efficacy and safety data, PFA has the potential to become a preferred energy source for cardiac ablation for some indications. This review outlines the basic principles and biophysics of IRE and its application to cardiac electrophysiology through a review of the existing preclinical and clinical data. Full article

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

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49 pages, 8327 KB

Open AccessEditor’s ChoiceReview

The Transformation Experiment of Frederick Griffith I: Its Narrowing and Potential for the Creation of Novel Microorganisms

by Günter A. Müller

Bioengineering 2025, 12(3), 324; https://doi.org/10.3390/bioengineering12030324 - 20 Mar 2025

Cited by 1 | Viewed by 3475

Abstract

The construction of artificial microorganisms often relies on the transfer of genomes from donor to acceptor cells. This synthetic biology approach has been considerably fostered by the J. Craig Venter Institute but apparently depends on the use of microorganisms, which are very closely [...] Read more.

The construction of artificial microorganisms often relies on the transfer of genomes from donor to acceptor cells. This synthetic biology approach has been considerably fostered by the J. Craig Venter Institute but apparently depends on the use of microorganisms, which are very closely related. One reason for this limitation of the “creative potential” of “classical” transformation is the requirement for adequate “fitting” of newly synthesized polypeptide components, directed by the donor genome, to interacting counterparts encoded by the pre-existing acceptor genome. Transformation was introduced in 1928 by Frederick Griffith in the course of the demonstration of the instability of pneumococci and their conversion from rough, non-pathogenic into smooth, virulent variants. Subsequently, this method turned out to be critical for the identification of DNA as the sole matter of inheritance. Importantly, the initial experimental design (1.0) also considered the inheritance of both structural (e.g., plasma membranes) and cybernetic information (e.g., metabolite fluxes), which, in cooperation, determine topological and cellular heredity, as well as fusion and blending of bacterial cells. In contrast, subsequent experimental designs (1.X) were focused on the use of whole-cell homogenates and, thereafter, of soluble and water-clear fractions deprived of all information and macromolecules other than those directing protein synthesis, including outer-membrane vesicles, bacterial prions, lipopolysaccharides, lipoproteins, cytoskeletal elements, and complexes thereof. Identification of the reasons for this narrowing may be helpful in understanding the potential of transformation for the creation of novel microorganisms. Full article

(This article belongs to the Section Biochemical Engineering)

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4 pages, 395 KB

Open AccessEditor’s ChoiceEditorial

Multiscale Modeling in Computational Biomechanics: A New Era with Virtual Human Twins and Contemporary Artificial Intelligence

by Tien-Tuan Dao

Bioengineering 2025, 12(3), 320; https://doi.org/10.3390/bioengineering12030320 - 20 Mar 2025

Viewed by 1017

Abstract

Over the last several decades, computational biomechanics has been intensively investigated as part of the study of human body systems (musculoskeletal, cardiovascular, digestive, etc [...] Full article

(This article belongs to the Special Issue Multiscale Modeling in Computational Biomechanics)

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3 pages, 144 KB

Open AccessEditor’s ChoiceEditorial

Musculoskeletal Disorders and Diseases: Biomechanical Modeling in Sport, Health, Rehabilitation and Ergonomics

by Philippe Gorce

Bioengineering 2025, 12(3), 300; https://doi.org/10.3390/bioengineering12030300 - 16 Mar 2025

Cited by 1 | Viewed by 1478

Abstract

Protecting people at work and at leisure, and improving their quality of life, is one of the major challenges faced in this century [...] Full article

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

23 pages, 2755 KB

Open AccessEditor’s ChoiceReview

A Sensor-Based Classification for Neuromotor Robot-Assisted Rehabilitation

by Calin Vaida, Gabriela Rus and Doina Pisla

Bioengineering 2025, 12(3), 287; https://doi.org/10.3390/bioengineering12030287 - 13 Mar 2025

Cited by 1 | Viewed by 2317

Abstract

Neurological diseases leading to motor deficits constitute significant challenges to healthcare systems. Despite technological advancements in data acquisition, sensor development, data processing, and virtual reality (VR), a suitable framework for patient-centered neuromotor robot-assisted rehabilitation using collective sensor information does not exist. An extensive [...] Read more.

Neurological diseases leading to motor deficits constitute significant challenges to healthcare systems. Despite technological advancements in data acquisition, sensor development, data processing, and virtual reality (VR), a suitable framework for patient-centered neuromotor robot-assisted rehabilitation using collective sensor information does not exist. An extensive literature review was achieved based on 124 scientific publications regarding different types of sensors and the usage of the bio-signals they measure for neuromotor robot-assisted rehabilitation. A comprehensive classification of sensors was proposed, distinguishing between specific and non-specific parameters. The classification criteria address essential factors such as the type of sensors, the data they measure, their usability, ergonomics, and their overall impact on personalized treatment. In addition, a framework designed to collect and utilize relevant data for the optimal rehabilitation process efficiently is proposed. The proposed classifications aim to identify a set of key variables that can be used as a building block for a dynamic framework tailored for personalized treatments, thereby enhancing the effectiveness of patient-centered procedures in rehabilitation. Full article

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

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16 pages, 6744 KB

Open AccessEditor’s ChoiceArticle

Effect of Decorin and Aligned Collagen Fibril Topography on TGF-β1 Activation of Corneal Keratocytes

by Nathaniel S. Tjahjono, Divya Subramanian, Tarik Z. Shihabeddin, Hudson D. Hicks, Victor D. Varner, W. Matthew Petroll and David W. Schmidtke

Bioengineering 2025, 12(3), 259; https://doi.org/10.3390/bioengineering12030259 - 5 Mar 2025

Cited by 2 | Viewed by 2059

Abstract

During corneal wound healing, transforming growth factor-beta 1 (TGF-β1) causes differentiation of quiescent keratocytes into myofibroblasts. Decorin has been investigated as a promising anti-fibrotic therapeutic for corneal healing due to its interaction with TGF-β1, collagen, and cell surface receptors. In this study, a [...] Read more.

During corneal wound healing, transforming growth factor-beta 1 (TGF-β1) causes differentiation of quiescent keratocytes into myofibroblasts. Decorin has been investigated as a promising anti-fibrotic therapeutic for corneal healing due to its interaction with TGF-β1, collagen, and cell surface receptors. In this study, a novel microfluidic method for coating aligned collagen fibrils with decorin was developed to mimic the presence of decorin within the corneal stroma. Decorin was found to bind selectively to collagen and remained bound for at least five days. To investigate the effects of decorin coatings on keratocyte activation, primary rabbit keratocytes were cultured in the presence of TGF-β1 for 5 days on substrates with or without decorin and stained for α-smooth muscle actin (α-SMA). The expression of α-SMA was reduced by similar amounts on monomeric collagen (40%), random collagen fibrils (32%), and aligned collagen fibrils (32%) coated with decorin as controls. However, α-SMA expression was differentially expressed between the collagen substrates not coated with decorin, with significantly lower expression on uncoated aligned collagen fibrils compared to uncoated collagen monomers. Addition of decorin directly to culture media, had a limited effect on reducing myofibroblast differentiation. Taken together, these results demonstrate the importance of topography and ECM composition on keratocyte activation. Full article

(This article belongs to the Special Issue Bioengineering and the Eye—2nd Edition)

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19 pages, 1675 KB

Open AccessEditor’s ChoiceArticle

A Method for Polyp Segmentation Through U-Net Network

by Antonella Santone, Mario Cesarelli and Francesco Mercaldo

Bioengineering 2025, 12(3), 236; https://doi.org/10.3390/bioengineering12030236 - 26 Feb 2025

Cited by 4 | Viewed by 2892

Abstract

Early detection of colorectal polyps through endoscopic colonoscopy is crucial in reducing colorectal cancer mortality. While automated polyp segmentation has been explored to enhance detection accuracy and efficiency, challenges remain in achieving precise boundary delineation, particularly for small or flat polyps. In this [...] Read more.

Early detection of colorectal polyps through endoscopic colonoscopy is crucial in reducing colorectal cancer mortality. While automated polyp segmentation has been explored to enhance detection accuracy and efficiency, challenges remain in achieving precise boundary delineation, particularly for small or flat polyps. In this work, we propose a novel U-Net-based segmentation framework specifically optimized for real-world endoscopic colonoscopy data. Unlike conventional approaches, our method leverages high-resolution frames with pixel-level ground-truth annotations to achieve superior segmentation performance. The U-Net architecture, with its symmetric encoder-decoder design and skip connections, is further adapted to enhance both high-level contextual understanding and fine-grained detail preservation. Our model has been rigorously evaluated on a real-world dataset, demonstrating state-of-the-art accuracy in polyp boundary segmentation, even in challenging cases. By improving detection consistency and reducing observer variability, our approach provides a robust tool to support gastroenterologists in clinical decision-making. Beyond real-time clinical applications, this work contributes to advancing automated and standardized polyp detection, paving the way for more reliable AI-assisted endoscopic analysis. Full article

(This article belongs to the Special Issue Applications of Computational Modeling in Biomedical Image and Signal Processing—2nd Edition)

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13 pages, 1473 KB

Open AccessEditor’s ChoiceArticle

Sensitivity of Lumbar Total Joint Replacement Contact Stresses Under Misalignment Conditions—Finite Element Analysis of a Spine Wear Simulator

by Steven M. Kurtz, Steven A. Rundell, Hannah Spece and Ronald V. Yarbrough

Bioengineering 2025, 12(3), 229; https://doi.org/10.3390/bioengineering12030229 - 24 Feb 2025

Cited by 2 | Viewed by 1390

Abstract

A novel total joint replacement (TJR) that treats lumbar spine degeneration was previously assessed under Mode I and Mode IV conditions. In this study, we relied on these previous wear tests to establish a relationship between finite element model (FEM)-based bearing stresses and [...] Read more.

A novel total joint replacement (TJR) that treats lumbar spine degeneration was previously assessed under Mode I and Mode IV conditions. In this study, we relied on these previous wear tests to establish a relationship between finite element model (FEM)-based bearing stresses and in vitro wear penetration maps. Our modeling effort addressed the following question of interest: Under reasonably worst-case misaligned conditions, do the lumbar total joint replacement (L-TJR) polyethylene stresses and strains remain below values associated with Mode IV impingement wear tests? The FEM was first formally verified and validated using the risk-informed credibility assessment framework established by ASME V&V 40 and FDA guidance. Then, based on criteria for unreasonable misuse outlined in the surgical technique guide, a parametric analysis of reasonably worst-case misalignment using the validated L-TJR FEM was performed. Reasonable misalignment was created by altering device positioning from the baseline condition in three scenarios: Axial Plane Convergence (20–40°), Axial Plane A-P Offset (0–4 mm), and Coronal Plane Tilt (±20°). We found that, for the scenarios considered, the contact pressures, von Mises stresses, and effective strains of the L-TJR-bearing surfaces remained consistent with Mode I (clean) conditions. Specifically, the mechanical response values fell below those determined under Mode IV (worst-case) boundary conditions, which provided the upper-bound benchmarks for the study (peak contact pressure 83.3 MPa, peak von Mises stress 32.2 MPa, and peak effective strain 42%). The L-TJR was judged to be insensitive to axial and coronal misalignment under the in vitro boundary conditions imposed by the study. Full article

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

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2 pages, 143 KB

Open AccessEditor’s ChoiceEditorial

Bioengineering of the Motor System

by Carlo Albino Frigo

Bioengineering 2025, 12(2), 199; https://doi.org/10.3390/bioengineering12020199 - 18 Feb 2025

Viewed by 759

Abstract

About fifty years ago, which seems very recent, new technologies for motion analysis were being developed, promising a more detailed and precise study of the human motor system [...] Full article

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

13 pages, 480 KB

Open AccessEditor’s ChoiceReview

Applications of Machine Learning-Driven Molecular Models for Advancing Ophthalmic Precision Medicine

by Rahul Kumar, Joshua Ong, Ethan Waisberg, Ryung Lee, Tuan Nguyen, Phani Paladugu, Maria Chiara Rivolta, Chirag Gowda, John Vincent Janin, Jeremy Saintyl, Dylan Amiri, Ansh Gosain and Ram Jagadeesan

Bioengineering 2025, 12(2), 156; https://doi.org/10.3390/bioengineering12020156 - 6 Feb 2025

Viewed by 2099

Abstract

Ophthalmic diseases such as glaucoma, age-related macular degeneration (ARMD), and optic neuritis involve complex molecular and cellular disruptions that challenge current diagnostic and therapeutic approaches. Advanced artificial intelligence (AI) and machine learning (ML) models offer a novel lens to analyze these diseases by [...] Read more.

Ophthalmic diseases such as glaucoma, age-related macular degeneration (ARMD), and optic neuritis involve complex molecular and cellular disruptions that challenge current diagnostic and therapeutic approaches. Advanced artificial intelligence (AI) and machine learning (ML) models offer a novel lens to analyze these diseases by integrating diverse datasets, identifying patterns, and enabling precision medicine strategies. Over the past decade, applications of AI in ophthalmology have expanded from imaging-based diagnostics to molecular-level modeling, bridging critical gaps in understanding disease mechanisms. This paper systematically reviews the application of AI-driven methods, including reinforcement learning (RL), graph neural networks (GNNs), Bayesian inference, and generative adversarial networks (GANs), in the context of these ophthalmic conditions. RL models simulate transcription factor dynamics in hypoxic or inflammatory environments, offering insights into disrupted molecular pathways. GNNs map intricate molecular networks within affected tissues, identifying key inflammatory or degenerative drivers. Bayesian inference provides probabilistic models for predicting disease progression and response to therapies, while GANs generate synthetic datasets to explore therapeutic interventions. By contextualizing these AI tools within the broader framework of ophthalmic disease management, this review highlights their potential to transform diagnostic precision and therapeutic outcomes. Ultimately, this work underscores the need for continued interdisciplinary collaboration to harness AI’s potential in advancing the field of ophthalmology and improving patient care. Full article

(This article belongs to the Special Issue Translational AI and Computational Tools for Ophthalmic Disease)

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3 pages, 130 KB

Open AccessEditor’s ChoiceEditorial

Editorial: Biomechanics, Health, Disease and Rehabilitation—2nd Edition

by Redha Taiar

Bioengineering 2025, 12(2), 121; https://doi.org/10.3390/bioengineering12020121 - 28 Jan 2025

Viewed by 1067

Abstract

In the original article [...] Full article

(This article belongs to the Special Issue Biomechanics, Health, Disease and Rehabilitation, 2nd Edition)

17 pages, 7767 KB

Open AccessEditor’s ChoiceArticle

A Novel Mechanics-Based Design for Overcorrection in Clear Aligner Orthodontics via Finite Element Analysis

by Sensen Yang and Yumin Cheng

Bioengineering 2025, 12(2), 110; https://doi.org/10.3390/bioengineering12020110 - 24 Jan 2025

Viewed by 2415

Abstract

A simplified mechanics model of aligner–tooth interaction was developed to establish a precise computational method for overcorrection design in clear aligner orthodontics. Validated through finite element analysis and experiments, the results demonstrated that designing the movement of only the target teeth on the [...] Read more.

A simplified mechanics model of aligner–tooth interaction was developed to establish a precise computational method for overcorrection design in clear aligner orthodontics. Validated through finite element analysis and experiments, the results demonstrated that designing the movement of only the target teeth on the aligner leads to uneven force distribution on adjacent teeth, while an overcorrection design can evenly distribute the reaction force generated by pushing the target teeth to the anchorage teeth, reducing the maximum force on the anchorage teeth, minimizing unplanned tooth movement, and improving the efficacy of the designed tooth movement for all teeth. Full article

(This article belongs to the Special Issue Orthodontic Biomechanics)

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31 pages, 1806 KB

Open AccessEditor’s ChoiceReview

Emerging Strategies for Revascularization: Use of Cell-Derived Extracellular Vesicles and Artificial Nanovesicles in Critical Limb Ischemia

by Vijay Murali Ravi Mythili, Ramya Lakshmi Rajendran, Raksa Arun, Vasanth Kanth Thasma Loganathbabu, Danyal Reyaz, ArulJothi Kandasamy Nagarajan, Byeong-Cheol Ahn and Prakash Gangadaran

Bioengineering 2025, 12(1), 92; https://doi.org/10.3390/bioengineering12010092 - 20 Jan 2025

Cited by 5 | Viewed by 3068

Abstract

Critical limb ischemia (CLI) poses a substantial and intricate challenge in vascular medicine, necessitating the development of innovative therapeutic strategies to address its multifaceted pathophysiology. Conventional revascularization approaches often fail to adequately address the complexity of CLI, necessitating the identification of alternative methodologies. [...] Read more.

Critical limb ischemia (CLI) poses a substantial and intricate challenge in vascular medicine, necessitating the development of innovative therapeutic strategies to address its multifaceted pathophysiology. Conventional revascularization approaches often fail to adequately address the complexity of CLI, necessitating the identification of alternative methodologies. This review explores uncharted territory beyond traditional therapies, focusing on the potential of two distinct yet interrelated entities: cell-derived extracellular vesicles (EVs) and artificial nanovesicles. Cell-derived EVs are small membranous structures naturally released by cells, and artificial nanovesicles are artificially engineered nanosized vesicles. Both these vesicles represent promising avenues for therapeutic intervention. They act as carriers of bioactive cargo, including proteins, nucleic acids, and lipids, that can modulate intricate cellular responses associated with ischemic tissue repair and angiogenesis. This review also assesses the evolving landscape of CLI revascularization through the unique perspective of cell-derived EVs and artificial nanovesicles. The review spans the spectrum from early preclinical investigations to the latest translational advancements, providing a comprehensive overview of the current state of research in this emerging field. These groundbreaking vesicle therapies hold immense potential for revolutionizing CLI treatment paradigms. Full article

(This article belongs to the Special Issue Innovations in Regenerative Therapy: Cell and Cell-Free Approaches)

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28 pages, 11306 KB

Open AccessEditor’s ChoiceArticle

Biomarker Investigation Using Multiple Brain Measures from MRI Through Explainable Artificial Intelligence in Alzheimer’s Disease Classification

by Davide Coluzzi, Valentina Bordin, Massimo W. Rivolta, Igor Fortel, Liang Zhan, Alex Leow and Giuseppe Baselli

Bioengineering 2025, 12(1), 82; https://doi.org/10.3390/bioengineering12010082 - 17 Jan 2025

Cited by 7 | Viewed by 3499

Abstract

As the leading cause of dementia worldwide, Alzheimer’s Disease (AD) has prompted significant interest in developing Deep Learning (DL) approaches for its classification. However, it currently remains unclear whether these models rely on established biological indicators. This work compares a novel DL model [...] Read more.

As the leading cause of dementia worldwide, Alzheimer’s Disease (AD) has prompted significant interest in developing Deep Learning (DL) approaches for its classification. However, it currently remains unclear whether these models rely on established biological indicators. This work compares a novel DL model using structural connectivity (namely, BC-GCN-SE adapted from functional connectivity tasks) with an established model using structural magnetic resonance imaging (MRI) scans (namely, ResNet18). Unlike most studies primarily focusing on performance, our work places explainability at the forefront. Specifically, we define a novel Explainable Artificial Intelligence (XAI) metric, based on gradient-weighted class activation mapping. Its aim is quantitatively measuring how effectively these models fare against established AD biomarkers in their decision-making. The XAI assessment was conducted across 132 brain parcels. Results were compared to AD-relevant regions to measure adherence to domain knowledge. Then, differences in explainability patterns between the two models were assessed to explore the insights offered by each piece of data (i.e., MRI vs. connectivity). Classification performance was satisfactory in terms of both the median true positive (ResNet18: 0.817, BC-GCN-SE: 0.703) and true negative rates (ResNet18: 0.816; BC-GCN-SE: 0.738). Statistical tests (p < 0.05) and ranking of the 15% most relevant parcels revealed the involvement of target areas: the medial temporal lobe for ResNet18 and the default mode network for BC-GCN-SE. Additionally, our findings suggest that different imaging modalities provide complementary information to DL models. This lays the foundation for bioengineering advancements in developing more comprehensive and trustworthy DL models, potentially enhancing their applicability as diagnostic support tools for neurodegenerative diseases. Full article

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

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13 pages, 2212 KB

Open AccessEditor’s ChoiceArticle

Effect of Adapted Ergometer Setup and Rowing Speed on Lower Extremity Loading in People with and Without Spinal Cord Injury

by Ying Fang and Karen L. Troy

Bioengineering 2025, 12(1), 75; https://doi.org/10.3390/bioengineering12010075 - 15 Jan 2025

Viewed by 2274

Abstract

Background: Functional electrical stimulation-assisted rowing (FES rowing) is a rehabilitation exercise used to prevent disuse osteoporosis, which is common in people with spinal cord injury (SCI). However, its effect on bone loss prevention varied in SCI patients, potentially due to inconsistent loading. This [...] Read more.

Background: Functional electrical stimulation-assisted rowing (FES rowing) is a rehabilitation exercise used to prevent disuse osteoporosis, which is common in people with spinal cord injury (SCI). However, its effect on bone loss prevention varied in SCI patients, potentially due to inconsistent loading. This study investigates the effect of ergometer setup and rowing speed on lower extremity loading during rowing. Methods: Twenty able-bodied participants and one participant with SCI rowed on an adapted ergometer with different speeds and setups. We calculated foot reaction force and knee moment for all participants, and tibiofemoral force for the rower with SCI. Results: Able-bodied rowers generated 0.22–0.45 body weight (BW) foot reaction forces, and a higher force was associated with a fast speed, forward seat position, and large knee range of motion (RoM). The rower with SCI had the greatest foot reaction force (0.39 BW) when rowing with a small knee RoM at a rear seat position, and the highest tibiofemoral force (2.23 BW) with a large knee RoM or at a rear seat position. Conclusions: Ergometer setup and speed both affect lower limb loading and should be further studied in more rowers with SCI. This can inform rehabilitation protocols to standardize ergometer configuration to improve bone health. Full article

(This article belongs to the Special Issue Biomechanics of Orthopaedic Rehabilitation)

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20 pages, 1270 KB

Open AccessEditor’s ChoiceReview

Current Understanding on the Heterogenous Expression of Plastic Depolymerising Enzymes in Pichia pastoris

by Shuyan Wu, David Hooks and Gale Brightwell

Bioengineering 2025, 12(1), 68; https://doi.org/10.3390/bioengineering12010068 - 14 Jan 2025

Cited by 1 | Viewed by 3063

Abstract

Enzymatic depolymerisation is increasingly recognised as a reliable and environmentally friendly method. The development of this technology hinges on the availability of high-quality enzymes and associated bioreaction systems for upscaling biodegradation. Microbial heterologous expression systems have been studied for meeting this demand. Among [...] Read more.

Enzymatic depolymerisation is increasingly recognised as a reliable and environmentally friendly method. The development of this technology hinges on the availability of high-quality enzymes and associated bioreaction systems for upscaling biodegradation. Microbial heterologous expression systems have been studied for meeting this demand. Among these systems, the Pichia pastoris expression system has emerged as a widely used platform for producing secreted heterologous proteins. This article provides an overview of studies involving the recombinant expression of polymer-degrading enzymes using the P. pastoris expression system. Research on P. pastoris expression of interested enzymes with depolymerising ability, including cutinase, lipase, and laccase, are highlighted in the review. The key factors influencing the heterologous expression of polymer-degrading enzymes in P. pastoris are discussed, shedding light on the challenges and opportunities in the development of depolymerising biocatalysts through the P. pastoris expression system. Full article

(This article belongs to the Special Issue Synthetic Biology and Bioprocess Engineering for High-Value Compounds)

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19 pages, 5155 KB

Open AccessEditor’s ChoiceArticle

Ex Vivo Regional Gene Therapy Compared to Recombinant BMP-2 for the Treatment of Critical-Size Bone Defects: An In Vivo Single-Cell RNA-Sequencing Study

by Arijita Sarkar, Matthew C. Gallo, Jennifer A. Bell, Cory K. Mayfield, Jacob R. Ball, Mina Ayad, Elizabeth Lechtholz-Zey, Stephanie W. Chang, Osamu Sugiyama, Denis Evseenko and Jay R. Lieberman

Bioengineering 2025, 12(1), 29; https://doi.org/10.3390/bioengineering12010029 - 1 Jan 2025

Cited by 2 | Viewed by 2537

Abstract

Ex vivo regional gene therapy is a promising tissue-engineering strategy for bone regeneration: osteogenic mesenchymal stem cells (MSCs) can be genetically modified to express an osteoinductive stimulus (e.g., bone morphogenetic protein-2), seeded onto an osteoconductive scaffold, and then implanted into a bone defect [...] Read more.

Ex vivo regional gene therapy is a promising tissue-engineering strategy for bone regeneration: osteogenic mesenchymal stem cells (MSCs) can be genetically modified to express an osteoinductive stimulus (e.g., bone morphogenetic protein-2), seeded onto an osteoconductive scaffold, and then implanted into a bone defect to exert a therapeutic effect. Compared to recombinant human BMP-2 (rhBMP-2), which is approved for clinical use, regional gene therapy may have unique benefits related to the addition of MSCs and the sustained release of BMP-2. However, the cellular and transcriptional mechanisms regulating the response to these two strategies for BMP-2 mediated bone regeneration are largely unknown. Here, for the first time, we performed single-cell RNA sequencing (10x Genomics) of hematoma tissue in six rats with critical-sized femoral defects that were treated with either regional gene therapy or rhBMP-2. Our unbiased bioinformatic analysis of 2393 filtered cells in each group revealed treatment-specific differences in their cellular composition, transcriptional profiles, and cellular communication patterns. Gene therapy treatment induced a more robust chondrogenic response, as well as a decrease in the proportion of fibroblasts and the expression of profibrotic pathways. Additionally, gene therapy was associated with an anti-inflammatory microenvironment; macrophages expressing canonical anti-inflammatory markers were more common in the gene therapy group. In contrast, pro-inflammatory markers were more highly expressed in the rhBMP-2 group. Collectively, the results of our study may offer insights into the unique pathways through which ex vivo regional gene therapy can augment bone regeneration compared to rhBMP-2. Furthermore, an improved understanding of the cellular pathways involved in segmental bone defect healing may allow for the further optimization of regional gene therapy or other bone repair strategies. Full article

(This article belongs to the Special Issue Advances in Bone Regeneration with Multipotential Stromal Cells and Bioactive Materials)

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17 pages, 5821 KB

Open AccessEditor’s ChoiceArticle

Development of a Microfluidic Viscometer for Non-Newtonian Blood Analog Fluid Analysis

by Yii-Nuoh Chang and Da-Jeng Yao

Bioengineering 2024, 11(12), 1298; https://doi.org/10.3390/bioengineering11121298 - 20 Dec 2024

Cited by 4 | Viewed by 6024

Abstract

The incidence of stroke is on the rise globally. This affects one in every four individuals each year, underscoring the urgent need for early warning and prevention systems. The existing research highlights the significance of monitoring blood viscosity in stroke risk evaluations. However, [...] Read more.

The incidence of stroke is on the rise globally. This affects one in every four individuals each year, underscoring the urgent need for early warning and prevention systems. The existing research highlights the significance of monitoring blood viscosity in stroke risk evaluations. However, the current methods lack the precision to measure viscosity under low shear rate conditions (<100 s⁻¹), which are observed during pulsatility flow. This study addresses this gap by introducing a novel microfluidic platform designed to measure blood viscosity with high precision under pulsatility flow conditions. The systolic blood viscosity (SBV) and diastolic blood viscosity (DBV) can be differentiated and evaluated by using this system. The non-Newtonian behavior of blood is captured across specific shear rate conditions. The platform employs a meticulously designed microarray to simulate the variations in blood viscosity during pulsation within blood vessels.The results demonstrate an impressive accuracy of 95% and excellent reproducibility when compared to traditional viscometers and rheometers and are within the human blood viscosity range of 1–10 cP. This monitoring system holds promise as a valuable addition to stroke risk evaluation methods, with the potential to enhance prediction accuracy. Full article

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

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15 pages, 3329 KB

Open AccessEditor’s ChoiceArticle

The Effect of Thigh Muscle Forces on Knee Contact Force in Female Patients with Severe Knee Osteoarthritis

by Tingting Liu, Hao Xie, Songhua Yan, Jizhou Zeng and Kuan Zhang

Bioengineering 2024, 11(12), 1299; https://doi.org/10.3390/bioengineering11121299 - 20 Dec 2024

Cited by 5 | Viewed by 2219

Abstract

Thigh muscles greatly influence knee joint loading, and abnormal loading significantly contributes to the progression of knee osteoarthritis (KOA). Muscle weakness in KOA patients is common, but the specific contribution of each thigh muscle to joint loading is unclear. The gait data from [...] Read more.

Thigh muscles greatly influence knee joint loading, and abnormal loading significantly contributes to the progression of knee osteoarthritis (KOA). Muscle weakness in KOA patients is common, but the specific contribution of each thigh muscle to joint loading is unclear. The gait data from 10 severe female KOA patients and 10 controls were collected, and the maximum isometric forces of the biceps femoris long head (BFL), semitendinosus (ST), rectus femoris (RF), vastus lateralis (VL), and vastus medialis (VM) were calibrated via ultrasound. Four musculoskeletal (MSK) models were developed based on EMG-assisted optimization, static optimization, and ultrasound data. The ultrasound-calibrated EMG-assisted MSK model achieved higher accuracy (R² > 0.97, RMSE < 0.045 Nm/kg). Patients exhibited increased VL and VM forces (p < 0.004) and decreased RF force (p < 0.006), along with elevated medial and total joint contact forces (p < 0.001) and reduced lateral forces (p < 0.001) compared to controls. The affected side relied on VL and BFL the most (p < 0.042), while RF was key for the unaffected side (p < 0.003). Ultrasound calibration and EMG-assisted optimization significantly enhanced MSK model accuracy. Patients exerted greater quadriceps and hamstring forces bilaterally, shifting knee loading medially, and depended more on the lateral thigh muscles on the affected side. Hamstrings contributed more to joint contact forces, while quadriceps’ contributions decreased. Full article

(This article belongs to the Special Issue Joint Biomechanics and Implant Design)

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12 pages, 1677 KB

Open AccessEditor’s ChoiceReview

Microfluidic Technology for Measuring Mechanical Properties of Single Cells and Its Application

by Yixin Yin and Ziyuan Liu

Bioengineering 2024, 11(12), 1266; https://doi.org/10.3390/bioengineering11121266 - 13 Dec 2024

Cited by 2 | Viewed by 2107

Abstract

Cellular mechanical properties are critical for tissue and organ homeostasis, which are associated with many diseases and are very promising non-labeled biomarkers. Over the past two decades, many research tools based on microfluidic methods have been developed to measure the biophysical properties of [...] Read more.

Cellular mechanical properties are critical for tissue and organ homeostasis, which are associated with many diseases and are very promising non-labeled biomarkers. Over the past two decades, many research tools based on microfluidic methods have been developed to measure the biophysical properties of single cells; however, it has still not been possible to develop a technique that allows for high-throughput, easy-to-operate and precise measurements of single-cell biophysical properties. In this paper, we review the emerging technologies implemented based on microfluidic approaches for characterizing the mechanical properties of single cells and discuss the methodological principles, advantages, limitations, and applications of various technologies. Full article

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

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16 pages, 5144 KB

Open AccessEditor’s ChoiceSystematic Review

Progress in 3D Printing Applications for the Management of Orbital Disorders: A Systematic Review

by Luca Michelutti, Alessandro Tel, Massimo Robiony, Salvatore Sembronio, Riccardo Nocini, Edoardo Agosti, Tamara Ius, Caterina Gagliano and Marco Zeppieri

Bioengineering 2024, 11(12), 1238; https://doi.org/10.3390/bioengineering11121238 - 7 Dec 2024

Cited by 3 | Viewed by 2073

Abstract

Introduction: 3D printing technology has gained considerable interest in the domain of orbital illnesses owing to its capacity to transform diagnosis, surgery planning, and treatment. This systematic review seeks to deliver a thorough examination of the contemporary applications of 3D printing in [...] Read more.

Introduction: 3D printing technology has gained considerable interest in the domain of orbital illnesses owing to its capacity to transform diagnosis, surgery planning, and treatment. This systematic review seeks to deliver a thorough examination of the contemporary applications of 3D printing in the treatment of ocular problems, encompassing tumors, injuries, and congenital defects. This systematic review of recent studies has examined the application of patient-specific 3D-printed models for preoperative planning, personalized implants, and prosthetics. Methods: This systematic review was conducted according to the PRISMA guidelines. The PICOS is “What are the current advances and applications of 3D printing for the management of orbital pathology?” The databases analyzed for the research phase are MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, ScienceDirect, Scopus, CINAHL, and Web of Science. Results: Out of 314 studies found in the literature, only 12 met the inclusion and exclusion criteria. From the included studies, it is evident that 3D printing can be a useful technology for the management of trauma and oncological pathologies of the orbital region. Discussion: 3D printing proves to be very useful mainly for the purpose of improving the preoperative planning of a surgical procedure, allowing for better preparation by the surgical team and a reduction in operative time and complications. Conclusions: 3D printing has proven to be an outstanding tool in the management of orbit pathology. Comparing the advantages and disadvantages of such technology, the former far outweigh the latter. Full article

(This article belongs to the Special Issue New Sights of Biomaterials and Regenerative Medicine)

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12 pages, 576 KB

Open AccessEditor’s ChoiceArticle

The Effect of EEG Biofeedback Training Frequency and Environmental Conditions on Simple and Complex Reaction Times

by Skalski Dariusz, Maciej Kostrzewa, Prończuk Magdalena, Jarosław Markowski, Jan Pilch, Marcin Żak and Adam Maszczyk

Bioengineering 2024, 11(12), 1208; https://doi.org/10.3390/bioengineering11121208 - 29 Nov 2024

Cited by 6 | Viewed by 2071

Abstract

The objective of this study is to evaluate the impact of EEG biofeedback training under normoxic and normobaric hypoxic conditions on both simple and complex reaction times in judo athletes, and to identify the optimal training frequency and environmental conditions that substantially enhance [...] Read more.

The objective of this study is to evaluate the impact of EEG biofeedback training under normoxic and normobaric hypoxic conditions on both simple and complex reaction times in judo athletes, and to identify the optimal training frequency and environmental conditions that substantially enhance reaction times in the examined athlete groups. The study comprised 20 male judo athlete members of the Polish national judo team in the middleweight and heavyweight categories. We randomly assigned participants to an experimental group and a control group. We conducted the research over four cycles, varying the frequency of EEG biofeedback sessions and environmental circumstances for both the experimental and control groups. Every research cycle had 15 training sessions. The results showed that the experimental group, following the theta/beta regimen, got significantly faster at complex reactions after a training cycle that included sessions every other day at normal oxygen levels. Following daily training sessions in normoxic circumstances, we noted enhancements in simple reaction speeds. Under normobaric hypoxia conditions, the judo athletes showed deterioration in both simple and complex reaction times. The control group showed no similar changes. Daily EEG training in normoxic settings markedly improved simple reaction time, but EEG-BF training conducted every other day greatly raised complicated reaction time. In contrast, training under normobaric hypoxia settings did not result in enhancements in basic or complicated reaction times following EEG training. Full article

(This article belongs to the Special Issue New Sights of EEG and Brain Diseases: Updates and Directions)

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3 pages, 153 KB

Open AccessEditor’s ChoiceEditorial

Computational Fluid Dynamics in Medicine and Biology

by Amirtahà Taebi

Bioengineering 2024, 11(11), 1168; https://doi.org/10.3390/bioengineering11111168 - 20 Nov 2024

Cited by 1 | Viewed by 2051

Abstract

This Special Issue of Bioengineering presents cutting-edge research on the applications of computational fluid dynamics (CFD) in medical and biological contexts [...] Full article

(This article belongs to the Special Issue Computational Fluid Dynamics in Medicine and Biology)

30 pages, 8578 KB

Open AccessEditor’s ChoiceArticle

Around-Body Versus On-Body Motion Sensing: A Comparison of Efficacy Across a Range of Body Movements and Scales

by Katelyn Rohrer, Luis De Anda, Camila Grubb, Zachary Hansen, Jordan Rodriguez, Greyson St Pierre, Sara Sheikhlary, Suleyman Omer, Binh Tran, Mehrail Lawendy, Farah Alqaraghuli, Chris Hedgecoke, Youssif Abdelkeder, Rebecca C. Slepian, Ethan Ross, Ryan Chung and Marvin J. Slepian

Bioengineering 2024, 11(11), 1163; https://doi.org/10.3390/bioengineering11111163 - 19 Nov 2024

Cited by 1 | Viewed by 1592

Abstract

Motion is vital for life. Currently, the clinical assessment of motion abnormalities is largely qualitative. We previously developed methods to quantitatively assess motion using visual detection systems (around-body) and stretchable electronic sensors (on-body). Here we compare the efficacy of these methods across predefined [...] Read more.

Motion is vital for life. Currently, the clinical assessment of motion abnormalities is largely qualitative. We previously developed methods to quantitatively assess motion using visual detection systems (around-body) and stretchable electronic sensors (on-body). Here we compare the efficacy of these methods across predefined motions, hypothesizing that the around-body system detects motion with similar accuracy as on-body sensors. Six human volunteers performed six defined motions covering three excursion lengths, small, medium, and large, which were analyzed via both around-body visual marker detection (MoCa version 1.0) and on-body stretchable electronic sensors (BioStamp version 1.0). Data from each system was compared as to the extent of trackability and comparative efficacy between systems. Both systems successfully detected motions, allowing quantitative analysis. Angular displacement between systems had the highest agreement efficiency for the bicep curl and body lean motion, with 73.24% and 65.35%, respectively. The finger pinch motion had an agreement efficiency of 36.71% and chest abduction/adduction had 45.55%. Shoulder abduction/adduction and shoulder flexion/extension motions had the lowest agreement efficiencies with 24.49% and 26.28%, respectively. MoCa was comparable to BioStamp in terms of angular displacement, though velocity and linear speed output could benefit from additional processing. Our findings demonstrate comparable efficacy for non-contact motion detection to that of on-body sensor detection, and offers insight as to the best system selection for specific clinical uses based on the use-case of the desired motion being analyzed. Full article

(This article belongs to the Special Issue Biomechanics and Motion Analysis)

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