Bioengineering

14 pages, 676 KiB

Open AccessReview

Very High Molecular Weight Hyaluronic Acid as an Enhanced Vehicle in Therapeutic Eye Drops: Application in a Novel Latanoprost Formulation for Glaucoma

by Jesús Pujol-Martí and Wolfgang G. K. Müller-Lierheim

Bioengineering 2025, 12(9), 907; https://doi.org/10.3390/bioengineering12090907 - 24 Aug 2025

Abstract

The efficacy of topical drug delivery via eye drops is often achieved at the expense of tolerability, and consequently, efforts are being made to design strategies that minimize the adverse effects associated with the passage of active pharmaceutical ingredients (APIs) across the ocular [...] Read more.

The efficacy of topical drug delivery via eye drops is often achieved at the expense of tolerability, and consequently, efforts are being made to design strategies that minimize the adverse effects associated with the passage of active pharmaceutical ingredients (APIs) across the ocular surface. Many of these approaches are too complex, costly and challenging to implement on an industrial scale, yet there is increasing evidence that hylan A, a very high molecular weight hyaluronic acid (≥3.0 MDa), may be a promising vehicle for topical drug delivery of ocular therapies. In this review, we explore how the mucoadhesive and viscoelastic properties of eye drop formulations based on hylan A help extend the residence time of APIs at the ocular surface, while maintaining patient comfort. Moreover, we examine how hylan A facilitates the dissolution and stabilization of APIs, as well as their transport across the ocular epithelial barrier, without the need to use toxic penetration enhancers, thereby preserving ocular surface health. Finally, we present evidence indicating that the intrinsic biological properties of hylan A, including its anti-inflammatory effects, help mitigate side effects commonly associated with certain APIs. To illustrate these advantages, we examine the pioneering use of a hylan A-based aqueous eye drop formulation as a vehicle to deliver latanoprost, a prostaglandin analogue widely used in the treatment of glaucoma. This case study demonstrates the potential of hylan A-based eye drops to offer safer and more effective topical drug delivery, especially for long-term ocular therapies where tolerability and biocompatibility are critical. Full article

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

20 pages, 3318 KiB

Open AccessReview

Review of Linear-Array-Transducer-Based Volumetric Ultrasound Imaging Techniques and Their Biomedical Applications

by Ninjbadgar Tsedendamba, Yuon Song, Eun-Yeong Park and Jeesu Kim

Bioengineering 2025, 12(9), 906; https://doi.org/10.3390/bioengineering12090906 - 23 Aug 2025

Abstract

Ultrasound imaging is one of the most widespread biomedical imaging techniques thanks to its advantages such as being non-invasive, portable, non-ionizing, and cost-effective. Ultrasound imaging generally provides two-dimensional cross-sectional images, but the quality and interpretative ability vary based on the experience of the [...] Read more.

Ultrasound imaging is one of the most widespread biomedical imaging techniques thanks to its advantages such as being non-invasive, portable, non-ionizing, and cost-effective. Ultrasound imaging generally provides two-dimensional cross-sectional images, but the quality and interpretative ability vary based on the experience of the examiner, leading to a lack of objectivity and accuracy. To address these issues, there is a growing demand for three-dimensional ultrasound imaging. Among the various types of transducers used to obtain three-dimensional ultrasound images, this paper focuses on the most standardized probe, the linear array transducer, and provides an overview of the system implementations, imaging results, and applications of volumetric ultrasound imaging from the perspective of scanning methods. Through this comprehensive review, future researchers will gain insights into the advantages and disadvantages of various approaches to three-dimensional imaging systems using linear arrays, providing direction and applicability for system configuration and application. Full article

(This article belongs to the Special Issue Biomedical Imaging and Data Analytics for Disease Diagnosis and Treatment, 3rd Edition)

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17 pages, 2271 KiB

Open AccessArticle

A Novel Protocol for Integrated Assessment of Upper Limbs Using the Optoelectronic Motion Analysis System: Validation and Usability in Healthy People

by Luca Emanuele Molteni, Luigi Piccinini, Daniele Panzeri, Ettore Micheletti and Giuseppe Andreoni

Bioengineering 2025, 12(9), 905; https://doi.org/10.3390/bioengineering12090905 - 23 Aug 2025

Abstract

(1) Background: Upper limb (UL) function plays a central role in daily life, enabling essential tasks such as reaching, grasping, and eating. While numerous tools exist to evaluate UL kinematics, their application in pediatric populations is often limited by a lack of age-specific [...] Read more.

(1) Background: Upper limb (UL) function plays a central role in daily life, enabling essential tasks such as reaching, grasping, and eating. While numerous tools exist to evaluate UL kinematics, their application in pediatric populations is often limited by a lack of age-specific validation. This study presents a novel motion analysis protocol featuring a customized marker set, aimed at assessing UL movements in the three anatomical planes across different age groups, with a focus on pediatric applicability. (2) Materials and Methods: A SmartDX motion capture system was used, with 30 markers positioned on the upper body, referencing the trunk as the root of the kinematic chain. Ten healthy participants (mean age: 18.69 ± 12.45 years; range: 8.0–41.4) without UL impairments were recruited. The broad age range was intentionally selected to assess the protocol’s transversal applicability. (3) Results: Results showed excellent intra-operator reliability for shoulder and wrist kinematics (ICC > 0.906) and good reliability for elbow movements (ICC > 0.755). Inter-operator reliability was good to excellent (shoulder ICC > 0.958; elbow ICC > 0.762; wrist ICC > 0.826) Usability, measured via the System Usability Scale, was rated as good (83.25). (4) Conclusions: The proposed protocol demonstrated strong reliability and practical usability, supporting its adoption in clinical and research settings. Its design allows for adaptability across motion capture platforms, promoting wider implementation in pediatric UL functional assessment. Full article

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

15 pages, 2968 KiB

Open AccessArticle

Engineered Neural Tissue (EngNT) Containing Human iPSC-Derived Schwann Cell Precursors Promotes Axon Growth in a Rat Model of Peripheral Nerve Injury

by Rebecca A. Powell, Emily A. Atkinson, Poppy O. Smith, Rickie Patani, Parmjit S. Jat, Owein Guillemot-Legris and James B. Phillips

Bioengineering 2025, 12(9), 904; https://doi.org/10.3390/bioengineering12090904 - 23 Aug 2025

Abstract

Tissue engineering has the potential to overcome the limitations of using autografts in nerve gap repair, using cellular biomaterials to bridge the gap and support neuronal regeneration. Various types of therapeutic cells could be considered for use in aligned collagen-based engineered neural tissue [...] Read more.

Tissue engineering has the potential to overcome the limitations of using autografts in nerve gap repair, using cellular biomaterials to bridge the gap and support neuronal regeneration. Various types of therapeutic cells could be considered for use in aligned collagen-based engineered neural tissue (EngNT), including Schwann cells and their precursors, which can be derived from human induced pluripotent stem cells (hiPSCs). Using Schwann cell precursors may have practical advantages over mature Schwann cells as they expand readily in vitro and involve a shorter differentiation period. However, the performance of each cell type needs to be tested in EngNT. By adapting established protocols, hiPSCs were differentiated into Schwann cell precursors and Schwann cells, with distinctive molecular profiles confirmed using immunocytochemistry and RT-qPCR. For the first time, both cell types were incorporated into EngNT using gel aspiration–ejection, a technique used to align and simultaneously stabilise the cellular hydrogels. Both types of cellular constructs supported and guided aligned neurite outgrowth from adult rat dorsal root ganglion neurons in vitro. Initial experiments in a rat model of nerve gap injury demonstrated the extent to which the engrafted cells survived after 2 weeks and indicated that both types of hiPSC-derived cells supported the infiltration of host neurons, Schwann cells and endothelial cells. In summary, we show that human Schwann cell precursors promote infiltrating endogenous axons in a model of peripheral nerve injury to a greater degree than their terminally differentiated Schwann cell counterparts. Full article

(This article belongs to the Special Issue Nerve Regeneration)

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20 pages, 5040 KiB

Open AccessArticle

Optimization and Analysis of Tangential Component Orientations in OPM-MEG Sensor Array

by Wenli Wang, Fuzhi Cao, Nan An, Wen Li, Chunhui Wang, Zhenfeng Gao, Min Xiang and Xiaolin Ning

Bioengineering 2025, 12(9), 903; https://doi.org/10.3390/bioengineering12090903 - 22 Aug 2025

Abstract

Optically pumped magnetometers (OPMs) have brought a transformative advancement to magnetoencephalography (MEG), enabling flexible, noncryogenic, and wearable neuroimaging systems. In particular, the development of triaxial OPM sensors allows for simultaneous measurement of full magnetic field vectors, including both radial and additional tangential components. [...] Read more.

Optically pumped magnetometers (OPMs) have brought a transformative advancement to magnetoencephalography (MEG), enabling flexible, noncryogenic, and wearable neuroimaging systems. In particular, the development of triaxial OPM sensors allows for simultaneous measurement of full magnetic field vectors, including both radial and additional tangential components. Previous studies have shown that incorporating tangential components helps enhance the separation between neural signals and external interference, but their optimal configurations remain unclear. This study systematically investigated the impact of tangential component configurations on array sensitivity and the lead field correlation coefficient (

R_{12}

) in triaxial OPM-MEG sensor arrays, considering tangential component rotations, relative orientations of sensor and source, source depths, and head model types. Based on the above analysis, we proposed an optimization strategy aimed at minimizing

R_{12}

, referred to as

R_{12}

-minimization array optimization (RMAO), to explore the optimal configuration of tangential components. The simulation results showed that the proposed method significantly enhanced sensitivity to cortical sources and effectively suppressed external interference, enabling more accurate source localization. This study highlights the critical role of tangential components in improving system performance and provides theoretical foundation and methodological guidance for the design of triaxial OPM-MEG sensor arrays. Full article

(This article belongs to the Section Biosignal Processing)

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10 pages, 307 KiB

Open AccessBrief Report

Association Between Optical Coherence Tomography Angiography (OCTA)-Based Retinal Vascular Densities and Empathy in Young Adults

by Bess Yin-Hung Lam, Carole Leung, Ka-Shun Lei, Kaiyip Choi and Henry H. L. Chan

Bioengineering 2025, 12(9), 902; https://doi.org/10.3390/bioengineering12090902 - 22 Aug 2025

Abstract

With the use of Optical Coherence Tomography Angiography (OCTA), the present study is the first study to examine if retinal vascular densities (vessel densities and perfusion densities) could be associated with empathetic levels in young and non-clinical adults. Methods: Fifty-one university students aged [...] Read more.

With the use of Optical Coherence Tomography Angiography (OCTA), the present study is the first study to examine if retinal vascular densities (vessel densities and perfusion densities) could be associated with empathetic levels in young and non-clinical adults. Methods: Fifty-one university students aged from 18 to 25 years (26 males and 24 females) were recruited from a university in Hong Kong. OCTA was conducted to assess their retinal vessel density (VD) and perfusion density (PD) in different scan patterns over the macula (1 mm center subfield, 3 × 3 mm scan, 6 × 6 mm scan). Empathy (cognitive, affective, and somatic) was measured by using the Cognitive, Affective, and Somatic Empathy Scales (CASES). Results: After controlling for age, the multiple linear regression results showed that both the VD and PD in the 1 mm center subfield were significantly and negatively associated with the empathy total score, the affective empathy subscore, and the somatic empathy subscore, respectively (ps < 0.05). Conclusion: The present findings indicate that a lower level of empathy is associated with increased retinal vascular densities in the 1 mm center subfield, specifically involving variations in vascular density (VD) and perfusion density (PD). This suggests the dilation of retinal venules might lead to lower empathy. These results establish a foundation for future studies investigating the underlying mechanism of retinal imaging and empathy in healthy individuals. Full article

(This article belongs to the Special Issue Retinal Circuit Engineering)

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19 pages, 4657 KiB

Open AccessArticle

Analysis of Extreme Thermal Variations in the Oral Cavity of a Patient with a Fixed Metallic Orthodontic Appliance Using the Finite Element Method

by Stelian-Mihai-Sever Petrescu, Anne-Marie Rauten, Mihai Popescu, Mihai Raul Popescu, Dragoș Laurențiu Popa, Gabriel Buciu, Eduard-Mihai Ciucă, Tiberius-Cătălin Dudan and Marilena Bătăiosu

Bioengineering 2025, 12(9), 901; https://doi.org/10.3390/bioengineering12090901 - 22 Aug 2025

Abstract

Several decades after the development of FEM in computer-based form, which is a milestone in the evaluation of mechanical systems, the method has been adopted to analyze the biomechanical response of human skeletal structures. This innovative technique has generated new questions, but also [...] Read more.

Several decades after the development of FEM in computer-based form, which is a milestone in the evaluation of mechanical systems, the method has been adopted to analyze the biomechanical response of human skeletal structures. This innovative technique has generated new questions, but also new results, and, at the same time, competitive environments with explosive development, in the recent period. This research is focused on analyzing, using FEM, the extreme thermal variations produced at the level of two oro-facial systems (one control and one subjected to orthodontic therapy using a fixed metallic orthodontic appliance). The objective of the study was to determine the temperature evolution in different dental structures subjected to extreme temperatures given by variations between very cold and very hot foods. Each system was exposed to a succession of extreme thermal regimes (70…−18…70… °C and −18…70…−18… °C). In order to conduct this research, we used the case of a 14-year-old female patient. Following an orthodontic evaluation, we discovered that the patient had dento-alveolar disharmony with crowding. The straight-wire method of applying a fixed metallic orthodontic appliance was chosen. As complementary examinations, the patient was subjected to a bimaxillary CBCT. Using a series of programs (InVesalius, Geomagic, SolidWorks, and AnsysWorkbench), a three-dimensional model was obtained. This model contained jaws and teeth. Also, brackets, tubes, and orthodontic wires can be incorporated into the model. Following the simulations carried out in this study, it was found that thermal variations from the dental pulp are more severe for the oro-facial system with a fixed metallic orthodontic appliance (regardless of the type of thermal stimulus used). Thus, even today, with all the facilities available in the dental materials industry, metallic orthodontic devices present significant thermal conductivity, generating harmful effects on the dental structures. The reading of the results was performed on the virtual model, more precisely, on the internal dental structures (enamel, dentin, and pulp). A statistical study was not performed because it was considered that, in other patients, the results would be similar. Full article

(This article belongs to the Special Issue Biomaterials and Technology for Oral and Dental Health)

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28 pages, 1314 KiB

Open AccessSystematic Review

Bioengineering Support in the Assessment and Rehabilitation of Low Back Pain

by Giustino Varrassi, Matteo Luigi Giuseppe Leoni, Ameen Abdulhasan Al-Alwany, Piercarlo Sarzi Puttini and Giacomo Farì

Bioengineering 2025, 12(9), 900; https://doi.org/10.3390/bioengineering12090900 - 22 Aug 2025

Abstract

Low back pain (LBP) remains one of the most prevalent and disabling musculoskeletal conditions globally, with profound social, economic, and healthcare implications. The rising incidence and chronic nature of LBP highlight the need for more objective, personalized, and effective approaches to assessment and [...] Read more.

Low back pain (LBP) remains one of the most prevalent and disabling musculoskeletal conditions globally, with profound social, economic, and healthcare implications. The rising incidence and chronic nature of LBP highlight the need for more objective, personalized, and effective approaches to assessment and rehabilitation. In this context, bioengineering has emerged as a transformative field, offering novel tools and methodologies that enhance the understanding and management of LBP. This narrative review examines current bioengineering applications in both diagnostic and therapeutic domains. For assessment, technologies such as wearable inertial sensors, three-dimensional motion capture systems, surface electromyography, and biomechanical modeling provide real-time, quantitative insights into posture, movement patterns, and muscle activity. On the therapeutic front, innovations including robotic exoskeletons, neuromuscular electrical stimulation, virtual reality-based rehabilitation, and tele-rehabilitation platforms are increasingly being integrated into multimodal treatment protocols. These technologies support precision medicine by tailoring interventions to each patient’s biomechanical and functional profile. Furthermore, the incorporation of artificial intelligence into clinical workflows enables automated data analysis, predictive modeling, and decision support systems, while future directions such as digital twin technology hold promise for personalized simulation and outcome forecasting. While these advancements are promising, further validation in large-scale, real-world settings is required to ensure safety, efficacy, and equitable accessibility. Ultimately, bioengineering provides a multidimensional, data-driven framework that has the potential to significantly improve the assessment, rehabilitation, and overall management of LBP. Full article

(This article belongs to the Special Issue Low-Back Pain: Assessment and Rehabilitation Research)

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10 pages, 1135 KiB

Open AccessArticle

A Bivalent Protease-Activated Receptor-Derived Peptide Mimics Neuronal Anti-Apoptotic Activity of Activated Protein C

by Abhay Sagare, Youbin Kim, Kassandra Kisler, Ruslan Rust, William J. Mack, José A. Fernández, Berislav V. Zlokovic and John H. Griffin

Bioengineering 2025, 12(9), 899; https://doi.org/10.3390/bioengineering12090899 - 22 Aug 2025

Abstract

Activated protein C (APC) exerts anticoagulant and cytoprotective cell signaling activities. APC’s cell signaling requires protease-activated receptor (PAR) PAR1 and PAR3, and APC’s PAR cleavages generate peptides capable of agonizing biased G-protein coupled receptor (GPCR) cytoprotective signaling, resulting in anti-inflammatory and anti-apoptotic activities [...] Read more.

Activated protein C (APC) exerts anticoagulant and cytoprotective cell signaling activities. APC’s cell signaling requires protease-activated receptor (PAR) PAR1 and PAR3, and APC’s PAR cleavages generate peptides capable of agonizing biased G-protein coupled receptor (GPCR) cytoprotective signaling, resulting in anti-inflammatory and anti-apoptotic activities and endothelial barrier stabilization. The PAR-sequence-derived 34-residue “G10 peptide” comprising PAR1 residues 47–55 covalently attached by a 10-glycine linker to PAR3 residues 51–65 is an orthosteric/allosteric bivalent GPCR agonist that potently mimics APC’s anti-inflammatory activity and endothelial barrier stabilization activity. The objective of this study was to determine whether the G10 peptide mimics APC’s anti-apoptotic activity using cultured murine neurons challenged by N-methyl-d-aspartate that provokes neuronal apoptosis. In these new studies, the G10 peptide mimicked APC’s anti-apoptotic activity. Thus, the PAR-derived 34-residue G10 peptide mimics APC’s three major cytoprotective activities, namely anti-inflammatory and anti-apoptotic activities and endothelial barrier stabilization. Peptides that agonize GPCRs provide promising and currently approved drugs; e.g., semaglutide and tirzepatide that contain 31 and 39 amino acid residues, respectively. Thus, this new study adds to the rationale for pursuing further studies of the G10 peptide for potential therapeutic value for multiple pathologies where APC or signaling-selective APC variants are therapeutic in preclinical animal studies. Full article

(This article belongs to the Section Biochemical Engineering)

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17 pages, 1378 KiB

Open AccessArticle

Effect of Surface Wettability and Energy on Bacterial Adhesion to Dental Aligners: A Comparative In Vitro Study

by A. Martínez Gil-Ortega, M. M. Paz-Cortés, M. J. Viñas, P. Cintora-López, A. Martín-Vacas, J. Gil and J. M. Aragoneses

Bioengineering 2025, 12(9), 898; https://doi.org/10.3390/bioengineering12090898 - 22 Aug 2025

Abstract

The use of orthodontic aligners has increased significantly due to their convenience and esthetic advantages. However, understanding their microbiological behavior and cytotoxicity is essential. This study aimed to evaluate the metabolic activity (MA) and proliferation of different bacterial strains—assessed through colony-forming unit (CFU) [...] Read more.

The use of orthodontic aligners has increased significantly due to their convenience and esthetic advantages. However, understanding their microbiological behavior and cytotoxicity is essential. This study aimed to evaluate the metabolic activity (MA) and proliferation of different bacterial strains—assessed through colony-forming unit (CFU) counts—as well as the cytotoxicity of three widely used aligner systems: Spark, Invisalign, and Smile. Wettability and surface free energy (both dispersive and polar components) were determined using the sessile drop technique. The bacterial strains Streptococcus oralis, Actinomyces viscosus, Streptococcus gordonii, Enterococcus faecalis, and Porphyromonas gingivalis were cultured, and their behavior on the aligner surfaces was assessed under simulated oral cavity conditions in both aerobic and anaerobic environments using a bioreactor. Cytocompatibility was evaluated with HFF-1 human fibroblasts. Distinct strain-specific behaviors were observed. For Spark aligners, the contact angle was 70.5°, Invisalign 80.6°, and Smile 91.2°, and the surface free energy was 60.8, 66.7, and 74. 2 mJ/m², respectively, highlighting the high polar component of the Spark aligner of 31.9 mJ/m² compared to 19.3 and 20.2 mJ/m² for Invisalign and Smile, respectively. The Spark aligner exhibited the lowest metabolic activity for Streptococcus oralis (23.1%), Actinomyces viscosus (43.2%), Porphyromonas gingivalis (17.7%), and biofilm formation (2.4%), likely due to its higher hydrophilicity. The Smile aligner showed the lowest metabolic activity for Streptococcus gordonii (23.6%) and Enterococcus faecalis (51.1%), attributed to its low polar surface free energy component. CFU counts were minimal for all aligners and bacterial strains, including biofilm. All aligners demonstrated cytocompatibility above 70% (Spark: 71.0%, Invisalign: 75.7%, and Smile: 75.6%). These findings highlight the importance of considering aligner material properties in clinical practice and underscore the need for proper oral hygiene and aligner maintenance. Full article

(This article belongs to the Special Issue Advancements in Biocompatible Materials for Implantable Medical Devices)

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12 pages, 1033 KiB

Open AccessArticle

A Time-Series Approach for Machine Learning-Based Patient-Specific Quality Assurance of Radiosurgery Plans

by Simone Buzzi, Pietro Mancosu, Andrea Bresolin, Pasqualina Gallo, Francesco La Fauci, Francesca Lobefalo, Lucia Paganini, Marco Pelizzoli, Giacomo Reggiori, Ciro Franzese, Stefano Tomatis, Marta Scorsetti, Cristina Lenardi and Nicola Lambri

Bioengineering 2025, 12(8), 897; https://doi.org/10.3390/bioengineering12080897 - 21 Aug 2025

Abstract

Stereotactic radiosurgery (SRS) for multiple brain metastases can be delivered with a single isocenter and non-coplanar arcs, achieving highly conformal dose distributions at the cost of extreme modulation of treatment machine parameters. As a result, SRS plans are at a higher risk of [...] Read more.

Stereotactic radiosurgery (SRS) for multiple brain metastases can be delivered with a single isocenter and non-coplanar arcs, achieving highly conformal dose distributions at the cost of extreme modulation of treatment machine parameters. As a result, SRS plans are at a higher risk of patient-specific quality assurance (PSQA) failure compared to standard treatments. This study aimed to develop a machine-learning (ML) model to predict the PSQA outcome (gamma passing rate, GPR) of SRS plans. Five hundred and ninety-two consecutive patients treated between 2020 and 2024 were selected. GPR analyses were performed using a 3%/1 mm criterion and a 95% action limit for each arc. Fifteen plan complexity metrics were used as input features to predict the GPR of an arc. A stratified and a time-series approach were employed to split the data into training (1555 arcs), validation (389 arcs), and test (486 arcs) sets. The ML model achieved a mean absolute error of 2.6% on the test set, with a 0.83% median residual value (measured/predicted). Lower values of the measured GPR tended to be overestimated. Sensitivity and specificity were 93% and 56%, respectively. ML models for virtual QA of SRS can be integrated into clinical practice, facilitating more efficient PSQA approaches. Full article

(This article belongs to the Special Issue Radiation Imaging and Therapy for Biomedical Engineering)

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10 pages, 705 KiB

Open AccessArticle

Introducing Holographic Surgical Navigation in Pediatric Wilms’ Tumor Patients: A Feasibility Study During Total Nephrectomy

by Nick T. de Groot, Jasper M. van der Zee, Guus M. J. Bökkerink, Annemieke S. Littooij, Caroline C. C. Hulsker, Cecilia E. J. Terwisscha van Scheltinga, Cornelis P. van de Ven, Ruud C. Wortel, Aart J. Klijn, Marc H. W. A. Wijnen, Matthijs Fitski and Alida F. W. van der Steeg

Bioengineering 2025, 12(8), 896; https://doi.org/10.3390/bioengineering12080896 - 21 Aug 2025

Abstract

Wilms’ tumor is a common pediatric renal malignancy. In selected cases, nephron-sparing surgery (NSS) may be employed as part of the surgical approach. To prevent positive margins, optimal understanding of the tumor–kidney edge is essential. Augmented reality (AR) enables intraoperative visualization of patient-specific [...] Read more.

Wilms’ tumor is a common pediatric renal malignancy. In selected cases, nephron-sparing surgery (NSS) may be employed as part of the surgical approach. To prevent positive margins, optimal understanding of the tumor–kidney edge is essential. Augmented reality (AR) enables intraoperative visualization of patient-specific three-dimensional (3D) holograms. In this study, we aim to validate the clinical feasibility of a holographic landmark-based registration system in pediatric patients planned for a total nephrectomy (TN), to ensure that the holographic visualization will not influence surgical decision making. In a single-center prospective study, ten pediatric patients undergoing TN were included. Patient-specific 3D holograms were created from preoperative MRI, and intraoperatively landmark-based registration was performed using the HoloLens 2. Clinical feasibility was conducted using accuracy measurements, the System Usability Scale (SUS), and a self-developed questionnaire. Three out of ten patients had a successful registration with a median measured accuracy of 7.0 mm (Interquartile Range (IQR) 6–13.5) and a median SUS score of 75 (IQR 65–77.5). Surgeons reported improved depth perception and anatomical understanding. However, in seven out of ten patients, registration failed due to multiple reasons. The most important factors were large tumor volumes obstructing landmark placement and insufficient spatial distributions of the landmarks, causing rotational misalignment. Although AR showed potential in improving the depth perception and relation in anatomical structures, the landmark-based registration with the HoloLens 2 was currently deemed insufficient for clinical implementation in pediatric abdominal surgery. Full article

(This article belongs to the Special Issue Augmented Reality, Virtual Reality and Extended Reality Solutions for Biomedical Applications)

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18 pages, 1143 KiB

Open AccessArticle

Enhancing Clinical Decision Support with Adaptive Iterative Self-Query Retrieval for Retrieval-Augmented Large Language Models

by Srinivasagam Prabha, Cesar A. Gomez-Cabello, Syed Ali Haider, Ariana Genovese, Maissa Trabilsy, Nadia G. Wood, Sanjay Bagaria, Cui Tao and Antonio J. Forte

Bioengineering 2025, 12(8), 895; https://doi.org/10.3390/bioengineering12080895 - 21 Aug 2025

Abstract

Retrieval-Augmented Generation (RAG) offers a promising strategy to harness large language models (LLMs) for delivering up-to-date, accurate clinical guidance while reducing physicians’ cognitive burden, yet its effectiveness hinges on query clarity and structure. We propose an adaptive Self-Query Retrieval (SQR) framework that integrates [...] Read more.

Retrieval-Augmented Generation (RAG) offers a promising strategy to harness large language models (LLMs) for delivering up-to-date, accurate clinical guidance while reducing physicians’ cognitive burden, yet its effectiveness hinges on query clarity and structure. We propose an adaptive Self-Query Retrieval (SQR) framework that integrates three refinement modules—PICOT (Population, Intervention, Comparison, Outcome, Time), SPICE (Setting, Population, Intervention, Comparison, Evaluation), and Iterative Query Refinement (IQR)—to automatically restructure and iteratively enhance clinical questions until they meet predefined retrieval-quality thresholds. Implemented on Gemini-1.0 Pro, we benchmarked SQR using thirty postoperative rhinoplasty queries, evaluating responses for accuracy and relevance on a three-point Likert scale and for retrieval quality via precision, recall, and F1 score; statistical significance was assessed by one-way ANOVA with Tukey post-hoc testing. The full SQR pipeline achieved 87% accuracy (Likert 2.4 ± 0.7) and 100% relevance (Likert 3.0 ± 0.0), significantly outperforming a non-refined RAG baseline (50% accuracy, 80% relevance; p < 0.01 and p = 0.03). Precision, recall, and F1 rose from 0.17, 0.39 and 0.24 to 0.53, 1.00, and 0.70, respectively, while PICOT-only and SPICE-only variants yielded intermediate improvements. These findings demonstrate that automated structuring and iterative enhancement of queries via SQR substantially elevate LLM-based clinical decision support, and its model-agnostic architecture enables rapid adaptation across specialties, data sources, and LLM platforms. Full article

(This article belongs to the Special Issue Application of Artificial Intelligence in Complex Diseases)

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17 pages, 5300 KiB

Open AccessArticle

Multimodal Integration Enhances Tissue Image Information Content: A Deep Feature Perspective

by Fatemehzahra Darzi and Thomas Bocklitz

Bioengineering 2025, 12(8), 894; https://doi.org/10.3390/bioengineering12080894 - 21 Aug 2025

Abstract

Multimodal imaging techniques have the potential to enhance the interpretation of histology by offering additional molecular and structural information beyond that accessible through hematoxylin and eosin (H&E) staining alone. Here, we present a quantitative approach for comparing the information content of different image [...] Read more.

Multimodal imaging techniques have the potential to enhance the interpretation of histology by offering additional molecular and structural information beyond that accessible through hematoxylin and eosin (H&E) staining alone. Here, we present a quantitative approach for comparing the information content of different image modalities, such as H&E and multimodal imaging. We used a combination of deep learning and radiomics-based feature extraction with different information markers, implemented in Python 3.12, to compare the information content of the H&E stain, multimodal imaging, and the combined dataset. We also compared the information content of individual channels in the multimodal image and of different Coherent Anti-Stokes Raman Scattering (CARS) microscopy spectral channels. The quantitative measurements of information that we utilized were Shannon entropy, inverse area under the curve (1-AUC), the number of principal components describing 95% of the variance (PC95), and inverse power law fitting. For example, the combined dataset achieved an entropy value of 0.5740, compared to 0.5310 for H&E and 0.5385 for the multimodal dataset using MobileNetV2 features. The number of principal components required to explain 95 percent of the variance was also highest for the combined dataset, with 62 components, compared to 33 for H&E and 47 for the multimodal dataset. These measurements consistently showed that the combined datasets provide more information. These observations highlight the potential of multimodal combinations to enhance image-based analyses and provide a reproducible framework for comparing imaging approaches in digital pathology and biomedical image analysis. Full article

(This article belongs to the Special Issue Medical Imaging Analysis: Current and Future Trends)

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28 pages, 814 KiB

Open AccessReview

Functional Carbon-Based Materials for Blood Purification: Recent Advances Toward Improved Treatment of Renal Failure and Patient Quality of Life

by Abolfazl Mozaffari, Farbod Alimohammadi and Mazeyar Parvinzadeh Gashti

Bioengineering 2025, 12(8), 893; https://doi.org/10.3390/bioengineering12080893 - 21 Aug 2025

Abstract

The accumulation of blood toxins, including urea, uric acid, creatinine, bilirubin, p-cresyl sulfate, and indoxyl sulfate, poses severe health risks for patients with renal failure. Effective removal strategies are essential to mitigate complications associated with chronic kidney disease (CKD) and improve patient outcomes. [...] Read more.

The accumulation of blood toxins, including urea, uric acid, creatinine, bilirubin, p-cresyl sulfate, and indoxyl sulfate, poses severe health risks for patients with renal failure. Effective removal strategies are essential to mitigate complications associated with chronic kidney disease (CKD) and improve patient outcomes. Functional carbon-based materials, such as activated carbon (activated charcoal) and graphene oxide, have emerged as promising adsorbents due to their large surface area, adjustable porosity, and biocompatibility. This review comprehensively explores the latest advancements in carbon-based materials for blood purification across three key therapeutic modalities: (1) Hemoperfusion, where activated and modified carbonaceous materials enhance the adsorption of small-molecule and protein-bound toxins; (2) Hemodialysis, where functionalized carbon materials improve clearance rates and reduce treatment duration; and (3) Oral Therapeutics, where orally administered carbon adsorbents show potential in lowering systemic toxin levels in CKD patients. Furthermore, we present a comparative analysis of these approaches, highlighting their advantages, limitations, and future research directions for optimizing carbon-based detoxification strategies. The findings discussed in this review emphasize the significance of material engineering in advancing blood purification technologies. By enhancing the efficiency of toxin removal, carbon-based materials have the potential to revolutionize renal failure treatment, offering improved clinical outcomes and enhanced patient quality of life. Full article

(This article belongs to the Special Issue Emerging Nanomaterials and Nanotechnologies for Biomedical and Related Applications)

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12 pages, 813 KiB

Open AccessArticle

Evaluating SnapshotNIR for Tissue Oxygenation Measurement Across Skin Types After Mastectomy

by Saif Badran, Sara Saffari, William R. Moritz, Gary B. Skolnick, Amanda M. Westman, Mitchell A. Pet and Justin M. Sacks

Bioengineering 2025, 12(8), 892; https://doi.org/10.3390/bioengineering12080892 - 21 Aug 2025

Abstract

Accurate monitoring of mastectomy skin flap (MSF) perfusion is critical, especially in patients with darker skin pigmentation at higher risk of misdiagnosed tissue ischemia. Near-infrared spectroscopy (NIRS) devices, such as SnapshotNIR, offer real-time tissue oxygen saturation measurements (StO₂), but their accuracy [...] Read more.

Accurate monitoring of mastectomy skin flap (MSF) perfusion is critical, especially in patients with darker skin pigmentation at higher risk of misdiagnosed tissue ischemia. Near-infrared spectroscopy (NIRS) devices, such as SnapshotNIR, offer real-time tissue oxygen saturation measurements (StO₂), but their accuracy across skin pigmentation levels remains unexplored. This quasi-experimental study included 33 patients undergoing mastectomy. MSF edge ΔStO₂, defined as preoperative minus postoperative StO_2, was measured using SnapshotNIR device (Kent Imaging, Calgary, AB, Canada) pre- and post-mastectomy. By definition, a positive ΔStO₂ indicates a decrease in tissue oxygenation, while a negative ΔStO₂ indicates an increase relative to baseline. ΔStO₂ was analyzed against Fitzpatrick scores to assess skin pigmentation impact on measurement accuracy. ΔStO₂ (mean ± SD) progressively decreased with increasing Fitzpatrick score: 14.0 ± 22.98 for score 1, 6.87 ± 17.45 for score 2, −3.13 ± 6.89 for score 3, and −40.75 ± 22.27 for score 5, indicating a shift from positive to negative O₂ change. Fitzpatrick scores significantly correlated with ΔStO₂ (ρ = −0.392, p = 0.016). ANOVA confirmed differences (p = 0.008), with Tukey’s post hoc testing showing significant differences between Fitzpatrick scores 1 and 5 (p = 0.022), and 2 and 5 (p = 0.006). SnapshotNIR technology demonstrated measurable sensitivity for detecting changes in StO₂ and predicting ischemia; however, NIRS-based devices may overestimate oxygenation in darker skin pigmentation, highlighting a need for device calibration to improve accuracy across skin tones. Full article

(This article belongs to the Special Issue Biomedical Engineering and Biomarkers in Plastic and Reconstructive Surgery Applications)

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15 pages, 5996 KiB

Open AccessArticle

A High-Fidelity mmWave Radar Dataset for Privacy-Sensitive Human Pose Estimation

by Yuanzhi Su, Huiying (Cynthia) Hou, Haifeng Lan and Christina Zong-Hao Ma

Bioengineering 2025, 12(8), 891; https://doi.org/10.3390/bioengineering12080891 - 21 Aug 2025

Abstract

Human pose estimation (HPE) in privacy-sensitive environments such as healthcare facilities and smart homes demands non-visual sensing solutions. Millimeter-wave (mmWave) radar emerges as a promising alternative, yet its development is hindered by the scarcity of high-fidelity datasets with accurate annotations. This paper introduces [...] Read more.

Human pose estimation (HPE) in privacy-sensitive environments such as healthcare facilities and smart homes demands non-visual sensing solutions. Millimeter-wave (mmWave) radar emerges as a promising alternative, yet its development is hindered by the scarcity of high-fidelity datasets with accurate annotations. This paper introduces mmFree-Pose, the first dedicated mmWave radar dataset specifically designed for privacy-preserving HPE. Collected through a novel visual-free framework that synchronizes mmWave radar with VDSuit-Full motion-capture sensors, our dataset covers 10+ actions, from basic gestures to complex falls. Each sample provides (i) raw 3D point clouds with Doppler velocity and intensity, (ii) precise 23-joint skeletal annotations, and (iii) full-body motion sequences in privacy-critical scenarios. Crucially, all data is captured without the use of visual sensors, ensuring fundamental privacy protection by design. Unlike conventional approaches that rely on RGB or depth cameras, our framework eliminates the risk of visual data leakage while maintaining high annotation fidelity. The dataset also incorporates scenarios involving occlusions, different viewing angles, and multiple subject variations to enhance generalization in real-world applications. By providing a high-quality and privacy-compliant dataset, mmFree-Pose bridges the gap between RF sensing and home monitoring applications, where safeguarding personal identity and behavior remains a critical concern. Full article

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

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22 pages, 5543 KiB

Open AccessArticle

Mapping Emerging Scientific Trends in Chronic Skin Disorders Using Machine Learning-Based Bibliometrics

by Nicoleta Cirstea, Andrei-Flavius Radu, Delia Mirela Tit, Ada Radu, Gabriela S. Bungau, Laura Maria Endres and Paul Andrei Negru

Bioengineering 2025, 12(8), 890; https://doi.org/10.3390/bioengineering12080890 - 20 Aug 2025

Abstract

Chronic dermatologic diseases are characterized by pathophysiologic complexity and the existence of many unmet patient management needs that can contribute to treatment failure, with poor adherence being a major issue. This study aims to identify key topics in this field, using the Web [...] Read more.

Chronic dermatologic diseases are characterized by pathophysiologic complexity and the existence of many unmet patient management needs that can contribute to treatment failure, with poor adherence being a major issue. This study aims to identify key topics in this field, using the Web of Science database. To perform this analysis, tools such as VOSviewer, Bibliometrix, and Excel were used. A Python script leveraging machine learning algorithms was developed to standardize terminology. The initial search yielded 35,373 documents, which were then refined to 12,952 publications spanning 1975 to 2024 through parameter optimization. The study found an increasing interest in this research domain, with a notable surge in 2019. The analysis identified the United States, Germany, and England as the most prolific countries in terms of scientific output. Canada ranked sixth in total document production, but its documents received the highest average citations, reflecting a significant impact. Normalization analysis revealed Italy as the most specialized country in chronic skin disease research relative to total national research output. Trend analysis revealed an evolution in research topics, particularly after 2020, with a growing focus on personalized treatment methods and long-term treatment outcomes. The study highlighted international collaboration, especially among countries with cultural or regional connections, such as those within the European Union. It underscores the growing need for continuous updates and the increasing global focus on chronic skin diseases, highlighting the critical role of staying current with emerging trends to drive advancements in treatment and patient care. Full article

(This article belongs to the Section Biosignal Processing)

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13 pages, 941 KiB

Open AccessArticle

Biomechanical Characterisation of Gait in Older Adults: A Cross-Sectional Study Using Inertial Sensor-Based Motion Capture

by Anna Letournel, Madalena Marques, Ricardo Vigário, Carla Quintão and Cláudia Quaresma

Bioengineering 2025, 12(8), 889; https://doi.org/10.3390/bioengineering12080889 - 20 Aug 2025

Abstract

The ageing of the global population, especially in developed countries, is driving significant societal changes. In Portugal, demographic data reflect a marked increase in the ageing index. Understanding gait alterations associated with ageing is essential for the early detection of mobility decline and [...] Read more.

The ageing of the global population, especially in developed countries, is driving significant societal changes. In Portugal, demographic data reflect a marked increase in the ageing index. Understanding gait alterations associated with ageing is essential for the early detection of mobility decline and fall risk. This study aimed to analyse gait patterns in older adults to contribute to a biomechanical ageing profile. Thirty-six community-dwelling older adults (29 female, 7 male; mean age: 74 years) participated. Gait data were collected using the Xsens full-body motion capture system, which combines inertial sensors with biomechanical modelling and sensor fusion. Spatiotemporal and kinematic parameters were analysed using descriptive statistics. Compared to younger adult norms, participants showed increased stance and double support phases, reduced swing phase, and lower gait speed, stride length, and cadence, with greater step width. Kinematic data showed reduced peak plantar flexion, knee flexion, and hip extension, but increased dorsiflexion peaks—adaptations aimed at stability. Despite a limited sample size and lack of clinical subgroups, results align with age-related gait literature. Findings support the utility of wearable systems like Xsens in capturing clinically relevant gait changes, contributing to normative biomechanical profiling and future mobility interventions. Full article

(This article belongs to the Section Biosignal Processing)

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