Bioengineering

18 pages, 1870 KB

Open AccessArticle

Transcranial Alternating Current Stimulation as an Adjuvant for Nonfluent Aphasia: A Proof-of-Concept Study

by Lynsey M. Keator, Lisa Johnson, Roger Newman-Norlund, Kyler Spell, Samaneh Nemati, Leigh Ann Spell, Dirk B. den Ouden, Christopher Rorden and Julius Fridriksson

Bioengineering 2026, 13(3), 372; https://doi.org/10.3390/bioengineering13030372 - 23 Mar 2026

Viewed by 792

Abstract

Effective rehabilitation tools are essential for improving language outcomes in chronic aphasia. Speech entrainment is a behavioral treatment that has shown promise in enhancing speech output in nonfluent aphasia, potentially by acting as an external mechanism to synchronize anterior and posterior language regions [...] Read more.

Effective rehabilitation tools are essential for improving language outcomes in chronic aphasia. Speech entrainment is a behavioral treatment that has shown promise in enhancing speech output in nonfluent aphasia, potentially by acting as an external mechanism to synchronize anterior and posterior language regions in the left hemisphere. Transcranial alternating current stimulation has been hypothesized to enhance functional connectivity between brain regions by amplifying endogenous oscillations. This proof-of-concept study explored whether high-definition tACS (HD-tACS) could improve speech fluency in nonfluent aphasia when paired with speech entrainment. In a double-blind, pseudorandomized study, 1 mA of HD-tACS at 7 Hz was applied to anterior and posterior left-hemisphere regions of individuals with nonfluent aphasia (N = 13). Stimulation was applied under three conditions: in-phase, anti-phase, and sham, and paired speech entrainment. Three outcome measures were examined: (1) number of words produced; (2) number of errors, and (3) ‘entrainment’ to the speech entrainment model. Group-level analyses for two of the three outcome measures reveal statistically significant differences between the experimental conditions. In-phase alternating current stimulation yielded more words and better entrainment to the audiovisual model than the sham condition. This study provides promising evidence that HD-tACS could improve speech production in individuals with nonfluent aphasia. These results contribute to growing evidence supporting the therapeutic potential of non-invasive brain stimulation approaches as an adjuvant to traditional behavioral speech-language therapy in stroke survivors. Full article

(This article belongs to the Special Issue Advancements in Physical Therapy and Rehabilitation: Neuromodulation, MRI-Based Neuroimaging and Functional Restoration Devices)

► Show Figures

Figure 1

18 pages, 6607 KB

Open AccessArticle

Engineering a Quantitative Organ-on-a-Chip Platform for Myogenic Mechanobiology

by Zepeng Zhou, Zhu Chen, Zhuojun Bai, Fengling Chen, Yujuan Huang and Yuan Guo

Bioengineering 2026, 13(3), 371; https://doi.org/10.3390/bioengineering13030371 - 23 Mar 2026

Viewed by 730

Abstract

Myogenic mechanobiology governs how mechanical cues regulate myocyte organization, alignment, and functional maturation; however, in vitro platforms that enable quantitative control and real-time readout of myogenic mechanical microenvironments remain limited. Here, we engineered a pneumatic-driven organ-on-a-chip platform integrating six parallel culture units and [...] Read more.

Myogenic mechanobiology governs how mechanical cues regulate myocyte organization, alignment, and functional maturation; however, in vitro platforms that enable quantitative control and real-time readout of myogenic mechanical microenvironments remain limited. Here, we engineered a pneumatic-driven organ-on-a-chip platform integrating six parallel culture units and a bead-embedded flexible PDMS membrane to deliver cyclic mechanical strain and enable quantitative stress–strain mapping in cardiomyocytes and skeletal muscle cells. Finite element-guided optimization ensured effective membrane deformation, and the platform generated stable and tunable cyclic strain with a strong linear relationship between applied negative pressure (50–700 mbar) and membrane stress and strain. Plasma treatment combined with type I collagen coating restored myogenic cell adhesion and growth on PDMS to levels comparable to standard culture conditions. Under 13% cyclic strain, both cardiomyocytes and skeletal muscle cells exhibited pronounced and highly uniform alignment, with cellular polarity oriented perpendicular to the stretch axis. Moreover, cyclic loading significantly enhanced the expression of contractile maturation markers, including MYH7 in cardiomyocytes and MYH6 in skeletal muscle cells (all p < 0.05), whereas expression of the differentiation regulator MyoG remained unchanged, indicating that mechanical stimulation preferentially promotes structural organization and contractile maturation rather than lineage commitment. Collectively, this quantitatively programmable organ-on-a-chip represents a bioengineered microdevice for studying myogenic mechanobiology, revealing conserved mechanosensitive alignment and maturation responses across myogenic lineages and providing a versatile framework for biomedical engineering research, disease modeling, and mechanotherapeutic screening. Full article

(This article belongs to the Section Nanobiotechnology and Biofabrication)

► Show Figures

Figure 1

37 pages, 2458 KB

Open AccessArticle

Cross-Modal Alignment and Rectified Flow-Based Latent Representation Synthesis for Enhanced Speech-Driven Alzheimer’s Disease Detection

by Shu Xiang, Haobo Ling and Meihong Wu

Bioengineering 2026, 13(3), 370; https://doi.org/10.3390/bioengineering13030370 - 23 Mar 2026

Viewed by 967

Abstract

To address the limited accuracy of speech-based Alzheimer’s Disease (AD) screening and the shortage of paired multimodal data, this paper proposes a detection framework based on feature alignment and Rectified Flow-driven latent representation generation. The EEG dataset consists of 36 AD patients and [...] Read more.

To address the limited accuracy of speech-based Alzheimer’s Disease (AD) screening and the shortage of paired multimodal data, this paper proposes a detection framework based on feature alignment and Rectified Flow-driven latent representation generation. The EEG dataset consists of 36 AD patients and 29 Healthy Controls (HC). The speech dataset contains 399 samples, which include 114 AD cases, 132 Mild Cognitive Impairment (MCI) cases, and 153 HC cases. We extracted multidimensional features of EEG signals, such as time-domain and frequency-domain characteristics, alongside behavioral representations of speech. A heterogeneous alignment network was used to map these features into a common semantic subspace, where an adaptive interpolation strategy reconstructed the missing pathological trajectories of MCI within the latent space. On this basis, a conditional Rectified Flow model was introduced to learn the optimal transport mapping from speech to EEG. This model generated physiological-information-rich latent representations to compensate for semantic gaps. Experimental results showed that the fused features from speech and latent representations achieved a three-class classification accuracy of 89.08%, a precision of 88.77%, and a recall of 88.71%. This performance represented an accuracy improvement of 9.28% compared with the speech-based baseline system. Our method combines the convenience of speech screening with the high reliability of neurophysiological signals, and it provides a new approach for low-cost early detection of AD. Full article

(This article belongs to the Special Issue Intelligent Healthcare and Auditory Health: Machine Learning-Based Multimodal Biomedical Data Mining for Diagnosis)

► Show Figures

Graphical abstract

18 pages, 1810 KB

Open AccessArticle

Comparative Evaluation of Beverage-Induced Surface Alterations on Dental Enamel: An In Vitro Biomaterial Study

by Ioana Elena Lile, Otilia Stana, Diana Marian, Carolina Cojocariu, Luminiţa Ligia Vaida, Anda Olivia Jesamine Samoilă and Iustin Olariu

Bioengineering 2026, 13(3), 369; https://doi.org/10.3390/bioengineering13030369 - 22 Mar 2026

Viewed by 801

Abstract

Background/Objectives: Despite advances in preventive dental care, tooth enamel erosion remains a relevant concern, and very few comparisons of surface topography have been carried out under controlled conditions in the laboratory. This study primarily aimed to conduct a qualitative morphological evaluation, supported by [...] Read more.

Background/Objectives: Despite advances in preventive dental care, tooth enamel erosion remains a relevant concern, and very few comparisons of surface topography have been carried out under controlled conditions in the laboratory. This study primarily aimed to conduct a qualitative morphological evaluation, supported by semi-quantitative image analysis, of the effects of commonly consumed beverages on human enamel morphology and colour, and to explore their relationship with beverage acidity in an in vitro model. Methods: Forty-two human teeth were allocated at random into seven different groups, each containing six molars. These groups were Coca-Cola, orange juice, lemon juice, coffee, chlorhexidine, regular mouthwash without chlorhexidine, and one control group. Following a 24 h exposure to a simulated saliva environment at 37 °C, the test samples were then subjected to a five-day erosion cycle. SEM analysis was used to examine the enamel alterations after evaluating the morphology of the enamel surface and by digital image analysis. Results: Scanning electron microscopy, SEM, showed how erosion of the teeth’s surface increased with the acidity of the drink. The extensive exposure of the crystal prisms, along with the severe loss of intercrystalline material and honeycomb weathering patterns, was all brought about by Coca-Cola and lemon juice. The moderate erosion brought on by orange juice in tests resulted in partially exposed prisms. Both the mouthwashes and the coffee exhibited similar impacts on the tooth enamel in a microscopic view. Minimal enamel prism rods were exposed due to either the coffee or the mouthwash. The surface characteristics were found through a digital image analysis, which indicated alterations in surface texture. Conclusions: Under these immersion conditions, highly acidic beverages produced the most pronounced enamel surface changes, whereas coffee induced mainly staining and neutral mouthwashes caused minimal modification. These results reflect qualitative morphological trends and should not be interpreted as clinical outcomes. Full article

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

► Show Figures

Figure 1

16 pages, 6169 KB

Open AccessArticle

Effect of Internal Structural Design on Stress Distribution in 3D-Printed Subperiosteal Implants Under Mechanical Loading

by Ádám Vörös, Balázs Lőrincz, János Kónya and Ibolya Zsoldos

Bioengineering 2026, 13(3), 368; https://doi.org/10.3390/bioengineering13030368 - 20 Mar 2026

Viewed by 713

Abstract

Custom-made subperiosteal implants are increasingly used in clinical cases where significant bone loss due to trauma or disease renders conventional endosseous implant placement unfeasible. This study investigated how different internal structural designs affect the deformation and stress distribution in mandibular subperiosteal implants under [...] Read more.

Custom-made subperiosteal implants are increasingly used in clinical cases where significant bone loss due to trauma or disease renders conventional endosseous implant placement unfeasible. This study investigated how different internal structural designs affect the deformation and stress distribution in mandibular subperiosteal implants under clinically relevant loading conditions. An idealized implant geometry was defined based on average human mandibular dimensions, and four configurations with identical outer shape and connection features were created, differing only in sidewall architecture (solid, top-relieved, top-relieved with lateral perforations, and top-relieved lattice framework). All specimens were manufactured by metal additive manufacturing and evaluated using cone-beam computed tomography (CBCT). Mechanical testing was performed in two stages: (i) cyclic loading consisting of 500 bite cycles at an overall force of ~326–350 N and (ii) a single static high-load event of 2000 N, applied parallel to the fixation pin axes. CT datasets acquired before and after each stage were compared to detect permanent deformation. No measurable residual deformation was identified in any configuration; the only observed macroscopic change was an adhesive-bond limitation in one case, rather than structural yielding of the implant. Finite element analysis further supported these findings by identifying localized stress concentrations mainly at the implant–prosthetic interface and by revealing the load-transfer zones that govern the mechanical response. Overall, the results indicate that lightweight, perforated, and lattice-based internal designs can preserve global structural integrity across physiological and supra-physiological load ranges while enabling design optimization to improve stress distribution. Full article

(This article belongs to the Special Issue Applications of Biomaterials in Dental Medicine)

► Show Figures

Figure 1

23 pages, 325 KB

Open AccessArticle

Changes in Ocular Biomechanics During Adolescence and Its Relationship with Lifestyle and Myopic Progression: The Oporto Myopia Study

by Pedro M. L. Baptista, Gabriel Santos, João H. Marques, André Ferreira, Beatriz Vieira, Paulo Sousa, Ricardo Parreira, Renato Ambrósio, Jr., Pedro M. A. M. Menéres and João N. M. Beirão

Bioengineering 2026, 13(3), 367; https://doi.org/10.3390/bioengineering13030367 - 20 Mar 2026

Viewed by 778

Abstract

The relationship between lifestyle, ocular biomechanical behavior, and myopia is not well established in the literature. The present study aims to describe changes in ocular biomechanics during adolescence and to explore their relationship with lifestyle factors and myopic progression. Prospective cohort study including [...] Read more.

The relationship between lifestyle, ocular biomechanical behavior, and myopia is not well established in the literature. The present study aims to describe changes in ocular biomechanics during adolescence and to explore their relationship with lifestyle factors and myopic progression. Prospective cohort study including 63 adolescents (126 eyes) with a mean age of 14.1 ± 2.6 years old examined twice over a 30 ± 0.9-month period. The data from biomechanics, biometry, corneal tomography, and lifestyle was addressed. The relationships between biomechanical changes, biometric and refractive variation, and lifestyle variables were analyzed using parametric and non-parametric statistics with a significance level of p < 0.05. A biomechanical stiffening trend was found. Axial elongation was 0.12 ± 0.17 mm, and refractive shift was −0.32 ± 0.87 D. The history of allergies was associated with greater axial growth (p = 0.032) and smaller increase in stress–strain-index (SSI) (p = 0.01). Myopization was higher in eyes with ocular surface symptoms (p = 0.049) and those with reported eye-rubbing habits (p = 0.04), with a lower gain in stiffness (p < 0.05). Outdoor activities were associated with higher gain in corneo-scleral stiffness (p < 0.05). Reduced myopization correlated directly with the increase in the SSI (p < 0.05) and inversely with the Integrated Radius (p < 0.05). Greater increases in axial length (AL), vitreous cavity length (VCL), and the ratio between VCL and AL (R_VCL/AL) correlated negatively with the increase in the SSI (p < 0.05). The increase in the R_VCL/AL correlated positively with the time spent on digital devices and negatively with the amount of outdoor activity (p < 0.05). Biomechanics may represent the physiological bridge between the environmental exposure and myopization, as lower gain in corneo-scleral stiffness was consistently associated with greater axial elongation and refractive myopization, with outdoor activity appearing to be protective. Full article

(This article belongs to the Special Issue Bioengineering and the Eye—3rd Edition)

18 pages, 256 KB

Open AccessReview

Clinical Evidence on Resorbable Calcium Phosphate Biomaterials for Alveolar Bone Regeneration: A Scoping Review Focusing on Brushite, Monetite, and Tricalcium Phosphates

by Francesco Bianchetti, Riccardo Fabozzi, Catherine Yumang, Paolo Pesce, Nicola De Angelis and Maria Menini

Bioengineering 2026, 13(3), 366; https://doi.org/10.3390/bioengineering13030366 - 20 Mar 2026

Viewed by 887

Abstract

Background: While hydroxyapatite (HA) is considered stable and non-resorbable, other calcium phosphate phases such as Tricalcium Phosphate (TCP), Brushite, and Monetite are characterized by higher solubility and biodegradation rates. This review aims to map the clinical evidence of these resorbable phases. Objective: The [...] Read more.

Background: While hydroxyapatite (HA) is considered stable and non-resorbable, other calcium phosphate phases such as Tricalcium Phosphate (TCP), Brushite, and Monetite are characterized by higher solubility and biodegradation rates. This review aims to map the clinical evidence of these resorbable phases. Objective: The aim of this scoping review was to map and synthesize the available clinical evidence on resorbable calcium phosphate phases, focusing on TCP-, brushite-, and monetite-based biomaterials in alveolar bone regeneration. The review evaluates clinical indications, surgical protocols, reported outcomes, and existing knowledge gaps. Methods: This scoping review was conducted in accordance with the PRISMA-ScR guidelines. A comprehensive literature search was performed in PubMed, MEDLINE, Scopus, and SCI Clarivate databases without language or time restrictions (from June 2025 to August 2025) using terms related to brushite, monetite, dicalcium phosphate anhydrous, ridge augmentation, bone regeneration, and dental implants. Clinical studies involving brushite- or monetite-based biomaterials used for alveolar bone regeneration were eligible, including randomized controlled trials, prospective cohort studies, and case series. Data were charted descriptively with respect to study design, patient characteristics, clinical scenario, biomaterials used, surgical approach, healing time, outcome measures, and reported complications. No meta-analysis or formal assessment of comparative clinical effectiveness was undertaken, in line with scoping review methodology. Results: Seven clinical studies were included. The identified evidence encompassed heterogeneous clinical scenarios, including post-extraction alveolar ridge preservation, localized ridge augmentation, and periodontal or intraosseous defects with relevance to future implant placement. Study designs, defect characteristics, biomaterial formulations, and outcome measures varied substantially. Across studies, brushite- and monetite-based materials were associated with new bone formation and progressive graft resorption, as assessed by clinical, radiographic, and histological outcomes. Direct comparisons between studies were not feasible due to methodological and clinical heterogeneity. Conclusions: The available literature on brushite- and monetite-based biomaterials in alveolar bone regeneration is limited and heterogeneous. Current evidence supports their biocompatibility and resorbable nature across different clinical contexts, but does not allow conclusions regarding comparative clinical effectiveness. This scoping review highlights important gaps in the literature, particularly the need for well-designed randomized clinical trials with standardized indications and outcome measures. Full article

(This article belongs to the Special Issue Advanced Dental Materials for Restorative Dentistry)

22 pages, 679 KB

Open AccessReview

Applications of Large Language Models in Medical Research: From Systematic Reviews to Clinical Studies

by Eun Jeong Gong, Chang Seok Bang and Yong Seok Shin

Bioengineering 2026, 13(3), 365; https://doi.org/10.3390/bioengineering13030365 - 20 Mar 2026

Viewed by 3148

Abstract

Background: Large Language Models (LLMs) are reshaping medical research workflows. Objective: This narrative review synthesizes evidence on LLM applications across systematic reviews, scientific writing, and clinical research. Methods: We reviewed literature from 2023–2025 examining LLM applications in medical research, identified through [...] Read more.

Background: Large Language Models (LLMs) are reshaping medical research workflows. Objective: This narrative review synthesizes evidence on LLM applications across systematic reviews, scientific writing, and clinical research. Methods: We reviewed literature from 2023–2025 examining LLM applications in medical research, identified through PubMed, Scopus, Web of Science, arXiv, medRxiv, and Google Scholar. Studies reporting empirical findings, methodological evaluations, or systematic analyses of LLM applications were included; editorials and commentaries without empirical data were excluded. Results: In systematic reviews, LLMs achieve 80–94% data extraction accuracy and 40% reduction in screening workload, but show only slight-to-moderate agreement (κ = 0.16–0.43) in risk-of-bias assessment. In scientific writing, hallucination rates of 47–55% for fabricated references and over 90% prevalence of demographic bias require rigorous verification. For clinical research, LLMs assist with statistical coding and protocol development but require human validation. Critically, excessive reliance on automated tools may cause cognitive offloading that compromises analytical capabilities. Conclusions: LLMs are powerful but unstable tools requiring constant verification. Success depends on maintaining human-in-the-loop approaches that preserve critical thinking while leveraging AI efficiency. Full article

(This article belongs to the Special Issue Advances in Intelligent Health Management and Rehabilitation Technology: Integrating Large Language Models and AI Solutions)

► Show Figures

Figure 1

29 pages, 9899 KB

Open AccessArticle

SAR-Based Thermal Assessment of Dielectrophoretic Pulsed Electromagnetic Stimulation in Tibia Fractures with Metallic Implants

by Abdullah Deniz Ertugrul, Erman Kibritoglu, Sinem Anil and Heba Yuksel

Bioengineering 2026, 13(3), 364; https://doi.org/10.3390/bioengineering13030364 - 20 Mar 2026

Viewed by 983

Abstract

Electromagnetic field-based stimulation has emerged as a promising noninvasive approach for enhancing bone fracture healing. Beyond conventional pulsed electromagnetic field (PEMF) therapies employing spatially uniform fields, dielectrophoretic-force-based (DEPF) stimulation exploits electromagnetic field non-uniformities to induce localized interactions to enhance fracture healing. However, the [...] Read more.

Electromagnetic field-based stimulation has emerged as a promising noninvasive approach for enhancing bone fracture healing. Beyond conventional pulsed electromagnetic field (PEMF) therapies employing spatially uniform fields, dielectrophoretic-force-based (DEPF) stimulation exploits electromagnetic field non-uniformities to induce localized interactions to enhance fracture healing. However, the thermal behavior associated with DEPF-driven PEMF exposure in the presence of metallic orthopedic implants remains largely unexplored. In this study, the thermal response of tissue-like tibia phantoms with and without metallic implants is investigated using an integrated experimental and numerical framework. A custom-designed conical coil is employed to generate non-uniform DEPF excitation capable of affecting the fracture site. Surface temperature evolution is measured using infrared thermal imaging, while electromagnetic power absorption is quantified through specific absorption rate (SAR)-based thermal measurement coupled with a bio-heat formulation. Anatomically realistic tibia phantoms reconstructed from computed tomography data are fabricated via a 3D printer to represent clinically relevant fracture configurations. Experimental results show that the metallic implant exhibits a rapid temperature increase of approximately

0.4 ° C

within the first few minutes of exposure, followed by thermal stabilization, corresponding to an effective absorbed power of

{SAR}_{eff, implant} \approx 2.2 W / kg

inferred from the initial temperature slope. In contrast, the non-conductive resin phantom displays a temperature rise of only

0.05 ° C

over the same interval, yielding

{SAR}_{eff, resin} \approx 0.8 W / kg

. These findings demonstrate that implant-related eddy-current losses dominate localized heating under DEPF excitation, while tissue-like media remain weakly affected. This work provides SAR-based experimental evaluation of DEPF stimulation in implanted tibia fracture models, offering new insight into implant-induced electromagnetic heating and its implications for the safety and optimization of DEPF-based bone-healing therapies. Full article

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

► Show Figures

Graphical abstract

30 pages, 2392 KB

Open AccessReview

Lab-on-a-Chip and Microfluidics Technologies for Nano Drug Delivery

by Bochun Guo, Yuchao Zhao and Xunli Zhang

Bioengineering 2026, 13(3), 363; https://doi.org/10.3390/bioengineering13030363 - 20 Mar 2026

Viewed by 2136

Abstract

Lab-on-a-Chip (LoC) and microfluidic technologies are rapidly reshaping the development pipeline for nano drug delivery systems (DDSs) by enabling precise control of physicochemical properties, high-throughput screening, and integrated biological evaluation within miniaturized platforms. This review synthesizes recent advances in microfluidic principles, fabrication strategies, [...] Read more.

Lab-on-a-Chip (LoC) and microfluidic technologies are rapidly reshaping the development pipeline for nano drug delivery systems (DDSs) by enabling precise control of physicochemical properties, high-throughput screening, and integrated biological evaluation within miniaturized platforms. This review synthesizes recent advances in microfluidic principles, fabrication strategies, and sensing modalities that facilitate continuous flow synthesis, real-time characterization, and adaptive formulation of nanoparticles. We highlight how LoC-enabled systems improve monodispersity, reproducibility, and tunability of liposomes, polymeric nanoparticles, and metallic nanocarriers, while providing powerful tools for assessing pharmacokinetics, drug release, and systemic responses using organ-on-chip (OoC) models. Emerging trends, including AI-driven autonomous optimization, stimuli-responsive materials, 3D-printed hybrid architectures, and self-powered portable devices, are discussed in the context of future integrated nano-pharmaceutics platforms. Despite existing challenges related to biocompatibility, standardization, data integration, and translation to industrial and clinical applications, the synergistic evolution of LoC engineering and nanomedicine holds transformative potential for personalized and next-generation therapeutic strategies. Full article

(This article belongs to the Special Issue Bioengineering Platforms for Drug Delivery)

► Show Figures

Figure 1

13 pages, 2095 KB

Open AccessArticle

Accuracy and Fit of Three-Unit Dental Restorations Fabricated from 3D-Printed Resins and CAD/CAM Milling Materials: A Micro-CT Study

by Jamila Yassine, Almira Ada Diken Türksayar, Florian Beuer, Nursena Öztemel and Franziska Schmidt

Bioengineering 2026, 13(3), 362; https://doi.org/10.3390/bioengineering13030362 - 19 Mar 2026

Viewed by 928

Abstract

(1) Purpose: To compare the fabrication accuracy, internal fit, and marginal adaptation of three-unit definitive resin fixed dental prostheses (FDPs) produced by subtractive milling and additive manufacturing. (2) Materials and Methods: A typodont mandible was prepared for a three-unit FDP, with full crown [...] Read more.

(1) Purpose: To compare the fabrication accuracy, internal fit, and marginal adaptation of three-unit definitive resin fixed dental prostheses (FDPs) produced by subtractive milling and additive manufacturing. (2) Materials and Methods: A typodont mandible was prepared for a three-unit FDP, with full crown preparations on teeth mandibular left canine and mandibular left second premolar featuring 1 mm chamfer finish lines. The FDP was designed with a 16 mm² connector and a 100 µm cement gap. Two milling materials (Ambarino High-Class, IPS e.max CAD) and two experimental 3D printing hybrid resins (3D-1, 3D-2) were used. All restorations were scanned using an intraoral scanner and compared to the original STL using reverse engineering software for surface trueness and deviation analysis. The internal fit was evaluated using the triple-scan method, while marginal fit was assessed via micro-CT imaging. Statistical analysis was conducted using one-way ANOVA and Kruskal–Wallis tests (α = 0.05). (3) Results: Milled groups demonstrated a lower prevalence of external, marginal, and overall surface deviations (p < 0.001), while 3D-1 exhibited comparable deviations within the internal region with M-E (p = 0.067). Milled groups had average gap values that were similar to 3D-1 (p > 0.08), but significantly lower than 3D-2 (p < 0.002). In marginal adaptation evaluated by micro-CT, the M-A and M-E groups provided significantly lower gaps, while the 3D-1 and 3D-2 groups exhibited wider marginal and axial gaps. (4) Conclusions: These results indicate that while milling remains a more reliable manufacturing method for achieving external and marginal precision, position 3D-1 is a compelling, chairside alternative to milling. Full article

(This article belongs to the Special Issue Advanced 3D-Printed Biomaterials in Dentistry)

► Show Figures

Figure 1

13 pages, 6953 KB

Open AccessTechnical Note

Robot-Assisted Placement of Thoracic Carbon-Fiber-Reinforced Polyetheretherketone (CFR-Peek) Pedicle Screws in the Cervical Spine for Giant Cell Tumor: Technical Note

by Emanuele Stucchi, Mario De Robertis, Gabriele Capo, Ali Baram, Giuseppe De Gennaro Aquino, Donato Creatura, Leonardo Anselmi, Maurizio Fornari, Federico Pessina and Carlo Brembilla

Bioengineering 2026, 13(3), 361; https://doi.org/10.3390/bioengineering13030361 - 19 Mar 2026

Cited by 1 | Viewed by 891

Abstract

Carbon-Fiber-Reinforced Polyetheretherketone (CFR-PEEK) instrumentation is increasingly preferred in spinal oncology for its physical properties, minimizing imaging artifacts and facilitating precise postoperative radiotherapy planning and tumor surveillance. However, a significant technical limitation exists: the current unavailability of dedicated CFR-PEEK pedicle screws for the cervical [...] Read more.

Carbon-Fiber-Reinforced Polyetheretherketone (CFR-PEEK) instrumentation is increasingly preferred in spinal oncology for its physical properties, minimizing imaging artifacts and facilitating precise postoperative radiotherapy planning and tumor surveillance. However, a significant technical limitation exists: the current unavailability of dedicated CFR-PEEK pedicle screws for the cervical spine. The smallest available implants are designed for thoracic use (minimum diameter 4.5 mm, minimum length 25 mm), posing substantial risks of neurovascular injury when applied to smaller cervical pedicles. We present a technical note/feasibility report illustrated by a single case of robot-assisted placement of thoracic CFR-PEEK screws in the cervical spine for the treatment of a C7 Giant Cell Tumor. Following neoadjuvant therapy with Denosumab, a single-stage, two-step circumferential resection and reconstruction was performed. The anterior step was complicated by an iatrogenic injury to the highly adherent left vertebral artery (VA), which was successfully repaired. Consequently, the posterior step required maximal precision to preserve the sole remaining intact VA on the right side. Given the anatomical mismatch between the 4.5 mm thoracic screws and the narrow cervical pedicles (measuring as narrow as 3.2 mm on the critical right side), robotic navigation (ExcelsiusGPS^®) was utilized to plan and execute safe trajectories. Specifically, on the side of the intact VA, a small, controlled medial cortical violation was planned to avoid lateral vascular compromise. The procedure resulted in rigid, artifact-free stabilization with no immediate neurological sequelae. This single-case experience suggests that robotic guidance may facilitate adaptation of thoracic CFR-PEEK instrumentation to the cervical spine in selected oncologic scenarios; reproducibility, costs, and long-term outcomes remain uncertain. Full article

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

► Show Figures

Figure 1

16 pages, 1317 KB

Open AccessArticle

Digital Gait Biomarkers for Parkinson’s Disease: Subject-Wise Validated Explainable AI Framework Using Vertical Ground Reaction Force Signals

by Moonhyeok Choi, Jaehyun Jo and Jinhyoung Jeong

Bioengineering 2026, 13(3), 360; https://doi.org/10.3390/bioengineering13030360 - 19 Mar 2026

Cited by 1 | Viewed by 976

Abstract

Parkinson’s disease (PD) is associated with progressive gait deterioration; however, widely used clinical scales such as the Hoehn & Yahr (H&Y) stage are limited in capturing continuous severity changes due to subjectivity and discrete grading. This study proposes a two-stage explainable AI framework [...] Read more.

Parkinson’s disease (PD) is associated with progressive gait deterioration; however, widely used clinical scales such as the Hoehn & Yahr (H&Y) stage are limited in capturing continuous severity changes due to subjectivity and discrete grading. This study proposes a two-stage explainable AI framework using vertical ground reaction force (VGRF) signals to achieve reproducible PD detection and continuous severity estimation. In the first stage, three deep learning models, temporal convolutional network (TCN), BiGRU with attention, and FCNN-Transformer, were trained using windowed VGRF signals under repeated subject-wise data segmentation. All models achieved high discrimination performance (AUC ≥ 0.93), with FCNN-Transformer showing the highest mean AUC (0.940) and statistically superior performance (paired Wilcoxon test, p < 0.05). Stability-based explainable AI using Integrated Gradients consistently identified variability-related VGRF features as the most informative, which were also significantly different between groups at the data level (p < 0.001, FDR-corrected). In the second stage, XGBoost regression was applied to PD subjects to predict continuous H&Y severity, achieving strong correlation with clinical grades (Spearman ρ = 0.921, p < 0.001), low error (MAE = 0.158, RMSE = 0.241), and high determination (R² = 0.953). This shows that gait-based features are a sensitive enough signal to continuously quantify disease progression. In addition, in the TREND prospective longitudinal cohort (n = 696), wearable walking indicators differed significantly from those of non-patients prior to diagnosis, and a decline in walking pace was observed approximately four years before Parkinson’s disease diagnosis, providing the basis for early screening and monitoring using gait-based digital biomarkers. These results demonstrate that gait-based digital biomarkers can objectively quantify both PD presence and disease progression. The proposed framework provides a reproducible, explainable, and clinically interpretable AI-based decision support approach for PD assessment. Full article

(This article belongs to the Special Issue Advancements in Artificial Intelligence for Wearable Devices: A New Perspective on Healthcare Applications—2nd Edition)

► Show Figures

Figure 1

29 pages, 3215 KB

Open AccessArticle

Techno-Economic Assessment of Integrated Wastewater Technologies for Sustainable Treatment of Highly Loaded Landfill Leachate Using GPS-X^TM

by Abdulmohsen Abdulkarim Mohammed Alkunaydiri, Nuhu Dalhat Mu’azu and Ahmad Hussaini Jagaba

Bioengineering 2026, 13(3), 359; https://doi.org/10.3390/bioengineering13030359 - 19 Mar 2026

Viewed by 828

Abstract

Landfill leachate is considered one of the most recalcitrant wastewaters due to its high organic strength, elevated ammonia concentrations, and complex chemical composition. This study evaluates integrated technologies for treating highly loaded landfill leachate from the Wadi Al-Asla landfill, Jeddah Saudi Arabia, using [...] Read more.

Landfill leachate is considered one of the most recalcitrant wastewaters due to its high organic strength, elevated ammonia concentrations, and complex chemical composition. This study evaluates integrated technologies for treating highly loaded landfill leachate from the Wadi Al-Asla landfill, Jeddah Saudi Arabia, using GPS-X^TM modeling combined with regulatory compliance and techno-economic assessment (TEA). The characterized mature leachate exhibited extremely high average concentrations of COD (17,050 mg L⁻¹), BOD₅ (10,058 mg L⁻¹), ammonia-N (989 mg L⁻¹), and total nitrogen (1223 mg L⁻¹), indicating severe pollution levels requiring integrated treatment technologies. Five (5) different scenarios involving integrated biological, physicochemical, and membrane-based processes were modelled, simulated and evaluated against local discharge standards complaince. Conventional and municipality-proposed upgrade configurations achieved ~80–83% COD removal, producing effluent COD > 2900 mg L⁻¹ and 1790–1801 mg L⁻¹ BOD₅, indicating persistent non-compliance for organic pollutants. Nitrogen removal improved substantially (93.7–95.7% ammonia-N and 91–93% total nitrogen removal), yet residual ammonia-N (44–63 mg L⁻¹) and total nitrogen (92–108 mg L⁻¹) remained above regulatory limits. Advanced hybrid systems achieved complete TSS removal and strong phosphorus control (TP ≤ 0.42 mg L⁻¹), while three(3) compartmental aerobic–anoxic membrane bioreactor coupled with reverse osmosis (MBR + RO) achieved near-complete nitrogen removal and reduced 90% COD removal. The lifecyle economic assessment indicated OPEX ranging from USD 1.1 to 5.6 m⁻³ of treated leachate with the aerobic–anoxic MBR + RO configuration yieding footprint advantage, lower CAPEX and moderate OPEX By combining process modeling, regulatory compliance evaluation, and economic assessment, this study provides a practical screening framework for selecting sustainable treatment strategies for high-strength landfill leachate and wastewater matices. Full article

(This article belongs to the Special Issue Biological Wastewater Treatment and Resource Recovery, 2nd Edition)

► Show Figures

Graphical abstract

26 pages, 3519 KB

Open AccessArticle

Subject-Independent Depression Recognition from EEG Using an Improved Bidirectional LSTM with Dynamic Vector Routing

by Ziqi Ji, Kunye Liu, Weikai Ma, Xiaolin Ning and Yang Gao

Bioengineering 2026, 13(3), 358; https://doi.org/10.3390/bioengineering13030358 - 19 Mar 2026

Viewed by 911

Abstract

Electroencephalography (EEG) has become an increasingly important tool in depression research due to its ability to capture objective neurophysiological abnormalities associated with depressive disorders, offering high temporal resolution, non-invasiveness, and cost-effectiveness.However, existing methods often fail to fully exploit the multi-domain information in EEG [...] Read more.

Electroencephalography (EEG) has become an increasingly important tool in depression research due to its ability to capture objective neurophysiological abnormalities associated with depressive disorders, offering high temporal resolution, non-invasiveness, and cost-effectiveness.However, existing methods often fail to fully exploit the multi-domain information in EEG signals, resulting in limited model generalization capabilities. This paper proposes an improved bidirectional long short-term memory (BiLSTM) model that segments continuous EEG into non-overlapping 2-s epochs and learns end-to-end from multi-channel temporal sequences. After band-pass filtering and resampling, each epoch is represented as a channel–time matrix

X \in R^{C \times T}

(with C = 128) and processed by a BiLSTM encoder followed by a dynamic-routing encapsulated-vector classifier. On the MODMA dataset under subject-independent five-fold cross-validation, the proposed method outperforms a set of reproduced representative baselines (SVM, EEGNet, InceptionNet, Self-attention-CNN and CNN–LSTM) and achieves 84.8% accuracy with an AUC of 0.899. We further discuss recent contemporary directions (e.g., attention/Transformer-based and emotion-aware expert models) and clarify the scope of our empirical comparisons. Furthermore, experiments comparing different frequency bands and band combinations indicate that joint multi-frequency input can enhance classification performance. This study provides an effective multi-domain fusion approach for the automatic diagnosis of depression based on EEG. Full article

(This article belongs to the Section Biosignal Processing)

► Show Figures

Graphical abstract

41 pages, 3361 KB

Open AccessSystematic Review

A Systematic Review on Amnion as a Cell Delivery Scaffolding Material for Cartilage Regeneration in Pre-Clinical and Clinical Studies

by Shu-Yong Liow, Sik-Loo Tan, Alvin Jiunn-Hieng Lu, Kwong Weng Loh, Seow Hui Teo, Chan Young Lee, Le Wan, Azlina Amir Abbas and Kyung-Soon Park

Bioengineering 2026, 13(3), 357; https://doi.org/10.3390/bioengineering13030357 - 18 Mar 2026

Cited by 1 | Viewed by 912

Abstract

Cartilage is an important yet vulnerable tissue with limited self-healing capacity, where damage often progresses to joint degeneration, which eventually leads to severe osteoarthritis (OA). Current tissue engineering strategies focus on biocompatible scaffolds for cartilage regeneration, particularly amnion (or amniotic membrane), emerging as [...] Read more.

Cartilage is an important yet vulnerable tissue with limited self-healing capacity, where damage often progresses to joint degeneration, which eventually leads to severe osteoarthritis (OA). Current tissue engineering strategies focus on biocompatible scaffolds for cartilage regeneration, particularly amnion (or amniotic membrane), emerging as a promising biomaterial due to its wide availability, low immunogenicity, and naturally derived microenvironment that is advantageous for cartilage regeneration. This systematic review aims to evaluate the existing evidence on the efficacy of amnion as a tissue scaffolding material for cartilage regeneration in both preclinical and clinical studies. Using terms such as “cartilage damage”, “cartilage injuries”, “amnion” and “amniotic membrane”, 19 relevant studies were identified across three major databases (PubMed, Scopus and Web of Science) until 25 December 2025. All preclinical and clinical studies that utilized amnion for cartilage repair or as cartilage tissue engineering scaffolding materials were included. Evidence quality was assessed using the OHAT and MINORS risk of bias tool. This study is prospectively registered in the PROSPERO database under the ID 1178444. The findings consistently indicate that amniotic scaffolds, regardless of processing methods or cell seeding, yield favorable outcomes without adverse effects across different species. In vitro analysis revealed that treatment groups with amnion show better cell attachment, viability, and proliferation, and higher content of cartilage-related markers expressed by the seeded cells, either chondrocyte, bone marrow-derived mesenchymal stem cells (MSCs), adipose tissue-derived MSCs, placenta-derived MSCs, umbilical cord-derived MSCs, amniotic MSCs or amniotic epithelial cells. In in vivo and ex vivo studies, amnion-treated groups demonstrated improved quality of the treated cartilage, with better integration, as indicated by higher histological scores and the presence of type II collagen (COL-II). There was an inconsistency in the reporting of cartilage defect dimensions in the in vivo models across the different studies. Nevertheless, the outcome measurements were consistently reported with histological analysis, with or without International Cartilage Repair Society (ICRS) scoring and immunohistochemistry (IHC) analysis, across the studies. Clinically, most subjects show improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Sports and Recreation score and KOOS Quality of Life score, as well as reduced Visual Analogue Scale (VAS) average and maximum pain scores. In conclusion, preclinical and clinical studies support amnion as an ideal scaffold material for cartilage tissue engineering and regeneration. Future research should focus on optimizing and standardizing amnion scaffold preparation at a production scale to facilitate the translation of these positive outcomes into clinical applications. This study is funded by the Ministry of Higher Education Malaysia via Prototype Research Grant Scheme (PRGS/1/2021/SKK01/UM/02/1) and UM International Collaboration Grant—2023 SATU Joint Research Scheme Program: ST007-2024. Full article

(This article belongs to the Special Issue Biomedical Materials Expansion in Tissue Regeneration: Material and Tissue Evaluation)

► Show Figures

Figure 1

26 pages, 4030 KB

Open AccessArticle

DuDeM: A Dual-Network Model for Early Gastric Cancer Detection Based on Capsule Endoscopy

by Tianyi Feng, Qian He, Tianqi Chen and Weibing Wang

Bioengineering 2026, 13(3), 356; https://doi.org/10.3390/bioengineering13030356 - 18 Mar 2026

Viewed by 734

Abstract

Early detection is critical for improving outcomes in gastric cancer, yet lesion recognition in capsule endoscopy is challenged by interference from different gastric anatomical sites, patient posture changes, and gastric peristalsis. This study aims to prompt a robust deep learning model to address [...] Read more.

Early detection is critical for improving outcomes in gastric cancer, yet lesion recognition in capsule endoscopy is challenged by interference from different gastric anatomical sites, patient posture changes, and gastric peristalsis. This study aims to prompt a robust deep learning model to address these challenges. A dual-network model, named DuDeM (DualNet Detection Model), was developed by integrating a ResNet50-based convolutional branch with a CapsuleNet branch incorporating dynamic routing. The convolutional branch extracts local lesion features that are transmitted to primary capsules, while dynamic routing enables adaptive matching between capsule layers to establish local–global feature associations. An attention-weighted strategy is applied for feature fusion. The model was trained using capsule endoscopy images from nine hospitals in China and public datasets, and its performance was compared with eight representative models, with ablation analyses validating key components. Results showed that DuDeM achieved an area under the curve (AUC) of 0.981 and an F1-score of 0.979, with sensitivity, specificity, and precision all exceeding 97%, and performance degradation limited to within 3% under mild image perturbations. These findings suggest that DuDeM enables reliable early gastric cancer (EGC) recognition and may support large-scale capsule endoscopy screening in clinical practice. Full article

(This article belongs to the Topic Artificial Intelligence and Big Data in Biomedical Engineering)

► Show Figures

Figure 1

15 pages, 2565 KB

Open AccessArticle

AI-Based Myocardial Segmentation and Attenuation Mapping Improved Detection of Myocardial Ischemia and Infarction on Emergency CT Angiography

by Martin Segeroth, Jan Vosshenrich, Hanns-Christian Breit, Helge Walter Anand Krebs-Fleischmann, Lorraine Abel, Markus Obmann, Shan Yang, Joshy Cyriac, Jakob Wasserthal, Ashraya Kumar Indrakanti, Michael Bach, Michael J. Zellweger, Alexander Sauter, Jens Bremerich, Philip Haaf and David Jean Winkel

Bioengineering 2026, 13(3), 355; https://doi.org/10.3390/bioengineering13030355 - 18 Mar 2026

Viewed by 690

Abstract

Purpose: To investigate whether an AI-based approach combining deep learning myocardial segmentation with attenuation-normalized myocardial mapping (colormaps) improves detection of myocardial ischemia and infarction on emergency ECG-gated CT angiography. Materials and Methods: In this retrospective study, 119 patients with acute chest pain who [...] Read more.

Purpose: To investigate whether an AI-based approach combining deep learning myocardial segmentation with attenuation-normalized myocardial mapping (colormaps) improves detection of myocardial ischemia and infarction on emergency ECG-gated CT angiography. Materials and Methods: In this retrospective study, 119 patients with acute chest pain who underwent ECG-gated CT angiography to exclude pulmonary embolism or acute aortic syndrome and invasive coronary angiography within 48 h were included. A deep learning model (nnU-Net) was used for automatic left-ventricular myocardial segmentation, serving as the basis for voxel-wise attenuation normalization to generate AI-based myocardial attenuation maps. Six readers with varying experience levels evaluated all cases for myocardial hypoattenuation in a multi-reader, multi-case design, with and without AI-generated attenuation maps. Results: AI-based myocardial attenuation mapping increased mean sensitivity for detection of myocardial ischemia or infarction by 12% [IQR 2–20%] compared with standard CT interpretation alone. Sensitivity improved by 15% [IQR 10–22%] in STEMI (ST-Elevation Myocardial Infarction) and 11% [IQR −1–18%] in NSTEMI (Non-STEMI) cases. The AI-assisted approach resulted in the correct reclassification of 11% of patients and improved inter-reader agreement, particularly among less experienced readers, demonstrating reduced reader dependency. Conclusions: AI-based myocardial segmentation and attenuation mapping enhance the detection of myocardial ischemia and infarction on emergency CT angiography and improve inter-reader agreement. This AI-assisted image processing approach provides clinically meaningful decision support in acute chest pain imaging workflows. Full article

(This article belongs to the Special Issue Artificial Intelligence in Medical Image Processing and Segmentation, Third Edition)

► Show Figures

Figure 1

21 pages, 5000 KB

Open AccessArticle

Immortalized Rat Tendon-Derived Stem Cells for Tendon Tissue Engineering

by Kat Tik Lau, Hui Wang, Jinxiang Zhang, Dan Michelle Wang and Dai Fei Elmer Ker

Bioengineering 2026, 13(3), 354; https://doi.org/10.3390/bioengineering13030354 - 18 Mar 2026

Viewed by 891

Abstract

Tendon-derived stem cells (TDSCs) are a unique cell population found in tendons, exhibiting both mesenchymal stem cell (MSC)-like phenotypes and tendon-specific markers. They have emerged as a promising research tool in tendon-related tissue engineering studies. However, there is currently no well-characterized TDSC line [...] Read more.

Tendon-derived stem cells (TDSCs) are a unique cell population found in tendons, exhibiting both mesenchymal stem cell (MSC)-like phenotypes and tendon-specific markers. They have emerged as a promising research tool in tendon-related tissue engineering studies. However, there is currently no well-characterized TDSC line with MSC-related phenotypes for investigating tendon biology or developing therapeutics. Here, we established an immortalized monoclonal TDSC, named iTDSC#6, from the Achilles tendon of an adult male Sprague-Dawley rat. Cell clones were characterized for MSC-associated cell surface markers, colony formation capacity, and trilineage differentiation potentials, tenogenic potential and SV40LT expression at both early (passage < 10) and late (passage > 30) stages. iTDSC#6 showed stable expression of Simian virus 40 large T antigen (SV40LT) and demonstrated similar MSC-like phenotypes as its wild-type counterpart at both early and late passages, including colony formation capability and multi-lineage differentiation potentials. iTDSC#6 was positive for the MSC markers CD90, CD44, CD29 and CD73 (≥95%) and negative for the hematopoietic markers CD34 and CD45 (<1%). Regarding its utility for basic research and therapeutic development, iTDSC#6 showed potential for modelling cells with increased levels of senescence-associated beta-galactosidase activity in response to hydrogen peroxide and for bioengineering scaffold-free, tendon-like 3D constructs as evidenced by its upregulation of tendon-related markers, high nuclear aspect ratio, and aligned collagen organization. In conclusion, an immortalized TDSC line was successfully established that shows promise as a useful research tool to study tendon biology and aid the development of therapeutics for tissue engineering and regenerative medicine. Full article

(This article belongs to the Special Issue 3D Cell Culture Systems: Current Technologies and Applications)

► Show Figures

Figure 1

22 pages, 1968 KB

Open AccessArticle

A PHMB-Functionalized Fully Absorbable Synthetic Matrix as a Novel Alternative to Biologics: Balancing Antibacterial Efficacy, Tissue Repair, and Safety

by Sean Chen, Christopher Bibbo, John Starinski, Xianghua Xu and Chenhong Wang

Bioengineering 2026, 13(3), 353; https://doi.org/10.3390/bioengineering13030353 - 18 Mar 2026

Viewed by 737

Abstract

Effective management of acute, complex, and chronic wounds requires constructs that simultaneously support tissue repair and provide sustained infection control. Biologic-derived materials, despite their regenerative potential, are limited by insufficient long-term antibacterial activity and susceptibility to enzymatic degradation. To overcome these limitations, a [...] Read more.

Effective management of acute, complex, and chronic wounds requires constructs that simultaneously support tissue repair and provide sustained infection control. Biologic-derived materials, despite their regenerative potential, are limited by insufficient long-term antibacterial activity and susceptibility to enzymatic degradation. To overcome these limitations, a fully absorbable synthetic matrix composed of electrospun composite fibers functionalized with polyhexamethylene biguanide (PHMB) (hereafter, PHMB Matrix) was developed to mimic extracellular matrix architecture while enabling durable antibacterial performance. Quantitative assessment per AATCC 100 demonstrated robust broad-spectrum efficacy (>99.99% reduction) against six clinically relevant Gram-positive and Gram-negative pathogens, with potency retained after 15 months of real-time aging. The matrix’s interconnected fibrous architecture enables a controlled, biphasic PHMB release coordinated with biodegradation, sustaining antibacterial protection throughout a 28-day healing period. In porcine full-thickness wound models, the PHMB Matrix achieved 63.53% ± 12.0% wound area reduction by Day 22, demonstrating accelerated mid-phase healing compared to an antibacterial collagen control (p < 0.05 on Day 22), with both treatments achieving comparable near-complete closure by Day 28. Pharmacokinetic analysis confirmed localized drug enrichment with negligible systemic exposure. These findings establish the PHMB-functionalized synthetic matrix as a safe, effective, fully absorbable alternative to biologic-derived materials for soft tissue repair, offering sustained antibacterial efficacy and a favorable safety profile. Full article

(This article belongs to the Special Issue Biomaterials for the Repair and Regeneration of Musculoskeletal Tissue)

► Show Figures

Figure 1

16 pages, 20498 KB

Open AccessArticle

Echo Intensity Correction Method for Ultrasound Computed Tomography in Musculoskeletal Imaging

by Junchao Zeng, Ding Lou, Qin Zhang, Hui Zhang, Hongyi Zhu, Xing Cheng, Tengfei Wang, Sanping Xu, Yan Ling and Mingyue Ding

Bioengineering 2026, 13(3), 352; https://doi.org/10.3390/bioengineering13030352 - 18 Mar 2026

Viewed by 584

Abstract

Ultrasound computed tomography (USCT) has emerged as a promising tool for quantitative assessment of musculoskeletal (MSK) diseases. However, the accuracy of echo intensity—a key imaging biomarker—is often compromised by non-optimal imaging conditions, such as probe tilt and limb eccentricity. In this study, we [...] Read more.

Ultrasound computed tomography (USCT) has emerged as a promising tool for quantitative assessment of musculoskeletal (MSK) diseases. However, the accuracy of echo intensity—a key imaging biomarker—is often compromised by non-optimal imaging conditions, such as probe tilt and limb eccentricity. In this study, we propose a novel echo intensity correction method for USCT that quantitatively compensates for these two major sources of error. The method integrates finite element simulation and phantom experiments to establish correction functions for each influencing factor. These functions are then applied to USCT images from volunteers through automated parameter extraction and intensity adjustment. Validation on both phantom and in vivo data showed that the proposed method significantly improved the uniformity and diagnostic accuracy of echo intensity measurements, leading to a clear improvement in the diagnostic accuracy of MSK diseases. This method enhances the reliability of USCT-based quantitative diagnosis and holds strong potential for broader clinical adoption. Full article

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

► Show Figures

Figure 1

23 pages, 7378 KB

Open AccessArticle

Improved AI-Assisted Image Recognition of Cervical Spine Vertebrae Enables Motion Pattern Analysis in Dynamic X-Ray Recordings

by Esther van Santbrink, Tijmen H. W. Hijzelaar, Valérie N. E. Schuermans, Anouk Y. J. M. Smeets, Henk van Santbrink, Rob de Bie, Mitko Veta and Toon F. M. Boselie

Bioengineering 2026, 13(3), 351; https://doi.org/10.3390/bioengineering13030351 - 18 Mar 2026

Viewed by 572

Abstract

Background: Qualitative motion analysis revealed that the cervical spine moves according to a consistent pattern. Current data analysis methods are limited by the extensive time required to process the retrieved data. A previous study demonstrated the feasibility of using a deep-learning model to [...] Read more.

Background: Qualitative motion analysis revealed that the cervical spine moves according to a consistent pattern. Current data analysis methods are limited by the extensive time required to process the retrieved data. A previous study demonstrated the feasibility of using a deep-learning model to automate analysis methods. However, segmentation accuracy needed to be improved. This study aims to improve segmentation model performance to enable reliable motion analysis. Methods: Four nnU-Net configurations were tested: baseline (A), pre-trained (B), with histogram equalization (C), and pre-trained with histogram equalization (D). Segmentation performance was evaluated using Dice Similarity Coefficient (DSC), Intersection over Union (IoU) and 95th percentile Hausdorff Distance (HD95). Vertebral rotation was estimated using mean shapes. Reliability was assessed using the Intraclass Correlation Coefficient (ICC). Sensitivity analyses were conducted. Results: Across all models, mean DSC ranged from 0.67 to 0.92, mean IoU from 0.55 to 0.85, and mean HD95 from 2.35 to 19.67 mm. After sensitivity analysis for low segmental range of motion (sROM) and low-quality recordings, the mean ICC ranged from 0.617 to 0.837 for model A, from 0.609 to 0.780 for model B, from 0.409 to 0.689 for model C, and from 0.480 to 0.835 for model D. Conclusions: This study shows that Models A and B can accurately analyze cervical motion patterns. High image contrast and an adequate sROM are essential for robust model performance. It also marks an important step toward automated qualitative motion analysis, increasing the accessibility of motion pattern evaluation. Full article

(This article belongs to the Special Issue Artificial Intelligence-Based Medical Imaging Processing)

► Show Figures

Figure 1

13 pages, 6144 KB

Open AccessArticle

Surface EMG-Validated Multi-DoF Wheelchair-Based Rehabilitation Device

by Jagan P and Madhav Rao

Bioengineering 2026, 13(3), 350; https://doi.org/10.3390/bioengineering13030350 - 18 Mar 2026

Viewed by 603

Abstract

Rehabilitation is a critical component in the recovery of patients with either complete or partial loss of motor movements. Repeated and slow limb movements are usually advised by practitioners. Advanced robotic systems can help to configure monotonous movements and accelerate the recovery process [...] Read more.

Rehabilitation is a critical component in the recovery of patients with either complete or partial loss of motor movements. Repeated and slow limb movements are usually advised by practitioners. Advanced robotic systems can help to configure monotonous movements and accelerate the recovery process as an alternative to therapist-assisted motions, especially during the later phase of recovery. In this work, robotic-assisted human limb movements are engineered and augmented with a novel electromyography (EMG) signal to characterize the movements. The proposed lower- and upper-limb assistive system is designed on a wheelchair platform and is IoT-enabled. The proposed assistive system is designed for patients affected with hemiplegia, paraplegia and tetraplegia. Existing state-of-the-art (SOTA) systems are typically focused on either the upper or lower limbs, with limited degrees of freedom (DoF). The IoT framework for remote access enables the possibility of home-based rehabilitation. A prototype was successfully developed and experiments to characterize various muscle movements using the proposed system were performed. Full article

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

► Show Figures

Figure 1

19 pages, 2500 KB

Open AccessEditor’s ChoiceArticle

Comparison of 2D, 3D In Vitro, and Ex Vivo Platforms for Modeling the Rat Small Intestine

by Shani Elias-Kirma, Reece McCoy, Douglas van Niekerk, Verena Stoeger, Sophie Oldroyd, Emma Sumner, Achilleas Savva and Róisín M. Owens

Bioengineering 2026, 13(3), 349; https://doi.org/10.3390/bioengineering13030349 - 17 Mar 2026

Viewed by 679

Abstract

Physiologically relevant in vitro intestinal models are essential for studying key physiological processes, including barrier function, drug screening and gut-microbiota interactions. However, conventional 2D culture systems often fail to recapitulate structural and functional complexity. Here, we aimed to validate a 3D bioelectronic transmembrane [...] Read more.

Physiologically relevant in vitro intestinal models are essential for studying key physiological processes, including barrier function, drug screening and gut-microbiota interactions. However, conventional 2D culture systems often fail to recapitulate structural and functional complexity. Here, we aimed to validate a 3D bioelectronic transmembrane platform, previously used for monitoring human intestinal epithelium and vascular endothelium, for modeling the rat small intestinal barrier in vitro. The device integrates a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) scaffold supporting co-cultures of rat intestinal epithelial cells (IEC-6) and rat fibroblasts (208F), enabling real-time monitoring of barrier formation through electrical measurements using electrochemical impedance spectroscopy (EIS). Barrier formation was monitored over 21 days and exhibited a time-dependent increase in barrier resistance. The 3D platform was compared with traditional 2D insert-based cultures and ex vivo rat tissue using an Ethylene Glycol Tetraacetic Acid (EGTA)-induced calcium switch assay to evaluate barrier disruption and recovery. EGTA treatment and removal induced reversible barrier disruption in the 3D in vitro and ex vivo models, whereas 2D in vitro cultures showed limited recovery. These findings demonstrate that the 3D platform more faithfully recapitulates native tissue architecture and function, closely paralleling ex vivo responses. Our study highlights the importance of validating advanced 3D in vitro models and establishes this bioelectronic platform as a robust tool for drug screening, barrier studies, and preclinical gastrointestinal research. Full article

(This article belongs to the Special Issue Advanced Physical Techniques in Tissue Engineering and Regenerative Medicine)

► Show Figures

Graphical abstract

13 pages, 2423 KB

Open AccessArticle

Early Knee Osteoarthritis Detection by Multi-Component T₂ Mapping

by Hector L. de Moura, Anmol Monga, Dilbag Singh, Marcelo V. W. Zibetti, Jonathan Samuels and Ravinder R. Regatte

Bioengineering 2026, 13(3), 348; https://doi.org/10.3390/bioengineering13030348 - 17 Mar 2026

Viewed by 649

Abstract

This study investigates whether multi-component T₂ mapping, using bi-exponential (BE) and stretched-exponential (SE) models, enhances the early detection of knee osteoarthritis (OA) compared with the conventional mono-exponential (ME) approach. T₂ relaxation maps were derived from 26 patients with early-stage OA and [...] Read more.

This study investigates whether multi-component T₂ mapping, using bi-exponential (BE) and stretched-exponential (SE) models, enhances the early detection of knee osteoarthritis (OA) compared with the conventional mono-exponential (ME) approach. T₂ relaxation maps were derived from 26 patients with early-stage OA and 26 healthy controls. To minimize the influence of age-related cartilage changes, all model-derived parameters were adjusted for age prior to analysis. Quantitative T₂ parameters were extracted from six anatomically defined cartilage sub-regions to capture spatially heterogeneous tissue alterations characteristic of early OA. These parameters were then integrated using linear discriminant analysis to assess combined diagnostic performance. Global whole-cartilage analyses demonstrated limited discriminatory power across all models, with area under the receiver operating characteristic curve (AUC) values not exceeding 0.65, indicating that diffuse averaging obscures subtle, localized degeneration. In contrast, sub-regional analysis improved classification accuracy, highlighting the importance of regional assessment in early disease. Among the evaluated models, the BE-T₂ model showed the highest performance, achieving an AUC of 0.68, and marginally outperforming both the SE model (AUC = 0.60) and the ME model (AUC = 0.51). These findings suggest that multi-component T₂ mapping, particularly when applied at a sub-regional level, may offer improved sensitivity to early cartilage compositional changes. Overall, this approach shows strong potential as a noninvasive imaging biomarker for the early detection of knee OA. Full article

(This article belongs to the Section Biosignal Processing)

► Show Figures

Figure 1

23 pages, 2876 KB

Open AccessArticle

Denoising and Baseline Correction of Low-Scan FTIR Spectra: A Benchmark of Deep Learning Models Against Traditional Signal Processing

by Azadeh Mokari, Shravan Raghunathan, Artem Shydliukh, Oleg Ryabchykov, Christoph Krafft and Thomas Bocklitz

Bioengineering 2026, 13(3), 347; https://doi.org/10.3390/bioengineering13030347 - 17 Mar 2026

Cited by 1 | Viewed by 970

Abstract

High-quality Fourier Transform Infrared (FTIR) imaging usually needs extensive signal averaging to reduce noise and drift, which severely limits clinical speed. Deep learning can accelerate imaging by reconstructing spectra from rapid, single-scan inputs. However, separating noise and baseline drift simultaneously without ground truth [...] Read more.

High-quality Fourier Transform Infrared (FTIR) imaging usually needs extensive signal averaging to reduce noise and drift, which severely limits clinical speed. Deep learning can accelerate imaging by reconstructing spectra from rapid, single-scan inputs. However, separating noise and baseline drift simultaneously without ground truth is an ill-posed inverse problem. Standard black-box architectures often rely on statistical approximations that introduce spectral hallucinations or fail to generalize to unstable atmospheric conditions. To solve these issues, we propose a physics-informed cascade Unet that separates denoising and baseline correction tasks using a new, deterministic Physics Bridge. This architecture forces the network to separate random noise from chemical signals using an embedded SNIP layer to enforce spectroscopic constraints instead of learning statistical approximations. We benchmarked this approach against a standard single Unet and a traditional Savitzky–Golay smoothing followed by SNIP baseline correction workflow. We used a dataset of human hypopharyngeal carcinoma cells (FaDu). The cascade model outperformed all other methods, achieving a 51.3% reduction in RMSE compared to raw single-scan inputs, surpassing both the single Unet (40.2%) and the traditional workflow (33.7%). Peak-aware metrics show that the cascade architecture eliminates spectral hallucinations found in standard deep learning. It also preserves peak intensity with much higher fidelity than traditional smoothing. These results show that the cascade Unet is a robust solution for diagnostic-grade FTIR imaging. It enables imaging speeds 32 times faster than current methods. Full article

(This article belongs to the Special Issue Advances in Computational Imaging and Artificial Intelligence for Biomedical and Clinical Applications)

► Show Figures

Graphical abstract

14 pages, 11989 KB

Open AccessEditor’s ChoiceArticle

Detecting Condylar Lift-Off with a Piezoelectric Smart Knee Replacement

by Brandon D. Hines, Ryan Willing and Steven R. Anton

Bioengineering 2026, 13(3), 346; https://doi.org/10.3390/bioengineering13030346 - 17 Mar 2026

Viewed by 449

Abstract

Smart knee replacement technology seeks to provide an in vivo method of tracking long-term postoperative joint loads with the goal of identifying clinically relevant phenomena linked to postoperative dissatisfaction in real time. This study evaluated the ability of a piezoelectric compartmental force and [...] Read more.

Smart knee replacement technology seeks to provide an in vivo method of tracking long-term postoperative joint loads with the goal of identifying clinically relevant phenomena linked to postoperative dissatisfaction in real time. This study evaluated the ability of a piezoelectric compartmental force and compartmental center of pressure sensing total knee replacement to sense condylar lift-off, which is a clinically relevant phenomenon commonly attributed to postoperative dissatisfaction. A commercially available total knee replacement was modified to include six piezoelectric transducers capable of measuring compartmental forces and tibiofemoral centers of pressure on the articular surface of the tibial bearing insert. The smart knee replacement was evaluated with a six-degree-of-freedom joint motion simulator applying a varus lift-off profile. The study demonstrated that the lift-off was evident in both the sensed joint loads and the localized tibiofemoral centers of pressure obtained from the piezoelectric sensing system. The results indicated that the piezoelectric smart knee replacement could be effective for detecting this clinically problematic mechanical issue. Full article

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

► Show Figures

Figure 1

25 pages, 6467 KB

Open AccessReview

Ultrasound Patches Toward Intelligent Theranostics: From Flexible Materials to Closed-Loop Biomedical Systems

by Jinpeng Zhao, Yi Huang, Yuan Zhang, Yuhang Xie, Wei Guo, Yang Li and Shidong Wang

Bioengineering 2026, 13(3), 345; https://doi.org/10.3390/bioengineering13030345 - 17 Mar 2026

Cited by 1 | Viewed by 1875

Abstract

Ultrasound patches represent a transformative advancement beyond conventional ultrasonography, evolving into intelligent theranostic systems for personalized healthcare. This evolution is propelled by synergistic innovations in flexible piezoelectric materials and integrated designs. The development of piezoelectric polymers, lead-free ceramics, and bio-composite materials has laid [...] Read more.

Ultrasound patches represent a transformative advancement beyond conventional ultrasonography, evolving into intelligent theranostic systems for personalized healthcare. This evolution is propelled by synergistic innovations in flexible piezoelectric materials and integrated designs. The development of piezoelectric polymers, lead-free ceramics, and bio-composite materials has laid the foundation for long-term, conformal, and biosafe interfacing with the human body. Structurally, miniaturized transducer arrays (e.g., CMOS-integrated arrays achieving ~200 μm focal spots and 100 kPa focal pressure), multimodal integration, and bioinspired interfaces have enabled high-precision deep-tissue sensing and spatiotemporally controlled energy delivery—exemplified by strain-sensing feedback improving the signal-to-noise ratio by 5 dB for precise neuromodulation. These capabilities are converging to create closed-loop platforms, as demonstrated in continuous cardiovascular monitoring (up to 164 mm depth for 12 h), image-guided neuromodulation for neurological disorders, on-demand drug delivery (achieving 100% higher plasma concentration than ultrasound alone), and integrated tumor therapy with real-time feedback. Despite persistent challenges in material biocompatibility, energy efficiency, and clinical standardization, the future of ultrasound patches lies in their deep integration with multimodal sensing, machine learning, and adaptive control algorithms. This path will ultimately realize their potential for intelligent, closed-loop theranostics in chronic disease management, telemedicine, and personalized therapy. Full article

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

► Show Figures

Figure 1

19 pages, 1982 KB

Open AccessArticle

Experimental Analysis and Modeling Study of Impedance Changes in Decellularized and Recellularized Peripheral Nerves

by Marialourdes Ingrosso, Livio D’Alvia, Marianna Cosentino, Giorgia Nanni, Zaccaria Del Prete and Emanuele Rizzuto

Bioengineering 2026, 13(3), 344; https://doi.org/10.3390/bioengineering13030344 - 16 Mar 2026

Viewed by 638

Abstract

Peripheral nerve injuries pose a significant clinical challenge due to the limited self-repair capacity and the complexity of neural tissue architecture. Tissue engineering strategies applied to the peripheral nerve system aim to restore functional nerve constructs by combining scaffolds, cells, and biochemical cues [...] Read more.

Peripheral nerve injuries pose a significant clinical challenge due to the limited self-repair capacity and the complexity of neural tissue architecture. Tissue engineering strategies applied to the peripheral nerve system aim to restore functional nerve constructs by combining scaffolds, cells, and biochemical cues to recreate the native microenvironment. This work aimed to propose the electrical conductivity as a functional readout of structural and biological remodeling in engineered peripheral nerve scaffolds, along with functional and molecular evaluations. To this end, bioimpedance measurements were combined with equivalent circuit modeling to track state-dependent changes across different levels of tissue organization. Murine sciatic nerves were decellularized and recellularized with neural populations to generate engineered constructs, and their electrical properties were assessed using broadband bioimpedance spectroscopy. Distinct impedance profiles were observed across control, decellularized, and recellularized samples, reflecting structural and functional changes associated with cell removal and repopulation. Furthermore, a multilayer series RC circuit model was implemented to accurately reproduce the measured spectra, enabling the extraction of layer-specific electrical parameters. Analysis of these parameters revealed that decellularization reduces compartmental resistances and increases inter-layer coupling, whereas recellularization restores outer-layer resistances and reduces coupling, consistent with functional tissue organization. Overall, the results demonstrate that bioimpedance provides a readout of the scaffold biological state and cellular integration, and that equivalent circuit modeling offers a quantitative framework to link structural remodeling to electrical function in engineered peripheral nerve tissues. 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))

► Show Figures

Figure 1

16 pages, 2225 KB

Open AccessArticle

Mid-Term Clinical Outcomes of Pullout Repair Combined with Osteochondral Autograft Transplantation for Medial Meniscus Posterior Root Tears with Focal Cartilage Defects: A Treatment-Stratified Cohort Study

by Naoki Akura, Koki Kawada, Yuki Okazaki, Keisuke Kintaka, Yuya Kodama, Toshiki Kohara and Takayuki Furumatsu

Bioengineering 2026, 13(3), 343; https://doi.org/10.3390/bioengineering13030343 - 16 Mar 2026

Viewed by 528

Abstract

Medial meniscus posterior root tears (MMPRTs) with focal cartilage defects present a therapeutic challenge, even in neutral-to-mild varus knees. Although transtibial pullout repair is standard for MMPRTs without advanced osteoarthritis, coexisting cartilage lesions may compromise outcomes and prompt unicompartmental knee arthroplasty (UKA). Combining [...] Read more.

Medial meniscus posterior root tears (MMPRTs) with focal cartilage defects present a therapeutic challenge, even in neutral-to-mild varus knees. Although transtibial pullout repair is standard for MMPRTs without advanced osteoarthritis, coexisting cartilage lesions may compromise outcomes and prompt unicompartmental knee arthroplasty (UKA). Combining pullout repair with osteochondral autograft transplantation (OAT) may offer a joint-preserving alternative by restoring meniscal hoop stress and reconstructing focal osteochondral defects. However, supporting evidence is limited. We retrospectively analyzed 150 patients treated surgically for MMPRT between 2015 and 2019, divided into three groups: pullout repair with OAT (Group O, n = 6), pullout repair alone (Group P, n = 120), and UKA (Group U, n = 24), with OAT being applied only in carefully selected patients based on strict clinical and radiographic indications. Clinical outcomes were assessed preoperatively, at 1 year, and at final follow-up (mean, 4.2–5.8 years). The primary outcome was the final clinical score, and secondary outcomes were changes from baseline. All groups improved postoperatively. Group O showed marked improvement in Knee Injury and Osteoarthritis Outcome Score—Symptom and Visual Analogue Scale—Pain score, achieving outcomes comparable to Group U at final follow-up. Group P showed consistent improvement from baseline. Radiographically, mild osteoarthritis progression was observed in Group O. Given the small sample size in Group O and the retrospective design, the findings are exploratory and warrant confirmation in larger prospective studies. Full article

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

► Show Figures

Figure 1

Journal Menu

Journal Browser

Bioengineering, Volume 13, Issue 3 (March 2026) – 117 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI