Bioengineering doi: 10.3390/bioengineering11040333
Authors: Jose Alberto Arano-Martinez José Alejandro Hernández-Benítez Hilario Martines-Arano Aída Verónica Rodríguez-Tovar Martin Trejo-Valdez Blanca Estela García-Pérez Carlos Torres-Torres
This work reports the modification in the homogeneity of ablation effects with the assistance of nonlinear optical phenomena exhibited by C. albicans ATCC 10231, forming a biofilm. Equivalent optical energies with different levels of intensity were irradiated in comparative samples, and significant changes were observed. Nanosecond pulses provided by an Nd:YAG laser system at a 532 nm wavelength in a single-beam experiment were employed to explore the photodamage and the nonlinear optical transmittance. A nonlinear optical absorption coefficient −2 × 10−6 cm/W was measured in the samples studied. It is reported that multiphotonic interactions can promote more symmetric optical damage derived by faster changes in the evolution of fractional photoenergy transference. The electrochemical response of the sample was studied to further investigate the electronic dynamics dependent on electrical frequency, and an electro-capacitive behavior in the sample was identified. Fractional differential calculations were proposed to describe the thermal transport induced by nanosecond pulses in the fungi media. These results highlight the nonlinear optical effects to be considered as a base for developing photothermally activated phototechnology and high-precision photodamage in biological systems.
]]>Bioengineering doi: 10.3390/bioengineering11040332
Authors: Mattia Spedicati Alice Zoso Leonardo Mortati Valeria Chiono Elena Marcello Irene Carmagnola
Skeletal muscle tissue (SMT) has a highly hierarchical and anisotropic morphology, featuring aligned and parallel structures at multiple levels. Various factors, including trauma and disease conditions, can compromise the functionality of skeletal muscle. The in vitro modeling of SMT represents a useful tool for testing novel drugs and therapies. The successful replication of SMT native morphology demands scaffolds with an aligned anisotropic 3D architecture. In this work, a 3D PCL fibrous scaffold with aligned morphology was developed through the synergistic combination of Melt-Extrusion Additive Manufacturing (MEAM) and porogen leaching, utilizing PCL as the bulk material and PEG as the porogen. PCL/PEG blends with different polymer ratios (60/40, 50/50, 40/60) were produced and characterized through a DSC analysis. The MEAM process parameters and porogen leaching in bi-distilled water allowed for the development of a micrometric anisotropic fibrous structure with fiber diameters ranging from 10 to 100 µm, depending on PCL/PEG blend ratios. The fibrous scaffolds were coated with Gelatin type A to achieve a biomimetic coating for an in vitro cell culture and mechanically characterized via AFM. The 40/60 PCL/PEG scaffolds yielded the most homogeneous and smallest fibers and the greatest physiological stiffness. In vitro cell culture studies were performed by seeding C2C12 cells onto a selected scaffold, enabling their attachment, alignment, and myotube formation along the PCL fibers during a 14-day culture period. The resultant anisotropic scaffold morphology promoted SMT-like cell conformation, establishing a versatile platform for developing in vitro models of tissues with anisotropic morphology.
]]>Bioengineering doi: 10.3390/bioengineering11040331
Authors: Carolin Bokelmann Alireza Ehsani Jochen Schaub Fabian Stiefel
Due to their high specificity, monoclonal antibodies (mAbs) have garnered significant attention in recent decades, with advancements in production processes, such as high-seeding-density (HSD) strategies, contributing to improved titers. This study provides a thorough investigation of high seeding processes for mAb production in Chinese hamster ovary (CHO) cells, focused on identifying significant metabolites and their interactions. We observed high glycolytic fluxes, the depletion of asparagine, and a shift from lactate production to consumption. Using a metabolic network and flux analysis, we compared the standard fed-batch (STD FB) with HSD cultivations, exploring supplementary lactate and cysteine, and a bolus medium enriched with amino acids. We reconstructed a metabolic network and kinetic models based on the observations and explored the effects of different feeding strategies on CHO cell metabolism. Our findings revealed that the addition of a bolus medium (BM) containing asparagine improved final titers. However, increasing the asparagine concentration in the feed further prevented the lactate shift, indicating a need to find a balance between increased asparagine to counteract limitations and lower asparagine to preserve the shift in lactate metabolism.
]]>Bioengineering doi: 10.3390/bioengineering11040330
Authors: Kyuseok Kim Bo Kyung Cha Hyun-Woo Jeong Youngjin Lee
In recent years, indirect digital radiography detectors have been actively studied to improve radiographic image performance with low radiation exposure. This study aimed to achieve low-dose radiation imaging with a thick scintillation detector while simultaneously obtaining the resolution of a thin scintillation detector. The proposed method was used to predict the optimal point spread function (PSF) between thin and thick scintillation detectors by considering image quality assessment (IQA). The process of identifying the optimal PSF was performed on each sub-band in the wavelet domain to improve restoration accuracy. In the experiments, the edge preservation index (EPI) values of the non-blind deblurred image with a blurring sigma of σ = 5.13 pixels and the image obtained with optimal parameters from the thick scintillator using the proposed method were approximately 0.62 and 0.76, respectively. The coefficient of variation (COV) values for the two images were approximately 1.02 and 0.63, respectively. The proposed method was validated through simulations and experimental results, and its viability is expected to be verified on various radiological imaging systems.
]]>Bioengineering doi: 10.3390/bioengineering11040329
Authors: Alexandra Hunter Aitchison Nicholas B. Allen Isabel R. Shaffrey Conor N. O’Neill Bijan Abar Albert T. Anastasio Samuel B. Adams
Cartilage damage presents a significant clinical challenge due to its intrinsic avascular nature which limits self-repair. Addressing this, our study focuses on an alginate-based bioink, integrating human articular cartilage, for cartilage tissue engineering. This novel bioink was formulated by encapsulating C20A4 human articular chondrocytes in sodium alginate, polyvinyl alcohol, gum arabic, and cartilage extracellular matrix powder sourced from allograft femoral condyle shavings. Using a 3D bioprinter, constructs were biofabricated and cross-linked, followed by culture in standard medium. Evaluations were conducted on cellular viability and gene expression at various stages. Results indicated that the printed constructs maintained a porous structure conducive to cell growth. Cellular viability was 87% post printing, which decreased to 76% after seven days, and significantly recovered to 86% by day 14. There was also a notable upregulation of chondrogenic genes, COL2A1 (p = 0.008) and SOX9 (p = 0.021), suggesting an enhancement in cartilage formation. This study concludes that the innovative bioink shows promise for cartilage regeneration, demonstrating substantial viability and gene expression conducive to repair and suggesting its potential for future therapeutic applications in cartilage repair.
]]>Bioengineering doi: 10.3390/bioengineering11040328
Authors: Suzanne Lightsey Blanka Sharma
Natural killer (NK) cells, which are an exciting alternative cell source for cancer immunotherapies, must sense and respond to their physical environment to traffic to and eliminate cancer cells. Herein, we review the mechanisms by which NK cells receive mechanical signals and explore recent key findings regarding the impact of the physical characteristics of solid tumors on NK cell functions. Data suggest that different mechanical stresses present in solid tumors facilitate NK cell functions, especially infiltration and degranulation. Moreover, we review recent engineering advances that can be used to systemically study the role of mechanical forces on NK cell activity. Understanding the mechanisms by which NK cells interpret their environment presents potential targets to enhance NK cell immunotherapies for the treatment of solid tumors.
]]>Bioengineering doi: 10.3390/bioengineering11040327
Authors: Yonghan Cha Jun Young Chung Jin-Woo Kim Jun-Il Yoo Woohyun Lee Jung-Taek Kim
Templating is essential in hip arthroplasty preparation, facilitating implant size prediction and surgical rehearsal. It ensures the selection of suitable implants according to patient anatomy and disease, aiming to minimize post-operative complications. Various templating methods exist, including traditional acetate templating on both analog and digital images, alongside digital templating on digital images, which is categorized into 2D and 3D approaches. Despite the popularity of acetate templating on digital images, challenges such as the requirement for physical templates and result preservation persist. To address these limitations, digital templating with software like OrthoSize and Orthoview has been suggested, although not universally accessible. This technical note advocates for Microsoft PowerPoint as an effective alternative for 2D digital templating, highlighting its user-friendly features for image manipulation without needing specialized software. The described method involves scanning acetate templates, adjusting the images in PowerPoint 365 for size, position, and calibration on patient radiographs, and demonstrating reliability through preliminary assessments, with intraclass correlation coefficient (ICC) values indicating a high level of agreement for cup and stem size (ICC = 0.860, 0.841, respectively) but moderate for neck length (ICC = 0.592). We have introduced a method for performing 2D digital templating in the clinical field without the need for specialized software dedicated to digital templating. We believe this method significantly improves the accessibility to 2D digital templating, which was previously limited by the need for digital templating software. Additionally, it enables surgeons to easily establish arthroplasty plans and share them, overcoming the limitations of acetate templates.
]]>Bioengineering doi: 10.3390/bioengineering11040326
Authors: Ante Jordan Igor Smojver Ana Budimir Dragana Gabrić Marko Vuletić
Polymicrobial biofilm removal and decontamination of the implant surface is the most important goal in the treatment of periimplantitis. The aim of this study is to evaluate the efficacy of four different decontamination methods for removing Acinetobacter baumannii and Staphylococcus aureus biofilms in vitro. Seventy-five dental implants were contaminated with a bacterial suspension and randomly divided into five groups (n = 15): the negative control group, which received no treatment; the positive control group, treated with 0.2% chlorhexidine; group 1, treated with a chitosan brush (Labrida BioCleanTM, Labrida AS, Oslo, Norway); group 2, treated with a chitosan brush and 0.2% chlorhexidine; and group 3, treated with a device based on the electrolytic cleaning method (GalvoSurge, GalvoSurge Dental AG, Widnau, Switzerland). The colony-forming unit (CFU) count was used to assess the number of viable bacteria in each sample, and statistical analyses were performed. When compared to the negative control group, all the decontamination methods reduced the CFU count. The electrolytic cleaning method decontaminated the implant surface more effectively than the other three procedures, while the chitosan brush was the least effective. Further research in more realistic settings is required to assess the efficacy of the decontamination procedures described in this study.
]]>Bioengineering doi: 10.3390/bioengineering11040325
Authors: Lu Zhang Xin Wu Liang Hong
Atherosclerosis (AS) is a severe vascular disease that results in millions of cases of mortality each year. The development of atherosclerosis is associated with vascular structural lesions, characterized by the accumulation of immune cells, mesenchymal cells, lipids, and an extracellular matrix at the intimal resulting in the formation of an atheromatous plaque. AS involves complex interactions among various cell types, including macrophages, endothelial cells (ECs), and smooth muscle cells (SMCs). Endothelial dysfunction plays an essential role in the initiation and progression of AS. Endothelial dysfunction can encompass a constellation of various non-adaptive dynamic alterations of biology and function, termed “endothelial reprogramming”. This phenomenon involves transitioning from a quiescent, anti-inflammatory state to a pro-inflammatory and proatherogenic state and alterations in endothelial cell identity, such as endothelial to mesenchymal transition (EndMT) and endothelial-to-immune cell-like transition (EndIT). Targeting these processes to restore endothelial balance and prevent cell identity shifts, alongside modulating epigenetic factors, can attenuate atherosclerosis progression. In the present review, we discuss the role of endothelial cells in AS and summarize studies in endothelial reprogramming associated with the pathogenesis of AS.
]]>Bioengineering doi: 10.3390/bioengineering11040324
Authors: Andrea Cataldo Sabatina Criscuolo Egidio De Benedetto Antonio Masciullo Marisa Pesola Raissa Schiavoni
Alzheimer’s disease (AD) is a neurodegenerative brain disorder that affects cognitive functioning and memory. Current diagnostic tools, including neuroimaging techniques and cognitive questionnaires, present limitations such as invasiveness, high costs, and subjectivity. In recent years, interest has grown in using electroencephalography (EEG) for AD detection due to its non-invasiveness, low cost, and high temporal resolution. In this regard, this work introduces a novel metric for AD detection by using multiscale fuzzy entropy (MFE) to assess brain complexity, offering clinicians an objective, cost-effective diagnostic tool to aid early intervention and patient care. To this purpose, brain entropy patterns in different frequency bands for 35 healthy subjects (HS) and 35 AD patients were investigated. Then, based on the resulting MFE values, a specific detection algorithm, able to assess brain complexity abnormalities that are typical of AD, was developed and further validated on 24 EEG test recordings. This MFE-based method achieved an accuracy of 83% in differentiating between HS and AD, with a diagnostic odds ratio of 25, and a Matthews correlation coefficient of 0.67, indicating its viability for AD diagnosis. Furthermore, the algorithm showed potential for identifying anomalies in brain complexity when tested on a subject with mild cognitive impairment (MCI), warranting further investigation in future research.
]]>Bioengineering doi: 10.3390/bioengineering11040323
Authors: Cynthia A. Hunn Justyna Lunkiewicz Christoph B. Noethiger David W. Tscholl Greta Gasciauskaite
The Philips Visual Patient Avatar, a user-centered visualization technology, offers an alternative approach to patient monitoring. Computer-based simulation studies indicate that it increases diagnostic accuracy and confidence, while reducing perceived workload. About three months after the technology’s integration into clinical practice, we conducted an assessment among anesthesia providers to determine their views on its strengths, limitations, and overall perceptions. This single-center qualitative study at the University Hospital of Zurich examined anesthesia providers’ perceptions of the Philips Visual Patient Avatar after its implementation. The study included an online survey to identify medical personnel’s opinions on the technology’s strengths and areas for improvement, which were analyzed using thematic analysis. A total of 63 of the 377 invited anesthesia providers (16.7%) responded to the survey. Overall, 163 comments were collected. The most prevalent positive themes were good presentation of specific parameters (16/163; 9.8%) and quick overview/rapid identification of problems (15/163; 9.2%). The most common perceived area for improvement was the ability to adjust the visualization thresholds of Visual Patient Avatar, which represent the physiological upper and lower vital-sign limits (33/163; 20.3%). The study showed that users consider Philips Visual Patient Avatar a valuable asset in anesthesia, allowing for easier identification of underlying problems. However, the study also revealed a user desire for the ability to freely adjust the thresholds of the Visual Patient Avatar by the handling caregivers, which were fixed to the departmental standard during the study.
]]>Bioengineering doi: 10.3390/bioengineering11040321
Authors: Elise Lupon Aylin Acun Corentin B. Taveau Ruben Oganesyan Hyshem H. Lancia Alec R. Andrews Mark A. Randolph Curtis L. Cetrulo Alexandre G. Lellouch Basak E. Uygun
Reconstructive techniques to repair severe tissue defects include the use of autologous fasciocutaneous flaps, which may be limited due to donor site availability or lead to complications such as donor site morbidity. A number of synthetic or natural dermal substitutes are in use clinically, but none have the architectural complexity needed to reconstruct deep tissue defects. The perfusion decellularization of fasciocutaneous flaps is an emerging technique that yields a scaffold with the necessary composition and vascular microarchitecture and serves as an alternative to autologous flaps. In this study, we show the perfusion decellularization of porcine fasciocutaneous flaps using sodium dodecyl sulfate (SDS) at three different concentrations, and identify that 0.2% SDS results in a decellularized flap that is efficiently cleared of its cellular material at 86%, has maintained its collagen and glycosaminoglycan content, and preserved its microvasculature architecture. We further demonstrate that the decellularized graft has the porous structure and growth factors that would facilitate repopulation with cells. Finally, we show the biocompatibility of the decellularized flap using human dermal fibroblasts, with cells migrating as deep as 150 µm into the tissue over a 7-day culture period. Overall, our results demonstrate the promise of decellularized porcine flaps as an interesting alternative for reconstructing complex soft tissue defects, circumventing the limitations of autologous skin flaps.
]]>Bioengineering doi: 10.3390/bioengineering11040322
Authors: Madhav Samudrala Sindhusri Dhaveji Kush Savsani Sivanesan Dakshanamurthy
Previous epitope-based cancer vaccines have focused on analyzing a limited number of mutated epitopes and clinical variables preliminarily to experimental trials. As a result, relatively few positive clinical outcomes have been observed in epitope-based cancer vaccines. Further efforts are required to diversify the selection of mutated epitopes tailored to cancers with different genetic signatures. To address this, we developed the first version of AutoEpiCollect, a user-friendly GUI software, capable of generating safe and immunogenic epitopes from missense mutations in any oncogene of interest. This software incorporates a novel, machine learning-driven epitope ranking method, leveraging a probabilistic logistic regression model that is trained on experimental T-cell assay data. Users can freely download AutoEpiCollectGUI with its user guide for installing and running the software on GitHub. We used AutoEpiCollect to design a pan-cancer vaccine targeting missense mutations found in the proto-oncogene PIK3CA, which encodes the p110ɑ catalytic subunit of the PI3K kinase protein. We selected PIK3CA as our gene target due to its widespread prevalence as an oncokinase across various cancer types and its lack of presence as a gene target in clinical trials. After entering 49 distinct point mutations into AutoEpiCollect, we acquired 361 MHC Class I epitope/HLA pairs and 219 MHC Class II epitope/HLA pairs. From the 49 input point mutations, we identified MHC Class I epitopes targeting 34 of these mutations and MHC Class II epitopes targeting 11 mutations. Furthermore, to assess the potential impact of our pan-cancer vaccine, we employed PCOptim and PCOptim-CD to streamline our epitope list and attain optimized vaccine population coverage. We achieved a world population coverage of 98.09% for MHC Class I data and 81.81% for MHC Class II data. We used three of our predicted immunogenic epitopes to further construct 3D models of peptide-HLA and peptide-HLA-TCR complexes to analyze the epitope binding potential and TCR interactions. Future studies could aim to validate AutoEpiCollect’s vaccine design in murine models affected by PIK3CA-mutated or other mutated tumor cells located in various tissue types. AutoEpiCollect streamlines the preclinical vaccine development process, saving time for thorough testing of vaccinations in experimental trials.
]]>Bioengineering doi: 10.3390/bioengineering11040319
Authors: Saba Heidari Gheshlaghi Chi Nok Enoch Kan Taly Gilat Schmidt Dong Hye Ye
Organ segmentation from CT images is critical in the early diagnosis of diseases, progress monitoring, pre-operative planning, radiation therapy planning, and CT dose estimation. However, data limitation remains one of the main challenges in medical image segmentation tasks. This challenge is particularly huge in pediatric CT segmentation due to children’s heightened sensitivity to radiation. In order to address this issue, we propose a novel segmentation framework with a built-in auxiliary classifier generative adversarial network (ACGAN) that conditions age, simultaneously generating additional features during training. The proposed conditional feature generation segmentation network (CFG-SegNet) was trained on a single loss function and used 2.5D segmentation batches. Our experiment was performed on a dataset with 359 subjects (180 male and 179 female) aged from 5 days to 16 years and a mean age of 7 years. CFG-SegNet achieved an average segmentation accuracy of 0.681 dice similarity coefficient (DSC) on the prostate, 0.619 DSC on the uterus, 0.912 DSC on the liver, and 0.832 DSC on the heart with four-fold cross-validation. We compared the segmentation accuracy of our proposed method with previously published U-Net results, and our network improved the segmentation accuracy by 2.7%, 2.6%, 2.8%, and 3.4% for the prostate, uterus, liver, and heart, respectively. The results indicate that our high-performing segmentation framework can more precisely segment organs when limited training images are available.
]]>Bioengineering doi: 10.3390/bioengineering11040320
Authors: Sogand Schafer Tina Swain Marcelo Parra Blaire V. Slavin Nicholas A. Mirsky Vasudev Vivekanand Nayak Lukasz Witek Paulo G. Coelho
The energy state of endosteal implants is dependent on the material, manufacturing technique, cleaning procedure, sterilization method, and surgical manipulation. An implant surface carrying a positive charge renders hydrophilic properties, thereby facilitating the absorption of vital plasma proteins crucial for osteogenic interactions. Techniques to control the surface charge involve processes like oxidation, chemical and topographical adjustments as well as the application of nonthermal plasma (NTP) treatment. NTP at atmospheric pressure and at room temperature can induce chemical and/or physical reactions that enhance wettability through surface energy changes. NTP has thus been used to modify the oxide layer of endosteal implants that interface with adjacent tissue cells and proteins. Results have indicated that if applied prior to implantation, NTP strengthens the interaction with surrounding hard tissue structures during the critical phases of early healing, thereby promoting rapid bone formation. Also, during this time period, NTP has been found to result in enhanced biomechanical fixation. As such, the application of NTP may serve as a practical and reliable method to improve healing outcomes. This review aims to provide an in-depth exploration of the parameters to be considered in the application of NTP on endosteal implants. In addition, the short- and long-term effects of NTP on osseointegration are addressed, as well as recent advances in the utilization of NTP in the treatment of periodontal disease.
]]>Bioengineering doi: 10.3390/bioengineering11040318
Authors: Hee-Ju Ahn Soo-Hwan Byun Sae-Hoon Baek Sang-Yoon Park Sang-Min Yi In-Young Park Sung-Woon On Jong-Cheol Kim Byoung-Eun Yang
With the growing demand for orthognathic surgery and other facial treatments, the accurate identification of anatomical landmarks has become crucial. Recent advancements have shifted towards using three-dimensional radiologic analysis instead of traditional two-dimensional methods, as it allows for more precise treatment planning, primarily relying on direct identification by clinicians. However, manual tracing can be time-consuming, mainly when dealing with a large number of patients. This study compared the accuracy and reliability of identifying anatomical landmarks using artificial intelligence (AI) and manual identification. Thirty patients over 19 years old who underwent pre-orthodontic and orthognathic surgery treatment and had pre-orthodontic three-dimensional radiologic scans were selected. Thirteen anatomical indicators were identified using both AI and manual methods. The landmarks were identified by AI and four experienced clinicians, and multiple ANOVA was performed to analyze the results. The study results revealed minimal significant differences between AI and manual tracing, with a maximum deviation of less than 2.83 mm. This indicates that utilizing AI to identify anatomical landmarks can be a reliable method in planning orthognathic surgery. Our findings suggest that using AI for anatomical landmark identification can enhance treatment accuracy and reliability, ultimately benefiting clinicians and patients.
]]>Bioengineering doi: 10.3390/bioengineering11040313
Authors: Yan Chen Masaharu Kobayashi Changyoung Yuhn Marie Oshima
Recent advancements in computational performance and medical simulation technology have made significant strides, particularly in predictive diagnosis. This study focuses on the blood flow simulation reduced-order models, which provide swift and cost-effective solutions for complex vascular systems, positioning them as practical alternatives to 3D simulations in resource-limited medical settings. The paper introduces a visualization platform for patient-specific and image-based 1D–0D simulations. This platform covers the entire workflow, from modeling to dynamic 3D visualization of simulation results. Two case studies on, respectively, carotid stenosis and arterial remodeling demonstrate its utility in blood flow simulation applications.
]]>Bioengineering doi: 10.3390/bioengineering11040317
Authors: Jahangir Alam Ghulam Murtaza Efstratios E. Tzirtzilakis Shuyu Sun Mohammad Ferdows
The flow and heat transfer of a steady, viscous biomagnetic fluid containing magnetic particles caused by the swirling and stretching motion of a three-dimensional cylinder has been investigated numerically in this study. Because fluid and particle rotation are different, a magnetic field is applied in both radial and tangential directions to counteract the effects of rotational viscosity in the flow domain. Partial differential equations are used to represent the governing three-dimensional modeled equations. With the aid of customary similarity transformations, this system of partial differential equations is transformed into a set of ordinary differential equations. They are then numerically resolved utilizing a common finite differences technique that includes iterative processing and the manipulation of tridiagonal matrices. Graphs are used to depict the physical effects of imperative parameters on the swirling velocity, temperature distributions, skin friction coefficient, and the rate of heat transfer. For higher values of the ferromagnetic interaction parameter, it is discovered that the axial velocity increases, whereas temperature and tangential velocity drop. With rising levels of the ferromagnetic interaction parameter, the size of the axial skin friction coefficient and the rate of heat transfer are both accelerated. In some limited circumstances, a comparison with previously published work is also handled and found to be acceptably accurate.
]]>Bioengineering doi: 10.3390/bioengineering11040316
Authors: Manh Hung-Nguyen
Chest X-ray (CXR) examination serves as a widely employed clinical test in medical diagnostics. Many studied have tried to apply artificial intelligence (AI) programs to analyze CXR images. Despite numerous positive outcomes, assessing the applicability of AI models for comprehensive diagnostic support remains a formidable challenge. We observed that, even when AI models exhibit high accuracy on one dataset, their performance may deteriorate when tested on another. To address this issue, we propose incorporating a variational information bottleneck (VIB) at the patch level to enhance the generalizability of diagnostic support models. The VIB introduces a probabilistic model aimed at approximating the posterior distribution of latent variables given input data, thereby enhancing the model’s generalization capabilities on unseen data. Unlike the conventional VIB approaches that flatten features and use a re-parameterization trick to sample a new latent feature, our method applies the trick to 2D feature maps. This design allows only important pixels to respond, and the model will select important patches in an image. Moreover, the proposed patch-level VIB seamlessly integrates with various convolutional neural networks, offering a versatile solution to improve performance. Experimental results illustrate enhanced accuracy in standard experiment settings. In addition, the method shows robust improvement when training and testing on different datasets.
]]>Bioengineering doi: 10.3390/bioengineering11040314
Authors: Karthika M S Harikumar Rajaguru Ajin R. Nair
Microarray gene expression analysis is a powerful technique used in cancer classification and research to identify and understand gene expression patterns that can differentiate between different cancer types, subtypes, and stages. However, microarray databases are highly redundant, inherently nonlinear, and noisy. Therefore, extracting meaningful information from such a huge database is a challenging one. The paper adopts the Fast Fourier Transform (FFT) and Mixture Model (MM) for dimensionality reduction and utilises the Dragonfly optimisation algorithm as the feature selection technique. The classifiers employed in this research are Nonlinear Regression, Naïve Bayes, Decision Tree, Random Forest and SVM (RBF). The classifiers’ performances are analysed with and without feature selection methods. Finally, Adaptive Moment Estimation (Adam) and Random Adaptive Moment Estimation (RanAdam) hyper-parameter tuning techniques are used as improvisation techniques for classifiers. The SVM (RBF) classifier with the Fast Fourier Transform Dimensionality Reduction method and Dragonfly feature selection achieved the highest accuracy of 98.343% with RanAdam hyper-parameter tuning compared to other classifiers.
]]>Bioengineering doi: 10.3390/bioengineering11040315
Authors: Seep Arora Anna Goralczyk Sujana Andra Soon Yew John Lim Yi-Chin Toh
Traditional eye irritation assessments, which rely on animal models or ex vivo tissues, face limitations due to ethical concerns, costs, and low throughput. Although numerous in vitro tests have been developed, none have successfully reconciled the need for high experimental throughput with the accurate prediction of irritation potential, attributable to the complexity of irritation mechanisms. Simple cell models, while suitable for high-throughput screening, offer limited mechanistic insights, contrasting with more physiologically relevant but less scalable complex organotypic corneal tissue constructs. This study presents a novel strategy to enhance the predictive accuracy of screening-compatible simple cell models in eye irritation testing. Our method combines the results of two in vitro assays—cell apoptosis and nociceptor (TRPV1) activation—using micropatterned chips to partition human corneal epithelial cells into numerous discrete small populations. Following exposure to test compounds, we measure apoptosis and nociceptor activation responses. The large datasets collected from the cell micropatterns facilitate binarization and statistical fitting to calculate a mathematical probability, which assesses the compound’s potential to cause eye irritation. This method potentially enables the amalgamation of multiple mechanistic readouts into a singular index, providing a more accurate and reliable prediction of eye irritation potential in a format amenable to high-throughput screening.
]]>Bioengineering doi: 10.3390/bioengineering11040312
Authors: Seong Son Michael Y. Oh Han Byeol Park Alexander M. Lopez
Percutaneous endoscopic lumbar discectomy (PELD) presents a challenging learning curve, and the correlation between surgeon experience and clinical outcomes remains contentious. This retrospective study aimed to compare the outcomes of PELD performed by a single surgeon at beginner and experienced stages. Propensity score matching selected 150 patients (75 per group) with a minimum 3-year follow-up. Clinical and radiological outcomes, perioperative complications, and adverse events were assessed. Baseline characteristics, pain improvement, patient satisfaction, and radiological outcomes did not differ between the groups. However, operation time was longer in the beginner group than in the experienced group (57.5 min [IQR, 50.0–70.0] versus 50.0 min [IQR, 45.0–55.0], p < 0.001). The beginner group had higher perioperative complication rates (eight patients [10.7%] versus one patient [1.3%], with a hazard ratio of 8.836 [95% CI, 1.077–72.514], p = 0.034) and lower 3-year survival without adverse events (19 patients [25.3%] in the beginner group and 10 patients [13.3%] in the experienced group, p = 0.045). Our findings indicate that the clinical outcomes were more favorable in patients operated on at the experienced stage compared to those treated at the beginner stage.
]]>Bioengineering doi: 10.3390/bioengineering11040310
Authors: Alwyn Gomez Izabella Marquez Logan Froese Tobias Bergmann Amanjyot Singh Sainbhi Nuray Vakitbilir Abrar Islam Kevin Y. Stein Younis Ibrahim Frederick A. Zeiler
Near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2)-based cerebrovascular reactivity (CVR) monitoring has enabled entirely non-invasive, continuous monitoring during both acute and long-term phases of care. To date, long-term post-injury CVR has not been properly characterized after acute traumatic neural injury, also known as traumatic brain injury (TBI). This study aims to compare CVR in those recovering from moderate-to-severe TBI with a healthy control group. A total of 101 heathy subjects were recruited for this study, along with 29 TBI patients. In the healthy cohort, the arterial blood pressure variant of the cerebral oxygen index (COx_a) was not statistically different between males and females or in the dominant and non-dominant hemispheres. In the TBI cohort, COx_a was not statistically different between the first and last available follow-up or by the side of cranial surgery. Surprisingly, CVR, as measured by COx_a, was statistically better in those recovering from TBI than those in the healthy cohort. In this prospective cohort study, CVR, as measured by NIRS-based methods, was found to be more active in those recovering from TBI than in the healthy cohort. This study may indicate that in individuals that survive TBI, CVR may be enhanced as a neuroprotective measure.
]]>Bioengineering doi: 10.3390/bioengineering11040311
Authors: Qian Zhang Yun Zeng Yang Zhao Xuqi Peng En Ren Gang Liu
Magnetic robots possess an innate ability to navigate through hard-to-reach cavities in the human body, making them promising tools for diagnosing and treating diseases minimally invasively. Despite significant advances, the development of robots with desirable locomotion and full biocompatibility under harsh physiological conditions remains challenging, which put forward new requirements for magnetic robots’ design and material synthesis. Compared to robots that are synthesized with inorganic materials, natural organisms like cells, bacteria or other microalgae exhibit ideal properties for in vivo applications, such as biocompatibility, deformability, auto-fluorescence, and self-propulsion, as well as easy for functional therapeutics engineering. In the process, these organisms can provide autonomous propulsion in biological fluids or external magnetic fields, while retaining their functionalities with integrating artificial robots, thus aiding targeted therapeutic delivery. This kind of robotics is named bio-hybrid magnetic robotics, and in this mini-review, recent progress including their design, engineering and potential for therapeutics delivery will be discussed. Additionally, the historical context and prominent examples will be introduced, and the complexities, potential pitfalls, and opportunities associated with bio-hybrid magnetic robotics will be discussed.
]]>Bioengineering doi: 10.3390/bioengineering11040309
Authors: Samy Al-Bourgol Guillaume Machinet Aboubakr Bakkali Marc Faucon Laura Gemini
Femtosecond (fs) laser technology is currently being considered in innovative fields such as osteotomy and treatment of hard tissue thanks to the achievable high resolution and ability to prevent tissue damage. In a previous study, suitable process parameters were obtained to achieve competitive ablation rates on pork femur processing. Nevertheless, a better control of thermal accumulation in the tissue during laser ablation could further improve the postoperative regeneration of the treated bone compared with conventional procedures and push forward the exploitation of such technology. This study presents methods for real time analyses of bone tissue temperature and composition during fs laser ablation and highlights the importance of implementing an efficient cooling method of bone tissue in order to achieve optimized results. Results show that it is possible to achieve a larger process window for bone tissue ablation where bone tissue temperature remains within the protein denaturation temperature in water-based processing environment. This is a key outcome towards a clinical exploitation of the presented technology, where higher process throughputs are necessary. The effects of process parameters and environments on bone tissue were confirmed by LIBS technique, which proved to be an efficient method by which to record real-time variation of bone tissue composition during laser irradiation.
]]>Bioengineering doi: 10.3390/bioengineering11040308
Authors: Ming-Chan Lee Cheng-Tang Pan Wen-Fan Chen Meng-Chi Lin Yow-Ling Shiue
This study proposed a composite tibia defect scaffold with radial gradient porosity, utilizing finite element analysis to assess stress in the tibial region with significant critical-sized defects. Simulations for scaffolds with different porosities were conducted, designing an optimal tibia defect scaffold with radial gradient porosity for repairing and replacing critical bone defects. Radial gradient porosity scaffolds resulted in a more uniform stress distribution, reducing titanium alloy stiffness and alleviating stress shielding effects. The scaffold was manufactured using selective laser melting (SLM) technology with stress relief annealing to simplify porous structure fabrication. The study used New Zealand white rabbits’ tibia defect sites as simulation parameters, reconstructing the 3D model and implanting the composite scaffold. Finite element analysis in ANSYS-Workbench simulated forces under high-activity conditions, analyzing stress distribution and strain. In the simulation, the titanium alloy scaffold bore a maximum stress of 122.8626 MPa, while the centrally encapsulated HAp material delivered 27.92 MPa. The design demonstrated superior structural strength, thereby reducing stress concentration. The scaffold was manufactured using SLM, and the uniform design method was used to determine a collection of optimum annealing parameters. Nanoindentation and compression tests were used to determine the influence of annealing on the elastic modulus, hardness, and strain energy of the scaffold.
]]>Bioengineering doi: 10.3390/bioengineering11040307
Authors: Sara Salehi Ernesto Lippert Lozano Yichuan Zhang Yinan Guo Renee Liu Kenny Tran Franka Messner Gerald Brandacher Warren L. Grayson
Static cold storage (SCS), the current clinical gold standard for organ preservation, provides surgeons with a limited window of time between procurement and transplantation. In vascularized composite allotransplantation (VCA), this time limitation prevents many viable allografts from being designated to the best-matched recipients. Machine perfusion (MP) systems hold significant promise for extending and improving organ preservation. Most of the prior MP systems for VCA have been built and tested for large animal models. However, small animal models are beneficial for high-throughput biomolecular investigations. This study describes the design and development of a multiparametric bioreactor with a circuit customized to perfuse rat abdominal wall VCAs. To demonstrate its concept and functionality, this bioreactor system was employed in a small-scale demonstrative study in which biomolecular metrics pertaining to graft viability were evaluated non-invasively and in real time. We additionally report a low incidence of cell death from ischemic necrosis as well as minimal interstitial edema in machine perfused grafts. After up to 12 h of continuous perfusion, grafts were shown to survive transplantation and reperfusion, successfully integrating with recipient tissues and vasculature. Our multiparametric bioreactor system for rat abdominal wall VCA provides an advanced framework to test novel techniques to enhance normothermic and sub-normothermic VCA preservations in small animal models.
]]>Bioengineering doi: 10.3390/bioengineering11040306
Authors: Mou Cui Xuhao Dong Yan Zhuang Shiyong Li Shimin Yin Zhencheng Chen Yongbo Liang
As an essential physiological indicator within the human body, noninvasive continuous blood pressure (BP) measurement is critical in the prevention and treatment of cardiovascular disease. However, traditional methods of blood pressure prediction using a single-wavelength Photoplethysmographic (PPG) have bottlenecks in further improving BP prediction accuracy, which limits their development in clinical application and dissemination. To this end, this study proposed a method to fuse a four-wavelength PPG and a BP prediction model based on the attention mechanism of a convolutional neural network and bidirectional long- and short-term memory (ACNN-BiLSTM). The effectiveness of a multi-wavelength PPG fusion method for blood pressure prediction was evaluated by processing PPG signals from 162 volunteers. The study compared the performance of the PPG signals with different individual wavelengths and using a multi-wavelength PPG fusion method in blood pressure prediction, assessed using mean absolute error (MAE), root mean squared error (RMSE) and AAMI-related criteria. The experimental results showed that the ACNN-BiLSTM model achieved a better MAE ± RMSE for a systolic BP and diastolic BP of 1.67 ± 5.28 and 1.15 ± 2.53 mmHg, respectively, when using the multi-wavelength PPG fusion method. As a result, the ACNN-BiLSTM blood pressure model based on multi-wavelength PPG fusion could be considered a promising method for noninvasive continuous BP measurement.
]]>Bioengineering doi: 10.3390/bioengineering11040305
Authors: Oleg Ardatov Jolita Pachaleva Viktorija Aleksiuk Algirdas Maknickas Ilona Uzieliene Raminta Vaiciuleviciute Eiva Bernotiene
The investigation examines the transference of stiffness from intervertebral discs (IVDs) to the lumbar body of the L1 vertebra and the interactions among adjacent tissues. A computational model of the vertebra was developed, considering parameters such as cortical bone thickness, trabecular bone elasticity, and the nonlinear response of the nucleus pulposus to external loading. A nonlinear dynamic analysis was performed, revealing certain trends: a heightened stiffness of the annulus fibrosus correlates with a significant reduction in the vertebral body’s ability to withstand external loading. At a supplied displacement of 6 mm, the vertebra with a degenerative disc reached its yielding point, whereas the vertebrae with a healthy annulus fibrosus exhibited a strength capacity exceeding 20%. The obtained findings and proposed methodology are potentially useful for biomedical engineers and clinical specialists in evaluating the condition of the annulus fibrosus and predicting its influence on the bone components of the spinal system.
]]>Bioengineering doi: 10.3390/bioengineering11040304
Authors: Sudha Srinivasan Patrick Kumavor Kristin Morgan
The pilot study assessed the utility of a training program using modified, commercially available dual-joystick-operated ride-on toys to promote unimanual and bimanual upper extremity (UE) function in children with cerebral palsy (CP). The ride-on-toy training was integrated within a 3-week, intensive, task-oriented training camp for children with CP. Eleven children with hemiplegia between 4 and 10 years received the ride-on-toy training program 20–30 min/day, 5 days/week for 3 weeks. Unimanual motor function was assessed using the Quality of Upper Extremity Skills Test (QUEST) before and after the camp. During ride-on-toy training sessions, children wore activity monitors on both wrists to assess the duration and intensity of bimanual UE activity. Video data from early and late sessions were coded for bimanual UE use, independent navigation, and movement bouts. Children improved their total and subscale QUEST scores from pretest to post-test while increasing moderate activity in their affected UE from early to late sessions, demonstrating more equal use of both UEs across sessions. There were no significant changes in the rates of movement bouts from early to late sessions. We can conclude that joystick-operated ride-on toys function as child-friendly, intrinsically rewarding tools that can complement conventional therapy and promote bimanual motor functions in children with CP.
]]>Bioengineering doi: 10.3390/bioengineering11040303
Authors: Eva Dohle Kamelia Parkhoo Francesco Bennardo Lena Schmeinck Robert Sader Shahram Ghanaati
The understanding that tumor cells might evade immunity through various mutations and the potential of an augmented immune system to eliminate abnormal cells led to the idea of utilizing platelet-rich fibrin (PRF), a blood concentrate containing the body’s immune elements as an adjunctive therapy for localized tumors. This study is the first that evaluated the effect of PRF generated with different relative centrifugal forces (RCFs) on osteoblastic and fibroblastic tumor cell lines MG63 and HT1080 with regard to cell viability, cytokine and growth factor release, and the gene expression of factors related to the cell cycle and apoptosis. Our findings could demonstrate decreased cell proliferation of MG63 and HT1080 when treated indirectly with PRF compared to cell cultures without PRF. This effect was more distinct when the cells were treated with low-RCF PRF, where higher concentrations of growth factors and cytokines with reduced RCFs can be found. Similar patterns were observed when assessing the regulation of gene expression related to the cell cycle and apoptosis in both MG63 and HT1080 cells treated with PRF. Despite variations, there was a consistent trend of an up-regulation of tumor-suppressive genes and a down-regulation of anti-apoptotic genes in both cell types following treatment with high- and, particularly, low-RCF PRF formulations.
]]>Bioengineering doi: 10.3390/bioengineering11040302
Authors: Naoki Yamamoto Noriko Hiramatsu Yoshinao Kato Atsushi Sato Hajime Kojima
In a previous study, a novel human corneal-like epithelium model utilizing an immortalized human corneal epithelial cell line (iHCE-NY1) was developed as an alternative to animal models to identify chemicals not classified under the United Nations Globally Harmonized System of Classification and Labeling of Chemicals (GHS) and was evaluated following the criteria of Test Guideline 492 of the Organization for Economic Co-operation and Development (OECD). In the present study, our aim was to establish an eye irritation test protocol using the iHCE-NY1 model to classify liquid chemicals under the GHS ocular hazard categories: no effect, no classification (No Cat.), Category 2 (Cat. 2) reversible effects, and Category 1 (Cat. 1) irreversible eye damage. The protocol involved exposing the iHCE-NY1 model to 31 liquid test chemicals for 5 min, followed by observation at post-incubation periods (PIPs) to assess recovery. Classification was based on cell viability, and histopathological findings on PIP days 7, 14, and 21. The outcomes were compared with an established database of classifications. All Cat. 1 liquid chemicals, 62.5% of No Cat., and 63.2% of Cat. 2 were correctly categorized. This study demonstrates that the iHCE-NY1 model can not only distinguish No Cat. test liquid chemicals but also differentiate between Cat. 2 and Cat. 1 liquid chemicals.
]]>Bioengineering doi: 10.3390/bioengineering11040301
Authors: Manuel Steinhardt Alexander W. Marka Sebastian Ziegelmayer Marcus Makowski Rickmer Braren Markus Graf Joshua Gawlitza
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death. Recent studies have underlined the importance of non-contrast-enhanced chest CT scans not only for emphysema progression quantification, but for correlation with clinical outcomes as well. As about 40 percent of the 300 million CT scans per year are contrast-enhanced, no proper emphysema quantification is available in a one-stop-shop approach for patients with known or newly diagnosed COPD. Since the introduction of spectral imaging (e.g., dual-energy CT scanners), it has been possible to create virtual non-contrast-enhanced images (VNC) from contrast-enhanced images, making it theoretically possible to offer proper COPD imaging despite contrast enhancing. This study is aimed towards investigating whether these VNC images are comparable to true non-contrast-enhanced images (TNC), thereby reducing the radiation exposure of patients and usage of resources in hospitals. In total, 100 COPD patients with two scans, one with (VNC) and one without contrast media (TNC), within 8 weeks or less obtained by a spectral CT using dual-layer technology, were included in this retrospective study. TNC and VNC were compared according to their voxel-density histograms. While the comparison showed significant differences in the low attenuated volumes (LAVs) of TNC and VNC regarding the emphysema threshold of −950 Houndsfield Units (HU), the 15th and 10th percentiles of the LAVs used as a proxy for pre-emphysema were comparable. Upon further investigation, the threshold-based LAVs (−950 HU) of TNC and VNC were comparable in patients with a water equivalent diameter (DW) below 270 mm. The study concludes that VNC imaging may be a viable option for assessing emphysema progression in COPD patients, particularly those with a normal body mass index (BMI). Further, pre-emphysema was generally comparable between TNC and VNC. This approach could potentially reduce radiation exposure and hospital resources by making additional TNC scans obsolete.
]]>Bioengineering doi: 10.3390/bioengineering11040300
Authors: Ahmad Alenezi Hamad Alhamad Ajit Brindhaban Yashar Amizadeh Ata Jodeiri Sebelan Danishvar
Artificial intelligence has been used effectively in medical diagnosis. The objective of this project is to examine the application of a collective AI model using weighted fusion of predicted probabilities from different AI architectures to diagnose various retinal conditions based on optical coherence tomography (OCT). A publicly available Noor dataset, comprising 16,822, images from 554 retinal OCT scans of 441 patients, was used to predict a diverse spectrum of age-related macular degeneration (AMD) stages: normal, drusen, or choroidal neovascularization. These predictions were compared with predictions from ResNet, EfficientNet, and Attention models, respectively, using precision, recall, F1 score, and confusion matric and receiver operating characteristics curves. Our collective model demonstrated superior accuracy in classifying AMD compared to individual ResNet, EfficientNet, and Attention models, showcasing the effectiveness of using trainable weights in the ensemble fusion process, where these weights dynamically adapt during training rather than being fixed values. Specifically, our ensemble model achieved an accuracy of 91.88%, precision of 92.54%, recall of 92.01%, and F1 score of 92.03%, outperforming individual models. Our model also highlights the refinement process undertaken through a thorough examination of initially misclassified cases, leading to significant improvements in the model’s accuracy rate to 97%. This study also underscores the potential of AI as a valuable tool in ophthalmology. The proposed ensemble model, combining different mechanisms highlights the benefits of model fusion for complex medical image analysis.
]]>Bioengineering doi: 10.3390/bioengineering11040299
Authors: Xiaomin Li Mykhailo Sakevych Gentry Atkinson Vangelis Metsis
Machine learning tasks involving biomedical signals frequently grapple with issues such as limited data availability, imbalanced datasets, labeling complexities, and the interference of measurement noise. These challenges often hinder the optimal training of machine learning algorithms. Addressing these concerns, we introduce BioDiffusion, a diffusion-based probabilistic model optimized for the synthesis of multivariate biomedical signals. BioDiffusion demonstrates excellence in producing high-fidelity, non-stationary, multivariate signals for a range of tasks including unconditional, label-conditional, and signal-conditional generation. Leveraging these synthesized signals offers a notable solution to the aforementioned challenges. Our research encompasses both qualitative and quantitative assessments of the synthesized data quality, underscoring its capacity to bolster accuracy in machine learning tasks tied to biomedical signals. Furthermore, when juxtaposed with current leading time-series generative models, empirical evidence suggests that BioDiffusion outperforms them in biomedical signal generation quality.
]]>Bioengineering doi: 10.3390/bioengineering11040298
Authors: Shimon Rochkind Sharon Sirota Alon Kushnir
This preliminary study aimed to investigate an ActiGraft blood clot implant (RedDress Ltd., Pardes-Hanna, Israel) attempting to treat and induce the regeneration of a completely injured peripheral nerve with a massive loss defect. The tibial portion of the sciatic nerve in 11 rabbits was transected, and a 25 mm nerve gap was reconnected using a collagen tube. A comparison was performed between the treatment group (eight rabbits; reconnection using a tube filled with ActiGraft blood clot) and the control group (three rabbits; gap reconnection using an empty tube). The post-operative follow-up period lasted 18 weeks and included electrophysiological and histochemical assessments. The pathological severity score was high in the tube cross sections of the control group (1.33) compared to the ActiGraft blood clot treatment group (0.63). Morphometric analysis showed a higher percentage of the positive myelin basic protein (MBP) stained area in the ActiGraft blood clot group (19.57%) versus the control group (3.67%). These differences were not statistically significant due to the small group sizes and the large intra-group variability. The results of this preliminary study suggest that the application of an ActiGraft blood clot (into the collagen tube) can enable nerve recovery. However, a future study using a larger animal group is required to achieve objective statistical results.
]]>Bioengineering doi: 10.3390/bioengineering11030297
Authors: Lucas Martinez Matthieu Lalevée Thomas Poirier Helena Brunel Jean Matsoukis Stéphane Van Driessche Fabien Billuart
Accurate estimation of hip joint center (HJC) position is crucial during gait analysis. HJC is obtained with predictive or functional methods. But in the functional method, there is no consensus on where to place the skin markers and which combination to use. The objective of this study was to analyze how different combinations of skin markers affect the estimation of HJC position relative to predictive methods. Forty-one healthy volunteers were included in this study; thirteen markers were placed on the pelvis and hip of each subject’s lower limbs. Various marker combinations were used to determine the HJC position based on ten calibration movement trials, captured by a motion capture system. The estimated HJC position for each combination was evaluated by focusing on the range and standard deviation of the mean norm values of HJC and the mean X, Y, Z coordinates of HJC for each limb. The combinations that produced the best estimates incorporated the markers on the pelvis and on proximal and easily identifiable muscles, with results close to predictive methods. The combination that excluded the markers on the pelvis was not robust in estimating the HJC position.
]]>Bioengineering doi: 10.3390/bioengineering11030296
Authors: Andrej Strahovnik Igor Strahovnik Samo Karel Fokter
Several studies have found a relationship between the rotational anatomy of the distal femur and the overall coronal lower limb alignment in knees with osteoarthritis (OA). Less is known about the rotation of the proximal tibia, especially in the context of total knee arthroplasty (TKA), where one of the goals of the surgery is to achieve the appropriate component-to-component rotation. The aim of this study was to investigate the relationship between the coronal alignment of the lower extremity and the relative proximal tibial rotation. A prospective cohort study of patients with an end-stage OA scheduled for TKA was conducted. All patients underwent a computed tomography (CT) scan and a standing X-ray of both lower limbs. A relative femorotibial rotation was measured separately for mechanical and kinematic alignment. A statistically significant correlation was found between the tibial varus and the external tibial rotation (p < 0.001). Out of 14 knees with high tibial varus (>5°), 13 (93%) and 7 (50%) knees had >10° of femorotibial rotation for the mechanical and kinematic alignment landmarks, respectively. In order to keep the component-to-component rotation within the 10° margin, more internal rotation of the tibial component is required in knees with higher tibial varus.
]]>Bioengineering doi: 10.3390/bioengineering11030295
Authors: Hadi Sedigh Malekroodi Nuwan Madusanka Byeong-il Lee Myunggi Yi
Speech impairments often emerge as one of the primary indicators of Parkinson’s disease (PD), albeit not readily apparent in its early stages. While previous studies focused predominantly on binary PD detection, this research explored the use of deep learning models to automatically classify sustained vowel recordings into healthy controls, mild PD, or severe PD based on motor symptom severity scores. Popular convolutional neural network (CNN) architectures, VGG and ResNet, as well as vision transformers, Swin, were fine-tuned on log mel spectrogram image representations of the segmented voice data. Furthermore, the research investigated the effects of audio segment lengths and specific vowel sounds on the performance of these models. The findings indicated that implementing longer segments yielded better performance. The models showed strong capability in distinguishing PD from healthy subjects, achieving over 95% precision. However, reliably discriminating between mild and severe PD cases remained challenging. The VGG16 achieved the best overall classification performance with 91.8% accuracy and the largest area under the ROC curve. Furthermore, focusing analysis on the vowel /u/ could further improve accuracy to 96%. Applying visualization techniques like Grad-CAM also highlighted how CNN models focused on localized spectrogram regions while transformers attended to more widespread patterns. Overall, this work showed the potential of deep learning for non-invasive screening and monitoring of PD progression from voice recordings, but larger multi-class labeled datasets are needed to further improve severity classification.
]]>Bioengineering doi: 10.3390/bioengineering11030294
Authors: Miguel Luna Philip Chikontwe Sang Hyun Park
Segmenting and classifying nuclei in H&E histopathology images is often limited by the long-tailed distribution of nuclei types. However, the strong generalization ability of image segmentation foundation models like the Segment Anything Model (SAM) can help improve the detection quality of rare types of nuclei. In this work, we introduce category descriptors to perform nuclei segmentation and classification by prompting the SAM model. We close the domain gap between histopathology and natural scene images by aligning features in low-level space while preserving the high-level representations of SAM. We performed extensive experiments on the Lizard dataset, validating the ability of our model to perform automatic nuclei segmentation and classification, especially for rare nuclei types, where achieved a significant detection improvement in the F1 score of up to 12%. Our model also maintains compatibility with manual point prompts for interactive refinement during inference without requiring any additional training.
]]>Bioengineering doi: 10.3390/bioengineering11030293
Authors: Fan Fu Dacheng Zhong Jiamin Liu Tianxiang Xu Qin Shen Wei Wang Songsheng Zhu Jianqing Li
The 12-lead electrocardiogram (ECG) is crucial in assessing patient decisions. However, portable ECG devices capable of acquiring a complete 12-lead ECG are scarce. For the first time, a deep learning-based method is proposed to reconstruct the 12-lead ECG from Frank leads (VX, VY, and VZ) or EASI leads (VES, VAS, and VAI). The innovative ECG reconstruction network called M2Eformer is composed of a 2D-ECGblock and a ProbDecoder module. The 2D-ECGblock module adaptively segments EASI leads into multi-periods based on frequency energy, transforming the 1D time series into a 2D tensor representing within-cycle and between-cycle variations. The ProbDecoder module aims to extract Probsparse self-attention and achieve one-step output for the target leads. Experimental results from comparing recorded and reconstructed 12-lead ECG using Frank leads indicate that M2Eformer outperforms traditional ECG reconstruction methods on a public database. In this study, a self-constructed database (10 healthy individuals + 15 patients) was utilized for the clinical diagnostic validation of ECG reconstructed from EASI leads. Subsequently, both the ECG reconstructed using EASI and the recorded 12-lead ECG were subjected to a double-blind diagnostic experiment conducted by three cardiologists. The overall diagnostic consensus among three cardiology experts, reaching a rate of 96%, indicates the significant utility of EASI-reconstructed 12-lead ECG in facilitating the diagnosis of cardiac conditions.
]]>Bioengineering doi: 10.3390/bioengineering11030292
Authors: Rami E. Maasri Jonathan R. Jarvie Jacob S. Karski Logan J. Smith Moh H. Malek
Background: The purpose of this study was to determine whether cold therapy after the first exercise test influences the physical working capacity at the fatigue threshold (PWCFT) during the second exercise test. We hypothesized that cold therapy would delay the onset of PWCFT for the second exercise test relative to the control visit (i.e., no cold therapy). Methods: Eight healthy college-aged men volunteered for the present study. For each of the two visits, subjects performed incremental, single-leg, knee-extensor ergometer, followed by either resting for 30 min (control visit) or having a cold pack applied for 15 min and then resting for 15 min (experimental visit). Then, the same exercise test was performed. The order of visits (control vs. experimental) was randomized for each subject. The exercise indices and PWCFT were determined for each of the two visits and statistically analyzed using two-way repeated measures analysis of variance. Results: The results indicate no significant (p > 0.05) mean differences for maximal power output, heart rate at end-exercise, and PWCFT between the control and cold therapy visits. Moreover, there were no significant (p > 0.05) mean differences between the first and second exercise workbout within each visit. Conclusions: The findings of this study suggest that cold therapy did not influence neuromuscular fatigue.
]]>Bioengineering doi: 10.3390/bioengineering11030291
Authors: Kenneth Y. T. Lim Minh Tuan Nguyen Thien Minh Anh Nguyen Duc Hugo F. Posada-Quintero
This paper describes the analysis of electrodermal activity (EDA) in the context of students’ scholastic activity. Taking a multidisciplinary, citizen science and maker-centric approach, low-cost, bespoken wearables, such as a mini weather station and biometric wristband, were built. To investigate both physical health as well as stress, the instruments were first validated against research grade devices. Following this, a research experiment was created and conducted in the context of students’ scholastic activity. Data from this experiment were used to train machine learning models, which were then applied to interpret the relationships between the environment, health, and stress. It is hoped that analyses of EDA data will further strengthen the emerging model describing the intersections between local microclimate and physiological and neurological stress. The results suggest that temperature and air quality play an important role in students’ physiological well-being, thus demonstrating the feasibility of understanding the extent of the effects of various microclimatic factors. This highlights the importance of thermal comfort and air ventilation in real-life applications to improve students’ well-being. We envision our work making a significant impact by showcasing the effectiveness and feasibility of inexpensive, self-designed wearable devices for tracking microclimate and electrodermal activity (EDA). The affordability of these wearables holds promising implications for scalability and encourages crowd-sourced citizen science in the relatively unexplored domain of microclimate’s influence on well-being. Embracing citizen science can then democratize learning and expedite rapid research advancements.
]]>Bioengineering doi: 10.3390/bioengineering11030290
Authors: Kenneth D. Harrison Christopher J. Dakin Anne Z. Beethe Talin Louder
Researchers commonly use the ‘free-fall’ paradigm to investigate motor control during landing impacts, particularly in drop landings and depth jumps (DJ). While recent studies have focused on the impact of vision on landing motor control, previous research fully removed continuous visual input, limiting ecological validity. The aim of this investigation was to evaluate the effects of stroboscopic vision on depth jump (DJ) motor control. Ground reaction forces (GRF) and lower-extremity surface electromyography (EMG) were collected for 20 young adults (11 male; 9 female) performing six depth jumps (0.51 m drop height) in each of two visual conditions (full vision vs. 3 Hz stroboscopic vision). Muscle activation magnitude was estimated from EMG signals using root-mean-square amplitudes (RMS) over specific time intervals (150 ms pre-impact; 30–60 ms, 60–85 ms, and 85–120 ms post-impact). The main effects of and interactions between vision and trial number were assessed using two-way within-subjects repeated measures analyses of variance. Peak GRF was 6.4% greater, on average, for DJs performed with stroboscopic vision compared to full vision (p = 0.042). Tibialis anterior RMS EMG during the 60–85 ms post-impact time interval was 14.1% lower for DJs performed with stroboscopic vision (p = 0.020). Vastus lateralis RMS EMG during the 85–120 ms post-impact time interval was 11.8% lower for DJs performed with stroboscopic vision (p = 0.017). Stroboscopic vision altered DJ landing mechanics and lower-extremity muscle activation. The observed increase in peak GRF and reduction in RMS EMG of the tibialis anterior and vastus lateralis post-landing may signify a higher magnitude of lower-extremity musculotendinous stiffness developed pre-landing. The results indicate measurable sensorimotor disruption for DJs performed with stroboscopic vision, warranting further research and supporting the potential use of stroboscopic vision as a sensorimotor training aid in exercise and rehabilitation. Stroboscopic vision could induce beneficial adaptations in multisensory integration, applicable to restoring sensorimotor function after injury and preventing injuries in populations experiencing landing impacts at night (e.g., military personnel).
]]>Bioengineering doi: 10.3390/bioengineering11030289
Authors: Chiara Scodellaro Raquel R. Pina Frederico Castelo Ferreira Paola Sanjuan-Alberte Tiago G. Fernandes
The field of regenerative medicine has recently witnessed groundbreaking advancements that hold immense promise for treating a wide range of diseases and injuries. At the forefront of this revolutionary progress are stem cells. Stem cells typically reside in specialized environments in vivo, known as microenvironments or niches, which play critical roles in regulating stem cell behavior and determining their fate. Therefore, understanding the complex microenvironments that surround stem cells is crucial for advancing treatment options in regenerative medicine and tissue engineering applications. Several research articles have made significant contributions to this field by exploring the interactions between stem cells and their surrounding niches, investigating the influence of biomechanical and biochemical cues, and developing innovative strategies for tissue regeneration. This review highlights the key findings and contributions of these studies, shedding light on the diverse applications that may arise from the understanding of stem cell microenvironments, thus harnessing the power of these microenvironments to transform the landscape of medicine and offer new avenues for regenerative therapies.
]]>Bioengineering doi: 10.3390/bioengineering11030288
Authors: Lorenzo Fiori Stefano Filippo Castiglia Giorgia Chini Francesco Draicchio Floriana Sacco Mariano Serrao Antonella Tatarelli Tiwana Varrecchia Alberto Ranavolo
The central nervous system (CNS) controls movements and regulates joint stiffness with muscle co-activation, but until now, few studies have examined muscle pairs during running. This study aims to investigate differences in lower limb muscle coactivation during gait at different speeds, from walking to running. Nineteen healthy runners walked and ran at speeds ranging from 0.8 km/h to 9.3 km/h. Twelve lower limb muscles’ co-activation was calculated using the time-varying multi-muscle co-activation function (TMCf) with global, flexor–extension, and rostro–caudal approaches. Spatiotemporal and kinematic parameters were also measured. We found that TMCf, spatiotemporal, and kinematic parameters were significantly affected by gait speed for all approaches. Significant differences were observed in the main parameters of each co-activation approach and in the spatiotemporal and kinematic parameters at the transition between walking and running. In particular, significant differences were observed in the global co-activation (CIglob, main effect F(1,17) = 641.04, p < 0.001; at the transition p < 0.001), the stride length (main effect F(1,17) = 253.03, p < 0.001; at the transition p < 0.001), the stride frequency (main effect F(1,17) = 714.22, p < 0.001; at the transition p < 0.001) and the Center of Mass displacement in the vertical (CoMy, main effect F(1,17) = 426.2, p < 0.001; at the transition p < 0.001) and medial–lateral (CoMz, main effect F(1,17) = 120.29 p < 0.001; at the transition p < 0.001) directions. Regarding the correlation analysis, the CoMy was positively correlated with a higher CIglob (r = 0.88, p < 0.001) and negatively correlated with Full Width at Half Maximum (FWHMglob, r = −0.83, p < 0.001), whereas the CoMz was positively correlated with the global Center of Activity (CoAglob, r = 0.97, p < 0.001). Positive and negative strong correlations were found between global co-activation parameters and center of mass displacements, as well as some spatiotemporal parameters, regardless of gait speed. Our findings suggest that walking and running have different co-activation patterns and kinematic characteristics, with the whole-limb stiffness exerted more synchronously and stably during running. The co-activation indexes and kinematic parameters could be the result of global co-activation, which is a sensory-control integration process used by the CNS to deal with more demanding and potentially unstable tasks like running.
]]>Bioengineering doi: 10.3390/bioengineering11030287
Authors: Andreas Kammerer Frederik Alexander Hartmann Christoph Nau Maximilian Leiblein Alexander Schaible Jonas Neijhoft Dirk Henrich René Verboket Maren Janko
Critical-size bone defects up to 25 cm can be treated successfully using the induced membrane technique established by Masquelet. To shorten this procedure, human acellular dermis (HAD) has had success in replacing this membrane in rat models. The aim of this study was to compare bone healing for smaller and larger defects using an induced membrane and HAD in a rat model. Using our established femoral defect model in rats, the animals were placed into four groups and defects of 5 mm or 10 mm size were set, either filling them with autologous spongiosa and surrounding the defect with HAD or waiting for the induced membrane to form around a cement spacer and filling this cavity in a second operation with a cancellous bone graft. Healing was assessed eight weeks after the operation using µ-CT, histological staining, and an assessment of the progress of bone formation using an established bone healing score. The α-smooth muscle actin used as a signal of blood vessel formation was stained and counted. The 5 mm defects showed significantly better bone union and a higher bone healing score than the 10 mm defects. HAD being used for the smaller defects resulted in a significantly higher bone healing score even than for the induced membrane and significantly higher blood vessel formation, corroborating the good results achieved by using HAD in previous studies. In comparison, same-sized groups showed significant differences in bone healing as well as blood vessel formation, suggesting that 5 mm defects are large enough to show different results in healing depending on treatment; therefore, 5 mm is a viable size for further studies on bone healing.
]]>Bioengineering doi: 10.3390/bioengineering11030286
Authors: Legeng Lin Wanyi Qing Yanhuan Huang Fuqiang Ye Wei Rong Waiming Li Jiao Jiao Xiaoling Hu
Focal vibratory stimulation (FVS) and neuromuscular electrical stimulation (NMES) are promising technologies for sensory rehabilitation after stroke. However, the differences between these techniques in immediate neuromodulatory effects on the poststroke cortex are not yet fully understood. In this research, cortical responses in persons with chronic stroke (n = 15) and unimpaired controls (n = 15) were measured by whole-brain electroencephalography (EEG) when FVS and NMES at different intensities were applied transcutaneously to the forearm muscles. Both FVS and sensory-level NMES induced alpha and beta oscillations in the sensorimotor cortex after stroke, significantly exceeding baseline levels (p < 0.05). These oscillations exhibited bilateral sensory deficiency, early adaptation, and contralesional compensation compared to the control group. FVS resulted in a significantly faster P300 response (p < 0.05) and higher theta oscillation (p < 0.05) compared to NMES. The beta desynchronization over the contralesional frontal–parietal area remained during NMES (p > 0.05), but it was significantly weakened during FVS (p < 0.05) after stroke. The results indicated that both FVS and NMES effectively activated the sensorimotor cortex after stroke. However, FVS was particularly effective in eliciting transient involuntary attention, while NMES primarily fostered the cortical responses of the targeted muscles in the contralesional motor cortex.
]]>Bioengineering doi: 10.3390/bioengineering11030285
Authors: Tea Sokač Cvetnić Korina Krog Davor Valinger Jasenka Gajdoš Kljusurić Maja Benković Tamara Jurina Tamara Jakovljević Ivana Radojčić Redovniković Ana Jurinjak Tušek
The reusability of by-products in the food industry is consistent with sustainable and greener production; therefore, the aim of this paper was to evaluate the applicability of multiple linear regression (MLR), piecewise linear regression (PLR) and artificial neural network models (ANN) to the prediction of grape-skin compost’s physicochemical properties (moisture, dry matter, organic matter, ash content, carbon content, nitrogen content, C/N ratio, total colour change of compost samples, pH, conductivity, total dissolved solids and total colour change of compost extract samples) during in-vessel composting based on the initial composting conditions (air-flow rate, moisture content and day of sampling). Based on the coefficient of determination for prediction, the adjusted coefficient of determination for calibration, the root-mean-square error of prediction (RMSEP), the standard error of prediction (SEP), the ratio of prediction to deviation (RPD) and the ratio of the error range (RER), it can be concluded that all developed MLR and PLR models are acceptable for process screening. Furthermore, the ANN model developed for predicting moisture and dry-matter content can be used for quality control (RER >11). The obtained results show the great potential of multivariate modelling for analysis of the physicochemical properties of compost during composting, confirming the high applicability of modelling in greener production processes.
]]>Bioengineering doi: 10.3390/bioengineering11030284
Authors: Lina Schütte Katharina Hausmann Christoph Schwarz Franziska Ersoy Ralf G. Berger
Following the idea of a circular bioeconomy, the use of side streams as substitutes for cultivation media (components) in bioprocesses would mean an enormous economic and ecological advantage. Costly compounds in conventional media for the production of the triterpene squalene in thraustochytrids are the main carbon source and complex nitrogen sources. Among other side streams examined, extracts from the spent mycelium of the basidiomycete Pleurotus ostreatus were best-suited to acting as alternative nitrogen sources in cultivation media for thraustochytrids. The total nitrogen (3.76 ± 0.01 and 4.24 ± 0.04%, respectively) and protein (16.47 ± 0.06 and 18.57 ± 0.18%, respectively) contents of the fruiting body and mycelium were determined. The fungal cells were hydrolyzed and extracted to generate accessible nitrogen sources. Under preferred conditions, the extracts from the fruiting body and mycelium contained 73.63 ± 1.19 and 89.93 ± 7.54 mM of free amino groups, respectively. Cultivations of Schizochytrium sp. S31 on a medium using a mycelium extract as a complex nitrogen source showed decelerated growth but a similar squalene yield (123.79 ± 14.11 mg/L after 216 h) compared to a conventional medium (111.29 ± 19.96 mg/L, although improvable by additional complex nitrogen source).
]]>Bioengineering doi: 10.3390/bioengineering11030283
Authors: Alicia Falcon-Caro Evtim Peytchev Saeid Sanei
Here, we present an effective application of adaptive cooperative networks, namely assisting disables in navigating in a crowd in a pandemic or emergency situation. To achieve this, we model crowd movement and introduce a cooperative learning approach to enable cooperation and self-organization of the crowd members with impaired health or on wheelchairs to ensure their safe movement in the crowd. Here, it is assumed that the movement path and the varying locations of the other crowd members can be estimated by each agent. Therefore, the network nodes (agents) should continuously reorganize themselves by varying their speeds and distances from each other, from the surrounding walls, and from obstacles within a predefined limit. It is also demonstrated how the available wireless trackers such as AirTags can be used for this purpose. The model effectiveness is examined with respect to the real-time changes in environmental parameters and its efficacy is verified.
]]>Bioengineering doi: 10.3390/bioengineering11030282
Authors: Nesrin Dursun Hakki Gülşen
Hydrogen creates water during combustion. Therefore, it is expected to be the most promising environmentally friendly energy alternative in the coming years. This study used extract liquid obtained from the waste nigella sativa generated by the black cumin oil industry. The performance of biological hydrogen manufacturing via dark fermentation was investigated in the fluidized bed reactor (FBR) and completely stirred tank reactor (CSTR) under the operation conditions of pH 5.0, 4.0, and 6.0 and a hydraulic retention time (HRT) of 36 and 24 h. The performance of hydrogen manufacturing was determined to be good under an organic loading ratio (OLR) of 6.66 g.nigella sativa extract/L and pH 4.0. According to these conditions, the maximum amount of hydrogen in CSTR and FBR was found to be 20.8 and 7.6 mL H2/day, respectively. The operating process of the reactors displayed that a reduction in HRT augmented biohydrogen manufacturing. The work that used mixed culture found that the dominant microbial population at pH 4.0 involved Hydrogenimonas thermophila, Sulfurospirillum carboxydovorans, Sulfurospirillum cavolei, Sulfurospirillum alkalitolerans, and Thiofractor thiocaminus. No research on waste black cumin extract was found in biohydrogen studies, and it was determined that this substrate source is applicable for biological hydrogen manufacturing.
]]>Bioengineering doi: 10.3390/bioengineering11030281
Authors: J. Shanthi Sravan Leonidas Matsakas Omprakash Sarkar
Advancements in biological wastewater treatment with sustainable and circularity approaches have a wide scope of application. Biological wastewater treatment is widely used to remove/recover organic pollutants and nutrients from a diverse wastewater spectrum. However, conventional biological processes face challenges, such as low efficiency, high energy consumption, and the generation of excess sludge. To overcome these limitations, integrated strategies that combine biological treatment with other physical, chemical, or biological methods have been developed and applied in recent years. This review emphasizes the recent advances in integrated strategies for biological wastewater treatment, focusing on their mechanisms, benefits, challenges, and prospects. The review also discusses the potential applications of integrated strategies for diverse wastewater treatment towards green energy and resource recovery, along with low-carbon fuel production. Biological treatment methods, viz., bioremediation, electro-coagulation, electro-flocculation, electro-Fenton, advanced oxidation, electro-oxidation, bioelectrochemical systems, and photo-remediation, are summarized with respect to non-genetically modified metabolic reactions. Different conducting materials (CMs) play a significant role in mass/charge transfer metabolic processes and aid in enhancing fermentation rates. Carbon, metal, and nano-based CMs hybridization in different processes provide favorable conditions to the fermentative biocatalyst and trigger their activity towards overcoming the limitations of the conventional process. The emerging field of nanotechnology provides novel additional opportunities to surmount the constraints of conventional process for enhanced waste remediation and resource valorization. Holistically, integrated strategies are promising alternatives for improving the efficiency and effectiveness of biological wastewater treatment while also contributing to the circular economy and environmental protection.
]]>Bioengineering doi: 10.3390/bioengineering11030280
Authors: Federica Camuncoli Giorgia Malerba Emilia Biffi Eleonora Diella Eugenio Di Stanislao Guerrino Rosellini Daniele Panzeri Luigi Piccinini Manuela Galli
Cerebral palsy poses challenges in walking, necessitating ankle foot orthoses (AFOs) for stability. Gait analysis, particularly on slopes, is crucial for effective AFO assessment. The study aimed to compare the performance of commercially available AFOs with a new sports-specific AFO in children with hemiplegic cerebral palsy and to assess the effects of varying slopes on gait. Eighteen participants, aged 6–11, with hemiplegia, underwent gait analysis using GRAIL technology. Two AFO types were tested on slopes (uphill +10 deg, downhill −5 deg, level-ground). Kinematic, kinetic, and spatiotemporal parameters were analyzed. The new AFO contributed to significant changes in ankle dorsi-plantar-flexion, foot progression, and trunk and hip rotation during downhill walking. Additionally, the new AFO had varied effects on spatiotemporal gait parameters, with an increased stride length during downhill walking. Slope variations significantly influenced the kinematics and kinetics. This study provides valuable insights into AFO effectiveness and the impact of slopes on gait in hemiplegic cerebral palsy. The findings underscore the need for personalized interventions, considering environmental factors, and enhancing clinical and research approaches for improving mobility in cerebral palsy.
]]>Bioengineering doi: 10.3390/bioengineering11030279
Authors: Florian Wichlas Marco Necchi Teresa Gruber Valeska Hofmann Susanne Deininger Sebastian Hubertus Markus Deininger Amelie Deluca Eva Steidle-Kloc Jan Pruszak Jörn Wittig Christian Deininger
Background: The lack of resources limits the treatment of craniomaxillofacial fractures (CMF) in low-income countries (LIC). Therefore, Barton bandages and/or interdental wiring are considered in these regions. Fracture reduction is maintained by permanent occlusion for 6 weeks, which often leads to limited compliance and dissatisfying results. The aim of this cadaver-based study is to evaluate the feasibility of the use of an external face fixator (EFF) for the treatment of CMF, its biomechanical values and to define the optimal pin insertion points and angles. Materials and Methods: An AO hand fixator was used. CMF of types Le Fort 1–3 with split fractures of the hard palate were treated with EFF on 13 anatomical specimens. Fractures were created using a chisel, and pins were placed in specific anatomical regions. The maximal pull-out force [N] of pins was analysed by a tensile force gauge, and Fmax of the mandibular pins was evaluated. Computer tomography scans were performed on the healthy, fractured and EFF-treated skulls. Results: The pull-out forces for the single pins were mandibular pins (n = 15, median 488.0 N), supraorbital pins (n = 15, median 455.0 N), zygomatic pins (n = 14, median 269.1 N), medial hard palate pins (n = 12, median 208.4 N) and lateral hard palate pins (n = 8, median 49.6 N). Conclusions: The results indicate that the operation technique is feasible, and the stability of the EFF is sufficient for maintaining the reduction. The required pins can safely be inserted into the described areas with good reduction results. Using EFF offers a feasible alternative to the non-surgical treatment of CMF in LIC.
]]>Bioengineering doi: 10.3390/bioengineering11030278
Authors: Christos Chadoulos Dimitrios Tsaopoulos Andreas Symeonidis Serafeim Moustakidis John Theocharis
In this paper, we propose a dense multi-scale adaptive graph convolutional network (DMA-GCN) method for automatic segmentation of the knee joint cartilage from MR images. Under the multi-atlas setting, the suggested approach exhibits several novelties, as described in the following. First, our models integrate both local-level and global-level learning simultaneously. The local learning task aggregates spatial contextual information from aligned spatial neighborhoods of nodes, at multiple scales, while global learning explores pairwise affinities between nodes, located globally at different positions in the image. We propose two different structures of building models, whereby the local and global convolutional units are combined by following an alternating or a sequential manner. Secondly, based on the previous models, we develop the DMA-GCN network, by utilizing a densely connected architecture with residual skip connections. This is a deeper GCN structure, expanded over different block layers, thus being capable of providing more expressive node feature representations. Third, all units pertaining to the overall network are equipped with their individual adaptive graph learning mechanism, which allows the graph structures to be automatically learned during training. The proposed cartilage segmentation method is evaluated on the entire publicly available Osteoarthritis Initiative (OAI) cohort. To this end, we have devised a thorough experimental setup, with the goal of investigating the effect of several factors of our approach on the classification rates. Furthermore, we present exhaustive comparative results, considering traditional existing methods, six deep learning segmentation methods, and seven graph-based convolution methods, including the currently most representative models from this field. The obtained results demonstrate that the DMA-GCN outperforms all competing methods across all evaluation measures, providing DSC=95.71% and DSC=94.02% for the segmentation of femoral and tibial cartilage, respectively.
]]>Bioengineering doi: 10.3390/bioengineering11030277
Authors: Jessica Podda Ludovico Pedullà Giampaolo Brichetto Andrea Tacchino
Background: People with multiple sclerosis (PwMS) frequently present both cognitive and motor impairments, so it is reasonable to assume they may have difficulties in executing dual-tasks (DT). The aim of the present study is to identify novel technology-based parameters to assess cognitive-motor interference (CMI) in PwMS. In particular, we focused on the definition of dual-task cost (DTC) measures using wearable and portable tools such as insoles and mobile apps. Methods: All participants underwent a verbal fluency task (cognitive single-task, ST), a motor ST of walking, and a combination of these tasks (DT). Number of words uttered in the cognitive ST and steps recorded by insoles were used to calculate the motor and cognitive DTC. Results: The number of steps strongly correlated with the walked meters for both single- (r = 0.88, p < 0.05) and dual- (r = 0.91, p < 0.05) tasks. Motor but not cognitive performances significantly worsened during DT. Over the cognitive ST and DT, the number of pronounced words progressively decreased, probably due to the activation of different cognitive processes. Cognitive efforts could be the cause of cognitive task prioritization. Conclusions: Our findings promote the use of low-cost devices to assess CMI easily in the clinical context and to detect ecologically valid DT impairments.
]]>Bioengineering doi: 10.3390/bioengineering11030276
Authors: Zaihao Wang Yuhao Ding Wei Yuan Hongyu Chen Wei Chen Chen Chen
EEG, which can provide brain alteration information via recording the electrical activity of neurons in the cerebral cortex, has been widely used in neurophysiology. However, conventional wet electrodes in EEG monitoring typically suffer from inherent limitations, including the requirement of skin pretreatment, the risk of superficial skin infections, and signal performance deterioration that may occur over time due to the air drying of the conductive gel. Although the emergence of dry electrodes has overcome these shortcomings, their electrode–skin contact impedance is significantly high and unstable, especially in hair-covered areas. To address the above problems, an active claw-shaped dry electrode is designed, moving from electrode morphological design, slurry preparation, and coating to active electrode circuit design. The active claw-shaped dry electrode, which consists of a claw-shaped electrode and active electrode circuit, is dedicated to offering a flexible solution for elevating electrode fittings on the scalp in hair-covered areas, reducing electrode–skin contact impedance and thus improving the quality of the acquired EEG signal. The performance of the proposed electrodes was verified by impedance, active electrode circuit, eyes open-closed, steady-state visually evoked potential (SSVEP), and anti-interference tests, based on EEG signal acquisition. Experimental results show that the proposed claw-shaped electrodes (without active circuit) can offer a better fit between the scalp and electrodes, with a low electrode–skin contact impedance (18.62 KΩ@1 Hz in the hairless region and 122.15 KΩ@1 Hz in the hair-covered region). In addition, with the active circuit, the signal-to-noise ratio (SNR) of the acquiring EEG signal was improved and power frequency interference was restrained, therefore, the proposed electrodes can yield an EEG signal quality comparable to wet electrodes.
]]>Bioengineering doi: 10.3390/bioengineering11030275
Authors: Qian Xiang Jiaxin Wang Yong Liu Shijie Guo Lei Liu
The gait recognition of exoskeletons includes motion recognition and gait phase recognition under various road conditions. The recognition of gait phase is a prerequisite for predicting exoskeleton assistance time. The estimation of real-time assistance time is crucial for the safety and accurate control of lower-limb exoskeletons. To solve the problem of predicting exoskeleton assistance time, this paper proposes a gait recognition model based on inertial measurement units that combines the real-time motion state recognition of support vector machines and phase recognition of long short-term memory networks. A recognition validation experiment was conducted on 30 subjects to determine the reliability of the gait recognition model. The results showed that the accuracy of motion state and gait phase were 99.98% and 98.26%, respectively. Based on the proposed SVM-LSTM gait model, exoskeleton assistance time was predicted. A test was conducted on 10 subjects, and the results showed that using assistive therapy based on exercise status and gait stage can significantly improve gait movement and reduce metabolic costs by an average of more than 10%.
]]>Bioengineering doi: 10.3390/bioengineering11030274
Authors: Giorgio Novelli Andrea Filippi Andrea Cartocci Sergio Mirabella Marco Talarico Elena De Ponti Maria Costanza Meazzini Davide Sozzi Gabriele Canzi Marco Anghileri
Mandibular fractures are very common in maxillofacial trauma surgery. While previous studies have focused on possible risk factors related to post-operative complications, none have tried to identify pre-existing conditions that may increase the risk of mandibular fractures. We hypothesized, through clinical observation, that anatomical conditions involving poor dental contacts, such as malocclusions, may increase the risk of mandibular fractures. This work was subdivided into two parts. In the first part, Digital Imaging and Communications in Medicine (DICOM) data of four healthy patients characterized by different dentoskeletal occlusions (class I, class II, class III, and anterior open bite) have been used to develop four finite element models (FEMs) that accurately reproduce human bone structure. A vertical and lateral impact have been simulated at increasing speed on each model, analyzing the force distribution within the mandibular bone. Both vertical and lateral impact showed higher level of stress at the impact point and in the condylar area in models characterized by malocclusion. Specifically, the class III and the open bite models, at the same speed of impact, had higher values for a longer period, reaching critical stress levels that are correlated with mandibular fracture, while normal occlusion seems to be a protective condition. In the second part of this study, the engineering results were validated through the comparison with a sample of patients previously treated for mandibular fracture. Data from 223 mandibular fractures, due to low-energy injuries, were retrospectively collected to evaluate a possible correlation between pre-existing malocclusion and fracture patterns, considering grade of displacement, numbers of foci, and associated CFI score. Patients were classified, according to their occlusion, into Class I, Class II, Class III, and anterior open bite or poor occlusal contact (POC). Class I patients showed lower frequencies of fracture than class II, III, and open bite or POC patients. Class I was associated with displaced fractures in 16.1% of cases, class II in 47.1%, class III in 48.8% and open bite/POC in 65.2% of cases (p-value < 0.0001). In class I patients we observed a single non-displaced fracture in 51.6% of cases, compared to 12.9% of Class II, 19.5% of Class III and 22.7% of the open bite/POC group. Our analysis shows that class I appears to better dissipate forces applied on the mandible in low-energy injuries. A higher number of dental contacts showed a lower rate of multifocal and displaced fractures, mitigating the effect of direct forces onto the bone. The correlation between clinical data and virtual simulation on FEM models seems to point out that virtual simulation successfully predicts fracture patterns and risk of association with different type of occlusion. Better knowledge of biomechanics and force dissipation on the human body may lead to the development of more effective safety devices, and help select patients to plan medical, orthodontic/dental, and/or surgical intervention to prevent injuries.
]]>Bioengineering doi: 10.3390/bioengineering11030273
Authors: Kenji Yoshitsugu Eisuke Shimizu Hiroki Nishimura Rohan Khemlani Shintaro Nakayama Tadamasa Takemura
Ophthalmological services face global inadequacies, especially in low- and middle-income countries, which are marked by a shortage of practitioners and equipment. This study employed a portable slit lamp microscope with video capabilities and cloud storage for more equitable global diagnostic resource distribution. To enhance accessibility and quality of care, this study targets corneal opacity, which is a global cause of blindness. This study has two purposes. The first is to detect corneal opacity from videos in which the anterior segment of the eye is captured. The other is to develop an AI pipeline to detect corneal opacities. First, we extracted image frames from videos and processed them using a convolutional neural network (CNN) model. Second, we manually annotated the images to extract only the corneal margins, adjusted the contrast with CLAHE, and processed them using the CNN model. Finally, we performed semantic segmentation of the cornea using annotated data. The results showed an accuracy of 0.8 for image frames and 0.96 for corneal margins. Dice and IoU achieved a score of 0.94 for semantic segmentation of the corneal margins. Although corneal opacity detection from video frames seemed challenging in the early stages of this study, manual annotation, corneal extraction, and CLAHE contrast adjustment significantly improved accuracy. The incorporation of manual annotation into the AI pipeline, through semantic segmentation, facilitated high accuracy in detecting corneal opacity.
]]>Bioengineering doi: 10.3390/bioengineering11030272
Authors: Ji-Ho Ahn Young-Jun Lim Jungwon Lee Yeon-Wha Baek Myung-Joo Kim Ho-Beom Kwon
Narrow-diameter implants (NDI) serve as a solution for treating limited bone volume in the anterior mandible. This study aimed to evaluate the one-year clinical outcomes of various NDIs in the mandibular incisor area after immediate loading in partially edentulous patients. This single-center, prospective, single-blinded, randomized controlled trial study included 21 patients, with 7 patients in each of the following groups: control (BLT NC SLActive®; Straumann), experimental group 1 (CMI IS-III Active® S-Narrow; Neobiotech), and experimental group 2 (CMI IS-III Active® Narrow; Neobiotech). Using full digital flow, two fixtures were placed in each patient and immediately provisionalized on the day of surgery. Evaluations encompassed periapical radiographs, implant stability quotient (ISQ), implant stability test (IST) readings, per-implant soft tissue health, patient satisfaction surveys, and esthetic score assessments. Definitive prostheses were delivered twelve weeks post-surgery (CRiS, number: KCT0007300). Following exclusions due to low stability values (n = 2), fixture failure (n = 5), and voluntary withdrawal (n = 1), the implant success rate for patients completing all clinical protocols stood at 100%. The resulting patient failure rates in the control, experimental group 1, and experimental group 2 were 50.0%, 42.9%, and 14.3%, respectively. There were no significant differences between the groups in terms of marginal bone loss, soft tissue health, patient satisfaction, and esthetic scores. Narrow implants showed superior clinical outcomes, followed by S-Narrow and Straumann implants. Calculated one-year survival rates at the implant level were 66.7% for the control group, 85.7% for experimental group 1, and 100% for experimental group 2. All three types of NDIs showed acceptable clinical and radiographic results during the year-long observation period.
]]>Bioengineering doi: 10.3390/bioengineering11030271
Authors: Sang Beom Han Yu-Chi Liu Chang Liu Jodhbir S. Mehta
Fuchs endothelial corneal dystrophy (FECD) is a complex genetic disorder characterized by the slow and progressive degeneration of corneal endothelial cells. Thus, it may result in corneal endothelial decompensation and irreversible corneal edema. Moreover, FECD is associated with alterations in all corneal layers, such as thickening of the Descemet membrane, stromal scarring, subepithelial fibrosis, and the formation of epithelial bullae. Hence, anterior segment imaging devices that enable precise measurement of functional and anatomical changes in the cornea are essential for the management of FECD. In this review, the authors will introduce studies on the application of various imaging modalities, such as anterior segment optical coherence tomography, Scheimpflug corneal tomography, specular microscopy, in vitro confocal microscopy, and retroillumination photography, in the diagnosis and monitoring of FECD and discuss the results of these studies. The application of novel technologies, including image processing technology and artificial intelligence, that are expected to further enhance the accuracy, precision, and speed of the imaging technologies will also be discussed.
]]>Bioengineering doi: 10.3390/bioengineering11030269
Authors: Aurèle Goetz Pablo Jeken-Rico Yves Chau Jacques Sédat Aurélien Larcher Elie Hachem
Computational fluid dynamics is intensively used to deepen our understanding of aneurysm growth and rupture in an attempt to support physicians during therapy planning. Numerous studies assumed fully rigid vessel walls in their simulations, whose sole haemodynamics may fail to provide a satisfactory criterion for rupture risk assessment. Moreover, direct in vivo observations of intracranial aneurysm pulsation were recently reported, encouraging the development of fluid–structure interaction for their modelling and for new assessments. In this work, we describe a new fluid–structure interaction functional setting for the careful evaluation of different aneurysm shapes. The configurations consist of three real aneurysm domes positioned on a toroidal channel. All geometric features, employed meshes, flow quantities, comparisons with the rigid wall model and corresponding plots are provided for the sake of reproducibility. The results emphasise the alteration of flow patterns and haemodynamic descriptors when wall deformations were taken into account compared with a standard rigid wall approach, thereby underlining the impact of fluid–structure interaction modelling.
]]>Bioengineering doi: 10.3390/bioengineering11030270
Authors: Luoyi Kong Mohan Huang Lingfeng Zhang Lawrence Wing Chi Chan
Medical imaging serves as a crucial tool in current cancer diagnosis. However, the quality of medical images is often compromised to minimize the potential risks associated with patient image acquisition. Computer-aided diagnosis systems have made significant advancements in recent years. These systems utilize computer algorithms to identify abnormal features in medical images, assisting radiologists in improving diagnostic accuracy and achieving consistency in image and disease interpretation. Importantly, the quality of medical images, as the target data, determines the achievable level of performance by artificial intelligence algorithms. However, the pixel value range of medical images differs from that of the digital images typically processed via artificial intelligence algorithms, and blindly incorporating such data for training can result in suboptimal algorithm performance. In this study, we propose a medical image-enhancement scheme that integrates generic digital image processing and medical image processing modules. This scheme aims to enhance medical image data by endowing them with high-contrast and smooth characteristics. We conducted experimental testing to demonstrate the effectiveness of this scheme in improving the performance of a medical image segmentation algorithm.
]]>Bioengineering doi: 10.3390/bioengineering11030268
Authors: Atefeh Ebrahimian Mona Schalk Mark Dürkop Michael Maurer Rudolf Bliem Harald Kühnel
Microcarrier-based cell culture is a commonly used method to facilitate the growth of anchorage-dependent cells like MA 104 for antigen manufacturing. However, conventionally, static cell culture is employed for cell propagation before seeding the production bioreactor with microcarriers (MCs). This study demonstrates the effective replacement of the conventional method by serial subculturing on MCs with in situ cell detachment under optimal conditions in closed culture units. This study proves that MA 104 can be subcultured at least five times on Cytodex 1 MC without the need for separating cells and MC after cell harvest. Process parameters impacting cell growth were studied post in situ cell detachment in a scaled-down model. Optimization, using augmented Design of Experiments (DoE) combined with hybrid modeling, facilitated rapid screening of the design space for critical process parameters (CPPs). Optimized conditions included an inoculation density of >16 cells/bead, 3.5–4.5 g/L of Cytodex 1, and a controlled agitation speed, starting at Njs (minimum agitation speed) for the first day with a maximum increase of 25% thereafter. With these design spaces for CPPs, a cell density of 2.6 ± 0.5 × 106 cells/mL was achieved after five days. This refined bioprocess methodology offers a reliable and efficient approach for seed training in stirred tank reactors, which is particularly beneficial for viral vaccine production.
]]>Bioengineering doi: 10.3390/bioengineering11030267
Authors: Ana Isabel Sousa Carlos Marques-Neves Pedro Manuel Vieira
Chromatic Pupillometry, used to assess Pupil Light Reflex (PLR) to a coloured light stimulus, has regained interest since the discovery of melanopsin in the intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). This technique has shown the potential to be used as a screening tool for neuro-ophthalmological diseases; however, most of the pupillometers available are expensive and not portable, making it harder for them to be used as a widespread screening tool. In this study, we developed a smartphone-based system for chromatic pupillometry that allows targeted stimulation of the ipRGCs. Using a smartphone, this system is portable and accessible and takes advantage of the location of the ipRGCs in the perifovea. The system incorporates a 3D-printed support for the smartphone and an illumination system. Preliminary tests were carried out on a single individual and then validated on eleven healthy individuals with two different LED intensities. The average Post-Illumination Pupil Light Response 6 s after the stimuli offsets (PIPR-6s) showed a difference between the blue and the red stimuli of 9.5% for both intensities, which aligns with the studies using full-field stimulators. The results validated this system for a targeted stimulation of the ipRGCs for chromatic pupillometry, with the potential to be a portable and accessible screening tool for neuro-ophthalmological diseases.
]]>Bioengineering doi: 10.3390/bioengineering11030266
Authors: Usharani Bhimavarapu Nalini Chintalapudi Gopi Battineni
There is no doubt that brain tumors are one of the leading causes of death in the world. A biopsy is considered the most important procedure in cancer diagnosis, but it comes with drawbacks, including low sensitivity, risks during biopsy treatment, and a lengthy wait for results. Early identification provides patients with a better prognosis and reduces treatment costs. The conventional methods of identifying brain tumors are based on medical professional skills, so there is a possibility of human error. The labor-intensive nature of traditional approaches makes healthcare resources expensive. A variety of imaging methods are available to detect brain tumors, including magnetic resonance imaging (MRI) and computed tomography (CT). Medical imaging research is being advanced by computer-aided diagnostic processes that enable visualization. Using clustering, automatic tumor segmentation leads to accurate tumor detection that reduces risk and helps with effective treatment. This study proposed a better Fuzzy C-Means segmentation algorithm for MRI images. To reduce complexity, the most relevant shape, texture, and color features are selected. The improved Extreme Learning machine classifies the tumors with 98.56% accuracy, 99.14% precision, and 99.25% recall. The proposed classifier consistently demonstrates higher accuracy across all tumor classes compared to existing models. Specifically, the proposed model exhibits accuracy improvements ranging from 1.21% to 6.23% when compared to other models. This consistent enhancement in accuracy emphasizes the robust performance of the proposed classifier, suggesting its potential for more accurate and reliable brain tumor classification. The improved algorithm achieved accuracy, precision, and recall rates of 98.47%, 98.59%, and 98.74% on the Fig share dataset and 99.42%, 99.75%, and 99.28% on the Kaggle dataset, respectively, which surpasses competing algorithms, particularly in detecting glioma grades. The proposed algorithm shows an improvement in accuracy, of approximately 5.39%, in the Fig share dataset and of 6.22% in the Kaggle dataset when compared to existing models. Despite challenges, including artifacts and computational complexity, the study’s commitment to refining the technique and addressing limitations positions the improved FCM model as a noteworthy advancement in the realm of precise and efficient brain tumor identification.
]]>Bioengineering doi: 10.3390/bioengineering11030265
Authors: Heejoo Lim Yoonji Joo Eunji Ha Yumi Song Sujung Yoon Taehoon Shin
Convolutional neural networks (CNNs) have been used widely to predict biological brain age based on brain magnetic resonance (MR) images. However, CNNs focus mainly on spatially local features and their aggregates and barely on the connective information between distant regions. To overcome this issue, we propose a novel multi-hop graph attention (MGA) module that exploits both the local and global connections of image features when combined with CNNs. After insertion between convolutional layers, MGA first converts the convolution-derived feature map into graph-structured data by using patch embedding and embedding-distance-based scoring. Multi-hop connections between the graph nodes are modeled by using the Markov chain process. After performing multi-hop graph attention, MGA re-converts the graph into an updated feature map and transfers it to the next convolutional layer. We combined the MGA module with sSE (spatial squeeze and excitation)-ResNet18 for our final prediction model (MGA-sSE-ResNet18) and performed various hyperparameter evaluations to identify the optimal parameter combinations. With 2788 three-dimensional T1-weighted MR images of healthy subjects, we verified the effectiveness of MGA-sSE-ResNet18 with comparisons to four established, general-purpose CNNs and two representative brain age prediction models. The proposed model yielded an optimal performance with a mean absolute error of 2.822 years and Pearson’s correlation coefficient (PCC) of 0.968, demonstrating the potential of the MGA module to improve the accuracy of brain age prediction.
]]>Bioengineering doi: 10.3390/bioengineering11030264
Authors: Deqiang Deng Tianli Hao Lisen Lu Muyang Yang Zhen Zeng Jonathan F. Lovell Yushuai Liu Honglin Jin
Currently, immunotherapy is one of the most effective treatment strategies for cancer. However, the efficacy of any specific anti-tumor immunotherapy can vary based on the dynamic characteristics of immune cells, such as their rate of migration and cell-to-cell interactions. Therefore, understanding the dynamics among cells involved in the immune response can inform the optimization and improvement of existing immunotherapy strategies. In vivo imaging technologies use optical microscopy techniques to visualize the movement and behavior of cells in vivo, including cells involved in the immune response, thereby showing great potential for application in the field of cancer immunotherapy. In this review, we briefly introduce the technical aspects required for in vivo imaging, such as fluorescent protein labeling, the construction of transgenic mice, and various window chamber models. Then, we discuss the elucidation of new phenomena and mechanisms relating to tumor immunotherapy that has been made possible by the application of in vivo imaging technology. Specifically, in vivo imaging has supported the characterization of the movement of T cells during immune checkpoint inhibitor therapy and the kinetic analysis of dendritic cell migration in tumor vaccine therapy. Finally, we provide a perspective on the challenges and future research directions for the use of in vivo imaging technology in cancer immunotherapy.
]]>Bioengineering doi: 10.3390/bioengineering11030263
Authors: Erfaneh Gharavi Nathan J. LeRoy Guangtao Zheng Aidong Zhang Donald E. Brown Nathan C. Sheffield
As available genomic interval data increase in scale, we require fast systems to search them. A common approach is simple string matching to compare a search term to metadata, but this is limited by incomplete or inaccurate annotations. An alternative is to compare data directly through genomic region overlap analysis, but this approach leads to challenges like sparsity, high dimensionality, and computational expense. We require novel methods to quickly and flexibly query large, messy genomic interval databases. Here, we develop a genomic interval search system using representation learning. We train numerical embeddings for a collection of region sets simultaneously with their metadata labels, capturing similarity between region sets and their metadata in a low-dimensional space. Using these learned co-embeddings, we develop a system that solves three related information retrieval tasks using embedding distance computations: retrieving region sets related to a user query string, suggesting new labels for database region sets, and retrieving database region sets similar to a query region set. We evaluate these use cases and show that jointly learned representations of region sets and metadata are a promising approach for fast, flexible, and accurate genomic region information retrieval.
]]>Bioengineering doi: 10.3390/bioengineering11030262
Authors: Roxana Iacob Emil Radu Iacob Emil Robert Stoicescu Delius Mario Ghenciu Daiana Marina Cocolea Amalia Constantinescu Laura Andreea Ghenciu Diana Luminita Manolescu
Breast cancer, affecting both genders, but mostly females, exhibits shifting demographic patterns, with an increasing incidence in younger age groups. Early identification through mammography, clinical examinations, and breast self-exams enhances treatment efficacy, but challenges persist in low- and medium-income countries due to limited imaging resources. This review assesses the feasibility of employing breast ultrasound as the primary breast cancer screening method, particularly in resource-constrained regions. Following the PRISMA guidelines, this study examines 52 publications from the last five years. Breast ultrasound, distinct from mammography, offers advantages like radiation-free imaging, suitability for repeated screenings, and preference for younger populations. Real-time imaging and dense breast tissue evaluation enhance sensitivity, accessibility, and cost-effectiveness. However, limitations include reduced specificity, operator dependence, and challenges in detecting microcalcifications. Automatic breast ultrasound (ABUS) addresses some issues but faces constraints like potential inaccuracies and limited microcalcification detection. The analysis underscores the need for a comprehensive approach to breast cancer screening, emphasizing international collaboration and addressing limitations, especially in resource-constrained settings. Despite advancements, notably with ABUS, the primary goal is to contribute insights for optimizing breast cancer screening globally, improving outcomes, and mitigating the impact of this debilitating disease.
]]>Bioengineering doi: 10.3390/bioengineering11030261
Authors: Aline Grein-Iankovski Karina Andrighetti de Oliveira Braga Daniel Formariz Legendre Paulo Francisco Guerreiro Cardoso Watson Loh
Cilia are biological structures essential to drive the mobility of secretions and maintain the proper function of the respiratory airways. However, this motile self-cleaning process is significantly compromised in the presence of silicone tracheal prosthesis, leading to biofilm growth and impeding effective treatment. To address this challenge and enhance the performance of these devices, we propose the fabrication of magnetic silicone cilia, with the prospect of their integration onto silicone prostheses. The present study presents a fabrication method based on magnetic self-assembly and assesses the interaction behavior of the cilia array with biological mucus. This protocol allows for the customization of cilia dimensions across a wide range of aspect ratios (from 6 to 85) and array densities (from 10 to 80 cilia/mm2) by adjusting the fabrication parameters, offering flexibility for adjustments according to their required characteristics. Furthermore, we evaluated the suitability of different cilia arrays for biomedical applications by analyzing their interaction with bullfrog mucus, simulating the airways environment. Our findings demonstrate that the fabricated cilia are mechanically resistant to the viscous fluid and still exhibit controlled movement under the influence of an external moving magnet. A correlation between cilia dimensions and mucus wettability profile suggests a potential role in facilitating mucus depuration, paving the way for further advancements aimed at enhancing the performance of silicone prostheses in clinical settings.
]]>Bioengineering doi: 10.3390/bioengineering11030260
Authors: Xi Yang Chengpeng Chai Hongzhi Zuo Yun-Hsuan Chen Junhui Shi Cheng Ma Mohamad Sawan
Optical-based imaging has improved from early single-location research to further sophisticated imaging in 2D topography and 3D tomography. These techniques have the benefit of high specificity and non-radiative safety for brain detection and therapy. However, their performance is limited by complex tissue structures. To overcome the difficulty in successful brain imaging applications, we conducted a simulation using 16 optical source types within a brain model that is based on the Monte Carlo method. In addition, we propose an evaluation method of the optical propagating depth and resolution, specifically one based on the optical distribution for brain applications. Based on the results, the best optical source types were determined in each layer. The maximum propagating depth and corresponding source were extracted. The optical source propagating field width was acquired in different depths. The maximum and minimum widths, as well as the corresponding source, were determined. This paper provides a reference for evaluating the optical propagating depth and resolution from an optical simulation aspect, and it has the potential to optimize the performance of optical-based techniques.
]]>Bioengineering doi: 10.3390/bioengineering11030259
Authors: Manjusha Annaji Nur Mita Ishwor Poudel Sai H. S. Boddu Oladiran Fasina R. Jayachandra Babu
Despite rapid progress in tissue engineering, the repair and regeneration of bone defects remains challenging, especially for non-homogenous and complicated defects. We have developed and characterized biodegradable drug-eluting scaffolds for bone regeneration utilizing direct powder extrusion-based three-dimensional (3D) printing techniques. The PLGA scaffolds were fabricated using poly (lactic-co-glycolic acid) (PLGA) with inherent viscosities of 0.2 dl/g and 0.4 dl/g and ketoprofen. The effect of parameters such as the infill, geometry, and wall thickness of the drug carrier on the release kinetics of ketoprofen was studied. The release studies revealed that infill density significantly impacts the release performance, where 10% infill showed faster and almost complete release of the drug, whereas 50% infill demonstrated a sustained release. The Korsmeyer–Peppas model showed the best fit for release data irrespective of the PLGA molecular weight and infill density. It was demonstrated that printing parameters such as infill density, scaffold wall thickness, and geometry played an important role in controlling the release and, therefore, in designing customized drug-eluting scaffolds for bone regeneration.
]]>Bioengineering doi: 10.3390/bioengineering11030258
Authors: Pei L. Robins Sergey N. Makaroff Michael Dib Sarah H. Lisanby Zhi-De Deng
Neurostimulation devices that use rotating permanent magnets are being explored for their potential therapeutic benefits in patients with psychiatric and neurological disorders. This study aims to characterize the electric field (E-field) for ten configurations of rotating magnets using finite element analysis and phantom measurements. Various configurations were modeled, including single or multiple magnets, and bipolar or multipolar magnets, rotated at 10, 13.3, and 350 revolutions per second (rps). E-field strengths were also measured using a hollow sphere (r=9.2 cm) filled with a 0.9% sodium chloride solution and with a dipole probe. The E-field spatial distribution is determined by the magnets’ dimensions, number of poles, direction of the magnetization, and axis of rotation, while the E-field strength is determined by the magnets’ rotational frequency and magnetic field strength. The induced E-field strength on the surface of the head ranged between 0.0092 and 0.52 V/m. In the range of rotational frequencies applied, the induced E-field strengths were approximately an order or two of magnitude lower than those delivered by conventional transcranial magnetic stimulation. The impact of rotational frequency on E-field strength represents a confound in clinical trials that seek to tailor rotational frequency to individual neural oscillations. This factor could explain some of the variability observed in clinical trial outcomes.
]]>Bioengineering doi: 10.3390/bioengineering11030257
Authors: Pei-An Lee Clark DuMontier Wanting Yu Levi Ask Junhong Zhou Marcia A. Testa Dae Kim Gregory Abel Tom Travison Brad Manor On-Yee Lo
The four-meter gait speed (4MGS) is a recommended physical performance test in older adults but is challenging to implement clinically. We developed a smartphone application (App) with a four-meter ribbon for remote 4MGS testing at home. This study aimed to assess the validity and reliability of this smartphone App-based assessment of the home 4MGS. We assessed the validity of the smartphone App by comparing it against a gold standard video assessment of the 4MGS conducted by study staff visiting community-dwelling older adults and against the stopwatch-based measurement. Moreover, we assessed the test–retest reliability in two supervised sessions and three additional sessions performed by the participants independently, without staff supervision. The 4MGS measured by the smartphone App was highly correlated with video-based 4MGS (r = 0.94), with minimal differences (mean = 0.07 m/s, ± 1.96 SD = 0.12) across a range of gait speeds. The test–retest reliability for the smartphone App 4MGS was high (ICC values: 0.75 to 0.93). The home 4MGS in older adults can be measured accurately and reliably using a smartphone in the pants pocket and a four-meter strip of ribbon. Leveraging existing technology carried by a significant portion of the older adult population could overcome barriers in busy clinical settings for this well-established objective mobility test.
]]>Bioengineering doi: 10.3390/bioengineering11030256
Authors: Itay Barnea Lior Luria Arik Girsault Ofira Dabah Matan Dudaie Simcha K. Mirsky Drorit Merkel Natan T. Shaked
Myelodysplastic syndromes (MDSs) are a group of potentially deadly diseases that affect the morphology and function of neutrophils. Rapid diagnosis of MDS is crucial for the initiation of treatment that can vastly improve disease outcome. In this work, we present a new approach for detecting morphological differences between neutrophils isolated from blood samples of high-risk MDS patients and blood bank donors (BBDs). Using fluorescent flow cytometry, neutrophils were stained with 2′,7′-dichlorofluorescin diacetate (DCF), which reacts with reactive oxygen species (ROS), and Hoechst, which binds to DNA. We observed that BBDs possessed two cell clusters (designated H and L), whereas MDS patients possessed a single cluster (L). Later, we used FACS to sort the H and the L cells and used interferometric phase microscopy (IPM) to image the cells without utilizing cell staining. IPM images showed that H cells are characterized by low optical path delay (OPD) in the nucleus relative to the cytoplasm, especially in cell vesicles containing ROS, whereas L cells are characterized by low OPD in the cytoplasm relative to the nucleus and no ROS-containing vesicles. Moreover, L cells present a higher average OPD and dry mass compared to H cells. When examining neutrophils from MDS patients and BBDs by IPM during flow, we identified ~20% of cells as H cells in BBDs in contrast to ~4% in MDS patients. These results indicate that IPM can be utilized for the diagnosis of complex hematological pathologies such as MDS.
]]>Bioengineering doi: 10.3390/bioengineering11030255
Authors: Olfa Ben Moussa Louise Parveau Inès Aouimeur Grégory Egaud Corantin Maurin Sofiane Fraine Sébastien Urbaniak Chantal Perrache Zhiguo He Sedao Xxx Oliver Dorado Cortez Sylvain Poinard Cyril Mauclair Philippe Gain Gilles Thuret
The bioengineering of corneal endothelial grafts consists of seeding in vitro cultured corneal endothelial cells onto a thin, transparent, biocompatible, and sufficiently robust carrier which can withstand surgical manipulations. This is one of the most realistic alternatives to donor corneas, which are in chronic global shortage. The anterior capsule of the crystalline lens has already been identified as one of the best possible carriers, but its challenging manual preparation has limited its use. In this study, we describe a femtosecond laser cutting process of the anterior capsule of whole lenses in order to obtain capsule discs of 8 mm diameter, similar to conventional endothelial grafts. Circular marks made on the periphery of the disc indicate its orientation. Immersion in water for 3 days is sufficient to completely remove the lens epithelial cells and to enable the seeding of corneal endothelial cells, which remain viable after 27 days of culture. Therefore, this method provides a transparent, decellularized disc ready to form viable tissue engineered endothelial grafts.
]]>Bioengineering doi: 10.3390/bioengineering11030254
Authors: Ritipong Wongkhuenkaew Sansanee Auephanwiriyakul Marasri Chaiworawitkul Nipon Theera-Umpon Uklid Yeesarapat
Three-dimensional registration with the affine transform is one of the most important steps in 3D reconstruction. In this paper, the modified grey wolf optimizer with behavior considerations and dimensional learning (BCDL-GWO) algorithm as a registration method is introduced. To refine the 3D registration result, we incorporate the iterative closet point (ICP). The BCDL-GWO with ICP method is implemented on the scanned commercial orthodontic tooth and regular tooth models. Since this is a registration from multi-views of optical images, the hierarchical structure is implemented. According to the results for both models, the proposed algorithm produces high-quality 3D visualization images with the smallest mean squared error of about 7.2186 and 7.3999 μm2, respectively. Our results are compared with the statistical randomization-based particle swarm optimization (SR-PSO). The results show that the BCDL-GWO with ICP is better than those from the SR-PSO. However, the computational complexities of both methods are similar.
]]>Bioengineering doi: 10.3390/bioengineering11030253
Authors: Sarah Al-Maawi Eva Dohle Robert Sader Shahram Ghanaati
Platelet-rich fibrin (PRF) has assumed an important role in supporting tissue regeneration in different fields. To date, the standard protocol for liquid PRF requires at least 10 mL of peripheral blood. The present study aimed to analyze the composition, growth factor release, and effects on the cell proliferation of PRF samples produced using 3 mL vs. 10 mL of peripheral blood in vitro. Peripheral venous blood from six healthy donors was used to prepare liquid PRF using either 3 mL or 10 mL tubes. Three different centrifugation protocols were used according to the low-speed centrifugation concept. The cellular distribution was evaluated using immunohistology and automated cell count. ELISA was used to determine the release of different growth factors (EGF, TGF-β1, and PDGF) and interleukin 8 at different time points. Primary human osteoblasts (pOBs) were cultivated for 7 days using PRF-conditioned media acquired from either 3 mL or 10 mL of peripheral blood. The results showed that 3 mL of peripheral blood is sufficient to produce a liquid PRF concentrate similar to that acquired when using 10 mL blood. The concentrations of platelets and leukocytes were comparable regardless of the initial blood volume (3 mL vs. 10 mL). Similarly, the release of growth factors (EGF, TGF-β1, and PDGF) and interleukin 8 was often comparable in both groups over 7 days. The cultivation of pOBs using PRF-conditioned media showed a similar proliferation rate regardless of the initial blood volume. This proliferation rate was also similar to that of pOBs treated with 20% FBS-conditioned media. These findings validated the use of 3 mL of peripheral blood to generate liquid PRF matrices according to the low-speed centrifugation concept, which may open new application fields for research purposes such as in vivo experiments and clinical applications such as pediatric surgery.
]]>Bioengineering doi: 10.3390/bioengineering11030252
Authors: Taimoor Shakeel Sheikh Migyung Cho
The histopathological segmentation of nuclear types is a challenging task because nuclei exhibit distinct morphologies, textures, and staining characteristics. Accurate segmentation is critical because it affects the diagnostic workflow for patient assessment. In this study, a framework was proposed for segmenting various types of nuclei from different organs of the body. The proposed framework improved the segmentation performance for each nuclear type using radiomics. First, we used distinct radiomic features to extract and analyze quantitative information about each type of nucleus and subsequently trained various classifiers based on the best input sub-features of each radiomic feature selected by a LASSO operator. Second, we inputted the outputs of the best classifier to various segmentation models to learn the variants of nuclei. Using the MoNuSAC2020 dataset, we achieved state-of-the-art segmentation performance for each category of nuclei type despite the complexity, overlapping, and obscure regions. The generalized adaptability of the proposed framework was verified by the consistent performance obtained in whole slide images of different organs of the body and radiomic features.
]]>Bioengineering doi: 10.3390/bioengineering11030251
Authors: Chun-Hong Cheng Zhikun Yuen Shutao Chen Kwan-Long Wong Jing-Wei Chin Tsz-Tai Chan Richard H. Y. So
Blood oxygen saturation (SpO2) is an essential physiological parameter for evaluating a person’s health. While conventional SpO2 measurement devices like pulse oximeters require skin contact, advanced computer vision technology can enable remote SpO2 monitoring through a regular camera without skin contact. In this paper, we propose novel deep learning models to measure SpO2 remotely from facial videos and evaluate them using a public benchmark database, VIPL-HR. We utilize a spatial–temporal representation to encode SpO2 information recorded by conventional RGB cameras and directly pass it into selected convolutional neural networks to predict SpO2. The best deep learning model achieves 1.274% in mean absolute error and 1.71% in root mean squared error, which exceed the international standard of 4% for an approved pulse oximeter. Our results significantly outperform the conventional analytical Ratio of Ratios model for contactless SpO2 measurement. Results of sensitivity analyses of the influence of spatial–temporal representation color spaces, subject scenarios, acquisition devices, and SpO2 ranges on the model performance are reported with explainability analyses to provide more insights for this emerging research field.
]]>Bioengineering doi: 10.3390/bioengineering11030250
Authors: Leo Yan Li-Han Moshe Eizenman Runjie Bill Shi Yvonne M. Buys Graham E. Trope Willy Wong
Perimetry and optical coherence tomography (OCT) are both used to monitor glaucoma progression. However, combining these modalities can be a challenge due to differences in data types. To overcome this, we have developed an autoencoder data fusion (AEDF) model to learn compact encoding (AE-fused data) from both perimetry and OCT. The AEDF model, optimized specifically for visual field (VF) progression detection, incorporates an encoding loss to ensure the interpretation of the AE-fused data is similar to VF data while capturing key features from OCT measurements. For model training and evaluation, our study included 2504 longitudinal VF and OCT tests from 140 glaucoma patients. VF progression was determined from linear regression slopes of longitudinal mean deviations. Progression detection with AE-fused data was compared to VF-only data (standard clinical method) as well as data from a Bayesian linear regression (BLR) model. In the initial 2-year follow-up period, AE-fused data achieved a detection F1 score of 0.60 (95% CI: 0.57 to 0.62), significantly outperforming (p < 0.001) the clinical method (0.45, 95% CI: 0.43 to 0.47) and the BLR model (0.48, 95% CI: 0.45 to 0.51). The capacity of the AEDF model to generate clinically interpretable fused data that improves VF progression detection makes it a promising data integration tool in glaucoma management.
]]>Bioengineering doi: 10.3390/bioengineering11030249
Authors: Tianyuan Guan Rigwed Tatu Koffi Wima Marc Oria Jose L. Peiro Chia-Ying Lin Marepalli. B. Rao
A biodegradable hybrid polymer patch was invented at the University of Cincinnati to cover gaps on the skin over the spinal column of a growing fetus, characterized by the medical condition spina bifida. The inserted patch faces amniotic fluid (AF) on one side and cerebrospinal fluid on the other side. The goal is to provide a profile of the roughness of a patch over time at 0, 4, 8, 12, and 16 weeks with a 95% confidence band. The patch is soaked in a test tube filled with either amniotic fluid (AF) or phosphate-buffered saline (PBS) in the lab. If roughness is measured at any time point for a patch, the patch is destroyed. Thus, it is impossible to measure roughness at all weeks of interest for any patch. It is important to assess the roughness of a patch because the rougher the patch is, the faster the skin grows under the patch. We use a model-based approach with Monte Carlo simulations to estimate the profile over time with a 95% confidence band. The roughness profiles are similar with both liquids. The profile can be used as a template for future experiments on the composition of patches.
]]>Bioengineering doi: 10.3390/bioengineering11030248
Authors: Wei-Hsuan Lin Tsung-Yu Huang Shu-Wei Chen Joseph Hamill Jung-Tang Kung Wen-Tzu Tang
This study investigates the influence of the quality of the “deep squat” movement, adapted from the Functional Movement Screen (FMS) system, on the lower extremity movement pattern during baseball throwing, and its potential impact on throwing performance and propulsion efficiency. Twenty-two baseball players were recruited and categorized into two groups: 13 in the high-score squat group (HSS) and 9 in the low-score squat group (LSS), based on their deep squat screening results. This research explored disparities in ball velocity, propulsion efficiency, propulsion ground reaction force (GRF) characteristics, and throwing kinematics between these two groups. The findings revealed no significant difference in ball velocity between the groups. However, the LSS group demonstrated a lower propulsion GRF efficiency (p < 0.030, ES = 0.46), along with a higher vertical peak GRF (p < 0.002, ES = 0.66). In the pivot leg, the HSS group exhibited significantly lower impulse forces in the Impulse Fresultant (p < 0.035, ES = 0.45), throwing direction (p < 0.049, ES = 0.42), and vertical direction (p < 0.048, ES = 0.42). Additionally, the contribution to the ball velocity of the pivot leg was significantly greater in the HSS group, along with significantly better efficiency in Impulse Fresultant (p < 0.035, ES = 0.45), throwing direction (p < 0.053, ES = 0.41), and vertical direction (p < 0.032, ES = 0.46). In the leading leg, the HSS group demonstrated significantly lower impulse forces in the Impulse Fresultant (p < 0.001, ES = 0.69), throwing direction (p < 0.007, ES = 0.58), and vertical direction (p < 0.001, ES = 0.70). Moreover, the contribution to the ball velocity of the leading leg was significantly greater in the HSS group, accompanied by significantly better efficiency in Impulse Fresultant (p < 0.003, ES = 0.63), throwing direction (p < 0.005, ES = 0.60), and vertical direction (p < 0.021, ES = 0.49). In conclusion, this study suggests that squat screening is a valuable tool for assessing propulsion efficiency. Coaches and trainers should be mindful of players with low squat quality but high throwing performance, as they may face increased impact and injury risks in the future.
]]>Bioengineering doi: 10.3390/bioengineering11030247
Authors: Alexander Nemeth Bruno Vasconcelos Gurgel Adam Lowenstein Luiz Juliasse Rafael S. Siroma Zoe Zhu Jamil Awad Shibli Carlos Fernando Mourão
Temporomandibular joint disorders (TMDs) are prevalent musculoskeletal conditions involving pain and dysfunction of jaw mobility and function, which have proven difficult to treat satisfactorily. The present study aimed to assess the effectiveness of a liquid platelet-rich fibrin (i-PRF) infusion during arthrocentesis versus other options using coadjuvant materials to reduce TMD symptoms. A literature search was conducted using PubMed, EMBASE, Web of Science, Scopus, and ClinicalTrials.gov for RCTs published before January 2024, comparing i-PRF to any other TMD treatment. This systematic review was registered on PROSPERO (CRD42023495364). The searches generated several recent RCTs that compared i-PRF injection combined with arthrocentesis (AC) to AC-only or AC with platelet-rich plasma (PRP). The outcomes analyzed included measures of pain (visual analog scale, VAS), maximum mouth opening, joint sounds, and MRI-verified changes in joint structure. Across the RCTs, the addition of i-PRF injection to AC resulted in significant improvements in pain relief, joint function, mouth opening, and structural changes compared to AC-only or with PRP over follow-up periods ranging from 6 to 12 months. Current clinical evidence favors using i-PRF as an adjunct to AC rather than AC-only or AC with PRP for the treatment of TMDs. The improvements in subjective and objective outcome measures are clinically meaningful. Still, additional high-quality RCTs with larger sample sizes and longer follow-ups are required to strengthen the evidence base and better define the role of i-PRF in TMD management guidelines.
]]>Bioengineering doi: 10.3390/bioengineering11030246
Authors: Daniel J. Cognetti Mikalyn T. Defoor Tony T. Yuan Andrew J. Sheean
The unique physical demands of tactical athletes put immense stress on the knee joint, making these individuals susceptible to injury. In order to ensure operational readiness, management options must restore and preserve the native architecture and minimize downtime, while optimizing functionality. Osteochondral lesions (OCL) of the knee have long been acknowledged as significant sources of knee pain and functional deficits. The management of OCL is predicated on certain injury characteristics, including lesion location and the extent of subchondral disease. Techniques such as marrow stimulation, allograft and autologous chondrocyte implantation are examined in detail, with a focus on their application and suitability in tactical athlete populations. Moreover, the restoration of the osteochondral unit (OCU) is highlighted as a central aspect of knee joint preservation. The discussion encompasses the biomechanical considerations and outcomes associated with various cartilage restoration techniques. Factors influencing procedure selection, including lesion size, location, and patient-specific variables, are thoroughly examined. Additionally, the review underscores the critical role of post-operative rehabilitation and conditioning programs in optimizing outcomes. Strengthening the surrounding musculature, enhancing joint stability, and refining movement patterns are paramount in facilitating the successful integration of preservation procedures. This narrative review aims to provide a comprehensive resource for surgeons, engineers, and sports medicine practitioners engaged in the care of tactical athletes and the field of cartilage restoration. The integration of advanced preservation techniques and tailored rehabilitation protocols offers a promising avenue for sustaining knee joint health and function in this demanding population.
]]>Bioengineering doi: 10.3390/bioengineering11030245
Authors: Yongxiao Li Wanting Xu Xinpei Wang Ruizhi Lai Xiaohui Qiu Zekai Zeng Zhe Wang Junqing Wang
In this study, we advance our exploration of Apolipoprotein A-I (apoA-I) peptide analogs (APAs) for their application in nanodisc (ND) assembly, focusing on the dynamic conformational characteristics and the potential for drug delivery. We explore APA-ND interactions with an emphasis on curcumin encapsulation, utilizing molecular dynamic simulations and in vitro assessments to evaluate the efficacy of various APA-ND formulations as drug carriers. The methodological approach involved the generation of three unique apoA-I α-11/3 helical mimics, resulting in fifteen distinct APAs. Their structural integrity was rigorously assessed using ColabFold-AF2, with particular attention to pLDDT and pTM scores. Extensive molecular dynamics simulations, covering 1.7 μs across 17 ND systems, were conducted to investigate the influence of APA sequence variations on ND stability and interactions. This study reveals that the composition of APAs, notably the presence of Proline, Serine, and Tryptophan, significantly impacts ND stability and morphology. Oligomeric APAs, in particular, demonstrated superior stability and distinct interaction patterns compared to their monomeric counterparts. Additionally, hydrodynamic diameter measurements over eight weeks indicated sequence-dependent stability, highlighting the potential of specific APA configurations for sustained colloidal stability. In vitro study successfully encapsulated curcumin in [AA]3/DMPC ND formulations, revealing concentration-dependent stability and interaction dynamics. The findings underscore the remarkable capability of APA-NDs to maintain structural integrity and efficient drug encapsulation, positioning them as a promising platform for drug delivery. The study concludes by emphasizing the tunability and versatility of APA-NDs in drug formulation, potentially revolutionizing nanomedicine by enabling customized APA sequences and ND properties for targeted drug delivery.
]]>Bioengineering doi: 10.3390/bioengineering11030243
Authors: Shun Iwasaki Koichi Deguchi Ryosuke Iwai Yasuhide Nakayama Hiroomi Okuyama
The treatment of long-tracheal lesion is difficult because there are currently no viable grafts for tracheal replacement. To solve this problem, we have developed an autologous Tissue-Engineered Trachea (aTET), which is made up of collagenous tissues and cartilage-like structures derived from rat chondrocytes. This graft induced successful long-term survival in a small-animal experiment in our previous study. In this study, we investigated the regeneration process of an aTET to attain reproducible success. We prepared an aTET by using a specially designed mold and performed patch tracheoplasty with an aTET. We assigned twenty-seven rats to three groups according to the three types of patch grafts used: aTET patches (the aTET group), fresh tracheal autograft patches (the Ag group), or polylactic acid and polycaprolactone copolymer sheets (the PPc group). In each group, gross and histological evaluations were performed at 1 month (n = 3), 3 months (n = 3), and 6 months (n = 3) after implantation. We obtained high survival rates in all groups, but only the PPc group attained thick tracheal walls with granular tissues and no tracheal regeneration. On the other hand, the aTET and Ag groups reproducibly achieved complete tracheal regeneration in 6 months. So, an aTET could be a promising candidate for tracheal regeneration grafts.
]]>Bioengineering doi: 10.3390/bioengineering11030244
Authors: Gianpaolo Serino Fabio Distefano Elisabetta M. Zanetti Giulia Pascoletti Gabriella Epasto
Polyether-ether-2-ketone (PEKK) is a high-performance thermoplastic polymer used in various fields, from aerospace to medical applications, due to its exceptional mechanical and thermal properties. Nonetheless, the mechanical behavior of 3D-printed PEKK still deserves to be more thoroughly investigated, especially in view of its production by 3D printing, where mechanical properties measured at different scales are likely to be correlated to one another and to all play a major role in determining biomechanical properties, which include mechanical strength on one side and osteointegration ability on the other side. This work explores the mechanical behavior of 3D-printed PEKK through a multiscale approach, having performed both nanoindentation tests and standard tensile and compression tests, where a detailed view of strain distribution was achieved through Digital Image Correlation (DIC) techniques. Furthermore, for specimens tested up to failure, their fractured surfaces were analyzed through Scanning Electron Microscopy (SEM) to clearly outline fracture modes. Additionally, the internal structure of 3D-printed PEKK was explored through Computed Tomography (CT) imaging, providing a three-dimensional view of the internal structure and the presence of voids and other imperfections. Finally, surface morphology was analyzed through confocal microscopy. The multiscale approach adopted in the present work offers information about the global and local behavior of the PEKK, also assessing its material properties down to the nanoscale. Due to its novelty as a polymeric material, no previous studies have approached a multiscale analysis of 3D-printed PEKK. The findings of this study contribute to a comprehensive understanding of 3D-printed PEKK along with criteria for process optimization in order to customize its properties to meet specific application requirements. This research not only advances the knowledge of PEKK as a 3D-printing material but also provides insights into the multifaceted nature of multiscale material characterization.
]]>Bioengineering doi: 10.3390/bioengineering11030242
Authors: Cheng Zhang Fanlei Ran Lei Du Xiaohui Wang Lei Liu Jinming Liu Quan Chen Yang Cao Lijun Bi Haiying Hang
The cellular prion protein (PrPc) is a cell surface glycoprotein that is highly expressed in a variety of cancer tissues in addition to the nervous system, and its elevated expression is correlated to poor prognosis in many cancer patients. Our team previously found that patients with colorectal cancer (CRC) with high-level PrPc expression had significantly poorer survival than those with no or low-level PrPc expression. Mouse antibodies for PrPc inhibited tumor initiation and liver metastasis of PrPc-positive human CRC cells in mouse model experiments. PrPc is a candidate target for CRC therapy. In this study, we newly cloned a mouse anti-PrPc antibody (Clone 6) and humanized it, then affinity-matured this antibody using a CHO cell display with a peptide antigen and full-length PrPc, respectively. We obtained two humanized antibody clones with affinities toward a full-length PrPc of about 10- and 100-fold of that of the original antibody. The two humanized antibodies bound to the PrPc displayed significantly better on the cell surface than Clone 6. Used for Western blotting and immunohistochemistry, the humanized antibody with the highest affinity is superior to the two most frequently used commercial antibodies (8H4 and 3F4). The two new antibodies have the potential to be developed as useful reagents for PrPc detection and even therapeutic antibodies targeting PrPc-positive cancers.
]]>Bioengineering doi: 10.3390/bioengineering11030241
Authors: Daheui Kim Jun Hyeok Lee Min Suk Park Ma Rhip Ahn Daiwon Jun Jung Ho Lee
Lower extremity reconstruction is challenging because of its intricate anatomy and dynamic biomechanics. Although microsurgical free tissue transfer offers pivotal solutions to limited local tissue availability, vascular pedicle exposure after free tissue transfer is common. We evaluated a novel method of managing pedicle exposure after free tissue transfer using a reprocessed micronized dermal substitute. Ten patients who underwent lower-extremity reconstruction using free tissue transfer and micronized dermal substitute between January and December 2023 were retrospectively reviewed. When native tissue could not be closed over the pedicle, reprocessed micronized artificial dermal matrix (rmADM) was cut and stacked to protect and stabilize it. Epithelialization was achieved by secondary skin grafting or healing by secondary intention. Flap dimensions, recipient artery and vein, ADM size, time required for granulation tissue maturation and complete epithelialization, and flap outcomes were analyzed. The mean age was 55.80 ± 20.70 years, and six patients (60%) were diabetic. The mean rmADM coverage area was 8.70 ± 8.41 cm2, and the average time required for complete epithelialization was 50.89 ± 14.21 days. Except for one total necrosis due to bypass graft failure, nine limbs were successfully salvaged. Application of rmADM offers numerous advantages, including vascular collapse prevention, moisture maintenance, granulation tissue growth promotion, and pedicle stabilization.
]]>Bioengineering doi: 10.3390/bioengineering11030240
Authors: Prakash Kumar Karn Waleed H. Abdulla
This paper presents a novel U-Net model incorporating a hybrid attention mechanism for automating the segmentation of sub-retinal layers in Optical Coherence Tomography (OCT) images. OCT is an ophthalmology tool that provides detailed insights into retinal structures. Manual segmentation of these layers is time-consuming and subjective, calling for automated solutions. Our proposed model combines edge and spatial attention mechanisms with the U-Net architecture to improve segmentation accuracy. By leveraging attention mechanisms, the U-Net focuses selectively on image features. Extensive evaluations using datasets demonstrate that our model outperforms existing approaches, making it a valuable tool for medical professionals. The study also highlights the model’s robustness through performance metrics such as an average Dice score of 94.99%, Adjusted Rand Index (ARI) of 97.00%, and Strength of Agreement (SOA) classifications like “Almost Perfect”, “Excellent”, and “Very Strong”. This advanced predictive model shows promise in expediting processes and enhancing the precision of ocular imaging in real-world applications.
]]>Bioengineering doi: 10.3390/bioengineering11030239
Authors: Sverre Gullikstad Johnsen
Computational rhinology is a specialized branch of biomechanics leveraging engineering techniques for mathematical modelling and simulation to complement the medical field of rhinology. Computational rhinology has already contributed significantly to advancing our understanding of the nasal function, including airflow patterns, mucosal cooling, particle deposition, and drug delivery, and is foreseen as a crucial element in, e.g., the development of virtual surgery as a clinical, patient-specific decision support tool. The current paper delves into the field of computational rhinology from a nasal airflow perspective, highlighting the use of computational fluid dynamics to enhance diagnostics and treatment of breathing disorders. This paper consists of three distinct parts—an introduction to and review of the field of computational rhinology, a review of the published literature on in vitro and in silico studies of nasal airflow, and the presentation and analysis of previously unpublished high-fidelity CFD simulation data of in silico rhinomanometry. While the two first parts of this paper summarize the current status and challenges in the application of computational tools in rhinology, the last part addresses the gross disagreement commonly observed when comparing in silico and in vivo rhinomanometry results. It is concluded that this discrepancy cannot readily be explained by CFD model deficiencies caused by poor choice of turbulence model, insufficient spatial or temporal resolution, or neglecting transient effects. Hence, alternative explanations such as nasal cavity compliance or drag effects due to nasal hair should be investigated.
]]>Bioengineering doi: 10.3390/bioengineering11030238
Authors: Sapir Hazan Shenberger Idit Avrahami
Percutaneous mechanical circulatory support (MCS) devices are designed for short-term treatment in cases of acute decompensated heart failure as a bridge to transplant or recovery. Some of the known complications of MCS treatments are related to their hemodynamics in the aorta. The current study investigates the effect of MCS on the aortic flow. The study uses combined experimental and numerical methods to delineate complex flow structures. Particle image velocimetry (PIV) is used to capture the vortical and turbulent flow characteristics in a glass model of the human aorta. Computational fluid dynamics (CFD) analyses are used to complete the 3D flow in the aorta. Three specific MCS configurations are examined: a suction pump with a counterclockwise (CCW) rotating impeller, a suction pump with a clockwise (CW) rotating impeller, and a discharge pump with a straight jet. These models were examined under varying flow rates (1–2.5 L/min). The results show that the pump configuration strongly influences the flow in the thoracic aorta. The rotating impeller of the suction pump induces a dominant swirling flow in the aorta. The swirling flow distributes the incoming jet and reduces the turbulent intensity near the aortic valve and in the aorta. In addition, at high flow rates, the local vortices formed near the pump are washed downstream toward the aortic arch. Specifically, an MCS device with a CCW rotating impeller induces a non-physiological CCW helical flow in the descending aorta (which is opposite to the natural helical flow), while CW swirl combines better with the natural helical flow.
]]>Bioengineering doi: 10.3390/bioengineering11030236
Authors: Anmol Monga Dilbag Singh Hector L. de Moura Xiaoxia Zhang Marcelo V. W. Zibetti Ravinder R. Regatte
Magnetic resonance imaging (MRI) stands as a vital medical imaging technique, renowned for its ability to offer high-resolution images of the human body with remarkable soft-tissue contrast. This enables healthcare professionals to gain valuable insights into various aspects of the human body, including morphology, structural integrity, and physiological processes. Quantitative imaging provides compositional measurements of the human body, but, currently, either it takes a long scan time or is limited to low spatial resolutions. Undersampled k-space data acquisitions have significantly helped to reduce MRI scan time, while compressed sensing (CS) and deep learning (DL) reconstructions have mitigated the associated undersampling artifacts. Alternatively, magnetic resonance fingerprinting (MRF) provides an efficient and versatile framework to acquire and quantify multiple tissue properties simultaneously from a single fast MRI scan. The MRF framework involves four key aspects: (1) pulse sequence design; (2) rapid (undersampled) data acquisition; (3) encoding of tissue properties in MR signal evolutions or fingerprints; and (4) simultaneous recovery of multiple quantitative spatial maps. This paper provides an extensive literature review of the MRF framework, addressing the trends associated with these four key aspects. There are specific challenges in MRF for all ranges of magnetic field strengths and all body parts, which can present opportunities for further investigation. We aim to review the best practices in each key aspect of MRF, as well as for different applications, such as cardiac, brain, and musculoskeletal imaging, among others. A comprehensive review of these applications will enable us to assess future trends and their implications for the translation of MRF into these biomedical imaging applications.
]]>Bioengineering doi: 10.3390/bioengineering11030237
Authors: Martin Stolz
We aim to develop new portable desktop tissue analysers (DTAs) to provide fast, low-cost, and precise test results for fast nanomechanical profiling of tumours. This paper will explain the reasoning for choosing indentation-type atomic force microscopy (IT-AFM) to reveal the functional details of cancer. Determining the subtype, cancer stage, and prognosis will be possible, which aids in choosing the best treatment. DTAs are based on fast IT-AFM at the size of a small box that can be made for a low budget compared to other clinical imaging tools. The DTAs can work in remote areas and all parts of the world. There are a number of direct benefits: First, it is no longer needed to wait a week for the pathology report as the test will only take 10 min. Second, it avoids the complicated steps of making histopathology slides and saves costs of labour. Third, computers and robots are more consistent, more reliable, and more economical than human workers which may result in fewer diagnostic errors. Fourth, the IT-AFM analysis is capable of distinguishing between various cancer subtypes. Fifth, the IT-AFM analysis could reveal new insights about why immunotherapy fails. Sixth, IT-AFM may provide new insights into the neoadjuvant treatment response. Seventh, the healthcare system saves money by reducing diagnostic backlogs. Eighth, the results are stored on a central server and can be accessed to develop strategies to prevent cancer. To bring the IT-AFM technology from the bench to the operation theatre, a fast IT-AFM sensor needs to be developed and integrated into the DTAs.
]]>Bioengineering doi: 10.3390/bioengineering11030235
Authors: Samo K. Fokter Živa Ledinek Milka Kljaić Dujić Igor Novak
The majority of contemporary total hip arthroplasty (THA) implants are constructed from Ti alloys, which are generally believed to generate fewer adverse local tissue reactions (ALTRs) compared to CoCr alloys. This study presents a case of unusual primary THA failure where a substantial release of Ti alloy debris was observed. A 52-year-old active male underwent THA after post-traumatic aseptic necrosis of the femoral head in 2006. Seventeen years after the procedure, the patient presented with groin pain and a restricted range of motion. X-rays revealed the protrusion of the alumina ceramic head through the Ti6Al4V acetabular cup. Trace element analysis indicated significantly elevated levels of serum Ti, Al, and V. CT and MRI confirmed Ti alloy cup failure and a severe ALTR. During revision surgery, it was found that the worn-out ceramic head was in direct contact with the acetabular cup, having protruded through a central hole it had created over time. No acetabular liner was found. Histological analysis of his tissue samples showed wear-induced synovitis with areas of multinucleated foreign body giant cells and the accumulation of numerous metal particles but no acute inflammatory response. Six months after the revision THA, the patient has experienced favourable outcomes. This case provides an instructive illustration for studying the consequences of the substantial release of Ti alloy debris from orthopedic implants.
]]>Bioengineering doi: 10.3390/bioengineering11030234
Authors: Veniamin Y. Sidorov Tatiana N. Sidorova Philip C. Samson Ronald S. Reiserer Clayton M. Britt M. Diana Neely Kevin C. Ess John P. Wikswo
The implementation of three-dimensional tissue engineering concurrently with stem cell technology holds great promise for in vitro research in pharmacology and toxicology and modeling cardiac diseases, particularly for rare genetic and pediatric diseases for which animal models, immortal cell lines, and biopsy samples are unavailable. It also allows for a rapid assessment of phenotype–genotype relationships and tissue response to pharmacological manipulation. Mutations in the TSC1 and TSC2 genes lead to dysfunctional mTOR signaling and cause tuberous sclerosis complex (TSC), a genetic disorder that affects multiple organ systems, principally the brain, heart, skin, and kidneys. Here we differentiated healthy (CC3) and tuberous sclerosis (TSP8-15) human induced pluripotent stem cells (hiPSCs) into cardiomyocytes to create engineered cardiac tissue constructs (ECTCs). We investigated and compared their mechano-elastic properties and gene expression and assessed the effects of rapamycin, a potent inhibitor of the mechanistic target of rapamycin (mTOR). The TSP8-15 ECTCs had increased chronotropy compared to healthy ECTCs. Rapamycin induced positive inotropic and chronotropic effects (i.e., increased contractility and beating frequency, respectively) in the CC3 ECTCs but did not cause significant changes in the TSP8-15 ECTCs. A differential gene expression analysis revealed 926 up- and 439 down-regulated genes in the TSP8-15 ECTCs compared to their healthy counterparts. The application of rapamycin initiated the differential expression of 101 and 31 genes in the CC3 and TSP8-15 ECTCs, respectively. A gene ontology analysis showed that in the CC3 ECTCs, the positive inotropic and chronotropic effects of rapamycin correlated with positively regulated biological processes, which were primarily related to the metabolism of lipids and fatty and amino acids, and with negatively regulated processes, which were predominantly associated with cell proliferation and muscle and tissue development. In conclusion, this study describes for the first time an in vitro TSC cardiac tissue model, illustrates the response of normal and TSC ECTCs to rapamycin, and provides new insights into the mechanisms of TSC.
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