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  • Correction to: Development and Multi-Scale Validation of a Finite Element Football Helmet Model
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-12-16
    William B. Decker, Alex M. Baker, Xin Ye, Philip J. Brown, Joel D. Stitzel, F. Scott Gayzik

    This correction is to add the middle initials of all authors, which were inadvertently omitted from the original article.

    更新日期:2020-01-09
  • Correction to: Curricular Advancement of Biomedical Engineering Undergraduate Design Projects Beyond 1 Year: A Pilot Study
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-12-20
    Amir Manbachi, Elizabeth A. Logsdon, Youseph Yazdi, Nicholas J. Durr

    This erratum is to add author Nicholas J. Durr as a co-corresponding author.

    更新日期:2020-01-09
  • Ultrasound-Based Optimal Parameter Estimation Improves Assessment of Calf Muscle-Tendon Interaction During Walking.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    T Delabastita,M Afschrift,B Vanwanseele,F De Groote

    We present and evaluate a new approach to estimate calf muscle-tendon parameters and calculate calf muscle-tendon function during walking. We used motion analysis, ultrasound, and EMG data of the calf muscles collected in six young and six older adults during treadmill walking as inputs to a new optimal estimation algorithm. We used estimated parameters or scaled generic parameters in an existing approach to calculate muscle fiber lengths and activations. We calculated the fit with experimental data in terms of root mean squared differences (RMSD) and coefficients of determination (R2). We also calculated the calf muscle metabolic energy cost. RMSD between measured and calculated fiber lengths and activations decreased and R2 increased when estimating parameters compared to using scaled generic parameters. Moreover, R2 between measured and calculated gastrocnemius medialis fiber length and soleus activations increased by 19 and 70%, and calf muscle metabolic energy decreased by 25% when using estimated parameters compared to using scaled generic parameters at speeds not used for estimation. This new approach estimates calf muscle-tendon parameters in good accordance with values reported in literature. The approach improves calculations of calf muscle-tendon interaction during walking and highlights the importance of individualizing calf muscle-tendon parameters.

    更新日期:2020-01-09
  • Quantifying Subresolution 3D Morphology of Bone with Clinical Computed Tomography.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    S S Karhula,M A J Finnilä,S J O Rytky,D M Cooper,J Thevenot,M Valkealahti,K P H Pritzker,M Haapea,A Joukainen,P Lehenkari,H Kröger,R K Korhonen,H J Nieminen,S Saarakkala

    The aim of this study was to quantify sub-resolution trabecular bone morphometrics, which are also related to osteoarthritis (OA), from clinical resolution cone beam computed tomography (CBCT). Samples (n = 53) were harvested from human tibiae (N = 4) and femora (N = 7). Grey-level co-occurrence matrix (GLCM) texture and histogram-based parameters were calculated from CBCT imaged trabecular bone data, and compared with the morphometric parameters quantified from micro-computed tomography. As a reference for OA severity, histological sections were subjected to OARSI histopathological grading. GLCM and histogram parameters were correlated to bone morphometrics and OARSI individually. Furthermore, a statistical model of combined GLCM/histogram parameters was generated to estimate the bone morphometrics. Several individual histogram and GLCM parameters had strong associations with various bone morphometrics (|r| > 0.7). The most prominent correlation was observed between the histogram mean and bone volume fraction (r = 0.907). The statistical model combining GLCM and histogram-parameters resulted in even better association with bone volume fraction determined from CBCT data (adjusted R2 change = 0.047). Histopathology showed mainly moderate associations with bone morphometrics (|r| > 0.4). In conclusion, we demonstrated that GLCM- and histogram-based parameters from CBCT imaged trabecular bone (ex vivo) are associated with sub-resolution morphometrics. Our results suggest that sub-resolution morphometrics can be estimated from clinical CBCT images, associations becoming even stronger when combining histogram and GLCM-based parameters.

    更新日期:2020-01-09
  • Triple Contrast CT Method Enables Simultaneous Evaluation of Articular Cartilage Composition and Segmentation.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Miitu K M Honkanen,Annina E A Saukko,Mikael J Turunen,Wujun Xu,Goran Lovric,Juuso T J Honkanen,Mark W Grinstaff,Vesa-Pekka Lehto,Juha Töyräs

    Early degenerative changes of articular cartilage are detected using contrast-enhanced computed tomography (CT) with a cationic contrast agent (CA). However, cationic CA diffusion into degenerated cartilage decreases with proteoglycan depletion and increases with elevated water content, thus hampering tissue evaluation at early diffusion time points. Furthermore, the contrast at synovial fluid-cartilage interface diminishes as a function of diffusion time hindering accurate cartilage segmentation. For the first time, we employ quantitative dual-energy CT (QDECT) imaging utilizing a mixture of three CAs (cationic CA4+ and non-ionic gadoteridol which are sensitive to proteoglycan and water contents, respectively, and bismuth nanoparticles which highlight the cartilage surface) to simultaneously segment the articulating surfaces and determine of the cartilage condition. Intact healthy, proteoglycan-depleted, and mechanically injured bovine cartilage samples (n = 27) were halved and imaged with synchrotron microCT 2-h post immersion in triple CA or in dual CA (CA4+ and gadoteridol). CA4+ and gadoteridol partitions were determined using QDECT, and pairwise evaluation of these partitions was conducted for samples immersed in dual and triple CAs. In conclusion, the triple CA method is sensitive to proteoglycan depletion while maintaining sufficient contrast at the articular surface to enable detection of cartilage lesions caused by mechanical impact.

    更新日期:2020-01-09
  • A Fluorescence Sensing Method with Reduced DNA Typing and Low-Cost Instrumentation for Detection of Sample Tampering Cases in Urinalysis.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Nuno M M Pires,Tao Dong,Zhaochu Yang,Simão M B Santos

    This work presents a method to unequivocally detect urine sample tampering in cases where integrity of the sample needs to be verified prior to urinalysis. The technique involves the detection of distinct patterns of a triplex short tandem repeats system in DNA extracted from human urine. The analysis is realized with single-dye fluorescence detection and using a regular smartphone camera. The experimental results had demonstrated the efficacy of the analytical approach to obtaining distinct profiles of amplicons in urine from different sample providers. Reproducibility tests with fresh and stored urine have revealed a maximum variation in the profiles within an interval of 5 to 9%. Cases of urine sample tampering via mixture were simulated in the study, and the experiments have identified patterns of mixed genotypes from dual mixtures of urine samples. Moreover, sample adulteration by mixing a non-human fluid with urine in a volume ratio over 25% can be detected. The low cost of the approach is accompanied by the compatibility of the technique to use with different DNA sample preparation protocols and PCR instrumentation. Furthermore, the possibility of realizing the method in an integrated microchip system open great perspectives to conducting sample integrity tests at the site of urine sample reception and/or at resource-limited settings.

    更新日期:2020-01-09
  • Pattern Reorganization of Corticomuscular Connection with the Tactile Stimulation
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-12-06
    Long Li, Jing Guo, Yanlong Zhang, Hongjian Wu, Lina Li, Tian Liu, Jue Wang

    Abstract Sensitivity to tactile stimuli is an indispensable feedback in human motion control. However, previous studies on tactile stimulation mainly focused on the effects of superficial tactile stimulation on the motor cortex, but the role of deep tactile feedback stimulation in motor tasks is not clear. Corticomuscular coherence (CMC) is an effective method for studying dynamic motion tasks. Recent evidence suggests that CMC is enhanced by tactile stimulation in the beta-band. But, the mechanism of tactile stimulation in dynamic motor tasks is still undetermined. In order to explore the role of tactile stimulation in dynamic motion tasks, we examined the correlation between EEG/EMG in a motor task with tactile stimulus input, including the corticomuscular coherence and the causal connections (convergent cross mapping, CCM). In this study, seventeen subjects were recruited to complete stimuli and non-stimuli motor tasks. After the experiment, the time–frequency analysis of CMC showed that the somatosensory association cortex was clearly involved in the dynamic motor tasks. During the contraction of hand muscles, the activity of CMC was concentrated in gamma band, while in the maintenance process, it was concentrated in beta-band. After eliminating the distractors of attention, we did not find a similar result as previous studies had found—tactile stimuli lead to increased CMC activity in gamma band. On the contrary, CCM causality analysis showed that tactile stimulation could significantly enhance the connection between the cerebral cortex and a muscle. We speculate that tactile stimulation can enhance the corticomuscular causal relationship, and that the effect of tactile stimulation on corticomuscular coherence may have more complex mechanisms. This study provides new insights into neural mechanism of tactile feedback and provides more information about the causality of brain networks in tactile feedback task.

    更新日期:2020-01-09
  • Straining 3D Hydrogels with Uniform Z -Axis Strains While Enabling Live Microscopy Imaging
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-12-04
    Avishy Roitblat Riba, Sari Natan, Avraham Kolel, Hila Rushkin, Oren Tchaicheeyan, Ayelet Lesman

    Abstract External forces play an important role in the development and regulation of many tissues. Such effects are often studied using specialized stretchers—standardized commercial and novel laboratory-designed. While designs for 2D stretchers are abundant, the range of available 3D stretcher designs is more limited, especially when live imaging is required. This work presents a novel method and a stretching device that allow straining of 3D hydrogels from their circumference, using a punctured elastic silicone strip as the sample carrier. The system was primarily constructed from 3D-printed parts and low-cost electronics, rendering it simple and cost-efficient to reproduce in other labs. To demonstrate the system functionality, > 100 μm thick soft fibrin gels (< 1 KPa) were stretched, while performing live confocal imaging. The subsequent strains and fiber alignment were analyzed and found to be relatively homogenous throughout the gel’s thickness (Z axis). The uniform Z-response enabled by our approach was found to be in contrast to a previously reported approach that utilizes an underlying elastic substrate to convey strain to a 3D thick sample. This work advances the ability to study the role of external forces on biological processes under more physiological 3D conditions, and can contribute to the field of tissue engineering.

    更新日期:2020-01-09
  • Effects of Physical, Chemical, and Biological Stimulus on h-MSC Expansion and Their Functional Characteristics.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    David A Castilla-Casadiego,Ana M Reyes-Ramos,Maribella Domenech,Jorge Almodovar

    Human adult mesenchymal stem or stromal cells (h-MSC) therapy has gained considerable attention due to the potential to treat or cure diseases given their immunosuppressive properties and tissue regeneration capabilities. Researchers have explored diverse strategies to promote high h-MSC production without losing functional characteristics or properties. Physical stimulus including stiffness, geometry, and topography, chemical stimulus, like varying the surface chemistry, and biochemical stimuli such as cytokines, hormones, small molecules, and herbal extracts have been studied but have yet to be translated to industrial manufacturing practice. In this review, we describe the role of those stimuli on h-MSC manufacturing, and how these stimuli positively promote h-MSC properties, impacting the cell manufacturing field for cell-based therapies. In addition, we discuss other process considerations such as bioreactor design, good manufacturing practice, and the importance of the cell donor and ethics factors for manufacturing potent h-MSC.

    更新日期:2020-01-09
  • A Reconfigurable In Vitro Model for Studying the Blood-Brain Barrier.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Monica L Moya,Michael Triplett,Melinda Simon,Javier Alvarado,Ross Booth,Joanne Osburn,David Soscia,Fang Qian,Nicholas O Fischer,Kristen Kulp,Elizabeth K Wheeler

    Much of what is currently known about the role of the blood-brain barrier (BBB) in regulating the passage of chemicals from the blood stream to the central nervous system (CNS) comes from animal in vivo models (requiring extrapolation to human relevance) and 2D static in vitro systems, which fail to capture the rich cell-cell and cell-matrix interactions of the dynamic 3D in vivo tissue microenvironment. In this work we have developed a BBB platform that allows for a high degree of customization in cellular composition, cellular orientation, and physiologically-relevant fluid dynamics. The system characterized and presented in this study reproduces key characteristics of a BBB model (e.g. tight junctions, efflux pumps) allowing for the formation of a selective and functional barrier. We demonstrate that our in vitro BBB is responsive to both biochemical and mechanical cues. This model further allows for culture of a CNS-like space around the BBB. The design of this platform is a valuable tool for studying BBB function as well as for screening of novel therapeutics.

    更新日期:2020-01-09
  • Mechanistic Understanding of High Flow Nasal Cannula Therapy and Pressure Support with an In Vitro Infant Model.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    John V Wilkins,Michelle T Gardner,Ross Walenga,Sana Hosseini,P Worth Longest,Laleh Golshahi

    Despite the increased use of high flow nasal cannula therapy, little has been done to predict airway pressures for a full breath cycle. A 3-month-old infant in vitro model was developed, which included the entire upper airway and the first three bifurcations of the lungs. A breathing simulator was used to create a realistic breath pattern, and high flow was provided using a Vapotherm unit. Four cannulas of varying sizes were used to assess the effects of the inner diameter and nasal occlusion of the cannulas on airway pressures. At 8 L min-1, end expiratory pressures of 0.821-1.306 cm H2O and 0.828-1.133 cm H2O were produced in the nasopharynx and trachea, respectively. Correlations were developed to predict full breath cycle airway pressures, based on the gas flow rate delivered, cannula dimensions, as well as the breathing flow rate, for the nasopharynx and trachea. Pearson correlation coefficients for the nasopharynx and trachea correlations were 0.991 and 0.992, respectively. The developed correlations could be used to determine the flow rate necessary for a cannula to produce pressures similar to CPAP settings. The proposed correlations accurately predict the regional airway pressure up to and including 7 cm H2O of support for the entire breath cycle.

    更新日期:2020-01-09
  • Regenerative and Resorbable PLA/HA Hybrid Construct for Tendon/Ligament Tissue Engineering.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    M C Araque-Monrós,D M García-Cruz,J L Escobar-Ivirico,L Gil-Santos,M Monleón-Pradas,J Más-Estellés

    Tendon and ligament shows extremely limited endogenous regenerative capacity. Current treatments are based on the replacement and or augmentation of the injured tissue but the repaired tissue rarely achieve functionality equal to that of the preinjured tissue. To address this challenge, tissue engineering has emerged as a promising strategy. This study develops a regenerative and resorbable hybrid construct for tendon and ligament engineering. The construct is made up by a hollow poly-lactic acid braid with embedded microspheres carrying cells and an anti-adherent coating, with all the parts being made of biodegradable materials. This assembly intends to regenerate the tissue starting from the interior of the construct towards outside while it degrades. Fibroblasts cultured on poly lactic acid and hyaluronic acid microspheres for 6 h were injected into the hollow braid and the construct was cultured for 14 days. The cells thus transported into the lumen of the construct were able to migrate and adhere to the braid fibers naturally, leading to a homogeneous proliferation inside the braid. Moreover, no cells were found on the outer surface of the coating. Altogether, this study demonstrated that PLA/HA hybrid construct could be a promising material for tendon and ligament repair.

    更新日期:2020-01-09
  • A Cohort Longitudinal Study Identifies Morphology and Hemodynamics Predictors of Abdominal Aortic Aneurysm Growth.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Florian Joly,Gilles Soulez,Simon Lessard,Claude Kauffmann,Irene Vignon-Clementel

    Abdominal aortic aneurysms (AAA) are localized, commonly occurring aortic dilations. Following rupture only immediate treatment can prevent morbidity and mortality. AAA maximal diameter and growth are the current metrics to evaluate the associated risk and plan intervention. Although these criteria alone lack patient specificity, predicting their evolution would improve clinical decision. If the disease is known to be associated with altered morphology and blood flow, intraluminal thrombus deposit and clinical symptoms, the growth mechanisms are yet to be fully understood. In this retrospective longitudinal study of 138 scans, morphological analysis and blood flow simulations for 32 patients with clinically diagnosed AAAs and several follow-up CT-scans, are performed and compared to 9 control subjects. Several metrics stratify patients between healthy, low and high risk groups. Local correlations between hemodynamic metrics and AAA growth are also explored but due to their high inter-patient variability, do not explain AAA heterogeneous growth. Finally, high-risk predictors trained with successively clinical, morphological, hemodynamic and all data, and their link to the AAA evolution are built from supervise learning. Predictive performance is high for morphological, hemodynamic and all data, in contrast to clinical data. The morphology-based predictor exhibits an interesting effort-predictability tradeoff to be validated for clinical translation.

    更新日期:2020-01-09
  • Patient-Specific Monitoring and Trend Analysis of Model-Based Markers of Fluid Responsiveness in Sepsis: A Proof-of-Concept Animal Study.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Liam Murphy,Shaun Davidson,J Geoffrey Chase,Jennifer L Knopp,Tony Zhou,Thomas Desaive

    Total stressed blood volume ([Formula: see text]) and arterial elastance ([Formula: see text]) are two potentially important, clinically applicable metrics for guiding treatment in patients with altered hemodynamic states. Defined as the total pressure generating blood in the circulation, [Formula: see text] is a potential direct measurement of tissue perfusion, a critical component in treatment of sepsis. [Formula: see text] is closely related to arterial tone thus provides insight into cardiac efficiency. However, it is not clinically feasible or ethical to measure [Formula: see text] in patients, so a three chambered cardiovascular system model using measured left ventricle pressure and volume, aortic pressure and central venous pressure is implemented to identify [Formula: see text] and [Formula: see text] from clinical data. [Formula: see text] and [Formula: see text] are identified from clinical data from six (6) pigs, who have undergone clinical procedures aimed at simulating septic shock and subsequent treatment, to identify clinically relevant changes. A novel, validated trend analysis method is used to adjudge clinically significant changes in state in the real-time [Formula: see text] and [Formula: see text] traces. Results matched hypothesised increases in [Formula: see text] during fluid therapy, with a mean change of + 21% during initial therapy, and hypothesised decreases during endotoxin induced sepsis, with a mean change of - 29%. [Formula: see text] displayed the hypothesised reciprocal behaviour with a mean changes of - 12 and + 30% during initial therapy and endotoxin induced sepsis, respectively. The overall results validate the efficacy of [Formula: see text] in tracking changes in hemodynamic state in septic shock and fluid therapy.

    更新日期:2020-01-09
  • Assessing Changes in Airflow and Energy Loss in a Progressive Tracheal Compression Before and After Surgical Correction.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Qiwei Xiao,Raul Cetto,Denis J Doorly,Alister J Bates,Jan N Rose,Charlotte McIntyre,Andrew Comerford,Gitta Madani,Neil S Tolley,Robert Schroter

    The energy needed to drive airflow through the trachea normally constitutes a minor component of the work of breathing. However, with progressive tracheal compression, patient subjective symptoms can include severe breathing difficulties. Many patients suffer multiple respiratory co-morbidities and so it is important to assess compression effects when evaluating the need for surgery. This work describes the use of computational prediction to determine airflow resistance in compressed tracheal geometries reconstructed from a series of CT scans. Using energy flux analysis, the regions that contribute the most to airway resistance during inhalation are identified. The principal such region is where flow emerging from the zone of maximum constriction undergoes breakup and turbulent mixing. Secondary regions are also found below the tongue base and around the glottis, with overall airway resistance scaling nearly quadratically with flow rate. Since the anatomical extent of the imaged airway varied between scans-as commonly occurs with clinical data and when assessing reported differences between research studies-the effect of sub-glottic inflow truncation is considered. Analysis shows truncation alters the location of jet breakup and weakly influences the pattern of pressure recovery. Tests also show that placing a simple artificial glottis in the inflow to a truncated model can replicate patterns of energy loss in more extensive models, suggesting a means to assess sensitivity to domain truncation in tracheal airflow simulations.

    更新日期:2020-01-09
  • Inter-foetus Membrane Segmentation for TTTS Using Adversarial Networks
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-12-05
    Alessandro Casella, Sara Moccia, Emanuele Frontoni, Dario Paladini, Elena De Momi, Leonardo S. Mattos

    Abstract Twin-to-Twin Transfusion Syndrome is commonly treated with minimally invasive laser surgery in fetoscopy. The inter-foetal membrane is used as a reference to find abnormal anastomoses. Membrane identification is a challenging task due to small field of view of the camera, presence of amniotic liquid, foetus movement, illumination changes and noise. This paper aims at providing automatic and fast membrane segmentation in fetoscopic images. We implemented an adversarial network consisting of two Fully-Convolutional Neural Networks. The former (the segmentor) is a segmentation network inspired by U-Net and integrated with residual blocks, whereas the latter acts as critic and is made only of the encoding path of the segmentor. A dataset of 900 images acquired in 6 surgical cases was collected and labelled to validate the proposed approach. The adversarial networks achieved a median Dice similarity coefficient of 91.91% with Inter-Quartile Range (IQR) of 4.63%, overcoming approaches based on U-Net (82.98%-IQR: 14.41%) and U-Net with residual blocks (86.13%-IQR: 13.63%). Results proved that the proposed architecture could be a valuable and robust solution to assist surgeons in providing membrane identification while performing fetoscopic surgery.

    更新日期:2020-01-09
  • The Effect of Downsizing on the Normal Tricuspid Annulus.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Mrudang Mathur,William D Meador,Tomasz Jazwiec,Marcin Malinowski,Tomasz A Timek,Manuel K Rausch

    Tricuspid annuloplasty is a surgical procedure that cinches the valve's annulus in order to reduce regurgitant blood flow. One of its critical parameters is the degree of downsizing. To provide insight into the effect of downsizing, we studied the annulus of healthy sheep during suture annuloplasty. To this end, we implanted fiduciary markers along the annulus of sheep and subsequently performed a DeVega suture annuloplasty. We performed five downsizing steps in each animal while recording hemodynamic and sonomicrometry data in beating hearts. Subsequently, we used splines to approximate the annulus at baseline and at each downsizing step. Based on these approximations we computed clinical metrics of annular shape and dynamics, and the continuous field metrics height, strain, and curvature. With these data, we demonstrated that annular area reduction during downsizing was primarily driven by compression of the anterior annulus. Similarly, reduction in annular dynamics was driven by reduced contractility in the anterior annulus. Finally, changes in global height and eccentricity of the annulus could be explained by focal changes in the continuous height profile and changes in annular curvature. Our findings are important as they provide insight into a regularly performed surgical procedure and may inform the design of transcatheter devices that mimic suture annuloplasty.

    更新日期:2020-01-09
  • ECM-Mimetic Multiresponsive Nanobullets Targeted Against Metastasizing Circulating Tumor Clusters in Breast Cancer.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Ramya Dhandapani,Anuradha Subramanian,Swaminathan Sethuraman

    Targeting smaller populations of circulating tumor clusters (CTC) with tumor-initiating and colonization potentials at distant sites in circulation remains a challenge as clusters possess both epithelial and mesenchymal characteristics. Bullet shaped ellipsoidal nanostructures of size 600 ± 11.3 nm (major axis) and 281.9 ± 5.3 nm (minor axis) with 2.2 aspect ratio were self-assembled using inorganic and organic GRAS biomaterials to preferentially target tumor-causing CTCs. Negatively-charged chondroitin sulfate in presence of gelatin guides unidirectional growth of calcium carbonate mesocrystals to form nanobullets, mediates CD44 targeting of CTCs. Switchable multi-responsive drug release profiles (temperature and pH) were recorded for nanobullets promoting spontaneous and efficient cell-killing. CD44 and E-cadherin overexpressing 'seeding' cell clusters of 170 ± 22 µm were developed as in vitro CTC model. pH responsive release of Dox into lysosome stimulates calcium influx resulting in cell death. CD44-blocked CTCs showed significantly reduced internalization when compared to CD44-expressing CTCs thereby confirming CD44 specific internalization of nanobullets. Significantly retarded expansion of clusters when shifted to cell adhesive surfaces depicts the potential of nanobullets against colonization of CTCs. Hence, newer insights on developed anisotropic ECM-mimetic nanohybrids would enhance targeted capture of tumor-initiating clusters in systemic circulation that would potentially reduce the progression of tumor in breast cancer patients.

    更新日期:2020-01-09
  • Developing a Model for Integrating Professional Practice and Evidence-Based Teaching Practices into BME Curriculum
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-12-06
    Aileen Huang-Saad, Jan Stegemann, Lonnie Shea

    Abstract Undergraduate biomedical engineering (BME) programs typically consist of courses from several different academic departments combined with BME-specific courses taught by faculty trained in a variety of disciplines. While some students embrace this diversity in courses and disciplinary perspectives, many students struggle with how to translate these experiences into career opportunities. BME students are often concerned that they are perceived as a “jack of all trades, master of none.” In 2016, our department sought to find new ways to integrate BME professional practice into our curriculum. Informed by organizational change theory, we asked: (1) is there potential for change; (2) what strategies facilitate change; and (3) how can these strategies be implemented? As a result, we developed an Instructional Design Sequence, a new approach to instruction in which students, post docs, and faculty create short Modules that use evidence-based teaching practices to expose BME students to BME professional practice. This paper describes how the Sequence was conceptualized and demonstrates how theory can be used to inform practice. The resultant Sequence is a transferrable model for transforming engineering education, offering a mechanism for integrating new career relevant curriculum into undergraduate curriculum, while training future educators in instructional evidence-based practices.

    更新日期:2020-01-09
  • In Vivo Modulation of the Blood–Brain Barrier Permeability by Transcranial Direct Current Stimulation (tDCS)
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2020-01-08
    Da Wi Shin, Jie Fan, Eric Luu, Wasem Khalid, Yifan Xia, Niranjan Khadka, Marom Bikson, Bingmei M. Fu

    tDCS has been used to treat various brain disorders and its mechanism of action (MoA) was found to be neuronal polarization. Since the blood–brain barrier (BBB) tightly regulates the neuronal microenvironment, we hypothesized that another MoA of tDCS is direct vascular activation by modulating the BBB structures to increase its permeability (P). To test this hypothesis, we used high resolution multiphoton microscopy to determine P of the cerebral microvessels in rat brain. We found that 20 min 0.1–1 mA tDCS transiently increases P to a small solute, sodium fluorescein (MW 376) and to a large solute, Dextran-70k, with a much higher increase in P to the large solute. By pretreating the vessel with a nitric oxide synthase inhibitor, we revealed that the tDCS-induced increase in P is NO dependent. A transport model for the BBB was further employed to predict the structural changes by the tDCS. Comparing model predictions with the measured data suggests that tDCS increases P by temporarily disrupting the structural components forming the paracellular pathway of the BBB. That the transient and reversible increase in the BBB permeability also suggests new applications of tDCS such as a non-invasive approach for brain drug delivery through the BBB.

    更新日期:2020-01-08
  • Optimizing Integrated Electrode Design for Irreversible Electroporation of Implanted Polymer Scaffolds
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2020-01-08
    Francisco Pelaez, Qi Shao, Pegah Ranjbartehrani, Tiffany Lam, Hak Rae Lee, Stephen O’Flanagan, Abby Silbaugh, John C. Bischof, Samira M. Azarin

    Irreversible electroporation (IRE) is an emerging technology for non-thermal ablation of solid tumors. This study sought to integrate electrodes into microporous poly(caprolactone) (PCL) scaffolds previously shown to recruit metastasizing cancer cells in vivo in order to facilitate application of IRE to disseminating cancer cells. As the ideal parallel plate geometry would render much of the porous scaffold surface inaccessible to infiltrating cells, numerical modeling was utilized to predict the spatial profile of electric field strength within the scaffold for alternative electrode designs. Metal mesh electrodes with 0.35 mm aperture and 0.16 mm wire diameter established electric fields with similar spatial uniformity as the parallel plate geometry. Composite PCL-IRE scaffolds were fabricated by placing cylindrical porous PCL scaffolds between two PCL dip-coated stainless steel wire meshes. PCL-IRE scaffolds exhibited no difference in cell infiltration in vivo compared to PCL scaffolds. In addition, upon application of IRE in vivo, cells infiltrating the PCL-IRE scaffolds were successfully ablated, as determined by histological analysis 3 days post-treatment. The ability to establish homogeneous electric fields within a biomaterial that can recruit metastatic cancer cells, especially when combined with immunotherapy, may further advance IRE technology beyond solid tumors to the treatment of systemic cancer.

    更新日期:2020-01-08
  • Differences Between Physical vs. Virtual Evoked Vestibular Responses
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2020-01-08
    Mehrangiz Ashiri, Brian Lithgow, Abdelbaset Suleiman, Brian Blakley, Behzad Mansouri, Zahra Moussavi

    Abstract Electrovestibulography (EVestG), a technology purported to measure vestibular activity at the vestibular periphery, was used to compare the vestibular responses to two sensory inputs: (1) back-forward physical tilt (with eyes-open and eyes-closed) and (2) virtual reality replica of the back-forward tilt (eyes-open, physically static). Twenty-seven healthy participants (10 females) were tested. From each of the EVestG recordings, two feature curves: (1) average field potential (FP), and (2) distribution of time intervals between the detected FPs were extracted. For the eyes-closed physical tilt, except for the background segment, the FP response curve was generally wider compared to that evoked during the virtual replica tilt (p < 0.05). Moreover, the eyes-closed physical tilt produced longer time intervals between FP’s compared to the virtual stimulus. For this measure, for the background segment, the eyes closed and open physical tilt responses were significantly different (p < 0.05) in both ears (repeated measure experimental design). The results support: (1) both vestibular and visual inputs evoking a measurably different EVestG response, (2) the differences between physical and virtual vestibular responses are dependent on the eyes being either open or closed, and (3) for the stimuli used, the modulation of vestibular afferent activity was measurably smaller for virtual than physical stimulation.

    更新日期:2020-01-08
  • A New Breakthrough Detection Method for Bone Drilling in Robotic Orthopedic Surgery with Closed-Loop Control Approach
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2020-01-02
    Yunis Torun, Ahmet Öztürk

    Breakthrough detection is a crucial task to reduce the risks of damaging soft tissue bone drilling operations during orthopedic surgery. Conventional drills are not equipped with this function while the recent literature has offered this capability with high cost and complex modification needs. In this study, a new breakthrough detection approach based on closed-loop control characteristics of the drilling operation is proposed. A feature set containing closed-loop signals and force sensor data is created to train K-Nearest and Ensemble Classifier for breakthrough detection tasks with drilling the synthetic bone model and animal bone with a robot manipulator. The best accuracy of breakthrough detection with only closed-loop control signal attributes is achieved as 96.9 ± 0.8% for the synthetic bone model and 98.1 ± 0.2% for sheep femur bone. Breakthrough detection delay which included sampling and operation time of the method guarantees that the drill bit would stop with acceptable breakthrough range of 1.0413 mm. The proposed method can be used to detect breakthrough and also to estimate the state of the drill bit in robotic orthopedic bone drilling processes using only closed-loop signals so that it would be no need to use extra high-cost sensors.

    更新日期:2020-01-04
  • Correction to: A High-Precision and Miniature Fiber Bragg Grating-Based Force Sensor for Tissue Palpation During Minimally Invasive Surgery
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-11-21
    Changhu Lv, Shuxin Wang, Chaoyang Shi

    The second equation in the section “Definition of Objective Functions and Constraints” was corrected to fix a mismatch between the PDF and HTML versions of the article.

    更新日期:2020-01-04
  • Scaffold Free Microtissue Formation for Enhanced Cartilage Repair
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-08-26
    Lise De Moor, Elien Beyls, Heidi Declercq

    Given the low self-healing capacity of fibrocartilage and hyaline cartilage, tissue engineering holds great promise for the development of new regenerative therapies. However, dedifferentiation of cartilage cells during expansion leads to fibrous tissue instead of cartilage. The purpose of our study was to generate 3D microtissues, spheroids, mimicking the characteristics of native fibrocartilage or articular cartilage to use as modular units for implantation in meniscal and articular cartilage lesions, respectively, within the knee joint. A set of parameters was assessed to create spheroids with a geometry compatible with 3D bioprinting for the creation of a biomimetic cartilage construct. Fibrochondrocytes (FC) and articular chondrocytes (AC) spheroids were created using a high-throughput microwell system. Spheroid morphology, viability, proliferation and extracellular matrix were extensively screened. After 2D expansion, FC and AC dedifferentiated, resulting in a loss of cartilage specific extracellular matrix proteins. Spheroid formation did not result in FC redifferentiation, but did lead to redifferentiation of AC, resulting in microtissues displaying collagen II, aggrecan and glycosaminoglycans. This study demonstrates 3D cartilage mimics that could have a potential application in the next generation of Autologous Chondrocyte Implantation procedures. Moreover, spheroids can be used as building blocks to create cartilage constructs by bioprinting in the future.

    更新日期:2020-01-04
  • Evaluation of a New Approach for Modeling Full Ring Stent Bundles with the Inclusion of Manufacturing Strains
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-07-17
    Faidon Kyriakou, David Bow, William Dempster, Robbie Brodie, David Nash

    Ring stent bundles have been used in several biomedical stent-graft devices for decades, yet in the published literature, the numerical models of these structures always present significant simplifications. In this paper, a finite element (FE) ring stent bundle has been developed and evaluated with a combination of beam and surface elements. With this approach, the shape, the global stiffness and the strains of the structure can all be well predicted at a low computational cost while the approach is suitable for application to non-symmetrical, patient-specific implant simulations. The model has been validated against analytical and experimental data showing that the manufacturing strains can be predicted to a 0.1% accuracy and the structural stiffness with 0–7% precision. The model has also been compared with a more computationally expensive FE model of higher fidelity, revealing a discrepancy of 0–5% of the strain value. Finally, it has been shown that the exclusion of the manufacturing process from the simulation, a technique used in the literature, quadruples the analysis error. This is the first model that can capture the mechanical state of a full ring stent bundle, suitable for complex implant geometry simulations, with such accuracy.

    更新日期:2020-01-04
  • In Vivo MRI Assessment of Blood Flow in Arteries and Veins from Head-to-Toe Across Age and Sex in C57BL/6 Mice
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-08-27
    A. Colleen Crouch, Amos A. Cao, Ulrich M. Scheven, Joan M. Greve

    Although widely used as a preclinical model for studying cardiovascular diseases, there is a scarcity of in vivo hemodynamic measurements of the naïve murine system in multiple arterial and venous locations, from head-to-toe, and across sex and age. The purpose of this study is to quantify cardiovascular hemodynamics in mice at different locations along the vascular tree while evaluating the effects of sex and age. Male and female, adult and aged mice were anesthetized and underwent magnetic resonance imaging. Data were acquired from four co-localized vessel pairs (carotid/jugular, suprarenal and infrarenal aorta/inferior vena cava (IVC), femoral artery/vein) at normothermia (core temperature 37 ± 0.2 °C). Influences of age and sex on average velocity differ by location in arteries. Average arterial velocities, when plotted as a function of distance from the heart, decrease nearly linearly from the suprarenal aorta to the femoral artery (adult and aged males: − 0.33 ± 0.13, R2 = 0.87; − 0.43 ± 0.10, R2 = 0.95; adult and aged females: − 0.23 ± 0.07, R2 = 0.91; − 0.23 ± 0.02, R2 = 0.99). Average velocity of aged males and average volumetric flow of aged males and females tended to be larger compared to adult comparators. With cardiovascular disease as the leading cause of death and with the implications of cardiovascular hemodynamics as important biomarkers for health and disease, this work provides a foundation for sex and age comparisons in pathophysiology by collecting and analyzing hemodynamic data for the healthy murine arterial and venous system from head-to-toe, across sex and age.

    更新日期:2020-01-04
  • Burst & High-Frequency Spinal Cord Stimulation Differentially Effect Spinal Neuronal Activity After Radiculopathy
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-08-05
    Alexander R. Kent, Christine L. Weisshaar, Lalit Venkatesan, Beth A. Winkelstein

    Although burst and high-frequency (HF) spinal cord stimulation (SCS) relieve neuropathic pain, their effects on neuronal hyperexcitability have not been compared. Specifically, it is unknown how the recharge components of burst SCS—either actively balanced or allowed to passively return—and/or different frequencies of HF SCS compare in altering neuronal activity. Neuronal firing rates were measured in the spinal dorsal horn on day 7 after painful cervical nerve root compression in the rat. Motor thresholds (MTs) and evoked neuronal recordings were collected during noxious stimuli before (baseline) and after delivery of SCS using different SCS modes: 10 kHz HF, 1.2 kHz HF, burst with active recharge, or burst with passive recharge. Spontaneous firing rates were also evaluated at baseline and after SCS. The average MT for 10 kHz SCS was significantly higher (p < 0.033) than any other mode. Burst with passive recharge was the only SCS mode to significantly reduce evoked (p = 0.019) and spontaneous (p = 0.0076) firing rates after noxious pinch. This study demonstrates that HF and burst SCS have different MTs and effects on both evoked and spontaneous firing rates, indicating they have different mechanisms of providing pain relief. Since burst with passive recharge was the only waveform to reduce firing, that waveform may be important in the neurophysiological response to stimulation.

    更新日期:2020-01-04
  • In Vivo Evaluation of Mg–5%Zn–2%Nd Alloy as an Innovative Biodegradable Implant Material
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-09-17
    L. Elkaiam, O. Hakimi, G. Yosafovich-Doitch, S. Ovadia, E. Aghion

    Abstract Mg-based alloys have been considered as potential structural materials for biodegradable implants in orthopedic and cardiovascular applications, particularly when combined with other biocompatible alloying elements. However, the performances of Mg-based alloys in in vitro conditions do not accurately reflect their behavior in an in vivo environment. As such, the present study aimed at evaluating the in vivo behavior of a novel Mg–5Zn–2Nd–0.13Y–0.35Zr alloy designated as ZE52 alloy. In vivo assessment was carried out using cylindrical disks implanted into the sub-cutaneous layer of the skin at the back midline of male Wistar rats for up to 11 weeks. Post-implantation responses evaluated included well-being behavior, blood biochemical tests and histology. The corrosion rate of the implants, expressed in terms of hydrogen gas formation, was evaluated by radiographic assessment and CT examination. Results of the well-being behavioral and blood biochemical tests indicated that the in vivo behavior of ZE52 alloy implants was similar to that of inert Ti–6Al–4V alloy implants introduced into a control group. Moreover, histological analysis did not reveal any severe inflammation, as compared to the reference alloy. However, significant sub-cutaneous gas cavities were observed, indicative of the accelerated degradation of the ZE52 alloy implants. The accelerated degradation was also manifested by the formation of alloy debris that was encapsulated within the gas cavities. Post-implantation gas bubble puncturing resulted in the complete degradation of the Mg-based implants, indicating that the inert nature of the gas prevented accelerated degradation of the alloy before it was naturally absorbed by the body.

    更新日期:2020-01-04
  • Head Impact Biomechanics Differ Between Girls and Boys Youth Ice Hockey Players
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-08-21
    Jason P. Mihalik, Erin B. Wasserman, Elizabeth F. Teel, Stephen W. Marshall

    Abstract The influence of sex on head impact biomechanics is unknown for youth ice hockey. We sought to determine sex differences in head impact severity and frequency in youth ice hockey players. Male (n = 110) and female (n = 25) players (13–16 years old) were recruited from a local hockey organization. Players wore helmets instrumented with the Head Impact Telemetry System for all competitions and practices throughout the season. Seven team-seasons were captured. Random intercepts general mixed linear models determined whether linear acceleration and rotational acceleration differed by sex. Linear regression models evaluated the relationship between sex and impact frequency. All head impact biomechanics were natural log-transformed as their distributions were right-skewed. Females sustained fewer impacts per player than males (27 fewer impacts per player-season, p < 0.0001) even when analysis was limited to games only (21 fewer impacts per player-season, p < 0.0001). The linear acceleration was higher among females (1.07 g; 95% CI 1.00, 1.13; p = 0.04). There were no other meaningful sex differences in head impact severity. Female players are not permitted to body check, and this likely explains why they sustain fewer head impacts than males. However, as a result, females likely sustain a higher proportion of head impacts through illegal or unintentional head contact, and these impacts may result in more force being delivered to the head.

    更新日期:2020-01-04
  • Hand-Held Instrument with Integrated Parallel Mechanism for Active Tremor Compensation During Microsurgery
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-09-17
    Tianci Zhang, Lun Gong, Shuxin Wang, Siyang Zuo

    Abstract Physiological hand tremor seriously influences the surgical instrument’s tip positioning accuracy during microsurgery. To solve this problem, hand-held active tremor compensation instruments are developed to improve tip positioning accuracy during microsurgery. This paper presents the design and performance of a new hand-held instrument that aims to stabilize hand tremors and increase accuracy in microsurgery. The key components are a three degrees of freedom (DOF) integrated parallel manipulator and a high-performance inertial measurement unit (IMU). The IMU was developed to sense the 3-DOF motion of the instrument tip. A customized filter was applied to extract specific hand tremor motion. Then, the instrument was employed to generate the reverse motion simultaneously to reduce tremor motion. Experimental results show that the tremor compensation mechanism is effective. The average RMS reduction ratio of bench test is 56.5% that is a significant tremor reduction ratio. For hand-held test, it has an average RMS reduction ratio of 41.0%. Hence, it could reduce hand tremor magnitudes by 31.7% RMS in 2-DOF.

    更新日期:2020-01-04
  • The Role of Recovery Lower Limb Segments in Post-Slip Determination of Falls Due to Instability or Limb Collapse
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-07-23
    Shuaijie Wang, Tanvi Bhatt, Xuan Liu, Yi-Chung Pai

    Abstract Slip-related falls can be induced by instability or limb collapse, but the key factors that determine these two fall causations remain unknown. The purpose of this study was to investigate the factors that contribute towards instability-induced and limb-collapse-induced slip-related falls by investigating 114 novel slip trials. The segment angles and moments of the recovery limb after slip-onset from pre-left-touchdown (pre-LTD) to post-left-touchdown (post-LTD) were calculated, and logistic regression was used to detect which variable contributed most to instability-induced and limb-collapse-induced falls. The results showed that recovery from instability was determined by the angle of the thigh at LTD (87.7%), while recovery from limb collapse was determined by the angle of the shank at post-LTD (90.4%). Correspondingly, instability-induced falls were successfully predicted (81.5%) based on the initial thigh angle at pre-LTD and the following peak thigh moment, while limb-collapse-induced falls were successfully predicted (85.5%) based on the initial shank angle at LTD and the following peak shank moment. According to our findings, taking a shorter recovery step and/or increasing the counterclockwise moment of the thigh after pre-LTD would help individuals resist instability-induced falls, while taking a larger recovery step and/or increasing the clockwise moment of the shank post-LTD would help resist limb-collapse-induced falls. The findings of this study are crucial for future clinical applications, because individually tailored reactive balance training could be provided to reduce vulnerability to specific types of falls and improve recovery rates post-slip exposure.

    更新日期:2020-01-04
  • Development of a Bioactive Polymeric Drug Eluting Coronary Stent Coating Using Electrospraying
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-08-22
    C. M. McKittrick, M. J. Cardona, R. A. Black, C. McCormick

    Drug-eluting stents are now routinely used in the treatment of acute coronary syndromes caused by coronary artery disease. Whilst the sustained release of anti-proliferative drugs from these devices has greatly reduced the need for repeat revascularisation procedures, this approach is not suitable for all patients and appears to delay regrowth of the endothelium, necessitating the use of prolonged dual anti-platelet therapy. Although the development of more advanced stent platforms and drug coatings has produced modest improvements in performance, these devices have not fully addressed the limitations experienced with their first-generation counterparts. In the present study, we developed a novel stent coating that provides controlled sirolimus release from a bioactive polymer (accelerate™ AT) that has previously been shown to support endothelial cell growth in vitro. A bespoke electrospray deposition process provided control over the coating thickness, surface roughness, drug load, and release kinetics. The resultant optimised coating combines rapid release of an anti-proliferative agent from a bioactive polymer coating that promotes re-endothelialisation, thereby offering potential protection against in-stent restenosis and thrombosis. This novel, dual-action coating therefore has significant therapeutic potential, with the enhanced control of drug load and release kinetics offered by electrospray deposition also opening up opportunities for more personalised treatment approaches. Further development and evaluation of these technologies in vitro and in vivo is therefore warranted.

    更新日期:2020-01-04
  • Biomechanical Testing of Additive Manufactured Proximal Humerus Fracture Fixation Plates
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-09-25
    Maryam Tilton, April Armstrong, Jennifer Sanville, Matthew Chin, Michael W. Hast, Gregory S. Lewis, Guha P. Manogharan

    Achieving satisfactory fracture fixation in osteoporotic patients with unstable proximal humerus fractures remains a major clinical challenge. Varus collapse is one of the more prominent complications that may lead to screw cutout. This aim of this study was to compare the fixation provided by conventional locking plates with novel design concepts that are only feasible through additive manufacturing (AM) techniques. In addition to reversed engineered implants, two novel implant designs with integrated struts were included in the study to provide medial support to humeral head. The medial strut was either solid or included a porous lattice structure intended to promote bone ingrowth. Biomechanical tests were performed using low density synthetic bones with simulated 3-part comminuted fractures. Nondestructive torsion and compression were performed, followed by increasing cyclic loading. The relative displacements between the bone fragments were determined using a 3D motion capture system. The AM manufactured implants with medial strut showed significant reduction of varus displacement during the increasing cyclic loading when compared to conventional designs. AM reversed-engineered locking plates showed similar mechanical behavior to conventional plates with identical geometry. This study demonstrates the feasibility and potential of employing alternative design via AM for fixation of unstable comminuted proximal humerus fractures to reduce fragment displacement.

    更新日期:2020-01-04
  • Evaluation of Local Tissue Reaction After the Application of a 3D Printed Novel Holdfast Device for Left Atrial Appendage Exclusion
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-07-15
    Maciej Brzeziński, Aleksandra Sejda, Rafał Pęksa, Maciej Pawlak, Kamil Bury, Zbigniew Adamiak, Maciej Kowalik, Dariusz Jagielak, Krzysztof Bartus, Mateusz K. Hołda, Radoslaw Litwinowicz, Jan Rogowski

    Abstract The left atrial appendage (LAA) is a small, finger-like extension of the left atrium and its exclusion is used as a treatment strategy to prevent ischemic stroke. Existing holdfast devices may damage the tissue, are unisized and not adjustable. A novel holdfast device for LAA exclusion devoid of these shortcomings was designed and 3D-printed using the Selective Laser Sintering (SLS) technology with polyamide powder and tested it on animal model. We selected the SLS 3D printing technology due to its wid14e availability and low production costs which could provide on-site 3D printing for specific patient. The purpose of this study was to evaluate the biocompatibility of the reported holdfast device and compare the histological results obtained for local tissue reactions to those obtained for an established grafting material. Thirty swine subdivided into two groups were examined. The LAA exclusion device was implanted and was either coated with a polyester vascular implant or not coated at all and the histological response to the device’s presence was evaluated which is a standard approach to test the device biocompatibility. In all cases, complete occlusion was seen without any pathological findings during the incubation time. In both groups, the surface of the atrium under a holdfast device was smooth and shiny and had no clots. The foreign body reaction of the LAA holdfast device made of polyamide powder was insignificantly lower compared to the polyester graft. Thus, it fulfils the parameters of biocompatibility at the highest degree, and makes it suitable material for the manufacturing of LAA holdfast devices.

    更新日期:2020-01-04
  • Membrane Deformation of Endothelial Surface Layer Interspersed with Syndecan-4: A Molecular Dynamics Study
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-09-13
    Xi Zhuo Jiang, Liwei Guo, Kai H. Luo, Yiannis Ventikos

    Abstract The lipid membrane of endothelial cells plays a pivotal role in maintaining normal circulatory system functions. To investigate the response of the endothelial cell membrane to changes in vascular conditions, an atomistic model of the lipid membrane interspersed with Syndecan-4 core protein was established based on experimental observations and a series of molecular dynamics simulations were undertaken. The results show that flow results in continuous deformation of the lipid membrane, and the degree of membrane deformation is not in monotonic relationship with the environmental changes (either the changes in blood velocity or the alteration of the core protein configuration). An explanation for such non-monotonic relationship is provided, which agrees with previous experimental results. The elevation of the lipid membrane surface around the core protein of the endothelial glycocalyx was also observed, which can be mainly attributed to the Coulombic interactions between the biomolecules therein. The present study demonstrates that the blood flow can deform the lipid membrane directly via the interactions between water molecules and lipid membrane atoms thereby affecting mechanosensing; it also presents an additional force transmission pathway from the flow to the lipid membrane via the glycocalyx core protein, which complements previous mechanotransduction hypothesis.

    更新日期:2020-01-04
  • A Concentric Tube Robot System for Rigid Bronchoscopy: A Feasibility Study on Central Airway Obstruction Removal
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-07-24
    Joshua B. Gafford, Scott Webster, Neal Dillon, Evan Blum, Richard Hendrick, Fabien Maldonado, Erin A. Gillaspie, Otis B. Rickman, S. Duke Herrell, Robert J. Webster

    Abstract New robotic systems have recently emerged to assist with peripheral lung access, but a robotic system for rigid bronchoscopy has yet to be developed. We describe a new robotic system that can deliver thin robotic manipulators through the ports of standard rigid bronchoscopes. The manipulators bend and elongate to provide maneuverability of surgical tools at the endoscope tip, without endoscope motion. We describe an initial feasibility study on the use of this system to bronchoscopically treat a central airway obstruction (CAO). CAO is prevalent and can be life-threatening in patients with large tumors, and conventional rigid bronchoscopic treatments place patients at risk of complications including broken teeth, neck trauma and damage to oropharyngeal structures due to significant forces induced by bronchoscope tilting and manipulation. In this study, we used an ex vivo ovine airway model to demonstrate the ability of a physician using the robotic system to efficiently remove tissue and restore the airway. Pre- and post-operative CT scans showed that the robot was able to reduce the degree of airway obstruction stenosis from 75 to 14% on average for five CAO resections performed in an ex vivo animal model. Using cadaver experiments, we demonstrated the potential of the robotic system to substantially reduce the intraoperative forces applied to the patient’s head and neck (from 80.6 to 4.1 N). These preliminary results illustrate that CAO removal is feasible with our new rigid bronchoscopy robot system, and that this approach has the potential to reduce forces applied to the patient due to bronchoscope angulation, and thereby reduce the risk of complications encountered during CAO surgery.

    更新日期:2020-01-04
  • An Effective CNN Method for Fully Automated Segmenting Subcutaneous and Visceral Adipose Tissue on CT Scans
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-08-26
    Zheng Wang, Yu Meng, Futian Weng, Yinghao Chen, Fanggen Lu, Xiaowei Liu, Muzhou Hou, Jie Zhang

    Abstract One major role of an accurate distribution of abdominal adipose tissue is to predict disease risk. This paper proposes a novel effective three-level convolutional neural network (CNN) approach to automate the selection of abdominal computed tomography (CT) images on large-scale CT scans and automatically quantify the visceral and subcutaneous adipose tissue. First, the proposed framework employs support vector machine (SVM) classifier with a configured parameter to cluster abdominal CT images from screening patients. Second, a pyramid dilation network (DilaLab) is designed based on CNN, to address the complex distribution and non-abdominal internal adipose tissue problems of biomedical image segmentation in visceral adipose tissue. Finally, since the trained DilaLab implicitly encodes the fat-related learning, the transferred DilaLab learning and a simple decoder constitute a new network (DilaLabPlus) for quantifying subcutaneous adipose tissue. The networks are trained not only all available CT images but also with a limited number of CT scans, such as 70 samples including a 10% validation subset. All networks are yielding more precise results. The mean accuracy of the configured SVM classifier yields promising performance of 99.83%, while DilaLabPlus achieves a remarkable performance improvement an with average of 98.08 ± 0.84% standard deviation and 0.7 ± 0.8% standard deviation false-positive rate. The performance of DilaLab yields average 97.82 ± 1.34% standard deviation and 1.23 ± 1.33% standard deviation false-positive rate. This study demonstrates considerable improvement in feasibility and reliability for the fully automated recognition of abdominal CT slices and segmentation of selected abdominal CT in subcutaneous and visceral adipose tissue, and it has a high agreement with a manually annotated biomarker.

    更新日期:2020-01-04
  • Differences in Pressure Recovery Between Balloon Expandable and Self-expandable Transcatheter Aortic Valves.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Hoda Hatoum,Rebecca T Hahn,Scott Lilly,Lakshmi Prasad Dasi

    Pressure recovery downstream of the aortic valve constitutes an important factor affecting the calculation of pressure gradient (PG) across the valve and therefore the accuracy of the calculated aortic valve area. Some clinical studies hypothesized that stent and valve cusps design contribute to flow acceleration and Doppler-measured valve gradients across the balloon-expandable transcatheter aortic valve. This study aims at elucidating the physical mechanisms behind pressure recovery variations between Edwards SAPIEN 3 and Medtronic Evolut TAVs through the measurements of sensitive and precise axial pressure profiles. A 23 mm Edwards SAPIEN3 and a 26 mm Medtronic Evolut were deployed in a pulse duplicator. A Millar catheter was used to record 50 cycles of pressure data along the centerline of the valve chamber upstream and downstream of the valve. The peak PG obtained with SAPIEN at vena contracta (VC) is 18.83 ± 0.75 mmHg and after recovery, 9.56 ± 0.78 mmHg. For Evolut at VC, peak PG is 18.25 ± 0.63 mmHg and after recovery, 10.3 ± 0.57 mmHg. The differences in peak PG at VC and at the recovery were statistically significant (p < 0.001). With SAPIEN 3 at VC, the mean PG obtained is 10.11 ± 0.63 mmHg and after recovery 7.06 ± 0.46 mmHg. For Evolut, mean PG at VC is 10.45 ± 0.67 mmHg and after recovery 7.99 ± 0.61 mmHg. The differences between the mean PG between the two valves was not statistically significant at VC (p = 0.71) but significant post-recovery (p < 0.00001). While gradients at the VC are higher with the SAPIEN 3, the net gradient after pressure recovery is significantly lower compared to Evolut TAV. Efficiency of pressure recovery significantly depends on valve type due to stent interference with the recovering blood flow.

    更新日期:2019-11-01
  • Decision Tree Based Classification of Abdominal Aortic Aneurysms Using Geometry Quantification Measures.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2018-08-23
    Shalin A Parikh,Raymond Gomez,Mirunalini Thirugnanasambandam,Sathyajeeth S Chauhan,Victor De Oliveira,Satish C Muluk,Mark K Eskandari,Ender A Finol

    Abdominal aortic aneurysm (AAA) is an asymptomatic aortic disease with a survival rate of 20% after rupture. It is a vascular degenerative condition different from occlusive arterial diseases. The size of the aneurysm is the most important determining factor in its clinical management. However, other measures of the AAA geometry that are currently not used clinically may also influence its rupture risk. With this in mind, the objectives of this work are to develop an algorithm to calculate the AAA wall thickness and abdominal aortic diameter at planes orthogonal to the vessel centerline, and to quantify the effect of geometric indices derived from this algorithm on the overall classification accuracy of AAA based on whether they were electively or emergently repaired. Such quantification was performed based on a retrospective review of existing medical records of 150 AAA patients (75 electively repaired and 75 emergently repaired). Using an algorithm implemented within the MATLAB computing environment, 10 diameter- and wall thickness-related indices had a significant difference in their means when calculated relative to the AAA centerline compared to calculating them relative to the medial axis. Of these 10 indices, nine were wall thickness-related while the remaining one was the maximum diameter (Dmax). Dmax calculated with respect to the medial axis is over-estimated for both electively and emergently repaired AAA compared to its counterpart with respect to the centerline. C5.0 decision trees, a machine learning classification algorithm implemented in the R environment, were used to construct a statistical classifier. The decision trees were built by splitting the data into 70% for training and 30% for testing, and the properties of the classifier were estimated based on 1000 random combinations of the 70/30 data split. The ensuing model had average and maximum classification accuracies of 81.0 and 95.6%, respectively, and revealed that the three most significant indices in classifying AAA are, in order of importance: AAA centerline length, L2-norm of the Gaussian curvature, and AAA wall surface area. Therefore, we infer that the aforementioned three geometric indices could be used in a clinical setting to assess the risk of AAA rupture by means of a decision tree classifier. This work provides support for calculating cross-sectional diameters and wall thicknesses relative to the AAA centerline and using size and surface curvature based indices in classification studies of AAA.

    更新日期:2019-11-01
  • Simulating Developmental Cardiac Morphology in Virtual Reality Using a Deformable Image Registration Approach.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2018-08-17
    Arash Abiri,Yichen Ding,Parinaz Abiri,René R Sevag Packard,Vijay Vedula,Alison Marsden,C-C Jay Kuo,Tzung K Hsiai

    While virtual reality (VR) has potential in enhancing cardiovascular diagnosis and treatment, prerequisite labor-intensive image segmentation remains an obstacle for seamlessly simulating 4-dimensional (4-D, 3-D + time) imaging data in an immersive, physiological VR environment. We applied deformable image registration (DIR) in conjunction with 3-D reconstruction and VR implementation to recapitulate developmental cardiac contractile function from light-sheet fluorescence microscopy (LSFM). This method addressed inconsistencies that would arise from independent segmentations of time-dependent data, thereby enabling the creation of a VR environment that fluently simulates cardiac morphological changes. By analyzing myocardial deformation at high spatiotemporal resolution, we interfaced quantitative computations with 4-D VR. We demonstrated that our LSFM-captured images, followed by DIR, yielded average dice similarity coefficients of 0.92 ± 0.05 (n = 510) and 0.93 ± 0.06 (n = 240) when compared to ground truth images obtained from Otsu thresholding and manual segmentation, respectively. The resulting VR environment simulates a wide-angle zoomed-in view of motion in live embryonic zebrafish hearts, in which the cardiac chambers are undergoing structural deformation throughout the cardiac cycle. Thus, this technique allows for an interactive micro-scale VR visualization of developmental cardiac morphology to enable high resolution simulation for both basic and clinical science.

    更新日期:2019-11-01
  • A Wearable Magnet-Based System to Assess Activity and Joint Flexion in Humans and Large Animals.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2018-08-08
    Feini Qu,Brendan D Stoeckl,Peter M Gebhard,Todd J Hullfish,Josh R Baxter,Robert L Mauck

    Functional outcomes, such as joint flexion and gait, are important indicators of efficacy in musculoskeletal research. Current technologies that objectively assess these parameters, including visual tracking systems and force plates, are challenging to deploy in long-term translational and clinical studies. To that end, we developed a wearable device that measures both physical activity and joint flexion using a single integrated sensor and magnet system, and hypothesized that it could evaluate post-operative functional recovery in an unsupervised setting. To demonstrate the feasibility of measuring joint flexion, we first compared knee motion from the wearable device to that acquired from a motion capture system to confirm that knee flexion measurements during normal human gait, predicted via changes in magnetic field strength, closely correlated with data acquired by motion capture. Using this system, we then monitored a porcine cohort after bilateral stifle arthrotomy to investigate longitudinal changes in physical activity and joint flexion. We found that unsupervised activity declined immediately after surgery, with a return to pre-operative activity occurring over a period of 2 weeks. By providing objective, individualized data on locomotion and joint function, this magnet-based system will facilitate the in vivo assessment of novel therapeutics in translational orthopaedic research.

    更新日期:2019-11-01
  • Classification of Tumor Epithelium and Stroma by Exploiting Image Features Learned by Deep Convolutional Neural Networks.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2018-07-28
    Yue Du,Roy Zhang,Abolfazl Zargari,Theresa C Thai,Camille C Gunderson,Katherine M Moxley,Hong Liu,Bin Zheng,Yuchen Qiu

    The tumor-stroma ratio (TSR) reflected on hematoxylin and eosin (H&E)-stained histological images is a potential prognostic factor for survival. Automatic image processing techniques that allow for high-throughput and precise discrimination of tumor epithelium and stroma are required to elevate the prognostic significance of the TSR. As a variant of deep learning techniques, transfer learning leverages nature-images features learned by deep convolutional neural networks (CNNs) to relieve the requirement of deep CNNs for immense sample size when handling biomedical classification problems. Herein we studied different transfer learning strategies for accurately distinguishing epithelial and stromal regions of H&E-stained histological images acquired from either breast or ovarian cancer tissue. We compared the performance of important deep CNNs as either a feature extractor or as an architecture for fine-tuning with target images. Moreover, we addressed the current contradictory issue about whether the higher-level features would generalize worse than lower-level ones because they are more specific to the source-image domain. Under our experimental setting, the transfer learning approach achieved an accuracy of 90.2 (vs. 91.1 for fine tuning) with GoogLeNet, suggesting the feasibility of using it in assisting pathology-based binary classification problems. Our results also show that the superiority of the lower-level or the higher-level features over the other ones was determined by the architecture of deep CNNs.

    更新日期:2019-11-01
  • On the Significance of Systolic Flow Waveform on Aortic Valve Energy Loss.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2018-07-22
    Hoda Hatoum,Brandon L Moore,Lakshmi Prasad Dasi

    This study aims to quantitatively and qualitatively assess energy dissipation in the aortic valve as a function of systolic aortic flow waveform representing pathologies where flow time-to-peak is delayed. A bioprosthetic valve was tested in the aortic position of a left-heart simulator under physiological pressure and flow conditions. The flow loop piston pump was programmed to generate three different flow waveforms each with a different peak time annotated as early peak (EP) with a rapid acceleration, mid peak (MP) and late peak (LP) with a rapid deceleration. Energy dissipation was calculated from flow and pressure measurements while sinus vorticity dynamics were evaluated using time-resolved planar particle image velocimetry. Average pressure gradients during systole are found 30.2 ± 0.19, 30.7 ± 0.25 and 32.9 ± 0.29 mmHg and average dissipation over systole is found 0.95 ± 0.026, 1.05 ± 0.034 and 1.25 ± 0.043 W for EP, MP and LP respectively. As systole's acceleration phase is slower, sinus vortices are more likely to form, necessitating more energy exchange from shear layers inducing more viscous dissipation. EP found in healthy individuals is superior in terms of reducing energy dissipation and increasing aortic valve efficiency. In the context of possible left ventricular dysfunction and aortic stenosis, this means that delayed time-to-peak in the aortic flow waveform seen is not compensatory.

    更新日期:2019-11-01
  • X-ray CT in Phase Contrast Enhancement Geometry of Alginate Microbeads in a Whole-Animal Model.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-05-28
    Jacob Brown,Sami Somo,Frank Brooks,Sergey Komarov,Weimin Zhou,Mark Anastasio,Eric Brey

    Imaging soft biomaterials in vivo is a significant challenge, as most conventional techniques are limited by biomaterial contrast, penetration depth, or spatial resolution. Exogeneous contrast agents used to increase contrast may also alter material properties or exhibit local toxicity. The capability to observe biomaterial constructs in vivo without introducing exogenous contrast would improve preclinical testing and evaluation. Conventional X-ray Computed Tomography allows fast, high-resolution imaging at high penetration depth, but biomaterial contrast is low. Previous studies employing X-ray phase contrast (XPC) and utilizing a synchrotron source provided support for the significant potential of XPC in imaging biomaterials without contrast agents. In this study, XPC tomography was used to image alginate hydrogel microspheres within a small animal omental pouch model using a commercially available X-ray source. Multilayer microbeads could be identified in the XPC images with volumetric and structural information not possible in histological analysis. The number of microbeads present and microbead volume and diameter could be quantified from the images. The results of this study show that XPC tomography can be a useful tool for monitoring of implanted soft biomaterials in small animal models.

    更新日期:2019-11-01
  • Impact Performance of Certified Bicycle Helmets Below, On and Above the Test Line.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Alyssa L DeMarco,Dennis D Chimich,Stephanie J Bonin,Gunter P Siegmund

    Bicycle helmets are effective in reducing many head injuries, but their effectiveness could be improved if they provided protection over a larger range of impact locations. We sought to quantify the impact performance of 12 helmet models below, on and above the CPSC prescribed test line. All helmets were drop tested at an impact speed of 6.2 m/s. One helmet adequately attenuated impacts below the CPSC limit of 300 g for all impact locations tested below, on and above the test line. Five helmets met this limit for impacts on or above the test line as required in the CPSC standard, but failed to meet it below the test line (not required in the standard). The remaining six helmets failed to meet the criterion on and/or above the test line. Our findings indicate that consumers should not assume that all portions of a helmet provide adequate and equivalent protection. Our findings also suggest that the CPSC's current system of self-regulation and self-testing by manufacturers does not prevent substandard bicycle helmets from being sold. Public availability of manufacturers' impact test data, an independent testing panel, and/or a wider distribution of impact locations are needed to better protect bicyclists.

    更新日期:2019-11-01
  • 2019 Athanasiou ABME Student Awards.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Bethany Rowson

    更新日期:2019-11-01
  • Annals of Biomedical Engineering 2018 Year in Review.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Bethany Rowson,Stefan M Duma

    更新日期:2019-11-01
  • Reporter Scaffolds for Clinically Relevant Cell Transplantation Studies.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-11-07
    Morgan Bolger,Rebecca Groynom,Kath Bogie,Erin Lavik

    There are a number of cell therapies that are either in clinical trials or moving toward clinical trials, particularly for diseases of the retina. One of the challenges with cell therapies is tracking the status of cells over time. Genetic manipulation can facilitate this, but it can limit the clinical application of the cells. There are a host of fluorophores that have been developed to assess the status of cells, but these molecules tend to be cleared rapidly from cells. There are preclinical strategies that use degradable scaffolds, and we hypothesized that these scaffolds could be used to track the state of cells during preclinical studies. In this work, we explored whether fluorophores could be delivered from simple scaffolds fabricated under extremely harsh conditions, be active upon release, and report on the cells growing on the scaffolds over time. We encapsulated CellROX® Green Reagent, and pHrodo™ Red AM in poly(lactic-co-glycolic acid) (PLGA) scaffolds, showed that they could be delivered over weeks and were still active upon release and taken up by cells. These experiments provide the foundation for using scaffolds to deliver molecules to report on cells.

    更新日期:2019-11-01
  • Encapsulation of Mesenchymal Stem Cells in 3D Ovarian Cell Constructs Promotes Stable and Long-Term Hormone Secretion with Improved Physiological Outcomes in a Syngeneic Rat Model.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-08-02
    Sivanandane Sittadjody,Kevin M Enck,Alexandra Wells,James J Yoo,Anthony Atala,Justin M Saul,Emmanuel C Opara

    Loss of ovarian function (e.g., due to menopause) leads to profound physiological effects in women including changes in sexual function and osteoporosis. Hormone therapies are a known solution, but their use has significantly decreased due to concerns over cardiovascular disease and certain cancers. We recently reported a tissue-engineering strategy for cell hormone therapy (cHT) in which granulosa cells and theca cells are encapsulated to mimic native ovarian follicles. cHT improved physiological outcomes and safety compared to pharmacological hormone therapies in a rat ovariectomy model. However, cHT did not achieve estrogen levels as high as ovary-intact animals. In this report, we examined if hormone secretion from cHT constructs is impacted by incorporation of bone marrow-derived mesenchymal stem cells (BMSC) since these cells contain regulatory factors such as aromatase necessary for estrogen production. Incorporation of BMSCs led to enhanced estrogen secretion in vitro. Moreover, cHT constructs with BMSCs achieved estrogen secretion levels significantly greater than constructs without BMSCs in ovariectomized rats from 70 to 90 days after implantation, while also regulating pituitary hormones. cHT constructs with BMSC ameliorated estrogen deficiency-induced uterine atrophy without hyperplasia. The results indicate that inclusion of BMSC in cHT strategies can improve performance.

    更新日期:2019-11-01
  • Correction to: A High-Precision and Miniature Fiber Bragg Grating-Based Force Sensor for Tissue Palpation During Minimally Invasive Surgery.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-11-23
    Changhu Lv,Shuxin Wang,Chaoyang Shi

    The second equation in the section "Definition of Objective Functions and Constraints" was corrected to fix a mismatch between the PDF and HTML versions of the article.

    更新日期:2019-11-01
  • A High-Precision and Miniature Fiber Bragg Grating-Based Force Sensor for Tissue Palpation During Minimally Invasive Surgery.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-11-07
    Changhu Lv,Shuxin Wang,Chaoyang Shi

    This paper presents a novel Fiber Bragg Grating (FBG)-based palpation force sensor to explore tissue abnormalities during minimally invasive surgery. The proposed sensor design mainly consists of a miniature force-sensitive flexure, one tightly suspended optical fiber embedded with one FBG element and associated connectors and fixations. The flexure design has been prototyped through the configuration synthesis of Sarrus mechanism by using a rigid-body replacement method to achieve an excellent axial linear force-deformation relationship and a large measurement range. The mounted fiber has been configured at the flexure's central line with its two ends glued, and its tight suspension configuration can achieve improved resolution and sensitivity and avoid the FBG chirping failure compared to the commonly used direct FBG-pasting methods. Finite element method (FEM)-based simulation has been performed to investigate both static and dynamic performance to aid in structural design. Simulation-enabled structural optimization design has also been implemented to further improve the proposed design and the sensor's sensitivity has been increased. The optimized sensor design has been prototyped and calibrated to demonstrate an excellent linearity with a small linearity error of 0.97% and achieve a high resolution of 2.55 mN within a relatively large measurement range of 0-5 N. Dynamic force stimulation experiments, in vitro palpation implementation on a silicone phantom embedded with simulated tumors and ex vivo indentation experiments on a porcine liver have validated the effectiveness of the presented sensor design.

    更新日期:2019-11-01
  • EndOxy: Dynamic Long-Term Evaluation of Endothelialized Gas Exchange Membranes for a Biohybrid Lung.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Sarah Klein,Felix Hesselmann,Suzana Djeljadini,Tanja Berger,Anja Lena Thiebes,Thomas Schmitz-Rode,Stefan Jockenhoevel,Christian G Cornelissen

    In the concept of a biohybrid lung, endothelial cells seeded on gas exchange membranes form a non-thrombogenic an anti-inflammatory surface to overcome the lacking hemocompatibility of today's oxygenators during extracorporeal membrane oxygenation. To evaluate this concept, the long-term stability and gas exchange performance of endothelialized RGD-conjugated polydimethylsiloxane (RGD-PDMS) membranes was evaluated. Human umbilical vein endothelial cells (ECs) were cultured on RGD-PDMS in a model system under physiological wall shear stress (WSS) of 0.5 Pa for up to 33 days. Gas exchange performance was tested with three biological replicates under elevated WSS of 2.5 Pa using porcine blood adjusted to venous values following ISO 7199 and blood gas analysis. EC morphology was assessed by immunocytochemistry (n = 3). RGD-PDMS promoted endothelialization and stability of endothelialized membranes was shown for at least 33 days and for a maximal WSS of 2.5 Pa. Short-term exposure to porcine blood did not affect EC integrity. The gas transfer tests provided evidence for the oxygenation and decarboxylation of the blood across endothelialized membranes with a decrease of transfer rates over time that needs to be addressed in further studies with larger sample sizes. Our results demonstrate the general suitability of RGD-PDMS for biohybrid lung applications, which might enable long-term support of patients with chronic lung failure in the future.

    更新日期:2019-11-01
  • Emerging Biomimetic Materials for Studying Tumor and Immune Cell Behavior.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-10-17
    Logan A Northcutt,Alejandra Suarez-Arnedo,Marjan Rafat

    Cancer is one of the leading causes of death both in the United States and worldwide. The dynamic microenvironment in which tumors grow consists of fibroblasts, immune cells, extracellular matrix (ECM), and cytokines that enable progression and metastasis. Novel biomaterials that mimic these complex surroundings give insight into the biological, chemical, and physical environment that cause cancer cells to metastasize and invade into other tissues. Two-dimensional (2D) cultures are useful for gaining limited information about cancer cell behavior; however, they do not accurately represent the environments that cells experience in vivo. Recent advances in the design and tunability of diverse three-dimensional (3D) biomaterials complement biological knowledge and allow for improved recapitulation of in vivo conditions. Understanding cell-ECM and cell-cell interactions that facilitate tumor survival will accelerate the design of more effective therapies. This review discusses innovative materials currently being used to study tumor and immune cell behavior and interactions, including materials that mimic the ECM composition, mechanical stiffness, and integrin binding sites of the tumor microenvironment.

    更新日期:2019-11-01
  • Estimation of Spinal Loading During Manual Materials Handling Using Inertial Motion Capture.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Frederik Greve Larsen,Frederik Petri Svenningsen,Michael Skipper Andersen,Mark de Zee,Sebastian Skals

    Musculoskeletal models have traditionally relied on measurements of segment kinematics and ground reaction forces and moments (GRF&Ms) from marked-based motion capture and floor-mounted force plates, which are typically limited to laboratory settings. Recent advances in inertial motion capture (IMC) as well as methods for predicting GRF&Ms have enabled the acquisition of these input data in the field. Therefore, this study evaluated the concurrent validity of a novel methodology for estimating the dynamic loading of the lumbar spine during manual materials handling based on a musculoskeletal model driven exclusively using IMC data and predicted GRF&Ms. Trunk kinematics, GRF&Ms, L4-L5 joint reaction forces (JRFs) and erector spinae muscle forces from 13 subjects performing various lifting and transferring tasks were compared to a model driven by simultaneously recorded skin-marker trajectories and force plate data. Moderate to excellent correlations and relatively low magnitude differences were found for the L4-L5 axial compression, erector spinae muscle and vertical ground reaction forces during symmetrical and asymmetrical lifting, but discrepancies were also identified between the models, particularly for the trunk kinematics and L4-L5 shear forces. Based on these results, the presented methodology can be applied for estimating the relative L4-L5 axial compression forces under dynamic conditions during manual materials handling in the field.

    更新日期:2019-11-01
  • 2019 ABME Paper Awards.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : null
    Bethany Rowson

    更新日期:2019-11-01
  • A Lifetime Achievement in Bioengineering: Professor Shu Chien.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-10-28
    Sheldon Weinbaum,Yi-Shuan Julie Li,Geert W Schmid-Schönbein

    更新日期:2019-11-01
  • Material Mapping of QCT-Derived Scapular Models: A Comparison with Micro-CT Loaded Specimens Using Digital Volume Correlation.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-07-13
    Nikolas K Knowles,Jonathan Kusins,Mohammadreza Faieghi,Melissa Ryan,Enrico Dall'Ara,Louis M Ferreira

    Subject- and site-specific modeling techniques greatly improve finite element models (FEMs) derived from clinical-resolution CT data. A variety of density-modulus relationships are used in scapula FEMs, but the sensitivity to selection of relationships has yet to be experimentally evaluated. The objectives of this study were to compare quantitative-CT (QCT) derived FEMs mapped with different density-modulus relationships and material mapping strategies to experimentally loaded cadaveric scapular specimens. Six specimens were loaded within a micro-CT (33.5 μm isotropic voxels) using a custom-hexapod loading device. Digital volume correlation (DVC) was used to estimate full-field displacements by registering images in pre- and post-loaded states. Experimental loads were measured using a 6-DOF load cell. QCT-FEMs replicated the experimental setup using DVC-driven boundary conditions (BCs) and were mapped with one of fifteen density-modulus relationships using elemental or nodal material mapping strategies. Models were compared based on predicted QCT-FEM nodal reaction forces compared to experimental load cell measurements and linear regression of the full-field nodal displacements compared to the DVC full-field displacements. Comparing full-field displacements, linear regression showed slopes ranging from 0.86 to 1.06, r-squared values of 0.82-1.00, and max errors of 0.039 mm for all three Cartesian directions. Nearly identical linear regression results occurred for both elemental and nodal material mapping strategies. Comparing QCT-FEM to experimental reaction forces, errors ranged from - 46 to 965% for all specimens, with specimen-specific errors as low as 3%. This study utilized volumetric imaging combined with mechanical loading to derive full-field experimental measurements to evaluate various density-modulus relationships required for QCT-FEMs applied to whole-bone scapular loading. The results suggest that elemental and nodal material mapping strategies are both able to simultaneously replicate experimental full-field displacements and reactions forces dependent on the density-modulus relationship used.

    更新日期:2019-11-01
  • Restricting Lower Limb Flail is Key to Preventing Fatal Pelvic Blast Injury.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-05-31
    Iain A Rankin,Thuy-Tien Nguyen,Diagarajen Carpanen,Jonathan C Clasper,Spyros D Masouros

    Pelvic vascular injury in the casualty of an explosive insult is a principal risk factor for increased mortality. The mechanism of injury has not previously been investigated in a physical model. In this study, a small-animal model of pelvic blast injury with a shock-tube mediated blast wave was utilised and showed that lower limb flail is necessary for an unstable pelvic fracture with vascular injury to occur. One hundred and seventy-three cadaveric mice underwent shock-tube blast testing and subsequent injury analysis. Increasingly displaced pelvic fractures and an increase in the incidence of pelvic vascular injury were seen with increasing lower limb flail; the 50% risk of vascular injury was 66° of lower limb flail out from the midline (95% confidence intervals 59°-75°). Pre-blast surgical amputation at the hip or knee showed the thigh was essential to result in pelvic displacement whilst the leg was not. These findings, corroborated by clinical data, bring a paradigm shift in our understanding of the mechanism of blast injury. Restriction of lower limb flail in the human, through personal protective equipment, has the potential to mitigate the effects of pelvic blast injury.

    更新日期:2019-11-01
  • Linking Joint Impairment and Gait Biomechanics in Patients with Juvenile Idiopathic Arthritis.
    Ann. Biomed. Eng. (IF 3.474) Pub Date : 2019-05-22
    Erica Montefiori,Luca Modenese,Roberto Di Marco,Silvia Magni-Manzoni,Clara Malattia,Maurizio Petrarca,Anna Ronchetti,Laura Tanturri de Horatio,Pieter van Dijkhuizen,Anqi Wang,Stefan Wesarg,Marco Viceconti,Claudia Mazzà,

    Juvenile Idiopathic Arthritis (JIA) is a paediatric musculoskeletal disease of unknown aetiology, leading to walking alterations when the lower-limb joints are involved. Diagnosis of JIA is mostly clinical. Imaging can quantify impairments associated to inflammation and joint damage. However, treatment planning could be better supported using dynamic information, such as joint contact forces (JCFs). To this purpose, we used a musculoskeletal model to predict JCFs and investigate how JCFs varied as a result of joint impairment in eighteen children with JIA. Gait analysis data and magnetic resonance images (MRI) were used to develop patient-specific lower-limb musculoskeletal models, which were evaluated for operator-dependent variability (< 3.6°, 0.05 N kg-1 and 0.5 BW for joint angles, moments, and JCFs, respectively). Gait alterations and JCF patterns showed high between-subjects variability reflecting the pathology heterogeneity in the cohort. Higher joint impairment, assessed with MRI-based evaluation, was weakly associated to overall joint overloading. A stronger correlation was observed between impairment of one limb and overload of the contralateral limb, suggesting risky compensatory strategies being adopted, especially at the knee level. This suggests that knee overloading during gait might be a good predictor of disease progression and gait biomechanics should be used to inform treatment planning.

    更新日期:2019-11-01
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