ABSTRACT
The global learning initiative at Northeastern University is focused on fostering intercultural communication skills. The Dialogue of Civilization (DOC) program serves as a mechanism to achieve such a goal by offering faculty-led international experiences. In this paper, we have presented a detailed account of a DOC program that took place in Norway. The primary objective of the program was to teach mechanical engineering and bio-engineering students computational skills while stimulating critical thinking about the cultural and social aspects of technology and engineering in Norway. The program focused on two courses: a technical course and a special topics course. The technical course introduced students to finite element analysis, with practical applications and site visits in Norway to enhance experiential learning. In the special topics course, the interplay between modern technologies, like green energy, state policies, and the rights and traditions of the indigenous Sámi people was explored. The course highlighted both the progressive social policies in Norway and the historical discrimination against the Sámi. Student feedback was positive and experiential learning components such as guest lectures and site visits were particularly appreciated. Additional surveys showed that students' self-confidence was higher following the DOC program. In addition, female-identifying students had higher confidence in their future success after completion of this program as compared to their male-identifying counterparts. Our paper is expected to serve as a resource for educators seeking to integrate technical education with intercultural experiences and discussions on social and cultural impacts in engineering.
Subject(s)
Eastern European People , Problem-Based Learning , Students , Female , Humans , Male , Bioengineering , Learning , NorwayABSTRACT
Aberrant expression of glycans, i.e., oligosaccharide moiety covalently attached to proteins or lipids, is characteristic of various cancers, including urothelial ones. The binding of lectins to glycans is classified as molecular recognition, which makes lectins a strong tool for understanding their role in developing diseases. Here, we present a quantitative approach to tracing glycan-lectin interactions in cells, from the initial to the steady phase of adhesion. The cell adhesion was measured between urothelial cell lines (non-malignant HCV29 and carcinoma HT1376 and T24 cells) and lectin-coated surfaces. Depending on the timescale, single-cell force spectroscopy, and adhesion assays conducted in static and flow conditions were applied. The obtained results reveal that the adhesion of urothelial cells to two specific lectins, i.e., phytohemagglutinin-L and wheat germ agglutinin, was specific and selective. Thus, these lectins can be applied to selectively capture, identify, and differentiate between cancer types in a label-free manner. These results open up the possibility of designing lectin-based biosensors for diagnostic or prognostic purposes and developing strategies for drug delivery that could target cancer-associated glycans.
Subject(s)
Lectins , Urinary Bladder Neoplasms , Humans , Lectins/metabolism , Urinary Bladder Neoplasms/metabolism , Phytohemagglutinins/pharmacology , Wheat Germ Agglutinins , Polysaccharides/metabolismABSTRACT
The net swelling dynamics in molecular responsive hydrogels can be viewed as an integrated effect of discernible processes involving transport of actuating species, reaction with network components like destabilization of physical crosslinks or cleavage of network strands and concomitant network relaxation. Here, we describe a finite element modeling approach coupling these interdependent, underlying processes in hydrogels including oligonucleotide duplexes as physical crosslinks that can be destabilized by a particular molecule. These molecular responsive hydrogels based on acrylamide including either DNA or oligomorpholinos (MO), a DNA analogue, as functional elements can be made with various content of dsDNA or dsMO supported cross-links. The dsDNA or dsMO integrated in the hydrogel can be fabricated with ssDNA designed to competitively displace the connectivity of the dsDNA supported crosslinks, and similar for the MO hydrogels. The overall processes can be framed in a diffusion-reaction scheme. This process is dependent on the concentration of the diffusing species, their diffusion coefficients and their location. Thus, the reaction taking place in particular molecular responsive hydrogels is coupled with the deformations due to swelling and mechanical constraints undergone by the gel. Numerical examples show the importance of coupling reaction-diffusion with mechanical deformations for such gels. Finally, our model is compared to swelling experiments of hemi-spheroidal molecular responsive hydrogels bound to an optical fiber. Parameters of the reaction-diffusion model were obtained by fitting the model to reported experimental data where molecular stimuli designed with different molecular parameters for the competitive displacement reaction were employed in the swelling experiments.
Subject(s)
DNA , Hydrogels , DNA, Single-Stranded , DiffusionABSTRACT
Composite soft materials are used as compounds for determining the effects of mechanical cues on cell behavior and cell encapsulation and for controlling drug release. The appropriate composite soft materials are conventionally prepared by selective deposition of polymers at the surface of an ionic hydrogel. In the present study we address the impact of a mechanically stratified two-layer structure of these materials on their overall mechanical characterization by applying a combination of nanoindentation, confocal microscopy and finite element modelling. We prepare covalent cross-linked hydrogels based on acrylamide (AAM) and including an anionic group, and impregnate them using a multilayer deposition strategy of alternating exposure to cationic chitosan and anionic alginate. The thickness of the chitosan-alginate layer on the hydrogels was determined to be 0.4 ± 0.05 µm for 4 bilayers, and 0.7 ± 0.1 µm for the 8 bilayer deposition procedure employing a fluorescently labelled chitosan and confocal microscopy. The force-indentation data for the AAM gels were highly reproducible, whereas 77% and 50% of the force-indentation data were reproducible following the 4 and 8 bilayer deposition. The main trends in the reproducible force-distance data were found to yield an apparent increased Young's modulus after the deposition. Finite element modelling showed that adaption of a homogeneous Young's modulus for the specimens with deposited layers yields approximately three times too low stiffness compared to the estimate of the mechanical properties of the outer part in the two-layered mechanical model. The thickness of the multilayer region determined by confocal microscopy was used in the model. This study shows that the mechanical layered property needs to be included in the interpretation of the nanoindentation data when there is a significant mechanical contrast.
ABSTRACT
Recruiting circulating cells based on interactions between surface receptors and corresponding ligands holds promise for capturing cells with specific adhesive properties. Our study investigates the adhesion of skin cells to specific lectins, particularly focusing on advancements in lectin-based biosensors with diagnostic potential. We explore whether we can successfully capture normal skin (melanocytes and keratinocytes) and melanoma (WM35, WM115, WM266-4) cells in a low-shear flow environment by coating surfaces with lectins. Specifically, we coated surfaces with Dolichos biflorus (DBA) and Maackia Amurensis (MAL) lectins, which were used to detect and capture specific skin cells from the flow of cell mixture. Alterations in glycan expression (confirmed by fluorescent microscopy) demonstrated that DBA binds predominantly to normal skin cells, while MAL interacts strongly with melanoma cells. Assessing adhesion under static and dynamic low-shear stress conditions (up to 30 mPa) underscores the reliability of DBA and MAL as markers for discriminating specific cell type. Melanocytes and keratinocytes adhere to DBA-coated surfaces, while melanoma cells prefer MAL-coated surfaces. A comprehensive analysis encompassing cell shape, cytoskeleton, and focal adhesions shows the independence of our approach from the inherent characteristics of cells, thus demonstrating its robustness. Our results carry practical implications for lectin-biosensor designs, emphasizing the significance of glycan-based discrimination of pathologically altered cells. Combined with microfluidics, it demonstrates the value of cell adhesion as a discriminant of cancer-related changes, with potential applications spanning diagnostics, therapeutic interventions, and advanced biomedical technologies.
Subject(s)
Biosensing Techniques , Cell Adhesion , Skin Neoplasms , Humans , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Glycosylation , Skin Neoplasms/pathology , Melanoma/pathology , Melanoma/diagnosis , Keratinocytes/cytology , Skin/pathology , Skin/chemistry , Lectins/chemistry , Lectins/metabolism , Cell Line, Tumor , Melanocytes/cytology , Melanocytes/metabolism , Microfluidics/methods , Microfluidic Analytical Techniques/instrumentationABSTRACT
Degenerative mitral valve disease is a common valvular disease with two arguably distinct phenotypes: fibroelastic deficiency and Barlow's disease. These phenotypes significantly alter the microstructures of the leaflets, particularly the collagen fibers, which are the main mechanical load carriers. The predominant method of investigation is histological sections. However, the sections are cut transmurally and provide a lateral view of the microstructure of the leaflet, while the mechanics and function are determined by the planar arrangement of the collagen fibers. This study, for the first time, quantitatively examined planar collagen distribution quantitatively in health and disease using second harmonic generation microscopy throughout the thickness of the mitral valve leaflets. Twenty diseased samples from eighteen patients and six control samples were included in this study. Healthy tissue had highly aligned collagen fibers. In fibroelastic deficiency they are less aligned and in Barlow's disease they are completely dispersed. In both diseases, collagen fibers have two preferred orientations, which, in contrast to the almost constant one orientation in healthy tissues, also vary across the thickness. The results indicate altered in vivo mechanical stresses and strains on the mitral valve leaflets as a result of disease-related collagen remodeling, which in turn triggers further remodeling.
Subject(s)
Collagen , Mitral Valve , Humans , Mitral Valve/metabolism , Mitral Valve/pathology , Collagen/metabolism , Male , Female , Middle Aged , Biomechanical Phenomena , Aged , Mitral Valve Prolapse/metabolism , Mitral Valve Prolapse/pathology , AdultABSTRACT
PURPOSE: Currently, the intra-operative visualization of vessels during endovascular aneurysm repair (EVAR) relies on contrast-based imaging modalities. Moreover, traditional image fusion techniques lack a continuous and automatic update of the vessel configuration, which changes due to the insertion of stiff guidewires. The purpose of this work is to develop and evaluate a novel approach to improve image fusion, that takes into account the deformations, combining electromagnetic (EM) tracking technology and finite element modeling (FEM). METHODS: To assess whether EM tracking can improve the prediction of the numerical simulations, a patient-specific model of abdominal aorta was segmented and manufactured. A database of simulations with different insertion angles was created. Then, an ad hoc sensorized tool with three embedded EM sensors was designed, enabling tracking of the sensors' positions during the insertion phase. Finally, the corresponding cone beam computed tomography (CBCT) images were acquired and processed to obtain the ground truth aortic deformations of the manufactured model. RESULTS: Among the simulations in the database, the one minimizing the in silico versus in vitro discrepancy in terms of sensors' positions gave the most accurate aortic displacement results. CONCLUSIONS: The proposed approach suggests that the EM tracking technology could be used not only to follow the tool, but also to minimize the error in the predicted aortic roadmap, thus paving the way for a safer EVAR navigation.
ABSTRACT
Objective: To predict the required mitral annular area reduction in patients with Barlow's disease to obtain a predefined leaflet area index by a novel in silico modeling method. Methods: Three-dimensional echocardiography was used to create patient-specific mitral valve models of 8 patients diagnosed with Barlow's disease and bileaflet prolapse preoperatively. Six patients were also studied postoperatively in a finite element framework, to quantify the optimal coaptation area index. For the patient-specific finite element analyses, realistic papillary muscle and annular motion are incorporated, also for the in silico annuloplasty analyses. The annuloplasty ring size is reduced moderately until the optimal coaptation area index is achieved for each patient. Results: The mean mitral annular area at end-diastole was reduced by 58 ± 7% postoperatively (P < .001), resulting in a postoperative coaptation area index of 20 ± 5%. To achieve the same coaptation area index with moderate annular reductions and no leaflet resection the annular reduction was 31 ± 6% (P < .001). Conclusions: In silico analysis in selected patients diagnosed with Barlow's disease demonstrates that annuloplasty with only moderate annular reduction may be sufficient to achieve optimal coaptation as compared to conventional surgical procedures.
ABSTRACT
The present study investigates silicone transfer occurring during microcontact printing (µCP) of lectins with polydimethylsiloxane (PDMS) stamps and its impact on the adhesion of cells. Static adhesion assays and single-cell force spectroscopy (SCFS) are used to compare adhesion of nonmalignant (HCV29) and cancer (HT1376) bladder cells, respectively, to high-affinity lectin layers (PHA-L and WGA, respectively) prepared by physical adsorption and µCP. The chemical composition of the µCP lectin patterns was monitored by time-of-flight secondary ion mass spectrometry (ToF-SIMS). We show that the amount of transferred silicone in the µCP process depends on the preprocessing of the PDMS stamps. It is revealed that silicone contamination within the patterned lectin layers inhibits the adhesion of bladder cells, and the work of adhesion is lower for µCP lectins than for drop-cast lectins. The binding capacity of microcontact printed lectins was larger when the PDMS stamps were treated with UV ozone plasma as compared to sonication in ethanol and deionized water. ToF-SIMS data show that ozone-based treatment of PDMS stamps used for µCP of lectin reduces the silicone contamination in the imprinting protocol regardless of stamp geometry (flat vs microstructured). The role of other possible contributors, such as the lectin conformation and organization of lectin layers, is also discussed.
ABSTRACT
Degenerative mitral valve disease is the main cause of primary mitral regurgitation with two phenotypes: fibroelastic deficiency (FED) often with localized myxomatous degeneration and diffuse myxomatous degeneration or Barlow's disease. Myxomatous degeneration disrupts the microstructure of the mitral valve leaflets, particularly the collagen fibers, which affects the mechanical behavior of the leaflets. The present study uses biaxial mechanical tests and second harmonic generation microscopy to examine the mechanical behavior of Barlow and FED tissue. Three tissue samples were harvested from a FED patient and one sample is from a Barlow patient. Then we use an appropriate constitutive model by excluding the collagen fibers under compression. Finally, we built an FE model based on the echocardiography of patients diagnosed with FED and Barlow and the characterized material model and collagen fiber orientation. The Barlow sample and the FED sample from the most affected segment showed different mechanical behavior and collagen structure compared to the other two FED samples. The FE model showed very good agreement with echocardiography with 2.02±1.8 mm and 1.05±0.79 mm point-to-mesh distance errors for Barlow and FED patients, respectively. It has also been shown that the exclusion of collagen fibers under compression provides versatility for the material model; it behaves stiff in the belly region, preventing excessive bulging, while it behaves very softly in the commissures to facilitate folding. STATEMENT OF SIGNIFICANCE: This study quantifies for the first time the collagen microstructure and mechanical behavior of degenerative mitral valve (DMV) leaflets. These data will then be used for the first disease-specific finite element (FE) model of DMV. While current surgical repair of DMV is based on surgical experience, FE modeling has the potential to support decision-making and make outcomes predictable. We adopt a constitutive model to exclude collagen fiber under compressions, an important consideration when modeling the mitral valve, where the leaflets are folded to ensure complete closure. The results of this study provide essential data for understanding the relationship between collagen microstructure and degenerative mitral valve mechanics.
Subject(s)
Mitral Valve Insufficiency , Mitral Valve Prolapse , Humans , Mitral Valve/diagnostic imaging , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Mitral Valve Prolapse/surgery , Finite Element Analysis , CollagenABSTRACT
Introduction and aims: During an Endovascular Aneurysm Repair (EVAR) procedure a stiff guidewire is inserted from the iliac arteries. This induces significant deformations on the vasculature, thus, affecting the pre-operative planning, and the accuracy of image fusion. The aim of the present work is to predict the guidewire induced deformations using a finite element approach validated through experiments with patient-specific additive manufactured models. The numerical approach herein developed could improve the pre-operative planning and the intra-operative navigation. Material and methods: The physical models used for the experiments in the hybrid operating room, were manufactured from the segmentations of pre-operative Computed Tomography (CT) angiographies. The finite element analyses (FEA) were performed with LS-DYNA Explicit. The material properties used in finite element analyses were obtained by uniaxial tensile tests. The experimental deformed configurations of the aorta were compared to those obtained from FEA. Three models, obtained from Computed Tomography acquisitions, were investigated in the present work: A) without intraluminal thrombus (ILT), B) with ILT, C) with ILT and calcifications. Results and discussion: A good agreement was found between the experimental and the computational studies. The average error between the final in vitro vs. in silico aortic configurations, i.e., when the guidewire is fully inserted, are equal to 1.17, 1.22 and 1.40 mm, respectively, for Models A, B and C. The increasing trend in values of deformations from Model A to Model C was noticed both experimentally and numerically. The presented validated computational approach in combination with a tracking technology of the endovascular devices may be used to obtain the intra-operative configuration of the vessels and devices prior to the procedure, thus limiting the radiation exposure and the contrast agent dose.
ABSTRACT
The purpose of this study was to investigate the effects of loading conditions and left ventricular (LV) contractility on mitral annular dynamics. In 10 anesthetized pigs, eight piezoelectric transducers were implanted equidistantly around the mitral annulus. High-fidelity catheters measured left ventricular pressures and the slope of the end-systolic pressure-volume relationship (Ees ) determined LV contractility. Adjustments of pre- and afterload were done by constriction of the inferior caval vein and occlusion of the descending aorta. Mitral annulus area indexed to body surface area (MAAi ), annular circularity index (ACI), and non-planarity angle (NPA) were calculated by computational analysis. MAAi was more dynamic in response to loading interventions than ACI and NPA. However, MAAi maximal cyclical reduction (-Δr) and average deformational velocity (- v ¯ $$ \overline{v} $$ ) did not change accordingly (p = 0.31 and p = 0.22). Reduced Ees was associated to attenuation in MAAi -Δr and MAAi - v ¯ $$ \overline{v} $$ (r2 = 0.744; p = 0.001 and r2 = 0.467; p = 0.029). In conclusion, increased cardiac load and reduced LV contractility may cause deterioration of mitral annular dynamics, likely impairing coaptation and increasing susceptibility to valvular incompetence.
Subject(s)
Mitral Valve , Ventricular Function, Left , Animals , Swine , Ventricular Function, Left/physiology , Mitral Valve/physiology , Heart Ventricles , Models, Animal , Vena Cava, InferiorABSTRACT
Collagen fibers are the main load carrier in the mitral valve (MV) leaflets. Their orientation and dispersion are an important factor for the mechanical behavior. Most recent studies of collagen fibers in MVs lack either entire thickness study or high transmural resolution. The present study uses second harmonic generation (SHG) microscopy in combination with planar biaxial mechanical tests to better model and examine collagen fibers and mechanical properties of MV leaflets. SHG in combination with tissue clearing enables the collagen fibers to be examined through the entire thickness of the MV leaflets. Planar biaxial mechanical tests, on the other hand, enable the characterization of the mechanical tissue behavior, which is represented by a structural tissue model. Twelve porcine MV leaflets are examined. The SHG recording shows that the mean fiber angle for all samples varies on average by ±12° over the entire thickness and the collagen fiber dispersion changes strongly over the thickness. A constitutive model based on the generalized structure tensor approach is used for the associated tissue characterization. The model represents the tissue with three mechanical parameters plus the mean fiber direction and the dispersion, and predicts the biomechanical response of the leaflets with a good agreement (average r2=0.94). It is found that the collagen structure can be represented by a mean direction and a dispersion with a single family of fibers despite the variation in the collagen fiber direction and the dispersion over the entire thickness of MV leaflets. STATEMENT OF SIGNIFICANCE: Despite its prominent role in the mechanical behavior of mitral valve (MV) leaflets, the collagen structure has not yet been investigated over the entire thickness with high transmural resolution. The present study quantifies the detailed through thickness collagen fiber structure and examines the effects of its variation on MV tissue modeling. This is important because the study evaluates the assumption that the collagen fibers can be modeled with a representative single fiber family despite the variation across the thickness. In addition, the current comprehensive data set paves the way for quantifying the disruption of collagen fibers in myxomatous MV leaflets associated with disrupted collagen fibers.
Subject(s)
Mitral Valve , Second Harmonic Generation Microscopy , Animals , Biomechanical Phenomena , Collagen/physiology , Mechanical Tests , Mitral Valve/physiology , Stress, Mechanical , SwineABSTRACT
Barlow's Disease affects the entire mitral valve apparatus causing mitral regurgitation. Standard annuloplasty procedures lead to an average of 55% annular area reduction of the end diastolic pre-operative annular area in Barlow's diseased valves. Following annular reduction, mitral valvuloplasty may be needed, usually with special focus on the posterior leaflet. An in silico pipeline to perform annuloplasty by utilizing the pre- and -postoperative 3D echocardiographic recordings was developed. Our objective was to test the hypothesis that annuloplasty ring sizes based on a percentage (10%-25%) decrease of the pre-operative annular area at end diastole can result in sufficient coaptation area for the selected Barlow's diseased patient. The patient specific mitral valve geometry and finite element model were created from echocardiography recordings. The post-operative echocardiography was used to obtain the artificial ring geometry and displacements, and the motion of the papillary muscles after surgery. These were used as boundary conditions in our annuloplasty finite element analyses. Then, the segmented annuloplasty ring was scaled up to represent a 10%, 20% and 25% reduction of the pre-operative end diastolic annular area and implanted to the end diastolic pre-operative finite element model. The pre-operative contact area decrease was shown to be dependent on the annular dilation at late systole. Constraining the mitral valve from dilating excessively can be sufficient to achieve proper coaptation throughout systole. The finite element analyses show that the selected Barlow's diseased patient may benefit from an annuloplasty ring with moderate annular reduction alone.
Subject(s)
Mitral Valve Annuloplasty , Mitral Valve Insufficiency/surgery , Mitral Valve Prolapse/surgery , Echocardiography, Three-Dimensional , Finite Element Analysis , Humans , Mitral Valve/anatomy & histology , Mitral Valve/diagnostic imaging , Mitral Valve/pathology , Mitral Valve Annuloplasty/adverse effects , Mitral Valve Annuloplasty/instrumentation , Mitral Valve Annuloplasty/methods , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/etiology , Mitral Valve Prolapse/complications , Mitral Valve Prolapse/diagnostic imaging , Mitral Valve Prolapse/etiology , Treatment OutcomeABSTRACT
OBJECTIVES: Barlow's mitral valve disease with late systolic mitral regurgitation provides diagnostic and therapeutic challenges. The mechanisms of the regurgitation are still unclear. We hypothesized that the onset and the severity of late systolic regurgitation are determined by annulus dynamics and the mechanical stresses imposed by the left ventricle. METHODS: Ten patients with Barlow's mitral valve disease and mitral annulus disjunction (MAD) were compared with 10 healthy controls. Resting blood pressure was measured, and transthoracic three-dimensional echocardiography was analyzed using a holographic display that allows tracking and measurements of mitral annulus surface area (ASA) throughout the cardiac cycle. A novel annulus elastance index (dASA/dP) was calculated between aortic valve opening and onset of mitral regurgitation. Severity of MAD was quantified as the disjunction index (mm × degree). Leaflet coaptation area was calculated using a finite element model. RESULTS: Peak systolic ASAs in controls and patients were 9.3 ± 0.6 and 21.1 ± 3.1 cm2, respectively (P < .001). In patients, the ASA increased rapidly during left ventricular ejection, and onset of mitral regurgitation coincided closely with peak upslope of annulus area change (dASA/dt). The finite element model showed a close association between rapid annulus displacement and coaptation area deficit in Barlow's mitral valve disease. Systolic annulus elastance index (0.058 ± 0.036 cm2/mm Hg) correlated strongly with disjunction index (r = 0.91, P < .0001). Moreover, regurgitation volume showed a positive correlation with systolic blood pressure (r = 0.80, P < .01). CONCLUSION: The present pilot study supports the hypothesis that annulus dilatation may accentuate mitral valve regurgitation in patients with Barlow's mitral valve disease. A novel annulus elastance index may predict the severity of mitral valve regurgitation in selected patients.
Subject(s)
Mitral Valve Insufficiency , Mitral Valve Prolapse , Diazonium Compounds , Elasticity , Humans , Mitral Valve/diagnostic imaging , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Prolapse/diagnosis , Pilot Projects , Sulfanilic AcidsABSTRACT
Aqueous microgels are distinct entities of soft matter with mechanical signatures that can be different from their macroscopic counterparts due to confinement effects in the preparation, inherently made to consist of more than one domain (Janus particles) or further processing by coating and change in the extent of crosslinking of the core. Motivated by the importance of the mechanical properties of such microgels from a fundamental point, but also related to numerous applications, we provide a perspective on the experimental strategies currently available and emerging tools being explored. Albeit all techniques in principle exploit enforcing stress and observing strain, the realization differs from directly, as, e.g., by atomic force microscope, to less evident in a fluid field combined with imaging by a high-speed camera in high-throughput strategies. Moreover, the accompanying analysis strategies also reflect such differences, and the level of detail that would be preferred for a comprehensive understanding of the microgel mechanical properties are not always implemented. Overall, the perspective is that current technologies have the capacity to provide detailed, nanoscopic mechanical characterization of microgels over an extended size range, to the high-throughput approaches providing distributions over the mechanical signatures, a feature not readily accessible by atomic force microscopy and micropipette aspiration.
ABSTRACT
Finite element modeling applied to analyze experimentally determined hydrogel swelling data provides quantitative description of the hydrogel in the aqueous solutions with well-defined ionic content and environmental parameters. In the present study, we expand this strategy to analysis of swelling of hydrogels over an extended concentration of salt where the Donnan contribution and specific ion effects are dominating at different regimes. Dynamics and equilibrium swelling were determined for acrylamide and cationic acrylamide-based hydrogels by high-resolution interferometry technique for step-wise increase in NaCl and NaBr concentration up to 2 M. Although increased hydrogel swelling volume with increasing salt concentration was the dominant trend for the uncharged hydrogel, the weakly charged cationic hydrogel was observed to shrink for increasing salt concentration up to 0.1 M, followed by swelling at higher salt concentrations. The initial shrinking is due to the ionic equilibration accounted for by a Donnan term. Comparison of the swelling responses at high NaCl and NaBr concentrations between the uncharged and the cationic hydrogel showed similar specific ion effects. This indicates that the ion non-specific Donnan contribution and specific ion effects are additive in the case where they are occurring in well separated ranges of salt concentration. We develop a novel finite element model including both these mechanisms to account for the observed swelling in aqueous salt solution. In particular, a salt-specific, concentration-dependent Flory-Huggins parameter was introduced for the specific ion effects. This is the first report on finite element modeling of hydrogels including specific ionic effects and underpins improvement of the mechanistic insight of hydrogel swelling that can be used to predict its response to environmental change.
ABSTRACT
A Hill model-based phenomenological method for muscle activation was used to investigate defectiveness of the palatal muscle tone during sleep for obstructive sleep apnea (OSA) patients. Based on the stretch-stress characteristic of muscle activation when the eccentric contraction is considered, a specifically defined phenomenological strain-energy function was used, as well as the Holzapfel-type strain-energy function for the passive part. A continuum mechanical framework, including the stress tensor and elasticity tensor, was obtained, based on the defined strain-energy function. The model parameters were obtained by fitting the constitutive model to experimental test data. Three-dimensional patient-specific geometry was modeled, accounting for the muscle tissue layer and based on the quantitative histology study of the soft palate. Anatomically representative boundary conditions for the finite element calculation were also considered. Palatal muscle activation level (electromyographic data) versus the negative pressure was defined in the simulations, and the patients' activation level was set to be lower than for the healthy people. The simulation results showed that reduced in activation level for the patients causes a less negative closing pressure, and this makes the soft palate more prone to collapse. In addition, if we account for the passive-active transfer displayed as the muscle contraction corresponding to the neurogenic reflex in the soft palate, the collapse is prevented. This numerical representation of the reduced activation for the OSA patients may provide increased understanding of OSA physiology.
Subject(s)
Models, Biological , Palatal Muscles/physiopathology , Palate, Soft/physiopathology , Sleep Apnea, Obstructive/physiopathology , Biomechanical Phenomena , Case-Control Studies , Computer Simulation , Electromyography , Humans , Imaging, Three-Dimensional , Palatal Muscles/diagnostic imaging , Palate, Soft/diagnostic imaging , Pressure , Reproducibility of Results , Sleep Apnea, Obstructive/diagnostic imaging , Stress, Mechanical , Tomography, X-Ray ComputedABSTRACT
Collapse of the soft palate in the upper airway contributes to obstructive sleeping apnea (OSA). In this study, we investigate the influence of the adhesion from the tongue on the soft palate global response. This is achieved using a cohesive zone finite element approach. A traction-separation law is determined to describe the adhesion effect from the surface tension of the lining liquid between the soft palate and the tongue. According to pull-off experimental tests of human lining liquid from the oral surface of the soft palate, the corresponding cohesive properties, including the critical normal traction stress and the failure separation displacement, are obtained. The 3D patient-specific soft palate geometry is accounted for, based on one specific patient's computed tomography (CT) images. The calculation results show that influence of the adhesion from the tongue surface on the global response of the soft palate depends on the length ratio between the cohesive length and the soft palate length. When the length of the cohesive zone is smaller than half of the soft palate length, the adhesion's influence is negligible. When the adhesion length is larger than 70 percent of soft palate length, the adhesion force contributes to preventing the soft palate from collapsing towards to the pharynx wall, i.e. the closing pressure is more negative than in the no adhesion case. These results may provide useful information to the clinical treatment of OSA patients.
Subject(s)
Palate, Soft , Patient-Specific Modeling , Tongue , Adhesiveness , Humans , Imaging, Three-Dimensional , Palate, Soft/diagnostic imaging , Polysomnography , Pressure , Tomography, X-Ray ComputedABSTRACT
Obstructive sleep apnea (OSA) affects a large percentage of the population and is increasingly recognized as a major global health problem. One surgical procedure for OSA is to implant polyethylene (PET) material into the soft palate, but its efficacy remains to be discussed. In this study, we provide input to this topic based on numerical simulations. Three 3 dimensional (3D) soft palate finite element models including mouth-close and mouth-open cases were created based on three patient-specific computed tomography (CT) images. A simplified material modeling approach with the Neo-Hookean material model was applied, and nonlinear geometry was accounted for. Young's modulus for the implant material was obtained from uniaxial tests, and the PET implant pillars were inserted to the 3D soft palate model. With the finite element model, we designed different surgical schemes and investigated their efficacy with respect to avoiding the soft palate collapse. Several pillar schemes were tested, including different placement directions, different placement positions, different settings for the radius and the array parameters of the implant pillars, and different Young's moduli for the pillars. Based on our simulation results, the longitudinal-direction implant surgery improved the stiffness of the soft palate to a small degree, and implanting in the transverse direction was evaluated to be a good choice for improving the existing surgical scheme. In addition, the Young's modulus of the polyethylene material implants has an influence on the reinforcement efficacy of the soft palate.