An Experiential Learning Opportunity in Norway: Computation for Bioengineering and Mechanical Engineering Students.

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.

Vascular Remodeling During Late-Gestation Pregnancy: An In-Vitro Assessment of the Murine Ascending Thoracic Aorta.

Maternal mortality due to cardiovascular disease is a rising concern in the U.S. Pregnancy triggers changes in the circulatory system, potentially influencing the structure of the central vasculature. Evidence suggests a link between a woman's pregnancy history and future cardiovascular health, but our understanding remains limited. To fill this gap, we examined the passive mechanics of the murine ascending thoracic aorta during late gestation. By performing biaxial mechanical testing on the ascending aorta, we were able to characterize the mechanical properties of both control and late-gestation tissues. By examining mechanical, structural, and geometric properties, we confirmed that remodeling of the aortic wall occurred. Morphological and mechanical properties of the tissue indicated an outward expansion of the tissue, as reflected in changes in wall thickness (∼12% increase) and luminal diameter (∼6% increase) at its physiologically loaded state in the pregnant group. With these geometric adaptations and despite increased hemodynamic loads, pregnancy did not induce significant changes in the tensile wall stress at the similar physiological pressure levels of the pregnant and control tissues. The alterations also included reduced intrinsic stiffness in the circumferential direction (∼18%) and reduced structural stiffness (∼26%) in the pregnant group. The observed vascular remodeling maintained the elastic stored energy of the aortic wall under systolic loads, indicating preservation of vascular function. Data from our study of pregnancy-related vascular remodeling will provide valuable insights for future investigations of maternal cardiovascular health.

Meta Data Analysis of Sex Distribution of Study Samples Reported in Summer Biomechanics, Bioengineering, & Biotransport Annual Conference Abstracts.

The biased use of male subjects in biomedical research has created limitations, underscoring the importance of including women to enhance the outcomes of evidence-based medicine and to promote human health. While federal policies (e.g., the 1993 Revitalization Act and the 2016 Sex as a Biological Variable Act) have aimed to improve sex balance in studies funded by the National Institutes of Health (NIH), data on sex inclusivity in non-NIH funded research remain limited. The objective of this study was to analyze the trend of sex inclusion in abstracts submitted to the Summer Biomechanics, Bioengineering, & Biotransport Conference (SB3C) over seven years. We scored every abstract accepted to SB3C and the findings revealed that approximately 20% of total abstracts included sex-related information, and this trend remained stable. Surprisingly, there was no significant increase in abstracts including both sexes or those with balanced male and female samples. The proportion of abstracts with balanced sexes was notably lower than those including both sexes. Additionally, we examined whether the exclusion of one sex from the corresponding studies was justified by the research questions. Female-only studies had a 50% justification rate, while male-only studies had only 2% justification. Disparity in sex inclusion in SB3C abstracts was apparent, prompting us to encourage scientists to be more mindful of the sex of the research samples. Addressing sex inclusivity in biomechanics and mechanobiology research is essential for advancing medical knowledge and for promoting better healthcare outcomes for everyone.

The Effect of Posterior Fossa Decompression Surgery on Brainstem and Cervical Spinal Cord Dimensions in Adults with Chiari Malformation Type 1.

OBJECTIVE: Posterior fossa decompression (PFD) surgery creates more space at the skull base, reduces the resistance to the cerebrospinal fluid motion, and alters craniocervical biomechanics. In this paper, we retrospectively examined the changes in neural tissue dimensions following PFD surgery on Chiari malformation type 1 adults. METHODS: Measurements were performed on T2-weighted brain magnetic resonance images acquired before and 4 months after surgery. Measurements were conducted for neural tissue volume and spinal cord/brainstem width at 4 different locations; 2 width measurements were made on the brainstem and 2 on the spinal cord in the midsagittal plane. Cerebellar tonsillar position (CTP) was also measured before and after surgery. RESULTS: Twenty-five adult patients, with a mean age of 38.9 ± 8.8 years, were included in the study. The cervical cord volume increased by an average of 2.3 ± 3.3% (P = 0.002). The width at the pontomedullary junction increased by 2.2 ± 3.5% (P < 0.01), while the width 10 mm caudal to this junction increased by 4.2 ± 3.9% (P < 0.0001). The spinal cord width at the base of second cervical vertebra and third cervical vertebra did not significantly change after surgery. The CTP decreased by 60 ± 37% (P < 0.0001) after surgery, but no correlation was found between CTP change and dimension change. CONCLUSIONS: The brainstem width and cervical cord volume showed a modest increase after PFD surgery, although standard deviations were large. A reduction in compression after PFD surgery may allow for an increase in neural tissue dimension. However, clinical relevance is unclear and should be assessed in future studies with high-resolution imaging.

Biomechanical remodeling of the murine descending thoracic aorta during late-gestation pregnancy.

With the rise in maternal mortality rates and the growing body of epidemiological evidence linking pregnancy history to maternal cardiovascular health, it is essential to comprehend the vascular remodeling that occurs during gestation. The maternal body undergoes significant hemodynamic alterations which are believed to induce structural remodeling of the cardiovascular system. Yet, the effects of pregnancy on vascular structure and function have not been fully elucidated. Such a knowledge gap has limited our understanding of the etiology of pregnancy-induced cardiovascular disease. Towards bridging this gap, we measured the biaxial mechanical response of the murine descending thoracic aorta during a normotensive late-gestation pregnancy. Non-invasive hemodynamic measurements confirmed a 50% increase in cardiac output in the pregnant group, with no changes in peripheral blood pressure. Pregnancy was associated with significant wall thickening ( ∼14%), an increase in luminal diameter ( ∼6%), and material softening in both circumferential and axial directions. This expansive remodeling of the tissue resulted in a reduction in tensile wall stress and intrinsic tissue stiffness. Collectively, our data indicate that an increase in the geometry of the vessel may occur to accommodate for the increase in cardiac output and blood flow that occurs in pregnancy. Similarly, wall thickening accompanied by increased luminal diameter, without a change in blood pressure may be a necessary mechanism to decrease the tensile wall stress, and avoid pathophysiological events following late gestation.

Association between resistance to cerebrospinal fluid flow and cardiac-induced brain tissue motion for Chiari malformation type I.

PURPOSE: Chiari malformation type I (CMI) patients have been independently shown to have both increased resistance to cerebrospinal fluid (CSF) flow in the cervical spinal canal and greater cardiac-induced neural tissue motion compared to healthy controls. The goal of this paper is to determine if a relationship exists between CSF flow resistance and brain tissue motion in CMI subjects. METHODS: Computational fluid dynamics (CFD) techniques were employed to compute integrated longitudinal impedance (ILI) as a measure of unsteady resistance to CSF flow in the cervical spinal canal in thirty-two CMI subjects and eighteen healthy controls. Neural tissue motion during the cardiac cycle was assessed using displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) technique. RESULTS: The results demonstrate a positive correlation between resistance to CSF flow and the maximum displacement of the cerebellum for CMI subjects (r = 0.75, p = 6.77 × 10-10) but not for healthy controls. No correlation was found between CSF flow resistance and maximum displacement in the brainstem for CMI or healthy subjects. The magnitude of resistance to CSF flow and maximum cardiac-induced brain tissue motion were not statistically different for CMI subjects with and without the presence of five CMI symptoms: imbalance, vertigo, swallowing difficulties, nausea or vomiting, and hoarseness. CONCLUSION: This study establishes a relationship between CSF flow resistance in the cervical spinal canal and cardiac-induced brain tissue motion in the cerebellum for CMI subjects. Further research is necessary to understand the importance of resistance and brain tissue motion in the symptomatology of CMI.

The Relationship Between Imbalance Symptom and Cardiac Pulsation Induced Mechanical Strain in the Brainstem and Cerebellum for Chiari Malformation Type I.

Chiari malformation Type I (CMI) is known to have an altered biomechanical environment for the brainstem and cerebellum; however, it is unclear whether these altered biomechanics play a role in the development of CMI symptoms. We hypothesized that CMI subjects have a higher cardiac-induced strain in specific neurological tracts pertaining to balance, and postural control. We measured displacement over the cardiac cycle using displacement encoding with stimulated echoes magnetic resonance imaging in the cerebellum, brainstem, and spinal cord in 37 CMI subjects and 25 controls. Based on these measurements, we computed strain, translation, and rotation in tracts related to balance. The global strain on all tracts was small (<1%) for CMI subject and controls. Strain was found to be nearly doubled in three tracts for CMI subjects compared to controls (p < 0.03). The maximum translation and rotation were ∼150 µm and ∼1 deg, respectively and 1.5-2 times greater in CMI compared to controls in four tracts (p < 0.005). There was no significant difference between strain, translation, and rotation on the analyzed tracts in CMI subjects with imbalance compared to those without imbalance. A moderate correlation was found between cerebellar tonsillar position and strain on three tracts. The lack of statistically significant difference between strain in CMI subjects with and without imbalance could imply that the magnitude of the observed cardiac-induced strain was too small to cause substantial damage to the tissue (<1%). Activities such as coughing, or Valsalva may produce a greater strain.

Who bears the load? IOP-induced collagen fiber recruitment over the corneoscleral shell.

Collagen is the main load-bearing component of cornea and sclera. When stretched, both of these tissues exhibit a behavior known as collagen fiber recruitment. In recruitment, as the tissues stretch the constitutive collagen fibers lose their natural waviness, progressively straightening. Recruited, straight, fibers bear substantially more mechanical load than non-recruited, wavy, fibers. As such, the process of recruitment underlies the well-established nonlinear macroscopic behavior of the corneoscleral shell. Recruitment has an interesting implication: when recruitment is incomplete, only a fraction of the collagen fibers is actually contributing to bear the loads, with the rest remaining "in reserve". In other words, at a given intraocular pressure (IOP), it is possible that not all the collagen fibers of the cornea and sclera are actually contributing to bear the loads. To the best of our knowledge, the fraction of corneoscleral shell fibers recruited and contributing to bear the load of IOP has not been reported. Our goal was to obtain regionally-resolved estimates of the fraction of corneoscleral collagen fibers recruited and in reserve. We developed a fiber-based microstructural constitutive model that could account for collagen fiber undulations or crimp via their tortuosity. We used experimentally-measured collagen fiber crimp tortuosity distributions in human eyes to derive region-specific nonlinear hyperelastic mechanical properties. We then built a three-dimensional axisymmetric model of the globe, assigning region-specific mechanical properties and regional anisotropy. The model was used to simulate the IOP-induced shell deformation. The model-predicted tissue stretch was then used to quantify collagen recruitment within each shell region. The calculations showed that, at low IOPs, collagen fibers in the posterior equator were recruited the fastest, such that at a physiologic IOP of 15 mmHg, over 90% of fibers were recruited, compared with only a third in the cornea and the peripapillary sclera. The differences in recruitment between regions, in turn, mean that at a physiologic IOP the posterior equator had a fiber reserve of only 10%, whereas the cornea and peripapillary sclera had two thirds. At an elevated IOP of 50 mmHg, collagen fibers in the limbus and the anterior/posterior equator were almost fully recruited, compared with 90% in the cornea and the posterior sclera, and 70% in the peripapillary sclera and the equator. That even at such an elevated IOP not all the fibers were recruited suggests that there are likely other conditions that challenge the corneoscleral tissues even more than IOP. The fraction of fibers recruited may have other potential implications. For example, fibers that are not bearing loads may be more susceptible to enzymatic digestion or remodeling. Similarly, it may be possible to control tissue stiffness through the fraction of recruited fibers without the need to add or remove collagen.

Lengthwise regional mechanics of the human aneurysmal ascending thoracic aorta.

The prognosis of patients undergoing emergency endovascular repair of ascending thoracic aortic aneurysm (ATAA) depends on defect location, with root disease bearing worse outcomes than proximal or distal aortopathy. We speculate that a spatial gradient in aneurysmal tissue mechanics through the length of the ascending thoracic aorta may fuel noted survival discrepancies. To this end, we performed planar biaxial testing on 153 root, proximal, and distal segments of ATAA samples collected from 80 patients receiving elective open surgical repair. Following data averaging via surface fitting-based interpolation of strain-controlled protocols, we combined in-vitro and in-vivo measurements of loads and geometry to resolve inflation-extension kinematics and evaluate mechanical metrics of stress, stiffness, and energy at consistent deformation levels. Representative (averaged) experimental data and simulated in-vivo conditions revealed significantly larger biaxial stiffness at the root compared to either proximal or distal tissues, which persisted as the entire aorta stiffened during aging. Advancing age further reduced biaxial stretch and energy storage, a measure of aortic function, across all ATAA segments. Importantly, age emerged as a stronger predictor of tissue mechanics in ATAA disease than either bicuspid aortic valve or connective tissue disorders. Besides strengthening the general understanding of aneurysmal disease, our findings provide specifications to customize the design of stent-grafts for the treatment of ATAA disease. Optimization of deployment and interaction of novel endovascular devices with the local native environment is expected to carry significant potential for improving clinical outcomes. STATEMENT OF SIGNIFICANCE: Elucidating the lengthwise regional mechanics of ascending thoracic aortic aneurysms (ATAAs) is critical for the design of endovascular devices tailored to the ascending aorta. Stent-grafts provide a less invasive alternative to support the long-term survival of ATAA patients ineligible for open surgical repair. In this study, we developed a numerical framework that combines semi-inverse constitutive and forward modeling with in-vitro and in-vivo data to extract mechanical descriptors of ATAA tissue behavior at physiologically meaningful deformation. Moving distally from the aortic root to the first ascending aortic branch, we observed a progressive decline in biaxial stiffness. Furthermore, we showed that aging leads to reduced aortic function and is a stronger predictor of mechanics than either valve morphology or underlying syndromic disorder.

Impact of Blood Rheology on Transition to Turbulence and Wall Vibration Downstream of a Stenosis.

Previous experimental flow studies have demonstrated a delay (∼20%) in transition to turbulence for whole blood compared to a Newtonian analog fluid in both a straight pipe and eccentric stenosis model with ridged walls. The impact of wall compliance on the transition to turbulence of blood compared to Newtonian analog and on wall vibration is unknown. The present study employed flexible walls downstream of an eccentric stenosis model and examined the wall vibration during the transition to turbulence with whole blood and a Newtonian analog. Measurements of tube wall vibration velocity (WVV) were used as an indicator of the turbulence level within the flexible tube. WVV was measured at 5, 10, and 15 diameters downstream of the stenosis using a laser Doppler vibrometer at Reynolds numbers 0, 200, 300, 350, 400, 450, 500, 550, 600, 650, 700, and 750. The root mean squares (RMS) of the measured WVV were utilized as an indirect measure of fluid velocity fluctuations present at that location, and hence, an indicator of transition to turbulence. WVV RMS was near-constant until approximately Reynolds number 400. It increased monotonically with Reynolds number for both whole blood and the Newtonian fluid. No differences in the transition to turbulence were observed between whole blood and the Newtonian fluid, as the WVV RMS curves were remarkably similar in shape. This result suggests that rheology had minimal impact on the WVV downstream of a stenosis for transition to turbulence since the fluids had a similar level of vibration.

The role of elastin on the mechanical properties of the anterior leaflet in porcine tricuspid valves.

Elastin is present in the extracellular matrix (ECM) of connective tissues, and its mechanical properties are well documented. In Marfan syndrome, however, the inability to properly code for the protein fibrillin-1 prematurely leads to the degradation and loss of elastin fiber integrity in the ECM. In this study, the role of elastin in the ECM of the anterior leaflet of the tricuspid valve was investigated by examining the biomechanical behavior of porcine leaflets before and after the application of the enzyme elastase. Five loading protocols were applied to the leaflet specimens in two groups (elastase-treated and control samples). The mechanical response following elastase application yielded a significantly stiffer material in both the radial and circumferential directions. At a physiological level of stress (85 kPa), the elastase group had an average strain of 26.21% and 6.32% in the radial and circumferential directions, respectively, at baseline prior to elastase application. Following elastase treatment, the average strain was 5.28% and 0.97% in the radial and circumferential directions, respectively. No statistically significant change was found in the control group following sham treatment with phosphate-buffered saline (PBS). Two-photon microscopy images confirmed that after the removal of elastin, the collagen fibers displayed a loss of undulation. With a significant reduction in radial compliance, the ability to withstand physiological loads may be compromised. As such, an extracellular matrix that is structurally deficient in elastin may hinder normal tricuspid valve function.

Effects of enzyme-based removal of collagen and elastin constituents on the biaxial mechanical responses of porcine atrioventricular heart valve anterior leaflets.

The leaflets of the atrioventricular heart valves (AHVs) regulate the one-directional flow of blood through a coordination of the extracellular matrix components, including the collagen fibers, elastin, and glycosaminoglycans. Dysfunction of the AHVs, such as those caused by unfavorable microstructural remodeling, lead to valvular heart diseases and improper blood flow, which can ultimately cause heart failure. In order to better understand the mechanics and remodeling of the AHV leaflets and how therapeutics can inadvertently cause adverse microstructural changes, a systematic characterization of the role of each constituent in the biomechanical properties is appropriate. Previous studies have quantified the contributions of the individual microstructural components to tissue-level behavior for the semilunar valve cusps, but not for the AHV leaflets. In this study, for the first time, we quantify the relationships between microstructure and mechanics of the AHV leaflet using a three-step experimental procedure: (i) biaxial tension and stress relaxation testing of control (untreated) porcine AHV anterior leaflet specimens; (ii) enzyme treatment to remove a portion of either the collagen or elastin constituent; and (iii) biaxial tensile and stress relaxation testing of the constituent-removed (treated) specimens. We have observed that the removal of ∼100% elastin resulted in a ∼10% decrease in the tissue extensibility with biaxial tension and a ∼10% increase in the overall stress reduction with stress relaxation. In contrast, removal of 46% of the collagen content insignificantly affected tissue extensibility with biaxial tension and significantly increased stress decay (10%) with stress relaxation. These findings provide an insight into the microstructure-mechanics relationship of the AHVs and will be beneficial for future developments and refinements of microstructurally informed constitutive models for the simulation of diseased and surgically intervened AHV function. STATEMENT OF SIGNIFICANCE: This study presents, for the first time, a thorough mechanical characterization of the atrioventricular heart valve leaflets before and after enzymatic removal of elastin and collagen. We found that the biaxial tensile properties of elastin-deficient tissues and collagen-deficient are stiffer. The fact of elastin supporting low-stress valve function and collagen as the main load-bearing component was evident in a decrease in the low-tension modulus for elastin-deficient tissues and in the high-tension modulus for collagen-deficient tissues. Our quantification and experimental technique could be useful in predicting the disease-related changes in heart valve mechanics. The information obtained from this work is valuable for refining the constitutive models that describe the essential microstructure-mechanics relationship.

Cerebellar and Brainstem Displacement Measured with DENSE MRI in Chiari Malformation Following Posterior Fossa Decompression Surgery.

Background Posterior fossa decompression (PFD) surgery is a treatment for Chiari malformation type I (CMI). The goals of surgery are to reduce cerebellar tonsillar crowding and restore posterior cerebral spinal fluid flow, but regional tissue biomechanics may also change. MRI-based displacement encoding with stimulated echoes (DENSE) can be used to assess neural tissue displacement. Purpose To assess neural tissue displacement by using DENSE MRI in participants with CMI before and after PFD surgery and examine associations between tissue displacement and symptoms. Materials and Methods In a prospective, HIPAA-compliant study of patients with CMI, midsagittal DENSE MRI was performed before and after PFD surgery between January 2017 and June 2020. Peak tissue displacement over the cardiac cycle was quantified in the cerebellum and brainstem, averaged over each structure, and compared before and after surgery. Paired t tests and nonparametric Wilcoxon signed-rank tests were used to identify surgical changes in displacement, and Spearman correlations were determined between tissue displacement and presurgery symptoms. Results Twenty-three participants were included (mean age ± standard deviation, 37 years ± 10; 19 women). Spatially averaged (mean) peak tissue displacement demonstrated reductions of 46% (79/171 µm) within the cerebellum and 22% (46/210 µm) within the brainstem after surgery (P < .001). Maximum peak displacement, calculated within a circular 30-mm2 area, decreased by 64% (274/427 µm) in the cerebellum and 33% (100/300 µm) in the brainstem (P < .001). No significant associations were identified between tissue displacement and CMI symptoms (r < .74 and P > .012 for all; Bonferroni-corrected P = .0002). Conclusion Neural tissue displacement was reduced after posterior fossa decompression surgery, indicating that surgical intervention changes brain tissue biomechanics. For participants with Chiari malformation type I, no relationship was identified between presurgery tissue displacement and presurgical symptoms. © RSNA, 2021 Online supplemental material is available for this article.

Regional Brain Tissue Displacement and Strain is Elevated in Subjects with Chiari Malformation Type I Compared to Healthy Controls: A Study Using DENSE MRI.

While the degree of cerebellar tonsillar descent is considered the primary radiologic marker of Chiari malformation type I (CMI), biomechanical forces acting on the brain tissue in CMI subjects are less studied and poorly understood. In this study, regional brain tissue displacement and principal strains in 43 CMI subjects and 25 controls were quantified using a magnetic resonance imaging (MRI) methodology known as displacement encoding with stimulated echoes (DENSE). Measurements from MRI were obtained for seven different brain regions-the brainstem, cerebellum, cingulate gyrus, corpus callosum, frontal lobe, occipital lobe, and parietal lobe. Mean displacements in the cerebellum and brainstem were found to be 106 and 64% higher, respectively, for CMI subjects than controls (p < .001). Mean compression and extension strains in the cerebellum were 52 and 50% higher, respectively, in CMI subjects (p < .001). Brainstem mean extension strain was 41% higher in CMI subjects (p < .001), but no significant difference in compression strain was observed. The other brain structures revealed no significant differences between CMI and controls. These findings demonstrate that brain tissue displacement and strain in the cerebellum and brainstem might represent two new biomarkers to distinguish between CMI subjects and controls.

Accuracy of cardiac-induced brain motion measurement using displacement-encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI): A phantom study.

PURPOSE: The goal of this study was to determine the accuracy of displacement-encoding with stimulated echoes (DENSE) MRI in a tissue motion phantom with displacements representative of those observed in human brain tissue. METHODS: The phantom was comprised of a plastic shaft rotated at a constant speed. The rotational motion was converted to a vertical displacement through a camshaft. The phantom generated repeatable cyclical displacement waveforms with a peak displacement ranging from 92 µm to 1.04 mm at 1-Hz frequency. The surface displacement of the tissue was obtained using a laser Doppler vibrometer (LDV) before and after the DENSE MRI scans to check for repeatability. The accuracy of DENSE MRI displacement was assessed by comparing the laser Doppler vibrometer and DENSE MRI waveforms. RESULTS: Laser Doppler vibrometer measurements of the tissue motion demonstrated excellent cycle-to-cycle repeatability with a maximum root mean square error of 9 µm between the ensemble-averaged displacement waveform and the individual waveforms over 180 cycles. The maximum difference between DENSE MRI and the laser Doppler vibrometer waveforms ranged from 15 to 50 µm. Additionally, the peak-to-peak difference between the 2 waveforms ranged from 1 to 18 µm. CONCLUSION: Using a tissue phantom undergoing cyclical motion, we demonstrated the percent accuracy of DENSE MRI to measure displacement similar to that observed for in vivo cardiac-induced brain tissue.

Iris stromal cell nuclei deform to more elongated shapes during pharmacologically-induced miosis and mydriasis.

Nuclear shape alteration in ocular tissues, which can be used as a metric for overall cell deformation, may also lead to changes in gene expression and protein synthesis that could affect the biomechanics of the tissue extracellular matrix. The biomechanics of iris tissue is of particular interest in the study of primary angle-closure glaucoma. As the first step towards understanding the mutual role of the biomechanics and deformation of the iris on the activity of its constituent stromal cells, we conducted an ex-vivo study in freshly excised porcine eyes. Iris deformation was achieved by activating the constituent smooth muscles of the iris. Pupillary responses were initiated by inducing miosis and mydriasis, and the irides were placed in a fixative, bisected, and sliced into thin sections in a nasal and temporal horizontal orientation. The tissue sections were stained with DAPI for nucleus, and z-stacks were acquired using confocal microscopy. Images were analyzed to determine the nuclear aspect ratio (NAR) using both three-dimensional (3D) reconstructions of the nuclear surfaces as well as projections of the same 3D reconstruction into flat two-dimensional (2D) shapes. We observed that regardless of the calculation method (i.e., one that employed 3D surface reconstructions versus one that employed 2D projected images) the NAR increased in both the miosis group and the mydriasis group. Three-dimensional quantifications showed that NAR increased from 2.52 ± 0.96 in control group to 2.80 ± 0.81 and 2.74 ± 0.94 in the mydriasis and miosis groups, respectively. Notwithstanding the relative convenience in calculating the NAR using the 2D projected images, the 3D reconstructions were found to generate more physiologically realistic values and, thus, can be used in the development of future computational models to study primary angle-closure glaucoma. Since the iris undergoes large deformations in response to ambient light, this study suggests that the iris stromal cells are subjected to a biomechanically active micro-environment during their in-vivo physiological function.

Self-Efficacy Versus Gender: Project-Based Active Learning Techniques in Biomedical Engineering Introductory Computer Programming Courses.

Engineering education has increasingly embraced active learning techniques within a variety of curricula. In particular, project-based active learning techniques have a significant potential to enhance students' learning experience. In this study, we implemented project-based techniques in biomedical engineering (BME) classes, and we investigated the effects of active learning on students' self-efficacy as an effective predictor of students' academic persistence and their career decision-making. Differences in self-efficacy were compared across genders. A high level of internal consistency was observed for both academic and career-oriented scales, as determined by Cronbach's alpha values of 0.908 and 0.862, respectively. While average scores of all survey questions indicated improvement in students' academic and career-oriented self-efficacy measures, significant improvements were observed in "clearer vision of programming application in engineering" and "BME careers," as well as in "expectation of success in a future BME career that involves developing medical devices" after the completion of the project-based activity (p = 0.002, 0.023, and 0.034, respectively). For two of the survey questions, female students reflected a significantly lower "self-confidence about understanding the most complex course material" as well as a significantly lower "willingness to have a future career in BME that involves intensive computer programing" as compared to male students (p = 0.035 and 0.024, respectively). We have further discussed possible explanations for the observed differences and multiple potential ways to enhance gender equality in STEM fields from a self-efficacy standpoint.

The effects of -80 °C short-term storage on the mechanical response of tricuspid valve leaflets.

Mechanical testing of soft tissues would ideally rely on using fresh specimens. In the event that fresh tissues are not readily available, alternative measures, such as storing fresh specimens at -80 °C, could be considered. Previous studies have shown that changes in the mechanical properties of the tissues due to freezing could be tissue-dependent. Prior to our study, however, such information was not available for the tricuspid valve leaflets. As such, for the first time, we examined whether fresh porcine specimens tested in a biaxial tensile machine would offer comparable results after being frozen at -80 °C. The stress-strain response of the tricuspid valve leaflets displayed no major deviation of the post-frozen leaflets as compared to fresh leaflets. We further compared the radial and circumferential strains as an indicator of deformation at similar stress states in fresh and thawed tissues, and we did not find any significant differences. Ice formation within the extra cellular matrix may modify the collagen fiber configuration, resulting in a slight change in the mechanical response. Nevertheless, our results indicated such a small deviation was negligible, thus enabling the possibility of using frozen porcine tricuspid valve specimens for future research.

Mechanical Response Changes in Porcine Tricuspid Valve Anterior Leaflet Under Osmotic-Induced Swelling.

Since many soft tissues function in an isotonic in-vivo environment, it is expected that physiological osmolarity will be maintained when conducting experiments on these tissues ex-vivo. In this study, we aimed to examine how not adhering to such a practice may alter the mechanical response of the tricuspid valve (TV) anterior leaflet. Tissue specimens were immersed in deionized (DI) water prior to quantification of the stress-strain responses using an in-plane biaxial mechanical testing device. Following a two-hour immersion in DI water, the tissue thickness increased an average of 107.3% in the DI water group compared to only 6.8% in the control group, in which the tissue samples were submerged in an isotonic phosphate buffered saline solution for the same period of time. Tissue strains evaluated at 85 kPa revealed a significant reduction in the radial direction, from 34.8% to 20%, following immersion in DI water. However, no significant change was observed in the control group. Our study demonstrated the impact of a hypo-osmotic environment on the mechanical response of TV anterior leaflet. The imbalance in ions leads to water absorption in the valvular tissue that can alter its mechanical response. As such, in ex-vivo experiments for which the native mechanical response of the valves is important, using an isotonic buffer solution is essential.

Fluorinated Methacrylamide Chitosan Hydrogel Dressings Improve Regenerated Wound Tissue Quality in Diabetic Wound Healing.

Objective: Oxygen therapy has shown promising results for treating diabetic wounds. However, clinically used oxygen therapies are cumbersome and expensive. Thus, there is a need to develop a localized oxygenating treatment that is easy to use and inexpensive. Approach: In this study, we tested a previously developed hydrogel sheet wound dressing based on fluorinated methacrylamide chitosan (MACF) for enhanced oxygenation and compared it with a commercial sheet hydrogel dressing, AquaDerm™, and no treatment controls in a splinted transgenic diabetic mouse wound model. Results: AquaDerm exhibited poor wound closure response compared with the MACF oxygenating hydrogel sheet dressing (MACF+O2) and no treatment. Histological analysis revealed enhanced collagen synthesis and neovascularization upon MACF+O2 treatment as indicated by higher collagen content and number of blood vessels/capillaries compared with AquaDerm and no treatment. MACF+O2 also improved wound collagen fiber alignment, thus demonstrating improved skin tissue maturation. Nuclear magnetic resonance spectroscopy-based biodistribution analysis revealed that the degradation products of the MACF-based dressing did not accumulate in lung, liver, and kidney tissues of the treated animals after 14 days of treatment. Innovation: This study presents the first application of a unique oxygenating biomaterial (MACF) made into a moist hydrogel wound dressing for treating diabetic wounds. Conclusion: The results of this study confirm the benefits of this novel biomaterial approach for improving regenerated tissue structure in diabetic wound healing.