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.

Fourier transform-based method for quantifying the three-dimensional orientation distribution of fibrous units.

Several materials and tissues are characterized by a microstructure composed of fibrous units embedded in a ground matrix. In this paper, a novel three-dimensional (3D) Fourier transform-based method for quantifying the distribution of fiber orientations is presented. The method allows for an accurate identification of individual fiber families, their in-plane and out-of-plane dispersion, and showed fast computation times. We validated the method using artificially generated 3D images, in terms of fiber dispersion by considering the error between the standard deviation of the reconstructed and the prescribed distributions of the artificial fibers. In addition, we considered the measured mean orientation angles of the fibers and validated the robustness using a measure of fiber density. Finally, the method is employed to reconstruct a full 3D view of the distribution of collagen fiber orientations based on in vitro second harmonic generation microscopy of collagen fibers in human and mouse skin. The dispersion parameters of the reconstructed fiber network can be used to inform mechanical models of soft fiber-reinforced materials and biological tissues that account for non-symmetrical fiber dispersion.

Macro-indentation testing of soft biological materials and assessment of hyper-elastic material models from inverse finite element analysis.

Mechanical characterization of hydrogels and ultra-soft tissues is a challenging task both from an experimental and material parameter estimation perspective because they are much softer than many biological materials, ceramics, or polymers. The elastic modulus of such materials is within the 1 - 100 kPa range, behaving as a hyperelastic solid with strain hardening capability at large strains. In the current study, indentation experiments have been performed on agarose hydrogels, bovine liver, and bovine lymph node specimens. This work reports on the reliable determination of the elastic modulus by indentation experiments carried out at the macro-scale (mm) using a spherical indenter. However, parameter identification of the hyperelastic material properties usually requires an inverse finite element analysis due to the lack of an analytical contact model of the indentation test. Hence a comprehensive study on the spherical indentation of hyperelastic soft materials is carried out through robust computational analysis. Neo-Hookean and first-order Ogden hyperelastic material models were found to be most suitable. A case study on known anisotropic hyperelastic material showed the inability of the inverse finite element method to uniquely identify the whole material parameter set.

Potential of computational models in personalized treatment of obstructive sleep apnea: a patient-specific partial 3D finite element study.

The upper airway experiences mechanical loads during breathing. Obstructive sleep apnea is a very common sleep disorder, in which the normal function of the airway is compromised, enabling its collapse. Its treatment remains unsatisfactory with variable efficacy in the case of many surgeries. Finite element models of the upper airway to simulate the effects of various anatomic and physiologic manipulations on its mechanics could be helpful in predicting surgical success. Partial 3D finite element models based on patient-specific CT-scans were undertaken in a pilot study of 5 OSA patients. Upper airway soft tissues including the soft palate, hard palate, tongue, and pharyngeal wall were segmented around the midsagittal plane up to a width of 2.5 cm in the lateral direction. Simulations of surgical interventions such as Uvulopalatopharyngoplasty (UPPP), maxillo-mandibular advancement (MMA), palatal implants, and tongue implants have been performed. Our results showed that maxillo-mandibular advancement (MMA) surgery of 1 cm improved the critical closing pressure by at least 212.2%. Following MMA, the best improvement was seen via uvulopalatopharyngoplasty (UPPP), with an improvement of at least 19.12%. Palatal and tongue implants also offered a certain degree of improvement. Further, we observed possible interacting mechanisms that suggested simultaneous implementation of UPPP and tongue stiffening; and palatal and tongue stiffening could be beneficial. Our results suggest that computational modeling is a useful tool for analyzing the influence of anatomic and physiological manipulations on upper airway mechanics. The goal of personalized treatment in the case of OSA could be achieved with the use of computational modeling.

Mechanical behavior and collagen structure of degenerative mitral valve leaflets and a finite element model of primary mitral regurgitation.

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.

In silico analysis provides insights for patient-specific annuloplasty in Barlow's disease.

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.

Recombinant irisin enhances the extracellular matrix formation, remodeling potential, and differentiation of human periodontal ligament cells cultured in 3D.

BACKGROUND: Irisin is expressed in human periodontal ligament (hPDL), and its administration enhances growth, migration and matrix deposition in hPDL cells cultured in monolayers in vitro. OBJECTIVES: To identify whether irisin affects the gene expression patterns directing the morphology, mechanical properties, extracellular matrix (ECM) formation, osteogenic activity and angiogenic potential in hPDL cell spheroids cultured in 3D. MATERIALS AND METHODS: Spheroids of primary human hPDL cells were generated in a rotational 3D culture system and treated with or without irisin. The gene expression patterns were evaluated by Affymetrix microarrays. The morphology of the spheroids was characterized using histological staining. Mechanical properties were quantified by nanoindentation. The osteogenic and angiogenic potential of spheroids were assessed through immunofluorescence staining for collagen type I, periostin fibronectin and von Willebrand factor (vWF), and mRNA expression of osteogenic markers. The secretion of multiple myokines was evaluated using Luminex immunoassays. RESULTS: Approximately 1000 genes were differentially expressed between control and irisin-treated groups by Affymetrix. Several genes related to ECM organization were differentially expressed, and multiple deubiquitinating enzymes were upregulated in the irisin-exposed samples analyzed. These represent cellular and molecular mechanisms indicative of a role for irisin in tissue remodeling. Irisin induced a rim-like structure on the outer region of the hPDL spheroids, ECM-related protein expression and the stiffness of the spheroids were enhanced by irisin. The expression of osteogenic and angiogenetic markers was increased by irisin. CONCLUSIONS: Irisin altered the morphology in primary hPDL cell-derived spheroids, enhanced its ECM deposition, mechanical properties, differentiation and remodeling potential.

Finite element analysis of mitral valve annuloplasty in Barlow's disease.

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.

Microstructure and mechanics of the bovine trachea: Layer specific investigations through SHG imaging and biaxial testing.

The trachea is a complex tissue made up of hyaline cartilage, fibrous tissue, and muscle fibers. Currently, the knowledge of microscopic structural organization of these components and their role in determining the tissue's mechanical response is very limited. The purpose of this study is to provide data on the microstructure of the tracheal components and its influence on tissue's mechanical response. Five bovine tracheae were used in this study. Adventitia, cartilage, mucosa/submucosa, and trachealis muscle layers were methodically cut out from the whole tissue. Second-harmonic generation(SHG) via multi-photon microscopy (MPM) enabled imaging of collagen fibers and muscle fibers. Simultaneously, a planar biaxial test rig was used to record the mechanical behavior of each layer. In total 60 samples were tested and analyzed. Fiber architecture in the adventitia and mucosa/submucosa layer showed high degree of anisotropy with the mean fiber angle varying from sample to sample. The trachealis muscle displayed neat layers of fibers organized in the longitudinal direction. The cartilage also displayed a structure of thick mesh-work of collagen type II organized predominantly towards the circumferential direction. Further, mechanical testing demonstrated the anisotropic nature of the tissue components. The cartilage was identified as the stiffest component for strain level < 20% and hence the primary load bearing component. The other three layers displayed a non-linear mechanical response which could be explained by the structure and organization of their fibers. This study is useful in enhancing the utilization of structurally motivated material models for predicting tracheal overall mechanical response.

Assembly of Graphene Platelets for Bioinspired, Stimuli-Responsive, Low Ice Adhesion Surfaces.

Design and fabrication of functional materials for anti-icing and deicing attract great attention from both the academic research and industry. Among them, the study of fish-scale-like materials has proved that enabling sequential rupture is an effective approach for weakening the intrinsic interface adhesion. Here, graphene platelets were utilized to construct fish-scale-like surfaces for easy ice detachment. Using a biomimicking arrangement of the graphene platelets, the surfaces were able to alter their structural morphology for the sequential rupture in response to external forces. With different packing densities of graphene platelets, all the surfaces showed universally at least 50% reduction in atomistic tensile ice adhesion strength. Because of the effect of sequential rupture, stronger ice-surface interactions did not lead to an obvious increase in ice adhesion. Interestingly, the high packing density of graphene platelets resulted in stable and reversible surface morphology in cyclic tensile and shearing tests, and subsequently high reproducibility of the sequential rupture mode. The fish-scale-like surfaces built and tested, together with the nanoscale deicing results, provided a close view of ice adhesion mechanics, which can promote future bioinspired, stress-responsive, anti-icing surface designs.

Biomechanics of mitral valve leaflets: Second harmonic generation microscopy, biaxial mechanical tests and tissue modeling.

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.

On the Determination of Mechanical Properties of Aqueous Microgels-Towards High-Throughput Characterization.

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.

Vitamin K2 Modulates Vitamin D-Induced Mechanical Properties of Human 3D Bone Spheroids In Vitro.

Rotational culture promotes primary human osteoblasts (hOBs) to form three-dimensional (3D) multicellular spheroids with bone tissue-like structure without any scaffolding material. Cell-based bone models enable us to investigate the effect of different agents on the mechanical strength of bone. Given that low dietary intake of both vitamin D and K is negatively associated with fracture risk, we aimed to assess the effect of these vitamins in this system. Osteospheres of hOBs were generated with menaquinone-4 (MK-4; 10µM) and 25-hydroxyvitamin D3 [25(OH)D3; 0.01µM], alone and in combination, or without vitamins. The mechanical properties were tested by nanoindentation using a flat-punch compression method, and the mineralized extracellular bone matrix was characterized by microscopy. The in vitro response of hOBs to MK-4 and 25(OH)D3 was further evaluated in two-dimensional (2D) cultures and in the 3D bone constructs applying gene expression analysis and multiplex immunoassays. Mechanical testing revealed that 25(OH)D3 induced a stiffer and MK-4 a softer or more flexible osteosphere compared with control. Combined vitamin conditions induced the same flexibility as MK-4 alone. Enhanced levels of periostin (p < 0.001) and altered distribution of collagen type I (COL-1) were found in osteospheres supplemented with MK-4. In contrast, 25(OH)D3 reduced COL-1, both at the mRNA and protein levels, increased alkaline phosphatase, and stimulated mineral deposition in the osteospheres. With the two vitamins in combination, enhanced gene expression of periostin and COL-1 was seen, as well as extended osteoid formation into the central region and increased mineral deposition all over the area. Moreover, we observed enhanced levels of osteocalcin in 2D and osteopontin in 3D cultures exposed to 25(OH)D3 alone and combined with MK-4. In conclusion, the two vitamins seem to affect bone mechanical properties differently: vitamin D enhancing stiffness and K2 conveying flexibility to bone. These effects may translate to increased fracture resistance in vivo. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Donnan Contribution and Specific Ion Effects in Swelling of Cationic Hydrogels are Additive: Combined High-Resolution Experiments and Finite Element Modeling.

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.

Data on residual stresses of mooring chains measured by neutron diffraction and hole drilling techniques.

Residual stresses in large offshore mooring chains have been measured for the first time and presented in this article. Two chain links with the same size and material, one only subjected to proof load and no cyclic service loads and the other exposed to service loads as well as the proof load, were selected for the experiment. Residual stresses just below the surface were measured using the hole-drilling technique and the neutron diffraction technique was employed for deeper measurements. The data can be used to investigate residual stress redistribution in the chain links because of material removal due to corrosion and cyclic service loads that the chains are exposed to during their service time. Moreover, the data can be used to validate numerical models for predicting residual stresses. A more detailed interpretation of the data presented in this article is provided in "Experimental and numerical study of mooring chain residual stresses and implications for fatigue life" [1].

Enabling sequential rupture for lowering atomistic ice adhesion.

State-of-the-art passive icephobicity relies mainly on static parameters such as surface energy, coating elastic modulus, crack sizes and so on. Low ice adhesion resulting from the dynamic de-icing process, for instance ice detaching modes from substrates, has not yet been explored. In the current study, atomistic modeling and molecular dynamics simulations were employed to identify ice rupture modes as crucial dynamic factors for surface icephobicity. A fish-scale-like icephobic surface prototype enabling low-adhesion sequential rupture of the atomistic interactions at the ice-solid interface was proposed. The novel surface has an intrinsic extended interface rupture pathway, which can lead to a ∼60% reduction in atomistic ice adhesion compared with concurrent ice rupture. This study sheds light on interface mechanical design for surface icephobicity, and could provide solutions for anti-icing, nanoscale tribology and many others. The concept of implementing interfacial rupture modes proposed in this study can also apply to interface design for tailored adhesion mechanics.

Soft palate muscle activation: a modeling approach for improved understanding of obstructive sleep apnea.

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.

3D patient-specific numerical modeling of the soft palate considering adhesion from the tongue.

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.

Adiponectin Reduces Bone Stiffness: Verified in a Three-Dimensional Artificial Human Bone Model In Vitro.

Primary human osteoblasts and osteoclasts incubated in a rotating coculture system without any scaffolding material, form bone-like tissue that may be used to evaluate effects of various compounds on mechanical strength. Circulating adiponectin has been found to be negatively associated with BMD and strength and was therefore assessed in this system. Osteospheres of human osteoblasts and osteoclasts were generated with and without adiponectin. The osteospheres were scanned using micro-computed tomography, the mechanical properties were tested by flat punch compression using nanoindentation equipment, and the cellular morphology characterized by microscopy. The association between autologously produced adiponectin and biomechanical properties was further evaluated by quantitation of adiponectin levels using quantitative polymerase chain reaction (qPCR) and immunoassays, and identification of stiffness by bending test of rat femurs. The molecular mechanisms were examined in vitro using human bone cells. Mechanical testing revealed that adiponectin induced a more compliant osteosphere compared with control. The osteospheres had a round, lobulated appearance with morphologically different areas; inner regions containing few cells embedded in a bone-like material surrounded by an external area with a higher cell quantity. The expression of adiponectin was found to correlate positively to ultimate bending moment and ultimate energy absorption and deflection, on the other hand, it correlated negatively to bending stiffness, indicating autocrine and/or paracrine effects of adiponectin in bone. Adiponectin enhanced proliferation and expression of collagen, leptin, and tumor necrosis factor-alpha in osteoblasts and stimulated proliferation, but not the functional activity of osteoclasts. Our results indicate that both administration of adiponectin during osteosphere production and in situ elevated levels of adiponectin in rat femurs, reduced stiffness of the bone tissues. An increase in undifferentiated cells and extracellular matrix proteins, such as collagen, may explain the reduced bone stiffness seen in the osteospheres treated with adiponectin.

Simulation of the upper airways in patients with obstructive sleep apnea and nasal obstruction: A novel finite element method.

OBJECTIVE: To evaluate the biomechanical properties of the soft palate and velopharynx in patients with obstructive sleep apnea (OSA) and nasal obstruction. STUDY DESIGN: Prospective experimental study. MATERIALS AND METHODS: Two finite element (FE) models of the soft palate were created in six patients undergoing nasal surgery, one homogeneous model based on CT images, and one layered model based on soft tissue composition. The influence of anatomy on displacement caused by a gravitational load and closing pressure were evaluated in both models. The strains in the transverse and longitudinal direction were obtained for each patient. RESULTS: The individual anatomy influences both its structural stiffness and its gravitational displacement. The soft palate width was the sole anatomical parameter correlated to the critical closing pressure, but the maximal displacement due to gravity may have a relationship to closing pressure of possibly an exponential order. The airway occlusion occurred mainly at the lateral attachments of the soft palate. The total transverse strain showed a strong correlation with maximal closing pressure. There was no relationship between the critical closing pressure and the preoperative AHI levels, or the change in AHI after surgery. CONCLUSION: Hyperelastic FE models both in the homogeneous and layered model represent a novel method of evaluating soft tissue biomechanics of the upper airway. The obstruction occurs mainly at the level of the lateral attachments to the pharyngeal wall, and the width of the soft palate is an indicator of the degree of critical closing pressure. A less negative closing pressure corresponds to small total transverse strain. The effect of nasal surgery on OSA is most likely not explained by change in soft palate biomechanics. LEVEL OF EVIDENCE: NA.