Nanoindentation and finite element modelling of chitosan-alginate multilayer coated hydrogels.

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.

Characterisation of global and regional mitral annular strains in an acute porcine model.

OBJECTIVES: This study aimed to explore regional mitral annular strain using a novel computational method. METHODS: Eight pigs underwent implantation with piezoelectric transducers around the mitral annulus. Interventions of pre- and afterload were performed by inferior vena cava constriction and endovascular balloon occlusion of the descending aorta. The mitral annulus was reconstructed in a mathematical model and divided into 6 segments. Global and segmental annular strain were calculated from a discrete mathematical representation. RESULTS: Global annular strain gradually decreased after isovolumetric contraction until late systole. Mitral annular end-systolic strain demonstrated shortening in all segments except the anterior segment, which showed the least deformation. The P2 annular segment demonstrated the most end-systolic shortening (-7.6 ± 1.1% at baseline, P < 0.001 compared to anterior segment). Systolic global annular strain showed no significant change in response to load interventions but correlated positively with left ventricular contractility at baseline and after preload reduction. CONCLUSIONS: Mitral annular systolic strain demonstrates cyclical variations with considerable regional heterogeneity, with the most pronounced deformation in posterior annular segments. Measurements appear independent of changes to pre- and afterload.

Mitral annular dynamics are influenced by left ventricular load and contractility in an acute animal model.

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.

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.

Palatal implant surgery effectiveness in treatment of obstructive sleep apnea: A numerical method with 3D patient-specific geometries.

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.