Biomechanics and Modeling in Mechanobiology最新文献

Thoracic endovascular aortic repair (TEVAR) procedure is sometimes discouraged from clinical guidelines in the presence of calcifications and thrombus along the sealing zones. This computational study aims to understand which is the effect of calcification on stent graft displacement after TEVAR procedure, simulated in a patient-specific anatomy with a penetrating aortic ulcer (PAU).

A patient-specific anatomy without calcification is taken as reference, and four models with idealized calcifications positioned in different regions and with different material properties are analyzed. Opening area, von Mises stresses and contact pressures are evaluated to provide a reliable comparison between the calcified (Ca) and the non-calcified models (noCa), and among the calcified models themselves.

Comparing qualitatively the Ca and noCa models, no particular changes in the stent graft apposition are observed. In addition, in the Ca models the opening area results lower with respect to the noCa models, but no significant differences are observed among the Ca models. Regarding the von Mises stresses, it seems that the calcifications act as load-bearing structures, absorbing the stresses and reducing them on the aorta. Decreasing the Young modulus of the calcifications, this effect is reduced. Higher contact pressures are observed when the highest Young’s modulus of calcification is adopted, with all Ca models having greater pressures than the noCa model.

From this analysis, the stent graft seems to be positioned correctly inside the aorta, even in the presence of calcifications. In this setting, the calcifications seem to reduce the stresses on the aorta, thus reducing the likelihood of aneurysm rupture.

Mechanical forces on cells and tissues are known to play key roles in regulating cell fate, function, and tissue repair. In bone tissue engineering, mechanical stimulation of cell-hydrogel constructs with low-intensity ultrasound has become a promising therapy for improving the pace and extent of bone regeneration in challenging defects, though its physical and biological mechanisms are not fully understood. In particular, the local ultrasound-induced forces that are imparted to fully encapsulated cells have not been directly quantified. Here, we have developed, validated, and applied a novel 3D force microscopy technique (3D-FM) that extends established principles of unconstrained, regularized, Fourier domain traction force microscopy to reconstruct forces within ultrasound-displaced 3D cell-hydrogel constructs. Validation tests with simulated data demonstrated that the algorithm is capable of reconstructing simple and complex force-density fields from simulated displacements and is robust against corruption with noise. 3D-FM was then used to estimate the ultrasound-induced forces around a bone marrow stromal cell within a soft collagen hydrogel. Localized forces near the cell had magnitudes comparable to other reported cell-scale forces (~ 100 nN), with components both parallel and perpendicular to the direction of ultrasound propagation. This work demonstrates that 3D-FM can elucidate the microscopic physical effects of low-intensity ultrasound on cells in soft matrices used in bone regeneration applications, which can provide valuable insight into the relationship between applied physical forces and cellular responses.

Left ventricular outflow tract obstruction (LVOTO) is a representative phenotype of obstructive hypertrophic cardiomyopathy (OHCM). Septal myectomy has been extensively demonstrated as an effective surgery for treating OHCM. However, it remains incompletely understood how the surgery would alter the mechanical and energetic states of the left ventricle (LV). In this study, microstructure-based finite element (FE) models were built for the LVs of two patients with OHCM to compute myocardial mechanics before and after septal myectomy. In addition, energy metrices spanning multiple scales were defined and calculated based on the results of FE analysis. The results showed that septal myectomy facilitated a significant improvement in the mechanical state of the LV, characterized mainly by the overall decreased while more homogeneously distributed myocardial tissue and cardiomyocyte stresses. Energetically, the total mechanical energies at the scales of the entire LV, myocardial tissue, and cardiomyocyte all decreased remarkably after septal myectomy. Moreover, the surgery induced a moderate increase in the efficiencies of mechanical energy conversion at the myocardial tissue and cardiomyocyte levels in the septal region. Although the mechanical and energetic parameters of the LV differed quantitatively between the two patients, they exhibited similar trends of change following septal myectomy. These results suggest that septal myectomy can improve the mechano-energetic state of the LV, and thereby may exert favorable influence on postoperative cardiac remodeling and adaptation. The proposed modeling method may offer a promising means for optimizing surgical planning or evaluating the therapeutic effects of septal myectomy for patients with OHCM.

Understanding how bone adapts to external forces is fundamental for exploring potential biomechanical interventions against skeletal diseases. This can be studied preclinically, combining in vivo experiments in rodents and in silico mechanoregulation models. While the in vivo tibial loading model is widely used to study bone adaptation, the common assumption of purely axial loading may be a simplification. This study quantifies the effect of the loading direction on the strain energy density (SED) distribution in the mouse tibia, a commonly used input for mechanoregulated bone remodelling models. To achieve this, validated micro-finite element (micro-FE) models were used to test the differences in local SED when the bone was loaded along different loading directions. In vivo micro-computed tomography (micro-CT) images were acquired from the tibiae of eleven ovariectomised mice at 18 weeks old before intervention and at 20 weeks old, after six mice underwent external mechanical loading. Micro-CT-based micro-FE models were generated for each tibia at both time points and loaded with a unit load in each Cartesian direction independently. The results from these unit load models were linearly combined to simulate various loading directions, defined by angles θ (inferior-superior) and ϕ (anterior–posterior). The results revealed a high sensitivity of the mouse tibia to the loading direction across both groups and time points. Several loading directions (e.g., θ = 10°, ϕ = 205–210°) resulted in lower medians of the top 5% SED values compared to those obtained for the nominal axial case (θ = 0°, ϕ = 0°). Conversely, higher values were observed for other directions (e.g., θ = 30°, ϕ = 35–50°). These findings emphasise the importance of considering the loading direction in experimental and computational bone adaptation studies.

The intricate three-dimensional organization of cardiac myofibers and sheetlets plays a critical role in the mechanical behavior of the human heart. Despite extensive research and the development of various rule-based myofiber architecture surrogate models, the precise arrangement of these structures and their impact on cardiac function remain subjects of debate. In this study, we present a novel myofiber architecture surrogate inspired by Streeter’s nested tori conjecture, modeling the left ventricle as a series of smoothly twisting toroidal surfaces populated by continuous myofiber and sheetlet fields. Leveraging high-fidelity cardiac computational modeling approaches, we systematically evaluated the biomechanical performance of this nested tori architecture against conventional rule-based nested ellipsoidal models. Our results demonstrate that the nested tori architecture aligns more closely with experimental data on physiological myofiber and sheetlet angles. Notably, it enhances sheetlet mobility—a key mechanism for effective cardiac pumping—resulting in higher ejection fraction, greater global deformation, and a more physiological wall rotation pattern. Additionally, it produces a more homogeneous myofiber stress distribution and increased myofiber shortening during ejection. These findings suggest that the nested tori architecture provides a compelling alternative to conventional nested ellipsoidal models, offering a more physiologically consistent representation of myocardial structure and its functional implications. By enabling improved biomechanical performance in silico, this approach supports further investigation into how detailed myoarchitectural continuity shapes cardiac function. Ultimately, it may open promising avenues for advancing cardiac diagnosis, guiding the design of bioinspired implants and devices, and deepening our understanding of both healthy and diseased cardiac mechanics.

Pediatric intussusception is frequently observed in the ileocecal region, where the terminal ileum invaginates into the colon. Previous studies have indicated an association between pediatric intussusception and inflammation as well as intestinal motility. However, the underlying mechanisms remain unclear, particularly with regard to the mechanics. We hypothesized that invagination occurs when longitudinal and circular smooth muscles are not coordinated during peristalsis. To test the hypothesis from a mechanical perspective, we developed a computational model of the terminal ileum, where the terminal ileum is modeled as a hyperelastic tube. We showed that circumferential contraction with longitudinal relaxation of the hyperelastic tube wall caused invagination in the contracting region of the tube. We also found that invagination occurred when a square-shaped contracting region emerged in the hyperelastic tube. These results indicate that uncoordinated motion of the circular and longitudinal muscles can lead to invagination of the intestinal wall. In addition, the configuration of peristalsis may serve as an indicator of the risk of pediatric intussusception.

The adventitia of blood vessels is their structural interface with surrounding tissues and may also contribute importantly to atherogenesis. Adventitial vasa vasorum and lymphatic vessels provide sources and sinks of interstitial fluid and solutes and remodel in disease. We constructed a mathematical model to investigate how soluble disease mediators, including lipoproteins and cytokines, are transported through the artery wall in healthy and atherosclerotic conditions. We derived model parameters from in vivo measurements where possible and extensively investigated the sensitivity of fluid flow and solute transport to them. Adventitial interstitial fluid pressure is predicted to increase in atherosclerosis because of a shift in transmural fluxes across vasa vasorum and lymphatics. In healthy conditions, 40–80% of the fluid gathered by lymphatics originates from vasa vasorum, and this increases to 60–90% in atherosclerosis. The increased dilution of fluid flowing from the inner layers in atherosclerosis implies that solute transport from the media to the adventitia is impaired. This implies increased concentration gradients near the external elastic lamina that may increase immune-cell retention there, and decreased gradients in the outer adventitia that may reduce immune-cell attraction from there.

Computational modeling has become an integral tool for understanding the interaction between structural organization and functional behavior in a wide range of biological tissues, including the human myocardium. Traditional constitutive models, and recent models generated by automated model discovery, are often based on the simplifying assumption of perfectly aligned fiber families. However, experimental evidence suggests that many fiber-reinforced tissues exhibit local dispersion, which can significantly influence their mechanical behavior. Here, we integrate the generalized structure tensor approach into automated material model discovery to represent fibers that are distributed with rotational symmetry around three mean orthogonal directions—fiber, sheet, and normal—by using probabilistic descriptions of the orientation. Using biaxial extension and triaxial shear data from human myocardium, we systematically vary the degree of directional dispersion and stress measurement noise to explore the robustness of the discovered models. Our findings reveal that up to a moderate dispersion in the fiber direction and arbitrary dispersion in the sheet and normal directions improve the goodness of fit and enable recovery of a previously proposed four-term model in terms of the isotropic second invariant, two dispersed anisotropic invariants, and one coupling invariant. Our approach demonstrates strong robustness and consistently identifies similar model terms, even in the presence of up to 7% random noise in the stress data. In summary, our study suggests that automated model discovery based on the powerful generalized structure tensors is robust to noise and captures microstructural uncertainty and heterogeneity in a physiologically meaningful way.

The frequent detection of wall enhancement by vessel wall imaging in unstable or ruptured intracranial aneurysms (IAs) implies the potential involvement of blood substance transport in the pathogenesis of IAs. In this study, we developed a new method for simulating the transport of low-density lipoprotein (LDL) in IAs. The method was characterized by the coupled solution of LDL transport behaviors in lumen, across endothelium, and within vessel wall, and the incorporation of a sub-model that accounts for the combined effect of wall shear stress (WSS) magnitude and oscillatory shear index (OSI) on endothelial permeability to LDL. Numerical simulations were conducted on the IAs of four patients with clinically confirmed wall enhancement status. Obtained results demonstrated the propensity of IAs for enhanced LDL deposition on the lumen surface and LDL accumulation within the wall compared to normal cerebral arteries. Notably, the spatial distributions of high LDL concentration on the lumen surface and within the vessel wall were not always consistent, indicating regional variations in biomechanical factors facilitating intraluminal retention and transmural transport of LDL. Furthermore, the IAs with wall enhancement exhibited remarkably larger area ratios of wall regions exposed to high LDL concentration than those without wall enhancement. Relatively, the area ratios of low WSS and high OSI were less predictive of aneurysm wall enhancement. These findings underscore the potential value of investigating mass transport over general hemodynamic behaviors in classifying the pathological state or assessing the risk of IAs.

Tendons are known to adapt their structural and mechanical properties in response to mechanical loading, but the precise mechanisms underlying this adaptation remain poorly understood. A previous study on rat Achilles tendons compared the effect of unloading (Botox injections and orthosis) with free cage activity (full loading) and revealed that unloading impaired the mechanical response and resulted in more dispersed collagen fibre orientations. The current study investigates tendon mechanobiology by integrating this experimental fibre data into a finite element model. The aim is to evaluate whether the altered mechanical response after unloading results from changes in collagen fibre orientation, tendon geometry, or material properties. Collagen fibre orientation analysis was performed based on phase-contrast enhanced synchrotron X-ray tomography images. Two levels of collagen fibre orientation detail were implemented into the finite element model: 1) global fibre orientation analysis that averaged fibre directions across the entire tendon and 2) local orientation analysis that introduced spatial heterogeneity by incorporating element-specific fibre distributions. Our results indicate that the impaired mechanical response in unloaded tendons is mainly due to changes in fibre orientation distribution and geometry. The local collagen orientation analysis showed a lower overall force response, but did not alter the relative differences between fully loaded and unloaded tendons. Incorporating the increased heterogeneity may still be important for future studies of tendon mechanobiology. The established framework provides a robust tool for exploring tendon biomechanics, capturing detailed fibre information, and offering valuable insights into tendon adaptation under various conditions.

Graphical abstract