Biomechanics and Modeling in Mechanobiology最新文献

Acute ischemic stroke remains a leading cause of global disability and mortality. While mechanical thrombectomy with stent retrievers has improved outcomes through rapid reperfusion, the main limitation is the lack of conformability in tortuous and bifurcated arteries, thus reducing the thrombus retention efficacy in such complex vascular anatomies. This study introduces a novel self-expandable stent retriever design featuring a segmented closed-cell structure with bridging elements, designed to enhance both radial force and flexibility. Finite element analysis evaluated mechanical performance under different loading configurations, aiming at assessing a few key biomechanical parameters such as maximum principal strain and radial force. Then, a multi-objective optimization was performed to increase the device radial force while maintaining low strains. Compared to commercial devices, the optimized stent demonstrated a 18.2% lower bending moment and maintained cross-sectional geometry more effectively under deformation, indicating improved flexibility and shape preservation during navigation in tortuous vessels. Preliminary proof-of-concept in vitro thrombectomy experiments demonstrated effective engagement with mechanically stiff thrombi in different realistic scenarios, such as in stenotic and curved vessel models. While retrieval in bifurcated models still presents some challenges, the results suggest that the proposed design offers a promising balance between flexibility and radial strength, potentially improving thrombectomy outcomes in complex vascular environments.

This paper deals with the development of a reduced order model (ROM) which could be used as an efficient tool for the reconstruction of the unsteady blood flow patterns in cardiovascular applications. The methodology relies on proper orthogonal decomposition to compute basis functions, combined with a Galerkin projection to compute the reduced coefficients. The main novelty of this work lies in the extension of the lifting function method, which typically is adopted for treating nonhomogeneous inlet velocity boundary conditions, to the handling of nonhomogeneous outlet boundary conditions for pressure, representing a very delicate point in numerical simulations of cardiovascular systems. Moreover, we incorporate a properly trained neural network in the ROM framework to approximate the mapping from time parameter to outflow pressure, which in the most general case is not available in closed form. We define our approach as “hybrid", because it merges equation-based elements with purely data-driven ones. The full order model (FOM) is related to a finite volume method which is employed for the discretization of unsteady Navier–Stokes equations while a two-element Windkessel model is adopted to enforce a reliable estimation of outflow pressure. Numerical results, firstly related to a 3D idealized blood vessel and then to a 3D patient-specific aortic arch, demonstrate that our ROM is able to accurately approximate the FOM with a significant reduction in computational cost.

Herniation, rotation, looping, and retraction of the midgut occur sequentially during midgut morphogenesis. Recent studies have demonstrated the importance of mechanical forces arising from the differential growth between the midgut and mesentery in the formation of small intestinal loops. However, the roles of mechanics and differential growth in the overall process remain unclear. In this study, we developed a computational model of midgut morphogenesis based on continuum mechanics. We showed that the protrusion, rotation, and retraction of the midgut can emerge sequentially because of temporal changes in differential growth. The midgut was modeled as a hyperelastic tube with a Gaussian shape. The differential growth of the midgut and mesentery was modeled by the spatial variation in spontaneous plastic deformation. The hyperelastic tube developed a protrusion by compression-induced deformation, suggesting that other external forces are not necessary for midgut herniation prior to rotation. Appropriate differential growth induced a (90^{circ }) rotation of the tube. A less-growing mesentery attempts to face inward to minimize the tensile forces, which causes tube twisting and results in midgut rotation. Excess differential growth may cause the retraction of the midgut before the formation of small intestinal loops. The results of this study will serve as reference in future studies on embryology and tissue engineering.

Patient-specific computational models of the cardiovascular system can inform clinical decision-making by providing physics-based, non-invasive calculations of quantities that cannot be measured or are impractical to measure and by predicting physiological changes due to interventions. In particular, mixed-dimensional 3D–0D coupled models can represent spatially resolved 3D myocardial tissue mechanics and 0D pressure–flow relationships in heart valves and vascular system compartments, while accounting for their interactions in a closed-loop setting. We present an inverse analysis framework for the automated identification of a set of 3D and 0D patient-specific parameters based on flow, pressure, and cine cardiac MRI measurements. We propose a novel decomposition of the underlying large, nonlinear, and mixed-dimensional inverse problem into an equivalent set of independently solvable, computationally efficient, and well-posed inverse subproblems. This decomposition is enabled by the availability of measurement data of the coupling quantities and ensures a faster convergence toward a unique minimum. The inverse subproblems are solved with a L-BFGS optimization algorithm and an adjoint gradient evaluation. The proposed framework is demonstrated in a clinical case study of an adult repaired tetralogy of Fallot (ToF) patient with severe pulmonary regurgitation. The identified parameters provide a good agreement between measured and computed flows, pressures, and chamber volumes, ensuring a patient-specific model response. The outcome prediction of an in silico pulmonary valve replacement using the personalized model is physiologically consistent and correlates well with postoperative measurements. The proposed framework is essential for developing accurate and reliable cardiovascular digital twins and exploiting their predictive capabilities for intervention planning.

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.