Biomechanics and Modeling in Mechanobiology最新文献

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

After total hip replacement, the primary and secondary implant stability is critical to ensure long-term success. Excessive migration of the femoral stem can cause implant loosening. In this work, a novel approach for the simulation of the femoral stem migration using the finite element method is presented. Currently, only a few mostly contact-based models exist for this purpose. Instead, a bio-active interface model is used for the bone-stem interface which transforms from the Drucker–Prager to the von Mises plasticity criterion during the osseointegration process. As the position of the implant generally stabilises within one week after the implantation, the migration and osseointegration simulations are decoupled. To understand the effects on the migration, various parameter combinations are examined and a sensitivity analysis is performed. The results indicate that the joint force and the adhesion parameter have the most substantial influence on the migration. Furthermore, the influence of the migration on the subsequent osseointegration process is explored for a numerical example. The proposed model is able to depict the femoral stem migration with values up to 0.27 mm, which are in the order of magnitude of clinically observed values. Further, the model is provided as an open-source Abaqus user material subroutine. Numerical simulation of the stem migration could assist in clinical decision-making by identifying optimal parameter combinations to improve implant stability.

This study explored the biomechanical behavior of co-polymeric swelling bone anchors and their bone remodeling induction using finite element analysis of a model with heterogeneous properties. First, a hygro-elastic finite element framework was developed to capture the swelling of the bone anchors over time by moisture gain, validated against the data from free swelling experiments. Afterward, finite element models were developed using micro-CT data to capture heterogeneous material properties, and finally, bone remodeling induced by the swelling, acting as a mechanical stimulus, was investigated. The study examined three co-polymeric ratios of methyl methacrylate and acrylic acid (MMA/AA)—80/20, 85/15, and 90/10—and assessed the impact of their associated swelling ratios on bone remodeling and fixation strength. Moreover, in parallel with the numerical investigations, an in vivo study using a sheep model was conducted to evaluate the biocompatibility of these anchors and bone remodeling response to the swelling. The numerical findings highlighted the importance of optimizing swelling ratios to enhance mechanical engagement without causing adverse resorption. More specifically, the results demonstrated that bone regeneration in the region of interest is highly sensitive to the swelling ratio. When the swelling is maintained within an optimal range—such as in the 85/15 composition—favorable densification occurs at the bone–implant interface, enhancing osteointegration. In contrast, excessive swelling (e.g., the 80/20 composition) induces localized overload resorption due to elevated stress concentrations at the interface, which may compromise implant success. Additionally, correlations found between the numerical and in vivo study outcomes supported the notion of an optimal swelling threshold and confirmed the predictive capabilities of the developed hygro-elastic finite element framework. To underscore the importance of favorable bone remodeling in the interface, a push-out study was performed to analyze the fixation strength prior and subsequent to bone remodeling. The significant difference in push-out forces before and after remodeling demonstrates that bone densification at the interface can substantially enhance fixation strength.

Acute ischemic stroke (AIS) is a leading cause of death worldwide. In recent years, several studies have characterized the material properties of clot types that were removed from stroke patients, showing a highly nonlinear, asymmetric behavior in compression and tension. However, little is still known about the clot phenotype underlying complications in endovascular thrombectomy (EVT). In this study, we propose a spectrum of clot surrogates for highly stiff, red blood cell-rich, aged, calcified clots that may underpin the outcomes of AIS procedures, often called ‘hyperdense middle cerebral artery signs’ by clinicians. This study aims to characterize the high-strain, rate-dependent mechanical properties of a broad range of aged and calcified clot analogs. Blood from healthy donors was used to form aged and calcified clots, which were subjected to rate-dependent uniaxial testing and structural analyses. A method for curve fitting standard linear solids with multiple hyperelastic elements is considered, and a subsequent procedure is outlined for fitting rate-dependent data. High-strain clot analog peak stresses and moduli are on the same order of magnitude as previous studies, with the hypercalcified clots nearly an order of magnitude stiffer than previously recorded. The calcification was shown to be time dependent, as the longer the clots incubated in the calcium solutions, the stiffer they became. SEM images show drastic changes in clot morphology, with mineral nucleation evident around all components of the clot. The curve fitting produced parameters for a host of models that can be used in numerical implementation. The authors note that when curve fitting, energy state of the system should be taken into consideration, in addition to the minimization of the relative error. We demonstrate a wide spectrum of clot properties that are captured well by rate-dependent models for the full dataset, the compressive data, and the tensile data. In this study, we provide a method for creating and characterizing hypercalcified clot analogs as surrogates for the clot phenotype underlying EVT complications. The library of clot properties reported here can be used in numerical simulations, with careful considerations of the curve fitting methods that are employed. These data highlight the need for further investigation into this clot phenotype, which may be related to the subset of AIS patients where clots are unable to be removed.

The rising use of biologic drugs has increased the demand for alternative gastric administration methods. Inception of devices engineered to insert medication into the mucosal lining overcomes limitations of traditional administration methods. Mechanical forces from such microneedle insertions can affect tissue and cellular behavior, particularly mechanotransduction markers. This study investigates the effects of needle insertion in gastric tissue to inform the design of alternative drug delivery devices. Experimental and computational approaches were utilized, using tension and radial compression tests on porcine gastric tissue to inform a finite element analysis (FEA) model. This model was validated with atomic force microscopy (AFM)-based micro-indentation to examine stiffness variations near the insertion site, and yes-associated-protein-1 (YAP-1) expression was analyzed to assess cellular mechanotransduction. AFM results revealed a distance-dependent decrease in tissue stiffness from the insertion site (p < 0.05), with significant differences in needle geometry (p < 0.05). The FEA model correlated well with AFM findings, confirming its validity for further cellular simulations. Mechanical stresses from needle insertion were shown to propagate through the tissue, affecting both cytoplasmic and nuclear stress distributions and altering nuclear morphology near the insertion site. The blunt needle produced a higher localized stress field compared to the sharp needle. Additionally, YAP-1 expression was lower in the injected samples than in control samples showing distance-dependent responses observed. This study demonstrates a validated model linking tissue mechanics and cellular responses, highlighting how needle geometry impacts gastric tissue mechanics and mechanotransduction, providing insights essential for designing gastric drug delivery devices.

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of severe aortic stenosis, yet paravalvular leakage (PVL) remains a significant complication, associated with increased mortality. Clinical studies have identified correlations between PVL and both anatomical features and calcification patterns. Numerical simulations, particularly patient-specific models, offer valuable insights into PVL, but the limited scale of these studies hinders robust statistical analysis. This study introduces a novel in silico clinical trial (ISCT) framework to investigate the correlation between calcification severity, localization and PVL. For this purpose, a synthetic cohort of calcified aortic roots was generated. A conditional convolutional variational autoencoder was used to create calcification patterns for an existing virtual cohort of the aortic root. The workflow includes finite element analyses for pre-dilation and deployment simulations as well as computational fluid dynamic simulations for PVL calculations of 243 virtual TAVR patients. The results show that the absolute amount of calcification in the device landing zone has no significant influence, but its regional distribution does, especially in the combined leaflet regions. In addition, sinotubular junction diameter, annular eccentricity index, oversizing as well as the combination of aortic angle and calcification in the combined non and left coronary leaflet region influence the occurrence of PVL. This framework not only advances our understanding of PVL mechanisms but also demonstrates the potential of ISCT to complement traditional clinical studies, enabling systematic exploration of complex factors influencing TAVR outcomes.

A nonlinear continuum theory is advanced for high-rate mechanics and thermodynamics of liver parenchyma. The homogenized continuum is idealized as a solid–fluid mixture of dense viscoelastic tissue and liquid blood. The solid consists of a matrix material comprising the liver lobules and a collagenous fiber network. Under high loading rates pertinent to impact and blast, the velocity difference between solid and fluid is assumed negligible, leading to a constrained mixture theory. The model captures nonlinear isotropic elasticity, viscoelasticity, temperature changes from thermoelasticity and dissipation, and tissue damage, the latter via a scale-free phase-field representation. Effects of blood volume and initial constituent pressures are included. The model is implemented in 3-D finite element software. Analytical and numerical solutions for planar shock loading are compared with observations of liver trauma from shock-tube experiments. Finite-element simulations of dynamic impact are compared with cylinder drop-weight experiments. Model results, including matrix damage exceeding fiber damage at high rates and reduced mechanical stiffness with higher perfused blood volume, agree with experimental trends. Viscoelasticity is important at modest impact speeds.