Three constitutive laws, that is the Skalak, neo-Hookean and Yeoh laws, commonly employed for describing the erythrocyte membrane mechanics are theoretically analyzed and numerically investigated to assess their accuracy for capturing erythrocyte deformation characteristics and morphology. Particular emphasis is given to the nonlinear deformation regime, where it is known that the discrepancies between constitutive laws are most prominent. Hence, the experiments of optical tweezers and micropipette aspiration are considered here, for which relationships between the individual shear elastic moduli of the constitutive laws can also be established through analysis of the tension-deformation relationship. All constitutive laws were found to adequately predict the axial and transverse deformations of a red blood cell subjected to stretching with optical tweezers for a constant shear elastic modulus value. As opposed to Skalak law, the neo-Hookean and Yeoh laws replicated the erythrocyte membrane folding, that has been experimentally observed, with the trade-off of sustaining significant area variations. For the micropipette aspiration, the suction pressure-aspiration length relationship could be excellently predicted for a fixed shear elastic modulus value only when Yeoh law was considered. Importantly, the neo-Hookean and Yeoh laws reproduced the membrane wrinkling at suction pressures close to those experimentally measured. None of the constitutive laws suffered from membrane area compressibility in the micropipette aspiration case.
INTRODUCTION: The biological and mechanical properties of circulating tumor cells (CTCs) in combination with the hemodynamics affect the preference of metastatic sites in the vasculature. Despite the extensive literature on the effects of biological properties on cell adhesion, the effects of hydrodynamic forces on primary attachment remains an active area of research. Using simulations in conjunction with experimentation, we provide new insight into the interplay of CTCs dynamics and local hydrodynamics. METHODS: A flow experiment of CTC attachment was performed within a bioprinted, double branching endothelialized vessel. Simulations of fluid flow and CTC transport in the reconstructed and idealized bifurcated vessel were respectively performed by HARVEY, our in-house massively parallel computational fluid dynamics solver. HARVEY is based on the lattice Boltzmann and finite element methods to model the fluid and cells dynamics. The immersed boundary method is employed for resolving the fluid-structure interaction. RESULTS: CTC attachment was quantified experimentally at all regions of the complex vessel. The results demonstrate a clear preference for CTCs to attach at the branch points. To elucidate the effect of the vessel topology on the location of attachment, a fluid-only simulation was performed assessing the differences in the hydrodynamics along the vessel. CTC transport in idealized bifurcated vessels was subsequently studied to examine the effects of cell deformability on the local hydrodynamics patterns and, thus, the preference of attachment sites. CONCLUSIONS: The current work provides evidence on the correlation of the hydrodynamics forces arising from the vessel topology and CTC properties on the attachment regions.
Various types of embolization devices have been developed for the treatment of cerebral aneurysms. However, it is challenging to properly evaluate device performance and train medical personnel for device deployment without the aid of functionally relevant models. Currentin vitroaneurysm models suffer from a lack of key functional and morphological features of brain vasculature that limit their applicability for these purposes. These features include the physiologically relevant mechanical properties and the dynamic cellular environment of blood vessels subjected to constant fluid flow. Herein, we developed three-dimensionally (3D) printed aneurysm-bearing vascularized tissue structures using gelatin-fibrin hydrogel of which the inner vessel walls were seeded with human cerebral microvascular endothelial cells (hCMECs). The hCMECs readily exhibited cellular attachment, spreading, and confluency all around the vessel walls, including the aneurysm walls. Additionally, thein vitroplatform was directly amenable to flow measurements via particle image velocimetry, enabling the direct assessment of the vascular flow dynamics for comparison to a 3D computational fluid dynamics model. Detachable coils were delivered into the printed aneurysm sac through the vessel using a microcatheter and static blood plasma clotting was monitored inside the aneurysm sac and around the coils. This biomimeticin vitroaneurysm model is a promising method for examining the biocompatibility and hemostatic efficiency of embolization devices and for providing hemodynamic information which would aid in predicting aneurysm rupture or healing response after treatment.
Bioprinting , Embolization, Therapeutic , Intracranial Aneurysm , Blood Vessel Prosthesis , Endothelial Cells , Humans , Intracranial Aneurysm/therapy
We extend a recently proposed ternary free-energy lattice Boltzmann model with high density contrast [Phys. Rev. Lett. 120, 234501 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.234501] by incorporating wetting boundaries at solid walls. The approaches are based on forcing and geometric schemes, with implementations optimized for ternary (and, more generally, higher-order multicomponent) models. Advantages and disadvantages of each method are addressed by performing both static and dynamic tests, including the capillary filling dynamics of a liquid displacing the gas phase and the self-propelled motion of a train of drops. Furthermore, we measure dynamic angles and show that the slip length critically depends on the equilibrium value of the contact angles and whether it belongs to liquid-liquid or liquid-gas interfaces. These results validate the model capabilities of simulating complex ternary fluid dynamic problems near solid boundaries, for example, drop impact solid substrates covered by a lubricant layer.
