Post-angioplasty remodeling of coronary arteries investigated via a chemo-mechano-biological in silico model.

This work presents the application of a chemo-mechano-biological constitutive model of soft tissues for describing tissue inflammatory response to damage in collagen constituents. The material model is implemented into a nonlinear finite element formulation to follow up a coronary standard balloon angioplasty for one year. Numerical results, compared with available in vivo clinical data, show that the model reproduces the temporal dynamics of vessel remodeling associated with subintimal damage. Such dynamics are bimodular, being characterized by an early tissue resorption and lumen enlargement, followed by late tissue growth and vessel constriction. Applicability of the modeling framework in retrospective studies is demonstrated, and future extension towards prospective applications is discussed.

Mechano-chemo-biological model of atherosclerosis formation based on the outside-in theory.

Atherosclerosis is a disease in blood vessels that often results in plaque formation and lumen narrowing. It is an inflammatory response of the tissue caused by disruptions in the vessel wall nourishment. Blood vessels are nourished by nutrients originating from the blood of the lumen. In medium-sized and larger vessels, nutrients are additionally provided from outside through a network of capillaries called vasa vasorum. It has recently been hypothesized (Haverich in Circulation 135:205-207, 2017) that the root of atherosclerotic diseases is the malfunction of the vasa vasorum. This, so-called outside-in theory, is supported by a recently developed numerical model (Soleimani et al. in Arch Comput Methods Eng 28:4263-4282, 2021) accounting for the inflammation initiation in the adventitial layer of the blood vessel. Building on the previous findings, this work proposes an extended material model for atherosclerosis formation that is based on the outside-in theory. Beside the description of growth kinematics and nutrient diffusion, the roles of monocytes, macrophages, foam cells, smooth muscle cells and collagen are accounted for in a nonlinear continuum mechanics framework. Cells are activated due to a lack of vessel wall nourishment and proliferate, migrate, differentiate and synthesize collagen, leading to the formation of a plaque. Numerical studies show that the onset of atherosclerosis can qualitatively be reproduced and back the new theory.

Arterial tissues and their inflammatory response to collagen damage: A continuum in silico model coupling nonlinear mechanics, molecular pathways, and cell behavior.

Damage in soft biological tissues causes an inflammatory reaction that initiates a chain of events to repair the tissue. This work presents a continuum model and its in silico implementation that describe the cascade of mechanisms leading to tissue healing, coupling mechanical as well as chemo-biological processes. The mechanics is described by means of a Lagrangian nonlinear continuum mechanics framework and follows the homogenized constrained mixtures theory. Plastic-like damage, growth and remodeling as well as homeostasis are taken into account. The chemo-biological pathways account for two molecular and four cellular species, and are activated by damage of collagen molecules in fibers. To consider proliferation, differentiation, diffusion and chemotaxis of species, diffusion-advection-reaction equations are employed. To the best of authors' knowledge, the proposed model combines for the first time such high number of chemo-mechano-biological mechanisms in a consistent continuum biomechanical framework. The resulting set of coupled differential equations describe balance of linear momentum, evolution of kinematic variables as well as mass balance equations. They are discretized in time according to a backward Euler finite difference scheme, and in space through a finite element Galerkin discretization. The features of the model are firstly demonstrated presenting the species dynamics and highlighting the influence of damage intensities on the growth outcome. In terms of a biaxial test, the chemo-mechano-biological coupling and the model's applicability to reproduce normal as well as pathological healing are shown. A last numerical example underlines the model's applicability to complex loading scenarios and inhomogeneous damage distributions. Concluding, the present work contributes towards comprehensive in silico models in biomechanics and mechanobiology.

Biomechanical Effects of a Cross Connector in Sacral Fractures - A Finite Element Analysis.

Background: Spinopelvic fractures and approaches of operative stabilization have been a source of controversial discussion. Biomechanical data support the benefit of a spinopelvic stabilization and minimally invasive procedures help to reduce the dissatisfying complication rate. The role of a cross connector within spinopelvic devices remains inconclusive. We aimed to analyze the effect of a cross connector in a finite element model (FE model). Study Design: A FE model of the L1-L5 spine segment with pelvis and a spinopelvic stabilization was reconstructed from patient-specific CT images. The biomechanical relevance of a cross connector in a Denis zone I (AO: 61-B2) sacrum fracture was assessed in the FE model by applying bending and twisting forces with and without a cross connector. Biomechanical outcomes from the numerical model were investigated also considering uncertainties in material properties and levels of osseointegration. Results: The designed FE model showed comparable values in range-of-motion (ROM) and stresses with reference to the literature. The superiority of the spinopelvic stabilization (L5/Os ilium) ± cross connector compared to a non-operative procedure was confirmed in all analyzed loading conditions by reduced ROM and principal stresses in the disk L5/S1, vertebral body L5 and the fracture area. By considering the combination of all loading cases, the presence of a cross connector reduced the maximum stresses in the fracture area of around 10%. This difference has been statistically validated (p < 0.0001). Conclusion: The implementation of a spinopelvic stabilization (L5/Os ilium) in sacrum fractures sustained the fracture and led to enhanced biomechanical properties compared to a non-reductive procedure. While the additional cross connector did not alter the resulting ROM in L4/L5 or L5/sacrum, the reduction of the maximum stresses in the fracture area was significant.

Computational model of damage-induced growth in soft biological tissues considering the mechanobiology of healing.

Healing in soft biological tissues is a chain of events on different time and length scales. This work presents a computational framework to capture and couple important mechanical, chemical and biological aspects of healing. A molecular-level damage in collagen, i.e., the interstrand delamination, is addressed as source of plastic deformation in tissues. This mechanism initiates a biochemical response and starts the chain of healing. In particular, damage is considered to be the stimulus for the production of matrix metalloproteinases and growth factors which in turn, respectively, degrade and produce collagen. Due to collagen turnover, the volume of the tissue changes, which can result either in normal or pathological healing. To capture the mechanisms on continuum scale, the deformation gradient is multiplicatively decomposed in inelastic and elastic deformation gradients. A recently proposed elasto-plastic formulation is, through a biochemical model, coupled with a growth and remodeling description based on homogenized constrained mixtures. After the discussion of the biological species response to the damage stimulus, the framework is implemented in a mixed nonlinear finite element formulation and a biaxial tension and an indentation tests are conducted on a prestretched flat tissue sample. The results illustrate that the model is able to describe the evolutions of growth factors and matrix metalloproteinases following damage and the subsequent growth and remodeling in the respect of equilibrium. The interplay between mechanical and chemo-biological events occurring during healing is captured, proving that the framework is a suitable basis for more detailed simulations of damage-induced tissue response.