Remodelling of the angular collagen fiber distribution in cardiovascular tissues

Understanding collagen fiber remodelling is desired to optimize the mechanical conditioning protocols in tissue-engineering of load-bearing cardiovascular structures. Mathematical models offer strong possibilities to gain insight into the mechanisms and mechanical stimuli involved in these remodelling processes. In this study, a framework is proposed to investigate remodelling of angular collagen fiber distribution in cardiovascular tissues. A structurally based model for collagenous cardiovascular tissues is extended with remodelling laws for the collagen architecture, and the model is subsequently applied to the arterial wall and aortic valve. For the arterial wall, the model predicts the presence of two helically arranged families of collagen fibers. A branching, diverging hammock-type fiber architecture is predicted for the aortic valve. It is expected that the proposed model may be of great potential for the design of improved tissue engineering protocols and may give further insight into the pathophysiology of cardiovascular diseases

Stress analysis in a layered aortic arch model under pulsatile blood flow

BACKGROUND: Many cardiovascular diseases, such as aortic dissection, frequently occur on the aortic arch and fluid-structure interactions play an important role in the cardiovascular system. Mechanical stress is crucial in the functioning of the cardiovascular system; therefore, stress analysis is a useful tool for understanding vascular pathophysiology. The present study is concerned with the stress distribution in a layered aortic arch model with interaction between pulsatile flow and the wall of the blood vessel. METHODS: A three-dimensional (3D) layered aortic arch model was constructed based on the aortic wall structure and arch shape. The complex mechanical interaction between pulsatile blood flow and wall dynamics in the aortic arch model was simulated by means of computational loose coupling fluid-structure interaction analyses. RESULTS: The results showed the variations of mechanical stress along the outer wall of the arch during the cardiac cycle. Variations of circumferential stress are very similar to variations of pressure. Composite stress in the aortic wall plane is high at the ascending portion of the arch and along the top of the arch, and is higher in the media than in the intima and adventitia across the wall thickness. CONCLUSION: Our analysis indicates that circumferential stress in the aortic wall is directly associated with blood pressure, supporting the clinical importance of blood pressure control. High stress in the aortic wall could be a risk factor in aortic dissections. Our numerical layered aortic model may prove useful for biomechanical analyses and for studying the pathogeneses of aortic dissection

Nondestructive and noninvasive assessment of mechanical properties in heart valve tissue engineering

Despite recent progress, mechanical behavior of tissue-engineered heart valves still needs improvement when native aortic valves are considered as a benchmark. Although it is known that cyclic straining enhances tissue formation, optimal loading protocols have not been defined yet. To obtain a better understanding of the effects of mechanical conditioning on tissue development, mechanical behavior of tissue constructs should be monitored and controlled during culture. However, currently used methods for mechanical characterization (e.g., tensile and indentation tests) are destructive and are only performed at the end-stage of tissue culture. In this study, an inverse experimental-numerical approach was developed that enables a noninvasive and nondestructive assessment of mechanical properties of engineered heart valves. The applied pressure and volumetric deformation of an engineered heart valve were measured during culture, and served as input for the estimation of mechanical properties using a computational model. To validate the method, six heart valves were cultured, and the mechanical properties obtained from the inverse experimental-numerical approach were in good agreement with uniaxial tensile test data. The method provides a real-time, noninvasive and nondestructive functionality and quality check of tissue-engineered heart valves and can be used to monitor and control the evolution of mechanical properties during tissue culture

A computational model for collagen fibre remodelling in the arterial wall

As the interaction between tissue adaptation and the mechanical condition within tissues is complex, mathematical models are desired to study this interrelation. In this study, a mathematical model is presented to investigate the interplay between collagen architecture and mechanical loading conditions in the arterial wall. It is assumed that the collagen fibres align along preferred directions, situated in between the principal stretch directions. The predicted fibre directions represent symmetrically arranged helices and agree qualitatively with morphometric data from literature. At the luminal side of the arterial wall, the fibres are oriented more circumferentially than at the outer side. The discrete transition of the fibre orientation at the media-adventitia interface can be explained by accounting for the different reference configurations of both layers. The predicted pressure-radius relations resemble experimentally measured sigma-shaped curves. As there is a strong coupling between the collagen architecture and the mechanical loading condition within the tissue, we expect that the presented model for collagen remodelling is useful to gain further insight into the processes involved in vascular adaptation, such as growth and smooth muscle tone adaptation

Tissue engineering of human heart valve leaflets: a novel bioreactor for a strain-based conditioning approach

Current mechanical conditioning approaches for heart valve tissue engineering concentrate on mimicking the opening and closing behavior of the leaflets, either or not in combination with tissue straining. This study describes a novel approach by mimicking only the diastolic phase of the cardiac cycle, resulting in tissue straining. A novel, yet simplified, bioreactor system was developed for this purpose by applying a dynamic pressure difference over a closed tissue engineered valve, thereby inducing dynamic strains within the leaflets. Besides the use of dynamic strains, the developing leaflet tissues were exposed to prestrain induced by the use of a stented geometry. To demonstrate the feasibility of this strain-based conditioning approach, human heart valve leaflets were engineered and their mechanial behavior evaluated. The actual dynamic strain magnitude in the leaflets over time was estimated using numerical analyses. Preliminary results showed superior tissue formation and non-linear tissuelike mechanical properties in the strained valves when compared to non-loaded tissue strips. In conclusion, the strain-based conditioning approach, using both prestrain and dynamic strains, offers new possibilities for bioreactor design and optimization of tissue properties towards a tissue-engineered aortic human heart valve replacement

Mechanical characterization of anisotropic planar biological soft tissues using finite indentation : experimental feasibility

Heart valve tissue engineering offers a promising alternative for current treatment and replacement strategies, e.g., synthetic or bioprosthetic heart valves. In vitro mechanical conditioning is an important tool for engineering strong, implantable heart valves. Detailed knowledge of the mechanical properties of the native tissue as well as the developing tissue construct is vital for a better understanding and control of the remodeling processes induced by mechanical conditioning. The nonlinear, anisotropic and inhomogeneous mechanical behavior of heart valve tissue necessitates a mechanical characterization method that is capable of dealing with these complexities. In a recent computational study we showed that one single indentation test, combining force and deformation gradient data, provides sufficient information for local characterization of nonlinear soft anisotropic tissue properties. In the current study this approach is validated in two steps. First, indentation tests with varying indenter sizes are performed on linear elastic PDMS rubbers and compared to tensile tests on the same specimen. For the second step, tissue constructs are engineered using uniaxial or equibiaxial static constrained culture conditions. Digital image correlation (DIC) is used to quantify the anisotropy in the tissue constructs. For both validation steps, material parameters are estimated by inverse fitting of a computational model to the experimental results