Modeling and remodeling of the collagen architecture in cardiovascular tissues

Heart valve replacement by a mechanical or biological prosthesis represents a common surgical therapy for end-stage valvular heart diseases. A critical drawback of these prostheses is the inability to grow, repair and remodel in response to changes in the tissue’s environment. Tissue engineering represents a promising alternative technology to overcome the disadvantages of the heart valve replacements currently used. The goal of tissue engineering is to create an autologous living tissue with properties that resemble those of the native tissue. The concept of tissue engineering is based on seeding autologous cells onto a biodegradable scaffold material and delivering the appropriate environmental cues to culture the construct. This technique is relatively successful and tissue-engineered heart valves have been placed at the pulmonary side in animal models. However, the mechanical properties of these tissue-engineered constructs are currently insufficient for implantation at the aortic side. In order to improve the mechanical properties of the constructs, tissue formation is stimulated via a conditioning protocol. The tissue is exposed to appropriate biochemical and biomechanical stimuli in a bioreactor system. As the mechanical properties of the engineered constructs are not yet optimal, the conditioning protocols should be improved and optimized. The load-bearing capacities of the aortic valve are mainly determined by a well organized network of collagen fibers which withstands the pressures during the cardiac cycle and transmits the forces into the aortic wall. For that reason, the conditioning protocol should focus on the deposition of sufficient amounts of properly organized collagen fibers. In these conditioning protocols mechanically induced tissue adaptation and remodeling play a crucial role. To optimize the protocols and to improve the mechanical properties of the tissue, it is desired to gain insight into these processes. However, the interaction between tissue remodeling and the mechanical loading condition is complex because these are highly coupled. Therefore, mathematical models are desired to study this interaction and to predict the tissue’s response to mechanical stimuli. The objective of this work is to gain insight into tissue remodeling due to mechanical stimuli. In this thesis, mathematical models are formulated that 1) describe the mechanical loading condition in the tissue, and 2) account for the effects of tissue remodeling on the mechanical behavior of the construct. The application of these models focuses on the aortic valve, but the models are also applied to arteries since these contain a specific architecture of collagen fibers as well. The starting point of this research is the formulation of remodeling laws which are based on the hyxi pothesis that the collagen fibers orient towards the strain field. The predicted fiber directions agree very well with experimental data from native aortic valves. However, the formulated hypothesis appears to be inadequate to describe the helical collagen orientation that is found in arterial walls. Subsequently, the hypothesis is successfully modified and the predicted fiber directions represent the architecture that is present in native arteries. The modified hypothesis is then applied to the aortic valve and this yields an improved prediction of the collagen architecture in the aortic valve. Next, a structurally-based constitutive model is presented to give an accurate description of the mechanical behavior of the tissues. This model contains structural parameters that describe the amount and orientation of collagen fibers and enables us to incorporate experimentally measured fiber distributions. Finally, the structural constitutive model is coupled with the hypotheses for collagen fiber remodeling. In this way, the evolution of the collagen fiber distribution and the mechanical properties of tissue-engineered cardiovascular tissues can be studied and predicted.