Abstract

Tissue engineered heart valves appear promising as autologous valvular substitutes that may have the ability to grow and remodel. From a mechanical point of view, the in vivo functionality and durability of the heart valve relies on the strength and anisotropic properties of the valve leaflets. In a mature heart valve, a distinct anisotropic collagen architecture enables flexibility of the valve leaflets in the radial direction, and creates the required strength in the circumferential direction. One of the challenges in heart valve tissue engineering is to mimic this anisotropic collagen structure in terms of collagen amount, collagen orientation and intrinsic properties of the collagen fibers. Mechanical stimulation has been shown to influence collagen synthesis, accumulation and organization. In a sequence of experiments the effect of mechanical loading on the synthesis and orientation of collagen as well as the structural properties of the collagen is investigated (1), (2), (3), (4), (5). This has resulted in a new bioreactor culture paradigm that yields heart valves with sufficient strength for implantation at the aortic position(6). Preclinical experiments in a sheep model, using a minimally invasive transapical approach, yields promising results(7). Yet, the precise mechanism of collagen orientation, as well as contractile force development when subject to static and dynamic loads is not fully understood. To further understanding of this mechanism microtissues (8) may be applied that can be visualized using multiphoton confocal microscopy. In addition, computational models are developed to analyse the development of cytoskeletal orientation and cellular traction forces in three-dimensional tissues. Comparisons with experimental results are made.

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