Understanding tissue prestress and homeostasis


Tissue prestress is an important factor in heart valve tissue engineering. By means of their actin stress fibers, cells apply forces to their surroundings, leading to tissue prestress and compaction. This phenomenon has shown to be beneficial for tissue formation, and is therefore exploited in many tissue engineering strategies. Moreover, prestress increases the apparent stiffness of the tissue, leading to different load carrying characteristics. On the other hand, these cell and tissue tensions lead to adverse tissue remodeling, which may induce valvular regurgitation. These cell-generated forces and resulting tissue prestress are influenced by mechanical cues, however, the exact mechanisms are unknown. A better understanding of how these cues influence cell and tissue generated tensions will grant new insights which can be used to improve heart valve tissue engineering strategies. In order to study cell and tissue forces, a
microfabricated tissue gauge (μTUG) setup is used. This setup consists of 4 polydimethylsiloxane (PDMS) microposts embedded inside a microwell (figure 1(a), [1]). Within 24 hours, a seeded cell/collagen suspension will self assemble into a microtissue which compacts around the microposts (figure 1(b)). Over time, a tissue prestress will develop, applying forces to the microposts. By tracking the displacements of the posts, we are able to determine the forces applied by the microtissues. In this study, factors influencing tissue prestress and the effects on tissue functionality will be investigated using a combined numerical-experimental approach.


Researchers: A.J. (Mathieu) van Kelle.
Supervisors: S. (Sandra) Loerakker, C.V.C. (Carlijn) Bouten.

Funding by CVON (Cardiovascular Research Netherlands) and De Hartstichting (Heart Foundation).



  1.  A.C.C. van Spreeuwel,  N.A.M. Bax,  A.J. Bastiaens, J. Foolen,  S. Loerakker, M. Borochin,  D.W.J. van der Schaft, C.S. Chen, F. P. T. Baaijens and  C.V.C. Bouten. The influence of matrix (an)isotropy on cardiomyocyte contraction in engineered cardiacmicrotissues, Integrative Biology 6(4):422-429, 2014.