Myocardial tissue engineering: the extracellular matrix.

More than a decade after the first reports on successful three-dimensional cardiac cell culture for experimental and potential therapeutic application, the interest and experimental efforts in the field of myocardial tissue engineering continues to grow. The hope that tissue cultures may one day act as graft substitute for malfunctioning myocardium continues to drive current scientific activity. Against this background interest seem to have progressively shifted towards the aim of engineering single tissue components. Accordingly, elements of the extracellular matrix (ECM) have gained increasing attention as potentially crucial mediators in developing and maintaining the characteristics of three-dimensional cardiac cell cultures. The ECM is now no longer regarded as merely a scaffold for developing tissue, a concept that is widely acknowledged in modern tissue engineering. The understanding of the role of precursor and stem cells has highlighted new complicated aspects of cell proliferation and differentiation and ECM proves to play an important role in providing essential signals to influence major intracellular pathways such as proliferation, differentiation and cell metabolism. Furthermore, progress in biochemical engineering has provided the perspective of application of synthetic ECM-linked molecules with bioactive potential. With the advent and continuous refinement of cell removal techniques, a new class of native acellular ECM has emerged with some striking advantages. The presently available ECM materials aim to closely resemble the in vivo microenvironment by acting as an active component of the developing tissue construct. It is therefore not surprising that most of the focus in myocardial tissue engineering has been on cell-matrix interaction, for both naturally derived and synthetic ECM. This article provides a review of established models of myocardial tissue engineering with respect to the employed ECM materials including current frontiers in material development.