87

C H A P T E R 7

Perfusion Bioreactors and

Stimulation Patterns in Cardiac

Tissue Engineering

CHAPTER SUMMARY

Regeneration of a thick functional cardiac patch in vitro presents a major engineering challenge, i.e., the need for reconstruction of a dynamic 3D cellular microenvironment with the appropriate chemical and mechanical signals to induce cell differentiation, maturation, and assembly into a functional tissue. In this chapter, we describe the creative design of various dynamic cell microenvironments, which promote the development of a thick cardiac patch, ready to face the harsh conditions in an infarcted heart. Among these microenvironments are unique perfusion bioreactor systems that increase mass transfer through the developing cardiac tissue at the in vitro engineering stage, and the use of modules which provide mechanical and electrical stimulation and induce the formation of a thick contractile cardiac tissue, in vitro.

7.1INTRODUCTION

Engineering of a full thickness functional human cardiac muscle ( 1-cm thick) is a great challenge for the tissue engineer. The cardiac muscle tissue constitutes densely packed cells and is composed of oxygenand shear-sensitive cardiomyocytes. It is almost impossible to grow such thick and densely packed tissues under a static cultivation mode, relying only on a molecular diffusion for nourishing the cells. Anoxic conditions developed in the a-vascular cardiac cell constructs lead to cell death and the formation of thin external tissue layer at the periphery of the construct. In addition, accumulated data over the last years indicated that different physical cues, such as electrical signaling, mechanical stimulation (e.g., stretching of the 3D cellular constructs), are required to attain more functional cardiac tissues [1, 2, 3, 4].These signals promote cardiomyocyte hypertrophy, increase the contractile protein content in tissue, and encourage the alignment of cells into myofibrillar structures, with contractility properties resembling those of a native cardiac muscle tissue.

The employment of bioreactors in tissue engineering has greatly advanced the field and contributed to the development of thicker and more functional cardiac tissue. Bioreactors are generally defined as devices in which biological and/or biochemical processes develop under closely moni-