Molecular signaling in bioengineered tissue microenvironments

Biological tissues and organs consist of specialized living cells arrayed within a complex structural and functional framework known generally as the extracellular matrix (ECM). The great diversity observed in the morphology and composition of the ECM contributes enormously to the properties and function of each organ and tissue. For example, the ECM contributes to the rigidity and tensile strength of bone, the resilience of cartilage, the flexibility and hydrostatic strength of blood vessels, and the elasticity of skin. The ECM is also important during growth, development, and wound repair: its own dynamic composition acts as a reservoir for soluble signaling molecules and mediates signals from other sources to migrating, proliferating, and differentiating cells. Artificial three-dimensional substitutes for ECM, called tissue scaffolds, may consist of natural or synthetic polymers or a combination of both. Scaffolds have been used successfully alone and in combination with cells and soluble factors to induce tissue formation or promote tissue repair. Appropriate numbers of properly functioning living cells are central to many tissue-engineering strategies, and significant efforts have been made to identify and propagate pluripotent stem cells and lineage-restricted progenitor cells. The study of these and other living cells in artificial microenvironments, in turn, has led to the identifcation of signaling events important for their controlled proliferation, proper differentiation, and optimal function.