Regulation of Cellular Response to Mechanical Signals by Matrix Design

Abstract

Despite the promise offered by tissue engineering and the significant advances made in the field, many engineered tissues still do not provide the functionality necessary for clinical applications. Gene expression, tissue development, and, ultimately, tissue function are determined by the chemical and mechanical cues presented to cells within the tissue. Therefore, restoring function to engineered tissues requires a better understanding of how the cellular microenvironment influences tissue formation and function, and the development of strategies to control the microenvironment to guide specific programs of gene expression. The ECM plays a vital role in regulating the response of cells to signals from their microenvironment through, as reviewed in this chapter, mediation of cell adhesion, regulation of the cellular force balance, and release of growth factors. This is critically important for tissue engineering, since the ability of the matrix to regulate the cellular microenvironment can be exploited by designing matrices that present the appropriate signals necessary to direct cell function to engineer functional tissues. Several design strategies were reviewed in this chapter, including incorporation of specific cell adhesion ligands, manipulation of the intrinsic mechanical mechanical properties of the matrix, and control of growth factor release. These approaches will be particularly important to engineer tissues that require mechanical stimulation for proper development, since the cellular response to mechanical signals is regulated by the properties of the matrix.