Defining design targets for tissue engineering scaffolds

Biological tissues are extremely complex three-dimensional (3D) structures with concomitant complicated mechanical function and mass transport characteristics. Tissue engineering seeks to recapitulate this complex structure and function using biomaterial scaffolds delivering therapeutic biologics such as cells, proteins, and genes for tissue reconstruction. It is clear that the biomaterial/biologic construct cannot replicate the complex tissue milieu, including multiple cell types interacting with numerous cytokines to produce extracellular matrices having hierarchical features exhibiting highly nonlinear, biphasic mechanical function. The biomaterial/biologic construct is, at best, a crude approximation to the normal tissue milieu. To improve the clinical potential of tissue engineering/regenerative medicine, we must be able to relate the goodness of this approximation to the success of tissue regeneration. In essence, we must be able to define relevant design criteria for tissue engineering therapies. For the scaffold, the focus of this chapter, the pertinent question becomes: How closely does a biomaterial scaffold have to approximate the normal tissue structure, mechanical function, mass transport, and cell-matrix interaction as a function of time to achieve desired tissue reconstruction?