Natural tissues are comprised of functionally diverse cell types that are organized in spatially complex arrangements. Organogenesis of complex tissues requires a coordinated sequential transformation process, with individual stages involving time-dependent expression of cell-cell, cell-matrix, cell-signal interactions in three dimensions. The common theme of temporal-spatial patterning of these cellular interactions is also observed in other physiological processes, such as growth and development, wound healing, and tumor migration. The "precursor tissue analog" (PTA) applies the temporal-spatial patterning theme to tissue engineering. The goal of PTA in tissue engineering is not to fabricate the final transplantable tissue but rather to guide the dynamic organization, maturation and remodeling leading to the formation of the normal and functional tissues. We describe the critical design principles of PTA. First, structural, mechanical and physiological requirements of the PTA as a temporary scaffold must be met with a fabrication method with flexibility. The fabrication potential incorporating biological materials such as living cells and plasmid DNA has been addressed. Second, the PTA concept is considered suitable for future tissue engineering in light of the use of undifferentiated stem cells, and may possess a capability to guide the stem cells toward the diverse differentiation characteristics in situ. To this end, the behavior of the engineered cell and tissue must be monitored in detail. The development of a practical phenotype monitoring system such as DNA microarray may be integral to the fabrication strategies of PTA. Third, the micro-topographical and micro-environmental control on the liquid-solid interaction may lead to a critical design for PTA to provide soluble factors, nutrients and gases to the cells embedded within the scaffold. We suggest that the level set numerical simulation method may be utilized to engineer the consistent circulation of bioactive liquid throughout the PTA microenvironment.
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