Regeneration: sooner rather than later.

The explosive growth of information from genetics and genomics has led to an appreciation of the conservation of gene regulatory networks between organisms, and between development and regeneration. With ever increasing knowledge, it will be possible to intervene therapeutically to regulate these networks, which will lead to new therapies to induce regeneration. The question then becomes how to do this, rather then when to try. Our thesis is that the time is now, and that this feat can be achieved by combining the insights provided by developmental biologists with the technologies being developed by biomaterial engineers, to achieve the goal of engineering regeneration. We thus envision regenerative engineering as the next step toward achieving the goal of human regeneration. Among the most important discoveries about regeneration from studies of salamanders that regenerate exceptionally well, is that both pattern-following and pattern-forming cells are required. Much progress is being made toward understanding the former cells, but little is known about the cells that control positional information and pattern formation. Within the near future, it will become possible to provide the information needed for regeneration exogenously in the form of an engineered extracellular matrix that is a biomimetic of the endogenous information. Since growth factors (morphogens) can control pattern formation, an engineered grid could be based on spatially organized patterns of sulfation of glycosaminoglycans that control the behavior of cells by modulating morphogen activity. Progress in engineering the positional information grid for regeneration will necessitate learning the sulfation codes associated with successful regeneration in animals such as salamanders.