Embryonic development and the principles of tissue engineering.

Tissue engineering has, historically, used empirical methods to devise reparative strategies for optimizing the repair of skeletal tissue defects. The acquired experience and observations indicate that several aspects of successful repair protocols involve the engineered recapitulation of certain embryonic events. A careful study of the details of embryonic limb formation and subsequent differentiation events into its component skeletal tissues suggests that aspects of these tissue formation events can provide guiding principles for the tissue-engineered regeneration of skeletal tissues in adults. A thesis is developed in reviewing selected aspects of embryonic limb formation whereby one could articulate broad tissue engineering principles that should be followed in order to regenerate portions of excised or damaged skeletal tissues. Central to the regeneration of skeletal tissues is the conversion of progenitor cells and tissue into the desired specialized tissue. For mesenchymal tissues, this requires the conversion of groups of mesenchymal cells with their relatively modest extracellular matrix (ECM) into functional skeletal tissues characterized by a voluminous and specialized ECM. Because of the absence of the complex signalling cascade characteristic of early embryonic events, it is improbable that adult tissue reconstruction strategies can recapitulate distinctive morphologies while forming newly differentiated skeletal tissues. Thus, tissue-engineered regeneration protocols must provide the scaffolds and boundaries to establish the contours and edges of reparative tissues and then must functionally and molecularly integrate this neo-tissue with the surrounding host tissue. Consequently, such scaffolds must provide the reparative cells or their progenitors or the specific attachment or binding sites for endogenous reparative cells. The scaffolds must also provide the signals to start the reparative process, the means and signals to expand the reparative cells, the space for the unique and oriented specialized ECM and, lastly, the capacity to functionally integrate this neo-tissue in a seamless manner with the host tissue. Several tissue-engineering principles based on the details of embryonic events provide guides for the development of scientific logics for new reparative strategies for the regeneration of skeletal tissues.