10. The Scaffold Regeneration Paradigm and Its Consequences

A theory which explains the data on spontaneous and induced regeneration based on use of collagen scaffolds is presented in the form of a regeneration paradigm. The paradigm is grounded in a set of five empirical rules that govern regeneration in animal models and in the clinic. A detailed mechanistic explanation of the regeneration process interprets the data using evidence that extends from the organ scale down to the scale of the molecule. Use of the scaffold regeneration paradigm explains mechanistically the available data on scarless healing in the early mammalian fetus, the successful use by several investigators of decellularized matrices to regenerate several organs, and suggests a proposed solution to the problem of the fibrotic liver. This chapter ends with a general theory of regeneration based on the speculative premise that early fetal healing, which is regenerative, is eventually turned off reversibly, rather than irreversibly, before birth; it lies dormant during the lifetime of the organism until it is turned back on by a suitable stimulus.