Description Background: The proposed studies address one of the most pressing needs of the wounded soldier population: the replacement of lost digits and limbs. These studies challenge a fundamental tenet of the mammalian response to tissue injury; specifically, the concept that regeneration of complex tissues following severe injury is not possible in adult mammals. We hypothesize that such regeneration is indeed possible and, to support this hypothesis, we have successfully recruited endogenous stem cells to the injury site thru the use of chemotactic matricryptic peptides derived from extracellular matrix (ECM). We call this cell mass a “multipotential cell cluster” and it is similar, but not identical, to the true blastema of regenerating species such as the newt. We now seek support to identify the genetic signature, the appropriate microenvironmental niche, and inductive molecular signals required to stimulate functional tissue formation from the multipotential cell cluster.