The astonishing regenerative ability of the urodele amphibian limb has long been investigated as the chief model for regeneration in vertebrates. The urodele limb responds to amputation via a process called epimorphic regeneration, and involves the formation of a blastema comprised of proliferating cells that are undifferentiated. The regeneration process involves a series of stages (e.g. inflammation, wound closure, dedifferentiation, cell migration, etc.) many of which are known to be essential for the successful replacement of the amputated structure. Such a stepwise view of regeneration points to the fact that the regenerative response involves a complex series of interconnecting processes, and not simply an event that can be toggled on or off. While the urodele limb represents a beacon for regeneration among higher vertebrates, mammals, including humans, are not without regenerative capabilities and can successfully regenerate the distal portion of the fingertip. This regeneration response is amputation level specific, in that conservative treatment of amputations distal to the nail matrix can successfully regenerate, while amputations proximal to the nail matrix results in a more traditional wound healing response that culminates with scar formation. This regenerative ability is particularly enhanced in children, however a similar response has been documented in adults. While human fingertip regeneration is well documented in the clinical literature, the details of this response have not been well characterized, thus it remains more a curiosity rather than a model upon which regenerative therapies might evolve.
