Fig. 7. Digit tip regeneration is a level-dependent and spatiotemporally controlled process.

After distal amputation of the digit tip, bone degradation is followed by transient upregulation of limb-specific developmental genes and osteogenesis, where the regenerating extracellular matrix becomes aligned in the direction of tissue elongation. In contrast, proximal amputation results in minimal bone remodeling or regrowth. Regenerative failure may be due to altered developmental signals and cell populations, and/or accelerated fibrosis.