Research
Endogenous Digit Tip Regeneration
Mammals display poor regenerative capabilities and typically respond to traumatic injury with fibrotic wound healing rather than regeneration. Although limited, mice and humans successfully regenerate the distal tip of the digit/finger following amputation. A substantial amount of work (including our own) has demonstrated that mammals are capable of regeneration after amputation of the digit tip (i.e., the terminal phalanx, P3). P3 regeneration proceeds through an overlapping series of interdependent stages.
However, P3 regeneration can more simply be divided in 2 stages: catabolic and anabolic. The catabolic stage includes inflammation and bone resorption, whereas the anabolic stage includes blastema formation and bone regeneration. A key conclusion of this research is that mammalian cells possess an innate ability to organize a complex regeneration response without exogenous intervention.
Induced Regeneration
Non-regenerative amputation responses are the norm among mammals and digit amputation at the level of the second phalanx (P2) has been studied as a model of regenerative failure and to test strategies to stimulate regeneration. Successful regenerative responses have been stimulated by growth factor treatment in neonatal and adult amputation models. BMP2 treatment of the P2 amputation stimulates regrowth of the P2 stump bone by forming an endochondral ossification center at the amputated stump that mediated skeletal regeneration of the stump bone. Alternatively, treatment of the P2 amputation with BMP9 stimulates a multi-tissue regenerative response that involves formation of a skeletal nodule and a synovial joint that articulates with the P2 stump. Moreover, sequential treatment with BMP2 followed by BMP9 induces the regeneration of both bone and joint. Together, these studies demonstrate that the wound cells of non-regenerative amputations are regeneration-competent but are limited by the local environment of the amputation wound.
