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The mammalian blastema and induced regeneration in mice.

Fingertips of humans and toe tips of mice possess the capacity to regenerate following amputation injury. The mouse toe tip has been developed as a regeneration competent model to investigate the regeneration process, and digit amputation at a more proximal level serves as a non‐regenerative wound model to test strategies for enhanced regeneration. The process of toe tip regeneration is divided into a series of overlapping events beginning with an inflammatory response, a bone degeneration response, epidermal closure, migration and proliferation of progenitor stem cells, blastema formation and redifferentiation. These stages are distinct from wound healing of a non‐regenerative amputation that results in truncated skeletal elements covered with scar tissue. BMP signaling has been shown to be essential for toe tip regeneration and BMP treatment is effective in enhancing the regenerative capacity of proximal level amputations. The ability to induce a regeneration response from non‐regenerative amputation wound identifies an unrealized regenerative potential of cells present at traumatic wounds in mammals. To date, we have determined that the regeneration of bone, cartilage, synovial cavity, tendon and ligament can be induced from a non‐regenerative amputation wound with different regimens of targeted growth factor treatments. These studies provide a road map for developing strategies to control regeneration events in mammals and serve as a new direction for the field of regenerative medicine.