81Days Post-AmputationAEIJK LMFGHBCDLength (mm)
ca^0050100150200250(^51015) Days post amputation
Percent bone volume
0.0 20 25 30
0.2
0.4
0.60.8
1.01.2
1.4
1.6
51015
TotalBone
2025
Fig. 5.1 ( a ) Photograph of the unamputated mouse digit illustrating the nail encasing the triangu-
lar shaped P3 bone. ( b ) Histological section of the unamputated digit, showing the nail matrix
(nm), the P3 bone ( b ), the bone marrow (bm), and the fat pad (fp). ( c ) Amputation removes the
distal digit tip without transecting the vasculature rich marrow cavity. ( d ) Simultaneous events at
7 DPA include epidermal retraction from the amputation plane ( arrow ) and osteoclast erosion
( asterisk ) of the bone stump proximal to the original amputation level. ( e ) TRAP staining at 7 DPA
detects osteoclasts adjacent to the eroded bone stump ( arrow ) and secondary amputation plane. ( f )
Epidermal migration ( arrow ) beneath the eroded bone stump at 7 DPA. ( g – i ) Quantifi cation of
bone length, volume, and μCT 3-D renderings illustrate the regeneration response is characterized
by an initial degradation of bone ( arrows in g and i ) and a corresponding decrease in bone length
and volume, followed by continued bone regeneration resulting in an overall overshoot in bone
volume. ( j ) The variable process of wound closure and wound epidermis (WE) formation occurs
between 8 and 12 DPA. At 12 DPA, the bone marrow cavity is open to the wound site and the
blastema (bl) is prominent, and regeneration of bone is evident in the proximal blastema ( arrow ).
( k ) By 17 DPA, proximal regeneration of woven bone ( b ) has enclosed the bone marrow cavity,
and the distal blastema is still present. ( l ) AT 28 DPA, the amputated digit is largely regenerated,
showing evidence of robust woven bone formation, soft connective tissue regeneration, and rees-
tablishment of pre- amputation bone and digit length. ( m ) At 128 DPA, the regenerated digit is
comprised of thick trabecular bone, and consequently is not a perfect replica of the unamputated
digit. ( a – f and j – m ) Distal is to the right , dorsal is to the top. ( i ) Distal is to the left , dorsal is to the
top. ( a – g and j – m ) are reprinted from Fernando et al. [ 6 ] and ( h ) and ( i ) are reprinted from
Sammarco et al. [ 7 ]
5 Digit Regeneration in Mammals