Figure 2.

Schematic Model of Scarful vs. Scarless Healing and the Adjuvant Effects of rPTH Therapy. An emerging model to explain the fundamental basis of a non-healing critical defect in bone posits that there is a temporal-spatial competition between coupled small vessel angiogenesis-osteogenesis at the leading edge of the healing defect, and large vessel arteriogenesis-fibrosis within the defect. In the first two weeks after injury small vessel (<10 mm) angiogenesis facilitates rapid defect filling (scarless healing) from the leading edge (~0.02 mm/day) via proliferating/migrating bone forming osteoblasts (green). Simultaneously, large vessel (>30 mm) arteriogenesis occurs with the appearance of pro-fibrotic mast cells (dark blue) in the center of the defect, which completely inhibits osteoblastic defect filling (0 mm/day) thereafter, resulting in “scarful healing” of the critical defect. Moreover, rPTH therapy facilitates critical defect healing by: (1) its well-known anabolic effects on osteogenic cells to increase defect filling at the healing front; (2) coupled osteogenic cell-induced small vessel angiogenesis at the healing front; and (3) inhibition of large vessel arteriogenesis/fibrosis within the defect, resulting in scarless healing and ultimate wound closure.