Figure 6.

rAAV-mediated gene transfer of RANKL and VEGF induces cortical bone resorption, vascularization and remodeling in processed allografts in vivo. Representative TRAP-stained histologic sections from mice in the combination group (a–d). An example of a rAAV-VEGF + rAAV-RANKL–coated allograft in which remodeled bone extends the entire length of the graft (arrow heads) is shown (a). The novel histologic features of the combination group were characterized by osteoclastic resorption of the necrotic bone (black arrows in b,d,g), osteoblastic new bone formation in the resorption lacunae (white arrows in c,d) and osteoclastic remodeling of the new woven bone (yellow arrows in d). Hematoxylin and eosin–stained sections of allografts from the combination group revealed asymmetric reversal lines (dashed line in e and shown at higher magnification without the lines in g, and black arrow in c) between dead bone and newly formed live bone, new blood vessel formation inside the marrow cavities (* in e,f), and active tunneling resorption (arrows in f) in the necrotic bone. In contrast, none of the other groups showed these features and were all characterized by a fibrotic tissue (f) that covered the periosteal surface and necrotic tissue (n) that filled the marrow cavity (h).