OP-1 application in bone allograft integration: preliminary results in sheep experimental surgery

Massive bone allografts are frequently used in orthopaedic reconstructive surgery. However the failure rate at long term follow-up is around 25%. Aim: Stimulation of allograft incorporation. Materials and Methods: In order to stimulate bone remodeling of an allograft we applied recombinant human osteogenic protein-1 (rh-OP-1, also know as bone morphogenetic protein-7, BMP-7) to a long bone critical size defect sheep model. In nine sheep we created a 3 cm osteoperiosteal metatarsal defect replaced with a structural allograft alone (control group, 4 animals), or an allograft added with rh-BMP-7 (BMP group, 5 animals). Radiographic, mechanical, histological and histomorphometric analysis were performed. Results: X-rays in the BMP group showed a better and faster callus formation, compared to the control group within the first 8 weeks after surgery. After 16 weeks there was a higher evidence of bone remodeling in the BMP group. Radiographic heating at junction sites was more evident in the BMP group at 4, 8 and 16 weeks. Mechanical testing on screw extraction showed no statistical differences between the two groups and histomorphometry showed no difference in terms of newly formed bone inside the allograft as well. The resorption rate of the graft was higher in the BMP group in comparison to the control group. The penetration of newly formed vessels was significantly higher in the BMP group. Conclusions: These findings indicate that BMP-7 added to a structural bone allograft inducing early remodeling of the graft through stimulation of neo-angiogenesis and osteociastic activity, without negative effects in mechanical strength and clinical outcome. (C) 2008 Elsevier Ltd. All rights reserved.