Free tendon graft is the standard procedure in reconstruc- tion of the ACL, most frequently using the patellar tendon and hamstring tendons. 4 The integration of tendon grafts used for replacement of the ACL is still unsatisfactory in about 13% of cases 1 and may be associated with postoper- ative anterior-posterior laxity and failure. 19,20 In the case of patellar tendon with bone block on each side of the graft, bone-to-bone healing occurs, and when hamstring tendons Bone Morphogenetic Protein–7 (Osteogenic Protein–1) Promotes Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction in Sheep Radovan Mihelic,* MD, PhD, Marko Pecina, † MD, PhD, Mislav Jelic, † MD, PhD, Sanja Zoricic, ‡ MD, PhD, Vesna Kusec, § MD, PhD, Petra Simic, ll MD, Dragica Bobinac, ‡ MD, PhD, Boris Lah,* MD, PhD, Dalen Legovic,* MD, and Slobodan Vukicevic, ¶ll MD, PhD From the *Orthopaedic Hospital, Lovran, Croatia, the † Department of Orthopaedic Surgery, School of Medicine, University of Zagreb, Zagreb, Croatia, the ‡ Department of Anatomy, School of Medicine, University of Rijeka, Rijeka, Croatia, § Clinical Institute of Laboratory Diagnosis, Clinical Hospital Centre, Zagreb, Croatia, and the ll Department of Anatomy, School of Medicine, University of Zagreb, Zagreb, Croatia Background: Bone morphogenetic proteins induce new bone both in patients with bone defects and at extraskeletal sites in animals. After anterior cruciate ligament rupture, tendon graft fixation into a bone tunnel is a widely used method for anterior cruciate ligament reconstruction. Hypothesis: Bone morphogenetic protein–7 applied to the bone-tendon interface enables better integration of a free tendon graft into the surrounding bone. Study Design: Controlled laboratory study. Methods: The anterior cruciate ligament was reconstructed using a free tendon graft in the right rear knees of 30 one-year-old male sheep. Recombinant human bone morphogenetic protein–7 (25 μg) was applied randomly to the bone-tendon interface in 15 animals, and a vehicle was applied in 15 control animals. At 3 weeks, 10 animals from each group were sacrificed, and the remaining sheep were sacrificed at 6 weeks after surgery. Subsequently, histologic analysis and mechanical testing were per- formed. In another group of 20 sheep, the same procedure was used and mechanical testing was performed after 3 weeks. Results: More new bone was formed at the bone-tendon interface in the knees treated with bone morphogenetic protein–7 as compared histologically with similar areas in control animals, creating areas of dense trabecular network with significantly greater invasion of the tendon fibrous tissue into the bone marrow space. Mechanical testing showed greater strain resistance to force (368 N) in the knees treated with bone morphogenetic protein–7 than in control specimens (214 N). There was no dif- ference between mechanical testing of samples from 3 and 6 weeks after surgery. Conclusion: Bone morphogenetic protein–7 promotes complete tendon graft integration into the newly formed surrounding tra- becular bone in the reconstruction of the anterior cruciate ligament. Clinical Relevance: Bone morphogenetic protein–7 in tendon graft integration might be successfully used in reconstructive sur- gery of ligaments. Keywords: bone morphogenetic protein–7 (BMP-7); osteogenic protein–1 (OP-1); anterior cruciate ligament (ACL); ligament reconstruction 1619 ¶ Address correspondence to Slobodan Vukicevic, MD, PhD, Department of Anatomy, School of Medicine, University of Zagreb, Salata 11, 10000 Zagreb, Croatia (e-mail: vukicev@mef.hr). No potential conflict of interest declared. See Acknowledgment for funding information. The American Journal of Sports Medicine, Vol. 32, No. 7 DOI: 10.1177/0363546504263703 © 2004 American Orthopaedic Society for Sports Medicine