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This Article Full Text Full Text (PDF) All Versions of this Article: 32/7/1619    most recent 0363546504263703v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Mihelic, R. Articles by Vukicevic, S. Search for Related Content PubMed PubMed Citation Articles by Mihelic, R. Articles by Vukicevic, S. Related Collections Reconstruction Animal studies

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, MD^||, Dragica Bobinac, MD, PhD, Boris Lah, MD, PhD^*, Dalen Legovic, MD^* and Slobodan Vukicevic, 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 ^|| Department of Anatomy, School of Medicine, University of Zagreb, Zagreb, Croatia

^¶ Address correspondence to Slobodan Vukicevic, MD, PhD, Department of Anatomy, School of Medicine, University of Zagreb, Salata 11, 10000 Zagreb, Croatia (e-mail: vukicev{at}mef.hr).

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 performed. 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 difference 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 trabecular 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 surgery of ligaments.

Key Words: bone morphogenetic protein—7 (BMP-7) • osteogenic protein—1 (OP-1) • anterior cruciate ligament (ACL) • ligament reconstruction

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