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Enhancement by Recombinant Human Bone Morphogenetic Protein-2 of Bone Formation by Means of Porous Hydroxyapatite in Mandibular Bone Defects

Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

K. Bessho

Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

K. Fujimura

Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

Y. Konishi

Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

K. Kusumoto

Department of Plastic and Reconstructive Surgery, Kansai Medical University

Y. Ogawa

Department of Plastic and Reconstructive Surgery, Kansai Medical University

T. Iizuka

Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

Hydroxyapatite is osteoconductive and can maintain an original biocompatible form. It is useful, in the reconstruction of bone defects, to enhance the osteoconduction of hydroxyapatite with an osteogenic protein. The aim of this study was to evaluate the bone formation in surgically created defects of rabbit mandibles by a combination of recombinant human bone morphogenetic protein-2 (rhBMP-2), with porous hydroxyapatite and atelopeptide type I collagen used as the carrier for rhBMP-2. A 10-µg rhBMP-2-implanted group (n = 15) and a control group (n = 15), in which only atelopeptide type I collagen and porous hydroxyapatite were implanted, were histologically examined 3, 7, and 21 days after implantation. The alkaline phosphatase activity was also quantitatively analyzed. No new bone formation was observed in either the tested or the control group after 3 days. At 7 days, immature bone tissue was observed in some pores of the rhBMP-2implanted group, while in the control group, immature mesenchymal cells were observed. At 21 days, trabecular bone lined some pore walls. In the central portion, the bone marrow, including angioid tissue, was observed. New trabecular bone formation was observed on portions of the external surface of the hydroxyapatite disk. On the other hand, the control group showed infiltration of immature mesenchymal cells into some pores. Marginal bone formation was found in the pores close to the surface of the disk which opposed mandibular bone. The control group showed a slow, small increase in alkaline phosphatase activity in this study, while the experimental group showed a marked increase at 21 days. This increase was significantly higher in the tested group than in the control group at both 7 and 21 days. The findings indicate that rhBMP-2 accelerated bone formation by osteoconduction from porous hydroxyapatite. The combination of rhBMP-2, atelopeptide type I collagen, and porous hydroxyapatite is suggested to be advantageous for clinical application in reconstructing mandibular bone defects.

Key Words: bone morphogenetic protein • hydroxyapatite • osteoinduction • osteoconduction • mandible

Journal of Dental Research, Vol. 78, No. 9, 1505-1510 (1999)
DOI: 10.1177/00220345990780090401


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