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A Novel Hydroxyapatite Fiber Mesh as a Carrier for Recombinant Human Bone Morphogenetic Protein-2 Enhances Bone Union in Rat Posterolateral Fusion Model

Morisue, Hikaru, MD*; Matsumoto, Morio, MD, PhD; Chiba, Kazuhiro, MD, PhD*; Matsumoto, Hideo, MD, PhD*; Toyama, Yoshiaki, MD, PhD*; Aizawa, Mamoru, PhD; Kanzawa, Nobuyuki, PhD§; Fujimi, Takahiro J., PhD§; Uchida, Hiroshi, PhD§; Okada, Isao, PhD§

doi: 10.1097/01.brs.0000217679.46489.1b
Basic Science

Study Design. An experimental study, in which spinal fusion in rats was conducted using a hydroxyapatite fiber mesh (HAM) as a carrier for recombinant human bone morphogenetic protein (rhBMP)-2.

Objectives. To study the usefulness of the HAM as a carrier and seek the possibility of clinical application in spinal fusion.

Summary of Background Data. Several biomaterials have been used as a carrier for BMP to achieve spine fusion, however, to our knowledge, the most effective carrier has not been established.

Methods. In experiment No. 1, HAMs and the controls (commercially available hydroxyapatite ceramic body), loaded with rhBMP-2, were immersed in phosphate-buffered saline to evaluate the time course of the release of rhBMP-2. In experiment No. 2, posterolateral fusion was conducted in rats using HAM and the control loaded with rhBMP-2. The fusion status was evaluated radiologically and histologically after surgery.

Results. In experiment No. 1, HAMs released a larger amount of rhBMP-2 for up to 28 days than the controls (49.5% vs 7.8%). In experiment No. 2, the fusion rate was significantly higher in the HAM group (>80%) than in the control group (20%). Dense new bone formed close to the spine, and the HAMs were markedly absorbed compared with the controls.

Conclusion. HAM provided more solid fusion mass than the control, suggesting that HAM is an efficient carrier for BMP.

We have synthesized a hydroxyapatite fiber mesh that has been proved to have high bioabsorbability, good ability to release recombinant human bone morphogenetic protein-2, and high porosity inducing dense bone ingrowth. The hydroxyapatite fiber mesh is a preferable material for delivering recombinant human bone morphogenetic protein-2 to the fusion site, thereby enhancing posterolateral spinal fusion.

From the Departments of *Orthopaedic Surgery, School of Medicine, Keio University, Tokyo; †Musculoskeletal Reconstruction & Regeneration Surgery, School of Medicine, Keio University, Tokyo; ‡Industrial Chemistry, School of Science and Technology, Meiji University, Kanagawa; and §Chemistry, Faculty of Science and Engineering, Sophia University, Tokyo, Japan.

Acknowledgment date: August 22, 2005. First revision date: November 12, 2005. Acceptance date: November 27, 2005.

The device(s)/drug(s) that is/are the subject of the manuscript does not apply to human subjects.

Federal funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Address correspondence and reprint requests to Morio Matsumoto, MD, PhD, Department of Musculoskeletal Reconstruction & Regeneration Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan; E-mail:

© 2006 Lippincott Williams & Wilkins, Inc.