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Additive Enhancement of Implant Fixation Following Combined Treatment with rhTGF-β2 and rhBMP-2 in a Canine Model
D.R. Sumner, PhD1; T.M. Turner, DVM2; R.M. Urban2; A.S. Virdi, PhD1; N. Inoue, MD, PhD2
1 Department of Anatomy and Cell Biology, Rush University Medical Center, 600 S. Paulina, Room 507, Chicago IL 60612. E-mail address for D.R. Sumner: rick_sumner@rush.edu
2 Department of Orthopedic Surgery, Rush University Medical Center, 1653 West Congress Parkway, Chicago IL 60612
View Disclosures and Other Information
In support of their research for or preparation of this manuscript, one or more of the authors received grants or outside funding from the National Institutes of Health (Grant AR42862) and the Grainger Foundation. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. Several commercial entities paid or directed, or agreed to pay or direct, benefits to a research fund, foundation, educational institution, or other charitable nonprofit organization with which the authors are affiliated or associated. Implants were provided by Zimmer, TGF-ß was provided by Genzyme, and BMP-2 was provided by Wyeth.
Investigation performed at the Department of Anatomy and Cell Biology and the Department of Orthopedic Surgery, Rush Arthritis and Orthopedics Institute, Rush Medical College, Rush University Medical Center, Chicago, Illinois

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2006 Apr 01;88(4):806-817. doi: 10.2106/JBJS.E.00846
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Background: Gaps at the interface between implant and bone increase the risk of diminished implant fixation and eventual loosening. The purpose of the present study was to determine if combined use of recombinant human transforming growth factor-beta 2 (rhTGF-ß2) and bone morphogenetic protein 2 (rhBMP-2) led to greater implant fixation strength in the presence of interface gaps than the use of either growth factor alone.

Methods: Twenty-eight skeletally mature adult male dogs received one porous-coated titanium implant in the proximal part of each humerus, for a total of fifty-six implantation sites. Spacers were used to establish an initial 3-mm gap between the implant and the host bone at all fifty-six sites. Forty-two implants were coated with hydroxyapatite-tricalcium phosphate and were used in three growth-factor-treatment groups in which the implants placed in the left humerus were loaded with 12 µg of rhTGF-ß2 (Group 1, seven animals), 25 µg of rhBMP-2 (Group 2, seven animals), or 12 µg of rhTGF-ß2 combined with 25 µg of rhBMP-2 (Group 3, seven animals). In these animals, the twenty-one implants that were placed in the right humerus were loaded with buffer only to serve as contralateral controls. In Group 4 (seven animals), the implants were not coated with hydroxyapatite-tricalcium phosphate, the gap in the left humerus was lightly packed with autogenous bone graft, and the gap in the right humerus was left empty to serve as a contralateral control. All animals were killed at twenty-eight days. The primary end points included three mechanical variables: fixation strength, interface stiffness, and energy to failure. Secondary end points included bone ingrowth and bone volume and trabecular architecture in the gap and in a region located 2 mm medial to the implantation site.

Results: The hydroxyapatite-tricalcium phosphate coating had no effect on implant fixation, bone ingrowth, or bone formation in the 3-mm gap. Individual growth factor treatments led to 2.3 to 3.2-fold increases in fixation strength and stiffness as compared with the values for the contralateral controls (p < 0.05). The combined growth factor treatment led to 5.7-fold increases in fixation strength and stiffness compared with the values for the contralateral controls (p < 0.01). Autogenous bone graft treatment was associated with 4.5 to 6.4-fold increases in implant fixation strength and stiffness as compared with the values for the contralateral controls (p < 0.01). Compared with the relevant contralateral controls, energy to failure was increased 3.5-fold in association with TGF-ß2 alone (p < 0.05), 4.5-fold in association with TGF-ß2 combined with BMP-2 (p < 0.01), and 2.5-fold in association with autogenous bone-grafting. As much as 63% of the variance in the mechanical end points was associated with variance in bone volume and architecture in the 3-mm gap and in the region of interest located 2 mm medial to the implantation site (p < 0.01).

Conclusions: In this animal model, the combined use of TGF-ß2 and BMP-2 led to more secure mechanical fixation of the implant than did the use of either growth factor alone and demonstrated results that were similar to those associated with the use of autogenous bone graft.

Clinical Relevance: This growth factor cocktail is more useful for enhancing implant fixation than individual growth factor therapy and may provide an alternative strategy to autogenous bone-grafting.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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