title: Additive enhancement of implant fixation following combined treatment with rhTGF-beta2 and rhBMP-2 in a canine model.
abstract: 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-beta2) 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 microg of rhTGF-beta2 (Group 1, seven animals), 25 microg of rhBMP-2 (Group 2, seven animals), or 12 microg of rhTGF-beta2 combined with 25 microg 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-beta2 alone (p < 0.05), 4.5-fold in association with TGF-beta2 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-beta2 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.
authors.affiliation: Department of Anatomy and Cell Biology, Rush Arthritis and Orthopedics Institute, Rush Medical College, Rush University Medical Center, 600 S. Paulina, Room 507, Chicago IL 60612, USA. rick_sumner@rush.edu
authors.forename: D R
authors.initials: DR
authors.lastname: Sumner
authors.forename: T M
authors.initials: TM
authors.lastname: Turner
authors.forename: R M
authors.initials: RM
authors.lastname: Urban
authors.forename: A S
authors.initials: AS
authors.lastname: Virdi
authors.forename: N
authors.initials: N
authors.lastname: Inoue
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D016348:Osseointegration / Q000187:drug effects*; D019919:Prosthesis Implantation; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000627:therapeutic use; D053781:Transforming Growth Factor beta2
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2