Healing of rat femoral segmental defect with bone morphogenetic protein-2: A dose response study

S.R. Angle (1, 2), K. Sena (1), D.R. Sumner (1, 2, 3), W.W. Virkus (3), A.S. Virdi (1, 2, 3)

(1) Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, USA;
(2) Department of Bioengineering, University of Illinois, Chicago, IL, USA;
(3) Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, USA

Abstract
Objective: Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) is becoming a common clinical approach to enhance bone repair. There is little or no information in the literature on the dose of rhBMP-2 required for effective healing of critical-sized defects such as those associated with trauma. In this study, we used a segmental defect model to assess the dose response of rhBMP-2 using quantitative and qualitative endpoints. Methods: Femoral defects in rats were replaced with absorbable collagen sponges carrying rhBMP-2 (0, 1, 5, 10 or 20 μg; N=5). At 4-weeks new bone formation was assessed using quantitative (radiography and microcomputed tomography) and qualitative (histology and backscattered-SEM) endpoints statistically compared. Results: rhBMP-2 showed increased bridging in the gap. Quantitative evaluation presented a bi-phasic dose response curve. Histological assessment revealed that with rhBMP-2 the defect showed the presence of spongy bone with the trabeculae layered with active osteoblasts and osteoclasts. The density and compactness of the bone varied with the dose of rhBMP-2. Conclusions: Our findings revealed that all doses of rhBMP-2 result in new bone formation. However, there is an optimum dose of 12 μg of rhBMP-2 for bone repair in this model, above which and below which less stimulation of bone occurs.

Keywords: Fracture, Growth Factors, Critical Size Defect