The goal of this study was to use a segmental defect model in the rat femur to determine if osteogenic protein-1 (OP-1) is capable of inducing bone formation in the presence of bacterial contamination. A 6 mm segmental defect was surgically created and stabilized with a polyacetyl plate and Kirschner wires in one femur in each of 126 Sprague-Dawley rats. The animals were divided into eight groups in which the defect was either left untreated, or subjected to various combinations of OP-1 (11 or 50 μg), lyophilized bovine type I collagen (carrier for the OP-1), and 105 colony-forming units of Staphylococcus aureus. The animals were euthanized at either 2, 4, or 9 weeks. Quantitative radiographic and histologic analyses were performed on the harvested tissue. The initial contamination progressed to infection in all animals receiving bacteria, as determined by qualitative bacteriology. There was very little, if any, bone formation in the untreated defects, and in the contaminated defects with or without collagen carrier. Bone formation was significantly greater in contaminated defects with either dose of OP-1, compared with contaminated defects without OP-1. The 50 μg dose of OP-1 induced significantly more bone formation than the 11 μg dose, both with and without bacteria. This investigation has demonstrated that OP-1 maintains its osteoinductive capability in a contaminated segmental defect. OP-1 may potentially be used in the clinical management of contaminated fractures.
Bibliographical noteFunding Information:
The authors thank Douglas Cooper, Ceasar Gustilo, M.D., Søren Kold, M.D., Thomas Reagan, Andrew Schmidt, M.D., Dean Tsukayama, M.D., and Barbara Wicklund, for their guidance and technical assistance. The osteogenic protein-1 and collagen carrier were generously donated by Stryker Biotech of Hopkinton, MA. This study was supported by the Midwest Orthopaedic Research Foundation, and a grant from the Orthopaedic Trauma Association.