Osteogenic protein‐1 induced bone formation in an infected segmental defect in the rat femur

Abstract

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 mni 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-l (1 I or 50 pg), lyophilized bovine type I collagen (carrier for the OP-I), and 10' colony-forming units of Strcphy1ococcu.r ciureus. 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 01'-1. The 50 pg dose of OP-1 induced significantly more bone formation than the 11 pg dose, both with and without bacteria. This investigation has demonstrated that OP-l maintains its osteoinductive capability in a contaminated segmental defect. OP-1 may potentially be used in the clinical management of Contaminated fractures.

Acinetobacter baumannii is not Associated with Osteomyelitis in a Rat Model: A Pilot Study

“…These controls may have shown that no bone formation occurs in the absence of MDR AB. Bone formation has not been observed in this model of infection without some form of osteogenic treatment [3][4][5]. One explanation could be that the newly formed bone may be the result of the presence of the absorbable collagen sponge used to retain the bacteria in the defect in the short term.…”

“…One explanation could be that the newly formed bone may be the result of the presence of the absorbable collagen sponge used to retain the bacteria in the defect in the short term. However, the presence of the collagen sponge in an uninfected defect is not osteogenic: we chose this defect model because it is critical, meaning no bone forms unless an osteogenic treatment is applied [3][4][5]. Seventh, the virulence of SA was such that the polymicrobial experiments were not performed past 3 weeks.…”

Osteogenic Protein-1 Overcomes Inhibition of Fracture Healing in the Diabetic Rat: A Pilot Study

“…The percentage increase in area of reparative callus with OP-1, compared with treatment groups without OP-1, did not necessarily translate into an equivalent percentage increase in torque to failure. Although our choices of the 25-lg dose of OP-1 and 4-week point initially seemed justified by the literature [4,15,18,21], our torsion failure testing results indicated the diabetic challenge in this model may have required a higher dose of OP-1 and longer followup to observe a difference in failure parameters. A time greater than 4 weeks may have allowed the callus to further remodel and become stronger.…”

“…Responding progenitor elements (stromal, periosteal, and perivascular cells) may retain their inductive response to BMPs, thereby overcoming an inhibitory environment [4]. Because BMP receptor II is downregulated in diabetes mellitus [33], it is possible treatment of a diabetic fracture with exogenous BMP may stimulate expression of BMP receptors [35].…”

“…Bone morphogenetic proteins upregulate the expression of vascular endothelial growth factor, a member of the PDGF superfamily [30]. In clinical and animal studies, BMPs promote fracture healing in a normal setting and in pathologic conditions, including infection [4,5,7,14,35].…”