Bone formation following OP‐1 implantation is improved by addition of autogenous bone marrow cells in a canine femur defect model

Abstract

Osteogenic Protein-1 (OP-1, BMP-7) acts locally on connective tissue progenitors (CTPs) to induce bone formation. The response to OP-1 and similar agents is potentially limited by the number of local CTPs. This study tested the hypothesis that supplementing local CTPs using autogenous bone marrow will enhance bone formation at an OP-1 implant. Four 1.0-cm diameter unicortical cylindrical defects in the left proximal femur were grafted in each of seven dogs. Radial ingrowth of new bone formation was assessed at 4 weeks using micro CT. The OP-1 (3.5 mg rhOP-1 in 1 g bovine collagen I matrix) was implanted in each site combined with either clotted blood or aspirated bone marrow (BM). Bone formation was increased in the group augmented with transplanted marrow. These data suggest that increasing the local population of cells and CTPs using aspirated bone marrow can enhance the performance of OP-1, but may not eliminate the effects of site variation on the response to OP-1 and similar agents. The canine multiple femoral defect model defined in this study is well suited to quantitatively evaluate strategies for augmenting bone repair using local cell targeting and cell transplantation strategies. ß

In VivoTransplantation of Autogenous Marrow-Derived Cells Following Rapid Intraoperative Magnetic Separation Based on Hyaluronan to Augment Bone Regeneration

“…[22][23][24] The left femur was exposed in an extraperiosteal plane by elevating the vastus lateralis. A customized drill template was fixed longitudinally on the lateral aspect of the femur with two 3.5-mm bicortical screws.…”

“…The value of directly comparing two grafting techniques in single animal controls for variation between subjects and increases statistical power by offering paired comparisons, which in turn reduce the number of subjects needed to address a given comparison. [22][23][24] Defect sites and performance are reproducible. Very importantly, the defects are large enough so that the center of the defect will become profoundly hypoxic within 2-3 days following surgery.…”

Polytherapy in Bone Regeneration: Clinical Applications and Preliminary Considerations

“…Similarly, in a dogs study, the simultaneous application of rhBMP-7 and MSC has increased the local population of cells and the connective tissue progenitors in a canine femur defect model (21). In another study conducted on tibial critical size defects ofmini-pigs, it has been revealed that area of new bone formation was significantly higher in the group treated with an association of PRP and ABG compared with the group treated with the application of ABG alone.…”

Evaluation of Osteoconductive Scaffolds in the Canine Femoral Multi-Defect Model

“…The CFMD model has been shown to be an effective tool for comparison of cell sourcing and processing strategies, 48 and methods involving growth factor delivery use. 38 The CFMD model is currently being evaluated for use in assessment of methods to optimizes the microenvironment for cell transplantation (e.g., the use of platelet gel preparations), and the selective surface modification of biomaterials (e.g., presentation of tethered growth factors).…”

“…The canine femoral multi-defect (CFMD) model 37,38 was used for these studies. The CFMD model provides four 10-mm-diameter and 15-mm-long defects for assessment in each subject.…”