Evaluation of rhBMP-2/collagen/TCP-HA bone graft with and without bone marrow cells in the canine femoral multi defect model

Abstract

Recombinant human bone morphogenetic protein-2, when applied to an absorbable type 1 bovine collagen sponge (rhBMP-2/ACS) is an effective therapy in many bone grafting settings. Bone marrow aspirate (BMA) has also been used as a source of transplantable osteogenic connective tissue progenitors. This study was designed to characterize the performance of a scaffold comprising rhBMP-2/ACS in which the sponge wraps around tricalcium phosphate hydroxyapatite granules (rhBMP-2/ ACS/TCP-HA) and to test the hypothesis that addition of BMA will improve the performance of this construct in the Canine Femoral Multi Defect Model. In each subject, two sites were grafted with rhBMP-2/ACS/TCP-HA scaffold loaded with BMA clot and two other sites with rhBMP-2/ACS/TCP-HA scaffold loaded with wound blood (WB). After correction for unresorbed TCP-HA granules, sites grafted with rhBMP-2/ACS/TCP-HA+BMA and rhBMP-2/ACS/TCP-HA+WB were similar, with mean percent bone volumes of 10.9 % ± 1.2 and 11.2 % ± 1.2, respectively. No differences were seen in quantitative histomorphometry. While bone formation using both constructs was robust, this study did not support the hypothesis that the addition of unprocessed bone marrow aspirate clot improved bone regeneration in a site engrafted with rhBMP-2/ACS/TCP-HA+BMA. In contrast to prior studies using this model, new bone formation was greater at the center of the defect where TCP-HA was distributed. This finding suggests a potential synergy between rhBMP-2 and the centrally placed ceramic and cellular components of the graft construct. Further optimization may also require more uniform distribution of TCP-HA, alternative cell delivery strategies, and a more rigorous large animal segmental defect model.

Assessment of Methods for Rapid Intraoperative Concentration and Selection of Marrow-Derived Connective Tissue Progenitors for Bone Regeneration Using the Canine Femoral Multidefect Model

“…The CFMD model with four unicortical 10 mm diameter × 15 mm cylindrical defects has been designed and used effectively as a local wound environment and systemic environment to assess the relative efficacy of scaffold materials, 8 cell sourcing/processing options, 9 , 26 and delivery of growth factors (e.g., bone morphogenetic proteins [BMPs]). 26 , 32 The availability of data from four sites in each subject enables comparison of two materials, while controlling for variation between implant sites and between subjects. The defects are sufficient in size to create a biological environment in which the interior of the defect is profoundly hypoxic.…”

“… 9 BMP-2 delivered with marrow-derived cells on a ceramic tricalcium phosphate (TCP) and collagen carrier has been shown to be very effective in the CFMD model. 32 …”

Biomimetics of Bone Implants: The Regenerative Road

“…In a canine femoral defect model, bone morphogenetic protein (BMP) in tandem with collagen type-1/TCP showed increased healing of the femur in the presence of bone marrow aspirate. 42 This study points to the use of collagen type 1 to match the modulus of the femur, and the utility of bone marrow-derived cells stimulated by pro-osteogenic growth factors in bone healing.…”

Patient-Derived Human Induced Pluripotent Stem Cells From Gingival Fibroblasts Composited With Defined Nanohydroxyapatite/Chitosan/Gelatin Porous Scaffolds as Potential Bone Graft Substitutes

“…Nondegradable bone scaffolds include titanium, ceramics, and so forth. The degradable scaffolds contain HA, chitosan, collagen, gelatin, poly(lactic-co-glycolic acid) [47,48], and others. Because a combination of degradable scaffolds will best mimic the natural bone components, the HCG composite has served as one of the favorite scaffolds for bone regeneration.…”