title: 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 tri-calcium 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.
authors.affiliation: Department of Biomedical Engineering (ND20), Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.muschlg@ccf.org.
authors.forename: V
authors.initials: V
authors.lastname: Luangphakdy
authors.forename: K
authors.initials: K
authors.lastname: Shinohara
authors.forename: H
authors.initials: H
authors.lastname: Pan
authors.forename: C
authors.initials: C
authors.lastname: Boehm
authors.forename: A
authors.initials: A
authors.lastname: Samaranska
authors.forename: G F
authors.initials: GF
authors.lastname: Muschler
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000379:methods; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D016025:Bone Transplantation / Q000379:methods*; D002130:Calcium Phosphates / Q000737:chemistry*; D003094:Collagen / Q000737:chemistry*; D004195:Disease Models, Animal; D004285:Dogs; D017886:Durapatite / Q000737:chemistry*; D005260:Female; D005269:Femur / Q000293:injuries / Q000601:surgery*; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D016896:Treatment Outcome; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D011994:Recombinant Proteins; D003094:Collagen; D017886:Durapatite; C018392:tricalcium phosphate