Evaluation of bovine-derived bone protein with a natural coral carrier as a bone-graft substitute in a canine segmental defect model.
The efficacy of a bone-graft substitute (bovine-derived bone protein in a carrier of natural coral) in the healing of a segmental defect of a weight-bearing long bone was evaluated. Twenty dogs, divided into two groups, underwent bilateral radial osteotomies with creation of a 2.5 cm defect. On one side of each dog, the defect was filled with autogenous cancellous bone graft. Contralateral defects received, in a blinded randomized fashion, cylindrical implants consisting of natural coral (calcium carbonate) or calcium carbonate enhanced with a standard dose of bovine-derived bone protein (3.0 mg/implant; 0.68 mg bone protein/cm3). The limbs were stabilized with external fixators, and all animals underwent monthly radiographs. They were killed at 12 (group 1) or 24 (group 2) weeks, and regenerated bone was studied by biomechanical testing and histology. Radiographic union developed in all 20 radii with autogenous cancellous bone grafts and in all 10 of the radii with the composite implants. None of the radii with implants of calcium carbonate alone showed radiographic evidence of union. This represented a statistically significant difference between implant types. In addition, calcium carbonate implants both with and without bone protein demonstrated radiographic evidence of near total resorption of the radiodense carrier by 12 weeks. This resorption facilitated radiographic evaluation of healing. Mean values for biomechanical parameters of radii with the composite implants exceeded those for the contralateral controls at 12 and 24 weeks; the difference was statistically significant at 12 weeks. Histology revealed scant residual calcium carbonate carrier at either time in the defects with calcium carbonate implants; however, a moderate amount was present in defects with the composite implants. In these specimens, the residual carrier was completely surrounded by newly formed bone that may have insulated the calcium carbonate from further degradation. The present study used a carrier of granular calcium carbonate reconstituted with bovine type-I collagen to deliver an osteoinductive protein to the defect site. This carrier is of nonhuman origin (eliminating the risk of disease transmission or antigenicity) and resorbs rapidly. In this model, bovine-derived bone protein in a natural coral carrier performed consistently better than the gold standard autogenous cancellous bone graft in terms of the amount of bone formation and strength of the healed defect. This may have implications for removal of hardware or resumption of weight-bearing in certain clinical situations. These data also indicate that coralline calcium carbonate alone represents a poor option as a bone-graft substitute in this critical-sized segmental defect model.
Sciadini
M F
MF
Department of Orthopaedics and Rehabilitation, Vanderbilt University, Nashville, Tennessee 37232-2550, USA. sciadimf@ctrvax.vanderbilt.edu
Dawson
J M
JM
Johnson
K D
KD
D000818:Animals; D001672:Biocompatible Materials; D001857:Bone Matrix / Q000000981:diagnostic imaging / Q000473:pathology / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D018786:Bone Substitutes; D016025:Bone Transplantation / Q000000981:diagnostic imaging / Q000379:methods* / Q000473:pathology; D002417:Cattle; D003063:Cnidaria; D004285:Dogs; D005069:Evaluation Studies as Topic; D005260:Female; D017102:Fracture Healing / Q000187:drug effects; D020007:Implants, Experimental; D008297:Male; D016348:Osseointegration / Q000187:drug effects / Q000502:physiology; D011859:Radiography; D011884:Radius / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D011897:Random Allocation; D016474:Weight-Bearing / Q000502:physiology
D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes