Histological and radiographic comparison of allograft substitutes using a continuous delivery model in segmental defects.
Demineralized bone matrix (DBM) has been shown to possess osteoinductive capability and one of the specific bone morphogenetic proteins (BMPs) found within DBM that has been attributed with this osteoinductive ability is BMP-7, also known as osteogenic protein-1 (OP-1). The specific aims of this study were (1) to compare the treatment of segmental bone defects with OP-l and DBM in a rat femur model and (2) to determine the effects of the two treatments given at high and low doses via sustained release drug delivery. Animals in Group 1 acted as the control and Group 2 had a created segmental defect with plating and placement of a calcined tricalcium phosphate lysine (TCPL) capsule containing antibiotic (sham). Group 3 and 4 animals had a created segmental defect and received a TCPL carrier containing antibiotic along with DBM or OP-1, respectively. After 4 weeks post-implantation, animals were sacrificed before the retrieval of the bone. The femora were analyzed radiographically and histologically for bone growth. Analysis of the gross specimens showed considerable bone regeneration at low and high doses for both DBM and OP-1 when compared to the shams. At low levels bone regeneration between DBM and OP-1 was very similar. However, at high doses, OP-1 was shown to cause bone overgrowth with a greater curvature and an increased thickness of the distal and proximal ends of the femur. The stained slides showed the defects treated with DBM and OP-1 to be bridged with lamellar and woven bone that was continuous with the original bone. Histologically, the experimental femora demonstrated natural remodeling processes with new osteons and angiogenesis.
Marks
Tyler
T
School of Medicine, School of Graduate Studies in Health Sciences, Department of Orthopaedic Surgery and Rehabilitation, University of Mississippi Medical Center, Jackson, MS 39216, USA. tgmarks@som.umsmed.edu
Wingerter
Scott
S
Franklin
Laura
L
Woodall
James
J
Tucci
Michelle
M
Russell
George
G
Patel
Ramesh
R
Benghuzzi
Hamed
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D018786:Bone Substitutes / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects*; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D014031:Tobramycin / Q000008:administration & dosage*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D016212:Transforming Growth Factor beta; D014031:Tobramycin