Healing course of primate ulna segmental defects treated with osteogenic protein-1.
Twelve African green monkeys were implanted with recombinant human osteogenic protein-1 (rhOP-1) placed on a bovine bone-derived Type I collagen carrier to characterize healing in an ulna segmental bone defect model at 1, 3, 12, and 20 weeks postoperative. Defect healing was evaluated by plain film radiography, computed tomography (CT), magnetic resonance imaging (MRI), bone mineral density (BMD), and histologic analysis. Radiographically, new bone formation was observed as early as 3 weeks postoperative. By 6 weeks, new bone was visible in five of six defects. Increased quantity and mineralization of the new bone were apparent by 12 weeks. Reformation of the medullary cavity with appearance of marrow elements was demonstrated by CT and MRI at 20 weeks. BMD studies revealed a significant increase in the presence of bone with time. Histology at 1 week demonstrated that the implant material was well contained in the defect, and a proliferation of cells occurred at the defect borders. At 3 weeks cell proliferation continued and cell phenotype differentiation was recognized. By 12 weeks substantially less residual carrier was found in the defects, and calcifying tissues with plump chondrocytes, osteoblasts, and immature woven bone were observed. Areas of lamellar and woven bone were identified at 12 weeks, with advanced remodeling and revascularization observed at 20 weeks. The use of osteoinductive implants may provide an alternative to autologous and allogeneic bone tissue in the therapeutic approach to bone defects and promotion of fusion by eliminating the donor site morbidity associated with autogenous bone and the decreased efficacy and potential for disease transmission associated with allogeneic bone.
Cook
Stephen D
SD
Department of Orthopedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. scook2@tulane.edu
Salkeld
Samantha L
SL
Patron
Laura P
LP
Sargent
M Catherine
MC
Rueger
David C
DC
D000818:Animals; D015519:Bone Density; D001847:Bone Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy*; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004343:Drug Implants; D008279:Magnetic Resonance Imaging; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta; D014457:Ulna / Q000000981:diagnostic imaging / Q000502:physiology* / Q000601:surgery; D014945:Wound Healing / Q000187:drug effects*
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004343:Drug Implants; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta