Repair of Ulnar Segmental Defect by Recombinant Human Bone Morphogenetic Protein-2 in Dogs.

Abstract

ABSTRACT. The efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with poly D, L lactic-co-glycolic acid (PLGA)/gelatin sponge complex (PGS) as a carrier on the repair of segmental long-bone defects was evaluated using an ulnar model in dogs. The defect was 2 cm in length and was fixed with bone plating. After implantation of PGS with or without rhBMP-2, the repair process of the defect was evaluated by serial radiography until 16 postoperative weeks. All defects treated with 160 µg or 640 µg of rhBMP-2/PGS revealed bone union radiographically by 12 postoperative weeks, whereas all defects treated with PGS alone revealed no radiographic evidence of healing throughout the experimental period. In defects treated with 40 µg of rhBMP-2/PGS, new bone appeared partially at the defects but did not accomplish union. Bone mineral contents at the defect sites after harvest at 16 weeks postoperatively were significantly (p<0.05) higher in those treated with 160 µg or 640 µg of rhBMP-2 than in those treated with 40 µg of rhBMP-2 or PGS alone. Histologically, defects radiographically diagnosed as having achieved union showed the appearance of cortical bone and bone marrow cells. These findings suggest the use of rhBMP-2/PGS as a potential bone graft substitute in reconstructive surgery in dogs. -KEY WORDS: canine, rhBMP-2, ulnar defect.

Femoral Nonunion Fracture Treated with Recombinant Human Bone Morphogenetic Protein-2 in a Dog.

“…PGS may also play a role to control the size and shape of the induced bone. PGS has been already proven to be a functional carrier of rhBMP-2 in our previous studies [6]. The result of this study also supported the effectiveness of this material.…”

“…To date, more than 12 recombinant human BMPs (rhBMPs) have been successfully produced [3,11,18], among which rhBMP-2 has been intensively investigated for clinical application because of its stronger osteoinductive activity than others [7,17]. Promising results using rhBMP-2 have been reported in experimental bone defect models in dogs [6,15], however, there have been no reports on the effect of rhBMP-2 in spontaneous nonunion fractures in dogs. This is the first report on successful treatment of spontaneous nonunion fracture of a dog.…”

“…Previous studies using a femoral defect model in rats demonstrated that rhBMP-2 could induce healing at doses from 0.93 to 3.1 µg in a dosedependent manner [9]. However, the effective dose of rhBMP-2 in dogs may be different from that in rats because higher animals with longer lifespans are known to need more rhBMP-2 for new bone formation [1,4,6,13]. Our previous study using canine ulnar defect models suggested that the lowest effective dose of rhBMP-2 for defect healing is between 25-and 100 µg of rhBMP-2/cm 3 PGS [6].…”

“…However, the effective dose of rhBMP-2 in dogs may be different from that in rats because higher animals with longer lifespans are known to need more rhBMP-2 for new bone formation [1,4,6,13]. Our previous study using canine ulnar defect models suggested that the lowest effective dose of rhBMP-2 for defect healing is between 25-and 100 µg of rhBMP-2/cm 3 PGS [6]. However, these results were obtained in freshly produced defect models, which might be different in environmental factors from the patient with nonunion fracture.…”

OP-1 Augments Glucocorticoid-inhibited Fracture Healing in a Rat Fracture Model

“…At present, only BMP-2 and BMP-7 are produced commercially as a therapy to enhance bone healing with BMP-7 called osteogenic protein 1 (OP-1). BMP-2 and OP-1 both promote bone formation in a variety of experimental models (rat [8,13,25,46,47,56], rabbit [3,10,29,48], sheep [15,20], dog [9,19,32,35,40,43]). Although these proteins are now used clinically, most of the information on their effects is known from these and other experimental studies.…”