Healing of a critical-sized defect in the rat femur with use of a vascularized periosteal flap, a biodegradable matrix, and bone morphogenetic protein.
BACKGROUND
The purpose of this study was to evaluate the osseous healing of a critical-sized femoral defect in a rat model with use of recombinant human bone morphogenetic protein-2 (rhBMP-2), a matrix fabricated of D,D-L,L-polylactic and hyaluronan acid (OPLA-HY), and a vascularized periosteal flap.


METHODS
The carrier matrix OPLA-HY with or without rhBMP-2 was implanted in a 1-cm-long femoral defect and secured with a plate and screws. In some groups, a vascularized periosteal flap was harvested from the medial surface of the tibia. In group 1, the femoral defects in the animals were filled with the OPLA-HY matrix alone; in group 2, the OPLA-HY matrix was covered by the vascularized periosteal flap; in group 3, 20 mug of rhBMP-2 was added to the OPLA-HY matrix; and in group 4, the femoral defect containing the OPLA-HY matrix and 20 mug of rhBMP-2 was wrapped circumferentially by the vascularized periosteal flap. The presence and density of new bone formation in the femoral defect were evaluated radiographically, histologically, and with histomorphometry at four and eight weeks postoperatively.


RESULTS
Groups 1 and 2, which were not treated with rhBMP-2, showed no radiographic or histologic evidence of mature bone formation at four or eight weeks. Both groups 3 and 4, which were treated with rhBMP-2, demonstrated excellent bone formation. However, with the periosteal flap, group 4 demonstrated more bone formation on histomorphometric analysis at eight weeks (43.1%) than did group 3 (28.3%) (p < 0.01). Additionally, heterotopic bone formed outside the boundaries of the defect in eight of the fifteen animals in group 3, which had no periosteal flap.


CONCLUSIONS
Bone-tissue engineering with use of the OPLA-HY matrix and rhBMP-2 produced good bone formation in the rat femoral defect model. However, the addition of a vascularized periosteal flap significantly increased bone formation within the boundaries of the defect and prevented heterotopic ossification.
Vögelin
E
E
Department of Orthopaedic Surgery, Division of Plastic and Reconstructive Surgery, and UCLA Hand Center, University of California at Los Angeles, 200 UCLA Medical Plaza, Suite 140, Los Angeles, CA 90095, USA.
Jones
N F
NF
Huang
J I
JI
Brekke
J H
JH
Lieberman
J R
JR
D000818:Animals; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006820:Hyaluronic Acid / Q000627:therapeutic use; D019344:Lactic Acid; D008297:Male; D023421:Models, Animal; D010012:Osteogenesis; D010521:Periosteum / Q000637:transplantation; D011091:Polyesters; D011108:Polymers; D019736:Prostheses and Implants; D051381:Rats; D011917:Rats, Inbred Lew; D013524:Surgical Flaps / Q000098:blood supply; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D014945:Wound Healing
C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011091:Polyesters; D011108:Polymers; D016212:Transforming Growth Factor beta; D019344:Lactic Acid; C033616:poly(lactide); D006820:Hyaluronic Acid