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
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 µg of rhBMP-2
was added to the OPLA-HY matrix; and in group 4, the femoral defect containing
the OPLA-HY matrix and 20 µg 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
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
Clinical Relevance: This tissue-engineering technique may provide
another option for reconstruction of segmental bone defects and chronic
nonunions, especially those associated with a defective wound environment, as
an alternative to conventional bone-grafting techniques.