Repair of large segmental bone defects: BMP-2 gene activated muscle grafts vs. autologous bone grafting

Background: Common cell based strategies for the treatment of
osseous defects require the isolation and expansion of autologous
cells. Since this makes such approaches time-consuming and
expensive, we developed a novel expedited technology creating gene
activated muscle grafts. We have previously shown that large
segmental bone defects in rats can be regenerated by implantation
of muscle tissue fragments activated by BMP-2 gene transfer.
Results: In the present study, we compared the bone healing
capacities of such gene activated muscle grafts with bone
isografts, mimicking autologous bone grafting, the clinical gold
standard for treatment of bone defects in patients. Two of 14 male,
syngeneic Fischer 344 rats used for this experiment served as
donors for muscle and bone. Muscle tissue was harvested from both
hind limbs and incubated with an adenoviral vector carrying the
cDNA encoding BMP-2. Bone was harvested from the iliac crest and
long bone epiphyses. Bone defects (5 mm) were created in the right
femora of 12 rats and were filled with either BMP-2 activated
muscle tissue or bone grafts. After eight weeks, femora were
evaluated by radiographs, micro-computed tomography (mu CT), and
biomechanical testing. In the group receiving BMP-2 activated
muscle grafts as well as in the bone-grafting group, 100\% of the
bone defects were healed, as documented by radiographs and mu
CT-imaging. Bone volume was similar in both groups and
biomechanical stability of the two groups was statistically
indistinguishable. Conclusions: This study demonstrates that
treatment of large bone defects by implantation of BMP-2 gene
activated muscle tissue leads to similar bone volume and stability
as bone isografts, mimicking autologous bone grafting.