The repair of critical-sized bone defects using expedited, autologous BMP-2 gene-activated fat implants.
The repair of bone defects can be induced experimentally with bone morphogenetic protein-2 (BMP-2) producing fat-derived stem cells, but this ex vivo tissue engineering method requires the isolation and long-term culture of autologous cells. To develop an expedited bone repair strategy, we transferred BMP-2 cDNA directly to autologous fat tissue fragments that were held in culture for only 24 h before implantation. We evaluated the ability of such gene-activated fat grafts to regenerate large segmental bone defects in rats. Fat tissue was harvested from 2 of 35 male Fischer 344 rats used for this study. The fat tissue fragments were incubated with an adenoviral vector carrying the cDNA encoding either BMP-2 or green florescent protein (GFP), or they remained unmodified. According to their group, the segmental femoral bone defects of 33 rats were filled press fit with either BMP-2-activated fat tissue, GFP-transduced fat tissue, or unmodified fat tissue. Another control group remained untreated. Femora were evaluated by radiographs, microcomputed tomography, biomechanical torsional testing, and histology. Radiographically and histologically, 100% of the femora treated with BMP-2-activated fat grafts were bridged at 6 weeks after surgery. The femora of this group exceeded the bone volume and the biomechanical stability of intact, contralateral femora. Control defects receiving no treatment, unmodified fat tissue, or GFP-transduced fat were filled with fibrous or adipose tissue, as evaluated by histology. The use of BMP-2 gene-activated fat tissue grafts represents an expedited and effective bone repair strategy that does not require the extraction and expansion of stem cells.
Betz
Oliver B
OB
Department of Orthopedic Surgery, University Hospital Grosshadern, Munich, Germany. oliver.betz@med.uni-muenchen.de
Betz
Volker M
VM
Abdulazim
Ahmed
A
Penzkofer
Rainer
R
Schmitt
Bärbel
B
Schröder
Christian
C
Mayer-Wagner
Susanne
S
Augat
Peter
P
Jansson
Volkmar
V
Müller
Peter E
PE
D000273:Adipose Tissue / Q000378:metabolism* / Q000637:transplantation; D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020007:Implants, Experimental; D008297:Male; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D019415:Torque; D015533:Transcriptional Activation; D014161:Transduction, Genetic; D014945:Wound Healing; D055114:X-Ray Microtomography
D055396:Bone Morphogenetic Protein 2; D049452:Green Fluorescent Proteins