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Combination of growth factors inhibits bone ingrowth in the bone harvest chamber
R L Vonau1, M P Bostrom, P Aspenberg
1The Bobst Hospital and Caspary Institute of the Animal Medical Center, New York, NY, USA.
Abstract:
Previous studies using bone harvest chambers have shown that bone morphogenetic protein-2 inhibits bone ingrowth. The authors hypothesized that the combination of bone morphogenetic protein-2 and a potent angiogenic factor, basic fibroblast growth factor, would result in increased bone formation in this model. Five New Zealand White rabbits were surgically implanted with bone harvest chambers in the proximal metaphyseal region of both tibias. The right leg of each rabbit was implanted with a bovine collagen sponge that was impregnated with recombinant human bone morphogenetic protein-2, basic fibroblast growth factor, or a combination of these factors. The left leg chamber was implanted with the collagen sponge with no growth factors as a control. The bone that grew into the chambers was harvested after 2 weeks, and histomorphologic analysis was performed to determine the amount of tissue and bone ingrowth. The tissue chambers were left empty for 2 weeks between test implants, and this tissue also was harvested, analyzed, and compared with the other samples. The results showed decreased bone formation for the bone morphogenetic protein-2, basic fibroblast growth factor, and combination of bone morphogenetic protein-2 and basic fibroblast growth factor treated groups when compared with the control and empty groups. The combination of bone morphogenetic protein-2 and basic fibroblast growth factor showed inhibition of bone formation that was greater than either growth factor individually. The reason for the inhibition of bone formation with the combination of factors is unknown.
Insights
Bone morphogenetic protein-2 and basic fibroblast growth factor were tested for bone formation. Unexpectedly, both factors, individually and combined, inhibited bone ingrowth in rabbit tibia models.
Area of Science:
- Orthopedics
- Biomaterials Science
- Regenerative Medicine
Background:
- Bone morphogenetic protein-2 (BMP-2) has been shown to inhibit bone ingrowth in previous studies.
- Basic fibroblast growth factor (bFGF) is a potent angiogenic factor.
- The combined effect of BMP-2 and bFGF on bone formation is not well understood.
Purpose of the Study:
- To investigate the hypothesis that combining BMP-2 and bFGF would enhance bone formation.
- To evaluate the individual and combined effects of BMP-2 and bFGF on bone ingrowth in a rabbit model.
Main Methods:
- Bone harvest chambers were implanted in the tibias of New Zealand White rabbits.
- Chambers were impregnated with recombinant human BMP-2, bFGF, a combination of both, or a control (no growth factors).
- Histomorphologic analysis was performed after 2 weeks to assess tissue and bone ingrowth.
Main Results:
- BMP-2, bFGF, and the combination of BMP-2 and bFGF all resulted in decreased bone formation compared to controls.
- The combination of BMP-2 and bFGF demonstrated greater inhibition of bone formation than either factor alone.
- The underlying mechanism for this observed inhibition remains unknown.
Conclusions:
- Contrary to the hypothesis, BMP-2 and bFGF, individually and in combination, inhibit bone formation in this model.
- The combination of BMP-2 and bFGF exhibits a synergistic inhibitory effect on bone ingrowth.
- Further research is needed to elucidate the mechanism behind this unexpected finding.