Fri., 10/17/08 Basic Science, Paper #19, 9:48 am OTA-2008
Δ Have We Hit the Critical Defect Trifecta? Immediate Weight Bearing, Healing and a Biodegradable Carrier in a Canine Model
Rena L. Stewart, MD1 (a-Synthes, Wyeth, OTA);
James P. Stannard, MD1 (a-Smith + Nephew, Synthes);
David A. Volgas, MD1 (a-Biomet (Interport-Cross), Smith + Nephew, Synthes, Pfizer);
Justin Duke, MD1 (n); Tien-Min Chu, PhD2 (n);
1University of Alabama at Birmingham, Birmingham, Alabama, USA;
2Indiana University, Indianapolis, Indiana, USA
Purpose: Segmental bone defects remain a tremendous challenge to the trauma surgeon. A promising new strategy is emerging that combines tissue-engineering techniques with the delivery of biologically active proteins to facilitate bone regeneration. The purpose of this study was twofold: (1) to investigate if a biodegradable, load-bearing scaffold, stabilized with an intramedullary nail, will facilitate early weight bearing in a critical-sized canine defect; and (2) to investigate if a biodegradable scaffold can function as a carrier for bone morphogenetic protein-2 (BMP-2) and induce boney healing across a critically sized canine defect.
Methods: A critical-size defect of 3 cm was created in the tibia of 10 dogs. In all 10 dogs, a cylindrical, biodegradable scaffold of (poly) propylene fumarate was inserted into the defect. The tibia was then stabilized with a reamed, locked intramedullary nail. Half of the scaffolds (n = 5) were impregnated with 300 μg BMP-2 and half (n = 5) remained as empty controls. The animals were allowed immediate weight bearing postoperatively. Radiographs were obtained at weeks 0, 1, 2, 3, 6, 12, 18, and 24 and were analyzed for loss of height, integrity of the scaffold, and presence of bridging callus formation. At 24 weeks, tibiae were harvested and biomechanical, histologic, dual-energy x-ray absorptiometry (DXA), and microCT evaluations were performed.
Results: All dogs demonstrated full weight bearing by postoperative day 3. Radiographs showed complete bridging callus across 4 cortices in all specimens treated with BMP by 6 weeks and these maintained height of the defect and overall length of the tibia. Control animals demonstrated minimal callus formation at all time points. By 3 weeks, significant loss of defect height was observed in controls. By 6 weeks, failure of hardware (breakage of interlocking screws and/or screw loosening) was evident in all controls. Statistically significant differences in all biomechanical parameters were seen between the two groups. The bending strength of the BMP specimens was 95% of normal, controls <5% of normal. DXA scanning revealed statistically significant differences between BMP and controls in bone mineral density within the defect. Histologically, the BMP specimens showed bridging callus while controls showed no bridging and scaffold collapse. No inflammatory response to the scaffold was seen in either group. MicroCT showed significant differences in volume of bone within the defect (BMP greater than control) and partial degradation of the scaffold in both groups.
Conclusion and Significance: This study shows that a biodegradable scaffold, treated with BMP-2 and implanted in a critical-sized defect, facilitates bridging callus formation and healing across the defect. Additionally, the scaffolds allow full, immediate weight bearing. The combined properties of these scaffolds offer marked advantages over current methods of treatment for segmental defects. The scaffolds have the initial mechanical strength to allow full weight bearing but are then biodegradable. The scaffolds are also easily contained within the defect. The scaffold’s design also allows transport of other molecules, antibiotics, and cells, which offers exciting future strategies for defect management. Investigations of these applications are currently underway.
If noted, the author indicates something of value received. The codes are identified as a-research or institutional support; b-miscellaneous funding; c-royalties; d-stock options; e-consultant or employee; n-no conflicts disclosed, and *disclosure not available at time of printing.
• The FDA has not cleared this drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an “off label” use). ◆FDA information not available at time of printing. Δ OTA Grant.